Radiological and clinical findings in acute and chronic exogenous lipoid pneumonia.
To describe the radiologic and clinical findings in a group of patients with exogenous lipoid pneumonia focusing on features that differentiate the acute and chronic presentations. We retrospectively identified 15 patients from a single institution with exogenous lipoid pneumonia 1992-2001. Inclusion criteria were: imaging with chest CT and either CT features diagnostic of lipoid pneumonia or intrapulmonary lipids on pathologic examination. Each chart was reviewed for the clinical presentation, history of ingestion/exposure, predisposing factors, treatment and response to therapy. Initial (n = 13) and follow-up (n = 11) chest radiographs were reviewed for the patterns and distribution of lung parenchymal abnormalities and pleural effusion. Initial (n = 15) and follow-up (n = 7) CT scans were reviewed for lung parenchymal abnormalities (consolidation, ground glass opacities, linear/nodular opacities, masses, and crazy paving), presence or absence of fat attenuation, and pleural effusion. The groups were compared using the Fischer exact test. Nine patients had acute lipoid pneumonia, 7 males and 2 females with a mean age of 45 (range 4.5-81) years. Six patients had chronic lipoid pneumonia, 4 men and 2 women with a mean age of 63 (range 37-83) years. 78% (7/9) of patients with acute and all of the patients with chronic presentations had a known ingestion and/or a predisposing condition associated with lipoid pneumonia. On chest radiographs, consolidation and lower lobe involvement were present in the majority of patients with acute and none of the patients with chronic presentations. On CT, consolidation and fat attenuation were present in the majority of patients with each presentation. However, masses were present in 67% (4/6) of patients with chronic and none of the patients with acute presentation (P < 0.05). 86% (6/7) of patients with acute presentation had improvement on follow-up chest radiograph in contrast to none of the patients with chronic presentation (P < 0.05). 75% (3/4) of patients with acute lipoid pneumonia had improvement on follow-up CT in contrast with 67% (2/3) of patients with chronic lipoid pneumonia who had progression on follow-up CT. The imaging features of acute and chronic lipoid pneumonia overlap with consolidation and lower lobe involvement present in both groups. However, only the patients with acute lipoid pneumonia had pleural effusions and improvement on follow-up. Only the patients with chronic lipoid pneumonia had pulmonary masses.


Specimen charging on thin films with one conducting layer: discussion of physical principles.
Although the most familiar consequences of specimen charging in transmission electron microscopy can be eliminated by evaporating a thin conducting film (such as a carbon film) onto an insulating specimen or by preparing samples directly on such a conducting film to begin with, a more subtle charging effect still remains. We argue here that specimen charging is in this case likely to produce a dipole sheet rather than a layer of positive charge at the surface of the specimen. A simple model of the factors that control the kinetics of specimen charging, and its neutralization, is discussed as a guide for experiments that attempt to minimize the amount of specimen charging. Believable estimates of the electrostatic forces and the electron optical disturbances that are likely to occur suggest that specimen bending and warping may have the biggest impact on degrading the image quality at high resolution. Electron optical effects are likely to be negligible except in the case of a specimen that is tilted to high angle. A model is proposed to explain how both the mechanical and electron-optical effects of forming a dipole layer would have much greater impact on the image resolution in a direction perpendicular to the tilt axis, a well-known effect in electron microscopy of two-dimensional crystals.


Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.
Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.


Fatigue behavior of the zinc-phosphate cement layer.
Fatigue behavior of luting cement film between model fixed partial dentures (FPD) and their dies was investigated to gain a better understanding of the mechanical properties of zinc-phosphate cement. Fifty-six brass dies were made, half of them with grooves and half without grooves. A cantilever FPD for each die was cast in Au-Pd-Ag alloy. Four linear strain gauges were attached to the marginal portions of each retainer. The FPDs were cemented to the dies using zinc-phosphate cement. A fatigue test machine was used to cyclically load the specimens with 50 or 100 N for 5.5 x 10(5) cycles (1 Hz) in 37 degrees C water. During the fatigue test, strain measurements were made after every 0.5 x 10(5) load cycles to discover if strain response was altered. After completion of the fatigue test, ultimate tensile strength of each specimen was measured and statistically analyzed by 2-way analysis of variance. With or without grooves, strain responses were the same at every periodic strain measurement throughout the 50-N fatigue test. For the 100-N fatigue test, strain responses for the specimens without grooves were different before and after cyclic testing, but there was no difference for the specimens with grooves. There were no significant differences in tensile strength among the specimens after the fatigue tests. No fatigue fracture was observed in zinc-phosphate cement film after repetitive loading. Repetitive loading may improve stress transmission within the zinc-phosphate cement film.


Early diagnosis and the clinical genetics of Alzheimer's disease.
Alzheimer's disease (AD) has a significant genetic background manifested as autosomal dominant inheritance in some early-onset families and as familial risk in late-onset cases. Three genes responsible for early-onset autosomal dominant AD have been identified, and one gene, apolipoprotein E, has been confirmed as a susceptibility gene for late-onset forms of the disorder. These findings raise the possibility of genetic testing, either for early diagnosis or prediction. For early-onset autosomal dominant AD genetic testing will have a limited but useful role in confirming diagnosis in established cases and in predictive counselling for relatives; a situation analogous to that for Huntington's disease. For late-onset AD significant problems remain to be overcome before the advances in molecular genetics have a direct clinical application


Dispersion relation in oscillatory reaction-diffusion systems with self-consistent flow in true slime mold.
In the large amoeboid organism Physarum, biochemical oscillators are spatially distributed throughout the organism and their collective motion exhibits phase waves, which carry physiological signals. The basic nature of this wave behaviour is not well-understood because, to date, an important effect has been neglected, namely, the shuttle streaming of protoplasm which accompanies the biochemical rhythms. Here we study the effects of self-consistent flow on the wave behaviour of oscillatory reaction-diffusion models proposed for the Physarum plasmodium, by means of numerical simulation for the dispersion relation and weakly nonlinear analysis for derivation of the phase equation. We conclude that the flow term is able to increase the speed of phase waves (similar to elongation of wave length). We compare the theoretical consequences with real waves observed in the organism and also point out the physiological roles of these effects on control mechanisms of intracellular communication.


In vitro activity of isepamicin and other aminoglycosides against clinical isolates of Gram-negative bacteria causing nosocomial bloodstream infections.
Isepamicin is a newly introduced aminoglycoside in Taiwan. Since in vitro data for isepamicin against nosocomial Gram-negative bloodstream infection from Taiwan are limited, we compared the activity of isepamicin, amikacin, gentamicin and tobramycin against nosocomial Gram-negative blood isolates. A total of 247 non-duplicate nosocomial blood isolates of Gram-negative bacteria collected between January 2003 and December 2003 in a major teaching hospital in Taiwan were tested for their in vitro susceptibilities to gentamicin, tobramycin, amikacin, and isepamicin using the agar dilution method. The isolates included Escherichia coli (31 isolates), Klebsiella pneumoniae (31), Enterobacter cloacae (30), Serratia marcescens (31), Morganella morganii (21), Citrobacter freundii (10), Pseudomonas aeruginosa (31), Acinetobacter baumannii (31), and Stenotrophomonas maltophilia (31). Overall, isepamicin had high antibacterial activity against the tested Gram-negative bacteria. For the 154 Enterobacteriaceae isolates, isepamicin had the lowest minimum concentration inhibiting 90% of isolates (MIC90) among the tested drugs, while its resistance rate (3.9%) was equal to that of amikacin (3.9%) and lower than those of tobramycin (18.2%) and gentamicin (21.4%). For the 93 of non-fermentative Gram-negative bacilli isolates, isepamicin had the lowest MIC90, and a resistance rate (23.7%) lower than those of amikacin (27.9%), tobramycin (38.7%) and gentamicin (40.9%). The in vitro activity of isepamicin against Gram-negative bacteria isolates was equal or similar to amikacin and superior to other tested aminoglycosides. In view of its potential for less nephrotoxicity and ototoxicity than other aminoglycosides, isepamicin is a drug of choice for the empirical treatment of nosocomial infections caused by Gram-negative bacteria.


Epithelialization of hydrogels achieved by amine functionalization and co-culture with stromal cells.
The aim of this study was to develop a hydrogel which would be suitable for corneal cell re-epithelialization when used as a corneal implant. To achieve this, a series of hydrogels were functionalized with primary amines by post-polymerization reactions between amine compounds and glycidyl ether groups attached to the hydrogels. We report a strong correlation between the structure of the amine and the viability of stromal cells and epithelial cells cultured on these hydrogels. Subsequent co-culture of epithelial and stromal cells on the amine modified hydrogels allowed successful expansion of epithelial cells on surfaces functionalized with alkyl alpha-omega diamines with carbon chain lengths of between 3 and 6. Analysis of variance showed that corneal epithelial cells had a strong preference for surfaces functionalized by the reaction of excess 1,3 diaminopropane with units of glycidyl methacrylate compared to the reaction products of other amines (ammonia; 1,2-diaminoethane; 1,4-diaminobutane or 1,6-diaminohexane). We suggest this approach of amine functionalization combined with stromal/epithelial co-culture offers a promising new approach to achieving a secure corneal epithelium.


Lung cancer incidence in erzurum city.
Known as an uncommon disease at the beginning of the 20(th) century, lung cancer has been the most frequent cause of cancer-related deaths in males since the 1950s and in females in the last two decades. The aim of this study was to determine the lung cancer incidence in Erzurum; its clinical properties, cancer subtypes, and application phases; the relationships of tumors with parameters of cigarette smoking and nutrition; radiological properties of the tumors; and the methods of diagnosis. This study analyzed data from a prospective database. The study included the patients who applied in 2005 to the Chest Disease, Chest Surgery, Medical Oncology or Radiation Oncology section of Research Hospital, Faculty of Medicine, Ataturk University; the Erzurum Nihat Kitapçı Chest Diseases Hospital; or the Palandöken State Hospital and were diagnosed with lung cancer. A standard questionnaire was used to obtain information about the patients. The figures of the 2005 census issued by the State Institute of Statistics were used for incidence calculations. During the study period, 255 patients with a lung cancer diagnosis were accepted, 220 of whom were male (86.3%) and 35 were female (13.7%). The mean age of the patients was 63±1 years. The lung cancer incidence in Erzurum according to the data given by the hospitals that can diagnose lung cancer was determined to be 14.4/100.000. Lung cancer frequency increased with age, it was observed in males six times more frequently than females, and histopathologically non-small cell lung cancer and advanced phase lung cancer were more frequent. The lung cancer incidence for Erzurum was not different from that reported in other studies carried out both in the region and the whole country, and the lung cancer diagnosis was related to advanced age, male sexuality, active smoking and low socioeconomic state.


Rapid Discrimination of Methicillin-Resistant Staphylococcus aureus by MALDI-TOF MS.
Methicillin-resistant Staphylococcus aureus (MRSA) is a serious pathogen in clinical settings and early detection is critical. Here, we investigated the MRSA discrimination potential of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) using 320 clinical S. aureus isolates obtained in 2005-2014 and 181 isolates obtained in 2018. We conducted polymerase chain reactions (PCR) for staphylococcal cassette chromosome mec (SCCmec) typing and MALDI-TOF MS to find specific markers for methicillin resistance. We identified 21 peaks with significant differences between MRSA and methicillin-susceptible S. aureus (MSSA), as determined by mecA and SCCmec types. Each specific peak was sufficient to discriminate MRSA. We developed two methods for simple discrimination according to these peaks. First, a decision tree for MRSA based on six MRSA-specific peaks, three MSSA-specific peaks, and two SCCmec type IV peaks showed a sensitivity of 96.5%. Second, simple discrimination based on four MRSA-specific peaks and one MSSA peak had a maximum sensitivity of 88.3%. The decision tree applied to 181 S. aureus isolates from 2018 had a sensitivity of 87.6%. In conclusion, we used specific peaks to develop sensitive MRSA identification methods. This rapid and easy MALDI-TOF MS approach can improve patient management.


The spring runoff in Nebraska's (USA) Elkhorn River watershed and its impact on two sentinel organisms.
The objectives of the present study were to determine 1) if temporal variability influenced the toxicity of Elkhorn River, Nebraska, USA, water, and 2) if the toxic effect was consistent between 2 sentinel organisms, the fathead minnow (Pimephales promelas) and the northern leopard frog (Rana pipiens). During spring 2012, atrazine indicator strips were used to document the occurrence of agrichemical pulses in the Elkhorn River. Polar organic chemical integrative samplers (POCIS) were deployed for 14 d during both a pulse and a postpulse period as indicated by the atrazine strips. Pesticide concentrations detected in the POCIS extracts ranged from 1.6-fold to 281-fold higher during the pulse period compared to the postpulse period. Fish and frog bioassays were conducted for 7 d, and hepatic mRNA expression of vitellogenin (VTG) and estrogen receptor alpha (ERα) was determined by quantitative real-time polymerase chain reaction. Compared with lab water controls, fish exposed to water collected during an agrichemical pulse experienced significant reductions in VTG and ERα, whereas exposed female frogs did not. Male leopard frogs, in contrast, experienced significant increases in the expression of ERα, whereas pulse-exposed male minnows did not. The significant effects observed following agrichemical pulse exposure demonstrate that episodic agrichemical runoff adversely impacts sentinel organisms, and that the adverse impacts observed depend on the sex and species of the sentinel organism.


CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets.
Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet α cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from α cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing α cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the KATP channel, but instead due to reduced operation of the Na+-K+ pump. These data suggest that counter-regulatory secretion of glucagon is driven by fatty acid metabolism, and that the Na+-K+ pump is an important ATP-dependent regulator of α cell function.


Anion and carboxylic acid binding to monotopic and ditopic amidopyridine macrocycles.
Binding of inorganic anions, carboxylic acids, and tetraalkylammonium carboxylates by macrocyclic compounds of different size was studied by NMR in DMSO-d6. It has been shown that at least a 15-membered ring is necessary for successful recognition of fluoride. Larger macrocycles were shown to bind HSO4(-), H2PO4(-), Cl(-), and carboxylic acid salts. Effects of binding topicity are discussed. The 30-membered macrocycles 4 and 4m selectively bind substrates that are size- and shape-complementary: maximum binding is observed for dicarboxylic acids and dicarboxylates with four-carbon chains, and the binding constant for association of fumaric acid and 4 is ca. 5 orders of magnitude higher than that of maleic acid. The 30-membered macrocycle 4m showed selectivity toward alpha-ketocarboxylic acids. Secondary amino groups were not crucial for binding of fluoride to the macrocycles; however, they proved to be very important for selectivity and strength of carboxylic acid binding. The X-ray structure of the adduct of 4 and nitrobenzoic acid confirmed the guest H-bonding with both the amide and the secondary amino groups of the 30-membered macrocyclic host.


The use of human tissues and cells in biomedical research: the unusual suspects.
There are compelling reasons to search for alternatives to the use of animals in medical and pharmaceutical research. Aside from the obvious animal welfare issues, both the well-established differences between animal models and humans, and the inherent inter-individual variability in human biological responses, indicate that human-based alternatives are urgently required. However, any such alternative must out-perform the animal-based alternative, otherwise there will be little or no uptake and adoption by end-users. Data obtained from inbred animal models is often highly reproducible, and is therefore attractive to researchers in the fields of biomedical and pharmaceutical research. The inter-individual variability observed during human volunteer and human tissue-based studies is often considered to be problematic, and has been highlighted further with the advent of the 'omics' technologies, which generate large biological datasets. However, the variability in both baseline data and response to pharmacological or toxicological challenge observed in human tissues potentially contains a veritable gold mine of information, which may be critical for the advancement of drug discovery.


Evaluation of fibrinolytic medical therapy for patients with acute myocardial infarction.
Fibrinolytic therapy is the standard therapeutic method for patients with acute myocardial infarction (AMI). This study endeavored to assess the delay in arrival to the emergency department and door to needle time for thrombolytic therapy. This study was conducted on 80 patients with AMI whom referred to our clinic from January 2009 to January 2010. We measured time of arrival, needle time and door to needle time for all patients. Moreover, the relations of these times to some variables such as age, gender and the referred shift of emergency department personnel were calculated. A total of 80 patients, 62 (77.5%) male and 18 (22.5%) female were evaluated for thrombolytic therapy. The arrival time of overnight shifts was 14.59 ± 1.23 minutes shorter than other shifts. The median door to needle time was 46.56 minutes and the mean time of the onset of chest pain to arrival at the emergency department was 19.44 minutes. Seventy-two patients (90%) received fibrinolytic therapy within the first 30 minutes of arrival. The needle time was significantly longer in the night shift (P < 0.05) (between 8 to 14 minutes), while the time of receiving Streptokinase therapy in the other shifts was not meaningfully different. Finally there was a statistically significant difference between the referred shifts and needle time (P < 0.05). Despite our good results for door to needle time, to improve and attain the gold standard's limits in administering fibrinolytic therapy, improvement of policies like training the personnel to shorten this time is recommend.


Youth Mental Health Services Utilization Rates After a Large-Scale Social Media Campaign: Population-Based Interrupted Time-Series Analysis.
Despite the uptake of mass media campaigns, their overall impact remains unclear. Since 2011, a Canadian telecommunications company has operated an annual, large-scale mental health advocacy campaign (Bell Let's Talk) focused on mental health awareness and stigma reduction. In February 2012, the campaign began to explicitly leverage the social media platform Twitter and incented participation from the public by promising donations of Can $0.05 for each interaction with a campaign-specific username (@Bell_LetsTalk). The intent of the study was to examine the impact of this 2012 campaign on youth outpatient mental health services in the province of Ontario, Canada. Monthly outpatient mental health visits (primary health care and psychiatric services) were obtained for the Ontario youth aged 10 to 24 years (approximately 5.66 million visits) from January 1, 2006 to December 31, 2015. Interrupted time series, autoregressive integrated moving average modeling was implemented to evaluate the impact of the campaign on rates of monthly outpatient mental health visits. A lagged intervention date of April 1, 2012 was selected to account for the delay required for a patient to schedule and attend a mental health-related physician visit. The inclusion of Twitter into the 2012 Bell Let's Talk campaign was temporally associated with an increase in outpatient mental health utilization for both males and females. Within primary health care environments, female adolescents aged 10 to 17 years experienced a monthly increase in the mental health visit rate from 10.2/1000 in April 2006 to 14.1/1000 in April 2015 (slope change of 0.094 following campaign, P<.001), whereas males of the same age cohort experienced a monthly increase from 9.7/1000 to 9.8/1000 (slope change of 0.052 following campaign, P<.001). Outpatient psychiatric services visit rates also increased for both male and female adolescents aged 10 to 17 years post campaign (slope change of 0.005, P=.02; slope change of 0.003, P=.005, respectively). For young adults aged 18 to 24 years, females who used primary health care experienced the most significant increases in mental health visit rates from 26.5/1000 in April 2006 to 29.2/1000 in April 2015 (slope change of 0.17 following campaign, P<.001). The 2012 Bell Let's Talk campaign was temporally associated with an increase in the rate of mental health visits among Ontarian youth. Furthermore, there appears to be an upward trend of youth mental health utilization in the province of Ontario, especially noticeable in females who accessed primary health care services.


Hydroxypropyl beta cyclodextrin: a water-replacement agent or a surfactant upon spray freeze-drying of IgG with enhanced stability and aerosolization.
The great potential of hydroxypropyl beta-cyclodextrin (HPßCD), as a dried-protein stabilizer, has been attributed to various mechanisms namely water-replacement, vitrification and surfactant-like effects. Highlighting the best result in our previous study (weight ratio IgG: HPßCD of 1:0.4), herein we designed to evaluate the efficacy of upper (1:2) and lower (1:0.05) ratios of HPßCD in stabilization and aerosol properties of spray freeze-dried IgG. The protective effect of HPβCD, as measured by size exclusion chromatography (SEC-HPLC) was most pronounced at C3' and C3″, IgG:trehalose:HPβCD ratios of 1:2:0.25 and 1:2:0.05 with aggregation rate constants of 0.46 ± 0.02 and 0.58 ± 0.01 (1/month), respectively. The secondary conformations were analyzed through Fourier transform infrared spectroscopy (FTIR) and all powders well-preserved with the lack of any visible fragments qualified through sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PPAGE). Scanning electron microscopy (SEM) and twin stage impinger (TSI) were employed to characterize the suitability of particles for further inhalation therapy of antibodies and the highest values of fine particle fraction (FPF) were achieved by C3' and C3″, 56.43 and 48.12%. The powders produced at the current ratio 1:2:0.25 and 1:2:0.05 are superior to our previous examination with regards to manifesting lower aggregation and comparable FPF values.


Coherent spontaneous activity identifies a hippocampal-parietal memory network.
Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF.


Comparison of single-slice computed tomography protocols for detection of pulmonary nodules in dogs.
Two dogs (4 and 38 kg) with radiographic evidence of pulmonary nodules were evaluated using single-slice, helical computed tomography (CT). Each thorax was scanned using 12 combinations of examination parameters that included slice collimation width (3 and 5mm for the small dog and 5 and 7mm for the large dog), pitch (1, 1.5, and 2), and reconstruction interval (0.5 and 1). Sensitivity, specificity, and accuracy for nodule detection were evaluated for each protocol by three different observers, their results being compared with a consensus evaluation of images acquired with the protocol providing the best theoretic resolution (narrow collimation, pitch of 1, reconstruction interval of 0.5). For all observers, sensitivity and accuracy were significantly increased when using a protocol with narrow collimation (P < 0.0001-0.005 and P = 0.0003-0.005, respectively). Pitch and reconstruction interval did not significantly influence the accuracy, sensitivity, or specificity for at least two of the observers. Additionally, nodule size (< 3mm vs. > 3mm) did not significantly affect nodule detection. Interobserver repeatability was variable among protocols (K = 0.32-0.78), highlighting the fact that nodule detection may be more dependent on the observer than on the choice of the CT protocol. For single-slice CT, the results of this study suggest that narrow collimation (3-5 mm, depending on the animal's size), a pitch of 2 and a reconstruction interval of 1 should be used in dogs for the detection of pulmonary nodules.


Spontaneous remission of post-transplant recurrent focal and segmental glomerulosclerosis.
A 12-year-old girl with a history of steroid and cyclosporine (CsA) resistant nephrotic syndrome owing to focal and segmental glomerulosclerosis (FSGS) has progressed to end-stage renal disease (ESRD) for which she underwent hemodialysis for 18 months before she successfully received a fully matched kidney transplant from her sister at the age of nine years. The post transplantation (Tx) period was marked by an early and massive proteinuria indicating recurrent FSGS for which she received 12 sessions of plasmapheresis (PP); unfortunately, she did not appear to have any response to the PP therapy; thereafter, a conservative management comprising essentially enalapril and losartan has been initiated and was also not successful during the first four months, however, a very gradual response has been noticed to occur after five months of conservative therapy and ultimately, the patient attained complete remission after 21 months of treatment. Amazingly, 15 months after discontinuation of enalapril and losartan, she remained in a complete and sustained remission with a good renal allograft function. To the best of our knowledge, this is the first case ever reported in the literature of a "spontaneous" remission of post transplant recurrent FSGS.


Shoulder weakness in professional baseball pitchers.
The purposes of this study were to: 1) compare shoulder range of motion and strength in professional baseball pitchers (N = 47) compared with age-matched controls (N = 16), and 2) examine the relationship of injury history to strength and range of motion. Based on injury history pitchers were categorized as: 1) none (N = 26), 2) injury requiring conservative intervention (N = 9), or 3) injury requiring surgical intervention (N = 12). Range of motion was measured for internal rotation (IROM) and external rotation (EROM). Eccentric strength was measured by hand-held dynamometer for internal rotation (IR), external rotation (ER), abduction (ABD), and supraspinatus muscle (SUP) strength. Injury history had no effect on strength and range of motion. Dominant EROM was greater in pitchers, P < 0.0001, and controls, P < 0.05, with pitchers having greater EROM motion bilaterally, P < 0.0001. Pitchers were weaker in SUP on the dominant vs nondominant side, P < 0.0001, and on the dominant side for weight adjusted ER, ABD, P < 0.01, and SUP, P < 0.0001, compared with controls. In conclusion, dominance and pitching resulted in soft tissue adaptation. Pitchers displayed weakness in three of four tests by comparison with controls, suggesting that the demands of pitching are insufficient to produce eccentric strength gains and may in fact lead to weakness. Dominant-side SUP weakness in pitchers may reflect subclinical pathology or chronic fatigue.


Ethics in technological culture: a programmatic proposal for a pragmatist approach.
Neither traditional philosophy nor current applied ethics seem able to cope adequately with the highly dynamic character of our modern technological culture. This is because they have insufficient insight into the moral significance of technological artifacts and systems. Here, much can be learned from recent science and technology studies (STS). They have opened up the black box of technological developments and have revealed the intimate intertwinement of technology and society in minute detail. However, while applied ethics is characterized by a certain "technology blindness," the most influential approaches within STS show a "normative deficit" and display on agnostic or even antagonistic attitude toward ethics. To repair the blind spots of both applied ethics and STS, the authors sketch the contours of a pragmatist approach. They will explore the tasks and tools of a pragmatist ethics and pay special attention to the exploration of future worlds disclosed and shaped by technology and the management of deep value conflicts inherent in a pluralistic society.


3-Methyl-1,2-BN-cyclopentane: a promising H2 storage material?
We provide detailed characterization of properties for 3-methyl-1,2-BN-cyclopentane 1 that are relevant to H(2) storage applications such as viscosity, thermal stability, H(2) gas stream purity, and polarity. The viscosity of 1 at room temperature is 25 ± 5 cP, about one fourth the viscosity of olive oil. TGA/MS analysis indicates that liquid carrier 1 is thermally stable at 30 °C but decomposes slowly at 50 °C. RGA data suggest that the H(2) desorption from 1 is a clean process, producing relatively pure H(2) gas. Compound 1 is a polar zwitterionic-type liquid consistent with theoretical predictions and solvatochromic studies.


Colour bio-factories: Towards scale-up production of anthocyanins in plant cell cultures.
Anthocyanins are widely distributed, glycosylated, water-soluble plant pigments, which give many fruits and flowers their red, purple or blue colouration. Their beneficial effects in a dietary context have encouraged increasing use of anthocyanins as natural colourants in the food and cosmetic industries. However, the limited availability and diversity of anthocyanins commercially have initiated searches for alternative sources of these natural colourants. In plants, high-level production of secondary metabolites, such as anthocyanins, can be achieved by engineering of regulatory genes as well as genes encoding biosynthetic enzymes. We have used tobacco lines which constitutively produce high levels of cyanidin 3-O-rutinoside, delphinidin 3-O-rutinoside or a novel anthocyanin, acylated cyanidin 3-O-(coumaroyl) rutinoside to generate cell suspension cultures. The cell lines are stable in their production rates and superior to conventional plant cell cultures. Scale-up of anthocyanin production in small scale fermenters has been demonstrated. The cell cultures have also proven to be a suitable system for production of 13C-labelled anthocyanins. Our method for anthocyanin production is transferable to other plant species, such as Arabidopsis thaliana, demonstrating the potential of this approach for making a wide range of highly-decorated anthocyanins. The tobacco cell cultures represent a customisable and sustainable alternative to conventional anthocyanin production platforms and have considerable potential for use in industrial and medical applications of anthocyanins.


Potentiometric multichannel cytometer microchip for high-throughput microdispersion analysis.
The parallelization of microfluidic cytometry is expected to lead to considerably enhanced throughput enabling point-of-care diagnosis. In this article, the development of a microfluidic potentiometric multichannel cytometer is presented. Parallelized microfluidic channels sharing a fluid path inevitably suffer from interchannel signal crosstalk that results from electrical coupling within the microfluidic channel network. By employing three planar electrodes within a single detection channel, we electrically decoupled each channel unit, thereby enabling parallel analysis by using a single cytometer microchip with multiple microfluidic channels. The triple-electrode configuration is validated by analyzing the size and concentration of polystyrene microbeads (diameters: 1.99, 2.58, 3, and 3.68 μm; concentration range: ∼2 × 10(5) mL(-1) to ∼1 × 10(7) mL(-1)) and bacterial microdispersion samples (Bacillus subtilis, concentration range: ∼4 × 10(5) CFU mL(-1) to ∼3 × 10(6) CFU mL(-1)). Crosstalk-free parallelized analysis is then demonstrated using a 16-channel potentiometric cytometer (maximum cross-correlation coefficients |r|: < 0.13 in all channel combinations). A detection throughput of ∼48,000 s(-1) was achieved; the throughout can be easily increased with the degree of parallelism of a single microchip without additional technical complexities. Therefore, this methodology should enable high-throughput and low-cost cytometry.


LDL-cholesterol reduction in chronic kidney disease: options beyond statins.
Individuals with chronic kidney disease (CKD) are at increased risk of atherosclerotic cardiovascular disease (ASCVD) events. LDL cholesterol (LDL-C) is a key modifiable cause of ASCVD and lowering LDL-C with statins reduces the risk of ASCVD events in a wide range of populations, including those with CKD. This review considers the utility of recently developed nonstatin LDL-C-lowering therapies in CKD. The cholesterol absorption inhibitor, ezetimibe, reduces LDL-C by 15-20% and is well tolerated in CKD. Monoclonal antibodies (mAbs) targeting proprotein convertase subtilisin kexin type 9 (PCSK9) reduce LDL-C by 50-60% and reduce the risk of ASCVD events. However, these agents require self-administration by subcutaneous injection every 2-4 weeks. The PCSK9 synthesis inhibitor, inclisiran, is administered approximately 6 monthly and may be more suitable for widespread use, although outcome trials are awaited. These PCSK9 targeting therapies require no dose adjustment in CKD and have no drug interactions. Statins and ezetimibe are safe and reduce ASCVD risk in CKD populations. PCSK9 targeting agents may be useful in high-risk CKD patients, including those with prior ASCVD.


Enhanced T cell function in a mouse model of human glycosylation.
Clinical evidence for a more active immune response in humans compared with our closest hominid relative, the chimpanzee, includes the progression of HIV infection to AIDS, hepatitis B- and C-related inflammation, autoimmunity, and unwanted harmful immune responses to viral gene transfer vectors. Humans have a unique mutation of the enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH), causing loss of expression of the sialic acid Neu5Gc. This mutation, occurring 2 million years ago, likely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind sialic acids. Previous work showed that human T cells proliferate faster than chimpanzee T cells upon equivalent stimulation. In this article, we report that Cmah(-/-) mouse T cells proliferate faster and have greater expression of activation markers than wild-type mouse T cells. Metabolically reintroducing Neu5Gc diminishes the proliferation and activation of both human and murine Cmah(-/-) T cells. Importantly, Cmah(-/-) mice mount greater T cell responses to an adenovirus encoding an adeno-associated virus capsid transgene. Upon lymphocytic choriomeningitis virus infection, Cmah(-/-) mice make more lymphocytic choriomeningitis virus-specific T cells than WT mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases.


Recognition of a human T-lymphocyte differentiation antigen by an IgM monoclonal antibody.
A monoclonal antibody directed at a determinant on human T cells was produced and characterized. This IgM antibody, MBG6, bound to human peripheral blood T lymphocytes and to medullary thymocytes. It was unreactive with normal B cells, B-cell lines and granulocytes. Apart from T lymphocytes, bone marrow cells (including cells positive for the terminal transferase marker, myeloid colony-forming cells, myeloblasts, and differentiating myeloid and erythroid cells) were negative. Peripheral blood cells that were treated with MBG6 and rabbit complement were no longer capable of proliferating in response to phytohaemagglutinin or concanavalin A; MBG6 did not have any direct mitogenic action on T lymphocytes. Double immunofluorescence studies using IgM MBG6 and OKT3, and IgG2a monoclonal antibody that recognizes all peripheral T cells, showed that these two antibodies identified exactly the same cell populations. Competitive binding studies, however, indicated that MBG6 and OKT3 recognized different epitopes. The antibody may have clinical applications in bone marrow transplantation.


Rescue from granzyme B-induced apoptosis by Wee1 kinase.
Granzymes are a family of granule-associated serine esterases that mediate apoptosis by cytotoxic T lymphocytes and natural killer cells. We have previously shown that cdc2, the mitosis-regulating cyclin-dependent kinase, is required for granzyme B-induced apoptosis in target cells. In addition, granzyme B induces premature activation and tyrosine dephosphorylation of cdc2 during apoptosis. Throughout most of the cell cycle and until the cell is prepared to enter mitosis, cdc2 kinase activity is negatively regulated by phosphorylation of a residue within its adenosine triphosphate-binding domain by Wee1, a nuclear kinase that maintains mitotic timing in eukaryotic cells. We have transiently expressed c-myc epitope-tagged Wee1 cDNA in BHK cells. Cells that expressed Wee1 in the nucleus became resistant to apoptosis induced by granzyme B and perforin. Wee1-transfected cells also exhibited markedly increased cdc2 tyrosine phosphorylation. Thus, Wee1 can rescue cells from granzyme-induced apoptosis by preventing cdc2 dephosphorylation.


Neighboring group participation in the transition state of human purine nucleoside phosphorylase.
The X-ray crystal structures of human purine nucleoside phosphorylase (PNP) with bound inosine or transition-state analogues show His257 within hydrogen bonding distance of the 5'-hydroxyl. The mutants His257Phe, His257Gly, and His257Asp exhibited greatly decreased affinity for Immucillin-H (ImmH), binding this mimic of an early transition state as much as 370-fold (Km/Ki) less tightly than native PNP. In contrast, these mutants bound DADMe-ImmH, a mimic of a late transition state, nearly as well as the native enzyme. These results indicate that His257 serves an important role in the early stages of transition-state formation. Whereas mutation of His257 resulted in little variation in the PNP x DADMe-ImmH x SO4 structures, His257Phe x ImmH x PO4 showed distortion at the 5'-hydroxyl, indicating the importance of H-bonding in positioning this group during progression to the transition state. Binding isotope effect (BIE) and kinetic isotope effect (KIE) studies of the remote 5'-(3)H for the arsenolysis of inosine with native PNP revealed a BIE of 1.5% and an unexpectedly large intrinsic KIE of 4.6%. This result is interpreted as a moderate electronic distortion toward the transition state in the Michaelis complex with continued development of a similar distortion at the transition state. The mutants His257Phe, His257Gly, and His257Asp altered the 5'-(3)H intrinsic KIE to -3, -14, and 7%, respectively, while the BIEs contributed 2, 2, and -2%, respectively. These surprising results establish that forces in the Michaelis complex, reported by the BIEs, can be reversed or enhanced at the transition state.


A new look at chronic fatigue syndrome/myalgic encephalomyelitis.
It has been 3 years since the Chief Medical Officer reported on chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and the time has come for a thorough investigation by an All Party Group drawn from the House of Commons and the House of Lords. We have received many written submissions and are engaged in taking oral evidence in 2-h sessions, which we open to the public as well as interested groups. The group has received a fantastic response to its requests for written evidence over the past few months. Questions that arise for a government response are the lack of provision and support for patients with CFS/ME, the issue of the clinical definition of CFS/ME, the need for a diagnostic test for CFS/ME, effectiveness of the National Institute for Clinical Excellence guidelines, and criteria used to decide which treatments are best for patients with CFS or myalgic encephalomyelitis.


Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor.
Ghrelin is a gastric peptide hormone that stimulates weight gain in vertebrates. The biological activities of ghrelin require octanoylation of the peptide on Ser(3), an unusual posttranslational modification that is catalyzed by the enzyme ghrelin O-acyltransferase (GOAT). Here, we describe the design, synthesis, and characterization of GO-CoA-Tat, a peptide-based bisubstrate analog that antagonizes GOAT. GO-CoA-Tat potently inhibits GOAT in vitro, in cultured cells, and in mice. Intraperitoneal administration of GO-CoA-Tat improves glucose tolerance and reduces weight gain in wild-type mice but not in ghrelin-deficient mice, supporting the concept that its beneficial metabolic effects are due specifically to GOAT inhibition. In addition to serving as a research tool for mapping ghrelin actions, GO-CoA-Tat may help pave the way for clinical targeting of GOAT in metabolic diseases.


Association of Down's syndrome and water fluoride level: a systematic review of the evidence.
A review of the safety and efficacy of drinking water fluoridation was commissioned by the UK Department of Health to investigate whether the evidence supported a beneficial effect of water fluoridation and whether there was any evidence of adverse effects. Down's syndrome was one of the adverse effects reported. The aim of this review is to examine the evidence for an association between water fluoride level and Down's syndrome. A systematic review of research. Studies were identified through a comprehensive literature search, scanning citations and online requests for papers. Studies in all languages which investigated the incidence of Down's syndrome in areas with different levels of fluoride in their water supplies were included. Study inclusion and quality was assessed independently by 2 reviewers. A qualitative analysis was conducted. Six studies were included. All were ecological in design and scored poorly on the validity assessment. The estimates of the crude relative risk ranged from 0.84 to 3.0. Four studies showed no significant associations between the incidence of Down's syndrome and water fluoride level and two studies by the same author found a significant (p < 0.05) positive association (increased Down's syndrome incidence with increased water fluoride level). Only two of the studies controlled for confounding factors and only one of these presented summary outcome measures. The evidence of an association between water fluoride level and Down's syndrome incidence is inconclusive.


Quantitative Structure-Activity Relationships of Aquatic Narcosis: A Review.
Prior estimation of toxicity of each and every, existing and yet to be synthesized chemicals is a must to elude their adverse effect on the environment. Experimental determination of such parameters is time consuming, cost effective and above all, it demands the sacrifice of many vertebrates. At this end, the REACH regulations advocate for the use of non-testing predictive methods such as read-across, weight-of-evidence and QSAR (quantitative structure-activity relationship) techniques. Among these methods, QSAR is found to be the best as it is based on molecular structure only. The descriptors used in deriving the model in QSAR vary according to the nature of the narcotics as well as the species used for. The success of a model in predicting the toxicity of a narcotic purely depends on the type of descriptors selected that explains the structural features closely related to the property under study. In this review, we have focused on the different types of descriptors and QSAR models used to explain the narcosis phenomenon. Literature was scanned for acute toxicity of chemicals on species like tadpoles, protozoa, planktonic crustaceans, and small fishes like million fish, rainbow fish etc. from different sources. The toxicity and toxicants were classified considering their polarity and specific interactions of the compounds. Due to complex nature of the substrate, the mechanism of action of toxicant is uncertain. However, the overall results obtained from the biological study have been subjected to QSAR studies to obtain various models, which can provide some ideas on the mode of toxicological action. Different types of molecular descriptors derived both experimentally and theoretically have been used in the QSAR studies. Mostly biochemicals have a specific signature on oil/water partition (Ko/w, P), which is the crux in biological activity. Accordingly, the toxicological activities have good correlations with log P. Addition of some more structural descriptors improves the structure-toxicity relationship. Among these, electronic descriptors like EHOMO, ELUMO and ΔE derived from molecular orbitals have been used in the QSAR. ELUMO describing the energy of excited species of the molecule is found to be the most suitable one. Other molecular descriptors used in the QSAR include constitutional, topological and Abraham's solute descriptors. The models derived from the QSAR studies were found to be highly significant to predict the toxicology as well as to throw light on the mechanism. The best descriptor for aquatic narcosis is the KO/W or P. Addition of an electronic parameter (ELUMO) improves the QSAR to some extent. However, substitution of ELUMO by other class of molecular descriptors has also some statistical significance. To have a global QSAR model, in addition to P, some more appropriate descriptors are to be derived either experimentally or theoretically, latter being the more cost effective and easy in derivation.


The 'electric stroke' and the 'electric spark': anatomists and eroticism at George Baker's electric eel exhibition in 1776 and 1777.
In 1776 and 1777 five living electric eels exhibited in London became a sensational spectacle that appealed to anatomists, electricians and connoisseurs of erotica. George Baker's exhibition made visible the 'electric spark' of the electrical eel and a series of experiments were both witnessed by and participated in by members of the Royal Society and the metropolitan elite. Some participants even grasped the eels firmly in their hands and felt the 'electric stroke' of the eel in addition to observing the spark. In their observation of the electric eel some of these spectators transposed the vivid electric spark from the sphere of electricians and anatomists into that of satirical and erotic literature. Here the erotic electric eel proliferated in the literature and the eel took on quite different connotations that nonetheless were reliant on readers knowledge and experience of the exhibition, experiments and the preoccupations of anatomists. George Baker's electric eel exhibition of 1776 and 1777 is then instructive in exploring the production and circulation of knowledge in Georgian Britain. The story of the electric eel in Georgian culture charts the creation of the electric spark and stroke as objects of observation and encounter, their exhibitionary context, and finally their divergent meanings as the electric eel became erotically charged for a metropolitan masculine elite.


Tears in the vagina, perineum, sphincter ani, and rectum and first sexual intercourse after childbirth: a nationwide follow-up.
The first sexual intercourse after childbirth may be challenging for women, especially if the birth resulted in injuries in the genital area. The purpose of this study was to investigate whether or not tears in the vagina, perineum, sphincter ani, or rectum hindered sexual intercourse during the year after childbirth. We obtained information from 2,490 women in a population-based cohort identified at antenatal care. Information about first sexual intercourse was collected by means of a questionnaire sent 1 year after birth to the women and about women's tears reported in the population-based Swedish Medical Birth Register. Adjusted relative risks with 95 percent confidence intervals for not having had sexual intercourse within 3 and 6 months, respectively, after childbirth were 1.5 (95% CI 1.2-1.8) and 1.6 (95% CI 1.2-2.3) for tears in the vagina, 1.4 (95% CI 1.1-1.6) and 1.5 (95% CI 1.1-2.1) for tears in the perineum, and 2.1 (95% CI 1.4-3.1) and 2.2 (95% CI 1.1-4.6) for tears in the sphincter ani and rectum. No statistically significant differences were found at 1-year follow-up. No associations between episiotomy and delay in resuming intercourse were found after adjusting the relative risks. Tears in the vagina, perineum, sphincter ani, or rectum are associated with a delay in women's resumption of sexual intercourse 6 months after childbirth in Sweden.


Contributions of demography and dispersal parameters to the spatial spread of a stage-structured insect invasion.
Stage-structured models that integrate demography and dispersal can be used to identify points in the life cycle with large effects on rates of population spatial spread, information that is vital in the development of containment strategies for invasive species. Current challenges in the application of these tools include: (1) accounting for large uncertainty in model parameters, which may violate assumptions of "local" perturbation metrics such as sensitivities and elasticities, and (2) forecasting not only asymptotic rates of spatial spread, as is usually done, but also transient spatial dynamics in the early stages of invasion. We developed an invasion model for the Diaprepes root weevil (DRW; Diaprepes abbreviatus [Coleoptera: Curculionidae]), a generalist herbivore that has invaded citrus-growing regions of the United States. We synthesized data on DRW demography and dispersal and generated predictions for asymptotic and transient peak invasion speeds, accounting for parameter uncertainty. We quantified the contributions of each parameter toward invasion speed using a "global" perturbation analysis, and we contrasted parameter contributions during the transient and asymptotic phases. We found that the asymptotic invasion speed was 0.02-0.028 km/week, although the transient peak invasion speed (0.03-0.045 km/week) was significantly greater. Both asymptotic and transient invasions speeds were most responsive to weevil dispersal distances. However, demographic parameters that had large effects on asymptotic speed (e.g., survival of early-instar larvae) had little effect on transient speed. Comparison of the global analysis with lower-level elasticities indicated that local perturbation analysis would have generated unreliable predictions for the responsiveness of invasion speed to underlying parameters. Observed range expansion in southern Florida (1992-2006) was significantly lower than the invasion speed predicted by the model. Possible causes of this mismatch include overestimation of dispersal distances, demographic rates, and spatiotemporal variation in parameter values. This study demonstrates that, when parameter uncertainty is large, as is often the case, global perturbation analyses are needed to identify which points in the life cycle should be targets of management. Our results also suggest that effective strategies for reducing spread during the asymptotic phase may have little effect during the transient phase.


Exercise training-induced remodeling of paraventricular nucleus (nor)adrenergic innervation in normotensive and hypertensive rats.
Activation of oxytocin (OT)ergic projections from the hypothalamic paraventricular nucleus (PVN) to the nucleus tractus solitarii contributes to cardiovascular adjustments during exercise training (EXT). Moreover, a deficit in this central OTergic pathway is associated with altered cardiovascular function in hypertension. Since PVN catecholaminergic inputs, known to be activated during EXT, modulate PVN cardiovascular-related functions, we aimed here to determine whether remodeling of PVN (nor)adrenergic innervation occurs during EXT and whether this phenomenon is affected by hypertension. Confocal immunofluorescence microscopy and tract tracing were used to quantify changes in (nor)adrenergic innervation density in PVN subnuclei and in identified dorsal vagal complex (DVC) projecting neurons (PVN-DVC) in EXT normotensive [Wistar-Kyoto rat (WKY)] and hypertensive [spontaneously hypertensive rat (SHR)] rats. In WKY, EXT increased the density of PVN dopamine beta-hydroxylase immunoreactivity (DBHir) (160%). Furthermore, the number and density of DBHir boutons overlapping PVN-DVC OTergic neurons were also increased during EXT (130%), effects that were blunted in SHR. Conversely, while DBHir in the medial parvocellular subnucleus (an area enriched in corticotropin-releasing hormone neurons) was not changed by EXT in WKY, a diminished DBHir was observed in trained SHR. Overall, these data support the concept that the PVN (nor)adrenergic innervation undergoes plastic remodeling during EXT, an effect that is differentially affected during hypertension. The functional implications of PVN (nor)adrenergic remodeling in relation to the central peptidergic control of cardiovascular function during EXT are discussed.


Local recording of biological magnetic fields using Giant Magneto Resistance-based micro-probes.
The electrical activity of brain, heart and skeletal muscles generates magnetic fields but these are recordable only macroscopically, such as in magnetoencephalography, which is used to map neuronal activity at the brain scale. At the local scale, magnetic fields recordings are still pending because of the lack of tools that can come in contact with living tissues. Here we present bio-compatible sensors based on Giant Magneto-Resistance (GMR) spin electronics. We show on a mouse muscle in vitro, using electrophysiology and computational modeling, that this technology permits simultaneous local recordings of the magnetic fields from action potentials. The sensitivity of this type of sensor is almost size independent, allowing the miniaturization and shaping required for in vivo/vitro magnetophysiology. GMR-based technology can constitute the magnetic counterpart of microelectrodes in electrophysiology, and might represent a new fundamental tool to investigate the local sources of neuronal magnetic activity.


Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes.
Concussion or mild traumatic brain injury (mTBI) represents the most common type of brain injury. However, in contrast with moderate or severe injury, there are currently few non-invasive experimental studies that investigate the cumulative effects of repetitive mTBI using rodent models. Here we describe and compare the behavioral and pathological consequences in a mouse model of single (s-mTBI) or repetitive injury (r-mTBI, five injuries given at 48 h intervals) administered by an electromagnetic controlled impactor. Our results reveal that a single mTBI is associated with transient motor and cognitive deficits as demonstrated by rotarod and the Barnes Maze respectively, whereas r-mTBI results in more significant deficits in both paradigms. Histology revealed no overt cell loss in the hippocampus, although a reactive gliosis did emerge in hippocampal sector CA1 and in the deeper cortical layers beneath the injury site in repetitively injured animals, where evidence of focal injury also was observed in the brainstem and cerebellum. Axonal injury, manifest as amyloid precursor protein immunoreactive axonal profiles, was present in the corpus callosum of both injury groups, though more evident in the r-mTBI animals. Our data demonstrate that this mouse model of mTBI is reproducible, simple, and noninvasive, with behavioral impairment after a single injury and increasing deficits after multiple injuries accompanied by increased focal and diffuse pathology. As such, this model may serve as a suitable platform with which to explore repetitive mTBI relevant to human brain injury.


Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation Study of Polyphenon E in Patients with Barrett's Esophagus.
This study was conducted to determine the safety and efficacy of the green tea-derived Polyphenon E (Poly E) in patients with Barrett's Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E-treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level--mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa.


Long-Term Stability of n-Alkane-in-Water Pickering Nanoemulsions: Effect of Aqueous Solubility of Droplet Phase on Ostwald Ripening.
High-pressure microfluidization is used to prepare a series of oil-in-water Pickering nanoemulsions using sterically-stabilized diblock copolymer nanoparticles as the Pickering emulsifier. The droplet phase comprised either n-octane, n-decane, n-dodecane, or n-tetradecane. This series of oils enabled the effect of aqueous solubility on Ostwald ripening to be studied, which is the primary instability mechanism for such nanoemulsions. Analytical centrifugation (LUMiSizer instrument) was used to evaluate the long-term stability of these Pickering nanoemulsions over time scales of weeks/months. This technique enables convenient quantification of the fraction of growing oil droplets and confirmed that using n-octane (aqueous solubility = 0.66 mg dm-3 at 20 °C) leads to instability even over relatively short time periods. However, using n-tetradecane (aqueous solubility = 0.386 μg dm-3 at 20 °C) leads to significantly improved long-term stability with respect to Ostwald ripening, with all droplets remaining below 1 μm diameter after 6 weeks storage at 20 °C. In the case of n-dodecane, the long-term stability of these new copolymer-stabilized Pickering nanoemulsions is significantly better than the silica-stabilized Pickering nanoemulsions reported in the literature by Persson et al. ( Colloids Surf., A, 2014, 459, 48-57). This is attributed to a much greater interfacial yield stress for the former system, as recently described in the literature (see P. J. Betramo et al. Proc. Natl. Acad. Sci. U.S.A., 2017, 114, 10373-10378).


Fracture Risk in Relation to Serum 25-Hydroxyvitamin D and Physical Activity: Results from the EPIC-Norfolk Cohort Study.
Vitamin D deficiency and physical inactivity have been associated with bone loss and fractures, but their combined effect has scarcely been studied either in younger or older adults. Therefore, we aimed to assess the associations between physical activity, age and 25-hydroxyvitamin D (25(OH)D) status separately and in combination with the incidence of fracture risk in the EPIC-Norfolk cohort study. Baseline (1993-1998) self-reported physical activity and serum 25(OH)D concentrations at follow-up (1998-2000) were collected in 14,624 men and women (aged 42-82 y between 1998 and 2000). Fracture incidence was ascertained up to March 2015. Cox proportional hazard model was used to determine HRs of fractures by plasma 25(OH)D (<30, 30 to <50, 50 to <70, 70 to <90, >90 nmol/L), age (<65 y and >65 y) and physical activity (inactive and active) categories, by follow-up time per 20 nmol/L increase in serum 25(OH)D and to explore age-25(OH)D and physical activity-25(OH)D interactions. The age-, sex-, and month-adjusted HRs (95% CIs) for all fractures (1183 fractures) by increasing vitamin D category were not significantly different. With additional adjustment for body mass index, smoking status, alcohol intake, supplement use and history of fractures, the fracture risk was 29% lower in those participants with 50 to 70 nmol/L compared with those in the lowest quintile (<30 nmol/L). Physical inactivity based on a single baseline assessment was not associated with fracture risk. Vitamin D status appeared inversely related to fractures in middle aged adults. In older adults, the relationship between vitamin D status and fracture risk was observed to be J-shaped. Clinical and public health practice in vitamin D supplementation could partially explain these findings, although definitive conclusions are difficult due to potential changes in exposure status over the long follow up period.


Botulinum toxin type A and acute drug costs in migraine with triptan overuse.
Patients with chronic migraine and medication overuse are significant consumers of health care resources. To determine whether botulinum toxin type A prophylaxis reduces the cost of acute migraine medications in patients with chronic migraine and triptan overuse. In this multicenter, open-label study, patients with chronic migraine (≥ 15 headache days/month) who were triptan overusers (triptan intake ≥ 10 days/month for ≥ 3 months) received botulinum toxin type A (95-130 U) at baseline and month three. Headache (HA) frequency and medication use were assessed with patient diaries, and headache-related disability by means of the MIDAS and Headache Impact Test-6 questionnaires. Of 53 patients enrolled (mean age ± standard deviation, 46.5 years ± 8.4; 47 [88.7%] females), 48 (90.6%) completed the study at month six. Based on headache diaries, significant (P ≤ 0.0002) decreases from baseline were observed for days per month with headache/migraine, days with any acute headache medication use, days with triptan use, and triptan doses taken per month. A significant (P < 0.0001) increase from baseline in headache-free days per month was also observed. Prescription medication costs for acute headache medications decreased significantly, including significant reductions in triptan costs (mean reduction of -C$106.32 ± 122.87/month during botulinum toxin type A prophylaxis; P < 0.0001). At baseline, 78% of patients had severe disability (MIDAS score) and 86.8% had severe impact due to headache (HIT-6 scores); at month six, this decreased to 60% and 68%, respectively. Botulinum toxin type A prophylactic therapy markedly decreased costs related to acute headache medication use in patients with chronic migraine and triptan overuse.


Cell culture propagation of bovine coronavirus.
Although most field strains of bovine coronavirus (BCV) grow poorly in cell culture and fail to produce cytopathic effects (CPE) until after blind passage, primary calf kidney (PCK) and Vero cells have permitted primary isolation of virus. Cell culture-adapted strains of BCV replicate in PCK, bovine embryonic lung, bovine fetal thyroid, bovine fetal brain, bovine skin cells, ovine fetal kidney cells, and the cell lines pig kidney K3 and 15, Vero, human embryonic lung fibroblasts, HRT-18, MDBK and BEK-1, with trypsin useful for enhancing replication. Organ culture as well as suckling mouse, rat, and hamster brains also support the growth of cell culture-adapted BCV strains. Viral growth is most commonly detected by CPE, immunofluorescence, hemagglutination, and hemadsorption assays or electron microscopy of supernatants from infected cells. In this report, the optimal conditions for the growth and plaque assay of the NCDV strain of BCV in MDBK cells are described.


Ongoing evolution of strand composition in bacterial genomes.
We tried to identify the substitutions involved in the establishment of replication strand bias, which has been recognized as an important evolutionary factor in the evolution of bacterial genomes. First, we analyzed the composition asymmetry of 28 complete bacterial genomes and used it to test the possibility that asymmetric deamination of cytosine might be at the origin of the bias. The model showed significant correlation to the data but left unexplained a significant portion of the variance and indicated a systematic underestimation of GC skews in comparison with TA skews. Second, we analyzed the substitutions acting on the genes from five fully sequenced Chlamydia genomes that had not suffered strand switch since speciation. This analysis showed that substitutions were not at equilibrium in Chlamydia trachomatis or in C. muridarum and that strand bias is still an on-going process in these genes. Third, we identified substitutions involved in the adaptation of genes that had switched strands after speciation. These genes adapted quickly to the skewed composition of the new strand, mostly due to C-->T, A-->G, and C-->G asymmetric substitutions. This observation was reinforced by the analysis of genes that switched strands after divergence between Bacillus subtilis and B. halodurans. Finally, we propose a more extended model based on the analysis of the substitution asymmetries of CHLAMYDIA: This model fits well with the data provided by bacterial genomes presenting strong strand bias.


[Effect of hypoxic preconditioning on the level of s-NGAL (lipocalin-2) in myocardial revascularization in the conditions of extracorporeal haemocirculation].
To assess the effect of hypoxic preconditioning (HPC) on the level of s-NGAL (lipocalin-2) in myocardial revascularization under conditions of extracorporeal haemocirculation (EH). We examined a total of 40 patients presenting with CAD (mean age 57.62±1.20 years) and subjected to coronary artery bypass grafting (CABG) under conditions of EH. All patients were subdivided into 2 groups. The study group comprised 20 patients who during CABG were subjected to HPC, and 20 patients made up the comparison group. Preconditioning was carried out in the mode of one cycle of 10-minute hypoxemia followed by a 5-minute period of reoxygenation. All patients were subjected to measuring the concentration of lipocalin in blood serum prior to CABG and 5 hours after the beginning of the operative intervention with the help of the test system Human Lipocain-2 NGAL, ELISA. Prior to operative treatment the average levels of lipocalin in blood serum of the patients of the compared groups significantly did not differ, with the inverse correlation between the levels of s-NGAL and the ejection fraction of the left ventricle (r=-0.37, p=0.02), as well as the glomerular filtration rate (according to the findings of radionuclide renoscintigraphy) and the level of lipocalin (r=-0.28, p=0.046). Five hours after the CABG, there was a statistically significant increase in the s-NGAL concentration as compared with the preoperative value both in the HPC group patients and the comparison group (from 70.65±10.72 to 127.58±22.59 ng/ml and from 65.01±8.64 to 171.65±20.10 ng/ml, respectively). There was a direct relationship between the duration of EH and the dynamics of the s-NGAL level in patients of the both groups. However, an increase in the NGAL concentration in the comparison group patients was considerably more manifested vs the study group patients (p=0.02). The median value of the difference between the pre- and postoperative values of the lipocalin level in Group I amounted to 56.94±19.76 ng/ml, being in Group II 106.64±18.94 ng/ml (p=0.004). Hypoxic preconditioning during myocardial revascularization under the conditions of extracorporeal haemocirculation prevents a critical elevation of the lipocalin-2 level, thus suggesting a decrease in the degree of the lesion of the renal parenchyma in cardiosurgical patients.


Trade-Off Between Field-of-View and Resolution in the Thermal-Integrated Argus II System.
To investigate the effect of a wider field-of-view (FOV) of a retinal prosthesis on the users' performance in locating objects. One female and four male subjects who were blind due to end-stage retinitis pigmentosa and had been implanted with the Argus II retinal prosthesis participated (aged 63.4 ± 15.4). Thermal imaging was captured by an external sensor and converted to electrical stimulation to the retina. Subjects were asked to localize and to reach for heat-emitting objects using two different FOV mappings: a normal 1:1 mapping (no zoom) that provided 18° × 11° FOV and a 3:1 mapping (zoom out) that provided 49° × 35° FOV. Their accuracy and response time were recorded. Subjects were less accurate and took longer to complete the tasks with zoom out compared to no zoom. Localization accuracy decreased from 83% (95% confidence interval, 75%, 90%) with no zoom to 76% (67%, 83%) with zoom out (P = 0.07). Reaching accuracy differed between the two mappings only in one subject. Response time increased by 43% for the localization task (24%, 66%; P < 0.001) and by 20% for the reaching task (0%, 45%; P = 0.055). Argus II wearers can efficiently find heat-emitting objects with the default 18° × 11° FOV of the current Argus II. For spatial localization, a higher spatial resolution may be preferred over a wider FOV. Understanding the trade-off between FOV and spatial resolution in retinal prosthesis users can guide device optimization.


Love thy neighbour or opposites attract? Patterns of spatial segregation and association among crested penguin populations during winter.
Competition for food among populations of closely related species and conspecifics that occur in both sympatry and parapatry can be reduced by interspecific and intraspecific spatial segregation. According to predictions of niche partitioning, segregation is expected to occur at habitat boundaries among congeners and within habitats among conspecifics, while negative relationships in the density of species or populations will occur in areas of overlap. We tested these predictions by modelling the winter distributions of two crested penguin species from three colonies in the south-western Atlantic. Penguins were tracked from two large colonies on the Falkland Islands and one in South Georgia, from where they dispersed through the South Atlantic, Southern Ocean and south-eastern Pacific. Forty macaroni penguins (Eudyptes chrysolophus) from South Georgia and 82 southern rockhopper penguins (Eudyptes chrysocome chrysocome) from two colonies in the Falkland Islands were equipped with global location sensors which log time and light, allowing positions to be estimated twice-daily, from April to August in 2011. Positions were gridded and converted into maps of penguin density. Metrics of overlap were calculated and density was related to remote-sensed oceanographic variables and competitor density using generalized additive models. Macaroni penguins from western South Georgia and southern rockhopper penguins from Steeple Jason Island, Falkland Islands, were spatially segregated by differences in their habitat preferences thus supporting our first prediction regarding interspecific segregation. However, southern rockhopper penguins from Beauchêne Island showed a marked spatial overlap with macaroni penguins as the two had similar habitat preferences and strong mutual associations when controlling for habitat. Contrary to our predictions relating to intraspecific segregation, southern rockhopper penguins from Beauchêne Island and Steeple Jason Island were segregated by differences in habitat selection. Morphological differentiation probably allows macaroni penguins from South Georgia and southern rockhopper penguins from Beauchêne Island to coexist in areas of spatial overlap, whereas segregation of the two Falkland rockhopper penguin populations may have arisen from two distinct lineages retaining cultural fidelity to ancestral wintering areas.


Coded aperture design in mismatched compressive spectral imaging.
Compressive spectral imaging (CSI) senses a scene by using two-dimensional coded projections such that the number of measurements is far less than that used in spectral scanning-type instruments. An architecture that efficiently implements CSI is the coded aperture snapshot spectral imager (CASSI). A physical limitation of the CASSI is the system resolution, which is determined by the lowest resolution element used in the detector and the coded aperture. Although the final resolution of the system is usually given by the detector, in the CASSI, for instance, the use of a low resolution coded aperture implemented using a digital micromirror device (DMD), which induces the grouping of pixels in superpixels in the detector, is decisive to the final resolution. The mismatch occurs by the differences in the pitch size of the DMD mirrors and focal plane array (FPA) pixels. A traditional solution to this mismatch consists of grouping several pixels in square features, which subutilizes the DMD and the detector resolution and, therefore, reduces the spatial and spectral resolution of the reconstructed spectral images. This paper presents a model for CASSI which admits the mismatch and permits exploiting the maximum resolution of the coding element and the FPA sensor. A super-resolution algorithm and a synthetic coded aperture are developed in order to solve the mismatch. The mathematical models are verified using a real implementation of CASSI. The results of the experiments show a significant gain in spatial and spectral imaging quality over the traditional grouping pixel technique.


Analysis of chromosomal aberrations and recombination by allelic bias in RNA-Seq.
Genomic instability has profound effects on cellular phenotypes. Studies have shown that pluripotent cells with abnormal karyotypes may grow faster, differentiate less and become more resistance to apoptosis. Previously, we showed that microarray gene expression profiles can be utilized for the analysis of chromosomal aberrations by comparing gene expression levels between normal and aneuploid samples. Here we adopted this method for RNA-Seq data and present eSNP-Karyotyping for the detection of chromosomal aberrations, based on measuring the ratio of expression between the two alleles. We demonstrate its ability to detect chromosomal gains and losses in pluripotent cells and their derivatives, as well as meiotic recombination patterns. This method is advantageous since it does not require matched diploid samples for comparison, is less sensitive to global expression changes caused by the aberration and utilizes already available gene expression profiles to determine chromosomal aberrations.


Attitudes and expectations of treating deep caries: a PEARL Network survey.
A survey was conducted within a practice-based dental research network to determine dentists' treatment methods for deep caries lesions and whether the dentists' intended treatment approaches were influenced by their expectations for pulpal exposure. The survey further examined how general dentistry practices have adopted scientific evidence of caries classification, excavation, and capping techniques. Dentists were queried regarding liner use, hypersensitivity considerations, point of endodontic therapy, and anticipated vitality outcomes from Class I resin-based composite restorations over three to five years. Of the 93 practitioner-investigators who were in the network at the time of the survey, 85 (92%) completed it. Of those who responded, 62% said that they would remove all caries when presented with a case in which one would expect pulpal exposure, while 18% would partially remove caries and 21% would initiate endodontic treatment; 17% reported that they would utilize an antimicrobial agent before a liner or bonding agent during restoration. The outcomes projected for tooth vitality over the next three to five years were equivalent regardless of the caries removal approach or the use of a liner/bonding agent. When beginning the preparation, the method of treatment did not change if a pulpal exposure was anticipated, other than a threefold increase in immediate endodontic treatment. When dentists were given a direct pulp cap scenario, the projected use of a liner/bonding agent changed little while the vitality projections decreased. Overall survey findings indicate that approximately 20% of network dentists favor partial caries removal techniques and that deep caries treatment outcome studies are warranted, given the various treatments employed.


An Examination of KCNE1 Mutations and Common Variants in Chronic Tinnitus.
Chronic tinnitus is a highly prevalent and often incapacitating condition frequently associated with sensorineural hearing loss. While its etiology remains incompletely understood there is a growing awareness of genetic factors that predispose to, or aggravate chronic tinnitus. Candidate genes for the disorder include KCNE1, a potassium channel subunit gene that has been implicated in maturation defects of central vestibular neurons, in Menière's disease, and in noise-induced hearing loss. 201 Caucasian outpatients with a diagnosis of chronic tinnitus were systematically screened for mutations in the KCNE1 open reading frame and in the adjacent sequence by direct sequencing. Allele frequencies were determined for 46 known variants, plus two novel KCNE1 mutations. These comprised one missense substitution (V47I) in the highly conserved region encoding the KCNE1 transmembrane domain, and one rare variant in the gene's 3'UTR. When genotypes were grouped assuming dominance of the minor alleles, no significant genotype or compound genotype effects were observed on tinnitus severity. The newly identified V47I substitution argues in favor of an enlarged spectrum of mutations in hearing disorders. However, with regard to allele frequencies in healthy control populations from earlier studies, more common KCNE1 variants are unlikely to play a major role in chronic tinnitus. Further investigations are invited to address variation in additional channel subunits as possible risk factors in tinnitus.


Embracing the Social Nature of Recovery: A Qualitative Study on the Resource Group Method for People With Severe Mental Illness.
Objective: The resource group method for people with severe mental illness might provide a useful framework to facilitate patient's empowerment and systematically engage significant others. However, no research has explored the perspectives and experiences of patients and their significant others. This is crucial for better adjustment to the needs of the people using the method. The aim of this study was to develop a useful framework for a deeper understanding of the resource group method and its outcomes. Method: The study used a longitudinal, qualitative multiple case-study design based on grounded theory methodology. During a period of 2 years, the developments and processes in eight resource groups were explored by conducting a total of 74 interviews (e.g., with patients, significant others, and mental health professionals) and 26 observations of resource group meetings. Results: Analysis showed that a well-functioning resource group set the stage for five processes to unfold: (i) experience of support; (ii) acknowledgment of significant others; (iii) activation; (iv) openness; and (v) integration. These processes facilitated recovery both in terms of an arousing curiosity within the patient as well as increasing reciprocity and equality in their social relations. In addition, the method emphasized the uniqueness of each recovery journey, thereby providing a framework to shape recovery-oriented care. The analysis also revealed three hindering factors: (i) embedding and implementation issues; (ii) predominant network; and (iii) tensions inherent in the resource group setting. Conclusion: Working according to the resource group method involves that the person's recovery work becomes a social process that takes place in relation to the social environment and everyday life in which it is important to acknowledge and integrate the needs of significant others in treatment and care. This study provides a first step toward a multidimensional comprehension of the resource group method, the working mechanisms and its influence on recovery for people with severe mental illness.


MRJP1-containing glycoproteins isolated from honey, a novel antibacterial drug candidate with broad spectrum activity against multi-drug resistant clinical isolates.
The emergence of extended- spectrum β-lactamase (ESBL) is the underlying cause of growing antibiotic resistance among Gram-negative bacteria to β-lactam antibiotics. We recently reported the discovery of honey glycoproteins (glps) that exhibited a rapid, concentration-dependent antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli that resembled action of cell wall-active β-lactam drugs. Glps showed sequence identity with the Major Royal Jelly Protein 1 (MRJP1) precursor that harbors three antimicrobial peptides: Jelleins 1, 2, and 4. Here, we used semi-quantitative radial diffusion assay and broth microdilution assay to evaluate susceptibility of a number of multi-drug resistant (MDR) clinical isolates to the MRJP1-contaning honey glycoproteins. The MDR bacterial strains comprised three methicillin-resistant Staphylococcus aureus (MRSA), four Pseudomonas aeruginosa, two Klebsiella pneumoniae, two vancomycin-resistant Enterococci (VRE), and five ESBL identified as one Proteus mirabilis, three E. coli, and one E. coli NDM. Their resistance to different classes of antibiotics was confirmed using automated system Vitek 2. MDR isolates differed in their susceptibility to glps with MIC90 values ranging from 4.8 μg/ml against B. subtilis to 14.4 μg/ml against ESBL K. pneumoniae, Klebsiella spp. ESBL and E. coli and up to 33 μg/ml against highly resistant strains of P. aeruginosa. Glps isolated from different honeys showed a similar ability to overcome bacterial resistance to β-lactams suggesting that (a) their mode of action is distinct from other classes of β-lactams and that (b) the common glps structure was the lead structure responsible for the activity. The results of the current study together with our previous evidence of a rapid bactericidal activity of glps demonstrate that glps possess suitable characteristics to be considered a novel antibacterial drug candidate.


Should children be screened to undergo early treatment for otitis media with effusion? A systematic review of randomized trials.
Otitis media with effusion (OME) is the most common cause of acquired hearing loss in childhood and has been associated with delayed language development and behavioural problems. Some have argued that children should be screened and treated early if found to have clinically important OME. The aim of this review was to assess evidence from randomized controlled trials about the effectiveness of screening and treating children with clinically important OME in the first 4 years of their life. The primary outcome was language development. We searched the Cochrane Controlled Trials Register, MEDLINE and EMBASE and reference lists of all included studies in February 2003. We also contacted the first authors of the studies included in this review. Search terms included otitis media; otitis media with effusion; glue ear; OME; screen; children; treatment; language; and behaviour. Data extraction and methodological quality assessment were performed by at least two of us for each study independently, using methods described in the Cochrane Collaboration Handbook. From the three included randomized controlled trials evaluating interventions among children with OME identified through screening, we found no evidence of clinically important benefit in language development. The identified randomized trials do not show an important benefit on language development from screening the general population of asymptomatic children in the first 4 years of life to undergo early treatment for OME. Screening asymptomatic children in the first 4 years of life for OME is not recommended.


Assessment of trace metal contamination in mangrove ecosystems from Senegal, West Africa.
The inorganic contamination of sediment and harvested molluscs was investigated in the mangrove environment of Southern West Senegal. Trace metals were analysed in surface sediments, two bivalves (Arca senilis and Crassostera gasar) and three gastropods (Conus spp., Hexaplex duplex and Pugilina morio) collected from four stations: Dionewar, Niodor and Falia localised in the Saloum Delta, and Fadiouth from the Petite Côte. A geochemical normalisation approach by using aluminium allowed for discrimination of sediment contamination among sites. Indeed, Fadiouth appeared highly contaminated with Cd, Hg and Ni compared to the Saloum Delta. For all mangrove sites, trace metals exhibited significant higher concentrations (on a dry weight basis) in shellfish compared to sediments, excepted for Ni and Pb. The distribution pattern followed a similar global trend in molluscs regardless of the spatio-temporal variability, with the predominance of Zn (80% of total metals) followed by Cu and Cd. However, strong differences of metal bioavailability and bioaccumulation in biota were demonstrated, revealing the requirement of employing a suite of organism bioindicators to monitor metal contamination in mangrove ecosystems. From an ecotoxicological point of view, trace metal levels in sediments from the Petite Côte and the Sine-Saloum Estuary were below the effects range-low (ERL) threshold limit of the sediment quality guidelines for adverse biological effects (SQGs). On the opposite, some concerns about Cd contamination of edible shellfish from Southern West Senegal were highlighted, from both the safety point of view of local populations' health, and the chemical quality point of view of exported resources.


Wilderness Medical Society practice guidelines for basic wound management in the austere environment: 2014 update.
In an effort to produce best-practice guidelines for wound management in the austere environment, the Wilderness Medical Society convened an expert panel charged with the development of evidence-based guidelines for the management of wounds sustained in an austere (dangerous or compromised) environment. Recommendations are made about several parameters related to wound management. These recommendations are graded based on the quality of supporting evidence and the balance between the benefits and risks or burdens for each parameter according to the methodology stipulated by the American College of Chest Physicians. This is an updated version of the original guidelines published in Wilderness & Environmental Medicine 2014;25(3):295-310.


Evaluation of a new strategy to modulate skeletal development in Thoroughbred performance horses by imposing track-based exercise during growth.
No data exist on the intensity of exercise required or on possible harmful effects of increasing exercise in foals over the natural level when free at pasture. To investigate whether an increase in workload over free pasture exercise in the period from directly after birth to the start of training is tolerated by Thoroughbred (TB) foals without increasing injury rate or producing other undesired side effects. Thirty-three TB foals were allocated to one of 2 exercise groups directly after birth. One group (PASTEX) was raised on pasture and the other (CONDEX) kept under identical circumstances, but was additionally subjected to an exercise protocol of gradually increasing intensity. Foals were monitored periodically and scored for the presence of clinical signs related to the musculoskeletal system (joint effusion, pain at flexion, occurrence of physeal swelling), and radiographs taken at the end of the conditioning phase. Also, behavioural studies were performed to detect any changes in behaviour related to the exercise programme. Cortisol levels were measured in both groups, to assess the level of stress. Workload in the CONDEX group was significantly higher than in the PASTEX group (approximately 30%). Conditioning increased the likelihood for joint effusion in the antebrachiocarpal joint, but reduced tarsocrural effusion and physeal swelling at the lateral distal radius, the third metacarpal bone (medial aspect) and lateral and medial aspects of the third metatarsal bone. The 30% increase in workload did not affect the animals' welfare, effects of conditioning exercise on clinical musculoskeletal health were few and there were no adverse effects. This study supports the feasibility of imposing early conditioning exercise in horses and is a benchmark for its effects on the development of equine musculoskeletal tissues.


Biological responses of Raw 264.7 macrophage exposed to two strains of Stachybotrys chartarum spores grown on four different wallboard types.
The many benefits of building "green" have motivated the use of sustainable products in the design and execution of the built environment. However, the use of these natural or recycled materials, some of which have been treated with antimicrobials, provides a growth opportunity for microorganisms with the potential to elicit adverse health effects especially in the presence of an antimicrobial. The focus of this research was to determine the effects of Stachybotrys chartarum (strains Houston and 51-11) grown under different conditions on a macrophage cell line (Raw 264.7) using endpoints, including cytotoxicity, and those associated with immunity specifically inflammation and MHC class II expression. The fungi were grown on four different gypsum products, and macrophages were exposed to whole spores of both strains and fragmented spores of strain 51-11. Whole spores of the Houston strain elicited no cytotoxicity with some level of inflammation, while exposure to whole spores of 51-11 caused variable responses depending on the wallboard type supporting the fungal growth. High concentrations of fragmented 51-11 spores primarily resulted in the apoptosis of macrophage with no inflammation. None of the fungal strains caused elevated levels of major histocompatibility complex (MHC) class II expression on the surface of Raw cells. Mycotoxin levels of 51-11 spores from all of the wallboard types measured >250 ng/μL of T2 equivalent toxin based on activity. Collectively, the data demonstrated that all of the wallboard types supported growth of fungi with the ability to elicit harmful biological responses with the potential to negatively impact human health.


Review of Robotic Surgery in Gynecology-The Future Is Here.
The authors present a systematic review of randomized and observational, retrospective and prospective studies to compare between robotic surgery as opposed to laparoscopic, abdominal, and vaginal surgery for the treatment of both benign and malignant gynecologic indications. The comparison focuses on operative times, surgical outcomes, and surgical complications associated with the various surgical techniques. PubMed was the main search engine utilized in search of study data. The review included studies of various designs that included at least 25 women who had undergone robotic gynecologic surgery. Fifty-five studies (42 comparative and 13 non-comparative) met eligibility criteria. After careful analysis, we found that robotic surgery was consistently connected to shorter post-surgical hospitalization when compared to open surgery, a difference less significant when compared to laparoscopic surgery. Also, it seems that robotic surgery is highly feasible in gynecology. There are quite a few inconsistencies regarding operative times and estimated blood loss between the different approaches, though in the majority of studies estimated blood loss was lower in the robotic surgery group. The high variance in operative times resulted from the difference in surgeon's experience. The decision whether robotic surgery should become mainstream in gynecological surgery or remain another surgical technique in the gynecological surgeon's toolbox requires quite a few more randomized controlled clinical trials. In any case, in order to bring robotic surgery down to the front row of surgery, training surgeons is by far the most important goal for the next few years.