Dual-Contrast Biphasic Liver Imaging With Iodine and Gadolinium Using Photon-Counting Detector Computed Tomography: An Exploratory Animal Study.
The aims of this study were to develop a single-scan dual-contrast protocol for biphasic liver imaging with 2 intravenous contrast agents (iodine and gadolinium) and to evaluate its effectiveness in an exploratory swine study using a photon-counting detector computed tomography (PCD-CT) system. A dual-contrast CT protocol was developed for PCD-CT to simultaneously acquire 2 phases of liver contrast enhancement, with the late arterial phase enhanced by 1 contrast agent (iodine-based) and the portal venous phase enhanced by the other (gadolinium-based). A gadolinium contrast bolus (gadobutrol: 64 mL, 8 mL/s) and an iodine contrast bolus (iohexol: 40 mL, 5 mL/s) were intravenously injected in the femoral vein of a healthy domestic swine, with the second injection initiated after 17 seconds from the beginning of the first injection; PCD-CT image acquisition was performed 12 seconds after the beginning of the iodine contrast injection. A convolutional neural network (CNN)-based denoising technique was applied to PCD-CT images to overcome the inherent noise magnification issue in iodine/gadolinium decomposition task. Iodine and gadolinium material maps were generated using a 3-material decomposition method in image space. A set of contrast samples (mixed iodine and gadolinium) was attached to the swine belly; quantitative accuracy of material decomposition in these inserts between measured and true concentrations was calculated using root mean square error. An abdominal radiologist qualitatively evaluated the delineation of arterial and venous vasculatures in the swine liver using iodine and gadolinium maps obtained using the dual-contrast PCD-CT protocol. The iodine and gadolinium samples attached to the swine were quantified with root mean square error values of 0.75 mg/mL for iodine and 0.45 mg/mL for gadolinium from the contrast material maps derived from the denoised PCD-CT images. Hepatic arteries containing iodine and veins containing gadolinium in the swine liver could be clearly visualized. Compared with the original images, better distinctions between 2 liver phases were achieved using CNN denoising, with approximately 60% to 80% noise reduction in contrast material maps acquired with the denoised PCD-CT images compared with the original images. Simultaneous biphasic liver imaging in a single multienergy PCD-CT acquisition using a dual-contrast (iodine and gadolinium) injection protocol and CNN denoising was demonstrated in a swine study, where the enhanced hepatic arteries (containing iodine) and the enhanced hepatic veins (containing gadolinium) could be clearly visualized and delineated in the swine liver.


[Lanzoptol efficiency for heartburn alleviation in patients with NERD].
Now you can find a growing interest in modern proton pump inhibitors. This article presents results of Lanzoptol (lansoprazol company "Krka", Slovenia) drug study. This study involved 30 people including 13 women and 17 men. Study included patients with NERD aged from 18 to 65 years with clinical manifestations like pyrosis, regurgitation, epigastrium pain and in with absence of esophageal ulcers and erosions at endoscopic study. Duration of disease ranged from 2 months to 20 years. Results of the therapy: completely stopped heartburn for 4 weeks of treatment at 26 people (87%), partly--at 4. 9 patients got acute pharmacological test with 48-hour pH meter. The average time percentage at pH <4 decreased in 2 times, amount of acid esophageal reflux at pH <4--decreased in 4,5 times, the number of long-Esophageal Reflux decreased in 1,5 times. De Meester combined ratio decreased in 2 times. According to the daily pH meter speed of antisecretory effect on the average was 135 minutes. Lanzopotol portability is good, side effects hasn't been identified. So, Lanzoptol demonstrated a high rate of antisecretory effect and high clinical efficacy with an excellent portability.


Dose-response effects of exercise training on the subjective sleep quality of postmenopausal women: exploratory analyses of a randomised controlled trial.
To investigate whether a dose-response relationship existed between exercise and subjective sleep quality in postmenopausal women. This objective represents a post hoc assessment that was not previously considered. Parallel-group randomised controlled trial. Clinical exercise physiology laboratory in Dallas, Texas. 437 sedentary overweight/obese postmenopausal women. Participants were randomised to one of four treatments, each of 6 months of duration: a non-exercise control treatment (n=92) or one of three dosages of moderate-intensity exercise (50% of VO(2peak)), designed to meet 50% (n=151), 100% (n=99) or 150% (n=95) of the National Institutes of Health Consensus Development Panel physical activity recommendations. Exercise dosages were structured to elicit energy expenditures of 4, 8 or 12 kilocalories per kilogram of body weight per week (KKW), respectively. Analyses were intent to treat. Continuous scores and odds of having significant sleep disturbance, as assessed by the Sleep Problems Index from the 6-item Medical Outcomes Study Sleep Scale. Outcome assessors were blinded to participant randomisation assignment. Change in the Medical Outcomes Study Sleep Problems Index score at 6 months significantly differed by treatment group (control: -2.09 (95% CI -4.58 to 0.40), 4 KKW: -3.93 (-5.87 to -1.99), 8 KKW: -4.06 (-6.45 to -1.67), 12 KKW: -6.22 (-8.68 to -3.77); p=0.04), with a significant dose-response trend observed (p=0.02). Exercise training participants had lower odds of having significant sleep disturbance at postintervention compared with control (4 KKW: OR 0.37 (95% CI 0.19 to 0.73), 8 KKW: 0.36 (0.17 to 0.77), 12 KKW: 0.34 (0.16 to 0.72)). The magnitude of weight loss did not differ between treatment conditions. Improvements in sleep quality were not related to changes in body weight, resting parasympathetic control or cardiorespiratory fitness. Exercise training induced significant improvement in subjective sleep quality in postmenopausal women, with even a low dose of exercise resulting in greatly reduced odds of having significant sleep disturbance. clinicaltrials.gov identifier: NCT00011193.


Optimal waste load allocation in river systems based on a new multi-objective cuckoo optimization algorithm.
Water pollution escalates with rising waste discharge in river systems, as the rivers' limited pollution tolerance and constrained self-cleaning capacity compel the release of treated pollutants. Although several studies have shown that the non-dominated sorting genetic algorithm-II (NSGA-II) is an effective algorithm regarding the management of river water quality to reach water quality standards, to our knowledge, the literature lacks using a new optimization model, namely, the multi-objective cuckoo optimization algorithm (MOCOA). Therefore, this research introduces a new optimization framework, including non-dominated sorting and ranking selection using the comparison operator densely populated towards the best Pareto front and a trade-off estimation between the goals of discharges and environmental protection authorities. The suggested algorithm is implemented for a waste load allocation issue in Jajrood River, located in the North of Iran. The limitation of this research is that discharges are point sources. To analyze the performance of the new optimization algorithm, the simulation model is linked with a hybrid optimization model using a cuckoo optimization algorithm and non-dominated sorting genetic algorithms to convert a single-objective algorithm to a multi-objective algorithm. The findings indicate that, in terms of violation index and inequity values, MOCOA's Pareto front is superior to NSGA-II, which highlights the MOCOA's effectiveness in waste load allocation. For instance, with identical population sizes and violation indexes for both algorithms, the optimal Pareto front ranges from 1.31 to 2.36 for NSGA-II and 0.379 to 2.28 for MOCOA. This suggests that MOCOA achieves a superior Pareto front in a more efficient timeframe. Additionally, MOCOA can attain optimal equity in the smaller population size.


Research on protective mechanism of ibuprofen in myocardial ischemia-reperfusion injury in rats through the PI3K/Akt/mTOR signaling pathway.
To study the protective mechanism of ibuprofen (Ib) in myocardial ischemia-reperfusion (I/R) injury in rats, and to analyze its regulatory effect on the phosphatidylinositol 3-hydroxy kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. The rat model of myocardial I/R injury was established via ligation of the left main coronary artery (LCA) for 30 min and then reperfusion for 120 min. A total of 36 Sprague-Dawley (SD) rats were randomly divided into sham group (S group, n=12), model group (I/R group, n=12) and Ib group (n=12). The levels of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in each group were detected. The rats were executed, the heart was isolated and the area of myocardial infarction was determined via 2,3,5-triphenyltetrazolium chloride (TTC) staining. The expression levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 (HIF-1) and apoptosis-related proteins in myocardial tissues in each group were detected via Western blotting. Moreover, the content of inflammatory factors in myocardial tissues in each group was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The expression levels of related proteins in the PI3K/Akt/mTOR signaling pathway in myocardial tissues were further analyzed. Compared with those in S group, the levels of CK-MB and LDH were significantly increased (p<0.01), the area of myocardial infarction was significantly increased (p<0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were increased (p<0.01), while Bcl-2/Bax declined (p<0.01), the content of interleukin-1 (IL-1), IL-6 and tumor necrosis factor-α (TNF-α) in myocardial tissues was increased (p<0.01), while the content of IL-10 declined (p<0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly decreased (p<0.01) in I/R group. Compared with those in I/R group, the levels of CK-MB and LDH were significantly decreased (p<0.01), the area of myocardial infarction was significantly decreased (p<0.01), the VEGF, HIF-1 and Cleaved caspase-3 protein levels in myocardial tissues were decreased (p<0.01), while Bcl-2/Bax was increased (p<0.01), the content of IL-1, IL-6 and TNF-α in myocardial tissues declined (p<0.01), while the content of IL-10 was significantly increased (p<0.01), and the expression levels of PI3K, p-Akt and p-mTOR proteins in myocardial tissues were significantly increased (p<0.01) in Ib group. Ib can activate the PI3K/Akt/mTOR signaling pathway, reduce the release of inflammatory factors and apoptosis, and alleviate the myocardial I/R injury in myocardial cells in rats.


HIV therapy in the post-eradication era.
Over the past three years, most efforts of virologists and immunologists involved in the field of Human Immunodeficiency Virus (HIV) have been focussed on strategies aimed at eradicating the infection. So far, however, all the approaches have been unsuccessful. Indeed, even if the currently available potent antiretroviral regimens are able to induce a profound and durable suppression of viral replication, they have poor effect on a viral reservoir of latently infected CD4+ T lymphocytes that rapidly reactivate after treatment discontinuation. Different approaches, including combined (immune based and antiretroviral) therapies, are therefore under investigation. The goal is to achieve an equilibrium where virus-induced immune dysfunction is prevented by an effective anti HIV immune response.


Lunchtime as a therapeutic moment: a health education approach with alcohol-dependent women.
Alcoholism is a relevant problem in public health. The use of alcohol among women has increased as well as the search for treatment. This research proposes the resignification of food to these women, as a harm reduction strategy. The research aimed to study and to discuss the experience of lunchtime as a therapeutic moment, presenting theoretic assumptions, strategies and immediate results. The clinical-qualitative methodology and the content analysis were used. The results, divided in seven categories, refer to the educational intervention process: environment as facilitator; sharing food--becoming a partner; broadening the perception of food; food and its meanings; sexuality; relapses; depression x motivation. The heath education performed during lunch is a possibility of therapeutic intervention, provided that the health professionals perceive the multidimensionality of food, considering the nutritional aspects as much as the symbolic ones, which are relevant for the creation of bonding and motivation for the treatment.


[Proximal row carpectomy in carpal collapse].
Proximal row carpectomy (PRC) is a generally accepted procedure in the treatment of an advanced radiocarpal arthrosis. The aim of this retrospective study was the evaluation of individual, functional and radiological results after proximal row carpectomy. Seventeen patients (15 male, two female) who had undergone proximal row carpectomy between 1991 and 1999, were reviewed. The most common indication was degenerative arthrosis secondary to carpal collapse associated with chronic scaphoid nonunion (SNAC), scapholunate advanced collapse (SLAC) deformity, late Kienböck's disease or perilunate dislocations. Clinical and subjective results were assessed using different scores (DASH-, modified Mayo wrist-score) and evaluating the individual wrist range of motion. Anteroposterior and lateral X-rays were obtained for radiological analysis. At follow-up evaluation (mean 65.4 months), the majority of patients reported pain relief and a significant increased range of motion for the operated wrist. Radiographical analysis showed degenerative changes at the radiocapitate articulation in ten patients. The intermediate-term results of this review would suggest that proximal row carpectomy is an effective procedure providing pain relief and a satisfactory range of motion in a variety of pathologic wrist disorders. Because of eventual radiocapitate arthrosis, we suggest PRC only in patients without significant degenerative changes at the proximal pole of the capitate or the lunate fossa.


Start shallow and grow deep: The development of a Hebrew reading brain.
Brain plasticity implies that readers of different orthographies can have different reading networks. Theoretical models suggest that reading acquisition in transparent orthographies relies on mapping smaller orthographic units to phonology, than reading opaque orthographies; but what are the neural mechanisms underlying this difference? Hebrew has a transparent (pointed) script used for beginners, and a non-transparent script used for skilled readers. The current study examined the developmental changes in brain regions associated with phonological and orthographic processes during reading pointed and un-pointed words. Our results highlight some changes that are universal in reading development, such as a developmental increase in frontal involvement (in bilateral inferior frontal gyrus (IFG) pars opercularis), and increase in left asymmetry (in IFG pars opercularis and superior temporal gyrus, STG) of the reading network. Our results also showed a developmental increase in activation in STG, which stands in contrast to previous studies in other orthographies. We further found an interaction of word length and diacritics in bilateral STG and the visual word form area (VWFA) across both groups. These findings suggest that children slightly adjust their reading depending on orthographic transparency, relying on smaller units when reading a transparent script and on larger units when reading an opaque script. Our results also showed that phonological abilities across groups correlated with activation in the VWFA, regardless of transparency, supporting the continued role of phonology at all levels of orthographic transparency. Our findings are consistent with multiple route reading models, in which both phonological and orthographic processing of multiple size units continue to play a role in children's reading of transparent and opaque scripts during reading development. The results further demonstrate the importance of taking into account differences between orthographies when constructing neural models of reading acquisition.


Gene transfer to the developing mouse inner ear by in vivo electroporation.
The mammalian inner ear has 6 distinct sensory epithelia: 3 cristae in the ampullae of the semicircular canals; maculae in the utricle and saccule; and the organ of Corti in the coiled cochlea. The cristae and maculae contain vestibular hair cells that transduce mechanical stimuli to subserve the special sense of balance, while auditory hair cells in the organ of Corti are the primary transducers for hearing. Cell fate specification in these sensory epithelia and morphogenesis of the semicircular canals and cochlea take place during the second week of gestation in the mouse and are largely completed before birth. Developmental studies of the mouse inner ear are routinely conducted by harvesting transgenic embryos at different embryonic or postnatal stages to gain insight into the molecular basis of cellular and/or morphological phenotypes. We hypothesize that gene transfer to the developing mouse inner ear in utero in the context of gain- and loss-of-function studies represents a complimentary approach to traditional mouse transgenesis for the interrogation of the genetic mechanisms underlying mammalian inner ear development(6). The experimental paradigm to conduct gene misexpression studies in the developing mouse inner ear demonstrated here resolves into three general steps: 1) ventral laparotomy; 2) transuterine microinjection; and 3) in vivo electroporation. Ventral laparotomy is a mouse survival surgical technique that permits externalization of the uterus to gain experimental access to the implanted embryos. Transuterine microinjection is the use of beveled, glass capillary micropipettes to introduce expression plasmid into the lumen of the otic vesicle or otocyst. In vivo electroporation is the application of square wave, direct current pulses to drive expression plasmid into progenitor cells. We previously described this electroporation-based gene transfer technique and included detailed notes on each step of the protocol(11). Mouse experimental embryological techniques can be difficult to learn from prose and still images alone. In the present work, we demonstrate the 3 steps in the gene transfer procedure. Most critically, we deploy digital video microscopy to show precisely how to: 1) identify embryo orientation in utero; 2) reorient embryos for targeting injections to the otocyst; 3) microinject DNA mixed with tracer dye solution into the otocyst at embryonic days 11.5 and 12.5; 4) electroporate the injected otocyst; and 5) label electroporated embryos for postnatal selection at birth. We provide representative examples of successfully transfected inner ears; a pictorial guide to the most common causes of otocyst mistargeting; discuss how to avoid common methodological errors; and present guidelines for writing an in utero gene transfer animal care protocol.


Baseline-transmitted V106V/I/M non-nucleoside reverse transcriptase inhibitor resistance in HIV-1 subtype B infection.
We report a case in which an antiretroviral therapy (ART)-naïve patient diagnosed with HIV-1 subtype B presented with baseline genotype and phenotype resistance tests, confirming a V106V/I/M nucleoside resistance mutation. The V106V/I/M mutation represents a mixture of virus strains conferring resistance to the non-nucleoside reverse transcriptase inhibitor antiretrovirals efavirenz and nevirapine. V106M mutation is not often observed as a primary resistance mutation in patients infected with HIV-1 subtype B. The patient responded well to an ART regimen consisting of tenofovir-emtricitabine and raltegravir, achieving and maintaining an undetectable HIV RNA.


Proteomic analysis of the phycobiliprotein antenna of the cryptophyte alga Guillardia theta cultured under different light intensities.
Plants and algae have developed various light-harvesting mechanisms for optimal delivery of excitation energy to the photosystems. Cryptophyte algae have evolved a novel soluble light-harvesting antenna utilizing phycobilin pigments to complement the membrane-intrinsic Chl a/c-binding LHC antenna. This new antenna consists of the plastid-encoded β-subunit, a relic of the ancestral phycobilisome, and a novel nuclear-encoded α-subunit unique to cryptophytes. Together, these proteins form the active α1β·α2β-tetramer. In all cryptophyte algae investigated so far, the α-subunits have duplicated and diversified into a large gene family. Although there is transcriptional evidence for expression of all these genes, the X-ray structures determined to date suggest that only two of the α-subunit genes might be significantly expressed at the protein level. Using proteomics, we show that in phycoerythrin 545 (PE545) of Guillardia theta, the only cryptophyte with a sequenced genome, all 20 α-subunits are expressed when the algae grow under white light. The expression level of each protein depends on the intensity of the growth light, but there is no evidence for a specific light-dependent regulation of individual members of the α-subunit family under the growth conditions applied. GtcpeA10 seems to be a special member of the α-subunit family, because it consists of two similar N- and C-terminal domains, which likely are the result of a partial tandem gene duplication. The proteomics data of this study have been deposited to the ProteomeXchange Consortium and have the dataset identifiers PXD006301 and 10.6019/PXD006301.


Use of estimated glomerular filtration rate to predict incident chronic kidney disease in patients at risk of cardiovascular disease: a retrospective study.
Patients with cardiovascular disease are at an increased risk of chronic kidney disease (CKD). However, data on incident CKD in patients with multiple vascular comorbidities are insufficient. In this study, we identified the predictors of CKD stages 3-5 in patients at risk of cardiovascular disease and used their estimated glomerular filtration rate (eGFR) to construct a nomogram to predict the 5-year risk of incident CKD. Ambulatory data on 622 adults with preserved kidney function and one or more cardiovascular disease risk factors who attended outpatient clinics at a tertiary care hospital in Al-Ain, United Arab Emirates were obtained retrospectively. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and assessed every 3 months from baseline to December 12, 2017. Fine and Gray competing risk regression model was used to identify the independent variables and construct a nomogram to predict incident CKD at 5 years, which is defined as eGFR < 60 mL/min/1.73 m2 for ≥3 months. Time-dependent area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the model. Calibration curves were applied to determine the calibration ability and adjusted for the competing risk of death. Internal validation of predictive accuracy was performed using K-fold cross-validation. Of the 622 patients, 71 had newly developed CKD stages 3-5 over a median follow-up of 96 months (interquartile range, 86-103 months). Baseline eGFR, hemoglobin A1c, total cholesterol, and history of diabetes mellitus were identified as significant predictors of CKD stages 3-5. The nomogram had good discrimination in predicting the disease stages, with a time-dependent AUC of 0.918 (95% confidence interval, 0.846-0.964) at 5 years, after internal validation by cross-validation. This study demonstrated that incident CKD could be predicted with a simple and practical nomogram in patients at risk of cardiovascular disease and with preserved kidney function, which in turn could help clinicians make more informed decisions for CKD management in these patients.


Clinical indicators of envenoming and serum levels of venom antigens in patients bitten by Bothrops lanceolatus in Martinique. Research Group on Snake Bites in Martinique.
An enzyme-linked immunosorbent assay was developed to measure venom antigen levels in the serum of 40 patients bitten by Bothrops lanceolatus. The grading system used for the severity of envenomation (grades 1 to 4, minor to major) was predominantly based on the presence of local signs. Serum venom levels increased with the grade of severity (P < 0.001, by Spearman's rank correlation test); they were 6 +/- 6 ng/mL (mean +/- SD) in clinically non-envenomed patients (grade 1, n = 3), 7.6 +/- 11.7 (n = 17), 44.3 +/- 41.8 (n = 17), and 80.3 +/- 34.1 ng/mL (n = 3) in patients diagnosed as grade 2, 3 and 4 respectively. However, venom antigens could not be detected in the serum of 54% of patients who showed clinical signs of envenomation. Most patients diagnosed as grade 2, 3 or 4 were given 20, 40 and 60 mL of a monospecific F(ab')2 antivenom, respectively. Venom concentrations > or = 15 ng/mL were observed in all patients with progressive aggravation of swelling despite the use of early antivenom therapy. No venom was detectable in blood samples taken after completion of serotherapy. All patients recovered. These results confirm the efficacy of both the clinical severity scoring system used and the therapeutic regimen.


Laser Welding of Ti6Al4V Titanium Alloy in Air and a Water Medium.
Ti6Al4V titanium alloys are widely used in a variety of scientific and industrial fields. Laser beam welding is one of the most effective techniques for the joining of titanium plates. The main objective of this study was to investigate the influence of the most important laser parameters on welding performance of titanium alloy in two different physical environments such as air and water (i.e., serum) media. Specifically, the laser beam welding of 2 mm thick Ti6Al4V samples was applied using an Nd:YAG laser in open-air welding using argon as a shielding gas, and in wet welding using a serum environment. The deepest penetration was achieved at -3 mm focal position with 11 J of laser energy in both investigated media (i.e., air and serum). The maximum hardness (1130 HV) was achieved for the focal position of -4 mm in serum medium while it was 795 HV for a focal position of -5 mm in air medium. The minimum (1200 μm and 800 μm) and maximum (1960 μm and 1900 μm) weld widths were observed for air and serum medium, respectively. After the welding process, martensite, massif martensite, and transformed martensite were observed in the microstructure of Ti6Al4V. To the best of our knowledge, the underwater wet welding of titanium alloy was carried out and reported for the first time in this study.


The 5' ends of Thogoto virus (Orthomyxoviridae) mRNAs are homogeneous in both length and sequence.
Thogoto (THO) virus is a tick-borne member of the Orthomyxoviridae whose genome consists of six segments of linear, negative sense, single-stranded RNA. To gain insight into the mechanism by which viral mRNA transcripts are initiated, poly(A)+ RNA isolated from THO virus-infected cells was characterized by (i) primer extension experiments, (ii) immunoprecipitation studies with an anticap monoclonal antibody, (iii) direct sequencing analysis of the isolated RNA, and (iv) cloning and sequencing of individual mRNA molecules. The results indicated that THO virus mRNAs are capped and homogeneous in both length and sequence at their 5' end. These findings contrast with the situation found in all other segmented, negative sense or ambisense, single-stranded RNA viruses so far analyzed in which the 5' ends of viral mRNAs are heterogeneous in length and sequence. These results are discussed in terms of the mechanism used by THO virus to initiate mRNA synthesis.


Risk factors and outcome in ICU-acquired infections.
Nosocomial infections are common in intensive care units (ICU). The objectives of this study were to determine risk factors of ICU-acquired infections, and potential mortality attributable to such infections. An observational study was performed in a 10-bed multidisciplinary ICU. For a period of 27 months, all patients admitted for >or=48 h were included. Infections were diagnosed according to Centers for Disease Control and Prevention definitions. Airway colonization was explored by molecular typing. Risk factors for infection were determined by multivariable logistic regression. Survival was analyzed with time-varying proportional hazards regression. Of 278 patients, 81 (29%) were infected: urinary tract infections in 39 patients (14%), primary bloodstream infections in 25 (9%), surgical site infections in 22 (8%) and pneumonia in 21 (8%). Of the total of 147 episodes, Gram-negative bacilli were isolated in 90, Gram-positive cocci in 49 and Candida sp. in 25. Risk factors for pneumonia were mechanical ventilation [odds ratio (OR=7.9, CI 1.8-35), lack of enteral nutriment (OR=8.0, CI 1.4-45) and length of time at risk (OR=1.8, CI 1.2-2.8), while gastric acid inhibitors did not affect the risk (OR=0.99, CI 0.32-3.0). Transmission of bacteria from the stomach to the airway was not confirmed. The risk of death was increased as patients were infected with pneumonia [hazard ratio (HR)=3.6; CI: 1.6-8.1], or primary bloodstream infection (HR=2.5; CI: 1.2-5.4), independent of age and disease severity. Mortality was increased by ICU-acquired pneumonia and primary bloodstream infections. Our findings did not support the gastro-pulmonary hypothesis of ICU-acquired pneumonia. The proposition that blood transfusions increase the risk of ICU-acquired nosocomial infections was not supported.


Why people believe they were exposed to biological or chemical warfare: a survey of Gulf War veterans.
The study sought to understand better how people come to believe they have been exposed to biological and chemical warfare. We conducted telephone interviews with 1,009 American veterans (65% response rate) deployed and not deployed to the Gulf War, a conflict during which there were credible threats that such warfare could be used. Only 6% of non-Gulf War veterans reported exposure to biological or chemical warfare, but most of Gulf War veterans reported exposure (64%). The majority of these were unsure whether the exposure was chemical or biological in nature. The most commonly reported exposure indicators were receiving an alert from the military and having physical symptoms. Veterans who were certain of the type of exposure (biological or chemical) were more likely to recall having been told by the military and to recall physical symptoms. Future communications with soldiers and the general public about biological and chemical warfare may need to emphasize the uncertain nature of such risk information. Evaluations of exposure diagnostic technologies should take into account the problem of people initially believing, but not later discounting, false positive results.


Late onset vitiligo and audiological abnormalities: is there any association?
There is scarce published data on late onset vitiligo. All the studies showing association of audiological abnormalities have been done on younger age group of patients. To study the clinical characteristics of the patients with late onset vitiligo. Also, to investigate the audiological abnormalities seen in these patients and compare them with age and sex matched healthy volunteers. One hundred and ninety-seven consecutive patients developing vitiligo after the age of 40 were studied. These patients were examined for the audiological abnormalities, and compared with those seen in age and sex matched healthy volunteers. Vitiligo started between 40 and 50 years of age in 68.02% of our patients. Vitiligo vulgaris was the commonest clinical pattern, and most patients reported onset of their vitiligo on the upper extremities. Fifty four had diabetes mellitus, 19 patients had autoimmune thyroid diseases, and 32 showed hypoacusis on audiometric examination. Eighteen controls (age and sex matched healthy volunteers) also showed hypoacusis. The difference in frequency was not significant (22.37% vs 18%, χ2-test, P>0.05). The sensorineural type of audiologic impairment was more commonly seen both in patients as well as in controls. Late onset vitiligo was not found to have statistically significant association with audiological abnormalities in this study.


Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration.
The use of intravitreal anti-VEGF agents in general, and of bevacizumab (Avastin) in particular, has become the common first-line treatment of neovascular age-related macular degeneration (AMD). Several reports addressed the possible elevation of intraocular pressure (IOP) following intravitreal injection of anti-VEGF. The aim of this study was to determine the prevalence of sustained IOP elevation following intravitreal bevacizumab injections for neovascular AMD and identify possible risk factors for the development of increased IOP. This retrospective cohort study included 174 consecutive patients (201 eyes) receiving intravitreal bevacizumab (1.25 mg/0.05 ml) as treatment for neovascular AMD. The records of the study patients were reviewed for age, gender, history of glaucoma, phakic status, IOP levels, length of follow-up, total number of injections, intervals between injections, and IOP management in eyes that exhibited IOP elevation. Sustained IOP elevation was defined as IOP ≥22 mmHg and a change from baseline of ≥6 mmHg recorded on at least two consecutive visits and lasting ≥30 days. Risk factors for an IOP increase were identified from the association between the studied variables and IOP elevations. Sustained IOP elevation was found in 22 of 201 eyes (11%). The increased IOP was controlled with topical medications in all eyes. Among the variables studied, only male gender [OR = 3.1, 95% CI (1.1, 8.5) p = 0.029] and length of interval between injections <8 weeks [OR = 3.0, 95%CI (1.1, 7.9), p = 0.028] emerged as risk factors for IOP elevation in a multivariable model. The prevalence of IOP elevation was significantly higher when the interval between injections was <8 weeks than ≥8 weeks (17.6 and 6%, respectively, p = 0.009). Pre-existing glaucoma was not associated with IOP elevation (p = 0.9). Sustained IOP elevations can occur in normotensive eyes undergoing intravitreal bevacizumab treatment for neovascular AMD. This phenomenon was related to shorter intervals between injections, with 8 weeks being taken as the cut-off point. AMD eyes that receive intravitreal bevacizumab injections need to be monitored for IOP changes, especially those in which the intervals between injections are <8 weeks.


Plasma Heparin Cofactor II Activity Is Inversely Associated with Hepatic Fibrosis of Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.
Thrombin exerts various pathophysiological functions by activating protease-activated receptors (PARs), and thrombin-induced activation of PARs promotes the development of non-alcoholic fatty liver disease (NAFLD). Since heparin cofactor II (HCII) specifically inactivates thrombin action, we hypothesized that plasma HCII activity correlates with the severity of NAFLD. A cross-sectional study was conducted. Plasma HCII activity and noninvasive clinical markers of hepatic fibrosis including fibrosis-4 (FIB-4) index, NAFLD fibrosis score (NFS) and aspartate aminotransferase-to-platelet ratio index (APRI) were determined in 305 Japanese patients with type 2 diabetes mellitus (T2DM). The relationships between plasma HCII activity and the clinical markers were statistically evaluated. Multiple regression analysis including confounding factors showed that plasma HCII activity independently contributed to decreases in FIB-4 index (p<0.001), NFS (p<0.001) and APRI (p=0.004). In addition, logistic regression analysis for the prevalence of advanced hepatic fibrosis defined by the cutoff points of the clinical scores showed that plasma HCII activity was the sole and common negative factor for prevalence of advanced hepatic fibrosis (FIB-4 index: p=0.002, NFS: p=0.026 and APRI: p=0.012). Plasma HCII activity was inversely associated with clinical hepatic fibrosis indices including FIB-4 index, NFS and APRI and with the prevalence of advanced hepatic fibrosis in patients with T2DM. The results suggest that HCII can serve as a novel biomarker for assessment of hepatic fibrosis of NAFLD in patients with T2DM.


Incidence of embolism associated with carotid artery stenting: open-cell versus closed-cell stents.
Carotid artery stenting (CAS) can be an alternative option for carotid endarterectomy in the prevention of ischemic stroke caused by carotid artery stenosis. The purpose of this study was to evaluate the influence of stent design on the incidence of procedural and postprocedural embolism associated with CAS treatment. Ninety-six symptomatic and asymptomatic patients, consisting of 79 males and 17 females, with moderate to severe carotid artery stenosis and a mean age of 69.0 years were treated with CAS. The stent type (48 closed-cell and 48 open-cell stents) was randomly allocated before the procedure. Imaging, procedural, and clinical outcomes were assessed and compared. The symptomatic subgroup (76 patients) was also analyzed to determine the influence of stent design on outcome. New lesions on postprocedural diffusion-weighted imaging (DWI) were significantly more frequent in the open-cell than in the closed-cell stent group (24 vs 12, respectively; p = 0.020). The 30-day clinical outcome was not different between the 2 stent groups. In the symptomatic patient group, stent design (p = 0.017, OR 4.173) and recent smoking history (p = 0.036, OR 4.755) were strong risk factors for new lesions on postprocedural DWI. Stent design may have an influence on the risk of new embolism, and selecting the appropriate stent may improve outcome.


Neural imaginaries and clinical epistemology: Rhetorically mapping the adolescent brain in the clinical encounter.
The social work of brain images has taken center stage in recent theorizing of the intersections between neuroscience and society. However, neuroimaging is only one of the discursive modes through which public representations of neurobiology travel. This article adopts an expanded view toward the social implications of neuroscientific thinking to examine how neural imaginaries are constructed in the absence of visual evidence. Drawing on ethnographic fieldwork conducted over 18 months (2008-2009) in a United States multidisciplinary pediatric pain clinic, I examine the pragmatic clinical work undertaken to represent ambiguous symptoms in neurobiological form. Focusing on one physician, I illustrate how, by rhetorically mapping the brain as a therapeutic tool, she engaged in a distinctive form of representation that I call neural imagining. In shifting my focus away from the purely material dimensions of brain images, I juxtapose the cultural work of brain scanning technologies with clinical neural imaginaries in which the teenage brain becomes a space of possibility, not to map things as they are, but rather, things as we hope they might be. These neural imaginaries rely upon a distinctive clinical epistemology that privileges the creative work of the imagination over visualization technologies in revealing the truths of the body. By creating a therapeutic space for adolescents to exercise their imaginative faculties and a discursive template for doing so, neural imagining relocates adolescents' agency with respect to epistemologies of bodily knowledge and the role of visualization practices therein. In doing so, it provides a more hopeful alternative to the dominant popular and scientific representations of the teenage brain that view it primarily through the lens of pathology.


Changes in cortical thickness and volume of cerebellar subregions in patients with bipolar disorders.
Numerous studies have suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). We aimed to investigate differences in the volume and cortical thickness of the cerebellar subregions between patients with BD and healthy controls (HCs). Ninety patients with BD and one hundred sixty-six HCs participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed the volume and cortical thickness of each cerebellar hemisphere divided into 12 subregions using T1-weighted images of participants. One-way analysis of covariance was used to evaluate differences between the groups, with age, sex, medication, and total intracranial cavity volume used as covariates. The BD group had significantly increased cortical thickness of the cerebellum in all cerebellar subregions compared to the HC group. The cortical thicknesses of the whole cerebellum and each hemisphere were also significantly thicker in the BD group than in the HC group. The volume of the left lobule IX was significantly lower in patients with BD than in HCs, whereas no significant differences in the volumes were observed in the other subregions. Our cross-sectional design cannot provide a causal relationship between the increased cortical thickness of the cerebellum and the risk of BD. We observed widespread and significant cortical thickening in all the cerebellar subregions. Our results provide evidence for the involvement of the cerebellum in BD. Further studies are required to integrate neurobiological evidence and structural brain imaging to elucidate the pathophysiology of BD.


Sites of hormone action in the mammalian nephron.
Hormone-dependent adenylate cyclase activity was measured separately in the different nephron portions by combining the microdissection of collagenase-treated rabbit kidneys and the use of a single tubule enzyme microassay. The results obtained in the rabbit for vasopressin, parathyroid hormone, calcitonin, and isoproterenol are given and discussed. Each hormone stimulated adenylate cyclase activity in several well-localized segments of tubule according to a highly specific and reproducible pattern. Sharp transitions were generally noted between responsive and unresponsive nephron portions. In the rat kidney, the functional segmentation of the distal convoluted tubule was not as clearly delineated as in the rabbit kidney. Various nephron segments of the rat kidney were observed to contain glucagon-sensitive adenylate cyclase activity. When the results obtained for vasopressin are compared in rabbit, rat, mouse, and human kidneys, species differences are noted with respect to the responsiveness to arginine vasopressin in the medullary portion of thick ascending limbs of Henle's loops. It is concluded that biochemical approaches can be used as a means of investigating problems dealing with kidney physiology very near the cell level.


LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis.
LncRNAs have critical roles in various biological processes ranging from embryonic development to human diseases, including cancer progression, although their detailed mechanistic functions remain illusive. The lncRNA linc-ROR has been shown to contribute to the maintenance of induced pluripotent stem cells and embryonic stem cells. In this study, we discovered that linc-ROR was upregulated in breast tumor samples, and ectopic overexpression of linc-ROR in immortalized human mammary epithelial cells induced an epithelial-to-mesenchymal transition (EMT) program. Moreover, we showed that linc-ROR enhanced breast cancer cell migration and invasion, which was accompanied by generation of stem cell properties. Contrarily, silencing of linc-ROR repressed breast tumor growth and lung metastasis in vivo. Mechanistically, our data revealed that linc-ROR was associated with miRNPs and functioned as a competing endogenous RNA to mi-205. Specifically, linc-ROR prevented the degradation of mir-205 target genes, including the EMT inducer ZEB2. Thus our results indicate that linc-ROR functions as an important regulator of EMT and can promote breast cancer progression and metastasis through regulation of miRNAs. Potentially, the findings of this study implicate the relevance of linc-ROR as a possible therapeutic target for aggressive and metastatic breast cancers.


Excellence in socio-technical teamwork requires both cognitive and emotional bonding.
Comments on the article Leadership, followership, and evolution: Some lessons from the past by Van Vugt, Hogan, and Kaiser. The current author states that Van Vugt, Hogan, and Kaiser came to three conclusions from their romp over 2.5 million years of earth history involving many species. In spite of these conclusions, Van Vugt et al. failed to mention or cite any recent articles on the research program that showed clearly that leadership is not only leader behavior toward a group but also is rooted in the mutual goal-enactment behavior and working relationship both between individual followers and between follower and leader at the dyadic and group levels (Graen, 1976, 2008; Graen, Hui, & Taylor, 2006; Graen & Uhl-Bien, 1995; Graen & Wakabayashi, 1994; Uhl-Bien, 2006). To best lead a team, one must build all possible working relationships to excellence. In no case should one let one's team divide into working factions based on working relationships.


mGluR1, but not mGluR5, activates feed-forward inhibition in the medial prefrontal cortex to impair decision making.
Cognitive flexibility depends on the integrity of the prefrontal cortex (PFC). We showed previously that impaired decision making in pain results from amygdala-driven inhibition of medial PFC neurons, but the underlying mechanisms remain to be determined. Using whole cell patch clamp in rat brain slices and a cognitive behavioral task, we tested the hypothesis that group I metabotropic glutamate receptors (mGluRs) activate feed-forward inhibition to decrease excitability and output function of PFC pyramidal cells, thus impairing decision making. Polysynaptic inhibitory postsynaptic currents (IPSCs) and monosynaptic excitatory postsynaptic currents (EPSCs) were evoked in layer V pyramidal cells by stimulating presumed amygdala afferents. An mGluR1/5 agonist [(S)-3,5-dihydroxyphenylglycine, DHPG] increased synaptic inhibition more strongly than excitatory transmission. The facilitatory effects were blocked by an mGluR1 [(S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, LY367385], but not mGluR5, antagonist, 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine. IPSCs were blocked by bicuculline and decreased by 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX). Facilitation of synaptic inhibition by DHPG was glutamate driven because it was blocked by NBQX. DHPG increased frequency but not amplitude of spontaneous IPSCs; consistent with action potential-dependent synaptic inhibition, tetrodotoxin (TTX) prevented the facilitatory effects. DHPG decreased synaptically evoked spikes (E-S coupling) and depolarization-induced spiking [frequency-current (f-I) relationship]. This effect was indirect, resulting from glutamate-driven synaptic inhibition, because it persisted when a G protein blocker was included in the pipette but was blocked by GABA(A) receptor antagonists and NBQX. In contrast, DHPG increased E-S coupling and f-I relationships in mPFC interneurons through a presynaptic action, further supporting the concept of feed-forward inhibition. DHPG also impaired the ability of the animals to switch strategies in a decision-making task; bicuculline restored normal decision making, whereas a GABA(A) receptor agonist (muscimol) mimicked the decision-making deficit. The results show that mGluR1 activates feed-forward inhibition of PFC pyramidal cells to impair cognitive functions.


LETTER TO THE EDITOR
Particle dehydration and interparticle binding have been advocated to explain the coagulation of silica sols by alkaline salts. Those approaches are reexamined in the light of experimental data that have recently been published. It is proposed that coagulation of silica by alkaline cations, when it occurs, is caused by interparticle hydroxo bridging. Copyright 1997 Academic Press. Copyright 1997Academic Press


[Secondary non-tuberculous mycobacterium infection in patients with bronchiectasis caused by Marfan syndrome].
In this article, we reported a 28-year-old female patient who presented with intermittent hemoptysis, cough, and sputum production. Laboratory tests showed no abnormalities in the blood counts or inflammatory markers, and the sputum cultures were negative. A chest computed tomography scan showed bronchiectasis associated with infection in the middle and lower lobes of the right lung and right pleural thickening. We performed bronchoalveolar lavage by bronchoscopy in the dorsal segment of the right lower lobe and found Mycobacterium avium intracellulare complex (MAC) by Next Generation Sequencing (NGS) of bronchoalveolar lavage fluid (BALF). The patient's symptoms improved significantly after anti-mycobacterium treatment and the extent of infection was reduced on imaging. To further identify the cause of bronchiectasis, the patient is tall and thin, with slender limbs. Cardiac color ultrasound showed the widening of aortic sinus. Her genetic testing of blood samples revealed the gene mutation in the FBN1 gene (c.4349G>A). Based on these results, she was diagnosed with Marfan syndrome.


Conceptual Considerations on the Integration of Quality Indicators into Clinical Pathways.
Health care systems need to cope with continuous changes such as with the current trends towards pay-for-performance and value-based health care. In this context, the article aims at analysing the potentials of the integration and utilisation of quality indicators in clinical pathways. It comprises the first steps of a design-oriented research process, i.e. problem motivation and objective definition. Therefore, a conceptual framework for pathway-integrated quality indicators is proposed. Potentials of the approach are outlined in three use case scenarios. The analysis points out great potentials for quality management on institutional and network level and for bridging the gap between medical research and practice. Further research topics are derived and summarised in an agenda.


Association of cdk2 kinase with the transcription factor E2F during S phase.
The transcription factor E2F controls the expression of several proliferation-related genes and is a target of the adenovirus E1A oncogene. In human cells, both cyclin A and the cdk2 protein kinase were found in complexes with E2F. Although the total amounts of cdk2 were constant in the cell cycle, binding to E2F was detected only when cells entered S phase, a time when the cdk2 kinase is activated. These data suggest that the interaction between cdk2 and E2F requires an active kinase that has cyclin A as a targeting component.


A review of forty-five years study of Hiroshima and Nagasaki atomic bomb survivors. Cancer risk among in utero-exposed survivors.
The Radiation Effects Research Foundation (RERF) continues to conduct a follow-up study initiated some years ago of cancer mortality and incidence among the survivors of the atomic bombing of Hiroshima and Nagasaki exposed in utero. Although only 18 incident cases of cancer were identified in the years 1950-1984 (of which 5 cases were in the 0 dose group), cancer risk appears to increase significantly as maternal uterine dose increases. Only two cases of childhood cancer were observed among these individuals in the first 14 years of life; both had been exposed to greater than or equal to 0.30 Gy. All other cases developed cancer in adulthood, and the cancers they developed are, in the main, the ones known to be elevated in frequency among the postnatally exposed survivors. The estimated relative risk for cancer at 1 Gy (uterine dose) is 3.77. The results suggest that the in utero group may have a higher risk than that seen among exposed adults because the individuals exposed in utero have not reached the major cancer prone age. However, since the observed cases are too few to allow a site-specific review, further follow-up studies are required to determine if the observed increased cancer risk can definitely be attributed to A-bomb radiation, although there appears to be a significant dose-related cancer response.


The 6 minute walk test and performance of upper limb in ambulant duchenne muscular dystrophy boys.
The Performance of Upper Limb (PUL) test was specifically developed for the assessment of upper limbs in Duchenne muscular dystrophy (DMD). The first published data have shown that early signs of involvement can also be found in ambulant DMD boys. The aim of this longitudinal Italian multicentric study was to evaluate the correlation between the 6 Minute Walk Test (6MWT) and the PUL in ambulant DMD boys. Both 6MWT and PUL were administered to 164 ambulant DMD boys of age between 5.0 and 16.17 years (mean 8.82). The 6 minute walk distance (6MWD) ranged between 118 and 557 (mean: 376.38, SD: 90.59). The PUL total scores ranged between 52 and 74 (mean: 70.74, SD: 4.66). The correlation between the two measures was 0.499. The scores on the PUL largely reflect the overall impairment observed on the 6MWT but the correlation was not linear. The use of the PUL appeared to be less relevant in the very strong patients with 6MWD above 400 meters, who, with few exceptions had near full scores. In patients with lower 6MWD the severity of upper limb involvement was more variable and could not always be predicted by the 6MWD value or by the use of steroids. Our results confirm that upper limb involvement can already be found in DMD boys even in the ambulant phase.


[Laboratory diagnostics in evaluation of acute respiratory viral infection morbidity in 2010 - 2011 epidemic season].
Study of etiological structure of ARVI and evaluation of acute respiratory virus infection morbidity in 2010 - 2011 epidemic season taking into account the data of laboratory diagnostics by method of polymerase chain reaction with hybridization-fluorescent detection. By using reagent kits produced by Central Research Institute of Epidemiology for the detection of primary causative agents of influenza and ARVI 129 children and 94 adult patients monitored in an outpatient setting as well as 103 children hospitalized due to ARI were examined. Etiological structure of ARVI was studied; proportion of influenza and other actual causative agents of ARVI in monthly dynamics were established. During epidemic rise of influenza (January-March 2011) the proportion of influenza A viruses was 24% (peak in January--31%), the proportion of influenza B viruses--5%, rhinoviruses--9%, metapneumovirus was detected in 6% of cases, parainfluenza viruses (1 - 4 type) and adenovirses--4% each, coronaviruses--in 3%, respiratory syncytial virus--in 2%, bocavirus--in 1% of the studied samples. In influenza structure A/H1N1pdm2009 virus, its proportion was 70%, influenza virus B (26.9%), influenza virus A/H3N2 (2.6%) predominated. Indexes for monthly morbidity caused by each of the ARVI causative agents were calculated. The proposed approach allowed to evaluate ARVI morbidity taking into account laboratory-confirmed etiological factors. A 5 time increase in ARI morbidity in adults in February 2011 was shown to be mostly due to an increase in influenza A morbidity as well as involvement of influenza B virus, metapneumoviruses, coronaviruses, parainfluenza viruses and rhinoviruses into the epidemic process. Increase of morbidity of children by 1.4 times was also seen during activization of influenza viruses and metapneumovirus. The analysis of monitoring results allowed to prognose increase of respiratory-syncytial viral infection epidemic activity from September 2011 to February 2012.


[Low-protein dietary therapy in patients with chronic kidney disease].
Several prospective studies and meta-analyses including the recent Cochrane meta-analysis have demonstrated that reducing the protein content in the diet delays renal death and the start of dialysis in patients with chronic kidney disease (CKD). Reducing the dietary protein intake offers other benefits such as lowering accumulation of uremic toxins and circulating phosphates and improving symptoms and metabolic derangements. Following the publication of the Cochrane meta-analysis, some of the most renowned experts in Italy on dietary therapy in the CKD patient established a working group within the Italian Society of Nephrology (SIN), the ''Nephrontieres'' project. The current supplement of GIN presents the views of the members of the ''Nephrontieres'' group on a range of issues related to dietary therapy in CKD. A CME program for Italian nephrologists also originated from the collaborative work of the group.


Quantum chemical study of the enzymatic repair of T(6-4)C/C(6-4)T UV-photolesions by DNA photolyases.
Several strategies have evolved to repair one of the abundant UV radiation-induced damages caused to DNA, namely the mutagenic pyrimidine (6-4) pyrimidone photolesions. DNA (6-4)-photolyases are enzymes repairing these lesions by a photoinitiated electron transfer. An important aspect of a possible repair mechanism is its generality and transferability to different (6-4) lesions. Therefore, previously suggested mechanisms for the repair of the T(6-4)T lesion are here transferred to the T(6-4)C and C(6-4)T lesions and investigated theoretically using quantum chemical methods. Despite the different functional groups of the pyrimidine bases involved, a general valid molecular mechanism was identified, in which the initial step is an electron transfer coupled to a proton transfer from the protonated HIS365 to the N3(') nitrogen of the 3(') pyrimidine, followed by an intramolecular OH/NH2 transfer in one concerted step, which does not require an oxetane/azetidine or isolated water/ammonia intermediate.


Long-term relapses of breast cancer: questions, interpretations and hypotheses.
The author has demonstrated in previous publications that the consistent characteristic of long-term relapses of carcinoma after more than 8 years from surgery is hormone dependence, since long-term relapses occur almost exclusively in hormone-dependent tumors such as carcinoma of the breast, prostate, endometrium and thyroid. Such publications presented a series of 237 long term relapses of breast cancer that occurred at no less than 8 years from the mastectomy, which proved that all the patients were estrogen-receptor positive. Estrogen-negative cases who did not relapse after 8 years from surgery should be considered cured, as is found for cases of non-hormone-dependent tumors. Therefore, the study demonstrates that breast cancer, without the presence of hormone receptors (which influence clinical behavior) is similar to neoplasms that arise in all parts of the body. The author herein presents a personal hypothesis relative to the possibility that the presence of receptors indirectly conditions the formation of antimitotic factors up to determining in some cases the phenomenon of long-term relapses. Such factors are presumably physiological, and the possibility that such a hypothesis can also serve to explain the results obtained with hormone therapy of breast cancer is examined.


Graded activity and graded exposure for persistent nonspecific low back pain: a systematic review.
Graded activity and graded exposure are increasingly being used in the management of persistent low back pain; however, their effectiveness remains poorly understood. The aim of this study was to systematically review randomized controlled trials that evaluated the effectiveness of graded activity or graded exposure for persistent (>6 weeks in duration or recurrent) low back pain. Trials were electronically searched and rated for quality by use of the PEDro scale (values of 0-10). Randomized controlled trials of graded activity or graded exposure that included pain, disability, global perceived effect, or work status outcomes were included in the study. Outcomes were converted to a scale from 0 to 100. Trials were pooled with software used for preparing and maintaining Cochrane reviews. are presented as weighted mean differences with 95% confidence intervals. Fifteen trials with 1,654 patients were included. The trials had a median quality score of 6 (range=3-9). Pooled effects from 6 trials comparing graded activity with a minimal intervention or no treatment favored graded activity, with 4 contrasts being statistically significant: mean values (95% confidence intervals) for pain in the short term, pain in the intermediate term, disability in the short term, and disability in the intermediate term were -6.2 (-9.4 to -3.0), -5.5 (-9.9 to -1.0), -6.5 (-10.1 to -3.0), and -3.9 (-7.4 to -0.4), respectively. None of the pooled effects from 6 trials comparing graded activity with another form of exercise, from 4 trials comparing graded activity with graded exposure, and from 2 trials comparing graded exposure with a waiting list were statistically significant. Limitations of this review include the low quality of the studies, primarily those that evaluated graded exposure; the use of various types of outome measures; and differences in the implementation of the interventions, adding to the heterogeneity of the studies. The available evidence suggests that graded activity in the short term and intermediate term is slightly more effective than a minimal intervention but not more effective than other forms of exercise for persistent low back pain. The limited evidence suggests that graded exposure is as effective as minimal treatment or graded activity for persistent low back pain.


Are self-collected samples comparable to physician-collected cervical specimens for human papillomavirus DNA testing? A systematic review and meta-analysis.
To compare the detection rate of genital human papillomavirus (HPV) infection in self- and physician-obtained samples. Systematic review and meta-analysis. Studies published between 1966 and November 2005 identified through Medline and Embase that compared both sampling methods. We calculated the concordance and kappa statistic between physician- and self-sampling and the difference between proportions of HPV positive samples. Weighted averages were reported with 95% confidence intervals (CI) using a random-effects model. Eighteen studies (5441 participants) were included that evaluated broad HPV type categories, 10 (3688 patients) that of high-risk (HR) HPV and three (530) that of low-risk (LR) HPV. A high level of concordance of 0.87 (95%CI, 0.82 to 0.91) between self- and physician-sampling was obtained for detection of HPV DNA (kappa 0.66, 95%CI, 0.56 to 0.76). The prevalence difference of HPV DNA between sampling methods was -0.5 (95%CI, -2.8 to 1.8). Results were similar when restricting the analysis to HR-HPV but the prevalence of LR-HPV types was higher in self-collected samples. Self-sampling was as sensitive as physician-obtained sampling to detect HR-HPV or HPV DNA. Self-sampling may be a suitable alternative method for studies on HPV transmission and vaccine trials.


Molecular pathology of vertebral deformities in hyperthermic Atlantic salmon (Salmo salar).
Hyperthermia has been shown in a number of organisms to induce developmental defects as a result of changes in cell proliferation, differentiation and gene expression. In spite of this, salmon aquaculture commonly uses high water temperature to speed up developmental rate in intensive production systems, resulting in an increased frequency of skeletal deformities. In order to study the molecular pathology of vertebral deformities, Atlantic salmon was subjected to hyperthermic conditions from fertilization until after the juvenile stage. Fish exposed to the high temperature regime showed a markedly higher growth rate and a significant higher percentage of deformities in the spinal column than fish reared at low temperatures. By analyzing phenotypically normal spinal columns from the two temperature regimes, we found that the increased risk of developing vertebral deformities was linked to an altered gene transcription. In particular, down-regulation of extracellular matrix (ECM) genes such as col1a1, osteocalcin, osteonectin and decorin, indicated that maturation and mineralization of osteoblasts were restrained. Moreover, histological staining and in situ hybridization visualized areas with distorted chondrocytes and an increased population of hypertrophic cells. These findings were further confirmed by an up-regulation of mef2c and col10a, genes involved in chondrocyte hypertrophy. The presented data strongly indicates that temperature induced fast growth is severely affecting gene transcription in osteoblasts and chondrocytes; hence change in the vertebral tissue structure and composition. A disrupted bone and cartilage production was detected, which most likely is involved in the higher rate of deformities developed in the high intensive group. Our results are of basic interest for bone metabolism and contribute to the understanding of the mechanisms involved in development of temperature induced vertebral pathology. The findings may further conduce to future molecular tools for assessing fish welfare in practical farming.


Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors.
We examined how the endogenous anticonvulsant adenosine might influence gamma-aminobutyric acid type A (GABA(A)) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM), GABA(A) receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABA(A)-current (I(GABA)) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced I(GABA) run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated I(GABA) run-down in approximately 40% and approximately 20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 microM) potentiated I(GABA) run-down but only in approximately 20% of tested oocytes. CGS15943 administration again decreased I(GABA) run-down in patch-clamped neurons from either human or rat neocortex slices. I(GABA) run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABA(A)-receptor stability is tonically influenced by A2A but not by A1 receptors. I(GABA) run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer therapeutic opportunities.


Symptoms associated with dietary fiber supplementation over time in individuals with fecal incontinence.
Knowledge about adverse symptoms over time from fiber supplementation is lacking. The aim of this study was to compare the severity of adverse gastrointestinal (GI) symptoms during supplementation with dietary fiber or placebo over time in adults with fecal incontinence. A secondary aim was to determine the relationship between symptom severity and emotional upset and their association with study attrition and reducing fiber dose. Participants (N = 189; 77% female; 92% White; age, M = 58 years, SD = 14 years) with fecal incontinence were randomly assigned to a placebo or a supplement of 16 g total dietary fiber per day from 1 of 3 sources: gum arabic, psyllium, or carboxymethylcellulose. They reported GI symptoms daily during baseline (14 days), incremental fiber dosing (6 days), and 2 segments of steady full fiber dose (32 days total). Severity of symptoms in all groups was minimal. Adjusting for study segment and day, a greater feeling of fullness in the psyllium group was the only symptom that differed from symptoms in the placebo group. The odds of having greater severity of flatus, belching, fullness, and bloating were 1.2-2.0 times greater in the steady dose segment compared with baseline. There was a positive association between symptom severity and emotional upset. Participants with a greater feeling of fullness or bloating or higher scores for total symptom severity or emotional upset were more likely to withdraw from the study sooner or reduce fiber dose. Persons with fecal incontinence experience a variety of GI symptoms over time. Symptom severity and emotional upset appear to influence fiber tolerance and study attrition. Supplements seemed well tolerated.


[Morphogenesis of tick-borne encephalitis virus in the brain of mice infected with its persistent strains].
The brain cells of adult albino rats underwent electron microscopic study after intracerebral infection with tickborne encephalitis virus (TBEV) strains isolated after long persistence in monkeys, Syrian hamsters, and a patient with chronic tick-borne encephalitis. The TBEV morphogenesis scheme was shown to be fundamentally similar for both high-virulent and long persistent TBEV strains. Data on the budding of newly forming particles on the degranulated membranes of the irregular endoplasmic network are presented. The morphogenesis and molecular mechanisms of TBEV reproduction call for further comprehensive studies.


The Content of Physiotherapy and Factors Impacting on Reablement - A National Study.
Reablement is a multidisciplinary intervention aimed at promoting function and independence for people with functional decline. Detailed descriptions of various professions' actions are needed for organization and evaluation of reablement services. This study describes physiotherapy practice in a reablement context in Swedish municipalities, focusing on the content and magnitude of interventions. Physiotherapists (n=108) from 34 municipalities answered a web-based survey covering the target group, content and duration of their actions, and number of contacts initiated over a 3-week period. Data were analyzed with descriptive statistics and multiple logistic regression. Overall, 1005 cases were reported, with a mean age of 78.9 years (SD: 11.7); about 91% (n=912) were aged ≥65 and 61% (n=612) were women. About 70% were allocated to home care; 16% (n=160) of these had minor functional limitations (eg, needing safety alarms/help with domestic tasks), and 55% (n=550) had major functional limitations (eg, needing help with personal activities of daily living). The most reported actions were providing technical aids (60.8%, n=576), instructions/counseling (41.5%, n=393), walking/climbing stairs (27.6%, n=262), strength training (27.2%, n=258), and fall prevention (25.5%, n=242). Almost half of the cases included one action (n=494) and about 89% (n=890) targeted primary needs (body functions, walking indoors, self-care, or domestic life), mainly in clients with major functional limitations (odds ratio=2.96; 95% confidence interval: 1.95-4.49). About 50% (n=517) of the cases involved 1-2 contacts; about 55% (n=549) were completed within 3 weeks. Exercise was associated with ≥6 visits over ≥7 weeks. Supervision of home care staff was performed in 19.1% (n=181) of cases. Reablement physiotherapy mostly comprises a few actions over a relatively short period. Whether this is a conscious strategy based on the purpose of home-based physiotherapy or clients' needs and wishes, or conversely an expression of limited resources, remains to be investigated.


The burden of rare cancers in the United States.
There are limited published data on the burden of rare cancers in the United States. By using data from the North American Association of Central Cancer Registries and the Surveillance, Epidemiology, and End Results program, the authors provide information on incidence rates, stage at diagnosis, and survival for more than 100 rare cancers (defined as an incidence of fewer than 6 cases per 100,000 individuals per year) in the United States. Overall, approximately 20% of patients with cancer in the United States are diagnosed with a rare cancer. Rare cancers make up a larger proportion of cancers diagnosed in Hispanic (24%) and Asian/Pacific Islander (22%) patients compared with non-Hispanic blacks (20%) and non-Hispanic whites (19%). More than two-thirds (71%) of cancers occurring in children and adolescents are rare cancers compared with less than 20% of cancers diagnosed in patients aged 65 years and older. Among solid tumors, 59% of rare cancers are diagnosed at regional or distant stages compared with 45% of common cancers. In part because of this stage distribution, 5-year relative survival is poorer for patients with a rare cancer compared with those diagnosed with a common cancer among both males (55% vs 75%) and females (60% vs 74%). However, 5-year relative survival is substantially higher for children and adolescents diagnosed with a rare cancer (82%) than for adults (46% for ages 65-79 years). Continued efforts are needed to develop interventions for prevention, early detection, and treatment to reduce the burden of rare cancers. Such discoveries can often advance knowledge for all cancers. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:261-272. © 2017 American Cancer Society.


Lack of specificity of commercially available antisera: better specifications needed.
The ideal antiserum for immunohistochemical (IHC) applications contains monospecific high-affinity antibodies with little nonspecific adherence to sections. Many commercially available antibodies are "affinity" purified, but it is unknown if they meet "hard" specificity criteria, such as absence of staining in tissues genetically deficient for the antigen or a staining pattern that is identical to that of an antibody raised against a different epitope on the same protein. Reviewers, therefore, often require additional characterization. Although the affinity-purified antibodies used in our study on the distribution of muscarinic receptors produced selective staining patterns on sections, few passed the preabsorption test, and none produced bands of the anticipated size on Western blots. More importantly, none showed a difference in staining pattern on sections or Western blots between wild-type and knockout mice. Because these antibodies were used in most studies published thus far, our findings cast doubts on the validity of the extant body of morphological knowledge of the whole family of muscarinic receptors. We formulate requirements that antibody-specification data sheets should meet and propose that journals for which IHC is a core technique facilitate consumer rating of antibodies. "Certified" antibodies could avoid fruitless and costly validation assays and should become the standard of commercial suppliers.


Maximal short term exercise capacity in healthy subjects aged 15-70 years.
Fifty males and 50 females, 15-71 years of age, exercised maximally for 30 s on an isokinetic ergometer at a pedalling frequency of 60 rev./min. Results were compared with maximal oxygen uptake (VO2 max.) obtained in a progressive incremental exercise test. Total work in 30 s was higher in males than females, declined linearly by about 6% per decade of age (r = -0.65), and was related closely to height (r = 0.75) and to lean thigh volume estimated anthropometrically (r = 0.84). A close association with vital capacity (r = 0.86) was also found that accounted statistically for the combined effects of age and height. The percentage decline in power during 30 s (fatigue index) was lower in subjects reporting greater leisure activity. A close relationship was found between total work in 30 s and VO2max. (r = 0.86), with vital capacity and leisure activity exerting additional influences on VO2max. (P less than 0.001; multiple r = 0.93). The well-established reduction with age in VO2max. is associated with an apparent parallel reduction in the power output capacity of large muscle groups recruited in heavy dynamic leg exercise.


[Effects of laser therapy on lipids and antioxidants in blood of patients with bronchial asthma].
Laser therapy was assessed for effects on lipoperoxides and free radical catchers in blood lipids of patients with bronchial asthma (BA). When a group of 52 BA patients was compared to healthy donors by dienic conjugates, vitamin E and overall lipid-soluble antioxidants levels in the whole blood and plasma, these appeared higher in the asthmatics. Combination of laser therapy with conventional treatment returned these parameters close to normal.


Extremely low genetic diversity indicating the endangered status of Ranodon sibiricus (Amphibia: Caudata) and implications for phylogeography.
The Siberian salamander (Ranodon sibiricus), distributed in geographically isolated areas of Central Asia, is an ideal alpine species for studies of conservation and phylogeography. However, there are few data regarding the genetic diversity in R. sibiricus populations. We used two genetic markers (mtDNA and microsatellites) to survey all six populations of R. sibiricus in China. Both of the markers revealed extreme genetic uniformity among these populations. There were only three haplotypes in the mtDNA, and the overall nucleotide diversity in the mtDNA was 0.00064, ranging from 0.00000 to 0.00091 for the six populations. Although we recovered 70 sequences containing microsatellite repeats, there were only two loci that displayed polymorphism. We used the approximate Bayesian computation (ABC) method to study the demographic history of the populations. This analysis suggested that the extant populations diverged from the ancestral population approximately 120 years ago and that the historical population size was much larger than the present population size; i.e., R. sibiricus has experienced dramatic population declines. Our findings suggest that the genetic diversity in the R. sibiricus populations is the lowest among all investigated amphibians. We conclude that the isolation of R. sibiricus populations occurred recently and was a result of recent human activity and/or climatic changes. The Pleistocene glaciation oscillations may have facilitated intraspecies genetic homogeneity rather than enhanced divergence. A low genomic evolutionary rate and elevated inbreeding frequency may have also contributed to the low genetic variation observed in this species. Our findings indicate the urgency of implementing a protection plan for this endangered species.


Arterial pressure gradient of upper extremity arteriovenous access steal syndrome: treatment implications.
Treatment options after arteriovenous fistula (AVF) associated steal include ligation, banding, and distal revascularization-interval ligation (DRIL). The purpose of this study was to evaluate the arterial pressure gradients in upper extremity steal syndrome. Preoperative arteriography and sequential intra-arterial pressure readings were performed on consecutive AVF patients with hand ischemia. Analysis of variance (ANOVA) with repeated measures analyzed intersubject comparisons, and post hoc analysis identified anatomic locations with highest inflow pressures. Nine patients presented with ischemic hand symptoms after AVF. Pullback arterial pressure measurements revealed gradual increases in systolic and mean pressures as the catheter position was moved proximally from the AVF anastomosis. Post hoc analysis after ANOVA revealed higher axillary artery systolic pressure compared to proximal brachial artery (153 vs 116.8, P = .007). AVF-related steal syndrome decreases arterial inflow pressure of the affected extremity more proximally than previously thought. When performing a DRIL procedure, consideration should be given to placing the anastomosis as proximally as possible.


Susac Syndrome: A Rare Case Report.
Susac syndrome is a rare autoimmune disease, which is characterized by microangiopathic changes that affects the brain, retina and cochlea. A 60-years-old female Muslim housewife, hypertensive, non-diabetic patient was admitted into Ophthalmology department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh on 18 December 2017 presented with the complains of gross dimness of vision of left eye for 10 years, vitiligo over the whole body for 5years,hearing loss with tinnitus in both ear for one year. Fluoresce in fundus angiography of Left eye shows Central retinal artery occlusion & was treated by Pan retinal photocoagulation in left eye, Magnetic resonance image of brain shows hyper intense lesions in periventricular white matter & corpus callosum, pure tone audiometry shows bilateral sensorineural type of hearing loss. Early diagnosis and early initiation of treatment is important in reducing the permanent disability.


The orientation of cytochromes in membrane multilayers prepared from aerobically grown Escherichia coli K12.
Centrifugation of membrane vesicles, prepared from ultrasonically disrupted Escherichia coli K12, on to a planar surface followed by slow, partial dehydration results in a high degree of parallel orientation of the membrane planes with respect to each other and the supporting surface. Rotation of such membrane multilayers about a single axis parallel with the membrane planes within the magnetic field of an electron paramagnetic resonance (e.p.r.) spectrometer allows the orientation of anisotropic paramagnetic centres to be deduced. Computer simulations of the angular dependence of cytochrome e.p.r. spectra show two, or perhaps three, cytochromes, well-oriented with respect to the membrane plane. A low-spin cytochrome is oriented with the normal to its haem plane lying in the membrane plane. One (or perhaps two) high-spin cytochrome(s) lies with its haem plane making an angle of 45 degrees with the membrane plane. The orientation of the low-spin cytochrome haem is thus the same as that of haems in b-type cytochromes and cytochrome oxidases of the a type found in the mitochondria of higher animal and microbial cells and the bacterium Paracoccus denitrificans (Erecińska et al., 1979). The possible identity of this low-spin component as the terminal oxidase, cytochrome o, is discussed.


Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells.
Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution. L1s can retrotranspose in the germline, during early development and in select somatic cells; however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors rapidly reverses this silencing, and chromatin immunoprecipitation experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing was also observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukaemia virus or human immunodeficiency virus, suggesting that these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, in itself, is not sufficient to reactivate previously silenced reporter genes. Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition.


Human pattern-evoked retinal responses are altered by optic atrophy.
Electrical signals in response to both diffuse flashes of light and phase-alternating spatial patterns were recorded from the eyes and from the occipital scalp of a subject with a traumatic unilateral (right) optic nerve section. Clinical examination disclosed a grossly normal right eye with no light perception, a Marcus Gunn pupil, and an atrophic optic disc. The left eye was normal. The electroretinogram responses on the lesioned side (OD) were normal, but there was no pattern-evoked retinal response (PERR) and no recordable visual-evoked response present. The conclusion is that the optic nerve and ganglion cells appear to be selectively responsible for the PERR potential.


Histidine 352 (His352) and tryptophan 355 (Trp355) are essential for flax UGT74S1 glucosylation activity toward secoisolariciresinol.
Flax secoisolariciresinol diglucoside (SDG) lignan is a natural phytoestrogen for which a positive role in metabolic diseases is emerging. Until recently however, much less was known about SDG and its monoglucoside (SMG) biosynthesis. Lately, flax UGT74S1 was identified and characterized as an enzyme sequentially glucosylating secoisolariciresinol (SECO) into SMG and SDG when expressed in yeast. However, the amino acids critical for UGT74S1 glucosyltransferase activity were unknown. A 3D structural modeling and docking, site-directed mutagenesis of five amino acids in the plant secondary product glycosyltransferase (PSPG) motif, and enzyme assays were conducted. UGT74S1 appeared to be structurally similar to the Arabidopsis thaliana UGT72B1 model. The ligand docking predicted Ser357 and Trp355 as binding to the phosphate and hydroxyl groups of UDP-glucose, whereas Cys335, Gln337 and Trp355 were predicted to bind the 7-OH, 2-OCH3 and 17-OCH3 of SECO. Site-directed mutagenesis of Cys335, Gln337, His352, Trp355 and Ser357, and enzyme assays revealed an alteration of these binding sites and a significant reduction of UGT74S1 glucosyltransferase catalytic activity towards SECO and UDP-glucose in all mutants. A complete abolition of UGT74S1 activity was observed when Trp355 was substituted to Ala355 and Gly355 or when changing His352 to Asp352, and an altered metabolite profile was observed in Cys335Ala, Gln337Ala, and Ser357Ala mutants. This study provided for the first time evidence that Trp355 and His352 are critical for UGT74S1's glucosylation activity toward SECO and suggested the possibility for SMG production in vitro.


Ibuprofen Degradation and Associated Bacterial Communities in Hyporheic Zone Sediments.
Ibuprofen, a non-steroidal anti-inflammatory pain reliever, is among pharmaceutical residues of environmental concern ubiquitously detected in wastewater effluents and receiving rivers. Thus, ibuprofen removal potentials and associated bacteria in the hyporheic zone sediments of an impacted river were investigated. Microbially mediated ibuprofen degradation was determined in oxic sediment microcosms amended with ibuprofen (5, 40, 200, and 400 µM), or ibuprofen and acetate, relative to an un-amended control. Ibuprofen was removed by the original sediment microbial community as well as in ibuprofen-enrichments obtained by re-feeding of ibuprofen. Here, 1-, 2-, 3-hydroxy- and carboxy-ibuprofen were the primary transformation products. Quantitative real-time PCR analysis revealed a significantly higher 16S rRNA abundance in ibuprofen-amended relative to un-amended incubations. Time-resolved microbial community dynamics evaluated by 16S rRNA gene and 16S rRNA analyses revealed many new ibuprofen responsive taxa of the Acidobacteria, Actinobacteria, Bacteroidetes, Gemmatimonadetes, Latescibacteria, and Proteobacteria. Two ibuprofen-degrading strains belonging to the genera Novosphingobium and Pseudomonas were isolated from the ibuprofen-enriched sediments, consuming 400 and 300 µM ibuprofen within three and eight days, respectively. The collective results indicated that the hyporheic zone sediments sustain an efficient biotic (micro-)pollutant degradation potential, and hitherto unknown microbial diversity associated with such (micro)pollutant removal.


Foraging habitat quality constrains effectiveness of artificial nest-site provisioning in reversing population declines in a colonial cavity nester.
Among birds, breeding numbers are mainly limited by two resources of major importance: food supply and nest-site availability. Here, we investigated how differences in land-use and nest-site availability affected the foraging behaviour, breeding success and population trends of the colonial cavity-dependent lesser kestrel Falco naumanni inhabiting two protected areas. Both areas were provided with artificial nests to increase nest-site availability. The first area is a pseudo-steppe characterized by traditional extensive cereal cultivation, whereas the second area is a previous agricultural zone now abandoned or replaced by forested areas. In both areas, lesser kestrels selected extensive agricultural habitats, such as fallows and cereal fields, and avoided scrubland and forests. In the second area, tracked birds from one colony travelled significantly farther distances (6.2 km ± 1.7 vs. 1.8 km ± 0.4 and 1.9 km ± 0.6) and had significant larger foraging-ranges (144 km(2) vs. 18.8 and 14.8 km(2)) when compared to the birds of two colonies in the extensive agricultural area. Longer foraging trips were reflected in lower chick feeding rates, lower fledging success and reduced chick fitness. Availability and occupation of artificial nests was high in both areas but population followed opposite trends, with a positive increment recorded exclusively in the first area with a large proportion of agricultural areas. Progressive habitat loss around the studied colony in the second area (suitable habitat decreased from 32% in 1990 to only 7% in 2002) is likely the main driver of the recorded population decline and suggests that the effectiveness of bird species conservation based on nest-site provisioning is highly constrained by habitat quality in the surrounding areas. Therefore, the conservation of cavity-dependent species may be enhanced firstly by finding the best areas of remaining habitat and secondly by increasing the carrying capacity of high-quality habitat areas through safe nest-site provisioning.


Seroprevalence of Leptospira in rattus norvegicus in Grenada, West Indies.
To determine the seroprevalence of Leptospira and the serovars responsible for Leptospira exposure in rats in Grenada in order to assess rats as a reservoir host for human infection. Rattus norvegicus rodents were collected from each of the six parishes on the island of Grenada. Serum from 237 rats was tested by the microscopic agglutination test (MAT) and an Immunoglobulin G (IgG) Enzyme-Linked Immunosorbent Assay (ELISA). Seroprevalence rates among parishes were compared using a chi-squared test of homogeneity. Of the 237 serum samples tested, 64 were positive by either MAT or ELISA for an overall seroprevalence of 27%. The ELISA identified 24.5% (57/233) of the rats positive at a titer of > or = 1:160. The MAT identified 7.1% (13/183) of the rats positive at a titer of > or = 1:100. Six of the 13 MAT positive samples had antibodies to multiple serovars. The serovars identified by the MAT with the greatest frequency were from the Icterohaemorrhagiae serogroup. Two rats had antibodies for serogroup Cynopteri, the first time this serogroup has been identified in Grenada. Our results for Leptospira exposure in rats in Grenada support R norvegicus as an important reservoir host for Leptospira, particularly those from the Icterohaemorrhagiae serogroup. Because this serogroup is the primary serogroup responsible for documented human exposure in Grenada, exposed rats represent a public health threat.


Excess SMAD signaling contributes to heart and muscle dysfunction in muscular dystrophy.
Disruption of the dystrophin complex causes muscle injury, dysfunction, cell death and fibrosis. Excess transforming growth factor (TGF) β signaling has been described in human muscular dystrophy and animal models, where it is thought to relate to the progressive fibrosis that characterizes dystrophic muscle. We now found that canonical TGFβ signaling acutely increases when dystrophic muscle is stimulated to contract. Muscle lacking the dystrophin-associated protein γ-sarcoglycan (Sgcg null) was subjected to a lengthening protocol to produce maximal muscle injury, which produced rapid accumulation of nuclear phosphorylated SMAD2/3. To test whether reducing SMAD signaling improves muscular dystrophy in mice, we introduced a heterozygous mutation of SMAD4 (S4) into Sgcg mice to reduce but not ablate SMAD4. Sgcg/S4 mice had improved body mass compared with Sgcg mice, which normally show a wasting phenotype similar to human muscular dystrophy patients. Sgcg/S4 mice had improved cardiac function as well as improved twitch and tetanic force in skeletal muscle. Functional enhancement in Sgcg/S4 muscle occurred without a reduction in fibrosis, suggesting that intracellular SMAD4 targets may be important. An assessment of genes differentially expressed in Sgcg muscle focused on those encoding calcium-handling proteins and responsive to TGFβ since this pathway is a target for mediating improvement in muscular dystrophy. These data demonstrate that excessive TGFβ signaling alters cardiac and muscle performance through the intracellular SMAD pathway.


[Laparoscopic interventions on choledochus: 5 year experience].
Complex examination of 69 patients with complicated cholelithic disease was performed. The elaborated in the clinic algorithm for preoperative examination of the patients was applied to reveal the main bile ducts pathology. Indications for the laparoscopic interventions on choledochus performance were substantiated.


A comparison of bone microarchitectural and transcriptomic changes in murine long bones in response to hindlimb unloading and aging.
Age- and disuse-related bone loss both result in decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. Disuse induces changes in the balance of bone formation and bone resorption like those seen with aging. There is a need to experimentally compare these two mechanisms at a structural and transcriptomic level to better understand how they may be similar or different. Bone microarchitecture and biomechanical properties were compared between 6- and 22-month-old C57BL/6 J male control mice and 6-month-old mice that were hindlimb unloaded (HLU) for 3 weeks. Epiphyseal trabecular bone was the compartment most affected by HLU and demonstrated an intermediate bone phenotype between age-matched controls and aged controls. RNA extracted from whole-bone marrow-flushed tibiae was sequenced and analyzed. Differential gene expression analysis additionally included 4-month-old male mice unloaded for 3 weeks compared to age-matched controls. Gene ontology analysis demonstrated that there were age-dependent differences in differentially expressed genes in young adult mice. Genes related to downregulation of cellular processes were most affected in 4-month-old mice after disuse whereas those related to mitochondrial function were most affected in 6-month-old mice. Cell-cycle transition was downregulated with aging. A publicly available dataset (GSE169292) from 3-month female C57BL/6 N mice unloaded for 7 days was included in ingenuity pathway analysis (IPA) with the other datasets. IPA was used to identify the leading canonical pathways and upstream regulators in each HLU age group. IPA identified "Senescence Pathway" as the second leading canonical pathway enriched in mice exposed to HLU. HLU induced activation of the senescence pathway in 3-month and 4-month-old mice but inhibited it in 6-month-old mice. In conclusion, we demonstrate that hindlimb unloading and aging initiate similar changes in bone microarchitecture and gene expression. However, aging is responsible for more significant transcriptome and tissue-level changes compared to hindlimb unloading.


A control hardware based on a field programmable gate array for experiments in atomic physics.
Experiments in Atomic, Molecular, and Optical (AMO) physics require precise and accurate control of digital, analog, and radio frequency (RF) signals. We present control hardware based on a field programmable gate array core that drives various modules via a simple interface bus. The system supports an operating frequency of 10 MHz and a memory depth of 8 M (223) instructions, both easily scalable. Successive experimental sequences can be stacked with no dead time and synchronized with external events at any instructions. Two or more units can be cascaded and synchronized to a common clock, a feature useful to operate large experimental setups in a modular way.