A comparative evaluation of smear layer removal by using ethylenediamine tetraacetic acid, citric acid, and maleic acid as root canal irrigants: An in vitro scanning electron microscopic study.
Irrigants remove or dissolve smear layer formed during instrumentation. Thus it is important to study the effect of different irrigant solutions on smear layer removal. The aim of this study is to determine which irrigant effectively removes the smear layer from the coronal, middle, and apical third of the root canal. One hundred and twenty single-rooted mandibular premolars were decoronated and biomechanical preparation was done through hand instrumentation up to size 40 k file with 2.5% NaOCl irrigation between each successive filing, followed by irrigation with 5 ml of saline. The teeth were divided into Groups I, II, III, and IV containing 30 samples each and irrigated with 5 ml of 17% ethylenediamine tetraacetic acid (EDTA), 10% Citric acid, 7% Maleic acid and normal saline respectively for 1 min and final irrigation was done with 5 ml of distilled water of each sample. The canals were dried with 2% absorbent paper points. The roots were then split with a chisel and mallet. One-half of each tooth was selected and then was analyzed using a scanning electron microscope. The dentinal surfaces were observed at the cervical, middle, and apical third with ×2000 for the smear layer. The scores were attributed, according to Torabinejad et al. rating system. 7% maleic acid and 10% citric acid both are equally effective in smear layer removal from coronal and middle third, but in apical third 7% maleic acid is more effective than 10% citric acid. Between citric acid and EDTA, both are equally effective in smear layer removal from coronal and middle third, but in apical third, 10% citric acid is more efficacious than 17% EDTA. Within the limitations of the study, it can be concluded that all three tested irrigants removed the smear layer from coronal, middle, and apical third. However, in apical third 7% maleic acid is the most efficacious irrigant in smear layer removal.


ROI-Finder: machine learning to guide region-of-interest scanning for X-ray fluorescence microscopy.
The microscopy research at the Bionanoprobe (currently at beamline 9-ID and later 2-ID after APS-U) of Argonne National Laboratory focuses on applying synchrotron X-ray fluorescence (XRF) techniques to obtain trace elemental mappings of cryogenic biological samples to gain insights about their role in critical biological activities. The elemental mappings and the morphological aspects of the biological samples, in this instance, the bacterium Escherichia coli (E. Coli), also serve as label-free biological fingerprints to identify E. coli cells that have been treated differently. The key limitations of achieving good identification performance are the extraction of cells from raw XRF measurements via binary conversion, definition of features, noise floor and proportion of cells treated differently in the measurement. Automating cell extraction from raw XRF measurements across different types of chemical treatment and the implementation of machine-learning models to distinguish cells from the background and their differing treatments are described. Principal components are calculated from domain knowledge specific features and clustered to distinguish healthy and poisoned cells from the background without manual annotation. The cells are ranked via fuzzy clustering to recommend regions of interest for automated experimentation. The effects of dwell time and the amount of data required on the usability of the software are also discussed.


Oncology outcomes in Retroperitoneal sarcomas: Prognostic factors in a Retrospective Cohort study.
Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. The aim of the study was to define the demographic characteristics and prognostic factors for patients with retroperitoneal sarcomas (RPS) in a Tertiary Referral Center at Mexico. A retrospective study of patients with RPS treated from January 2005 to December 2012 at the National Cancer Institute at Mexico. Patient, tumor and treatment variables were analyzed including use of adjuvant therapy and survival status. Survival and local recurrence curves were estimated using the Kaplan-Meier method. Ninety-five patients with a mean age of 47 years with retroperitoneal sarcoma were included. Median follow-up was 25 months (range 1-108 months). The average tumor size was 23.7 cm. Histology, 58 (61.1%) were liposarcoma, 14 (14.7%), leiomyosarcomas and 23 (24.2%) were from other histologies. In 64 (67.4%) patients were high-grade malignancies. The median survival was 51 months for patients with complete resection, 25.1 months for those with incomplete resection, and 4.4 months for those with unresectable tumors. Complete resection (p = 0.0001), and liposarcoma (p = 0.03) were prognostic factors for overall survival. In this study of patients with retroperitoneal, complete resection and liposarcoma histology are prognostic factors related to the disease-free and overall survival. Patients approached with curative intent should undergo aggressive attempts at complete surgical resection.


[Hemorrhagic complications following vascular reconstructions in arterial occlusive disease of the lower extremity].
In comparison with the results of international literature the authors present their experiences gained from 515 arterial reconstructions for chronic arterial vascular occlusion of lower limb with respect to early and late hemorrhage. In this connection hemorrhage following infections of angioplasty using artificial material is of special significance. Despite of its rare occurrence the aorto-enteric fistula should also be known.


Neotropical Monogenoidea 64. Cosmetocleithrum falsunilatum sp. n. (Monogenoidea, Dactylogyridae) parasite of the gills of Megalodoras uranoscopus (Siluriformes, Doradidae) from the Solimões river, near Iquitos, Peru.
Megalodoras uranoscopus (Eigenmann & Eigenmann) (Siluriformes, Doradidae) (the giant-talking catfish or the giant-raphael catfish), from the Peruvian Amazon, hosts a new species of Cosmetocleithrum described herein as Cosmetocleithrum falsunilatum sp. n. The male copulatory organ of the new species closely resembles that of Unilatus spp. - with multiple tight loops and non-articulated accessory piece - which reveals its morphological uniqueness among members of Cosmetocleithrum. A phylogenetic analysis using 28S rDNA of available sequences suggests that Cosmetocleithrum is composed by two basal clades, one of them composed by sequences of the new species and C. trachydorasi.


ISG15-USP18 Dysregulation by Oxidative Stress Promotes IFN-γ Secretion from CD8+ T Cells in Vitiligo.
Excessive oxidative stress is thought to play pathologic roles in cellular senescence and autoimmune disorders by inducing inflammation and breaking down immune tolerance. In this study, we sought to identify the factors linking oxidative stress to autoimmunity and cellular senescence in vitiligo, where elevated oxidative stress plays an important role. RNA sequencing analysis of hydrogen peroxide-treated melanocytes revealed upregulation of ISG15. The upregulation of ISG15 was observed in vitiligo skin tissues as well as in the blood of patients with vitiligo, whereas USP18 downregulation was observed in vitiligo melanocytes and vitiligo skin tissues. Oxidative stress induced hypermethylation of the USP18 promoter region in keratinocytes and melanocytes, and USP18 promoter hypermethylation was also confirmed in vitiligo skin tissues. Our results indicate that USP18 promoter hypermethylation caused by oxidative stress increases ISG15 expression in keratinocytes and melanocytes along with senescence changes, leading CD8+ T cells to produce IFN-γ, the main pathogenic cytokine in vitiligo. Therefore, the ISG15-USP18 network may be important in oxidative stress-induced autoimmunity and cellular senescence in vitiligo pathogenesis.


Short term deuterium depletion in drinking water reduced tumor induced oxidative stress in mice liver.
The aim of current work was able to show the oxidant effect of cancer cells found in any part of the body on the liver and to investigate the possible protective effect of deuterium-depleted water (DDW) on this oxidant effect by determining of some liver parameters. Ehrlich ascites tumor bearing BALB/c mice were used for this purpose. BALB/c mice were selected randomly and divided into four groups (n = 5 in each group) as control group, tumor group, control+DDW group, tumor+DDW group, fifteen days after tumor cell injection, liver tissue samples were taken for all groups. In the tumor group, liver lipid peroxidation, sialic acid and protein carbonyl levels, xanthine oxidase, myeloperoxidase, catalase, gamma-glutamyl transferase, sorbitol dehydrogenase, glutathione peroxidase and glutathione reductase activities, were significantly higher than those in the control group while glutathione levels and paraoxonase1, sodium potassium ATPase, glutathione-S-transferase, alanine transaminase and aspartate transaminase activities decreased significantly. Compared with the tumor group, the changes in all parameters except sialic acid, catalase, alanine transaminase and aspartate transaminase were reversed in the DDW given tumor groups, while sialic acid and catalase values continued to increase, and alanine transaminase and aspartate transaminase values continued to decrease. In conclusion, the consumption of DDW may be beneficial and protective against excessive oxidative stress in cancer complications.


Harnessing rhizobacteria to fulfil inter-linked nutrient dependency on soil and alleviate stresses in plants.
Plant rhizo-microbiome comprises complex microbial communities that colonize at the interphase of plant roots and soil. Plant growth-promoting rhizobacteria (PGPR) in the rhizosphere provide important ecosystem services ranging from the release of essential nutrients for enhancing soil quality and improving plant health to imparting protection to plants against rising biotic and abiotic stresses. Hence, PGPR serve as restoring agents to rejuvenate soil health and mediate plant fitness in the facet of changing climate. Though it is evident that nutrient availability in soil is managed through inter-linked mechanisms, how PGPR expedite these processes remain less recognized. Promising results of PGPR inoculation on plant growth are continually reported in controlled environmental conditions, however, their field application often fails due to competition with native microbiota and low colonization efficiency in roots. The development of highly efficient and smart bacterial synthetic communities by integrating bacterial ecological and genetic features provides better opportunities for successful inoculant formulations. This review provides an overview of the interplay between nutrient availability and disease suppression governed by rhizobacteria in soil followed by the role of synthetic bacterial communities in developing efficient microbial inoculants. Moreover, an outlook on the beneficial activities of rhizobacteria in modifying soil characteristics to sustainably boost agroecosystem functioning is also provided.


ACTA, a fluorescent analogue of thapsigargin, is a potent inhibitor and a conformational probe of skeletal muscle Ca2+-ATPase.
Thapsigargin is a highly potent and selective inhibitor of sarco-endoplasmic reticulum (SERCA) family of Ca2+-ATPases and a useful tool in research concerning the function of intracellular Ca2+ stores. We describe here a novel fluorescent derivative (8-O-(4-aminocinnamoyl)-8-O-debutanoylthapsigargin, termed ACTA) of this compound, acting as a Ca2+-ATPase inhibitor with a potency approaching that of thapsigargin. Binding of ACTA to the skeletal muscle sarcoplasmic reticulum vesicles results in a strong fluorescence enhancement, approximately 66% of which depends on ACTA association with Ca2+-ATPase. This specific component of ACTA fluorescence is sensitive to the E1-E2 conformational equilibrium of the pump. The combined properties of high potency and binding-dependent fluorescence suggest ACTA to be a useful probe for a range of studies involving the SERCA class of ATPases.


Removal of PCDD/Fs from contaminated sediment and released effluent gas by charcoal in a proposed cost-effective thermal treatment process.
A novel cost-effective thermal treatment technology has been proposed for the removal of PCDD/Fs from contaminated sediment and released effluent gas using charcoal as both an adsorbent and a thermal source. When a reactor was used for thermal treatment, the PCDD/Fs removal efficiency exceeded 98% from the sediment at the three different air superficial velocities employed in this study. The total PCDD/F international toxic equivalent (I-TEQ) contents, both in the treated sediments and effluent gas, were below the Japanese emission standard limit. Analysis of the PCDD/F contents in different fractions showed that large quantities of PCDDs but not PCDFs were evaporated from the sediment and adsorbed in the moist sediment column. This difference was attributed to the formation of PCDDs from pentachlorophenol (PCP) during the cooling process following the thermal treatment process in the reactor. This proposed thermal process provides a promising alternative to the conventional methods.


Pathogenesis of lupus dermatoses in autoimmune mice. IV. Association between cutaneous immunoglobulin deposition and anti-single-stranded DNA antibodies in sera.
The skin of New Zealand, MRL and BXSB mice was immunohistopathologically examined in order to study the appearance of skin immunoglobulin (Ig) deposition and its correlation with the occurrence of anti-single-stranded (ss) DNA antibodies in sera. Our studies revealed Ig deposition at the dermoepidermal junction (DEJ) in non-lesional skin and a significant age-related correlation between skin Ig deposition and serum anti-ssDNA antibodies. However, immunofluorescent study of autoimmune mice using anti-ultraviolet-irradiated DNA antiserum failed to demonstrate DNA antigens at the DEJ.


Medical mentoring via the evolving world wide web.
Mentoring, for physicians and surgeons in training, is advocated as an essential adjunct in work-based learning, providing support in career and non-career related issues. The World Wide Web (WWW) has evolved, as a technology, to become more interactive and person centric, tailoring itself to the individual needs of the user. This changing technology may open new avenues to foster mentoring in medicine. DESIGN, SYSTEMATIC REVIEW, MAIN OUTCOME MEASURES: A search of the MEDLINE database from 1950 to 2012 using the PubMed interface, combined with manual cross-referencing was performed using the following strategy: ("mentors"[MeSH Terms] OR "mentors"[All Fields] OR "mentor"[All Fields]) AND ("internet"[MeSH Terms] OR "internet"[All Fields]) AND ("medicine"[MeSH Terms] OR "medicine"[All Fields]) AND ("humans"[MeSH Terms] AND English[lang]). Abstracts were screened for relevance (UJ) to the topic; eligibility for inclusion was simply on screening for relevance to online mentoring and web-based technologies. Forty-five papers were found, of which 16 were relevant. All studies were observational in nature. To date, all medical mentoring applications utilizing the World Wide Web have enjoyed some success limited by Web 1.0 and 2.0 technologies. With the evolution of the WWW through 1.0, 2.0 and 3.0 generations, the potential for meaningful tele- and distance mentoring has greatly improved. Some engagement has been made with these technological advancements, however further work is required to fully realize the potential of these technologies.


Bicyclic peptides: solution conformation and Ca2+ binding of the heterodetic bicyclic decapeptide cyclo(Glu1-Leu2-Pro3-Gly4-Ser5-Ile6-Pro7-Ala8)- cyclo(1 gamma----5 beta)Phe9-Gly10.
The conformational behavior of a heterodetic bicyclic decapeptide (BCPLT) in the absence and in the presence of calcium ions has been studied by means of mono and two-dimensional nmr techniques. Free BCPLT possesses a quite compact structure stabilized by intramolecular bonds and turns. In the structure a cluster of carbonyls is located in a cavity that is supposed to be the cation binding site.


Herpes Simplex Virus Type 2 Seroprevalence in Pregnant Women in Urmia, Northwest of Iran, during 2014-2015
Herpes simplex virus type 2 (HSV-2) seroprevalence has been shown to be a potential sign of infection in pregnant women, and it could be applied to check HSV-2 transmission. This study evaluated the anti-HSV-2 IgG prevalence in pregnant women who were referred to health centers in Urmia, Northwest of Iran, during 2014-2015. Serum samples were collected from 86 pregnant women and tested for Anti-HSV-2-specific IgG using a commercial enzyme-linked immunosorbent assays kit. Five (5.8%) pregnant women showed the presence of Anti-HSV-2-specific IgG antibodies. Previous abortion was reported in 16 (19.7%) and 2 subjects in the seronegative and seropositive groups, respectively. Data from the present study indicate a lower number of HSV-2 seropositives among the pregnant women in Urmia. This reduction would be a result of low number of studied subjects used in the present study; hence, assessing a large sample is recommended.


Methodological and clinical challenges associated with biomarkers for psychiatric disease: A scoping review.
Over the past decade, psychiatric research has been on an important hunt for biomarkers of psychiatric disease. In psychiatry, the term "biomarker" is a broad umbrella term used to identify any biological variable that can be objectively measured and applied to a diagnosis; this includes genetic and epigenetic assessments, hormone levels, measures of neuro-anatomy and many other scientific modalities. However, despite hundreds of studies on the topic being published yearly and other medical specialties having success in discovering biomarkers, clinical psychiatric practice has not had the same success. This paper aims to consolidate the many opinions on the search for psychiatric biomarkers to suggest key methodological and clinical challenges that psychiatric biomarker research faces. Psychiatry as a specialty has many fundamental differences compared to other medical specialties in methods of diagnosing, underlying etiology and disease pathologies that may be limiting the success of biomarker research in itself and puts strict requirements on the research being conducted. The academic and clinical environment in which the research is being conducted also heavily influences the translation of the findings. Finally, once biomarkers are identified, more often than not they are inapplicable to clinical settings, unable to integrate into clinical practice and fail to outperform current diagnostic practices and guidelines. We also make six recommendations for more promising future research in psychiatric biomarkers.


Efficiency and acceptability of intrauterine contraceptive devices.
The efficacy and side effects of 6 different IUDs used by 790 women during 22826 menstrual cycles is reported. The conclusion is that modern IUDs have a negligible effect on the health of users if properly followed by regular checkups.


Neuromuscular transmission modulation by adenosine upon aging.
In infant rats adenosine A(2A) receptor-mediated modulation of neuromuscular transmission predominates over A1 receptor-mediated neuromodulation. We investigated whether aging affects this A(2A)/A(1) receptor balance. Evoked (EPPs) and miniature end plate potentials (MEPPs) were recorded from single fibers of (weeks-old) infant (3-4), young adult (12-16), older (36-38), and aged (80-90) male rat-diaphragm. The non A1/A(2A) selective agonist, 2-chloroadenosine (CADO; 30 nM) and the adenosine kinase inhibitor, iodotubericidin (ITU; 10 μM) increased mean amplitude and quantal content of EPPs in infant, young adult, and older adult rats, but not in aged rats. The facilitatory effects were prevented by the A(2A) receptor antagonist, ZM241385 (50 nM) and mimicked by the A(2A) receptor agonist, CGS21680 (10 nM). The A1 receptor agonist, 6-cyclopentyladenosine (CPA; 100 nM), decreased EPPs amplitude in all age groups. It is concluded that aging differently influences adenosine A1 receptor and A(2A) receptor-mediated presynaptic modulation of neuromuscular transmission, so that the facilitatory influence decreases upon aging, whereas the inhibitory influence remains unchanged in aged animals. The reduction of adenosine A(2A) receptors upon aging may contribute to the age-related changes in neuromuscular function.


The isolation and characterization of a mouse myeloma protein with anti-dextran activity.
A myeloma protein in ascitic fluid from BALB/c mice bearing W3129 plasma cell tumors was isolated by affinity chromatography. This protein exhibits anti-dextran activity and has been obtained in highly purified form by selective adsorption on isomaltosyl-Sepharose and elution with isomaltose solution. The isomaltosyl-Sepharose was synthesized from maltose, p-aminophenyl glucoside and cyanogen bromide-activated Sepharose by a new procedure utilizing glucosyltransferase and chemical coupling reactions. Results of gel electrophoresis, isoelectrofocusing and agar diffusion experiments showed that the purified myeloma protein consisted of 6 isomeric proteins with each isomer possessing anti-dextran activity. Data from hapten inhibition studies were interpreted to show that the W3129 myeloma protein combines with terminal isomaltosyl units of branched dextrans and oligosaccharides.


Hypercalcemia during initiation of antiretroviral therapy in human immunodeficiency virus and Leishmania coinfection: A case report.
Hypercalcemia is a common complication of many granulomatous diseases but is not typically associated with leishmaniasis. Here we report an unusual case of hypercalcemia during the initiation of antiviral therapy in a patient with acquired immunodeficiency syndrome coinfected with visceral leishmaniasis. Our patient presented with malaise and altered mental status following antiretroviral therapy initiation. He was found to have de novo hypercalcemia complicated by acute kidney injury. An extensive workup for other etiologies of hypercalcemia was negative. The patient was ultimately thought to have hypercalcemia secondary to visceral leishmaniasis in the setting of immune reconstitution inflammatory syndrome. He was treated with intravenous volume expansion, bisphosphonates, and oral corticosteroid therapy with complete resolution. This case highlights an unusual presentation of immune reconstitution inflammatory syndrome, in which proinflammatory cytokine signaling during the restoration of cellular immunity may have led to increased ectopic calcitriol production by granuloma macrophages, thereby altering bone-mineral metabolism and driving hypercalcemia.


Out-of-pocket expenditure and its correlates for institutional deliveries in private and public healthcare sectors in India: findings from NFHS 5.
Increased coverage for institutional delivery (ID) is one of the essential factors for improved maternal and child health (MCH). Though, ID increased over time, out-of-pocket expenditure (OOPE) for the care-seeking families had been found to be growing, parallelly. Hence, we estimated OOPE in public and private health centres for ID, along with their sources and attributing factors and compared state and union territory-wise, so that financial risk protection can be improved for MCH related services. We used women's data from the National Family Health Survey, 2019-2021 (NFHS-5). Reproductive aged women (15-49 years) delivering one live child in last 5 years (n = 145,386) in any public or private institutions, were included. Descriptive statistics were presented as frequency and proportions. OOPE, was summarized as median and interquartile range (IQR). To estimate the extent for each covariate's effect, linear regression model was conducted. Overall median OOPE for ID was Rs. 4066 (median OOPE: private hospitals: Rs.25600, public hospitals: Rs.2067). Health insurance was not sufficient to slash OOPE down at private facilities. Factors associated significantly to high OOPE were mothers' education, elderly pregnancy, complicated delivery, birth order of the latest child etc. CONCLUSION: A standard norm for ID should be implemented as a component of overseeing and controlling inequality. Aiding the needy is probably just one side of the solution, while the focus is required to be shifted towards reducing disparity among the health facilities, so that the beneficiaries do not need to spend on essential services or during emergencies.


Fatal cervical dislocation related to wearing a seat belt: a case report.
A case of fatal cervical dislocation in a front seat passenger restrained by a retractable three-point belt is described. A biomechanical and technical analysis is given.


Uni-axial cyclic stretch induces c-src activation and translocation in human endothelial cells via SA channel activation.
The kinase activity of c-src increased and peaked at 15 min after an application of uni-axial cyclic stretch in HUVECs followed by a translocation of c-src to Triton-insoluble fraction. Suppression of c-src by an antisense S-oligodeoxynucleotide inhibited the stretch-induced tyrosine phosphorylation and morphological changes. The stretch-induced increase in c-src activity was inhibited by FK506, a specific inhibitor for calcineurin, by Gd3+, a blocker for stretch activated channels, and by the extracellular Ca2+ depletion suggesting the involvement of SA channels. These results strongly suggest c-src plays an important role in the downstream of SA channel activation followed by the morphological changes.


An analysis on the relationship between safety awareness and safety behaviors of healthcare professionals, Ankara/Turkey.
This descriptive study aims to examine the relationship between the safety awareness of healthcare professional and their safety behaviors. The study was carried out on 418 healthcare professionals working in a training and research hospital in Ankara/Turkey. The survey method was used as data collection tool. The questionnaire consisted of 3 sections and 18 questions. First section consisted of questions on sociodemographic characteristics and, second section consisted of the awareness scale and third section consisted of safety behaviors scale. The safety awareness and safety behaviors are scored on a scale from 1 (completely disagree) to 5 (completely agree). The safety awareness and safety behaviors has an average score of 3.85 ± 0.81 and 3.56 ± 0.82, respectively. The safety awareness and safety behavior levels of healthcare professionals were found to be high. A significant positive correlation was found between safety awareness and safety behaviors and it was concluded that the increase in safety awareness led to an increase in safety behavior.


Transanal endoscopic microsurgery for giant benign rectal tumours: is large size a contraindication?
The purpose of this study is to look at our early postoperative results, recurrence rates and need for further radical surgery in treating large (> 5 cm) rectal tumours by transanal endoscopic microsurgery (TEM). Patients who underwent TEM for rectal tumours greater than 5 cm were included. Tumour diameter was determined based on fresh specimen measurements. We recorded the demographics, operative details, final pathology, length of hospital stay, complications and recurrence rates. Mean tumour size was 5.9 ± 1.5 cm. 68.4% of tumours (13/19) were in the middle part of the rectum. Three patients (15.8%) developed postoperative complications: two had postoperative bleeding (10.5%), one had wound dehiscence (5.3%). Three patients had involved margins (15.8%). After a median follow up of 25.2 months, there were two recurrences (10.5%). One patient developed rectal cancer 6 years after removal of rectal adenoma. TEM is feasible and safe for the treatment of giant benign rectal tumours. It may be an alternative method for proctectomy in selected patients.


Dermatomyositis unleashed by immune checkpoint inhibitors. Three additional cases and a review of the literature.
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of several locally advanced and metastatic tumors. They enhance the effector function of the immune system, consequently leading to different immune-related adverse events. The aim of the present study was to describe three cases of dermatomyositis (DM) triggered by ICI diagnosed at our institution and to perform a review of the literature. We performed a retrospective clinical, laboratory, and pathological evaluation of three cases of DM triggered by ICI belonging to a cohort of 187 DM patients from the Clinic Hospital Muscle Research Group of Barcelona from January 2009 to July 2022. Moreover, we undertook a narrative review of the literature from January 1990 to June 2022. Cases from our institution were triggered by avelumab, an anti-PD-1 ligand (PD-L1), nivolumab, and pembrolizumab, both anti-programmed death-1 (PD-1). One of these patients had locally advanced melanoma, and two had urothelial carcinoma. The severity and response to treatment were heterogeneous among the different cases. All were positive at high titers for anti-TIF1γ autoantibodies; in one of them, serum before the onset of ICI was available, and anti-TIF1γ autoantibodies were already present. RNA expression of IFNB1, IFNG and genes stimulated by these cytokines were markedly elevated in these patients. In conclusion, data from our patients and the narrative review suggest that early positivity to anti-TIF1γ unleashed by ICI may play a role in the development of full-blown DM, at least in some cases.


Effect of spatial smoothing on t-maps: arguments for going back from t-maps to masked contrast images.
Voxelwise statistical analysis has become popular in explorative functional brain mapping with fMRI or PET. Usually, results are presented as voxelwise levels of significance (t-maps), and for clusters that survive correction for multiple testing the coordinates of the maximum t-value are reported. Before calculating a voxelwise statistical test, spatial smoothing is required to achieve a reasonable statistical power. Little attention is being given to the fact that smoothing has a nonlinear effect on the voxel variances and thus the local characteristics of a t-map, which becomes most evident after smoothing over different types of tissue. We investigated the related artifacts, for example, white matter peaks whose position depend on the relative variance (variance over contrast) of the surrounding regions, and suggest improving spatial precision with 'masked contrast images': color-codes are attributed to the voxelwise contrast, and significant clusters (e.g., detected with statistical parametric mapping, SPM) are enlarged by including contiguous pixels with a contrast above the mean contrast in the original cluster, provided they satisfy P < 0.05. The potential benefit is demonstrated with simulations and data from a [11C]Carfentanil PET study. We conclude that spatial smoothing may lead to critical, sometimes-counterintuitive artifacts in t-maps, especially in subcortical brain regions. If significant clusters are detected, for example, with SPM, the suggested method is one way to improve spatial precision and may give the investigator a more direct sense of the underlying data. Its simplicity and the fact that no further assumptions are needed make it a useful complement for standard methods of statistical mapping.


The opportunity for and significance of alteration of ribulose 1,5-bisphosphate carboxylase activities in crop production.
Increased population and the dietary changes accompanying increased affluence are creating a need for a suggested doubling of world cereal grain production (a 3% per year compounding rate) and quadrupling of grain legume production (a 6% per year compounding rate) during this quarter century (1). CO2 enrichment of field-grown crops has demonstrated the possibility of enhancing RuBP carboxylase activity to achieve improved crop production; it increases the production of grain legumes by 50 to 100% and that of cereal grains, for which the studies are less complete, by perhaps 10 to 50%. Results of O2 alteration of growth-room legumes and cereal grains are consistent with the results of CO2 enrichment except for a second role of O2 in assimilate partitioning. It may be necessary to include other components of the system, e.g., additional soil fertility, especially for non-N2-fixing plants, to enable an improved RuBP carboxylase to increase production. No practical method--chemical, genetic, or physical--of improving RuBP carboxylase activity has been reported.


Farmácia Popular Program: changes in geographic accessibility of medicines during ten years of a medicine subsidy policy in Brazil.
The Brazilian constitution guarantees the right to health, including access to medicines. In May 2004, Brazil's government announced the "Farmácia Popular" Program (FPP) as a new mechanism to improve the Brazilian population's access to medicines. Under FPP, a selected list of medicines is subsidized by the government and provided in public and private pharmacies. The aim of this study is to describe the historical stages of the FPP and to identify associated changes in the geographical accessibility of medicines through the FPP over time. It was performed documentary review and an ecological study assessing program coverage in terms of number of facilities and a FPP Pharmacy Facilities Density (PFD) index at national and regional levels from 2004 to 2013, using the FPP database. We used geographic information system mapping to depict a pharmaceutical facilities density (PFD) index at the municipality level on thematic maps. A growth of the PFD index coincident with the phases of the FPP was noticed. In the public sector, the program started in 2004; by 2006, there was a sharp increase in the numbers of participating pharmacies, stabilizing in 2009. In the private sector, the program started in 2006; by 2009 the PFD ratio had increased substantially and it continued to grow through 2011. There was an increase in FPP coverage in most regions between 2006, when the private pharmacy component started, and 2013, but participating pharmacies remain unequally distributed across geographical regions. Specifically, the wealthy areas in the South and Southeast have higher coverage, with lower coverage mostly in the North and Northeast, relatively poorer areas with greater need for access to medicines, health care, and other basic services such as potable water and sanitization. There has been a substantial increase in the number of pharmacies participating in the FPP over time. This has led to greater program coverage and has potentially improved access to FPP medicines in the country. Nevertheless, disparities in pharmacy coverage remain among the regions.


DRAGen - A deep learning supported RVE generator framework for complex microstructure models.
In this study an improved version of the Discrete RVE Automation and Generation Framework, also called DRAGen, is presented. The Framework incorporates a generator for Representative Volume Elements (RVEs). Several complex microstructure features, extracted from real microstructures, have been added to the generator, to enable it to generate RVEs with realistic microstructures. DRAGen is now capable of reading trained neural networks as well as .csv-files as input data for the microstructure generation. Furthermore, features such as pores and inclusions, martensite bands, hierarchical substructures, and crystallographic textures can be reconstructed in the RVEs. Besides the features, the functionality for different solvers was introduced. Therefore, the code was extended by modules for the generation of Finite Element (FE) and spectral solver input files. DRAGen now has the ability to create models for three powerful multiphysics frameworks used in the community: DAMASK, Abaqus and MOOSE. The evaluation of the features, as well as the simulations performed on sample models, show that the new version of DRAGen is a very powerful tool with flexible applicability for scientists in the ICME community. Also, due to the modular architecture of the project, the code can easily be expanded with features of interest. Therefore, it delivers a variety of functions and possible outputs, which offers researchers a broad spectrum of microstructures that can be used in microstructure studies or microstructure design developments.


Optimisation of 2-cyano-pyrimidine inhibitors of cathepsin K: improving selectivity over hERG.
Several structure-guided optimisation strategies were explored in order to improve the hERG selectivity profile of cathepsin K inhibitor 1, whilst maintaining its otherwise excellent in vitro and in vivo profile. Ultimately, attenuation of clogP and pK(a) properties proved a successful approach and led to the discovery of a potent analogue 23, which, in addition to the desired selectivity over hERG (>1000-fold), displayed a highly attractive overall profile.


Elevated levels of the 90 kd heat shock protein in a proportion of SLE patients with active disease.
The human 90 kd heat shock protein (hsp 90) is associated with the receptor for glucocorticoid hormones and is believed to play a role in the cellular response to corticosteroids. The levels of this protein in the peripheral blood lymphocytes of patients with systemic lupus erythematosus (SLE) have been investigated and compared with those observed in normal individuals and patients with rheumatoid arthritis. Fifteen percent of SLE patients were found to exhibit hsp 90 levels well in excess of those observed in the other groups. These patients all had active disease. The significance of these findings is discussed both in terms of the disease processes occurring in these patients and the efficacy of steroid therapy.


Rapid progression of recurrent disease in a patient with renal cell carcinoma with vaginal metastasis.
We report a rare case of renal cell carcinoma with vaginal metastasis that recurred with rapid progression and was resistant to sunitinib and nivolumab. A 68-year-old woman presented with renal cell carcinoma and vaginal metastasis. Multiple lung metastasis appeared 3 months after simultaneous radical nephrectomy and hysterectomy with vaginal resection. Despite the treatment with sunitinib and nivolumab, the patient died 7 months after surgery. Immunohistochemical staining of primary and metastatic tumor specimens was CD8 and programmed death ligand-1 negative. Although vaginal metastasis of renal cell carcinoma is rare, lack of CD8 and programmed death ligand-1 expression may cause nivolumab resistance and may be useful markers in patients with metastatic renal cell carcinoma.


Exploring the regulation of tRNA distribution on the genomic scale.
Though up to 20% of the total RNA in bacterial cells is tRNA, the regulation of tRNA distribution on the genomic level remains unclear. tRNA distribution is governed by four processes: transcription, processing of precursor tRNA, degradation of precursor tRNA and degradation of mature tRNA. To elucidate the relationship between these processes in the regulation of tRNA production, the relative tRNA distribution was measured using a microarray specifically designed for tRNA. We developed a procedure that selectively labels 3'-CCA-containing RNAs with the fluorophores Cy3 or Cy5. The labeled tRNAs were then hybridized to microarrays printed with complementary DNA probes. The regulation of tRNA distribution in Bacillus subtilis was explored for a wild-type strain and a mutant strain with significantly decreased levels of RNase P, the enzyme required for the 5' maturation of all tRNA. The strains were either grown under a variety of conditions at doubling times ranging from 0.1 to 2.2 doublings per hour to investigate growth-related changes in the tRNA abundance or treated with the transcriptional inhibitor rifampicin to analyze mature tRNA degradation. Our results confirm that transcription and processing contribute significantly to the distribution of the 35 tRNA species in B.subtilis, and suggest a role for the degradation of precursor tRNA. Mature tRNA degradation occurs with little specificity for individual tRNA species and on the hour time-scale, indicating that degradation of mature tRNA plays only a minor role in the regulation of tRNA distribution. Aside from transcription, the final tRNA distribution appears to be derived from a balance between processing and precursor degradation activities.


Oncogene expression in related cancer lines differing in metastatic capacity.
Various murine tumor cell lines with different metastatic capacities were tested in vitro for oncogene expression, especially of the p21-Ha-ras protein. Small differences were seen in the expression of several distinct oncogenes in the case of a high metastatic lymphoma variant (ESb) and its low metastatic parental line (Eb). In one instance we observed a 30-fold Ha-ras gene amplification in a metastasis-derived cell line from a spontaneous mouse mammary carcinoma. In spite of this amplification we did not find an increased p21 expression in these cells.


Tracing enteric pathogen contamination in sub-Saharan African groundwater.
Quantitative PCR (qPCR) can rapidly screen for an array of faecally-derived bacteria, which can be employed as tracers to understand groundwater vulnerability to faecal contamination. A microbial DNA qPCR array was used to examine 45 bacterial targets, potentially relating to enteric pathogens, in 22 groundwater supplies beneath the city of Kabwe, Zambia in both the dry and subsequent wet season. Thermotolerant (faecal) coliforms, sanitary risks, and tryptophan-like fluorescence, an emerging real-time reagentless faecal indicator, were also concurrently investigated. There was evidence for the presence of enteric bacterial contamination, through the detection of species and group specific 16S rRNA gene fragments, in 72% of supplies where sufficient DNA was available for qPCR analysis. DNA from the opportunistic pathogen Citrobacter freundii was most prevalent (69% analysed samples), with Vibrio cholerae also perennially persistent in groundwater (41% analysed samples). DNA from other species such as Bifidobacterium longum and Arcobacter butzleri was more seasonally transient. Bacterial DNA markers were most common in shallow hand-dug wells in laterite/saprolite implicating rapid subsurface pathways and vulnerability to pollution at the surface. Boreholes into the underlying dolomites were also contaminated beneath the city highlighting that a laterite/saprolite overburden, as occurs across much of sub-Saharan aquifer, does not adequately protect underlying bedrock groundwater resources. Nevertheless, peri-urban boreholes all tested negative establishing there is limited subsurface lateral transport of enteric bacteria outside the city limits. Thermotolerant coliforms were present in 97% of sites contaminated with enteric bacterial DNA markers. Furthermore, tryptophan-like fluorescence was also demonstrated as an effective indicator and was in excess of 1.4μg/L in all contaminated sites.


[The value of knee joint orthoses in performance sports].
Commercial limited-motion braces are now being propagated both for prophylaxis and treatment of traumatic knee instabilities. This article presents a general classification of braces used in sports medicine and discusses their effectiveness and indication criteria.


Mechanisms of Myocardial Ischemia Inducing Sudden Cardiac Death in Athletes with Anomalous Coronary Origin from the Opposite Sinus: Insights from a computational fluid dynamic study.
The left coronary anomalous origin from the opposite sinus (L- ACAOS) constitutes the most clinically relevant arterial abnormality among the wide spectrum of coronary artery anomalies. We investigated the physiology of L-ACAOS with and without intramural course (IM) in athletes, using the computational fluid dynamic (CFD) analysis. The coronary artery circulation with L-ACAOS with and without IM has been segmented and then reconstructed, after reviewing both the angiographic and computed tomography findings of 13 consecutive athletes (10 males, mean age 45.1 ± 8.2 years) with L-ACAOS collected in our institution between 1st January 2003 and 1st January 2018. Vorticity magnitude, static pressure and wall shear stress (WSS) have been analysed in a model of L-ACAOS with no IM course and in L-ACAOS-IM at rest and during exercise. The mean vorticity magnitude and WSS significantly increased from rest to exercise in both models, in right coronary artery, left anterior descending and left circumflex coronary arteries. The mean static pressure significantly increased with exercise in IM (1.118e + 004 vs 1.164e + 004 Pa, p < 0.001) as well as the mean vorticity magnitude and the mean WSS (7012.78 1/s vs 9019.56 1/s, p < 0.001, Δ = 2006.78 1/s and 3.02 Pa vs 2.11 Pa, p < 0.001, Δ = 0.91 Pa). This net increment was transmitted to the entire left coronary system in L-ACAOS-IM but not in L-ACAOS with no IM. In L-ACAOS, different hemodynamic parameters observed in the intramural segment seem to confirm that IM is compressed during exercise. These rheological properties might propagated along the left coronary system, potentially predisposing, if confirmed in vivo, distal coronary segments to a higher risk of spasm and thrombosis in athletes.


Family planning and abortion services in COVID 19 pandemic.
Many routine and elective services have already been postponed or suspended by both Government and private setups in most parts of the world because of the unprecedented pandemic of COVID-19. Healthcare systems everywhere in the world are under pressure. Being a component of essential health services, family planning and abortion services should continue to cater the population in order to prevent the complications arising from unintended pregnancies and sudden rise in STIs. Due to airborne nature of transmission of the virus, it is advisable for all consultations relating to family planning services to be done remotely unless and until visit is absolutely necessary. Contraception initiation and continuation can be done by telemedicine in most individuals. Post partum contraception can be advised before discharge from hospital. In an individual planning for pregnancy, currently it is not advisable to discontinue contraceptive and plan for pregnancy as not much is known about the effect of the virus on foetal development. Also, pregnancy requires routine antenatal and peripartum care and complications arising from pregnancy may necessitate frequent hospital visits, exposing the individual to the risk of infection. Abortion services are time sensitive therefore should not be denied or delayed beyond legal limit. We need to change from real to virtual consultation to prevent the rise in unplanned pregnancies, sexually transmitted infections and unsafe abortions.


A critical assessment of proposed outbreaks of plague and other epidemic diseases in Ancient Egypt.
The current coronavirus disease 2019 (COVID-19) pandemic has reminded us of past epidemics. Pharaonic Egypt has often been associated with epidemics and disasters through the 10 plagues in the Bible. The aim of this study was to examine which epidemics and serious diseases can be effectively proven for Ancient Egypt through mummies and historical source texts. The biblical plagues cannot be proven because there is no agreement on the dating of the Exodus, or the Exodus is a conglomeration of memories of different events. Other diseases such as malaria and schistosomiasis have been proven for Ancient Egypt, while polio and smallpox are still uncertain. There are indications of a bubonic disease from the time of the middle 18th Dynasty, but its exact nature cannot be determined from source texts or mummies, as they are too vague.


Spinal cord repair: is tissue oxygenation an important variable?
We have demonstrated the reliability and feasibility of making PtO2 recordings from graft and host tissue in the injured spinal cord. The data suggest that the oxygen microenvironment of developing graft and host spinal tissue is clearly different from that found in normal spinal tissue or in transplants that have not survived or integrated well. These same constraints seem to apply to cavitation in developing grafts and poorly developed graft/host interfaces. The similarity between these findings and those from previous studies in other fetal vertebrates suggests that oxygen tensions in the spinal cord probably reflect the developmental status of the regenerating tissue. Our future studies will seek to define the relationship between anatomical development of transplant tissue and these functional (PtO2, microvascular development and tissue metabolism) indicators of graft development. These investigations should also provide a background for those later studies which seek to establish the mechanisms by which these relationships come about i.e. oxygen consumption of host/transplant tissue, blood flow to transplants, studies of glycolytic metabolism (2-DG autoradiography), etc. In this way, we can begin to understand the role of tissue metabolism in graft-mediated repair.


ShRNA-mediated gene silencing of lipoprotein lipase improves insulin sensitivity in L6 skeletal muscle cells.
In previous studies, we demonstrated that down-regulation of lipoprotein lipase in L6 muscle cells increased insulin-stimulated glucose uptake. In the current study, we used RNA interference technology to silence the LPL gene in L6 cells and generate a LPL-knock-down (LPL-KD) cell line. ShRNA transfected cells showed a 88% reduction in the level of LPL expression. The metabolic response to insulin was compared in wild-type (WT) and LPL-KD cells. Insulin-stimulated glycogen synthesis and glucose oxidation were respectively, 2.4-fold and 2.6-fold greater in LPL-KD cells compared to WT cells. Oxidation of oleic acid was reduced by 50% in LPL-KD cells compared to WT cells even in the absence of insulin. The contribution of LPL in regulating fuel metabolism was confirmed by adding back purified LPL to the culture media of LPL-KD cells. The presence of 10 μg/mL LPL resulted in LPL-KD cells reverting back to lower glycogen synthesis and glucose oxidation and increased fatty acid oxidation. Thus, LPL depletion appeared to mimic the action of insulin. These finding suggests an inverse correlation between muscle LPL levels and insulin-stimulated fuel homeostasis.


Identification of plaque location using indocyanine green videoangiography during carotid endarterectomy.
The aim of the present study was to assess whether surgical microscope-based indocyanine green (ICG) videoangiography (ICG-VA) using FLOW 800 software provides useful evaluation of blood flow during carotid endarterectomy (CEA). Twenty CEA procedures were performed in 19 patients between July 2011 and January 2012. ICG was injected intravenously before and after CEA, and ICG-VA video sequences were analyzed using FLOW 800. Regions of interest were identified in the common carotid artery, plaque, internal carotid artery, and external carotid artery, and changes in intensity values were evaluated. The distal and proximal ends of the carotid plaque were identified in 87.5 and 75 % of cases, respectively. After CEA, intensity values in the common carotid artery, plaque, internal carotid artery, and external carotid artery had increased by 162 ± 129, 337 ± 212, 139 ± 151, and 177 ± 143, respectively. The intensity values in the region of the plaque showed the greatest improvement. ICG-VA can provide information regarding plaque location vessel patency during CEA. FLOW 800 software provides semiquantitative information regarding blood flow, especially in cases of severe stenosis with collapse of the internal carotid artery.


Detection of newly discovered KIs virus in India.
KIs virus (KIs-V) is a putative new hepatitis virus recently identified from Japan. Prevalence of this virus was found to be significantly higher in individuals with past exposure to hepatitis E virus and having moderately raised alanine aminotransferase levels. The present work was undertaken to see the circulation of this virus in India. Blood samples (n=648) collected during hepatitis E outbreaks from different states (1990-2014) were screened by PCR. One anti- HEV IgM positive serum was found to be positive for two closely related viruses, one with 100% and other with 94.4% homology with the KIs-V sequence reported from Japan. This is the first evidence of KIs-V occurrence in India. Significance of association between KIs-V and hepatitis E virus still remains unanswered. Further studies are needed for understanding pathogenesis of KIs-V in humans.


Quercetin Downregulates Cyclooxygenase-2 Expression and HIF-1α/VEGF Signaling-Related Angiogenesis in a Mouse Model of Abdominal Aortic Aneurysm.
Abdominal aortic aneurysm (AAA) development has been characterized by increased expression of vascular endothelial growth factor (VEGF), which contributes to angiogenesis via cyclooxygenase-2 (COX-2). Quercetin, one of the most common and well-researched flavonoids and abundant in vegetables and fruits, has beneficial effects in inhibiting angiogenesis. This study investigated the antiangiogenic effects of quercetin on experimental aneurysms. We utilized the in vivo AAA mouse model induced by the periaortic application of CaCl2 to examine the effectiveness of quercetin in blocking angiogenesis. Quercetin was administered at 60 mg/kg once daily on the day of the AAA induction and then continued for 6 weeks. Celecoxib, a selective COX-2 inhibitor, was used as the positive control. Our results demonstrated that quercetin significantly attenuated aneurysm growth in AAA mice and medial neovascularization. Accordingly, quercetin decreased the expression of proangiogenic mediators, including VEGF-A, intercellular adhesion molecule-1, vascular cell adhesion molecule 1, and vascular endothelial cadherin. Quercetin treatment also inhibited the expression of COX-2 and hypoxia-inducible factor 1α (HIF-1α). It was also found that quercetin-3-glucuronide, a major quercetin metabolite, downregulated the expression of COX-2, HIF-1α, VEGF-A, and matrix metalloproteinase activities in aortic vascular smooth muscle cells isolated from AAA mice. Quercetin attenuates neovascularization during AAA growth, and this effect is mediated via the inhibition of COX-2, which decreases HIF-1α/VEGF signaling-related angiogenesis.


Pulse oxygen saturation levels and arterial oxygen tension values in newborns receiving oxygen therapy in the neonatal intensive care unit: is 85% to 93% an acceptable range?
Our aim was to define the relationship of PaO(2) and pulse oxygen saturation values during routine clinical practice and to evaluate whether pulse oxygen saturation values between 85% and 93% were associated with PaO(2) levels of <40 mmHg. Prospective comparison of PaO(2) and pulse oxygen saturation values in 7 NICUs at sea level in 2 countries was performed. The PaO(2) measurements were obtained from indwelling arterial catheters; simultaneous pulse oxygen saturation values were recorded if the pulse oxygen saturation values changed <1% before, during, and after the arterial gas sample was obtained. We evaluated 976 paired PaO(2)/pulse oxygen saturation values in 122 neonates. Of the 976 samples, 176 (18%) from infants breathing room air had a mean pulse oxygen saturation of 93.9 +/- 4.3% and a median of 95.5%. The analysis of 800 samples from infants breathing supplemental oxygen revealed that, when pulse oxygen saturation values were 85% to 93%, the mean PaO(2) was 56 +/- 14.7 mmHg and the median 54 mmHg. At this pulse oxygen saturation level, 86.8% of the samples had PaO(2) values of 40 to 80 mmHg, 8.6% had values of <40 mmHg, and 4.6% had values of >80 mmHg. When the pulse oxygen saturation values were >93%, the mean PaO(2) was 107.3 +/- 59.3 mmHg and the median 91 mmHg. At this pulse oxygen saturation level, 39.5% of the samples had PaO(2) values of 40 to 80 mmHg and 59.5% had values of >80 mmHg. High PaO(2) occurs very rarely in neonates breathing supplemental oxygen when their pulse oxygen saturation values are 85% to 93%. This pulse oxygen saturation range also is infrequently associated with low PaO(2) values. Pulse oxygen saturation values of >93% are frequently associated with PaO(2) values of >80 mmHg, which may be of risk for some newborns receiving supplemental oxygen.


Rhabdomyolysis: a genetic perspective.
Rhabdomyolysis (RM) is a clinical emergency characterized by fulminant skeletal muscle damage and release of intracellular muscle components into the blood stream leading to myoglobinuria and, in severe cases, acute renal failure. Apart from trauma, a wide range of causes have been reported including drug abuse and infections. Underlying genetic disorders are also a cause of RM and can often pose a diagnostic challenge, considering their marked heterogeneity and comparative rarity.In this paper we review the range of rare genetic defects known to be associated with RM. Each gene has been reviewed for the following: clinical phenotype, typical triggers for RM and recommended diagnostic approach. The purpose of this review is to highlight the most important features associated with specific genetic defects in order to aid the diagnosis of patients presenting with hereditary causes of recurrent RM.


Pterostilbene, a bioactive component of blueberries, suppresses the generation of breast cancer stem cells within tumor microenvironment and metastasis via modulating NF-κB/microRNA 448 circuit.
Tumor-associated macrophages (TAMs) have been shown to promote metastasis and malignancy. Pterostilbene, a natural stilbene isolated from blueberries, has been suggested for anti-cancer effects. Here, we explored the potential cancer stem cells (CSCs)/TAM modulating effects of pterostilbene in breast cancer. Using flowcytometric and Boyden chamber assay, we showed MCF7 and MDA-MB-231 cells cocultured with M2 TAMs exhibited increased percentage of CD44(+) /CD24(-) CSC population and migratory/invasive abilities. RT-PCR results showed that CD44(+) /CD24(-) cells expressed an increased level of HIF-1α, β-catenin, Twist1, and NF-κB and enhanced tumor sphere forming ability. Additionally, pterostilbene treatment dose dependently overcame M2 TAM-induced enrichment of CSCs and metastatic potential of breast cancer cells. Mechanistically, pterostilbene suppressed NFκB, Twist1, vimentin, and increased E-cadherin expression. Using siRNA technique, we demonstrated that pterostilbene-mediated NFκB downregulation was correlated to an increased amount of microRNA 448. Finally, pterostilbene-mediated suppression in tumorigenesis and metastasis was validated by noninvasive bioluminescence in mice bearing M2 TAM cocultured MDA-MB-231 tumor. Pterostilbene effectively suppresses the generation of CSCs and metastatic potential under the influence of M2 TAMs via modulating EMT associated signaling pathways, specifically NF-κB/miR488 circuit. Thus, pterostilbene could be an ideal anti-CSC agent in clinical settings.


Machine Learning & Molecular Radiation Tumor Biomarkers.
Developing radiation tumor biomarkers that can guide personalized radiotherapy clinical decision making is a critical goal in the effort towards precision cancer medicine. High-throughput molecular assays paired with modern computational techniques have the potential to identify individual tumor-specific signatures and create tools that can help understand heterogenous patient outcomes in response to radiotherapy, allowing clinicians to fully benefit from the technological advances in molecular profiling and computational biology including machine learning. However, the increasingly complex nature of the data generated from high-throughput and "omics" assays require careful selection of analytical strategies. Furthermore, the power of modern machine learning techniques to detect subtle data patterns comes with special considerations to ensure that the results are generalizable. Herein, we review the computational framework of tumor biomarker development and describe commonly used machine learning approaches and how they are applied for radiation biomarker development using molecular data, as well as challenges and emerging research trends.


Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon-beta production by interfering with the RIG-I signaling pathway.
Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an economically important swine disease that has been devastating the swine industry since the late 1980s. Accumulating evidences have revealed that PRRSV infection fails to induce type I interferon (IFN-alpha/beta), which are normally induced rapidly during virus replication in virus-infected cells. However, the potential mechanisms remain largely unclear. In this study, we showed that PRRSV infection activated the signal transduction components of NF-kappaB and AP-1, but not of interferon regulatory factor 3 (IRF3), an essential IFN-beta transcription factor. Furthermore, PRRSV infection significantly blocked synthetic dsRNA-induced IFN-beta production and IRF3 nuclear translocation. To better understand the upstream signaling events that suppress IRF3 activation, we further investigated the roles of individual components of the retinoic acid-inducible gene I (RIG-I)- and Toll-like receptor 3 (TLR3)-mediated signaling pathway for IFN-beta production during PRRSV infection. We observed that PRRSV infection significantly inhibited dsRNA-induced IRF3 activation and IFN-beta generation by inactivating IFN-beta promoter stimulator 1 (IPS-1), an adaptor molecule of RIG-I. In contrast, PRRSV infection only partially reduced the activation of TIR domain-containing adaptor inducing IFN-beta (TRIF), an adaptor molecule of TLR3. Our results suggest that PRRSV infection suppresses production of IFN-beta primarily by interfering with the IPS-1 activation in the RIG-I signaling pathway.


Late hematogenous infection of penile prostheses.
Late deep wound infection caused by hematogenous bacterial spread from a remote focus is a rare but disastrous complication of prosthetic devices. Six patients with probable late hematogenous infection are described. The initial implantation was free of contamination and infection, and a long functional interval ensued. A febrile process associated with a painful, swollen penis followed a probable remote infection source that was not covered with prophylactic antibiotics. All prostheses required removal. Prophylactic antibiotics may prevent these late hematogenous infections.


BRCA1/2 Testing in Massachusetts Among Women With Private Insurance or Medicaid, 2011-2015.
Testing for BRCA1/2 mutations has increased among privately insured women in the United States. However, little is known about testing rates or trends among women with Medicaid. We sought to determine whether BRCA1/2 testing rates differed between women with private insurance compared with women with Medicaid in a state where both insurance types cover the test, and to compare testing trends from 2011 to 2015. We conducted a retrospective cohort study of medical claims from January 2011 through June 2015. We included Massachusetts women aged 18-64 with private insurance or Medicaid and at least 12 months of continuous enrollment. We used multivariable linear regression to examine the association of insurance type, age, and time with testing rates. Mean monthly BRCA1/2 testing rates were lower among women with Medicaid compared with those with private insurance. Among privately insured women, mean monthly rates rose from 9.3 per 100,000 in 2011 to 18.4 per 100,000 in 2015, while among Medicaid-insured women, rates increased from 3.7 to 14.7. There was no difference in the monthly rate of increase in both groups (P=0.07). In adjusted analyses, rates were lower among Medicaid-insured women (7 fewer tests per month than privately insured women, P<0.001), and differed by age, with women aged 44-54 most likely to receive testing and women 18-34 the least likely. BRCA1/2 testing rates were lower among women insured by Medicaid compared with those with private insurance, though rates increased from 2011 to 2015 among both groups of women at a similar rate.


[Spinal anesthesia (saddle block) in Friedreich's diseases].
Friedreich's disease is a very rare neurological disorder that causes degeneration of the posterior roots of the spinal nerves and progresses to the anterior roots, even in young adults. Hospital emergency teams face the question of choice of anaesthesia in such patients should general anaesthesia be preferred to regional anaesthesia. We report a 36-year-old patient with spinocerebellar heredoataxia (Friedreich's disease) who underwent a proctological procedure after administration of spinal anaesthesia with 3 mg hyperbaric bupivacaine in a sitting position. Both the intra- and post-operative courses were unremarkable; in particular, with regard to the underlying neurological disease, no complications were observed.


Efficacy and Safety of a Novel Three-Step Medial Release Technique in Varus Total Knee Arthroplasty.
We investigated the efficacy and safety of our novel three-step medial release technique in varus total knee arthroplasty (TKA) over time. Two hundred sixty seven consecutive varus TKAs were performed by applying the algorithmic release technique which consisted of sequential release of the deep medial collateral ligament (step 1), the semimembranosus (step 2), and multiple needle puncturing of the superficial medial collateral ligament (step 3). One hundred seventeen, 114, and 36 knees were balanced after step 1, 2, and 3 releases, respectively. There were no significant differences in changes of medial and lateral laxities between groups in over a year. Our novel stepwise medial release technique was efficacious and safe in balancing varus knees during TKA.


CAN'T MISS: conquer any number task by making important statistics simple. Part 7. Statistical process control: x-s control charts.
Statistical process control (SPC) can be thought of as the frequent monitoring of processes using inferential statistics. The feature that distinguishes SPC from the typical use of inferential statistics for analyzing populations is that in the former frequent samples are taken over time, whereas in inferential statistics a single sample is generaLLy taken before and after some intervention or treatment. An x-s control chart is used to monitor a continuous variable that reflects the output of a process. The x-s control chart is a graph that includes serial sample means (x) as the variables of interest, a centerline that represents the grand mean of the samples (x), and upper control limit (UCL) and lower control limit (LCL) that represent three standard errors (SEx) above and below the centerline. An x-s control chart is used to estimate with 99.7% confidence that the population mean of a continuous output variable was within the interval defined by the UCL and LCL during a period of baseline monitoring. It is further assumed that if the process remains stable, future population means wiLL remain between the control Limits for additional process outputs. Control charts allow the evaluation of both common- and special-cause variation. AnaLysis of the common-cause variation aLLows an assessment of the current process performance. Special-cause variation is identified when there is a sample mean that is beyond the UCL or LCL.


Relationship between granulocyte elastase and C3a under protamine dosing in on-pump cardiac surgery.
The complement cascade and granulocytes are activated in on-pump cardiac surgery. If activation of complement directly regulates granulocytes, granulocyte elastase (GEL) should increase significantly after protamine administration. We examined the effect of protamine on granulocytes by protamine administration and observation of the effect on GEL and C3a. Thirty patients who underwent coronary artery bypass grafting were randomly assigned to two groups. In 15 patients, protamine was administered 5 min after the termination of cardiopulmonary bypass, and was administered 35 min after cardiopulmonary bypass in the other 15 patients. All patients were perfused with heparin-coated circuits and received 300 IU/kg heparin and 3 mg/kg protamine. GEL and C3a concentrations were measured at 7 time points. GEL concentrations increased significantly just before aortic declamping and did not increase significantly after protamine administration. C3a concentrations, however, did not increase during cardiopulmonary bypass and did increase significantly after protamine administration. This study indicates that GEL does not increase after protamine administration and that complement concentration does not directly affect GEL release.


High radio-isotope uptakes in patients with hypothyroidism.
Hypothyroidism is usually associated with a low radio-isotope uptake by the thyroid gland. We report 8 cases of Hashimoto's thyroiditis with clinical and biochemical hypothyroidism and with borderline high or overtly increased technetium-99m pertechnetate and/or iodine-131 uptakes.


Acute community-acquired bacterial meningitis in adults admitted to the intensive care unit: clinical manifestations, management and prognostic factors.
To study the clinical features, management and prognostic factors associated with adverse clinical outcome in a series of patients with acute community-acquired bacterial meningitis admitted to the intensive care unit (ICU). Descriptive, prospective study at two ICUs of a university hospital over a 6-year period. Sixty-four episodes in 62 adults with acute community-acquired bacterial meningitis admitted to the ICU. Most of the patients (95.3%) were admitted to the ICU presenting with altered mental status (the median value of Glasgow Coma Scale (GCS) was 11). Overall mortality rate was 10.9% (7 patients) and 11 (17.1%) developed adverse clinical outcome (death or severe neurologic deficit). The features associated with adverse clinical outcome were: age over 50 years, seizures or focal neurologic signs at admission, a GCS score of 10 or less and an APACHE II score more than 13 at admission to the ICU. Only the severity of the disease determined according to the APACHE II scale was independently associated with adverse clinical outcome after a multivariate analysis was performed (adjusted odds ratio =8.74; 95% CI =1.70-44.77; p=0.009). All patients were empirically treated with third-generation cephalosporins and dexamethasone was used in 40 cases (62.5%). Ten patients (15.6%) received mannitol, nine of them after a transcranial Doppler sonography recording had been performed. In adult patients with acute community-acquired bacterial meningitis admitted to the ICU, the overall severity of the disease within 24 h of admission may be the major indicator of adverse in-hospital clinical outcome.


Serial Evaluation of Endometrial Blood Flow for Prediction of Pregnancy Outcomes in Patients Who Underwent Controlled Ovarian Hyperstimulation and In Vitro Fertilization and Embryo Transfer.
To investigate endometrial blood flow during the menstrual cycle in patients undergoing controlled ovarian hyperstimulation (COH), in vitro fertilization (IVF), and embryo transfer (ET) and prediction of pregnancy outcomes based on these characteristics. Endometrial blood flow was measured in 35 patients undergoing COH and IVF-ET (nonpregnant [n = 15] and pregnant [n = 20]) by measuring the resistive index (RI) of the uterine radial artery using 2-dimensional Doppler ultrasonography. Measurements were obtained in 4 different phases of the menstrual cycle day: early follicular, midfollicular, preovulatory, and midluteal. The uterine radial artery RI during the early follicular phase was significantly lower in the pregnant group than in the nonpregnant group (mean ± SD, 0.61 ± 0.01 versus 0.66 ± 0.01; P = .029). There was no significant difference between groups during the midfollicular, preovulatory, and midluteal phases (mean ± SD, 0.60 ± 0.02 versus 0.60 ± 0.01; P = .84; 0.61 ± 0.09 versus 0.57 ± 0.01; P = .12; 0.54 ± 0.01 versus 0.57 ± 0.02; P = .32, respectively). There was a significant difference in endometrial blood flow between the pregnant and nonpregnant groups during each phase (P = .016). The difference in the changes of the uterine radial artery RI from the preovulatory to midluteal phase between the pregnant and non pregnant groups was significant (-0.002 ± 0.03 versus 0.07 ± 0.02; P = .038). Increased endometrial blood flow during the midluteal phase, compared to the preovulatory phase, may correlate with successful COH and IVF-ET. Additionally, sufficient blood flow at initiation of COH may affect COH and IVF-ET results.


Testing the Question-Behavior Effect of Self-Administered Surveys Measuring Youth Drug Use.
Concern that asking about a specific behavior could elicit that behavior is often cited as a reason that communities and schools should not administer surveys about youth drug use. In this study, we investigated if this question-behavior effect exists related to substance use. We examined if simply asking a student about their current drug use leads to an increase in drug use 1 year later. This study tests the validity of the question-behavior effect on youth drug use in a longitudinal panel of 2,002 elementary school students. The sample of students was drawn from the Community Youth Development Study, a community-randomized test of the Communities That Care prevention system. If the prevalence of self-reported drug use in sixth grade in a sample surveyed in fifth and sixth grades was higher than in an accretion sample surveyed only in sixth grade, the difference could indicate a question-behavior effect. Results from logistic regression analyses did not provide any evidence of a question-behavior effect on 30-day or lifetime prevalence of alcohol, tobacco, inhalant, or marijuana use reported in sixth grade. Asking youth about drug use in a survey did not increase the rates of self-reported drug use measured 1 year later. The absence of evidence of a question-behavior effect should ease concerns of communities and schools when administering surveys asking youth about their drug use.


Effects of urea on the cattle tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).
This study aimed at evaluating the effects of urea on Rhipicephalus (Boophilus) microplus. The experiment was divided into two stages. In Stage I, Brachiaria brizantha was placed into 30 pots, each with an area of 18 cm(2).These were divided into three groups of ten pots each: G1 non-treated control group, G2 treated with 15 g of urea per pot and G3 treated with 15 g of urea+10% of ammonium sulphate. Three engorged female ticks were placed in each pot and then 1.8l of water were added. In the second stage, a control group was maintained without the addition of urea and another group was treated with urea, each group comprising ten Mombaça grass (Panicum maximum cv. Mombaça) beds. On day zero, 12 engorged females were placed in each grass bed where were then fertilized with 60 g of urea per bed, only in the grass beds of the treated group. On the 27th day, the grass was cut in beds 1-5 in both groups and beds 1-5 in the treated group were fertilized a second time. On the 40th day, pieces of white flannel measuring 1.60 m × 1.00 m were spread over the grass to check for larvae presence. In stage I, observations conducted 24h after contact with urea showed a 100% death rate among the engorged females in G2; in group 3, only one engorged female still remained alive. In stage II, the counting of larvae reported 85.97% (P<0.0001) fewer parasites in the treated group compared to the control group.


Essential tremor: the most common form of cerebellar degeneration?
The degenerative cerebellar ataxias comprise a large and heterogeneous group of neurological diseases whose hallmark clinical feature is ataxia, and which are accompanied, to variable degrees, by other features that are attributable to cerebellar dysfunction. Essential tremor (ET) is an exceptionally common neurological disease whose primary motor feature is action tremor, although patients often manifest intention tremor, mild gait ataxia and several other features of cerebellar dysfunction. In this paper, we review the abundant evidence derived from clinical, neuroimaging and postmortem studies, linking ET to cerebellar dysfunction. Furthermore, we review the combination of clinical, natural history and postmortem features suggesting that ET is neurodegenerative. We then compare the prevalence of ET (400 - 900 cases per 100,000) to that of the other cerebellar degenerations (ranging from <0.5 - 9 cases per 100,000, and in composite likely to be on the order of 20 cases per 100,000) and conclude that ET is 20 to 45 times more prevalent than all other forms of cerebellar degeneration combined. Given the data we present, it is logical to conclude that ET is, by far, the most common form of cerebellar degeneration.


Myelomeningocele: characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease.
The purpose of this study was to determine how closely the surgically induced sheep myelomeningocele (MMC) model resembles the central nervous system derangements seen in human disease, and identify which aspects of MMC are the result of the early neuronal developmental defect, and which are secondary to the cerebrospinal fluid (CSF) drainage. An MMC-like lesion was created surgically in 16 fetal sheep at 75 days' gestation: 5 died in utero, 7 underwent no fetal repair, 4 were repaired (2-layer closure or biological glue) at 100 days' gestation. MMC sheep were delivered at term and allowed to survive up to 17 days for analysis of behavioral status and feeding behavior. Animals not repaired in utero were repaired at birth. All lambs were sacrificed and analyzed for hindbrain herniation, hydrocephalus, and other CNS derangements. Hindbrain herniation was observed in 43% of animals not repaired in utero, and in 1 lamb repaired with Bioglue. No animal developed hydrocephalus or other CNS derangements. Although this sheep MMC-like model reproduces the CSF leak, but not the developmental defect seen in humans, it suggests CSF leak contributes to hindbrain herniation seen in humans. This model may be useful to develop new minimally invasive techniques to halt CSF leak in utero.


Contamination of food-borne parasites from green-leafy vegetables sold in public markets of San Jose City, Nueva Ecija, Philippines.
Vegetables contribute a significant portion of the typical Filipino diet. Hence, it is a concern that based on previous studies, vegetables could potentially act as vectors for parasitic transmission. This study aimed to further investigate these occurrences by assessing the food-borne parasitic contamination of vegetables sold in the public markets of San Jose City, Nueva Ecija. A total of 288 vegetable samples (cabbage, lettuce and Chinese cabbage) were collected from March to August 2018 in the wet market and supermarkets of San Jose City, Nueva Ecija. Results showed that 116 out of 288 (40.28%) vegetable samples were positive of food-borne parasites such as Ascaris sp., Hymenolepis diminuta, Isospora sp., Hookworm/Strongylid sp./free-living nematode larvae, Strongylid sp. egg, Taenia sp., and Trichuris sp. Isospora sp. has the highest contamination rate (16.67%) and mean density (13 eggs/g) from the sampled vegetables. Possible sources of these identified parasites are contaminated soil and water harbored by the sampled vegetables during cultivation, transport and handling/preparation by vendors. Further studies are needed to establish a more reliable information that could lead to public health improvement and food safety awareness for the community.


Early symptomatic neurosyphilis and ocular syphilis: A comparative study between HIV-positive and HIV-negative patients.
Since the 2000s, there has been an increase in prevalence of neurosyphilis (NS) and ocular syphilis (OS). As data about symptomatic NS/OS is limited, this study aims to assess the characteristics of symptomatic NS/OS, according to HIV status. We compared the clinical and biological presentation of early symptomatic NS/OS and its outcome in HIV-positive and HIV-negative patients. Ninety-six patients (93% men, 49% HIV-positive) were included from 2000 to 2016 in two centers, with 67 (69%) having OS, 15 (16%) NS, and 14 (14%) both. HIV-positive patients were younger (P=0.006) and more likely to be males having sex with males (P=0.00048) or to have a history of syphilis (P=0.01). Among 81 OS, there were 43 posterior uveitis (57%), and bilateral involvement was more common in HIV-positive patients (62% versus 38%, P=0.045). Among 29 NS there were 21 cases of cranial nerve involvement (72%), seven meningitis (24%) and 11 paresthesia (38%). Involvement of the VIIIth cranial nerve was the most common (16 cases). Treponemal tests were more commonly found positive in cerebrospinal fluid in HIV-positive patients (88% versus 76%, P=0.04). Visual acuity (VA) always improved after treatment (initial VA logMAR 0.8±0.8 versus 0.1±0.1 at 3 months), but 32% and 18% of the patients still had neurological or ocular impairment respectively six and 12 months after treatment. Non-treponemal serological reversion was observed in 43/50 patients (88%) at six months. HIV infection has no consequence on the outcome of NS and OS. Sequelae are common, emphasizing the importance of prevention, and screening, and questioning enhanced treatment.


An evaluation of the severity and progression of epistaxis in hereditary hemorrhagic telangiectasia 1 versus hereditary hemorrhagic telangiectasia 2.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia whose hallmark symptom is spontaneous recurrent epistaxis. Two major genetic subtypes of this syndrome are HHT1 and HHT2. Severity of epistaxis ranges from occasional low-volume bleeding to frequent large-volume hemorrhage. This study evaluated the severity and progression of epistaxis in HHT1 versus HHT2. Retrospective cohort study. A retrospective chart review was performed for 183 genotyped HHT patients seen at our center from 2010 to 2013. Data collected included epistaxis severity score (ESS), age of epistaxis onset, number and type of treatments, age at which treatments were sought, complete blood count values, ferritin, number of telangiectases, blood transfusions, iron therapy history, and patient demographics. 115 subjects with HHT2 were compared to 68 with HHT1. Subjects with HHT2 had a higher ESS compared to HHT1 (P = .043) and a later age of onset of epistaxis (P = .005). HHT2 subjects were more likely to use oral iron (P = .032) and were more likely to seek interventions to control their epistaxis (P = .029). HHT2 is associated with more severe epistaxis and a subsequent higher rate of interventions, requiring more aggressive therapy as compared to HHT1. 4.


Experiences of recovery and a new care pathway for people with pain after total knee replacement: qualitative research embedded in the STAR trial.
Approximately 20% of people experience chronic postsurgical pain after total knee replacement. The STAR randomised controlled trial (ISCRTN92545361) evaluated the clinical- and cost-effectiveness of a new multifaceted and personalised care pathway, compared with usual care, for people with pain at three months after total knee replacement. We report trial participants' experiences of postoperative pain and the acceptability of the STAR care pathway, which consisted of an assessment clinic at three months, and up to six follow-up telephone calls over 12 months. Semi-structured interviews were conducted with 27 people (10 men, 17 women) between February 2018 and January 2020. Participants were sampled purposively from the care pathway intervention group and interviewed after completion of the final postoperative trial questionnaire at approximately 15 months after knee replacement. Interviews were audio-recorded, transcribed, anonymised and analysed using inductive thematic analysis. Many participants were unprepared for the severity and impact of postoperative pain, which they described as extreme and constant and that tested their physical and mental endurance. Participants identified 'low points' during their recovery, triggered by stiffening, pain or swelling that caused feelings of anxiety, depression, and pain catastrophising. Participants described the STAR assessment clinic as something that seemed "perfectly normal" suggesting it was seamlessly integrated into NHS care. Even in the context of some ongoing pain, the STAR care pathway had provided a source of support and an opportunity to discuss concerns about their ongoing recovery. People who have knee replacement may be unprepared for the severity and impact of postoperative pain, and the hard work of recovery afterwards. This highlights the challenges of preparing patients for total knee replacement and suggests that clinical attention is needed if exercise and mobilising is painful beyond the three month postoperative period. The STAR care pathway is acceptable to people with pain after total knee replacement.


In-Vitro Screening and Biosynthesis of Secondary Metabolites from a New Streptomyces sp. SA1 from a Marine Environment.
Streptomyces sp. produces various antibiotic agents and the number of lead molecules from the genus Streptomyces increased rapidly in recent years. Drug resistance against various commercially available antibiotics is one of the important problems throughout the world. Streptomyces spp. produce various antimicrobials with potent activity against drug-resistant bacteria. Streptomyces sp. SA1 was isolated from the marine environment for the biosynthesis of antibiotics. The important variables influencing secondary metabolite biosynthesis were optimized to increase the biosynthesis of antimicrobial agents using the traditional method and statistical approach. Streptomyces sp. SA1 produced novel antibiotics and the process variables were optimized by the traditional method (One-variable-at-a-time approach). Maltose showed maximum antimicrobial activity (220 U/mL). Analysis of the nitrogen, the effect of nitrogen sources revealed that beef extract incorporated culture medium showed rich antibacterial activity (188/mL). Among the ionic sources, KCl significantly influenced antibiotic production. Maltose, beef extract and KCl were considered as the most influencing medium components. Antimicrobial agent biosynthesis was achieved with maltose 1.22 g/L, beef extract 0.93 g/L and KCl 0.27 g/L in response surface methodology. Actinomycetes, especially Streptomyces, play an important role as a source for bioactive compounds that are used to treat infections, and many other diseases. The isolated Streptomyces sp. was a good producer of antibacterial agent, which required various nutritional supplements in the culture medium. The optimized medium components investigated in this study will be useful for future studies with the mass production of secondary metabolites.


Efficacy of Ultrasound-Guided Thoracic Paravertebral Block on Postoperative Quality of Recovery in Patients Undergoing Percutaneous Nephrolithotomy: A Randomized Double-Blind Placebo-Controlled Trial.
This study aimed to examine the effectiveness of ultrasound-guided thoracic paravertebral block on postoperative quality of recovery in patients undergoing percutaneous nephrolithotomy. In this randomized, double-blind, placebo-controlled trial, we enrolled patients scheduled for unilateral percutaneous nephrolithotomy. Patients were randomly allocated to receive thoracic paravertebral block either with 20 mL of 0.5% ropivacaine (PVB group) or an equal volume of saline (control group). The primary outcome was the quality of patient recovery at 24 h postoperatively, assessed using the 15-item Quality of Recovery scale. The secondary outcomes included the area under the curve of pain scores over time, time to first rescue analgesia, and postoperative 24 h morphine consumption. We analyzed the data of 70 recruited participants. The median Quality of Recovery-15 score at 24 h postoperatively was 127 (interquartile range, 117-133) in the PVB group, which was significantly higher than 114 (interquartile range, 109-122) in the control group, with a median difference of 10 points (95% confidence interval, 5-14; P<0.001). The area under the curve of pain scores over time was lower in patients receiving thoracic PVB than in those receiving saline block (P<0.001). The median time to first rescue analgesia in the PVB group (10.8 h, interquartile range 7.1-22.8 h) was longer than that in the control group (1.9 h, interquartile range 0.5-4.3 h) (P<0.001). Similarly, the median postoperative 24-hour morphine consumption was nearly half as low in the PVB group as in the control group (P<0.001). The occurrence of postoperative nausea and vomiting, and pruritus were significantly higher in the control group (P=0.016 and P=0.023, respectively). Preoperative ultrasound-guided single injection of thoracic paravertebral block with ropivacaine improved the postoperative quality of recovery and analgesia in patients undergoing percutaneous nephrolithotomy.


Design and evaluation of learning strategies for a group of radiographers in radiostereometric analysis (RSA).
The purpose of this study was to design and evaluate a radiostereometric analysis (RSA) program aimed at radiographers in order to increase their cognitive and practical skills, thereby increasing image quality and minimizing exposure repetition. Twenty radiographers were randomized into two identically sized study groups. Training consisted of a theoretical and practical workshop using a phantom. Tests were performed to compare the effect of training to nontraining, and the effect of time duration on the maintenance of RSA skills. The effect of training was measured by a written test and three defined parameters influencing image quality. Group A reduced significantly (p < 0.001) by 31.3 mm (21-31%) the distance between the centrum of the prosthesis (CP) and the centrum of the calibration field (CCF) and increased the number of beads (NB) visible by 3.6 (out of 18). A further significant reduction of 5.1 mm (p = 0.023), 1.0 bead more (p < 0.001) and a 2.1 (p = 0.022) point better rotation of the prosthesis (RP) was registered two months later. Group B was tested twice without training and no significant improvement was registered. One month after training group B had experienced overall significant improvement on a par with group A. It is realistic to implement an RSA X-ray training program where radiographers significantly improve their theoretical and practical skills in centering the CP closer to the CCF, NB and RP. A duration of up to two months after training does not influence the quality of participants' performance.


Role of [18F]FDG-PET/CT after radiofrequency ablation of liver metastases: preliminary results.
Focal metastasis may be treated with radiofrequency ablation (RFA), a low invasive method yet limited by the lack of direct evidence of radicality of treatment. We, hereby, aimed at assessing the role of positron emission tomography-computed tomography (PET/CT) with fluoride radiolabeled deoxy-glucose ([(18)F]FDG) in RFA treatment success evaluation and early diagnosis of local relapse of liver metastasis after RFA procedure. RFA was performed in nine patients on 12 liver metastasis, serially imaged through [(18)F]FDG-PET/CT and multidetector CT (MDCT) at 1, 3, 6, and 9 months after treatment. Eight lesions were also scanned with [(18)F]FDG-PET/CT at 1 week after treatment. Imaging analyses were performed on 47 [(18)F]FDG-PET/CT and 51 MDCT. Imaging reading outcomes were compared to each other and to biopsy tissue results when available. In one case, [(18)F]FDG-PET/CT revealed radiotracer uptake at RFA site a week after procedure. Negative concordant outcome was obtained on eight lesions at 1 month after RFA, on eight cases at 3 months, on four at 6 months, and on two cases at 9 months. Extra-liver (peritoneal) disease was detected in one case by both [(18)F]FDG-PET/CT and MDCT. In seven cases, [(18)F]FDG-PET/CT revealed the presence of local recurrence earlier than MDCT. In no cases did MDCT detect local relapse earlier than [(18)F]FDG-PET/CT. [(18)F]FDG-PET/CT may detect RFA treatment failure as well as local relapse after RFA earlier than MDCT.


Effects of mobile augmented reality apps on impulse buying behavior: An investigation in the tourism field.
Many of today's online services are designed specifically to encourage impulse buying. Moreover, many studies have shown that with the assistance of Mobile Augmented Reality, retailers have the potential to significantly improve their sales. However, the effects of Mobile AR on consumer impulse buying behavior have yet to be examined, particularly in the tourism field. Consequently, the present study integrates the Technology Acceptance Model (TAM), Stimulus-Organism-Response (SOR) framework, and flow theory to examine the effects of Mobile AR apps on tourist impulse buyingbehavior. The research model is implemented using an online questionnaire, with the results analyzed by Partial-Least-Squares Structural Equation Modeling (PLS-SEM) approach. The results obtained from 479 valid samples show that the characteristics of Mobile AR apps play an important role in governing tourist behavior in making unplanned purchases. In particular, as the utility, ease-of-use, and interactivity of the apps increase, the perceived enjoyment and satisfaction of the user also increase and give rise to a stronger impulse buying behavior. The results also reveal a mediating effect of the flow experience on the relationship between the perceived ease of use of the Mobile AR app and the user satisfaction in using the app. Overall, the findings presented in this study provide a useful source of reference for Mobile AR app developers, retailers, and tourism marketers in better understanding users' preferences for Mobile AR apps and strengthening their impulse buying behavior in the tourism context as a result.


Release-Recapture Test of Dispersal and Survival of Sterile Males of Ceratitis capitata (Diptera: Tephritidae).
The sterile insect technique is used around the world to suppress or eradicate populations of Ceratitis capitata (Wiedemann) with successful results. It consists of inundative releases of sterile insects into a wide area to reduce reproduction in a field population of the same species. It is necessary to know the dispersion of the sterile males in the field in order to define the maximum distance between the release points that ensures the distribution of the sterile flies in the entire target area. The release methods may vary depending on the area to be covered and the resources available. Manual ground release requires less technology. The aim of this research was to estimate the ability of sterile males to survive and disperse in the field, in the two main areas of citrus production in Uruguay. A release of 20,000 sterile males of C. capitata TslV8 (-inv D53) was performed at the central point of each area defined for the trials. Around these points, a network of 54 Jackson traps baited with trimedlure was installed forming five concentric rings, which were placed on days 1, 3, 5, and 7 after the release and were removed at 24 h in all cases. The emergence rate, flight ability, dispersion, and longevity were estimated. The standard distances obtained by the regression models were 127 m and 131 m for Salto and San José respectively. In Salto, the traps had catches until the eighth day, and in San José, there were no catches after the sixth day.


Doublet preference and gene evolution.
Doublet preference analysis was carried out on coding and noncoding regions of Escherichia coli, Saccharomyces cerevisiae, and human mitochondrial and nuclear DNA. The preference pattern in 1-2 and 2-3 doublets in E. coli and S. cerevisiae correlated with that in noncoding regions. The 3-1 doublet preference in E. coli genes with low optimal codon frequency and in S. cerevisiae genes also showed a correlation with each of their noncoding doublet preference. A mechanism to explain these double preference correlations in doublet preference is presented: mutational biases, the origin of the noncoding region doublet preference, evolved so as to maintain the 1-2 and 2-3 doublet preference, which is determined by codon usage. These biases then acted on the 3-1 doublet, which was almost free of coding constraints, resulting in a similar preference in this doublet.


Is the Fatty Acids Profile in Blood a Good Predictor of Liver Changes? Correlation of Fatty Acids Profile with Fatty Acids Content in the Liver.
Existing data show a correlation between the profile of fatty acids, liver, and blood. Therefore, the aim of our study was to investigate the correlation between the fatty acids profile in blood pallets and the liver. The experiment was performed on 60 eight-week-old male Sprague-Dawley rats. The study group (n = 30, 5 groups, 6 rats each) received a cholesterol diet; the control group (n = 30, 5 groups, 6 rats each) received standard food for laboratory rats. The rats from both the study and control groups were sacrificed after 2, 4, 8, 12, and 16 weeks of dietary exposure. The fatty acids profile was measured using gas chromatography (GC). In both the control and study group, the highest correlations were observed in palmitoleic acid (RHO = 0.68), heptadecanoic acid (RHO = 0.65), vaccenic acid (RHO = 0.72), eicosapentaenoic acid (RHO = 0.68), docosapentaenoic acid (RHO = 0.77), and docosahexaenoic (RHO = 0.77). Among liver indexes, the highest correlations were desaturase-18 (0.61). Fatty acids profile is a sensitive marker of the development of potentially pathological changes in the liver. The potential markers of fatty liver are: oleic acid, vaccenic acid, EPA, DHA, docosapentaenoic acid, and desaturase index (SCD-18 index).