A comparison of stimulus types in online classification of the P300 speller using language models.
The P300 Speller is a common brain-computer interface communication system. There are many parallel lines of research underway to overcome the system's low signal to noise ratio and thereby improve performance, including using famous face stimuli and integrating language information into the classifier. While both have been shown separately to provide significant improvements, the two methods have not yet been implemented together to demonstrate that the improvements are complimentary. The goal of this study is therefore twofold. First, we aim to compare the famous faces stimulus paradigm with an existing alternative stimulus paradigm currently used in commercial systems (i.e., character inversion). Second, we test these methods with language model integration to assess whether different optimization approaches can be combined to further improve BCI communication. In offline analysis using a previously published particle filter method, famous faces stimuli yielded superior results to both standard and inverting stimuli. In online trials using the particle filter method, all 10 subjects achieved a higher selection rate when using the famous faces flashing paradigm than when using inverting flashes. The improvements achieved by these methods are therefore complementary and a combination yields superior results to either method implemented individually when tested in healthy subjects.


Neuromuscular electric stimulation in patellofemoral dysfunction: literature review.
Patellofemoral dysfunction is a fairly common deficiency among young individuals that primarily affects females and may be characterized by pain, swelling and retropatellar crepitation. The purpose of this review of literature from the period between 2005 and 2011 was to systematize knowledge in relation to the increase in quadriceps muscle strength and pain relief in patients with patellofemoral dysfunction, using neuromuscular electrical stimulation and resistance exercises. The inclusion criteria were intervention articles from the past six years, in English, Spanish and Portuguese, which used muscle strengthening and neuromuscular electrical stimulation for rehabilitation obtained through searches in the electronic databases Medline and Lilacs and in the Bireme library. The bibliographic search yielded 28 references, of which nine were excluded in accordance with the aims and inclusion criteria while 16 articles were selected for reading of the abstracts and subsequent analysis. Mediumfrequency Neuromuscular Electrical Stimulation (NMES) can be used in association with resistance exercises as an adjuvant in the treatment of patellofemoral dysfunction (PFD), both to achieve muscle rebalance and for pain relief.


Family planning counseling for women living with HIV: a systematic review of the evidence of effectiveness on contraceptive uptake and pregnancy incidence, 1990 to 2011.
Family planning is an important public health intervention with numerous potential health benefits for all women. One of those key benefits is the prevention of mother-to-child transmission of HIV, through the prevention of unintended pregnancies among women living with HIV. We conducted a systematic review of the effectiveness of family planning counseling interventions for HIV infected women in low- and middle-income countries. We found nine articles which met the inclusion criteria for this review, all from Africa. Though these studies varied in the specifics of the interventions provided, research designs and measures of outcomes, key features were discernible. Providing concerted information and support for family planning use, coupled with ready access to a wide range of contraceptive methods, seemed most effective in increasing use. Effects on pregnancy overall were difficult to measure, however: no studies assessed the effect on unintended pregnancy. Though these results are far from definitive, they do highlight the need for strengthened efforts to integrate family planning counseling and access to services into HIV prevention, and for greater consistency of effort over time. Studies which specifically investigate fertility intentions and desires of women living with HIV, contraception use following interventions to increase knowledge, awareness, motivation and access to the means to act on those intentions and unintended pregnancies would be valuable to help clinic personnel, programme planners and policy makers guide the development of the integrated services they offer.


Alloplast as an alternative for dorsal augmentation.
With an ever increasing ethnic population in the United States, dorsal augmentation has become a fairly common accompaniment to rhinoplasty. But procurement of adequate graft material of suitable nature and amount persists as a challenge to plastic surgeons. This dilemma has become even more pressing in recent years as a variety of other exceptional graft applications for the patient's limited cartilage bank have become not just an option but also mandatory for our higher expectations. The debate of the past century over alloplast in the dorsum persists in the present. "When and if ever" is the commonly asked question. Surely, no alloplast can match the ideal graft, but no graft is ideal either as it always comes in limited supply. There is now more than 15 years of experience with expanded polytetrafluoroethylene in the nose. It appears that with proper patient selection and technique, expanded polytetrafluoroethylene can be used in the nasal dorsum with relatively low complication rates and high patient satisfaction.


Arginase and vascular aging.
Vascular and associated ventricular stiffness is one of the hallmarks of the aging cardiovascular system. Both an increase in reactive oxygen species production and a decrease in nitric oxide (NO) bioavailability contribute to the endothelial dysfunction that underlies this vascular stiffness, independent of other age-related vascular pathologies such as atherosclerosis. The activation/upregulation of arginase appears to be an important contributor to age-related endothelial dysfunction by a mechanism that involves substrate (L-arginine) limitation for NO synthase (NOS) 3 and therefore NO synthesis. Not only does this lead to impaired NO production but also it contributes to the enhanced production of reactive oxygen species by NOS. Although arginase abundance is increased in vascular aging models, it appears that posttranslational modification by S-nitrosylation of the enzyme enhances its activity as well. The S-nitrosylation is mediated by the induction of NOS2 in the endothelium. Furthermore, arginase activation contributes to aging-related vascular changes by mechanisms that are not directly related to changes in NO signaling, including polyamine-dependent vascular smooth muscle proliferation and collagen synthesis. Taken together, arginase may represent an as yet elusive target for the modification of age-related vascular and ventricular stiffness contributing to cardiovascular morbidity and mortality.


Successful pregnancy renal transplantation.
Pregnancy in a renal homograft recipient resulted in the delivery of a 2770-g male fetus by classic cesarean section. Renal function remained stable throughout the gestation. The fetoplacental unit was monitored by the concurrent assay of 24-hour urinary estrogen excretion and human placental lactogen (hPL) in light of the spuriously low estrogen levels often found in these patients on chronic glucocorticoid immunosuppression.


Intensity of intestinal infection with multiple worm species is related to regulatory cytokine output and immune hyporesponsiveness.
Increasing immunological dysfunction (atopy and autoimmunity) in western society may be linked to changes in undetermined environmental agents. We hypothesize that increased exposure to multiple gut worm species promotes stronger immunological regulation. We report here that African children constitutively secrete more immunoregulatory cytokines (interleukin [IL]-10 and transforming growth factor [TGF]- beta1) under conditions of hyperendemic exposure to the intestinal nematodes Ascaris lumbricoides and Trichuris trichiura, compared with conditions of mesoendemic exposure. Under conditions of hyperendemic exposure, estimators of combined intestinal nematode infection level relate positively to combined constitutive IL-10 and TGF-beta1 production and negatively to total immune reactivity (determined as IL-4, interferon-gamma, and cellular proliferative responses to Ascaris or Trichuris helminth antigens, Streptococcus pneumoniae bacterial antigen, or the mitogen phytohemaglutinin). Total immune reactivity and anti-inflammatory cytokine production relate inversely. Our data suggest that gut nematodes are important mediators of immunoregulation.


Response characterstics of spinothalamic tract neurons that project to the posterior thalamus in rats.
A sizeable number of spinothalamic tract axons terminate in the posterior thalamus. The functional roles and precise areas of termination of these axons have been a subject of recent controversy. The goals of this study were to identify spinothalamic tract neurons (STT) within the cervical enlargement that project to this area, characterize their responses to mechanical and thermal stimulation of their receptive fields, and use microantidromic tracking methods to determine the nuclei in which their axons terminate. Forty-seven neurons were antidromically activated using low-amplitude (< or =30 microA) current pulses in the contralateral posterior thalamus. The 51 points at which antidromic activation thresholds were lowest were surrounded by ineffective tracks indicating that the surrounded axons terminated within the posterior thalamus. The areas of termination were located primarily in the posterior triangular, medial geniculate, posterior and posterior intralaminar, and suprageniculate nuclei. Recording points were located in the superficial and deep dorsal horn. The mean antidromic conduction velocity was 6.4 m/s, a conduction velocity slower than that of other projections to the thalamus or hypothalamus in rats. Cutaneous receptive fields appeared to be smaller than those of neurons projecting to other areas of the thalamus or to the hypothalamus. Each of the examined neurons responded exclusively or preferentially to noxious stimuli. These findings indicate that the STT carries nociceptive information to several target nuclei within the posterior thalamus. We discuss the evidence that this projection provides nociceptive information that plays an important role in fear conditioning.


[Study on geographical distribution of leptospirosis in China].
Since 1955, Leptospirosis has been recognized as a notifiable infectious disease in China. According to the data gathered from 26 provinces of China (except for Taiwan) in 1955-1993, the average morbidity and mortality were 7.08/10(5) and 1.02% respectively. Distribution of the disease involved 26 provinces in China (not including Taiwan). The trend of the disease has been steady for recent years but outbreaks occasionally occurred, especially in several southern provinces of China. Potential risk factors may exist in these areas. Distribution of endemic areas of this disease is located between 25 degrees-35 degrees latitude and 100 degrees-120 degrees longitude i, e. those provinces along with drainage areas of the Yangtze River and the Huaihe River.


Intranasal Midazolam Sedation in a Pediatric Emergency Dental Clinic.
The purpose of this study was to compare the effectiveness and recovery times of 0.3 and 0.5 mg/kg intranasal midazolam (INM) administered with a mucosal atomizer device (MAD) in a pediatric emergency dental hospital clinic. One hundred eighteen children aged from 4 to 6 years were randomly administered either 0.3 or 0.5 mg/kg INM via an MAD in a triple-blinded randomized controlled trial. Sedation was achieved to some degree in 100% of the sample. The pulse rate and oxygen saturation were within the normal range in 99% of the patients. A burning sensation was reported in 9% of children. The recovery time of the 0.5 mg/kg group was statistically longer than that of the 0.3 mg/kg group (16.5 vs 18.8 minutes) but the difference was not clinically significant. The findings of this study show that 0.3 or 0.5 mg/kg doses of INM resulted in safe and effective sedation. The 0.5 mg/kg dose was more effective than the 0.3 mg/kg dose in reducing anxiety.


HMG-CoA reductase inhibitors activate the unfolded protein response and induce cytoprotective GRP78 expression.
Since apoptosis of macrophages induced by stress to the endoplasmic reticulum (ER) contributes to advanced atherosclerotic lesions, we sought to understand the effects of statins on the unfolded protein response (UPR). We used pharmacological, biochemical, and siRNA (small interfering ribonucleic acid) approaches to determine the signalling cascades of statin-induced 78 kDa glucose-regulated protein (GRP78) gene transcription and its role in cytoprotection. Exposure of RAW264.7 macrophages to statins increased the expression of GRP78, activating transcription factor 6, X box protein-1, and phosphorylated eukaryotic translation initiation factor 2alpha, while it had no effect on CCAAT/enhancer binding protein-homologous protein. GRP78 induction was abolished by co-treatment with mevalonate and 1,2-bis(o-aminophenoxy)ethane-N, N, N',N'-tetraacetic acid, indicating the involvement of both 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase-dependent and -independent mechanisms. Studies on promoter activity measurements indicated that phosphoinositide turnover, cellular homologue of v-src (c-Src), protein kinase C (PKC), extracellular signal-regulated kinase (ERK), and p38 are involved in upregulating GRP78 gene transcription. We also observed that elevation of intracellular Ca(2+) and interruption of small G proteins are two bifurcated but cooperative signalling pathways for c-Src activation, leading to downstream activation of phospholipase C, PKC, ERK, and p38. Functionally we demonstrated that fluvastatin could protect macrophages from hypoxia-induced cell death through GRP78 induction. We demonstrate a novel action of statins of inducing a cytoprotective UPR, providing new insights into the clinical potential of statins for ameliorating ER stress-related diseases.


Impact of Canada's menthol cigarette ban on quitting among menthol smokers: pooled analysis of pre-post evaluation from the ITC Project and the Ontario Menthol Ban Study and projections of impact in the USA.
Between 2015 and 2018, Canada banned menthol cigarettes. This study pooled data from two pre-post cohort studies (the Ontario Menthol Ban Study, and the International Tobacco Control Policy Evaluation (ITC) Canada Survey, conducted in seven provinces) to derive more precise estimates of the impact of Canada's menthol ban on quitting and to apply these estimates to project the impact of a menthol ban in the USA. Weighted multivariable logistic analyses compared post-ban quit success of menthol smokers with non-menthol smokers (for daily smokers and for all (daily + non-daily) smokers), controlling for sex, age, ethnicity, education, baseline smoking status, baseline cigarettes per day and study regions. Projections to the USA were created by multiplying the effect size of the Canadian menthol ban on quitting (percentage of increased quitting among menthol smokers) by the number of menthol smokers overall and among African Americans, from the 2019 National Survey on Drug Use and Health. After the menthol cigarette ban, menthol smokers were more likely than non-menthol smokers to have quit smoking among daily smokers (difference=8.0%; 95% CI: 2.4% to 13.7%,p=0.005) and all (daily+non-daily) smokers (difference=7.3%; 95% CI: 2.1% to 12.5%,p=0.006). The projected number of smokers who would quit after a US menthol ban would be 789 724 daily smokers (including 199 732 African Americans) and 1 337 988 daily+non-daily smokers (including 381 272 African Americans). This pooled analysis of Canada's menthol cigarette ban provides the foundation for estimating the impact of menthol bans in the USA and other countries. Projections suggest that a US menthol cigarette ban would have a substantial impact on increasing quitting.


Heliotropism in modern stromatolites.
Modern microbial mats and stromatolites exhibiting a preferred orientation toward specular sunlight were found at two sites. In Hamelin Pool of Shark Bay, Western Australia, subtidal decimeter-sized columns and intertidal centimeter-sized tufts were found pointing north. In thermal spring effluents and pools of Yellowstone National Park, mats were found with columnar and conical centimeter-sized structures inclined to the south. These examples of heliotropism in modern stromatolites are each built by a different community of photosynthetic microbes under markedly different environmental conditions. These new observations support the proposal that stromatolites can orient themselves toward the sun.


Multiplatform optical monitoring of eutrophication in temporally and spatially variable lakes.
Representative spatial patterns of eutrophication variables cannot be produced using traditional in situ sampling techniques. Spatial heterogeneity complicates the study of seasonal and long-term trends and the evaluation of water management policies. Remote sensing, however, with its broad view has the potential to deliver the relevant information. This paper will address the added value of synoptic eutrophication maps to the standard monitoring program of two large, spatially and temporally variable lakes in the Netherlands, Lakes IJssel and Marken. Remote sensing images were obtained from SeaWiFS; and combined with hyperspectral reflectance data from the airborne EPS-a sensor and the shipboard PR-650 spectroradiometer. The PR-650 data were used in selecting the most appropriate algorithms for SeaWiFS and EPS-a. A special algorithm for case II waters with high chlorophyll content was applied to SeaWiFS data to obtain chlorophyll concentrations. Synoptic maps of suspended matter were retrieved using inversion of a model for irradiance reflectance. For the airborne sensor inversion of reflectance was used for both suspended matter and chlorophyll. Satellite and airborne sensors clearly are complementary to each other. Comparison of satellite data with the airborne data and the (scarcely available) in situ data reveal underlying problems with: (i) validation of remote sensing images; and (ii) comparing data at different spatial and temporal scales. In our study, we found a reasonable agreement between different data sources at seasonal time scales, but at shorter time scales the differences can be (much) larger. In situ data suffer from poor reproducibility, related to the natural variability at small spatial scales (patchiness), combined with a significant temporal variability. The standard in situ monitoring program in Lakes IJssel and Marken lacks both the necessary spatial coverage as well as an appropriate sampling frequency. This indicates that for reliable monitoring, a synoptic data set, sampled at a high frequency is required. Remote sensing can partially fulfil this demand but still lacks the demanded frequency, mainly due to regular cloud cover. The answer may be in a multiplatform monitoring approach, as used in our study (combining in situ data with shipboard, airborne and satellite optical data) and in combining monitoring data with models. Satellite remote sensing is most powerful in determining properties that are inherent to the whole lake system, like the overall mean chlorophyll-a concentration. Computational models may meet the demand for a sufficiently high sampling frequency by deterministic interpolation of the data in time.


Penetration of antibiotics through Staphylococcus aureus and Staphylococcus epidermidis biofilms.
This study was carried out to elucidate the role of reduced antibiotic penetration in the resistance of Staphylococcus aureus and Staphylococcus epidermidis biofilms to different antibiotics. The biofilms of S. aureus ATCC 29213 and S. epidermidis ATCC 35984 were grown on black, polycarbonate membranes (diameter, 13 mm; pore size, 0.4 microm) placed on tryptic soy agar plates at 37 degrees C for 48 h. The penetration of oxacillin, cefotaxime, amikacin, ciprofloxacin and vancomycin through the biofilms was determined by measuring the diameter of zones of growth inhibition (of S. aureus ATCC 25923, a quality control strain) on Mueller-Hinton agar plates following diffusion of each antibiotic from an overlying antibiotic disc through the biofilm to the agar medium versus the respective control assemblies. The penetration of oxacillin and cefotaxime (beta-lactams) and vancomycin (a glycopeptide) was significantly reduced through S. aureus and S. epidermidis biofilms whereas that of amikacin (an aminoglycoside) and ciprofloxacin (a fluoroquinolone) was unaffected. The results of this study indicate that the role of reduced antibiotic penetration in the drug resistance of S. aureus and S. epidermidis biofilms may vary with the antibiotic being used.


Heterogeneity of Escherichia coli STb enterotoxin isolated from diseased pigs.
To investigate the presence and frequency of estB variant(s), a collection of 100 STb-positive enterotoxigenic Escherichia coli (ETEC) strains isolated from 1980 to 2007 inclusively and randomly selected from diseased pigs in Québec, Canada, was analysed. A wide diversity of virulence gene profiles (virotypes) was detected in the strain collection. The estB gene was amplified by PCR using primers designed from the signal sequence and the C-terminal end, and the amplified fragment was sequenced using the forward primer. The translated DNA sequence revealed a His(12)-->Asn change in 23 of the 100 ETEC isolates tested. The STb-variant strains were observed throughout the sampling period covered in the study. No other STb-variant type was found in this study. All 23 variant strains were also positive for the STa enterotoxin and were resistant to tetracycline, as for strain 2173. The STb variant was associated with Stx2-positive strains (5/6) and STa : STb strains that did not harbour any of the tested porcine fimbrial adhesins (13/17). The remaining variant strains were associated with fimbriae F4 (1/40), F5 (1/6), F6 (1/1) and F18 (2/7; excluding F18 : Stx2 strains).


Preactive multiple sclerosis lesions offer novel clues for neuroprotective therapeutic strategies.
For the development of novel central nervous system (CNS) drugs to promote neuroprotection, it is helpful to gain a betterunderstanding of natural neuroprotective phenomena. Microglia play key roles in endogenous neuroprotective pathways and their activation is a common theme in several neurodegenerative disorders. Yet, while it is widely appreciated that activated microglia can have neuroprotective qualities, their contribution to tissue destruction and neurodegeneration within the CNS is equally obvious. This apparent duality in microglial functions renders it difficult to determine whether microglial activation under certain conditions is something to counteract, or to support. Also, it is far from clear which microglial functions support neuroprotection, and which support destruction. Here, we review evidence that a special phenomenon in multiple sclerosis (MS) patients offers a unique possibility to study polarized protective functions of microglia. During MS, small clusters of activated microglia frequently emerge throughout normalappearing white matter. Several lines of evidence suggest that these clusters, which are referred to as preactive MS lesions, represent a reversible first stage in the development of inflammatory, demyelinating MS lesions. Progression onto this final destructive stage may occur but, importantly, does not seem to be inevitable. Instead, resolution of preactive lesions is probably the rule rather than the exception. For as long as preactive lesions remain non-infiltrated by peripheral lymphocytes, they reflect a local neuroprotective and reparative response. A critical factor in the emergence of preactive lesions is oligodendrocyte stress, which leads to accumulation of factors such as small heat shock proteins. At least some of these can induce an immune-regulatory response in neighboring microglia. A closer understanding of the molecular make-up of preactive MS lesions, of the signals which cause microglial activation, and of the protective mediators produced by microglia in this context, will help uncover novel clues for neuroprotective therapeutic strategies with relevance for clinical applications well beyond the field of MS alone.


NMR characterization of the metallo-beta-lactamase from Bacteroides fragilis and its interaction with a tight-binding inhibitor: role of an active-site loop.
Understanding the structure and dynamics of the enzymes that mediate antibiotic resistance of pathogenic bacteria will allow us to take steps to combat this increasingly serious public health hazard. Complete backbone NMR resonance assignments have been made for the broad-specificity metallo-beta-lactamase CcrA from Bacteroides fragilis in the presence and absence of a tight-binding inhibitor. Chemical shift indices show that the secondary structure of the CcrA molecule in solution is very similar to that in published crystal structures. A loop adjacent to the two-zinc catalytic site exhibits significant structural variation in the published structures, but appears from the NMR experiments to be a regular beta-hairpin. Backbone heteronuclear NOE measurements indicate that this region has slightly greater flexibility on a picosecond to nanosecond time scale than the molecule as a whole. The loop appears to have an important role in the binding of substrates and inhibitors. Binding of the inhibitor 3-[2'-(S)-benzyl-3'-mercaptopropanoyl]-4-(S)-carboxy-5, 5-dimethylthiazolidine causes a marked increase in the stability of the protein toward unfolding and aggregation, and causes changes in the NMR resonance frequencies of residues close to the active (zinc-binding) site, including the beta-hairpin loop. There is a small but significant increase in the heteronuclear NOE for this loop upon inhibitor binding, indicative of a decrease in flexibility. In particular, the NOE of the indole ring of tryptophan 49, at the tip of the beta-hairpin loop, changes from a low value characteristic of a random coil chain to a significantly higher value, close to that observed for the backbone amides in this region of the protein. These results strongly suggest that the hairpin loop participates in the binding of substrate and in the shielding of the zinc sites from solvent. The broad specificity of the CcrA metallo-beta-lactamase may in fact reside in the plasticity of this part of the protein, which allows it to accommodate and bind tightly to substrates of a variety of shapes and sizes.


The molecular mechanism of fetal alcohol syndrome (FAS). I. Ethanol-induced growth suppression.
Of the birth defects associated with alcohol consumption during pregnancy, in situ growth retardation resulting in neonates that are small for gestational age is the most common observation in both humans and animal models. A variety of alcohol-induced alterations in maternal, placental and/or fetal physiology have been proposed as the basis for this retarded fetal growth. The molecular mechanism(s) of this retardation, however, is obscure; and it remains to be determined whether the growth suppression is the result of the action of ethanol or its metabolites on embryonic, maternal or placental tissue. Using the embryonic chick as a model which circumvents changes in maternal and placental function, we have measured ethanol-induced growth suppression as a function of embryonic age and ethanol dosage. The data suggest that ethanol per se suppresses the rate of cell division in embryonic tissue resulting in fewer cells/embryo for a given time of gestation. The suppression of cell division is proportional to the ethanol dose and appears to be related to ethanol-induced changes in the metabolism of the prostaglandin hormones and resulting changes in the cyclic-AMP levels of the developing embryos.


Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration.
It has been previously reported that early after Roux-en-Y-gastric bypass, dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BPND ) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BPND and whether such changes are explained by neuroendocrine regulation. Fifteen females with obesity (BMI = 39 ± 6 kg/m2 ) were studied before and after ∼10 days of a very-low-calorie-diet (VLCD). Outcome measures included fasting insulin, leptin, acyl ghrelin, and glucose, and insulin sensitivity and disposition index were estimated using the oral-minimal model (OMM) method. Participants underwent positron emission tomography scanning with the displaceable radioligand [18 F]fallypride to estimate available regional D2/3R levels. Regions of interest included the caudate, putamen, ventral striatum, hypothalamus, and substantia nigra (SN). With the VLCD, weight decreased slightly (-3 kg). Insulin, glucose, and leptin decreased significantly, but there was no change in acyl ghrelin or measures from OMM. SN D2/3R BPND decreased significantly, with trends toward decreased levels in the remaining regions. The decrease in leptin concentration strongly predicted the change in D2/3R BPND in all regions (all P ≤ 0.004). In obesity, reductions in regional D2/3R availability after VLCD are suggestive of increased endogenous DA competing with the radioligand. Changes in regional D2/3R availability were associated with decreases in leptin concentrations that occurred before clinically significant weight loss.


Functional Traits, Flocking Propensity, and Perceived Predation Risk in an Amazonian Understory Bird Community.
Within a community, different species might share similar predation risks, and, thus, the ability of species to signal and interpret heterospecific threat information may determine species' associations. We combined observational, experimental, and phylogenetic approaches to determine the extent to which evolutionary history and functional traits determined flocking propensity and perceived predation risk (response to heterospecific alarm calls) in a lowland Amazonian bird community. We predicted that small birds that feed myopically and out in the open would have higher flocking propensities and account for a higher proportion of positive responses to alarms. Using generalized linear models and the incorporation of phylogeny on data from 56 species, our results suggest that phylogenetic relationships alongside body size, foraging height, vegetation density, and response to alarm calls influence flocking propensity. Conversely, phylogenetic relationships did not influence response to heterospecific alarm calls. Among functional traits, however, foraging strategy, foraging density, and flocking propensity partially explained responses to alarm calls. Our results suggest that flocking propensity and perceived predation risk are positively related and that functional ecological traits and evolutionary history may explain certain species' associations.


A Crime Scene Fabricated as Suicide.
When ascertaining the manner of death, the forensic pathologist should be careful, because in some instances, attempts are made by the criminals to conceal homicides as suicides. The case under discussion highlights the contribution of the forensic pathologist in the ascertainment of the manner in firearm deaths. The deceased was a poacher and his dead body was found in a cashew land with his shotgun lying over him. The shirt had a roughly circular defect with muzzle mark, and burnt and blackened margin. Beneath that, on front of the left upper chest a 2cm diameter circular, perforated laceration, with muzzle imprint and, burnt and blackened margin was found. Shelving was found at the upper margin. Chest X-ray showed the downward pellet distribution. Cause of death was chest injuries due to pellets discharged from a smooth bore weapon. Length of the upper arm reach was 65cm (25 inches) and the length from the muzzle to the trigger was 79cm (31 inches). In conclusion, it was found to be a fabricated suicide scene and the manner of death was ascertained as homicide. This reiterates that the postmortem investigation of firearm deaths should be performed or conducted under direct supervision of forensic specialist to deliver justice.


Polymyxin B-Induced Diffuse Cutaneous Hyperpigmentation.
Polymyxin B is a polypeptide-antibiotic, primarily used for resistant Gram-negative infections, first obtained from bacterium Bacillus polymyxa in the late 1940s. Antibiotic spectrum are restricted to mainly gram negative bacterias like Enterobacter, E. coli, Klebsiella, Salmonella, Pasteurella, Bordetella, Shigella; and particularly organisms like Pseudomonas aeruginosa and Acinetobacter baumannii, which are extremely potent to acquire antibiotic resistance. Side effects include neurotoxicity and acute renal tubular necrosis. Here, we present a rare case of skin hyper-pigmentation in a 65-year-old elderly male of Indian origin, diagnosed as a case of Multi-Drug Resistant (MDR) Klebsiella pneumonia, treated with intravenous antibiotics. The manifestations were observed after 4 days of Polymyxin B therapy initiation. All other concomitant drugs, infections, or immunologic disorders that, could have caused this symptom, were carefully excluded. An objective causality assessment reveals that, the cutaneous hyperpigmentation was possibly associated with Polymyxin B therapy, though further studies may be needed to explain the underlying mechanism.


From early to adult sport success: analysing athletes' progression in national squads.
Although some prospective studies have shown that many successful young athletes do not maintain the same level of success when they reach adulthood, there is still a lack of information regarding athletes who started their international involvement at early ages. Therefore, the purpose of the present study was to investigate the international pathway of male and female athletes in different sports from the moment of their competitive debut, in order to determine how many international athletes at early ages competed or did not compete internationally as juniors and/or seniors. The sample included 395 athletes (soccer, volleyball, swimming and judo), born between 1974 and 1981, who could have competed in their national squads between 1988 and 2008. Results showed that only a third of international pre-junior athletes reappeared as senior athletes, confirming the difficulties of predicting late success based on early identification and selection.


Bioengineering the ameloblastoma tumour to study its effect on bone nodule formation.
Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 [Formula: see text] 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.


Characterization of ligand-binding properties and selectivities of three rat tachykinin receptors by transfection and functional expression of their cloned cDNAs in mammalian cells.
We investigated the ligand-binding properties and selectivities of rat substance P, substance K and neuromedin K receptors by transfection and functional expressions of the cDNAs for these receptor subtypes in monkey kidney COS cells. Selective radioligand binding analysis of both substance P and substance K receptors revealed the presence of high-affinity and low-affinity components which are governed primarily by the difference in rates of dissociation of the ligand-receptor complex. The two affinity components were interconvertible by the presence and absence of a guanine nucleotide, suggesting the involvement of a G protein in the two affinity states. The ligand bindings of the three receptors were inhibited in different potencies by naturally occurring tachykinins and a series of carboxyl-terminal fragments containing a common tachykinin sequence, and this comprehensive analysis indicated that a high and selective affinity of each of the tachykinin receptors is governed by interaction with several key amino acids under recognition of the fundamental core sequence of the tachykinin peptides. The potencies and selectivities of several synthetic agonists and an antagonist for the three receptors were also examined, and senktide was found to be a highly selective and potent agonist for neuromedin K receptor. This investigation thus indicates the detailed properties and binding selectivities characteristic of the three tachykinin receptors and also the usefulness of this receptor expression system for examination and development of a new receptor agonist or antagonist.


Genomes, phylogeny, and evolutionary systems biology.
With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics, and computer science are now known as systems biology. Here, I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.


On the ionization and ion transmission efficiencies of different ESI-MS interfaces.
The achievable sensitivity of electrospray ionization mass spectrometry (ESI-MS) is largely determined by the ionization efficiency in the ESI source and ion transmission efficiency through the ESI-MS interface. These performance characteristics are difficult to evaluate and compare across multiple platforms as it is difficult to correlate electrical current measurements to actual analyte ions reaching the detector of a mass spectrometer. We present an effective method to evaluate the overall ion utilization efficiency of an ESI-MS interface by measuring the total gas-phase ion current transmitted through the interface and correlating it to the observed ion abundance measured in the corresponding mass spectrum. Using this method, we systematically studied the ion transmission and ionization efficiencies of different ESI-MS interface configurations, including a single emitter/single inlet capillary, single emitter/multi-inlet capillary, and a subambient pressure ionization with nanoelectrospray (SPIN) MS interface with a single emitter and an emitter array, respectively. Our experimental results indicate that the overall ion utilization efficiency of SPIN-MS interface configurations exceeds that of the inlet capillary-based ESI-MS interface configurations.


Minimally invasive transgingival implant therapy: A literature review.
Transgingival (flapless) implant placement procedure is a minimally invasive surgical technique in which implant is placed without reflecting mucoperiosteal flap and hence the blood supply of bone is not hampered which is advantageous in many ways. To compare the outcomes of various implant placement techniques, an electronic database of various journals from January 1990 to March 2017 were analyzed and only human clinical trials with 6 months follow-up and at least five implants in each group were reviewed. The present literature review focuses on the comparative aspects of flapped versus flapless implants in terms of their survival, marginal bone loss, soft-tissue parameters, and patient-centered outcomes. When the proper protocol is followed by experienced surgeons, no significant difference was observed in survival rate, marginal bone loss, and keratinized mucosal width between flapless and conventional flap technique. Although transgingival approach for implant placement is reported to significantly reduce the surgical time, increased patient comfort and acceptance, i.e. the patient centered outcomes such as postoperative pain, swelling, and visual analog score, are minimized. Hence, it is concluded that transgingival (flapless) implant placement technique is well accepted by the patient with potential outcomes as compared to the conventional implant placement approach.


[Chronic HB virus hepatitis in children. A study of 29 cases].
Clinical, biochemical and histological features of chronic hepatitis type B were studied in 29 children aged 8 months to 13 years. On entry into the study, all were known to have had hepatitis B surface antigen (HBsAg) with elevated serum transaminase levels for at least six months. A possible source of infection was found in 15 children. When they entered the study, all patients were anicteric and all but one asymptomatic. Hepatomegaly was detected in 15 patients and was associated with splenomegaly in two. Hypergammaglobulinemia was present in 4 children. Serological evaluation of hepatitis B virus markers showed evidence of complete viral replication (HBeAg positivity) in 24 cases and incomplete replication (anti-HBeAg positivity) in 5. Liver histology showed chronic persistent hepatitis (CPH) in 18 children, and chronic aggressive hepatitis (CAH) in 10 (3 moderately active and 7 with major signs of aggressivity ) associated with cirrhosis in 5. One patient had only minimal histological changes. Evaluation of clinical, biochemical and virological parameters did not strictly parallel the histological diagnosis in terms of "activity" of the disease. Follow-up for a mean period of 13 months showed good clinical tolerance to the disease in both CPH and CAH patients. Only 2 children with CAH were given corticosteroids and/or azathioprine for a short period. During follow-up no children with active disease developed liver insufficiency or evidence of portal hypertension. No significant difference in the percentage of children who had seroconversion to antiHBe was found between CPH and CAH groups. Only one child with CAH became HBsAg negative.(ABSTRACT TRUNCATED AT 250 WORDS)


Real-Time In Vivo Characterization of Primary Liver Tumors With Diffuse Optical Spectroscopy During Percutaneous Needle Interventions: Feasibility Study in Woodchucks.
This study presents the first in vivo real-time optical tissue characterization during image-guided percutaneous intervention using near-infrared diffuse optical spectroscopy sensing at the tip of a needle. The goal of this study was to indicate transition boundaries from healthy tissue to tumors, namely, hepatic carcinoma, based on the real-time feedback derived from the optical measurements. Five woodchucks with hepatic carcinoma were used for this study. The woodchucks were imaged with contrast-enhanced cone beam computed tomography with a flat panel detector C-arm system to visualize the carcinoma in the liver. In each animal, 3 insertions were performed, starting from the skin surface toward the hepatic carcinoma under image guidance. In 2 woodchucks, each end point of the insertion was confirmed with pathologic examination of a biopsy sample. While advancing the needle in the animals under image guidance such as fluoroscopy overlaid with cone beam computed tomography slice and ultrasound, optical spectra were acquired at the distal end of the needles. Optical tissue characterization was determined by translating the acquired optical spectra into clinical parameters such as blood, water, lipid, and bile fractions; tissue oxygenation levels; and scattering amplitude related to tissue density. The Kruskal-Wallis test was used to study the difference in the derived clinical parameters from the measurements performed within the healthy tissue and the hepatic carcinoma. Kurtoses were calculated to assess the dispersion of these parameters within the healthy and carcinoma tissues. Blood and lipid volume fractions as well as tissue oxygenation and reduced scattering amplitude showed to be significantly different between the healthy part of the liver and the hepatic carcinoma (P < 0.05) being higher in normal liver tissue. A decrease in blood and lipid volume fractions and tissue oxygenation as well as an increase in scattering amplitude were observed when the tip of the needle crossed the margin from the healthy liver tissue to the carcinoma. The kurtosis for each derived clinical parameter was high in the hepatic tumor as compared with that in the healthy liver indicating intracarcinoma variability. Tissue blood content, oxygenation level, lipid content, and tissue density all showed significant differences when the needle tip was guided from the healthy tissue to the carcinoma and can therefore be used to identify tissue boundaries during percutaneous image-guided interventions.


[Technics for isolation of ATP from microorganisms].
A technique for isolation of ATP from microorganisms is suggested. The technique is based on increasing permeability of the cell membrane for substances of low molecular weight during dehydration. Treatment of the dry biomass with boiling water gives a higher yield of ATP from the cells of eukaryote and prokaryote microorganisms as compared with other techniques, and permits to register the amount of APT at the moment of experiment.


[Lyme disease in Cuba? Report of possible cases].
Two possible cases of Lyme disease, which has not been reported in Cuba, but whose existence has been suspected for some years, are reported. These cases that were bitten by ticks and presented signs and symptoms compatible with this disease, according to literature, were serologically confirmed by different laboratory techniques (indirect immunofluorescence, ELISA and Western Blotting). The results suggest the presence of this borreliosis in Cuba.


Forecasting land-cover growth using remotely sensed data: a case study of the Igneada protection area in Turkey.
Human activities in many parts of the world have greatly affected natural areas. Therefore, monitoring and forecasting of land-cover changes are important components for sustainable utilization, conservation, and development of these areas. This research has been conducted on Igneada, a legally protected area on the northwest coast of Turkey, which is famous for its unique, mangrove forests. The main focus of this study was to apply a land use and cover model that could quantitatively and graphically present the changes and its impacts on Igneada landscapes in the future. In this study, a Markov chain-based, stochastic Markov model and cellular automata Markov model were used. These models were calibrated using a time series of developed areas derived from Landsat Thematic Mapper (TM) imagery between 1990 and 2010 that also projected future growth to 2030. The results showed that CA Markov yielded reliable information better than St. Markov model. The findings displayed constant but overall slight increase of settlement and forest cover, and slight decrease of agricultural lands. However, even the slightest unsustainable change can put a significant pressure on the sensitive ecosystems of Igneada. Therefore, the management of the protected area should not only focus on the landscape composition but also pay attention to landscape configuration.


Frailty and mortality in dialysis: evaluation of a clinical frailty scale.
Frailty is associated with poor outcomes for patients on dialysis; however, previous studies have not taken into account the severity of frailty as a predictor of outcomes. The purpose of this study was to assess if there was an association between the degree of frailty and mortality among patients on incident dialysis. A cohort study of incident chronic dialysis patients was conducted between January of 2009 and June of 2013 (last follow-up in December of 2013). On the basis of overall clinical impression, the Clinical Frailty Scale (CFS) score was determined for patients at the start of dialysis by their primary nephrologist. This simple scale allocates a single point to different states of frailty (1, very fit; 2, well; 3, managing well; 4, vulnerable; 5, mildly frail; 6, moderately frail; 7, severely frail or terminally ill) with an emphasis on function of the assessed individual. The primary outcome was time to death. Patients were censored at the time of transplantation. The cohort consisted of 390 patients with completed CFS scores (mean age of 63±15 years old). Most were Caucasian (89%) and men (67%), and 30% of patients had ESRD caused by diabetic nephropathy. The median Charlson Comorbidity Index score was 4 (interquartile range =3-6), and the median CFS score was 4 (interquartile range =2-5). There were 96 deaths over 750 patient-years at risk. In an adjusted Cox survival analysis, the hazard ratio associated with each 1-point increase in the CFS was 1.22 (95% confidence interval, 1.04 to 1.43; P=0.02). A higher severity of frailty (as defined by the CFS) at dialysis initiation is associated with higher mortality.


[Assertive medicine: a proposal against defensive medicine].
More than ever the physician-patient relationship is deteriorated by diverse factors, among these liability complaints stand out, and have propitiated the practice of defensive medicine, an attitude considered in many countries as inappropriate, expensive and unethical. Defensive medicine widens the distance between a physician and his patient. To revert this vice and its noxious effects which corrupt the patient-physician relationship in our country, we propose that physicians put to practice actions which permit the renewal of the essence of humanistic medicine in their daily practice and the restoration of the relationship. These changes in attitude sum up to a proposition of professional practice which we have denominated assertive medicine. This offer is resumed in four points: 1) Maintain a proper verbal and non verbal communication with each patient, 2) Keep continuously up to date skills, knowledge and abilities, 3) Respect the patient's rights and 4) Defend their own rights as physicians.


Modeling human fertility in the presence of measurement error.
The probability of conception in a given menstrual cycle is closely related to the timing of intercourse relative to ovulation. Although commonly used markers of time of ovulation are known to be error prone, most fertility models assume the day of ovulation is measured without error. We develop a mixture model that allows the day to be misspecified. We assume that the measurement errors are i.i.d. across menstrual cycles. Heterogeneity among couples in the per cycle likelihood of conception is accounted for using a beta mixture model. Bayesian estimation is straightforward using Markov chain Monte Carlo techniques. The methods are applied to a prospective study of couples at risk of pregnancy. In the absence of validation data or multiple independent markers of ovulation, the identifiability of the measurement error distribution depends on the assumed model. Thus, the results of studies relating the timing of intercourse to the probability of conception should be interpreted cautiously.


Potentially lethal suicide attempts using sharp objects during psychotic illness.
Recent studies have reported that serious violence toward self and others is more common in the first episode of psychosis than after treatment. To estimate the proportion of survivors of potentially lethal suicide attempts with sharp objects who have a diagnosis of psychotic illness, and the proportion of those patients who had never received treatment for psychosis with antipsychotic medication. An audit of the medical records of patients from three major teaching hospitals in Sydney, Australia, who survived a self inflicted stab wound to the abdomen, torso, or a laceration to the neck. The files of 95 survivors of self-inflicted wounds by cutting or stabbing who met the inclusion criteria for the study were examined. A psychotic illness was diagnosed in 46 cases (48%), of which 26 (57%) had never received treatment with antipsychotic medication and, hence, were in the first episode of psychosis. Psychosis is strongly associated with potentially lethal suicide attempts using sharp objects and patients who have never received treatment for psychosis appear to be at particular risk.


Additional Octreotide Therapy to Sirolimus Achieved a Decrease in Sirolimus-refractory Chylous Effusion Complicated with Lymphangioleiomyomatosis.
Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control postoperative chylous effusion, in addition to the sirolimus therapy. This combination therapy reduced the chylothorax and chylous ascites. For patients with LAM, octreotide therapy in addition to sirolimus may be effective for treating sirolimus-refractory chylous effusion.


Effects of prebiotic dietary fibers and probiotics on human health: With special focus on recent advancement in their encapsulated formulations.
Dietary fibers (DFs) are known as potential formulations in human health due to their beneficial effects in control of life-threatening chronic diseases including cardiovascular disease (CVD), diabetes mellitus, obesity and cancer. In recent decades scientists around the globe have shown tremendous interest to evaluate the interplay between DFs and gastrointestinal (GIT) microbiota. Evidences from various epidemiological and clinical trials have revealed that DFs modulate formation and metabolic activities of the microbial communities residing in the human GIT which in turn play significant roles in maintaining health and well-being. Furthermore, interestingly, a rapidly growing literature indicates success of DFs being prebiotics in immunomodulation, namely the stimulation of innate, cellular and humoral immune response, which could also be linked with their significant roles in modulation of the probiotics (live beneficial microorganisms). The main focus of the current review is to expressively highlight the importance of DFs being prebiotics in human health in association with their influence on gut microbiota. Now in order to significantly achieve the promising health benefits from these prebiotics, it is aimed to develop novel formulations to enhance and scale up their efficacy. Therefore, finally, herein unlike previously published articles, we highlighted different kinds of prebiotic and probiotic formulations which are being regarded as hot research topics among the scientific community now a days. The information in this article will specifically provide a platform for the development of novel functional foods the demands for which has risen drastically in recent years.


Examination of local and systemic in vivo responses to electrical injury using an electrical burn delivery system.
Electrical injuries are devastating and are difficult to manage due to the complexity of the tissue damage and physiological impacts. A paucity of literature exists which describes models for electrical injury. To date, those models have been used primarily to demonstrate thermal and morphological effects at the points of contact. Creating a more representative model for human injury and further elucidating the physics and pathophysiology of this unique form of tissue injury could be helpful in designing stage-appropriate therapy and improving limb salvage. An electrical burn delivery system was developed to accurately and reliably deliver electrical current at varying exposure times. A series of Sprague-Dawley rats were anesthetized and subjected to injury with 1000 V of direct current at incremental exposure times (2-20 seconds). Whole blood and plasma were obtained immediately before shock, immediately postinjury, and then hourly for 3 hours. Laser Doppler images of tissue adjacent to the entrance and exit wounds were obtained at the outlined time points to provide information on tissue perfusion. The electrical exposure was nonlethal in all animals. The size and the depth of contact injury increased in proportion to the exposure times and were reproducible. Skin adjacent to injury (both entrance and exit sites) exhibited marked edema within 30 minutes. In adjacent skin of upper extremity wounds, mean perfusion units increased immediately postinjury and then gradually decreased in proportion to the severity of the injuries. In the lower extremity, this phenomenon was only observed for short contact times, while longer contact times had marked malperfusion throughout. In the plasma, interleukin-10 and vascular endothelial growth factor levels were found to be augmented by injury. Systemic transcriptome analysis revealed promising information about signal networks involved in dermatological, connective tissue, and neurological pathophysiological processes. A reliable and reproducible in vivo model has been developed for characterizing the pathophysiology of high-tension electrical injury. Changes in perfusion were observed near and between entrance and exit wounds that appear consistent with injury severity. Further studies are underway to correlate differential mRNA expression with injury severity.


Effects of a Laboratory Health Information Exchange Intervention on Antiretroviral Therapy Use, Viral Suppression, and Racial/Ethnic Disparities.
Although antiretroviral therapy (ART) is available to treat HIV+ persons and prevent transmission, ineffective delivery of care may delay ART use, impede viral suppression (VS), and contribute to racial/ethnic disparities along the continuum of care. This study tested the effects of a bi-directional laboratory health information exchange (LHIE) intervention on each of these outcomes. We used a quasi-experimental, interrupted time-series design to examine whether the LHIE intervention improved ART use and VS, and reduced racial/ethnic disparities in these outcomes among HIV+ patients (N = 1181) in a comprehensive HIV/AIDS clinic in Southern California. Main outcome measures were ART pharmacy fill and HIV viral load laboratory data extracted from the medical records over 3 years. Race/ethnicity and an indicator for the intervention (after vs. before) were the main predictors. The analysis involved 3-stage, multivariable logistic regression with generalized estimating equations. Overall, the intervention predicted greater odds of ART use (odds ratio [OR] = 2.50; 95% confidence interval: 2.29 to 2.73; P < 0.001) and VS (OR = 1.12; 95% confidence interval: 1.04 to 1.21; P < 0.05) in the final models that included sociodemographic, behavioral, and clinical covariates. Before the intervention, there were significant black/white disparities in ART use OR = 0.75 (0.58-0.98; P = 0.04) and VS OR = 0.75 (0.61-0.92; P = 0.001). After the intervention, the black/white disparities decreased after adjusting for sociodemographics and the number of HIV care visits, and Latinos had greater odds than whites of ART use and VS, adjusting for covariates. The intervention improved overall ART treatment and VS, and reduced black/white disparities. LHIE interventions may hold promise if implemented among similar patients.


THE NATURE OF HERPES ZOSTER: A LONG-TERM STUDY AND A NEW HYPOTHESIS.
Dr Hope-Simpson presents a study of all cases of herpes zoster occurring in his general practice during a sixteen-year period. The rate was 3.4 per thousand per annum, rising with age, and the distribution of lesions reflected that of the varicella rash.It was found that severity increased with age, but that the condition did not occur in epidemics, and that there was no characteristic seasonal variation. A low prevalence of varicella was usually associated with a high incidence of zoster.Dr Hope-Simpson suggests that herpes zoster is a spontaneous manifestation of varicella infection. Following the primary infection (chickenpox), virus becomes latent in the sensory ganglia, where it can be reactivated from time to time (herpes zoster). Herpes zoster then represents an adaptation enabling varicella virus to survive for long periods, even without a continuous supply of persons susceptible to chickenpox.


Regional cerebral glucose utilization in immature fetal guinea pigs during maternal isocapnic hypoxemia.
Recent studies in immature fetal animals demonstrated only a slight or variable increase in the cerebral glycolytic rate during moderate isocapnic hypoxemia. However, the methods used in those studies did not allow for detection of small differences or of regional redistributions of the cerebral glycolytic rate. Hence, a global increase or a regional redistribution of the cerebral glycolytic rate during hypoxemia accompanied by a severe increase in tissue lactate concentration in a few brain areas may have been overlooked in these studies. Because these pathophysiologic mechanisms seem to considerably exacerbate neuronal cell damage due to hypoxic/ischemic insults, we were keen to clarify this point. We, therefore, applied the 2-deoxyglucose method to fetal guinea pigs in utero and measured total and regional cerebral glucose utilization in fetuses of this species at 0.75 of gestation during maternal isocapnic hypoxemia. At 0.75 of gestation guinea pig dams were chronically catheterized. Control groups were exposed to room air, whereas study groups were exposed to a hypoxic atmosphere (10% oxygen, 2% carbon dioxide, and 88% nitrogen). To measure total and regional cerebral glucose utilization during normoxemia and isocapnic hypoxemia, we injected i.v. 100 microCi of 2-[3H]deoxyglucose into the dams. Total and regional cerebral glucose utilization were determined from the steady-state clearance of 2-deoxyglucose between the maternal arterial plasma and the fetal brain, the glucose concentration in the maternal arterial plasma, and the "lumped constant." During isocapnic hypoxemia, total fetal cerebral glucose utilization was not significantly higher than that previously measured during normoxemia (8 +/- 0.8 versus 8 +/- 1.0 micromol/100 g/min). Furthermore, no redistribution of cerebral glucose utilization could be detected. We conclude that moderate isocapnic hypoxemia in the immature fetal brain does not lead to any significant increase or redistribution of glucose utilization or to any major lactate accumulation. This may be related to the low cerebral metabolic demands of brain tissue at this stage of development. Whether this is the main reason for the known resistance of the immature fetal brain toward ischemic neuronal cell damage remains to be established.


A Longitudinal Cohort Study of Emergency Room Utilization Following Mifepristone Chemical and Surgical Abortions, 1999-2015.
Existing research on postabortion emergency room visits is sparse and limited by methods which underestimate the incidence of adverse events following abortion. Postabortion emergency room (ER) use since Food and Drug Administration approval of chemical abortion in 2000 can identify trends in the relative morbidity burden of chemical versus surgical procedures. To complete the first longitudinal cohort study of postabortion emergency room use following chemical and surgical abortions. A population-based longitudinal cohort study of 423 000 confirmed induced abortions and 121,283 subsequent ER visits occurring within 30 days of the procedure, in the years 1999-2015, to Medicaid-eligible women over 13 years of age with at least one pregnancy outcome, in the 17 states which provided public funding for abortion. ER visits are at greater risk to occur following a chemical rather than a surgical abortion: all ER visits (OR 1.22, CL 1.19-1.24); miscoded spontaneous (OR 1.88, CL 1.81-1.96); and abortion-related (OR 1.53, CL 1.49-1.58). ER visit rates per 1000 abortions grew faster for chemical abortions, and by 2015, chemical versus surgical rates were 354.8 versus 357.9 for all ER visits; 31.5 versus 8.6 for miscoded spontaneous abortion visits; and 51.7 versus 22.0 for abortion-related visits. Abortion-related visits as a percent of total visits are twice as high for chemical abortions, reaching 14.6% by 2015. Miscoded spontaneous abortion visits as a percent of total visits are nearly 4 times as high for chemical abortions, reaching 8.9% of total visits and 60.9% of abortion-related visits by 2015. The incidence and per-abortion rate of ER visits following any induced abortion are growing, but chemical abortion is consistently and progressively associated with more postabortion ER visit morbidity than surgical abortion. There is also a distinct trend of a growing number of women miscoded as receiving treatment for spontaneous abortion in the ER following a chemical abortion.


Influence of low Bi contents on phase transformation properties of VO2 studied in a VO2:Bi thin film library.
A thin-film materials library in the system V-Bi-O was fabricated by reactive co-sputtering. The composition of Bi relative to V was determined by Rutherford backscattering spectroscopy, ranging from 0.06 to 0.84 at% along the library. The VO2 phase M1 was detected by X-ray diffraction over the whole library, however a second phase was observed in the microstructure of films with Bi contents > 0.29 at%. The second phase was determined by electron diffraction to be BiVO4, which suggests that the solubility limit of Bi in VO2 is only ∼0.29 at%. For Bi contents from 0.08 to 0.29 at%, the phase transformation temperatures of VO2:Bi increase from 74.7 to 76.4 °C by 8 K per at% Bi. With X-ray photoemission spectroscopy, the oxidation state of Bi was determined to be 3+. The V5+/V4+ ratio increases with increasing Bi content from 0.10 to 0.84 at%. The similarly increasing tendency of the V5+/V4+ ratio and T c with Bi content suggests that although the ionic radius of Bi3+ is much larger than that of V4+, the charge doping effect and the resulting V5+ are more prominent in regulating the phase transformation behavior of Bi-doped VO2.


Community demand for comprehensive primary health care from malaria volunteers in South-East Myanmar: a qualitative study.
Malaria volunteers have contributed significantly to malaria control achieving a reduction of annual parasite incidence to pre-elimination levels in several townships across Myanmar. However, the volunteers' role is changing as Myanmar transitions from a malaria control to elimination programme and towards the goal of universal health coverage. The aim of the study is to explore the perspectives of community leaders, members and malaria volunteers in South-East Myanmar on community-delivered models to inform an optimal design that targets malaria elimination in the context of primary health care in Myanmar. Qualitative methods including focus group discussions (FGDs) with community members and current or ex-malaria volunteers, and participatory workshops with community leaders were conducted. All data collection tools were pilot tested with similar participants. The FGDs were stratified into male and female participants in consideration of diverse gender roles among the ethnic groups of Myanmar. Data saturation was the key cut-off point to cease recruitment of participants. Inductive thematic analysis was used. Community members were willing to be tested for malaria because they were concerned about the consequences of malaria although they were aware that malaria prevalence is low in their villages. Malaria volunteers were the main service providers for malaria and other infectious diseases in the community. Apart from malaria, the community identified common health problems such as the flu (fever, sneezing and coughing), diarrhoea, skin infections and tuberculosis as priority diseases in this order. Incorporating preventive, and whenever possible curative, services for those diseases into the current malaria volunteer model was recommended. There was a gap between the communities' expectations of health services and the health services currently being delivered by volunteers in the community that highlights the need for reassessment and reform of the volunteer model in the changing context. An evidence-based, community preferred, pragmatic community-delivered integrated model should be constructed based on the context of malaria elimination and progressing towards universal health coverage in Myanmar.


Is mannitol the treatment of choice for patients with ciguatera fish poisoning?
Ciguatera fish poisoning arises primarily from consumption of carnivorous reef fish caught in tropical and sub-tropical waters. Ciguatoxins, a class of tasteless, heat-stable, polycyclic toxins produced by dinoflagellates, accumulate through the food chain and concentrate in various carnivorous fish, such as groupers, barracudas, wrasses, amberjack, kingfishes, and eels. Characteristics of ciguatera fish poisoning include early nausea, vomiting, and diarrhea in the first one to two days post ingestion, followed by the appearance of sensory disturbances. The classic dysaesthesia is cold allodynia, often described as reversal of hot and cold sensation, but a more accurate description is burning pain on exposure to cold. To discuss and appraise the evidence regarding the use of mannitol or other drugs in treating ciguatera framed in the historical context of the last four decades. We searched PubMed and Embase for all years from 1966 to March 31, 2017 with search terms "ciguatera", "mannitol", and "treatment". These searches identified 85 articles, of which 36 were relevant to the review question. We searched Google Scholar to supplement the primary search and reviewed the references of articles for sources overlooked in the original searches. These secondary searches identified another 23 references. We excluded six clinical reports (two case series and four case reports) which did not clearly describe ciguatera or which lacked information on treatment or outcome. Fifty-three clinical articles remained for review. We searched PubMed using "ciguatera" AND "treatment" NOT "mannitol" to better identify reports describing other treatments. The search identified 128 articles, of which nine described specific pharmacological treatments and their outcomes. We combined our findings into a consensus review of the evidence both for and against the use of mannitol or other medications for ciguatera fish poisoning. Early human evidence of effectiveness of mannitol: A 1988 report described an unexpected discovery that intravenous mannitol could rapidly and effectively treat ciguatera fish poisoning. Several other uncontrolled case series and case reports appeared to support the use of mannitol. In 2002, a small randomized, controlled trial reported no significant difference between mannitol and normal saline. Subsequent case reports have cited this study as the reason for or to withhold mannitol. Thus, some controversy exists regarding whether mannitol is useful or not for treating ciguatera fish poisoning. Basic science and animal research on ciguatera and mannitol: In vitro experiments of isolated neurons demonstrate that ciguatoxins produce neuronal edema, open certain sodium channels, block potassium channels, cause uncontrolled and repetitive action potentials after a stimulus. Addition of mannitol decreases the edema and reduces the uncommanded action potentials. However, intraperitoneal injection of ciguatoxin in rats increases neuronal refractory period and slows nerve conduction velocity. Treatment with mannitol fails to correct these effects. Comparative trials of mannitol: Evidence supporting mannitol for ciguatera fish poisoning includes four uncontrolled case series, one prospective, unblinded comparative trial and several case reports. Evidence against mannitol consists of one RCT, which has a small sample size and several potential limitations. Empirical human experience with other treatments: Evidence regarding other treatments consists only of ten case reports and three overlapping case series that describe using amitriptyline, fluoxetine, duloxetine, gabapentin, pregabalin, or tocainide. For each of these, a long duration of treatment appears to be necessary to maintain symptomatic improvement. None of these treatments has been shown to be superior to mannitol. It is reasonable to consider using intravenous mannitol in cases of acute ciguatera fish poisoning. Medications used in other neuropathic syndromes appear to suppress the paresthesiae of persistent ciguatera cases. However, the human evidence is of low quality for all treatments.


[Social policies and violence: a proposal from Ribeirão Preto-SP, Brazil].
This bibliographical research and analysis of official documents on social policies and violence aims to present a great and rewarding challenge that is oriented by a new municipal administration guideline, implementing a Network for Children's and Adolescent's Care-RAICA. This Network is aimed at articulation with a view to the integration of different services and their professionals in order to intervene in the problems children and adolescents are facing due to increased violence in several areas.


Adjunctive risperidone treatment and sleep symptoms in combat veterans with chronic PTSD.
Sleep disturbances are core symptoms of posttraumatic stress disorder (PTSD) and are often resistant to treatment. One reason for the recent use of atypical antipsychotics in PTSD appears to be their effects on sleep. Study objectives were (1) to evaluate preliminarily the sleep effects of adjunctive risperidone, and (2) to evaluate the use of sleep diaries versus the more standard retrospective sleep assessments. This was a pilot, open-label, 12-week, flexible-dose trial of adjunctive risperidone in male veterans with a primary diagnosis of chronic, combat-related PTSD, partially responsive to current medications. Diagnostic interviews were administered at baseline, and PTSD ratings were obtained at baseline and at 6 and 12 weeks. Self-report sleep measures, including morning logs, were obtained at baseline and 6 weeks. Seventeen patients completed at least 6 weeks of the trial. Global ratings of sleep disturbance improved. Changes in frequency of awakenings and reductions in trauma-related dreams were only evident via morning log assessments. Nighttime awakening frequency derived from the sleep logs but not from the Pittsburgh Sleep Quality Index (PSQI) decreased significantly. There were no changes in the PSQI nightmare item; however, sleep log data indicated a reduced proportion of traumatic dreams at 6 weeks. Preliminary results suggest that adjunctive risperidone may benefit sleep disturbances associated with chronic PTSD. Prospective logs may be more sensitive to change than are retrospective scales.


Fabrication of two-layered channel system with embedded electrodes to measure resistance across epithelial and endothelial barriers.
This manuscript describes a straightforward fabrication process for embedding Ag/AgCl electrodes within a two-layer poly(dimethylsiloxane) (PDMS) microfluidic chip where an upper and a lower channel are separated by a semiporous membrane. This system allows for the reliable real-time measurement of transendothelial and transepithelial electrical resistance (TEER), an accepted quantification of cell monolayer integrity, across cells cultured on membranes inside the microchannels using impedance spectroscopy. The technique eliminates the need for costly or specialized microelectrode fabrication, enabling commercially available wire electrodes to easily be incorporated into PDMS microsystems for measuring TEER under microfluidic environments. The capability of measuring impedance across a confluent cell monolayer is confirmed using (i) brain-derived endothelial cells (bEND.3), (ii) Madin Darby Canine Kidney Cells (MDCK-2), and mouse myoblast (C2C12) (all from ATCC, Manassas, VA). TEER values as a function of cell type and cell culture time were measured and both agree with previously published values from macroscale culture techniques. This system opens new opportunities for conveniently resolving both transendothelial and transepithelial electrical resistance to monitor cell function in real-time in microfluidic cell cultures.


Dissemination of herpes simplex virus in nude mice after intracutaneous inoculation and effect of antibody on the course of infection.
Dissemination of herpes simplex virus (HSV) in nude mice after intracutaneous inoculation in the midflank, and the effect of passively administered antibody on the course of infection were investigated. In untreated infected mice the skin lesions developed rapidly and HSV could first be recovered from the homogenate of the dorsal root ganglia on day 3 after infection, from the spinal cord on day 7 and from the brain on day 11. HSV could not be recovered from the blood, spleen or liver. In mice passively immunized with human gamma globulin, development of the skin lesions was rather slow and HSV could not be recovered from the homogenate of the dorsal root ganglia until day 16. From the results of explant culture of the ganglia, HSV was found to have reached the ganglia as early as 48 h after infection, even in mice administered human gamma globulin. The protective action of antibody seems to originate from the inhibition of virus growth not only at the inoculation site but also in the dorsal root ganglia.


Impairment in Social Functioning differentiates youth meeting Ultra-High Risk for psychosis criteria from other mental health help-seekers: A validation of the Italian version of the Global Functioning: Social and Global Functioning: Role scales.
Social and occupational impairments are present in the schizophrenia prodrome, and poor social functioning predicts transition to psychosis in Ultra-High Risk (UHR) individuals. We aimed to: 1) validate the Italian version of the Global Functioning: Social (GF: S) and Global Functioning: Role (GF: S) scales; 2) evaluate their association with UHR criteria. Participants were 12-21-years-old (age, mean=15.2, standard deviation=2.1, male/female ratio=117/120) nonpsychotic help-seekers, meeting (N=39) or not (N=198) UHR criteria. Inter-rater reliability was excellent for both scales, which also showed good to excellent concurrent validity, as measured by correlation with Global Assessment of Functioning (GAF) scores. Furthermore, GF:S and GF: R were able to discriminate between UHRs and non-UHRs, with UHRs having lower current scores. After adjusting for current GAF scores, only current GF:S scores independently differentiated UHR from non-UHR (OR=1.33, 95%CI: 1.02-1.75, p=0.033). Finally, UHR participants showed a steeper decrease from highest GF:S and GF: R scores in the past year to their respective current scores, but not from highest past year GAF scores to current scores. GF:S/GS: R scores were not affected by age or sex. GF:S/GF: R are useful functional level and outcome measures, having the advantage over the GAF to not confound functioning with symptom severity. Additionally, the GF:S may be helpful in identifying UHR individuals.


The hemodynamic complexities underlying transient ischemic attacks in early-stage Moyamoya disease: an exploratory CFD study.
Moyamoya disease (MMD) is a rare cerebro-occlusive disease with unknown etiology that can cause both ischemic and hemorrhagic stroke. MMD is characterized by progressive stenosis of the terminal internal carotid artery (ICA) and development of basal brain collaterals. Early-stage MMD is known to cause hemodynamic insufficiency despite mild or moderate stenosis of the intracranial arteries, but the exact mechanism underlying this pathophysiological condition is undetermined. We used high-resolution Large Eddy Simulations to investigate multiple complex hemodynamic phenomena that led to cerebral ischemia in five patients with early-stage MMD. The effects of transitional flow, coherent flow structures and blood shear-thinning properties through regions of tortuous and stenosed arteries were explored and linked to symptomatology. It is evidently shown that in some cases complex vortex structures, such as Rankine-type vortices, redirects blood flow away from some arteries causing significant reduction in blood flow. Moreover, partial blood hammer (PBH) phenomenon was detected in some cases and led to significant hemodynamic insufficiency. PBH events were attributed to the interaction between shear-thinning properties, transitional flow structures and loss of upstream pressure-velocity phase lag. We clearly show that the hemodynamic complexities in early-stage MMD could induce ischemia and explain the non-responsiveness to antiplatelet therapy.


Impacts of oak pollen on allergic asthma in the United States and potential influence of future climate change.
Future climate change is expected to lengthen and intensify pollen seasons in the U.S., potentially increasing incidence of allergic asthma. We developed a proof-of-concept approach for estimating asthma emergency department (ED) visits in the U.S. associated with present-day and climate-induced changes in oak pollen. We estimated oak pollen season length for moderate (Representative Concentration Pathway (RCP) 4.5) and severe climate change scenarios (RCP8.5) through 2090 using five climate models and published relationships between temperature, precipitation, and oak pollen season length. We calculated asthma ED visit counts associated with 1994-2010 average oak pollen concentrations and simulated future oak pollen season length changes using the Environmental Benefits Mapping and Analysis Program, driven by epidemiologically derived concentration-response relationships. Oak pollen was associated with 21,200 (95% confidence interval, 10,000-35,200) asthma ED visits in the Northeast, Southeast, and Midwest U.S. in 2010, with damages valued at $10.4 million. Nearly 70% of these occurred among children age <18 years. Severe climate change could increase oak pollen season length and associated asthma ED visits by 5% and 10% on average in 2050 and 2090, with a marginal net present value through 2090 of $10.4 million (additional to the baseline value of $346.2 million). Moderate versus severe climate change could avoid >50% of the additional oak pollen-related asthma ED visits in 2090. Despite several key uncertainties and limitations, these results suggest that aeroallergens pose a substantial U.S. public health burden, that climate change could increase U.S. allergic disease incidence, and that mitigating climate change may have benefits from avoided pollen-related health impacts.


The stromal component of large endometrial polyps.
Benign endometrial polyps belong in the differential diagnosis of adenofibroma and adenosarcoma. There is, however, little information about the range of stromal mitotic activity, stromal cellularity, and stromal atypia in benign endometrial polyps, rendering the differential diagnosis with the aforementioned tumors problematic. In this study, the stroma of 66 polyps 1 cm or more in greatest dimension from 56 patients was analyzed for stromal mitotic activity, cellularity, and atypia. Sixteen (24%) had an almost completely fibrotic stroma that had rare mitoses, little cellularity, and no atypia. However, 50 polyps (76%) had stroma that was predominantly endometrial or was a mixture of endometrial-type stroma and fibrous stroma. In these polyps stromal mitoses were relatively common, averaging 1.2/10 MFs/HPFs (range, 0-5.8 MFs/10 HPFs). Stromal cellularity was frequently equal to or mildly increased over adjacent nonpolypoid endometrial stroma and mild nuclear atypia (enlarged stromal nuclei) was also common. Twelve polyps (24%) from the group of 50 had two or more MFs/10 HPFs, a mitotic rate present in some adenosarcomas. None of these polyps had other features necessary for the diagnosis of adenofibroma or adenosarcoma and follow-up in all patients was uneventful (average follow-up, 96 months). It is concluded that benign polyps that retain areas of endometrial-type stroma often have mitotic activity and that significant stromal mitotic activity (> or = 2 MFs/HPFs) is relatively common. These polyps do not have significant stromal atypia nor do they have a marked increase in stromal cellularity. Thus, in the absence of other supportive features, stromal mitotic activity alone should not be regarded as a worrisome finding.


Localized and disseminated histiocytic sarcoma of dendritic cell origin in dogs.
Canine histiocytic proliferative disorders include a wide spectrum of diseases characterized by different biologic behaviors. The etiology and pathogenesis of these diseases are largely unknown. The clinicopathologic, morphologic and immunophenotypic characteristics of canine localized and disseminated histiocytic sarcoma were examined in 39 dogs. Rottweilers, Bernese Mountain Dogs, and retrievers were most commonly affected (79%). Localized histiocytic sarcomas (19 dogs) arose from a single site, and metastatic lesions were observed in draining lymph nodes. Predilection sites were subcutis and underlying tissues on extremities, but tumors occurred in other locations, including spleen, lung, brain, nasal cavity, and bone marrow. Disseminated histiocytic sarcomas (20 dogs), a multisystem disease previously described as malignant histiocytosis, primarily affected spleen, lungs, bone marrow, liver, and lymph nodes. Both localized and disseminated canine histiocytic sarcomas were composed of pleomorphic tumor cell populations. CD1+, CD4-, CD11c+, CD11d-, MHC II+, ICAM-1 +, Thy-1 +/- tumor cells were identified in all snap-frozen samples (31 dogs). This phenotype is characteristic for myeloid dendritic antigen-presenting cell lineage. Hence, canine localized and disseminated histiocytic sarcomas are likely myeloid dendritic cell sarcomas. Dendritic antigen-presenting cells are a heterogeneous cell population with regards to their ontogeny, phenotype, function, and localization. The exact sublineage of the proliferating dendritic antigen-presenting cells involved in canine histiocytic sarcomas remains to be determined. Phenotypic analysis of formalin-fixed tissues from eight dogs was limited by available markers. Morphologic features and the phenotype CD18+, CD3-, and CD79a- were the most useful criteria to indicate likely histiocytic origin.


Diversity of lactic acid bacteria during fermentation of a traditional Chinese fish product, Chouguiyu (stinky mandarinfish).
Chouguiyu, or stinky mandarinfish, is a traditional Chinese fermented fish product made of mandarinfish by spontaneous fermentation at the anaerobic condition with low-salt concentration. In order to get a primary understanding of the microbial community presenting in the Chouguiyu fermentation, 61 cultures of lactic acid bacteria (LAB) from various fermentation period were isolated using MRS agar plates and characterized based on a combination of phenotypic and genotypic approaches including amplified ribosomal DNA restriction analysis (ARDRA) and 16S rRNA partial gene sequencing analysis. Eight distinct bacterial species belonging to 6 genera were identified in total. Among them, Lactobacillus sakei was the dominant species (63%) during the fermentation, which exhibited great variety in phenotypic tests but unique genotypic characters. Meanwhile, the other LAB species including Lactococcus (Lc.) garvieae, Lc. lactis, Lc. raffinolactis, Vagococcus sp., Enterococcus hermanniensis, Macrococcus caseolyticus as well as Streptococcus parauberis were also recovered from the different fermentation periods, especially at the initial point of the fermentation. This seems to be the 1st report investigating the LAB composition involved in Chouguiyu fermentation and the data obtained in this study may be valuable for selecting starter culture for Chouguiyu industrial-scale production.


Features and management of pyrexia with combined dabrafenib and trametinib in metastatic melanoma.
The combination of dabrafenib and trametinib (CombiDT) is an effective treatment for BRAF-mutant metastatic melanoma; however, over 70% of patients develop drug-related pyrexia, and little is known about this toxicity. We sought to examine the features and management of CombiDT pyrexia. The association between pyrexia and patient demographics, disease characteristics and outcome variables was assessed in patients treated with CombiDT at a single institution. The clinicopathological features of pyrexic events were analysed. Fourteen of 32 (44%) patients developed pyrexia (temperature≥38.5°C). Pyrexia was recurrent in 11/14 (79%). The median time to pyrexia was 38 days. Pyrexia was not associated with age, sex nor disease burden, and did not correlate with RECIST response, progression-free nor overall survival. Paracetamol, NSAIDs and/or dose reduction (DR) were ineffective secondary prophylaxis for pyrexia, whereas corticosteroids were effective in all patients (n=8), including two with multiple previous pyrexic events despite several DRs. In patients with previous DRs who commenced steroids (n=3), CombiDT doses were re-escalated without pyrexia. Pyrexia is a frequent and recurrent toxicity with CombiDT, with no predictive clinical characteristics. Pyrexia does not correlate with clinical outcome. Neither DR nor antipyretics are effective secondary prophylaxis, whereas corticosteroids are effective, prevent DR and enable re-escalation of CombiDT dosing.


p63 promotes cell survival through fatty acid synthase.
There is increasing evidence that p63, and specifically DeltaNp63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN), a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or DeltaN-specific p63 isoforms in squamous cell carcinoma (SCC9) or immortalized prostate epithelial (iPrEC) cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT) was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects.


Dithieno[3,2-b:2',3'-d]pyrrole-benzo[c][1,2,5]thiadiazole conjugate small molecule donors: effect of fluorine content on their photovoltaic properties.
Two new small molecule donors, namely ICT4 and ICT6 with D1-A-D2-A-D1 architecture having 2,4-bis(2-ethylhexyl)-4H-dithieno[3,2-b:2',3'-d]pyrrole (EHDTP, D1) and 4,8-bis((2-ethylhexyl)oxy)benzo[1,2-b:4,5-b']dithiophene (OBDT, D2) as the terminal and central donor, and benzo[c][1,2,5]thiadiazole (BT for ICT4) and 5,6-difluorobenzo[c][1,2,5]thiadiazole (F2BT for ICT6) as the acceptor (A) moieties, are synthesized and their optical, electronic and photovoltaic properties are investigated. Both ICT4 and ICT6 have considerable solubility in various solvents and possess efficient light absorption ability [ε (×105 mol-1 cm-1) is 0.99 and 1.06, respectively for ICT4 and ICT6] and appropriate frontier molecular orbital energy offsets with [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM). Bulk heterojunction solar cells (BHJSCs) are fabricated using ICT4/ICT6 and PC71BM as donors and acceptors, respectively and BHJSCs with two-step annealed (thermal followed by solvent vapor annealing) active layers of ICT4 and ICT6 show overall power conversion efficiencies (PCEs) of 5.46% and 7.91%, respectively. The superior photovoltaic performance of the ICT6 based BHJSCs is due to the favourable morphology with a nanoscale interpenetrating network in the ICT6:PC71BM active layer induced by the fluorine atoms on the BT acceptor, which significantly enhances the dissociation of excitons, charge transport and the charge collection efficiency, and suppresses bimolecular recombination in the BHJ. The observed higher PCE of 7.91% indicates that ICT6 is one of the best BT based donor material for small molecular BHJSCs.


Dental management of a child with familial dysautonomia.
Familial dysautonomia is a hereditary sensory neuropathy that involves sensory, motor, and central components of the nervous system. Orofacial features include a tendency toward facial concavity in the child, and convexity in the adult. There is increased salivation, and crowded teeth and malocclusion are characteristic. This patient is not Jewish; this makes his case an extremely rare one.


Evolution of gene expression and expression plasticity in long-term experimental populations of Drosophila melanogaster maintained under constant and variable ethanol stress.
Gene expression responds to the environment and can also evolve rapidly in response to altered selection regimes. Little is known, however, about the extent to which evolutionary adaptation to a particular type of stress involves changes in the within-generation ('plastic') responses of gene expression to the stress. We used microarrays to quantify gene expression plasticity in response to ethanol in laboratory populations of Drosophila melanogaster differing in their history of ethanol exposure. Two populations ('R' populations) were maintained on regular medium, two ('E') were maintained on medium supplemented with ethanol, and two ('M') were maintained in a mixed regime in which half of the population was reared on one medium type, and half on the other, each generation. After more than 300 generations, embryos from each population were collected and exposed to either ethanol or water as a control, and RNA was extracted from the larvae shortly after hatching. Nearly 2000 transcripts showed significant within-generation responses to ethanol exposure. Evolutionary history also affected gene expression: the E and M populations were largely indistinguishable in expression, but differed significantly in expression from the R populations for over 100 transcripts, the majority of which did not show plastic responses. Notably, in no case was the interaction between selection regime and ethanol exposure significant after controlling for multiple comparisons, indicating that adaptation to ethanol in the E and M populations did not involve substantial changes in gene expression plasticity. The results give evidence that expression plasticity evolves considerably more slowly than mean expression.


The NAC-like gene ANTHER INDEHISCENCE FACTOR acts as a repressor that controls anther dehiscence by regulating genes in the jasmonate biosynthesis pathway in Arabidopsis.
ANTHER INDEHISCENCE FACTOR (AIF), a NAC-like gene, was identified in Arabidopsis. In AIF:GUS flowers, β-glucuronidase (GUS) activity was detected in the anther, the upper parts of the filaments, and in the pollen of stage 7-9 young flower buds; GUS activity was reduced in mature flowers. Yellow fluorescent protein (YFP)+AIF-C fusion proteins, which lacked a transmembrane domain, accumulated in the nuclei of the Arabidopsis cells, whereas the YFP+AIF fusion proteins accumulated in the membrane and were absent in the nuclei. Further detection of a cleaved AIF protein in flowers revealed that AIF needs to be processed and released from the endoplasmic reticulum in order to function. The ectopic expression of AIF-C caused a male-sterile phenotype with indehiscent anthers throughout flower development in Arabidopsis. The presence of a repressor domain in AIF and the similar phenotype of indehiscent anthers in AIF-C+SRDX plants suggest that AIF acts as a repressor. The defect in anther dehiscence was due to the down-regulation of genes that participate in jasmonic acid (JA) biosynthesis, such as DAD1/AOS/AOC3/OPR3/OPCL1. The external application of JA rescued the anther indehiscence in AIF-C and AIF-C+SRDX flowers. In AIF-C+VP16 plants, which are transgenic dominant-negative mutants in which AIF is converted to a potent activator via fusion to a VP16-AD motif, the anther dehiscence was promoted, and the expression of DAD1/AOS/AOC3/OPR3/OPCL1 was up-regulated. Furthermore, the suppression of AIF through an antisense strategy resulted in a mutant phenotype similar to that observed in the AIF-C+VP16 flowers. The present data suggest a role for AIF in controlling anther dehiscence by suppressing the expression of JA biosynthesis genes in Arabidopsis.