Understanding the patterns of antibiotic susceptibility of bacteria causing urinary tract infection in West Bengal, India.
Urinary tract infection (UTI) is one of the most common infectious diseases at the community level. In order to assess the adequacy of empirical therapy, the susceptibility of antibiotics and resistance pattern of bacteria responsible for UTI in West Bengal, India, were evaluated throughout the period of 2008-2013. The infection reports belonging to all age groups and both sexes were considered. Escherichia coli was the most abundant uropathogen with a prevalence rate of 67.1%, followed by Klebsiella spp. (22%) and Pseudomonas spp. (6%). Penicillin was least effective against UTI-causing E. coli and maximum susceptibility was recorded for the drugs belonging to fourth generation cephalosporins. Other abundant uropathogens, Klebsiella spp., were maximally resistant to broad-spectrum penicillin, followed by aminoglycosides and third generation cephalosporin. The antibiotic resistance pattern of two principal UTI pathogens, E. coli and Klebsiella spp. in West Bengal, appears in general to be similar to that found in other parts of the Globe. Higher than 50% resistance were observed for broad-spectrum penicillin. Fourth generation cephalosporin and macrolides seems to be the choice of drug in treating UTIs in Eastern India. Furthermore, improved maintenance of infection incident logs is needed in Eastern Indian hospitals in order to facilitate regular surveillance of the occurrence of antibiotic resistance patterns, since such levels continue to change.


Physical and Mechanical Therapies for Lower-Limb Problems in Juvenile Idiopathic ArthritisA Systematic Review with Meta-Analysis.
Juvenile idiopathic arthritis (JIA), a chronic, autoimmune, inflammatory joint disease, is the most common arthritis affecting children younger than 16 years. Children with JIA commonly experience lower-limb dysfunction and disability. We systematically reviewed the effectiveness of physical and mechanical therapies for lower-limb problems in JIA. Randomized controlled trials of physical and mechanical interventions for lower-limb problems in children with JIA were included. Primary outcome was pain. Secondary outcomes included disability, functional ability, and health-related quality of life. Several databases were searched for eligible studies. Authors of included studies and researchers in the field were contacted to identify additional studies. Two studies evaluating the effectiveness of customized/custom foot orthoses in treating foot and ankle pain in children with JIA (N = 100) were included. One study also evaluated simple cushioned inserts. Meta-analyses for comparisons between custom/customized foot orthoses and a control intervention after 3 months were not significant for the outcomes of pain (mean difference, -8.97; 95% confidence interval [CI], -18.01 to 0.07), child-rated health-related quality of life (mean difference, 4.38; 95% CI, -3.68 to 12.44), and parent-rated health-related quality of life (mean difference, 1.77; 95% CI, -6.35 to 9.90). Meta-analyses were supported by sensitivity analyses. There is a paucity of research evaluating physical and mechanical therapies for lower-limb problems in JIA. No physical therapy has been evaluated in randomized controlled trials, and mechanical therapy evaluation is limited to foot orthoses and shoe inserts for foot and ankle pain. The existing research is hampered by small sample sizes. Until further research is conducted, the effectiveness of mechanical and physical therapies for lower-limb problems in JIA remains unclear.


A model of professional nurse caring: nursing students' experience.
Research into caring from the perspective of nursing students is poorly documented. This paper presents a study which described the construct of caring as experienced by students in pre-registration programmes at two universities in New South Wales, Australia. Qualitative data were collected using a questionnaire and semi-structured interviews. From the analysis of the data a model of professional nurse caring from the student's perspective was created. In this model, compassion, as the core of caring is actualized in the students' nursing of patients by communicating, providing comfort, being competent, being committed, having conscience, being confident and being courageous. Communication is not only an actualization of this caring but constitutes an important medium for the expression of caring actions.


Recent omics-based computational methods for COVID-19 drug discovery and repurposing.
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the main reason for the increasing number of deaths worldwide. Although strict quarantine measures were followed in many countries, the disease situation is still intractable. Thus, it is needed to utilize all possible means to confront this pandemic. Therefore, researchers are in a race against the time to produce potential treatments to cure or reduce the increasing infections of COVID-19. Computational methods are widely proving rapid successes in biological related problems, including diagnosis and treatment of diseases. Many efforts in recent months utilized Artificial Intelligence (AI) techniques in the context of fighting the spread of COVID-19. Providing periodic reviews and discussions of recent efforts saves the time of researchers and helps to link their endeavors for a faster and efficient confrontation of the pandemic. In this review, we discuss the recent promising studies that used Omics-based data and utilized AI algorithms and other computational tools to achieve this goal. We review the established datasets and the developed methods that were basically directed to new or repurposed drugs, vaccinations and diagnosis. The tools and methods varied depending on the level of details in the available information such as structures, sequences or metabolic data.


Effects of mild temperature conditions during dehydration procedures on saffron quality parameters.
The dehydration procedure is responsible for saffron sensorial properties: colour, taste and aroma. Changes in the compounds responsible for these characteristics have been studied when dehydration processes at high and low temperature are employed. However, the evolution of these changes at mild temperatures is not available in the current bibliography. In this paper the effect of different mild conditions (18-20 degrees C for 24 h, 40-50 degrees C for 75 min and 55 degrees C for 75 min) applied to 45 saffron samples with the same origin was investigated. Crocetin esters, the compounds responsible for saffron colour, increased their content with no significant differences from other processes when high temperatures (55 degrees C) were used, thus producing a noticeable increment in saffron colouring capability. Similar behaviour was obtained for picrocrocin, the compound responsible for saffron taste, with higher average content at the highest temperature (55 degrees C) but without significant differences with the inferior conditions (40-50 degrees C). However, more volatile compounds were generated, especially safranal,at higher temperatures, e.g. 55 degrees C, during the dehydration procedure. The results found support the idea for employing mild to high temperatures during the dehydration process of saffron.


Factors Influencing Frequency of Pediatric Clinically Distinguishable Influenza: A 2 Season Case-Control Study.
Little is known about the individual differences in susceptibility to, or lifetime frequency of clinically distinguishable influenza in children. Rapid enzyme linked immunoassay-confirmed influenza pediatric cases (n = 96) in season 1 (2017-2018) were compared to age-matched (mean 7.7 years) controls (n = 171) with no evidence of influenza in season 1. The 2 cohorts were again studied in season 2 (2018-2019) for influenza outcomes and influences. Medical records, questionnaires, and interviews were used to determine past influenza disease and vaccine histories. After season 2, known lifetime influenza illnesses per year of age averaged 22.6% in cases and 5.6% in controls, with 62% of controls still having never experienced known influenza. Having had prior influenza was marginally significant as a risk for season 1 influenza in cases versus controls (P = .055), yet a significant risk factor in controls for season 2 (P = .018). Influenza vaccine rates were significantly higher in controls than in cases for season 1, with a greater female vaccine benefit. Lack of previous influenza had greater calculated effectiveness (52%) than vaccination (17%-26%) in escaping season 2 influenza. Lifetime rates of vaccination did not correlate with lifetime rates of known influenza in either cohort. Lifetime clinically distinguishable influenza rates varied among children, with many escaping it for years even without being immunized against it. Findings of less than expected clinical influenza, no correlation between vaccination frequency and disease frequency, sex differences, and an association between past clinical influenza and current risk, point to innate differences in individual influenza experiences.


Mycobacterium malmoense isolated from soil.
Mycobacterium malmoense was isolated from a soil sample, and biological, biochemical, antigenic, and genetic characteristics of the isolate were described. This is the first report of isolation of this organism in Japan.


Impact of Point-of-Care Xpert MTB/RIF on Tuberculosis Treatment Initiation. A Cluster-randomized Trial.
Point-of-care (POC) diagnostics have the potential to reduce pretreatment loss to follow-up and delays to initiation of appropriate tuberculosis (TB) treatment. To evaluate the effect of a POC diagnostic strategy on initiation of appropriate TB treatment. We conducted a cluster-randomized trial of adults with cough who were HIV positive and/or at high risk of drug-resistant TB. Two-week time blocks were randomized to two strategies: (1) Xpert MTB/RIF test (Cepheid, Sunnyvale, CA) performed at a district hospital laboratory or (2) POC Xpert MTB/RIF test performed at a primary health care clinic. All participants provided two sputum specimens: one for the Xpert test and the other for culture as a reference standard. The primary outcome was the proportion of participants with culture-positive pulmonary tuberculosis (PTB) initiated on appropriate TB treatment within 30 days. Between August 22, 2011, and March 1, 2013, 36 two-week blocks were randomized, and 1,297 individuals were enrolled (646 in the laboratory arm, 651 in the POC arm), 159 (12.4%) of whom had culture-positive PTB. The proportions of participants with culture-positive PTB initiated on appropriate TB treatment within 30 days were 76.5% in the laboratory arm and 79.5% in the POC arm (odds ratio, 1.13; 95% confidence interval, 0.51-2.53; P = 0.76; risk difference, 3.1%; 95% confidence interval, -16.2 to 10.1). The median time to initiation of appropriate treatment was 7 days (laboratory) versus 1 day (POC). POC positioning of the Xpert test led to more rapid initiation of appropriate TB treatment. Achieving one-stop diagnosis and treatment for all people with TB will require simpler, more sensitive diagnostics and broader strengthening of health systems. Clinical trial registered with www.isrctn.com (ISRCTN 18642314) and www.sanctr.gov.za (DOH-27-0711-3568).


Discrimination of Odors Associated With Conspecific and Heterospecific Frass by Sibling Species Dendroctonus frontalis (Coleoptera: Curculionidae: Scolytinae) and Dendroctonus mesoamericanus (Coleoptera: Curculionidae: Scolytinae).
In the Central American region, the aggressive, sibling bark beetles Dendroctonus frontalis Zimmermann (Coleoptera: Curculionidae: Scolytinae) and Dendroctonus mesoamericanus Armendáriz-Toledano & Sullivan (Coleoptera: Curculionidae: Scolytinae) commonly colonize pines concurrently, and in nature they avoid heterospecific pairing, although it can be produced in the lab. We performed walking arrestment bioassays in the lab to examine the capacity of both sexes of both species to discriminate odors from frass expelled from gallery entrances of either solitary females or conspecific pairs of either species. Males of both species strongly preferred odors of frass from solitary, conspecific females over those of heterospecific females or pairs of either species. Female D. frontalis did not discriminate among these frass categories, whereas female D. mesoamericanus preferred frass of conspecific females. In gas chromatography-electroantennographic detection and gas chromatography-mass spectrometry analyses, we determined that males of both species could sense a nearly identical spectrum of approximately 16 host- and beetle-produced compounds present in frass of females of one or both species. Only two of these compounds, endo-brevicomin and ipsdienol, which were present in frass of female D. mesoamericanus and pairs of either species but absent in frass of solitary D. frontalis females, qualitatively distinguished these categories. Several known attractants and synergists for either species declined in concentration postpairing. Our results complement earlier research and indicate how semiochemical composition and concentration in frass might mediate male discrimination of attack sites of conspecific, unpaired females. Furthermore, our data indicate that semiochemical responses for walking females differ from those of males and between species.


Genetic basis of neural tube defects. I. Regulatory genes for the neurulation process.
Neural tube defects (NTD) together with cardiovascular system defects are the most common malformations in the Polish population (2.05-2.68/1000 newborns). They arise during early embryogenesis and are caused by an improper neural groove closure during the neurulation process. NTD can arise from the influence of specific environmental factors on the foetus. The genetic factor is also very important, because NTDs have multigenetic conditioning. It was suggested that genes connected with the regulation of neurulation could also be involved in NTD aetiology, especially when their deletion or modification leads to neural tube defects in the mouse model. Examples are genes from the PAX family, T (Brachyury), BRCA1 and PDGFRA genes.


Molecular analysis of complement component C4 gene copy number.
Classical, alternative, or lectin pathways may activate the complement system cascade. The classical pathway includes the C4 protein and functions in the prevention of immune complex precipitation and in clearance of immune complexes.Two isotypes of C4-C4A and C4B-are coded by genes located at two loci within the major histocompatibility complex (MHC) on chromosome 6. While these isotypes share over 99% amino acid sequence homology, five nucleotide differences located in exon 26 are responsible for major structural and functional differences between the C4 isotypes.C4A and C4B are highly polymorphic with over 40 alleles, gene duplications, and "null alleles". C4 genes may be short (14.6 kb) or long (21 kb), due to the absence or presence of an endogenous retroviral sequence-HERV-K(C4)-in intron 9, respectively. The C4 gene copy number (GCN) can vary from 1-3 per haplotype or 2-6 per diploid genome. The variation in GCN leads to a range of C4 plasma protein concentrations among healthy subjects. In subjects with equal numbers of C4 genes, subjects with short genes have C4 plasma levels relatively higher than subjects with long genes.Variation of the C4 GCN, the gene size (long or short) and the C4 isotypes (C4A and C4B) may also lead to susceptibility to autoimmune disease. Therefore, in subjects with autoimmune disease, a low serum C4 level may be due to ongoing disease activity associated with complement activation and consumption or it may be due to genetic factors. Distinguishing between these will have clinical implications.Exact determination of GCN can be difficult, at least in part due to the high degree of homology between C4A and C4B and a variety of techniques has been described. This chapter describes a quantitative TaqMan real-time PCR (qPCR) copy number assay, based on our laboratory experience using this assay.


Status of echocardiography in clinical cardiology.
Echocardiography (ECHO) is at present the most important and most useful non-invasive diagnostic method employed in cardiology. Its dominant position is the result of dramatic development of its technology and methodology enabling a wide range of clinical applications. Apart from M-mode and two-dimensional ECHO, these methods include mainly Doppler ECHO (pulse and continuous, colour), computer, contrast, exertional, transoesophageal ECHO, ultrasound characteristics of tissue (textural analysis). Moreover, technical improvements have enabled to quantify, standardise and unify ECHO measurements and nomenclature. The most general contribution of ECHO to present-day clinical cardiology lies in the confirmation or exclusion of a suspected cardiovascular disease and assessment of the degree of circulatory system involvement.


Pulmonary complications resembling Wegener's granulomatosis in ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody.
After a 17-year-old woman with ulcerative colitis was treated with granulocyte apheresis, chest imaging showed multiple nodular infiltrates, including one which seemed to have a cavity. Wegener's granulomatosis was suspected because proteinase-3 anti-neutrophil cytoplasmic antibody levels were increased. Transbronchial lung biopsy specimen showed nonspecific findings. Chest imaging showed clearing of pulmonary infiltrates without any therapy or discontinuation of mesalazine, which is known to cause lung toxicity. To the best of our knowledge, this is the first report of extra-intestinal pulmonary complications of ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody resembling Wegener's granulomatosis and spontaneous improvement.


De novo formation of large arteriovenous shunting and a vascular nidus mimicking an arteriovenous malformation within an anaplastic oligodendroglioma: treatment with embolization and resection.
The authors report the de novo occurrence and treatment of an arteriovenous lesion within an anaplastic oligodendroglioma in a patient with previously unremarkable brain imaging. Intracranial arteriovenous malformations (AVMs) are believed to be congenitally acquired lesions, and their association with brain neoplasms is extremely rare. Diagnostic imaging revealed a mass lesion with large arteriovenous shunts and a vascular nidus mimicking a true AVM. Histological and immunohistochemical testing showed an anaplastic oligodendroglioma mixed with an AVM. The clinical, radiological, and operative data are reviewed, as are the histopathological findings. To the authors' knowledge this is the first case of de novo occurrence of an arteriovenous lesion with large shunts and a vascular nidus within an anaplastic oligodendroglioma.


Constitutive expression of the brg1 gene requires GC-boxes near to the transcriptional start site.
We previously reported that BRG1, an ATPase subunit of SWI/SNF chromatin remodelling complexes, is constitutively expressed and that the alternative ATPase subunit (BRM) is inducibly expressed through differentiation in mammalian cells. In the present study, the regulatory elements that confer constitutive expression on brg1 were explored. First, we analysed the promoter proximal region surrounding its transcriptional start site. Using computer-aided analysis, a TATA-less, GC-rich promoter containing four putative binding sites for Sp1/3 was predicted. One of the putative Sp1/3-binding sites (from -21 to -15 bp) overlapped with a putative YY1-binding site. A gel-shift assay showed that YY1 but not Sp1/3 bound to this sequence and that Sp3 but not Sp1 bound to the other three predicted binding sites. Furthermore, chromatin immunoprecipitation analysis showed that Sp3 and YY1 bound to the promoter region together with TATA-binding protein in vivo. In vivo and in vitro binding assays showed that Sp3 and YY1 interacted with each other. Together, these results suggest that Sp3 and YY1 recruit general transcription factors and facilitate the assembly of a preinitiation complex.


Further studies on bovine serum amylase. 2. Affinity electrophoresis.
The polymorphism of bovine serum amylase, which is controlled by the AmI locus, has previously only been demonstrated by starch gel electrophoresis. The addition of maltose to starch gels has been demonstrated to inhibit any subsequent separation of the AmI isozymes by starch gel electrophoresis. When electrophoresis was conducted in a support medium in the absence of starch no polymorphic variation was detected amongst samples from animals of different AmI phenotypes. The addition of starch to agarose gels has been shown to facilitate the subsequent detection of the AmI polymorphism by agarose/starch gel electrophoresis. The electrophoretic resolution of the AmI isozymes has been demonstrated to depend upon differences in affinity for starch rather than differences in net charge. The starch gel electrophoretic separation of the AmI isozymes is, therefore, another example of affinity electrophoresis. All the AmI amylases have been shown to share a common isoelectric point of pH 3.5.


Pseudo-obstruction of the colon.
"Pseudo-obstruction of the colon" refers to a condition in which physical and radiological findings identical to those associated with mechanical obstruction of the large bowel are found but in which no organic cause for the colonic distention is present. These cases may involve progressive proximal large bowel dilatation to the point of cecal perforation or necrosis. We have collected eight cases of our own which will be presented. The various etiologic factors reported in the literature will be discussed and analyzed and we will offer an anatomicophysiologic explanation of a possible mechanism, based on sympathetic-parasympathetic neurostimulatory imbalance.


Upregulation of neuronal kynurenine 3-monooxygenase mediates depression-like behavior in a mouse model of neuropathic pain.
Pain and depression often co-occur, but the underlying mechanisms have not been elucidated. Here, we used the spared nerve injury (SNI) model in mice to induce both neuropathic pain and depression-like behavior. We investigated whether brain interleukin (IL)-1 signaling and activity of kynurenine 3-monoxygenase (KMO), a key enzyme for metabolism of kynurenine into the neurotoxic NMDA receptor agonist quinolinic acid, are necessary for comorbid neuropathic pain and depression-like behavior. SNI mice showed increased expression levels of Il1b and Kmo mRNA in the contralateral side of the brain. The SNI-induced increase of Kmo mRNA was associated with increased KMO protein and elevated quinolinic acid and reduced kynurenic acid in the contralateral hippocampus. The increase in KMO-protein in response to SNI mostly took place in hippocampal NeuN-positive neurons rather than microglia. Inhibition of brain IL-1 signaling by intracerebroventricular administration of IL-1 receptor antagonist after SNI prevented the increase in Kmo mRNA and depression-like behavior measured by forced swim test. However, inhibition of brain IL-1 signaling has no effect on mechanical allodynia. In addition, intracerebroventricular administration of the KMO inhibitor Ro 61-8048 abrogated depression-like behavior without affecting mechanical allodynia after SNI. We show for the first time that the development of depression-like behavior in the SNI model requires brain IL-1 signaling and activation of neuronal KMO, while pain is independent of this pathway. Inhibition of KMO may represent a promising target for treating depression.


The role of zinc(II) in the absorption-desorption of CO2 by aqueous NH3, a potentially cost-effective method for CO2 capture and recycling.
The absorption of CO2 by aqueous NH3 solutions has been investigated at atmospheric pressure and 0 degrees C. The CO2 absorption is fast and occurs with high efficiency (88-99%). The maximum CO2-removal efficiency increases slightly with the NH3 concentration. Addition of zinc(II) salts (as chloride, nitrate or sulfate) to the NH3 absorbent solution increases the overall CO2-absorption capacity without appreciably affecting the removal efficiency. Stripping of pure CO2 from HCO3(-) solutions is achieved by adding the calculated amount of ZnII salts, which under ambient conditions lead to rapid release of about 30-35% of the initially captured CO2. At the same time, about 65-70% of the captured CO2 is transformed into solid basic zinc carbonates. The recovery of these valuable solid products and the release of only 1/3 of free CO2 at room temperature and pressure reduces the cost of the overall process of CO2 capture, making it a potentially attractive method for CO2 capture on a larger scale.


Morphology and Phylogeny of the Soil Ciliate Parabistichella multilineae sp. nov. (Protozoa: Ciliophora: Hypotricha).
The morphology and molecular phylogeny of Parabistichella multilineae sp. nov., which was discovered in soil from Gagye Beach, South Korea, were investigated. The new species is characterized as follows: body size about 200 × 47 µm in vivo, slenderly lanceolate and twisted; two ellipsoidal macronuclei and usually two globular micronuclei; two types of cortical granules; four or five frontoventral rows, of which rows 1 and 2 are conspicuously developed and rows 3 and 4 are fully extended; and caudal cirri are lacking. Phylogenetic analyses based on the SSU rDNA sequences showed that the new species clusters in a soft polytomy with P. variabilis and Uroleptoides magnigranulosus.


Individual differences in nurse and teacher training students' attitudes toward and use of information technology.
Students in both nurse and teacher training are now expected to learn to make effective use of IT for their profession. However, they enter training with a variety of experience in IT which will affect how they respond to further IT skills training. In this survey, 154 nursing and 128 teacher training students reported on the uses they had made of computers and their attitudes towards them. Also, as a sense of being in control of the computer is important for becoming involved in its use, they completed a questionnaire to locate their locus of internal control. The teacher training students were more likely than the nursing students to have access to a home computer, to use computers more often and to have used a greater variety of software. However, this may be a gender effect as a greater proportion of the teacher trainees were male. For both teacher training and nursing students, having a more internal locus of control was correlated with more positive attitudes towards computers. This finding is important for those introducing students to the use of IT in their professions, so that appropriate software and teaching styles involving less open-ended tasks may be provided for the less internally controlled individuals. Interestingly, a much stronger relationship between being more internally controlled and being less scared of using a computer was found for teacher trainees than for nurse trainees. Thus for nurse trainees it is more likely that there are other individual factors predisposing them to fear using computers.


Greater gender diversity among autistic children by self-report and parent-report.
Gender diversity broadly refers to the way in which an individual experiences (expressions and/or identities) their gender distinctly to that which would be expected based upon social norms for their gender assigned at birth. Recent research has shown a higher representation of gender diversity among autistic youth. Previous research in this area has relied on parent-report based on a single question from the Child Behavior Checklist Item-110, asking whether their child "Wishes to be the opposite sex." The Gender Diversity Screening Questionnaire Self-Report and Parent-Report were used to assess the experience of gender diversity in 244 children (140 autism spectrum disorder and 104 typically developing) between 10 and 13 years. The Item-110 was also collected. Results showed that autistic children endorsed much higher rates of Binary Gender Diversity (less identification with their designated sex and more with the other binary sex) and Nonbinary Gender Diversity (identification as neither male nor female) than typically developing children. Similarly, parents of autistic children reported significantly more gender-body incongruence experienced by their child than parents of typically developing children. Specifically, parents of autistic females-assigned-at-birth reported significantly more gender-body incongruence than autistic males-assigned-at-birth. Parent- and self-report measures were largely related. Moreover, statistical comparisons between and within the groups revealed associations between gender profiles and symptoms of anxiety, depression, and suicidality. Results extend previous reports showing increased rates of gender diversity in autistic children, now based on both self-report and parent-report, and highlight the need to better understand and support the unique and complex needs of autistic children who experience gender diversity.


An update on medical therapy for obesity.
Obesity is a risk factor and exacerbates many chronic conditions, particularly diabetes, but also hypertension, hyperlipidemia, heart disease, stroke, certain cancers, arthritis, and obstructive sleep apnea. Despite increased awareness within the public and healthcare system, there has still been a persistent rise in the prevalence of obesity over the past half-century. Failure to halt this epidemic is related to difficulties in adherence to lifestyle changes, forceful counter-regulatory mechanisms opposing weight loss, and the lack of efficient long-term therapy for obesity. This article summarizes the current medical approach to the treatment of obesity, reviewing strategies for lifestyle modification, available pharmacotherapy both as an adjunct to diet and exercise and to ameliorate comorbidities, and an overview of new pharmaceutical agents being developed.


[Concentration of Malondialdehyde in Subjects Living at High Altitudes: Exploratory Study].
The objective of this study was to determine the levels of malondialdehyde (MDA), an oxidative stress biomarker, in individuals living at high altitudes (3500-4200 m). This exploratory study evaluated 91 subjects from La Paz and El Alto using a questionnaire and clinical examination. MDA levels were measured using a colorimetric technique. Measures of central tendency, dispersion, and percentages were used to describe data, and the Mann-Whitney test and Kruskal-Wallis test were used to assess differences between the sexes, age groups, and altitudes. The median concentration of MDA was 4.1 μmol/L (RIC 2.4-5.4) and the highest concentration of MDA was found in individuals older than 40 years. The average MDA levels were higher than those found at sea level, a result we believe is due to the effect of hypoxia. However, there were no differences in the MDA levels between the sexes or age groups.


Experimental Research and Numerical Analysis of the Elastic Properties of Paper Cell Cores before and after Impregnation.
The research hypothesis states that the impregnation of the honeycomb paper core of lightweight sandwich panels with modified starch, sodium silicate and epoxy resin (LiquidWood®) resin has a significant effect on its elastic properties. In this study, a recycled paper was used in three thicknesses, seven types of cell shapes, including two after numerical optimization and three types of impregnating agents. The method of digital image analysis determined the elastic constants of manufactured paper cores, which were subjected to axial compression in two directions. Based on the experimental results, elastic constants of the cores were calculated and compared with the results of numerical calculations. It has been shown that each of the impregnating solutions used improved the stiffness of the paper core. The best results were obtained for LiquidWood® epoxy resin and modified starch. An important parameter of cell geometry affecting their rigidity is the angle of the cell wall φ, as well as the arrangement of the common cell wall in relation to the direction of load. The numerical models developed were positively verified.


A neurodynamic model of the interaction between color perception and color memory.
The memory color effect and Spanish castle illusion have been taken as evidence of the cognitive penetrability of vision. In the same manner, the successful decoding of color-related brain signals in functional neuroimaging studies suggests the retrieval of memory colors associated with a perceived gray object. Here, we offer an alternative account of these findings based on the design principles of adaptive resonance theory (ART). In ART, conscious perception is a consequence of a resonant state. Resonance emerges in a recurrent cortical circuit when a bottom-up spatial pattern agrees with the top-down expectation. When they do not agree, a special control mechanism is activated that resets the network and clears off erroneous expectation, thus allowing the bottom-up activity to always dominate in perception. We developed a color ART circuit and evaluated its behavior in computer simulations. The model helps to explain how traces of erroneous expectations about incoming color are eventually removed from the color perception, although their transient effect may be visible in behavioral responses or in brain imaging. Our results suggest that the color ART circuit, as a predictive computational system, is almost never penetrable, because it is equipped with computational mechanisms designed to constrain the impact of the top-down predictions on ongoing perceptual processing.


[Treatment of chronic heart failure: is deprescribing possible?]
Deprescribing is a scheduled withdrawal, dose reduction, or replacement of a medicine with a safer one. Several groups of medicinal products (MPs) are used simultaneously in the treatment of chronic heart failure. This increases the risk of adverse drug reactions, particularly in elderly and senile patients. A systematic search for literature allowed evaluating possibilities of deprescribing for the following pharmaceutic groups: 1) MPs influencing the renin-angiotensin-aldosterone system; 2) beta-blockers; 3) digoxin; and 4) diuretics. Three systematic reviews and several studies were analyzed to determine the most feasible and potentially optimal regimens of deprescribing in CHF. It was established that in CHF, deprescribing has a very limited potential for use due to the documented, obvious effect of some MP groups on prediction and severity of clinical symptoms in CHF patients.


Effectiveness of DTPA treatments following the injection of particulate plutonium.
A limited long-term experiment has been completed in which the chronic toxicity resulting from a single intravenous injection of 31.4 kBq of a poly-disperse 239Pu colloid sol per kg of body weight was tested in Beagle dogs. The Pu deposited mostly in the phagocytic cells of liver, spleen and to a lesser degree in lung and bone marrow. Slow solubilization of the Pu particles by endogenous ligands caused translocation of the nuclide and redeposition mostly as monomeric Pu in the skeleton and in liver hepatocytes. Thus, the deposit behaved as expected from a pulmonary or wound contamination in humans with a moderately soluble depot of Pu such as Class W hot particles. Therefore, this type of deposit provided the basis for a practical model to study the ensuing radiation effects under various experimental conditions. The dogs were divided into three groups of four animals each, and the following conditions were applied: (a) no further treatment was given, allowing free translocation of the Pu to its secondary deposition sites; (b) interception of the Pu translocation by weekly injections of 30 mumol of Ca-DTPA/kg of body weight (Ca-chelate of diethylene-triaminepentaacetic acid); and (c) interception of translocation by daily injections of 30 mumol/kg body weight of Zn-DTPA. For each of the groups (b) and (c), three dogs were used in a lifetime study, and one was sacrificed for nuclide distribution studies. Free translocation and subsequent deposition in the skeleton resulted in the death of each of the non-chelated dogs from osteosarcoma between 1267 and 1594 days after injection. Weekly treatment with Ca-DTPA reduced the total Pu burden significantly, but these dogs also died with osteosarcoma between 1462 and 1783 days. Daily injections with Zn-DTPA reduced the total Pu burden more efficiently than Ca-DTPA and prevented continuous deposition of solubilized Pu on bone surfaces. The mean post-injection survival of these dogs was 3520 days or about 2.1 times that of the animals receiving Ca-DTPA, while the latent period for bone tumour induction was about 2.6 times longer. This treatment reduced the severity of liver lesions and eliminated the occurrence of persistent leukopenia, but it did not prevent the formation of bone cancer.


[Teat endoscopy as a diagnostic procedure in the goat].
Teat endoscopy as a diagnostic procedure in the goat is described in a clinical case of a proliferation in the wall of the teat cisterna. Modifications in proceeding and equipment compared to the common use of endoscopy in the teat of cattle are shown and the additional amount of information in comparison to palpation, sounding and sonography is evaluated.


High-grade myxofibrosarcoma of the abdominal wall.
The authors present a case of a 57-year-old man, who presented to the surgical clinic with a mass in the suprapubic region. A CT scan revealed a well-circumscribed lobular, heterogeneous soft tissue mass measuring 12×8.6×7.8 cm. The final histopathological diagnosis from the resection of the lesion was a myxofibrosarcoma (MFS), grade 3. The management of MFS includes surgical and oncological options which are reviewed here. These are aimed at complete excision and reducing the risk of local occurrence.


Effect of time of harvesting on yield and quality of melissa officinalis L. In doon valley, India.
A field experiment on the effect of time of harvesting on yield and quality of Melissa officinalis L. was conducted under the agroclimatic conditions of Doon valley, Uttarakhand in order to assess the performance of four harvesting times (H1-120 days, H2-140 days, H3-160 days and H4-180 days after planting). The fresh and dry herbage and oil yield of the aerial parts showed greater response in H3 i.e. harvesting at 160 days after planting, followed by H2 harvesting time. The quality of essential oil was evaluated using GC and GC-MS analysis. Geranial (24.53 %) and neral (18.80 %) were the major constituents found in the essential oil followed by trans-caryophyllene (7.70 %).


Selective inhibition of absorption and long distance transport in relation to the dual mechanisms of ion absorption in maize seedlings.
The influence of several uncouplers of oxidative phosphorylation and inhibitors of terminal electron transport was studied on absorption and long distance transport of both K and C1 at concentrations within each range of the dual isotherm typical of ion uptake by maize roots. At low concentrations in the range of system 1, the system considered to implement ion movement through the plasma membrane, root absorption and long distance transport are equally inhibited by a given inhibitor. In the high range of system 2, the system considered to mediate ion passage through the tonoplast, long distance transport is markedly less sensitive to inhibitors than is absorption. The observations are in accord with the hypothesis that only system 1 is involved in the uptake of ions from the external solution into the symplast, and hence into the xylem. At high concentrations, entrance into the symplasm is deemed to be largely by diffusion and therefore less inhibitor sensitive. With respect to absorption by the roots, the plasma membrane system is more inhibitor sensitive than is the tonoplast system. It is suggested that the difference in sensitivity is real, and not the consequence of an inequality of inhibitor concentration in the vicinity of the plasma membrane and tonoplast respectively.


Synthesis of ultrasound contrast agents: characteristics and size distribution analysis (secondary publication).
The purpose of this study was to establish a method for ultrasound (US) contrast agent synthesis and to evaluate the characteristics of the synthesized US contrast agent. A US contrast agent, composed of liposome and sulfur hexafluoride (SF6), was synthesized by dissolving 21 μmol 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC, C40H80NO8P), 9 μmol cholesterol, and 1.9 μmol of dihexadecylphosphate (DCP, [CH3(CH2)15O]2P(O)OH) in chloroform. After evaporation in a warm water bath and drying for 12-24 hours, the contrast agent was synthesized using the sonication process by the addition of a buffer and SF6 gas. The size distribution of the bubbles was analyzed using dynamic light scattering measurement methods. The degradation curve was evaluated by assessing the change in the number of contrast agent bubbles using light microscopy immediately, 12, 24, 36, 48, 60, 72, and 84 hours after synthesis. The echogenicity of the synthesized microbubbles was compared with commercially available microbubbles (SonoVue, Bracco). contrast agent was synthesized successfully using an evaporation-drying-sonication method. Most bubbles had a mean diameter of 154.2 nm and showed marked degradation 24 hours after synthesis. Although no statistically significant differences were observed between SonoVue and the synthesized contrast agent, a difference in echogenicity was observed between the synthesized contrast agent and saline (P<0.01). We successfully synthesized a US contrast agent using an evaporation-dryingsonication method. These results may help future research in the fields of anticancer drug delivery, gene delivery, targeted molecular imaging, and targeted therapy.


Classification of cardioactive drugs in vivo by using programmed electrical stimulation in combination with monophasic action potential recordings at different pacing rates.
The effect of antiarrhythmic drugs on myocardial refractoriness may be due to changes either in Vmax of phase 0 or the phase of repolarization of the AP or both. By using programmed electrical stimulation in combination with MAP recordings at different pacing rates in the intact dog heart, it was possible to classify and to a certain extent to elucidate the mode of action of various cardioactive drugs in vivo.


The insulin-like growth factor 2 gene in mammals: Organizational complexity within a conserved locus.
The secreted protein, insulin-like growth factor 2 (IGF2), plays a central role in fetal and prenatal growth and development, and is regulated at the genetic level by parental imprinting, being expressed predominantly from the paternally derived chromosome in mice and humans. Here, IGF2/Igf2 and its locus has been examined in 19 mammals from 13 orders spanning ~166 million years of evolutionary development. By using human or mouse DNA segments as queries in genome analyses, and by assessing gene expression using RNA-sequencing libraries, more complexity was identified within IGF2/Igf2 than was annotated previously. Multiple potential 5' non-coding exons were mapped in most mammals and are presumably linked to distinct IGF2/Igf2 promoters, as shown for several species by interrogating RNA-sequencing libraries. DNA similarity was highest in IGF2/Igf2 coding exons; yet, even though the mature IGF2 protein was conserved, versions of 67 or 70 residues are produced secondary to species-specific maintenance of alternative RNA splicing at a variable intron-exon junction. Adjacent H19 was more divergent than IGF2/Igf2, as expected in a gene for a noncoding RNA, and was identified in only 10/19 species. These results show that common features, including those defining IGF2/Igf2 coding and several non-coding exons, were likely present at the onset of the mammalian radiation, but that others, such as a putative imprinting control region 5' to H19 and potential enhancer elements 3' to H19, diversified with speciation. This study also demonstrates that careful analysis of genomic and gene expression repositories can provide new insights into gene structure and regulation.


Effects of damping and stiffness of AFM cantilever on the imaging of fine surfaces.
In this paper, by applying the differential quadrature (DQ) method, a semi analytical model has been developed for atomic force microscope cantilever, and then by using the interfacial forces between the cantilever tip and imaged surfaces, a 2D model has been extracted for imaging nano-sized fine samples. By employing the present model, several simple and standard samples have been imaged, and finally the effects of the microcantilever's structural damping and its stiffness on the imaging results have been investigated. It has been observed that, through the control of damping, the quality of the acquired images is considerably improved. It has also been shown that the self-softening and self-hardening properties of cantilever have serious effects on the obtained images. The present model can be used to study the effects of different parameters on the process of imaging small-scale samples. Also, as one of its most important applications, this model can be used in common multiscale models for simulating and predicting the effects of large and small fields on each other.


Surfactant selection for a liquid foam-bed photobioreactor.
A novel liquid foam-bed photobioreactor has been shown to hold potential as an innovative technology for microalgae production. In this study, a foam stabilizing agent has been selected which fits the requirements of use in a liquid foam-bed photobioreactor. Four criteria were used for an optimal surfactant: the surfactant should have good foaming properties, should not be rapidly biodegradable, should drag up microalgae in the foam formed, and it should not be toxic for microalgae. Ten different surfactants (nonionic, cationic, and anionic) and two microalgae genera (Chlorella and Scenedesmus) were compared on the above-mentioned criteria. The comparison showed the following facts. Firstly, poloxameric surfactants (Pluronic F68 and Pluronic P84) have acceptable foaming properties described by intermediate foam stability and liquid holdup and small bubble size. Secondly, the natural surfactants (BSA and Saponin) and Tween 20 were easily biodegraded by bacteria within 3 days. Thirdly, for all surfactants tested the microalgae concentration is reduced in the foam phase compared to the liquid phase with exception of the cationic surfactant CTAB. Lastly, only BSA, Saponin, Tween 20, and the two Pluronics were not toxic at concentrations of 10 CMC or higher. The findings of this study indicate that the Pluronics (F68 and P84) are the best surfactants regarding the above-mentioned criteria. Since Pluronic F68 performed slightly better, this surfactant is recommended for application in a liquid foam-bed photobioreactor. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:711-720, 2018.


Cor triatriatum: short review of the literature upon ten new cases.
Cor triatriatum is defined as a membrane within the left atrium, which might lead to restricted pulmonary venous return. Diagnosis is usually achieved by echocardiography, therapy of choice is excision of the membrane. Upon ten new cases, the association with other congenital heart diseases (CHDs), clinical symptoms and the surgical approach are discussed. Eight of ten patients were children, six of them aged<1 year. Additional CHDs included atrial and ventricular septal defects, partial anomalous pulmonary venous return and complex CHD. Surgery was performed in all cases. Prognosis is related to associated CHD.


Association between Social Activities and Cognitive Function among the Elderly in China: A Cross-Sectional Study.
Participation in social activities is one of important factors for older adults' health. The present study aims to examine the cross-sectional association between social activities and cognitive function among Chinese elderly. A total of 8966 individuals aged 60 and older from the 2015 China Health and Retirement Longitudinal Study were obtained for this study. Telephone interviews of cognitive status, episodic memory, and visuospatial abilities were assessed by questionnaire. We used the sum of all three of the above measures to represent the respondent's cognitive status as a whole. Types and frequencies of participation in social groups were used to measure social activities. Multiple linear regression analysis was used to explore the relationship between social activities and cognitive function. After adjustment for demographics, smoking, drinking, depression, hypertension, diabetes, basic activities of daily living, instrumental activities of daily living, and self-rated health, multiple linear regression analysis revealed that interaction with friends, participating in hobby groups, and sports groups were associated with better cognitive function among both men and women (p < 0.05); doing volunteer work was associated with better cognitive function among women but not among men (p < 0.05). These findings suggest that there is a cross-sectional association between participation in social activities and cognitive function among Chinese elderly. Longitudinal studies are needed to examine the effects of social activities on cognitive function.


Kinetics and metabolism of theobromine in male and female non-pregnant and pregnant rabbits.
The kinetics and metabolism of theobromine (3,7- DMX ) were investigated in male rabbits after a single oral dose and 14 days oral dosing at 1, 5, 10, 50 and 100 mg/kg/day. Female non-pregnant and pregnant rabbits were also studied after single oral doses of 1, 5 and 50 mg/kg. No significant difference was found in the pharmacokinetic profile of 3,7- DMX due to either sex, pregnancy or after chronic oral administration for 14 days. Intravenous (i.v.) administration of 3,7- DMX at 1 and 5 mg/kg resulted in calculated kinetic parameters in close agreement with oral doses. Irrespective of sex, there was a reduction in the absorption rate constant as the dose increased, coupled with a linear dose-related increase in AUC values. No qualitative difference in the metabolism of 3,7- DMX in the rabbit was observed as linked to sex, pregnancy or treatment schedule. Twenty-five percent of the administered dose of 3,7- DMX was excreted unchanged, the major metabolite being 7-methylxanthine (40%). There appeared to be a shift in the metabolic pathway at 100 mg/kg/day in the males and at 50 mg/kg/day in the females with more unchanged 3,7- DMX excreted. Only at these highest doses (100 mg/kg for males and 50 mg/kg for pregnant rabbits) was there a tendency toward accumulation.


Response to vincristine of recurrent brain tumors in children.
Seventeen children with clinical evidence of a recurrent brain tumor were treated with vincristine 1.5 mg/sq m weekly for 12 weeks with doses on alternate weeks thereafter. Eight of the 16 patients who received four or more doses of vincristine showed significant objective responses; these included patients with high-and low-grade astrocytomas and patients with medulloblastoma. Six of the eight who responded remained asymptomatic for more than 2 years. The toxicity encountered was minimal except for seizures possibly related to vincristine in three children, who were able to resume treatment. Vincristine therapy results in long-term regression in a wide variety of pediatric brain tumors and causes little or no toxicity.


Source mask optimization for extreme-ultraviolet lithography based on thick mask model and social learning particle swarm optimization algorithm.
Extreme ultraviolet (EUV) lithography plays a vital role in the advanced technology nodes of integrated circuits manufacturing. Source mask optimization (SMO) is a critical resolution enhancement technique (RET) or EUV lithography. In this paper, an SMO method for EUV lithography based on the thick mask model and social learning particle swarm optimization (SL-PSO) algorithm is proposed to improve the imaging quality. The thick mask model's parameters are pre-calculated and stored, then SL-PSO is utilized to optimize the source and mask. Rigorous electromagnetic simulation is then carried out to validate the optimization results. Besides, an initialization parameter of the mask optimization (MO) stage is tuned to increase the optimization efficiency and the optimized mask's manufacturability. Optimization is carried out with three target patterns. Results show that the pattern errors (PE) between the print image and target pattern are reduced by 94.7%, 76.9%, 80.6%, respectively.


Ablation of the leptin receptor in myeloid cells impairs pulmonary clearance of Streptococcus pneumoniae and alveolar macrophage bactericidal function.
Leptin is a pleiotropic hormone produced by white adipose tissue that regulates appetite and many physiological functions, including the immune response to infection. Genetic leptin deficiency in humans and mice impairs host defenses against respiratory tract infections. Since leptin deficiency is associated with obesity and other metabolic abnormalities, we generated mice that lack the leptin receptor (LepRb) in cells of the myeloid linage (LysM-LepRb-KO) to evaluate its impact in lean metabolically normal mice in a murine model of pneumococcal pneumonia. We observed higher lung and spleen bacterial burdens in LysM-LepRb-KO mice following an intratracheal challenge with Streptococcus pneumoniae. Although numbers of leukocytes recovered from bronchoalveolar lavage fluid did not differ between groups, we did observe higher levels of pulmonary IL-13 and TNFα in LysM-LepRb-KO mice 48 h post infection. Phagocytosis and killing of ingested S. pneumoniae were also impaired in alveolar macrophages (AMs) from LysM-LepRb-KO mice in vitro and were associated with reduced LTB4 and enhanced PGE2 synthesis in vitro. Pretreatment of AMs with LTB4 and the cyclooxygenase inhibitor, indomethacin, restored phagocytosis but not bacterial killing in vitro. These results confirm our previous observations in leptin-deficient ( ob/ob) and fasted mice and demonstrate that decreased leptin action, as opposed to metabolic irregularities associated with obesity or starvation, is responsible for the defective host defense against pneumococcal pneumonia. They also provide novel targets for therapeutic intervention in humans with bacterial pneumonia.


Spontaneous direct inguinal hernia rupture and intestinal mesenteric separation: A case report.
Spontaneous evisceration is a rare complication that becomes life-threatening in direct inguinal hernia. A female at the age of 44, weighing 50 kg looked cachectic and was suffering from swelling on the left groin for the last several years. The evisceration of the small intestine as separated from the mesenterium transpired in the subsequent stage of a spontaneous rupture in the left inguinal region after severe coughing. The region ruptured was sealed after small intestine resection carried out through the incision perforated; mesh herniorrhaphy was implemented at the end of the 3rd month. The spontaneous rupture may transpire depending on malnutrition and cachexia not only after the complications by hernia, such as incarceration, strangulation but also after factors increasing intra-abdominal pressure. Elective surgical treatment must be implemented in hernia regardless of its kind. Complications likely to transpire in cases where intervention is conducted too late may threaten the patient's life.


miRNA engineering of CHO cells facilitates production of difficult-to-express proteins and increases success in cell line development.
In recent years, coherent with growing biologics portfolios also the number of complex and thus difficult-to-express (DTE) therapeutic proteins has increased considerably. DTE proteins challenge bioprocess development and can include various therapeutic protein formats such as monoclonal antibodies (mAbs), multi-specific affinity scaffolds (e.g., bispecific antibodies), cytokines, or fusion proteins. Hence, the availability of robust and versatile Chinese hamster ovary (CHO) host cell factories is fundamental for high-yielding bioprocesses. MicroRNAs (miRNAs) have emerged as potent cell engineering tools to improve process performance of CHO manufacturing cell lines. However, there has not been any report demonstrating the impact of beneficial miRNAs on industrial cell line development (CLD) yet. To address this question, we established novel CHO host cells constitutively expressing a pro-productive miRNA: miR-557. Novel host cells were tested in two independent CLD campaigns using two different mAb candidates including a normal as well as a DTE antibody. Presence of miR-557 significantly enhanced each process step during CLD in a product independent manner. Stable expression of miR-557 increased the probability to identify high-producing cell clones. Furthermore, production cell lines derived from miR-557 expressing host cells exhibited significantly increased final product yields in fed-batch cultivation processes without compromising product quality. Strikingly, cells co-expressing miR-557 and a DTE antibody achieved a twofold increase in product titer compared to clones co-expressing a negative control miRNA. Thus, host cell engineering using miRNAs represents a promising tool to overcome limitations in industrial CLD especially with regard to DTE proteins. Biotechnol. Bioeng. 2017;114: 1495-1510. © 2017 Wiley Periodicals, Inc.


Intrinsic and Dopant-Related Luminescence of Undoped and Tb Plus Tm Double-Doped Lithium Magnesium Phosphate (LiMgPO4, LMP) Crystals.
In this work, the luminescence properties of undoped, Tm3+ doped, and Tb3+ plus Tm3+ double-doped crystals of the lithium magnesium phosphate (LiMgPO4, LMP) compound were investigated. The crystals under study were grown from melt using the micro-pulling-down method. The intrinsic and dopant-related luminescence of these crystals were studied using cathodo-, radio-, photo-, and thermoluminescence methods. Double doping with Tb3+ and Tm3+ ions was analyzed as these dopants are expected to exhibit an opposite trapping nature, namely to create the hole and electron-trapping sites, respectively. The spectra measured for the undoped samples revealed three prominent broad emission bands with maxima at around 3.50, 2.48, and 1.95 eV, which were associated with intrinsic structural defects within the studied compound. These were expected due to the anion vacancies forming F+-like centers while trapping the electrons. The spectra measured for Tb and Tm double-doped crystals showed characteristic peaks corresponding to the 4f-4f transitions of these dopants. A simplified model of a recombination mechanism was proposed to explain the temperature dependence of the measured thermally stimulated luminescence spectra. It seems that at low temperatures (below 300 °C), the charge carriers were released from 5D3-related Tb3+ trapping sites and recombination took place at Tm-related sites, giving rise to the characteristic emission of Tm3+ ions. At higher temperatures, above 300 °C, the electrons occupying the Tm3+-related trapping sites started to be released, and recombination took place at 5D4-related Tb3+ recombination centers, giving rise to the characteristic emission of Tb3+ ions. The model explains the temperature dependence observed for the luminescence emission from double-doped LiMgPO4 crystals and may be fully applicable for the consideration of emissions of other double-doped compounds.


Herpes simplex virus-infected cells contain a function(s) that destabilizes both host and viral mRNAs.
The herpes simplex virus virion contains a function that mediates the shutoff of host-protein synthesis and the degradation of host mRNA. Viral mutants affected in this function (vhs mutants) have previously been derived. Cells infected with these mutants exhibit a more stable synthesis of host as well as the immediate early (alpha)-viral proteins. We now show that a function associated with purified virions of the wild-type virus reduces the half-life of host and alpha mRNAs, whereas purified vhs-1 mutant virions lack this activity. The functional half-life of many early (beta)- and late (gamma)-viral mRNAs is also prolonged in mutant virus infections. These studies suggest that the wild-type virion brings into cells a function that indiscriminately reduces the half-life of both host and viral transcripts and that the early translational shutoff of the host is a consequence of this function. This function may facilitate rapid transitions in the expression of groups of genes that are transcriptionally turned on at different times after infection.


Endothelin receptor A blockade enhances taxane effects in prostate cancer.
Endothelin (ET) 1 is important in the growth of prostate cancer cells through the activation of the endothelin A (ET(A)) receptor. ET receptor blockade is a new therapeutic target in treating advanced prostate cancer. This study investigates the impact of the combination of the ET(A) antagonist atrasentan (ABT-627) and taxane chemotherapy on prostate cancer cell survival in vitro and on the delay of prostate cancer in a xenograft mouse model. In vitro, PPC-1 cells transfected with an ET(A)-overexpressing vector were treated with ABT-627, paclitaxel/docetaxel, or both. Clonogenic viability and cell death assays were used to determine cell survival and apoptosis, respectively. ABT-627 and docetaxel combination treatment was used in vivo to treat mice with established ET(A)-overexpressing PPC-1 xenograft tumors, and tumor growth rates were assessed. Cell proliferation and vascularity were determined with Ki-67 and CD31 staining, respectively. Cells treated with combination therapy had significantly fewer viable cells and more programmed cell death than cells given monotherapy. Xenograft tumor growth rates were significantly lower in mice treated with combination therapy than in animals given a single agent. Ki-67 immunostaining demonstrated significantly fewer proliferative cells following combination therapy than following monotherapy. This study demonstrates ABT-627 to have additive antitumor effects when used in combination with taxane drugs both in vitro and in vivo.


[Household smoking and stunting for children under five years].
Maternal tobacco use during pregnancy is one of the most important factors for low birth weight and length. However, postnatal exposure to environmental tobacco smoke has not been explored in children's growth studies. It is known that smoking is more prevalent in low socioeconomic groups and that stunting is also associated with socioeconomic variables. The objective of this study was to verify the effect of socioeconomic variables and environmental tobacco smoke on growth. Children under five years (n = 2,037) attending a primary health care clinic had their weight and stature measured, and a questionnaire on exposure to household passive smoking and socio-demographic characteristics was applied to parents. Prevalence of stunting (defined as a z-score lower than -2) was 4.3%. There was a negative association between stature and smoking during pregnancy, and positive associations with socioeconomic levels, family income, and parents' education. Linear hierarchical regression analysis showed that maternal and paternal smoking remains associated with low stature even after adjusting for maternal smoking during pregnancy and for socio-demographic variables.


DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin.
DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.


Relationship between psychotropic drugs and thyroid function: a review.
Some widely used psychoactive drugs, such as tricyclic antidepressants and antipsychotic phenothiazines exhibit iatrogenic effects on the thyroid. These side effects may arise from interactions at different steps of thyroid hormone biosynthesis. These drugs can induce a change in iodine capture by thyroid cells or can complex iodine, making it unavailable for thyroid hormone synthesis and thus decreasing thyroid hormone blood levels; they can also inhibit thyroid peroxidase activity and thus T3 and T4 synthesis or enhance deiodination of T4 to T3 or to Rt3 by stimulation of deiodinase activity. Moreover, tricyclic antidepressants interfere with the hypothalamic-pituitary-thyroid axis via the noradrenergic or serotonergic systems and might therefore decrease T4 or T3 blood levels, respectively. Phenothiazines can induce autoimmune hypothyroidism, as shown by an increase in the expression of the major histocompatibility complex antigen and by a production of antithyroglobulin or antithyroperoxidase antibodies. However, all these mechanisms are only speculative in humans, as they have only been demonstrated in vitro or in animal experiments. Clinically, thyroid function and affective disorders are closely linked. On one hand, the therapeutic response to antidepressants could be influenced by the thyroid status; on the other hand, the larger the thyroxin decrease induced by antidepressants, the better the therapeutic effect might be. Moreover, cotreatment with thyroid hormones and antidepressant drugs could allow either a decrease in the rate of treatment failure or a faster recovery from depression. As antipsychotic or antidepressant treatments are administered over long periods in humans, their thyroid toxic effects must be taken seriously.


A surview of recent patents on anti-infective therapy for Clostridium difficile.
Clostridium difficile has become the most common infectious cause of healthcare-associated diarrhea, with serious morbidity, prolonged hospitalization and even death. Treatment of the disease utilizing today's therapies does not guarantee a successful outcome. In the past decade, many new ideas and inventions have surfaced exploring different treatment strategies of Clostridium difficile associated diarrhea (CDAD). These treatments include antitoxins, novel antimicrobials, immunoglobulins and large inert synthetic compounds. In this paper, we survey of a number of representative patents issued from 2000 to the present targeting treatment of this difficult and dreaded disease.


Alpha-lipoic acid improves acetic acid-induced gastric ulcer healing in rats.
To evaluate the role of ALA treatment on the healing of acetic acid-induced gastric ulcer, rats were given ALA (35 mg/kg/day) or saline for 3 days before the induction of ulcer and the treatment was continued twice daily for 2 days (early) or 10 days (late) until they were decapitated. Gastric ulcer index, microscopic score, elevated DNA fragmentation and chemiluminescence levels of the saline-treated ulcer groups were all reduced by ALA treatment. Likewise, ALA treatment inhibited chemiluminescence levels in both early and late ulcer groups. Marked reduction in glutathione levels of the saline-treated early ulcer group was reversed by ALA treatment, while ALA treatment was effective in depressing gastric myeloperoxidase activity in the late ulcer group. In conclusion, ALA treatment shows protective role in the healing of acetic acid-induced gastric injury in rats via the suppression of neutrophil accumulation, preservation of endogenous glutathione, inhibition of reactive oxidant generation and apoptosis.


Synthesis of trifluoromethyl N,N-aminals from nitrogen containing heterocycles by using a plasma flow microreactor.
Trifluoromethyl N,N-aminals are important precursors allowing access to fluorinated building blocks. In this work, the direct synthesis of trifluoromethyl N,N-aminals from nitrogen containing heterocycles is reported using argon plasma in a continuous flow microreactor without any additives or metal catalysts. Their transformation to N-trifluoroethyl amines is also reported.


Functions of motor proteins in echinoderm embryos: an argument in support of antibody inhibition experiments.
Antibody inhibition experiments are proving to be extremely valuable in probing the in vivo functions of actin- and microtubule-based motor proteins in the early development of echinoderm embryos, despite some skepticism among many cell biologists concerning the reliability of this approach. Antibody inhibition has revealed that motor proteins participate in diverse events during early echinoderm development, including mitosis, cytokinesis, the transport of exocytotic vesicles, and the assembly of motile cilia.


Victims of our own success: will immunization remain the paradigm of effective prevention? Grantmakers In Health.
As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened a select group of grantmakers and national experts who have made a major commitment to childhood immunization. The roundtable explored various factors influencing public acceptance of childhood immunization, with discussions ultimately centering on the importance of ensuring and conveying accurate information to the public and policymakers. Current and potential roles for health philanthropy were also discussed. This report brings together key points from the day's discussion with factual information on childhood immunization drawn from a background paper prepared for the meeting. When available, recent findings, facts, and figures have been incorporated.


Quality of Communication Questionnaire for Patients Hospitalized in Intensive and Palliative Care: Validity Evidence for Use in Brazil.
The Quality of Communication Questionnaire (QoC) was culturally adapted for Brazil due to its importance and use in several studies and different scenarios. The objective of this study was to evaluate the validity evidence of the Brazilian version of the QoC. A validation study was carried out involving 253 patients admitted to five public hospitals in Southern Brazil. Data were analyzed using descriptive analysis, Cronbach's alpha (α) to assess internal consistency, exploratory factor analysis, and goodness-of-fit index. One hundred and three patients were in intensive care (IC), and 150 were in palliative care (PC). The participants' mean age was 51 years (SD = 14.2). QoC,and its general communication subscale, and end-of-life communication subscale means were 5.5 (SD = 1.6), 8.8 (SD = 1.5), and 5.5 (SD = 1.6) respectively. Among patients in IC, QoC Cronbach's alpha was .75, and .84 in the general communication subscale and .51 in the end-of-life communication subscale. Among patients in PC, QoC Cronbach's alpha was .83, and .88 in the general communication subscale, and .71 in the end-of-life communication subscale. The root mean square error of approximation was .07 (90% CI: .04 - .08); Tucker-Lewis index was .97 (95% CI: .95 - .98); comparative fit index was .98 (95% CI: .97 - .99), and χ2/df ratio was 1.33 (χ2[53] = 70.858, p = .05). The authors conclude that the general communication subscale of QoC Brazilian version has good validity evidence for patients in IC and PC, whereas the end-of-life communication subscale is only valid for patient in PC.


The role of acroblast formation during Drosophila spermatogenesis.
Protein recycling is important for maintaining homeostasis of the Golgi and its cisternae. The Vps54 (Scat) protein, a subunit of the GARP tethering complex, is a central factor in retrograde transport to the trans-Golgi. We found the scat(1) mutant to be male sterile in Drosophila with individualization problems occurring during spermatogenesis. Another typically observed phenotype was the abnormal nuclear structure in elongated mutant cysts. When examining the structure and function of the Golgi, a failure in acrosome formation and endosome-Golgi vesicular transport were found in the scat(1) mutant. This acrosome formation defect was due to a fault in the trans-Golgi side of the acroblast ribbon. When testing a mutation in a second retrograde transport protein, Fws, a subunit of the conserved oligomeric Golgi (COG) tethering complex, the acroblast structure, was again disrupted. fws(P) caused a similar, albeit milder, acrosome and sperm individualization phenotype as the scat(1) mutant. In the case of fws(P) the cis side of the acroblast ribbon was dispersed, in-line with the intra-Golgi retrograde function of COG. Our results highlight the importance of an intact acroblast for acrosome formation, nuclear elongation and therefore sperm maturation. Moreover, these results suggest the importance of retrograde tethering complexes in the formation of a functional Golgi ribbon.


Two new species in the genus Phoxokalliapseudes Drumm & Heard, 2011 (Crustacea: Tanaidacea: Kalliapseudidae) from the southwestern and southern coasts of Korea.
Two new species of Phoxokalliapseudes from the southwestern and southern coasts of Korea are described. Phoxokalliapseudes aculeatus n. sp. is distinguished by the two robust spiniform setae on the ventral margin of the cheliped basis, pereonites 2-6 each with a hyposphaenium and small spinules, and the setiferous lobe on the mandibles with different numbers of serrated spiniform setae in the female and male (five and six, respectively). Phoxokalliapseudes cinctus n. sp. can be distinguished by the propodus of the male cheliped with the largest length to width ratio (2.5: 1) of the genus, and the fixed finger with small denticles on the cutting edge and near the insertion of the dactylus. The female has the largest dactylus to propodus length ratio of pereopod 6 in the genus. Only four species of Phoxokalliapseudes have been described or redescribed previously, of which some exhibit morphological differences with the type specimens, possibly indicating additional new species. To minimize identification difficulties caused by morphometric variations in developmental stages, the morphological characteristics of the new species are described in detail for a fixed size range and compared to different-sized individuals. Additionally, a comprehensive comparison of the new Phoxokalliapseudes species with the other known species is provided and discussed.


Image Restoration by Iterative Denoising and Backward Projections.
Inverse problems appear in many applications, such as image deblurring and inpainting. The common approach to address them is to design a specific algorithm for each problem. The Plug-and-Play (P&P) framework, which has been recently introduced, allows solving general inverse problems by leveraging the impressive capabilities of existing denoising algorithms. While this fresh strategy has found many applications, a burdensome parameter tuning is often required in order to obtain high-quality results. In this paper, we propose an alternative method for solving inverse problems using off-the-shelf denoisers, which requires less parameter tuning. First, we transform a typical cost function, composed of fidelity and prior terms, into a closely related, novel optimization problem. Then, we propose an efficient minimization scheme with a P&P property, i.e., the prior term is handled solely by a denoising operation. Finally, we present an automatic tuning mechanism to set the method's parameters. We provide a theoretical analysis of the method and empirically demonstrate its competitiveness with task-specific techniques and the P&P approach for image inpainting and deblurring.


Cross-regulation of cortisol secretion by adrenocorticotropin and platelet-activating factor in perfused guinea pig adrenals.
We examined the cross-regulation of signaling between ACTH-and platelet-activating factor (PAF)-mediated steroidogenesis in the perfused guinea pig adrenal gland. Our method of in situ perfusion using an artificial medium can evaluate whether cortisol secretion in response to ACTH and PAF is interactive. Treating adrenal glands with 100 pg/ml ACTH diminished the subsequent cortisol response to 10 nM PAF. By contrast, PAF resulted in subsequent potentiation of ACTH-induced cortisol secretion. A mixture of 50 microM L-alpha-1-oleoyl-2-acetyl-sn-glycerol (OAG), an activator of protein kinase C (PKC), and 3.3 microM calcium ionophore (A23187), or 10 microM forskolin (FRK) diminished the cortisol response to PAF, whereas that to ACTH was unaffected. Each of PAF, ACTH, or FRK eliminated the cortisol response to OAG plus A23187, whereas that to FRK was unaffected. These data show that the protein kinase A (PKA)-dependent processes activated by ACTH or FRK can interfere with PAF-induced signal transduction at receptor and post-receptor levels. In contrast, PKC-dependent processes activated by PAF promoted ACTH-signaling at receptor and post-receptor level. Cross-regulation between processes activated by PAF receptor-PKC and by ACTH receptor-PKA might function in the multifactorial regulation of adrenocortical steroidogenesis.


A review and experimental study on the application of classifiers and evolutionary algorithms in EEG-based brain-machine interface systems.
Considering the importance and the near-future development of noninvasive brain-machine interface (BMI) systems, this paper presents a comprehensive theoretical-experimental survey on the classification and evolutionary methods for BMI-based systems in which EEG signals are used. The paper is divided into two main parts. In the first part, a wide range of different types of the base and combinatorial classifiers including boosting and bagging classifiers and evolutionary algorithms are reviewed and investigated. In the second part, these classifiers and evolutionary algorithms are assessed and compared based on two types of relatively widely used BMI systems, sensory motor rhythm-BMI and event-related potentials-BMI. Moreover, in the second part, some of the improved evolutionary algorithms as well as bi-objective algorithms are experimentally assessed and compared. In this study two databases are used, and cross-validation accuracy (CVA) and stability to data volume (SDV) are considered as the evaluation criteria for the classifiers. According to the experimental results on both databases, regarding the base classifiers, linear discriminant analysis and support vector machines with respect to CVA evaluation metric, and naive Bayes with respect to SDV demonstrated the best performances. Among the combinatorial classifiers, four classifiers, Bagg-DT (bagging decision tree), LogitBoost, and GentleBoost with respect to CVA, and Bagging-LR (bagging logistic regression) and AdaBoost (adaptive boosting) with respect to SDV had the best performances. Finally, regarding the evolutionary algorithms, single-objective invasive weed optimization (IWO) and bi-objective nondominated sorting IWO algorithms demonstrated the best performances. We present a general survey on the base and the combinatorial classification methods for EEG signals (sensory motor rhythm and event-related potentials) as well as their optimization methods through the evolutionary algorithms. In addition, experimental and statistical significance tests are carried out to study the applicability and effectiveness of the reviewed methods.


Molecular Network for Regulation of Seed Size in Plants.
The size of seeds is particularly important for agricultural development, as it is a key trait that determines yield. It is controlled by the coordinated development of the integument, endosperm, and embryo. Large seeds are an important way of improving the ultimate "sink strength" of crops, providing more nutrients for early plant growth and showing certain tolerance to abiotic stresses. There are several pathways for regulating plant seed size, including the HAIKU (IKU) pathway, ubiquitin-proteasome pathway, G (Guanosine triphosphate) protein regulatory pathway, mitogen-activated protein kinase (MAPK) pathway, transcriptional regulators pathway, and phytohormone regulatory pathways including the auxin, brassinosteroid (BR), gibberellin (GA), jasmonic acid (JA), cytokinin (CK), Abscisic acid (ABA), and microRNA (miRNA) regulatory pathways. This article summarizes the seed size regulatory network and prospective ways of improving yield. We expect that it will provide a valuable reference to researchers in related fields.


Overcoming Heterogeneity of Antigen Expression for Effective CAR T Cell Targeting of Cancers.
Chimeric antigen receptor (CAR) gene-modified T cells (CAR T cells) can eradicate B cell malignancies via recognition of surface-expressed B lineage antigens. Antigen escape remains a major mechanism of relapse and is a key barrier for expanding the use of CAR T cells towards solid cancers with their more diverse surface antigen repertoires. In this review we discuss strategies by which cancers become amenable to effective CAR T cell therapy despite heterogeneous phenotypes. Pharmaceutical approaches have been reported that selectively upregulate individual target antigens on the cancer cell surface to sensitize antigen-negative subclones for recognition by CARs. In addition, advanced T cell engineering strategies now enable CAR T cells to interact with more than a single antigen simultaneously. Still, the choice of adequate targets reliably and selectively expressed on the cell surface of tumor cells but not normal cells, ideally by driving tumor growth, is limited, and even dual or triple antigen targeting is unlikely to cure most solid tumors. Innovative receptor designs and combination strategies now aim to recruit bystander cells and alternative cytolytic mechanisms that broaden the activity of CAR-engineered T cells beyond CAR antigen-dependent tumor cell recognition.


Diurnal Flight Activity of House Flies (Musca domestica) is Influenced by Sex, Time of Day, and Environmental Conditions.
House flies (Musca domestica L.) are common synanthropic pests associated with confined animal operations, including dairy farms. House flies can cause substantial nuisance and may transmit human and animal pathogens. Surprisingly little is known about the daily flight activity of house flies. This study examined diurnal house fly flight activity on two southern California dairies using clear sticky traps to capture flies over hourly intervals. Flight activity for both males and females combined started near dawn and generally increased to a single broad activity peak during mid to late morning. Male flight activity peaked earlier than female flight activity and this separation in peak activity widened as mean daytime temperature increased. Flight activity for both sexes increased rapidly during early morning in response to the combined effects of increasing light intensity and temperature, with decreasing flight activity late in the day as temperature decreased. During midday, flight activity was slightly negatively associated with light intensity and temperature. Collection period (time of day) was a useful predictor of house fly activity on southern California dairies and the diurnal pattern of flight activity should be considered when developing house fly monitoring and control programs.


Migration and Morphology of Colloidal Gel Clusters in Cylindrical Channel Flow.
We report the cluster-level structural parameters of colloidal thermogelling nanoemulsions in channel flow as a function of attractive interactions and local shear stress. The spatiotemporal evolution of the gel microstructure is obtained by directly visualizing the dispersed phase near the edge of a cylindrical channel. We observe the flow of the nanoemulsion gels in a range of radial positions (r) and shear stresses between 70 and 220 Pa, finding that the r-dependent cluster sizes are due to a balance between shear forces that yield bonds and attractive interactions that rebuild the inter-colloid bonds. In addition, the largest clusters appear to be affected by confinement and accumulate toward the central axis of the channel, resulting in a volume fraction gradient. Cluster size and volume fraction variabilities are most prominent when the attractive interactions are the strongest. Specifically, a distinct transition from sparse, fluidized clusters near the walls to concentrated, large clusters toward the center is observed. These two structural states coincide with a velocity-based transition from higher shear rates near the walls to lower shear rates toward the center of the channel. We find a compounding effect where larger gel clusters, formed under strong attractions and low shear stresses, are susceptible to shear-induced migration that intensifies r-dependent heterogeneity and deviations in the flow behavior from predictive models.


Negative mood-induced alcohol-seeking is greater in young adults who report depression symptoms, drinking to cope, and subjective reactivity.
Acute negative mood powerfully motivates alcohol-seeking behavior, but it remains unclear whether sensitivity to this effect is greater in drinkers who report depression symptoms, drinking to cope, and subjective reactivity. To examine these questions, 128 young adult alcohol drinkers (ages 18-25) completed questionnaires of alcohol use disorder symptoms, depression symptoms, and drinking to cope with negative affect. Baseline alcohol choice was measured by preference to enlarge alcohol versus food thumbnail images in two-alternative forced-choice trials. Negative mood was then induced by depressive statements and music, before alcohol choice was tested. Subjective reactivity was indexed by increased sadness pre- to post-mood induction. Baseline alcohol choice correlated with alcohol dependence symptoms (p = .001), and drinking coping motives (ps ≤ .01). Mood induction increased alcohol choice and subjective sadness overall (ps < .001). The mood-induced increase in alcohol choice was associated with depression symptoms (p = .007), drinking to cope (ps ≤ .03), and subjective reactivity (p = .007). The relationship between mood-induced alcohol choice and drinking to cope remained significant after covarying for other drinking motives. Furthermore, the three predictors (depression, drinking to cope, and subjective reactivity) accounted for unique variance in mood-induced alcohol choice (ps ≥ .03), and collectively accounted for 18% of the variance (p < .001). These findings validate the pictorial alcohol choice task as sensitive to the relative value of alcohol and acute negative mood. The findings also accord with the core prediction of negative reinforcement theory that sensitivity to the motivational impact of negative mood on alcohol-seeking behavior may be an important mechanism that links depression and alcohol dependence. (PsycINFO Database Record


Nisin Damages the Septal Membrane and Triggers DNA Condensation in Methicillin-Resistant Staphylococcus aureus.
Nisin is applied as a food preservative in processed foods and has the potential to be used synergistically with antibiotics for treatment of patients infected by antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus. The present study explores the antimicrobial effect of nisin on S. aureus viability and membrane integrity and, for the first time, used super-resolution microscopy to study morphological changes induced in S. aureus cells exposed to nisin. The exposure of S. aureus to nisin caused membrane depolarization and rapid killing. Super-resolution structured-illumination microscopy and transmission electron microscopy confirmed that nisin damages the cellular membrane and causes lysis of cells. Strikingly, condensation of chromosomal DNA was observed in all cells exposed to nisin, a phenotype not previously reported for this compound. Moreover, cells exposed to nisin were significantly smaller than non-exposed cells indicating the emergence of cell shrinkage. The strong association of DNA condensation with nisin exposure indicates that nisin interferes with chromosome replication or segregation in S. aureus.


Retinoic Acid Enhances Apolipoprotein E Synthesis in Human Macrophages.
Apolipoprotein E (ApoE) represents a pivotal target in Alzheimer's disease (AD) and is modulated through retinoic acid (RA), an endogenous neuroprotective and anti-inflammatory compound. A major source of ApoE are microglia, which are pathologically activated in AD. Activated microglia are known to block RA signaling. This suggests a vicious cycle between inflammation, RA signaling, and ApoE homeostasis in AD pathogenesis. To test this hypothesis, we investigated effects of RA and proinflammatory activation on ApoE synthesis in primary human macrophage-derived microglial-like cells. Our results indicate that proinflammatory activation attenuates ApoE synthesis, an effect blocked by RA.


Proteasomal Dysfunction Induced By Diclofenac Engenders Apoptosis Through Mitochondrial Pathway.
Diclofenac is the most commonly used phenylacetic acid derivative non-steroidal anti-inflammatory drug (NSAID) that demonstrates significant analgesic, antipyretic, and anti-inflammatory effects. Several epidemiological studies have demonstrated anti-proliferative activity of NSAIDs and examined their apoptotic induction effects in different cancer cell lines. However, the precise molecular mechanisms by which these pharmacological agents induce apoptosis and exert anti-carcinogenic properties are not well known. Here, we have observed that diclofenac treatment induces proteasome malfunction and promotes accumulation of different critical proteasome substrates, including few pro-apoptotic proteins in cells. Exposure of diclofenac consequently elevates aggregation of various ubiquitylated misfolded proteins. Finally, we have shown that diclofenac treatment promotes apoptosis in cells, which could be because of mitochondrial membrane depolarization and cytochrome c release into cytosol. This study suggests possible beneficial insights of NSAIDs-induced apoptosis that may improve our existing knowledge in anti-proliferative interspecific strategies development. J. Cell. Biochem. 118: 1014-1027, 2017. © 2016 Wiley Periodicals, Inc.


Interleukin-10 anti-inflammatory response to Borrelia burgdorferi, the agent of Lyme disease: a possible role for suppressors of cytokine signaling 1 and 3.
It has been established that interleukin-10 (IL-10) inhibits inflammatory cytokines produced by macrophages in response to Borrelia burgdorferi or its lipoproteins. The mechanism by which IL-10 exerts this anti-inflammatory effect is still unknown. Recent findings indicate that suppressors of cytokine signaling (SOCS) proteins are induced by cytokines and Toll-like receptor (TLR)-mediated stimuli, and in turn they can down-regulate cytokine and TLR signaling in macrophages. Because it is known that SOCS are induced by IL-10 and that B. burgdorferi and its lipoproteins most likely interact via TLR2 or the heterodimers TLR2/1 and/or TLR2/6, we hypothesized that SOCS are induced by IL-10 and B. burgdorferi and its lipoproteins in macrophages and that SOCS may mediate the inhibition by IL-10 of concomitantly elicited cytokines. We report here that mouse J774 macrophages incubated with IL-10 and added B. burgdorferi spirochetes (freeze-thawed, live, or sonicated) or lipidated outer surface protein A (L-OspA) augmented their SOCS1/SOCS3 mRNA and protein expression, with SOCS3 being more abundant. Pam(3)Cys, a synthetic lipopeptide, also induced SOCS1/SOCS3 expression under these conditions, but unlipidated OspA was ineffective. Neither endogenous IL-10 nor the translation inhibitor cycloheximide blocked SOCS1/SOCS3 induction by B. burgdorferi and its lipoproteins, indicating that the expression of other genes is not required. This temporally correlated with the IL-10-mediated inhibition of the inflammatory cytokines IL-1beta, IL-6, IL-12p40, IL-18, and tumor necrosis factor alpha. Our data are evidence to suggest that expression of SOCS is part of the mechanism of IL-10-mediated inhibition of inflammatory cytokines elicited by B. burgdorferi and its lipoproteins.


Lack of host specialization despite selective host use in brood parasitic cuckoo catfish.
Host-parasite dynamics involve coevolutionary arms races, which may lead to host specialization and ensuing diversification. Our general understanding of the evolution of host specialization in brood parasites is compromised by a restricted focus on bird and insect lineages. The cuckoo catfish (Synodontis multipunctatus) is an obligate parasite of parental care of mouthbrooding cichlids in Lake Tanganyika. Given the ecological and taxonomic diversity of mouthbrooding cichlids in the lake, we hypothesized the existence of sympatric host-specific lineages in the cuckoo catfish. In a sample of 779 broods from 20 cichlid species, we found four species parasitized by cuckoo catfish (with prevalence of parasitism of 2%-18%). All parasitized cichlids were from the tribe Tropheini, maternal mouthbrooders that spawn over a substrate (rather than in open water). Phylogenetic analysis based on genomic (ddRAD sequencing) and mitochondrial (Dloop) data from cuckoo catfish embryos showed an absence of host-specific lineages. This was corroborated by analyses of genetic structure and co-ancestry matrix. Within host species, parasitism was not associated with any individual characteristic we recorded (parent size, water depth), but was costly as parasitized parents carried smaller clutches of their own offspring. We conclude that the cuckoo catfish is an intermediate generalist and discuss costs, benefits and constraints of host specialization in this species and brood parasites in general.


Sclerosing peritonitis: report of three cases.
Sclerosing peritonitis is a dramatic complication of continuous ambulatory peritoneal dialysis and chronic peritoneal inflammation. Both visceral and parietal surfaces of the peritoneal cavity are involved. A thickened peritoneum encloses the small intestine in a "cocoon" formation which often leads to intestinal occlusion. CT scan may help obtaining an early diagnosis but diagnosis is often established with some delay or even at the time of laparotomy. Our report describes three cases of this uncommon peritoneal fibrosis syndrome which caused intestinal obstruction requiring surgical intervention.


Graves' disease after treatment with alemtuzumab for multiple sclerosis.
Alemtuzumab, a humanized monoclonal antibody against CD52, is effective in the treatment of early relapsing-remitting multiple sclerosis (MS). Common adverse effects include an acute-phase reaction, infections and autoimmune diseases, including thyroid disorders. Patients from two phase 3 trials (CARE MS 1 and 2, n=15) were studied in a clinical research center. Five out of fifteen patients developed severe Graves' disease after a mean of 32 months following the first alemtuzumab treatment. Thyroid function tests and thyroid antibodies were assessed. In addition, endocrine tests and measurement of antibodies indicative of autoimmunity were performed. Of the five patients developing Graves' disease, four patients were initially treated with antithyroid drugs, whereas the fifth patient had mild and self-limiting hyperthyroidism. Of the four patients treated with antithyroid drugs, one is currently under medical treatment in a dose-reducing regimen, whereas three patients underwent near-total thyroidectomy 2, 12 and 16 months later. Two patients developed endocrine ophthalmopathy. Pituitary, adrenal and gonadal hormones were normal in all patients. While four out of five patients were positive for several other autoantibodies, none developed other autoimmune diseases. Since autoimmune thyroid disease is common after alemtuzumab treatment for MS, pretreatment screening and careful follow-up may allow for early diagnosis and treatment.


[Recommendations for the prevention of respiratory syncytial virus infection].
Premature babies < or = 35 weeks gestation, with or without chronic lung disease (CLD), and infants affected by severe congenital heart disease should be considered high risk population for RSV infection and hospitalization. Hygienic measures and RSV monoclonal antibodies (palivizumab) have been found useful in decreasing rates of RSV hospitalization in these patients. Guidelines for their administration include: a) strongly recommended use in premature babies < or = 28 weeks gestation, or born between 29-32 weeks gestation and less than 6 months at start of RSV station or discharged along it, or affected by CLD in treatment during last 6 months or by severe congenital heart disease. Last two groups could be prophylaxed for two RSV seasons. b) Recommended use among premature babies between 32-35 weeks gestation and less than 6 months of age and presenting two or more risk factors: chronologic age < 10 weeks at start of RSV station, breastfeeding < or = 2 months (physician prescription), sibling < 14 years old, day-care assistance, family history of wheezing, > or = 4 adults at home, airways malformation or neuromuscular disease.