Cortical activity and functional hyperconnectivity by simultaneous EEG recordings from interacting couples of professional pilots.
Controlling an aircraft during a flight is a compelling condition, which requires a strict and well coded interaction between the crew. The interaction level between the Captain and the First Officer changes during the flight, ranging from a maximum (during takeoff and landing, as well as in case of a failure of the instrumentation or other emergency situations) to a minimum during quiet mid-flight. In this study, our aim is to investigate the neural correlates of different kinds and levels of interaction between couples of professional crew members by means of the innovative technique called brain hyperscanning, i.e. the simultaneous recording of the hemodynamic or neuroelectrical activity of different human subjects involved in interaction tasks. This approach allows the observation and modeling of the neural signature specifically dependent on the interaction between subjects, and, even more interestingly, of the functional links existing between the brain activities of the subjects interacting together. In this EEG hyperscanning study, different phases of a flight were reproduced in a professional flight simulator, which allowed, on one side, to reproduce the ecological setting of a real flight, and, on the other, to keep under control the different levels of interaction induced in the crew by means of systematic and simulated failures of the aircraft instrumentation. Results of the procedure of linear inverse estimation, together with functional hyperconnectivity estimated by means of Partial Directed Coherence, showed a dense network of connections between the activity in the two brains in the takeoff and landing phases, when the cooperation between the crew is maximal, while conversely no significant links were shown during the phases in which the activity of the two pilots was independent.


Modeling low-coherence enhanced backscattering using Monte Carlo simulation.
Constructive interference between coherent waves traveling time-reversed paths in a random medium gives rise to the enhancement of light scattering observed in directions close to backscattering. This phenomenon is known as enhanced backscattering (EBS). According to diffusion theory, the angular width of an EBS cone is proportional to the ratio of the wavelength of light lambda to the transport mean-free-path length l(s)* of a random medium. In biological media a large l(s)* approximately 0.5-2 mm >> lambda results in an extremely small (approximately 0.001 degrees ) angular width of the EBS cone, making the experimental observation of such narrow peaks difficult. Recently, the feasibility of observing EBS under low spatial coherence illumination (spatial coherence length Lsc << l(s)*) was demonstrated. Low spatial coherence behaves as a spatial filter rejecting longer path lengths and thus resulting in an increase of more than 100 times in the angular width of low coherence EBS (LEBS) cones. However, a conventional diffusion approximation-based model of EBS has not been able to explain such a dramatic increase in LEBS width. We present a photon random walk model of LEBS by using Monte Carlo simulation to elucidate the mechanism accounting for the unprecedented broadening of the LEBS peaks. Typically, the exit angles of the scattered photons are not considered in modeling EBS in the diffusion regime. We show that small exit angles are highly sensitive to low-order scattering, which is crucial for accurate modeling of LEBS. Our results show that the predictions of the model are in excellent agreement with the experimental data.


A role for beta-actin in RNA polymerase III transcription.
When transcription from the human U6 snRNA gene is reconstituted with recombinant factors and purified RNA polymerase III (pol III), pol III must be treated with CK2 to be active. We show that highly purified pol III contains associated beta-actin, and beta-actin localizes to an active U6 promoter in vivo. Pol III immunoprecipitated from IMR90 cells treated with a genotoxic agent lacks associated beta-actin and is inactive in the reconstituted assay. Transcription is regained upon treatment of pol III with CK2 and addition of beta-actin. This suggests that beta-actin associated with pol III is essential for basal pol III transcription.


Denitrification potential of the eastern oyster microbiome using a 16S rRNA gene based metabolic inference approach.
The eastern oyster (Crassostrea virginica) is a foundation species providing significant ecosystem services. However, the roles of oyster microbiomes have not been integrated into any of the services, particularly nitrogen removal through denitrification. We investigated the composition and denitrification potential of oyster microbiomes with an approach that combined 16S rRNA gene analysis, metabolic inference, qPCR of the nitrous oxide reductase gene (nosZ), and N2 flux measurements. Microbiomes of the oyster digestive gland, the oyster shell, and sediments adjacent to the oyster reef were examined based on next generation sequencing (NGS) of 16S rRNA gene amplicons. Denitrification potentials of the microbiomes were determined by metabolic inferences using a customized denitrification gene and genome database with the paprica (PAthway PRediction by phylogenetIC plAcement) bioinformatics pipeline. Denitrification genes examined included nitrite reductase (nirS and nirK) and nitrous oxide reductase (nosZ), which was further subdivided by genotype into clade I (nosZI) or clade II (nosZII). Continuous flow through experiments measuring N2 fluxes were conducted with the oysters, shells, and sediments to compare denitrification activities. Paprica properly classified the composition of microbiomes, showing similar classification results from Silva, Greengenes and RDP databases. Microbiomes of the oyster digestive glands and shells were quite different from each other and from the sediments. The relative abundance of denitrifying bacteria inferred by paprica was higher in oysters and shells than in sediments suggesting that oysters act as hotspots for denitrification in the marine environment. Similarly, the inferred nosZI gene abundances were also higher in the oyster and shell microbiomes than in the sediment microbiome. Gene abundances for nosZI were verified with qPCR of nosZI genes, which showed a significant positive correlation (F1,7 = 14.7, p = 6.0x10-3, R2 = 0.68). N2 flux rates were significantly higher in the oyster (364.4 ± 23.5 μmol N-N2 m-2 h-1) and oyster shell (355.3 ± 6.4 μmol N-N2 m-2 h-1) compared to the sediment (270.5 ± 20.1 μmol N-N2 m-2 h-1). Thus, bacteria carrying nosZI genes were found to be an important denitrifier, facilitating nitrogen removal in oyster reefs. In addition, this is the first study to validate the use of 16S gene based metabolic inference as a method for determining microbiome function, such as denitrification, by comparing inference results with qPCR gene quantification and rate measurements.


Cell migration in paediatric glioma; characterisation and potential therapeutic targeting.
Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed. Here, we examine the migratory characteristics and treatment effect of small molecule glycogen synthase kinase-3 inhibitors, lithium chloride (LiCl) and the indirubin derivative 6-bromoindirubin-oxime (BIO), previously shown to inhibit the migration of adult glioma cells, on two pHGG cell lines (SF188 and KNS42) and one patient-derived DIPG line (HSJD-DIPG-007) using 2D (transwell membrane, immunofluorescence, live cell imaging) and 3D (migration on nanofibre plates and spheroid invasion in collagen) assays. All lines were migratory, but there were differences in morphology and migration rates. Both LiCl and BIO reduced migration and instigated cytoskeletal rearrangement of stress fibres and focal adhesions when viewed by immunofluorescence. In the presence of drugs, loss of polarity and differences in cellular movement were observed by live cell imaging. Ours is the first study to demonstrate that it is possible to pharmacologically target migration of paediatric glioma in vitro using LiCl and BIO, and we conclude that these agents and their derivatives warrant further preclinical investigation as potential anti-migratory therapeutics for these devastating tumours.


Does the rise of the Internet bring erosion of strong ties? Analyses of social media use and changes in core discussion networks.
We derive hypotheses from popular accounts of how use of social media affects our strong ties. Several authors have suggested that social media use erodes our strong ties by increasing the volume of social interactions and decreasing their depth. Using two-wave panel data representative of the Dutch population between 15 and 45 years, we examine changes in the core discussion networks (CDNs) of 5312 respondents (with 10,896 relations). Contradicting an erosion of strong ties, we found positive effects of social media use on CDN size, both cross-sectionally and longitudinally. Social media use was positively related to talking to CDN members in our cross-sectional model. Finally, we found that the CDNs of frequent social media users were more dynamic than those of less frequent users: they are more likely to both lose old and gain new ties. This suggests that Internet use is associated with more, and more dynamic, social interaction.


Hypoxia-induced endothelial apoptosis through nuclear factor-kappaB (NF-kappaB)-mediated bcl-2 suppression: in vivo evidence of the importance of NF-kappaB in endothelial cell regulation.
The transcription factor nuclear factor-kappaB (NF-kappaB) plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes involved in endothelial activation. Although recent reports have documented the contribution of NF-kappaB to apoptosis, it is still controversial. Especially, the role of NF-kappaB in endothelial apoptosis is largely unknown. Hypoxia significantly induced human aortic endothelial cell death and apoptosis in a time-dependent manner (P<0.01), accompanied by NF-kappaB activation. Decrease in total cell number and increase in apoptotic cells induced by hypoxia were significantly attenuated by NF-kappaB decoy, but not by scrambled decoy, oligodeoxynucleotides (ODNs) (P<0.01). Increase in DNA fragmentation induced by hypoxia was also significantly inhibited by NF-kappaB decoy ODNs as compared with scrambled decoy ODNs (P<0.01). Moreover, transfection of NF-kappaB decoy ODNs resulted in a significant decrease in caspase-3-like activity, which is a common pathway for apoptosis, compared with scrambled decoy ODNs. Importantly, transfection of NF-kappaB decoy ODNs significantly increased protein of bcl-2, an inhibitor of apoptosis, and did not alter bax, a promoter of apoptosis, thereby resulting in a significant increase in the ratio of bcl-2 to bax (P<0.01). bcl-2 mRNA was also decreased by hypoxia, whereas transfection of NF-kappaB decoy ODNs significantly attenuated decrease in bcl-2 mRNA. These results demonstrate that activation of NF-kappaB by hypoxia induced endothelial apoptosis in a bcl-2-dependent manner. The importance of NF-kappaB in endothelial apoptosis was confirmed by the observation that pyrrolidine dithiocarbamate, a potent NF-kappaB inhibitor, prevented endothelial apoptosis, caspase 3-like activity, and bcl-2 downregulation induced by hypoxia. To test this hypothesis in vivo, we transfected NF-kappaB decoy ODNs into rat intact carotid artery after reperfusion injury. Reperfusion injury was associated with a significant increase in endothelial apoptosis at 24 hours, whereas NF-kappaB decoy ODN treatment markedly decreased terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive endothelial cells at 24 hours after reperfusion (P<0.01). Here, using synthetic double-stranded DNA with high affinity for NF-kappaB as a decoy approach, we demonstrated that activation of NF-kappaB by hypoxia caused aortic endothelial cell death and apoptosis through the suppression of bcl-2. NF-kappaB-mediated endothelial apoptosis induced by hypoxia may be involved in the pathogenesis of endothelial dysfunction observed in cardiovascular ischemic diseases.


Reliable scar scoring system to assess photographs of burn patients.
Several scar-scoring scales exist to clinically monitor burn scar development and maturation. Although scoring scars through direct clinical examination is ideal, scars must sometimes be scored from photographs. No scar scale currently exists for the latter purpose. We modified a previously described scar scale (Yeong et al., J Burn Care Rehabil 1997) and tested the reliability of this new scale in assessing burn scars from photographs. The new scale consisted of three parameters as follows: scar height, surface appearance, and color mismatch. Each parameter was assigned a score of 1 (best) to 4 (worst), generating a total score of 3-12. Five physicians with burns training scored 120 representative photographs using the original and modified scales. Reliability was analyzed using coefficient of agreement, Cronbach alpha, intraclass correlation coefficient, variance, and coefficient of variance. Analysis of variance was performed using the Kruskal-Wallis test. Color mismatch and scar height scores were validated by analyzing actual height and color differences. The intraclass correlation coefficient, the coefficient of agreement, and Cronbach alpha were higher for the modified scale than those of the original scale. The original scale produced more variance than that in the modified scale. Subanalysis demonstrated that, for all categories, the modified scale had greater correlation and reliability than the original scale. The correlation between color mismatch scores and actual color differences was 0.84 and between scar height scores and actual height was 0.81. The modified scar scale is a simple, reliable, and useful scale for evaluating photographs of burn patients.


Thermodynamic differences between agonist and antagonist interactions with binding sites for [3H]spiroperidol in rat striatum.
The characteristics of the binding of the dopamine receptor antagonist [3H]spiroperidol to rat striatal membranes were examined at six different incubation temperatures ranging from 1 degree to 37 degrees. Although the number of receptors labeled at each temperature was identical, the affinity of the receptor for [3H]spiroperidol decreased 10-fold as the incubation temperature was lowered from 37 degrees to 1 degree. The binding of [3H]spiroperidol was entropy-driven (delta S degree = +80 cal/mole-deg), endothermic (delta H degree = +10 kcal/mole), and exergonic (delta G degree = -13 kcal/mole). Qualitatively similar results were found for (+)-butaclamol, another dopamine receptor antagonist. The binding of the agonists dopamine and (+/-)-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene to sites labeled by [3H]spiroperidol in the striatum also appeared to be entropy-driven (delta S degree = +35 cal/mole-deg). In contrast to the results obtained in studies with antagonists, however, the affinity of the receptor for agonists was independent of the incubation temperature between 8 degrees and 37 degrees. Competition curves for the inhibition of [3H]spiroperidol binding by agonists became increasingly complex as the incubation temperature was lowered. The addition of GTP reduced the affinity of the receptor for agonists at all temperatures but did not simplify interpretation of these complex curves. At 1 degree there was a decrease in the affinity of the receptor for dopamine, and the effect of GTP was abolished.


Foot problems in diabetes: an overview.
Diabetes is the leading cause of nontraumatic lower-extremity amputations in the United States. Most amputations are preceded by an ulcer, and ulcers are costly in their own right. Most ulcers are neuropathic in etiology and plantar in location. They occur typically at sites of high mechanical loading because of repetitive trauma in people with loss of pain sensation. In an adequately perfused limb, such ulcers are not difficult to heal. When they are properly mechanically off-loaded, approximately 90% of these wounds heal in approximately 6 weeks. The reference standard off-loading device is the total contact cast, but other reasonably efficacious methods exist. Screening and implementation of preventive measures in the high-risk patient are highly recommended and can reduce the incidence of ulceration. All patients with diabetes should be screened annually for loss of protective sensation, with the 10-g Semmes-Weinstein monofilament being the easiest tool to use. Education to prevent complications should be implemented for all patients with loss of protective sensation.


A method for mapping intranuclear protein-DNA interactions and its application to a nuclease hypersensitive site.
We have devised a method for mapping sites on DNA within the nucleus that are protected against nuclease attack by interaction with bound protein or other factors. This "footprinting" method uses an end-labeled sequence-specific DNA probe, which is annealed to the DNA from nuclear digests under carefully controlled conditions. The annealed complexes are treated with single-strand-specific nuclease, the resulting duplex molecules are electrophoresed on gels, and the gels are autoradiographed. The high sensitivity and resolution of the method have made it possible to obtain a detailed map of DNase I cutting patterns in the 5' flanking sequence of the chicken adult beta (beta A)-globin gene within nuclei from various tissues. In nuclei from adult erythrocytes, this domain is hypersensitive to nucleases. However, we detect within the domain two well-defined regions that are protected against attack, indicating the presence of one or more bound factors. Nuclei from oviduct or 5-day-old embryonic erythrocytes, in which the domain is not hypersensitive, show limited and different patterns of protection.


Disaggregation and reconstitution of oligomeric complexes of simian virus 40 large T-antigen.
Biochemical properties of multiple species of simian virus 40 (SV40) large T-antigen produced in SV40-infected monkey cells were investigated by zonal sedimentation centrifugation of radiolabelled cell extracts on sucrose gradients. Two major subpopulations of T-antigen detected by immunoprecipitation and gel electrophoresis could be distinctly separated: low molecular weight forms ranging approximately between 5S and 10S and higher oligomeric forms at about 16S to 23S. Removal of divalent cations by chelating agents such as EDTA disassembled higher oligomers into low molecular weight forms (5S to 10S). Adding divalent cations in excess of the EDTA concentration reassembled the higher oligomeric forms, showing a sedimentation behaviour like T-antigen in untreated cell extracts. Our results are compatible with the hypothesis that divalent cation binding properties of T-antigen participate in the natural pathway of assembling multiple oligomeric species.


Asthma and COVID-19: a systematic review.
Severe coronavirus disease-19 (COVID-19) presents with progressive dyspnea, which results from acute lung inflammatory edema leading to hypoxia. As with other infectious diseases that affect the respiratory tract, asthma has been cited as a potential risk factor for severe COVID-19. However, conflicting results have been published over the last few months and the putative association between these two diseases is still unproven. Here, we systematically reviewed all reports on COVID-19 published since its emergence in December 2019 to June 30, 2020, looking into the description of asthma as a premorbid condition, which could indicate its potential involvement in disease progression. We found 372 articles describing the underlying diseases of 161,271 patients diagnosed with COVID-19. Asthma was reported as a premorbid condition in only 2623 patients accounting for 1.6% of all patients. As the global prevalence of asthma is 4.4%, we conclude that either asthma is not a premorbid condition that contributes to the development of COVID-19 or clinicians and researchers are not accurately describing the premorbidities in COVID-19 patients.


Trunk extensor muscle endurance and its relationship to action potential conduction velocity and spectral parameters estimated using high-density electromyography.
Trunk extensor muscle fatigue typically manifests as a decline in spectral content of surface electromyography. However, previous research on the relationship of this decline with trunk extensor muscle endurance have shown inconsistent results. The decline of spectral content mainly reflects the decrease in average motor unit action potential conduction velocity (CV). We evaluated whether the rate of change in CV, as well as two approaches employing the change in spectral content, are related to trunk extensor muscle endurance. Fourteen healthy male participants without a low-back pain history performed a non-strictly controlled static forward trunk bending trial until exhaustion while standing. For 13 participants, physiologically plausible CV estimates were obtained from high-density surface electromyography bilaterally from T6 to L5. Laterally between L1 and L2, the linear rate of CV change was strongly correlated to endurance time (R2 = 0.79), whereas analyses involving the linear rate of change in spectral measures showed a lower (R2 = 0.38) or no correlation. For medial electrode locations, estimating CV and its relationship with endurance time was less successful, while the linear rate of change in spectral measures correlated moderately to endurance time (R2 = 0.44; R2 = 0.56). This study provides guidance on monitoring trunk extensor muscle fatigue development using electromyography.


Ontario adults' health behaviors, mental health, and overall well-being during the COVID-19 pandemic.
Public health measures such as physical distancing and work-from-home initiatives have been implemented to slow the spread of COVID-19. These measures may also be associated with unhealthy lifestyle behaviors, which could be particularly problematic for those already at highest risk for losing years of healthy life due to chronic disease (i.e., 30-59-year-olds). The purpose of this paper is two-fold: (1) to provide an overview of Ontario adults' health behaviors (i.e., physical activity, sedentary behaviors, and dietary intake), mental health, and well-being during the first few months of the COVID-19 pandemic (April-July 2020); and (2) to explore the difference between physical activity and various health behaviors (i.e., well-being, mental health, and dietary intake). As a part of a larger, longitudinal study, participants completed an online survey that included demographic information, the Global Physical Activity Questionnaire, Starting the Conversation, the Mental Health Inventory, and the Personal Wellbeing Index-Adult. Data analyses involved computing measures of central tendency and dispersion for demographic characteristics and tools followed by descriptive statistics. Separate independent t-tests were conducted to investigate the difference between physical activity status and well-being, mental health, and dietary intake. A total of 2157 Ontarians completed an online survey. Descriptive statistics indicated that respondents met physical activity and sedentary behavior guidelines, reported double the amount of recommended recreational screen time, practiced moderately healthy dietary behaviors, experienced mental health problems, and scored below "normal" in some well-being domains. As the end of the COVID-19 pandemic is currently unknown, its associated restrictions and society changes may influence adults' behaviors in both the short- and longer-term. As such, our findings might provide immediate insight into the development of timely and evidence-informed health promotion and disease prevention strategies for Canadians, which could support adults' health behaviors, mental health, and well-being during the COVID-19 pandemic and other, future pandemics.


Impact of school sealant programs on oral health among youth and identification of potential barriers to implementation.
School sealant programs (SSPs) increase sealant prevalence among children lacking access to oral health care. SSPs, however, are substantially underused. From 2013 through 2018, the Centers for Disease Control and Prevention funded 18 states for SSP activities in high-need schools (≥ 50% free and reduced-price meal program participation). From 2019 through 2020, the authors assessed SSPs' impact in reducing caries and how states expanded SSPs. The authors also discuss potential barriers to expansion. For Aim 1, the authors used a published methodology and SSP baseline screening and 1-year retention data to estimate averted caries over 9 years attributable to SSPs. For Aim 2, the authors used state responses to an online survey, phone interviews, and annual administrative reports. Using data for 62,750 children attending 18.6% of high-need schools in 16 states, the authors estimated that 7.5% of sound, unsealed molars would develop caries annually without sealants and placing 4 sealants would prevent caries in 1 molar. Fourteen states reported SSP expansion in high-need schools. The 2 most frequently reported barriers to SSP expansion were levels of funding and policies requiring dentists to be present at assessment or sealant placement. The authors found that SSPs typically served children at elevated caries risk and reduced caries. In addition, the authors identified funding levels and policies governing supervision of dental hygienists as possible barriers to SSP expansion. Increasing SSP prevalence could reduce caries. Further research on potential barriers to SSP implementation identified in this study could provide critical information for long-term SSP sustainability.


Structural equation models of sexual harassment: longitudinal explorations and cross-sectional generalizations.
Sexual harassment and its corresponding outcomes develop and change over time, yet research on this issue has been limited primarily to cross-sectional data. In this article, longitudinal models of harassment were proposed and empirically evaluated via structural equations modeling using data from 217 women who responded to a computerized questionnaire in 1994 and again in 1996. Results indicate that sexual harassment influences both proximal and distal work-related variables (e.g., job satisfaction, work withdrawal, job withdrawal) and psychological outcomes (e.g., life satisfaction, psychological well-being, distress). In addition, a replication of the L. F. Fitzgerald, F. Drasgow, C.L. Hulin, M.J. Gelfand, and V.J. Magley (1997) model of harassment was supported. This research was an initial attempt to develop integrated models of the dynamic effects of sexual harassment over time.


Peri-procedural management of bleeding risks in critical care patients: A local audit and national survey.
Estimation of bleeding risk in critical care patients undergoing interventional radiological procedures is frequently made on the basis of blood tests. If these tests are abnormal, fresh frozen plasma and/or platelet transfusions may be given to reduce the risk of bleeding. We performed an audit and national survey of the use of fresh frozen plasma and platelet transfusions prior to interventional radiological procedures. We identified 68 consecutive chest, abdominal or pelvic drain insertions in 54 critical care patients between 2008 and 2011 at a single intensive care unit. Eight (12.3%) patients were transfused fresh frozen plasma prior to drain insertion despite having a prothrombin time below 22 s. One patient with a prothrombin time above this threshold received fresh frozen plasma. One patient received a platelet transfusion, at double dose, despite a platelet count above 50 × 109/l. A national survey of interventional radiologists demonstrated extensive variability in safe thresholds for invasive procedures and usage of fresh frozen plasma. There is a need for further clarification around coagulopathy and interventional radiology in the critical care setting.


Resilience against the impacts of climate change in an ecologically and economically significant native oyster.
Climate change is acidifying and warming our oceans, at an unprecedented rate posing a challenge for marine invertebrates vital across the globe for ecological services and food security. Here we show it is possible for resilience to climate change in an ecologically and economically significant oyster without detrimental effects to the energy budget. We exposed 24 pair-mated genetically distinct families of the Sydney rock oyster, Saccostrea glomerata to ocean acidification and warming for 4w and measured their resilience. Resilience was identified as the capacity to defend their acid-base balance without a loss of energy available for Scope for Growth (SFG). Of the 24 families, 13 were better able to defend their acid-base balance while eight had no loss of energy availability with a positive SFG. This study has found oyster families with reslience against climate change without a loss of SFG, is an essential mitigation strategy, in a critical mollusc.


New chromanone derivatives containing thiazoles: Synthesis and antitumor activity evaluation on A549 lung cancer cell line.
Novel 2-[2-(chroman-4-ylidene)hydrazinyl]-4/5-substituted thiazole derivatives (2a-i) were synthesized and investigated for their anticancer activity. Cytotoxic activity on A549 and NIH/3T3 cell lines was determined, most of the compounds exhibited high cytotoxic profile with selectivity. Selected compounds 2b, 2c, 2e, 2g, 2h, and 2i were tested to determine induction of apoptosis, mitochondrial membrane depolarization, and cell cycle arrest. The results showed that the compounds induced apoptosis intrinsically that they triggered loss of mitochondrial potential through increasing the accumulation of cells in G2/M. Besides, intrinsic apoptotic pathway was supported by down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of proapoptotic protein Bax. Molecular docking study for compounds 2b, 2c, and 2g was promoted experimental outcomes.


Combining density functional theory and 23Na NMR to characterize Na2FePO4F as a potential sodium ion battery cathode.
Sodium ion batteries offer an inexpensive alternative to lithium ion batteries, particularly for large-scale applications such as grid storage that do not require fast charging rates and high power output. Moreover, the use of polyanionic structures as cathode materials afford incredibly high structural stability relative to layered transition metal oxides that can undergo a structural collapse upon full removal of the charge carrying ions. Sodium iron fluorophosphate, Na2FePO4F, has demonstrated its viability as a potential cathode material for sodium ion batteries, having a robust framework even after multiple charge-discharge cycles. Although solid-state NMR has traditionally been an excellent method for the determination of local structure and dynamic properties of cathode materials during the electrochemical cycling process, reliable assignment of the 23Na chemical shifts resulting from the paramagnetic hyperfine interaction can be difficult when using only empirical rules. Here we present the use of density functional theory calculations to assign the experimentally observed NMR shifts to the crystallographic sites in Na2FePO4F, where it is found that the results do not agree with the previously reported assignment based upon simple geometry arguments. Furthermore, we report the justification of the proposed desodiation mechanism in Na2FePO4F on the basis of theoretical arguments, in good agreement with experimental NMR results reported previously.


The argument for conservative, delayed surgery in the management of prostatic rhabdomyosarcoma.
Exenteration is no longer required for most patients who have rhabdomyosarcoma (RMS) of the prostate. This site comprised only about 5% of newly diagnosed cases in the IRS-III (1984-1991). The mean age at the time of diagnosis was 5.3 yrs (range, 0 to 19 years). Most tumors were relatively large, had embryonal histology, and were clinically localized but unresectable without major loss of organ function. The 44 patients with group III tumors (gross residual disease) were treated according to the IRS-III protocol. Forty-three of them underwent biopsy only, and one patient had subtotal resection as the initial procedure. The average number of surgical procedures per patient was two (range, one to five). Six of the 44 patients had no additional surgery. The second-look procedures performed in the other 38 patients included exenteration (14), prostatectomy (7), cystoscopic/perineal needle biopsy (8), laparotomy with biopsy (6), and subtotal excision with bladder salvage (3). Additional surgery was required for four patients, for evaluation of a residual mass, postoperative fistula, ureteral stricture, or small bowel obstruction. Six patients with relapse or residual disease underwent additional chemotherapy and late exenteration (3), prostatectomy (1), or biopsy (2). Four of the six have been cured, one is in treatment for a second malignancy, and the other has residual disease after exenteration. Thirty-six of the 44 patients with group III tumors have been cured (minimum follow-up period, 6 years; range, 6 to 11 years), compared with 23 of the 47 in IRS-II (1978-1984) (P = .001). Two of the six deaths in this group were caused by infection. The bladder salvage rate for those cured of their disease also was better (64% v 57% for IRS-II). The two patients with group IIA tumors were cured by gross primary excision, local radiotherapy, and vincristine and actinomycin therapy. By contrast, all patients with metastatic disease (group IV) died of the tumor. Conservative, delayed surgery, performed after intensive chemotherapy with or without radiotherapy, yields a better cure rate while maintaining a high rate of bladder salvage in children with group III prostatic RMS.


Interfacial colloidal sedimentation equilibrium. II. Closure-based density functional theory.
In Part I [R. E. Beckham and M. A. Bevan, J. Chem. Phys. 127, 164708 (2007)], results were presented for the sedimentation equilibrium of concentrated colloidal dispersions using confocal scanning laser microscopy experiments, Monte Carlo (MC) simulations, and a local density approximation perturbation theory. In this paper, we extended the modeling effort on those systems to include nonlocal density functional theory (DFT), which is capable of predicting the microstructure of the sediment at length scales comparable to the colloidal particle dimension. Specifically, we use a closure-based DFT formulation to predict interfacial colloidal sedimentation equilibrium density profiles. The colloid-colloid and colloid-surface interactions were modeled with DLVO screened electrostatic potentials using parameters taken directly from the experimental work. The DFT profiles were compared to the experimental and MC results from Part I. Good agreement was found for relatively dilute interfacial colloidal fluids, but agreement was less satisfactory as interfacial layering became more pronounced for conditions approaching the onset of interfacial crystallization. We also applied DFT in an inverse sense using the measured colloid density profile to extract the underlying colloid-surface potential; this can be thought of as a microscopic analog to the well-known procedure of using the macroscopic (coarse-grained) density profile to extract the osmotic equation of state. For the dilute interfacial fluid, the inverse DFT calculations reproduced the true colloid-surface potential to within 0.5kT at all elevations.


Effects of Boric Acid on Fracture Healing: An Experimental Study.
Boric acid (BA) has positive effects on bone tissue. In this study, the effects of BA on fracture healing were evaluated in an animal model. Standard closed femoral shaft fractures were created in 40 male Sprague-Dawley rats under general anesthesia. The rats were allocated into five groups (n = 8 each): group 1, control with no BA; groups 2 and 3, oral BA at doses of 4 and 8 mg/kg/day, respectively; group 4, local BA (8 mg/kg); and group 5, both oral and local BA (8 mg/kg/day orally and 8 mg/kg locally). After closed fracture creation, the fracture line was opened with a mini-incision, and BA was locally administered to the fracture area in groups 4 and 5. In groups 2, 3, and 5, BA was administered by gastric gavage daily until sacrifice. The rats were evaluated by clinical, radiological, and histological examinations. The control group (group 1) significantly differed from the local BA-exposed groups (groups 4 and 5) in the clinical evaluation. Front-rear and lateral radiographs revealed significant differences between the local BA-exposed groups and the control and other groups (p < 0.05). Clinical and radiological evaluations demonstrated adequate agreement between observers. The average histological scores significantly differed across groups (p = 0.007) and were significantly higher in groups 4 and 5 which were the local BA (8 mg/kg) and both oral and local BA (8 mg/kg/day orally and 8 mg/kg locally), respectively, compared to the controls. This study suggests that BA may be useful in fracture healing. Further research is required to demonstrate the most effective local dosage and possible use of BA-coated implants.


[Biomarkers in neuroimmunology].
Biomarkers of clinical relevance are very important in the workup of patients presenting with neurological autoimmune diseases. Nervous biopsy remains often the "gold standard procedure" but is limited in practice due to the risk of complication and insufficient yield. These biomarkers, most often auto-antibodies, can be the direct cause of the neurological syndrome or be detected as an epiphenomenon of the pathogenic process. The detection of these biomarkers, when performed in well defined clinical conditions, may help the clinician to establish a definite diagnosis which may in turn facilitate the therapeutic decision. The purpose of this article is to review the biomarkers that are available in daily practice to investigate immune-mediated neurological conditions.


Does multiple paternity affect seed mass in angiosperms? An experimental test in Dalechampia scandens.
Flowers fertilized by multiple fathers may be expected to produce heavier seeds than those fertilized by a single father. However, the adaptive mechanisms leading to such differences remain unclear, and the evidence inconsistent. Here, we first review the different hypotheses predicting an increase in seed mass when multiple paternity occurs. We show that distinguishing between these hypotheses requires information about average seed mass, but also about within-fruit variance in seed mass, bias in siring success among pollen donors, and whether siring success and seed mass are correlated. We then report the results of an experiment on Dalechampia scandens (Euphorbiaceae), assessing these critical variables in conjunction with a comparison of seed mass resulting from crosses with single vs. multiple pollen donors. Siring success differed among males when competing for fertilization, but average seed mass was not affected by the number of fathers. Furthermore, paternal identity explained only 3.8% of the variance in seed mass, and siring success was not correlated with the mass of the seeds produced. Finally, within-infructescence variance in seed mass was not affected by the number of fathers. These results suggest that neither differential allocation nor sibling rivalry has any effect on the average mass of seeds in multiply sired fruits in D. scandens. Overall, the limited paternal effects observed in most studies and the possibility of diversification bet hedging among flowers (but not within flowers), suggest that multiple paternity within fruits or infructescence is unlikely to affect seed mass in a large number of angiosperm species.


New Method of Inhibition of Activity of Tumor Necrosis Factor Alpha In Patients with Psoriasis.
A new method of reduction of tumor necrosis factor alpha activity via intradermal immunization with inactivated autoleukocytes (patent UA97493 (2015) [1]) has been presented in the article. New patents from various countries have been analyzed [2-7]. Patients with psoriasis (24) with high level of tumor necrosis factor alpha in their blood (. 30pg/ml) were immunized with autoleukocytes. Leukocytes were isolated by centrifuging plasma, obtained after precipitation of a patient's heparinized peripheral venous blood. Precipitate was suspended in 1.0 - 1.5ml of a patient's blood serum and 0.1ml of blood was injected into the skin of the back. For determination of autoleukocyte immunization efficacy, concentration of tumor necrosis factor alpha in a patient's blood was compared prior to immunization and at different periods after immunization. In 30 days after single immunization, a considerable decrease in cytokine concentration was observed in all patients (100%); it reduced to zero in 16 out of 24 of immunized individuals (66.7%). The degree of reduction and duration of the achieved effect were individual, thus, if necessary the immunization was repeated several times. The procedure was well tolerated, and general condition of patients was improved. The method of reduction of tumor necrosis factor alpha activity is recommended for implementation into clinical practice.


Transcription from efficient promoters can interfere with plasmid replication and diminish expression of plasmid specified genes.
The copy number of plasmids containing the ColE1 replicon is affected by changes in the transcriptional activity within the plasmid if these changes lead to transcriptional readthrough into the replication region towards the promoter priming DNA replication. Such readthrough e.g., from the tet region in pBR322 not only causes overproduction of a peptide known to affect the copy number negatively but also appears to interfere negatively with the replication of the plasmid itself. The proper placement of efficient transcriptional terminators prevents such interference and permits the stable integration of strong promoters. Due to this termination effect, up to 9-fold differences in plasmid copy number were observed, depending upon the particular growth conditions. The higher copy number is of course reflected by higher yields of plasmid-specified gene products indicating the relevance of the above effects for studies of gene expression.


Generation of uniform liver spheroids from human pluripotent stem cells for imaging-based drug toxicity analysis.
Recent advances in pluripotent stem cell technology provide an alternative source of human hepatocytes to overcome the limitations of current toxicity tests. However, this approach requires optimization and standardization before it can be used as a fast and reliable toxicity screening system. Here, we designed and tested microwell culture platforms with various diameters. We found that large quantities of uniformly-sized hepatocyte-like cell (HLC) spheroids (3D-uniHLC-Ss) could be efficiently and reproducibly generated in a short period time from a small number of differentiating human pluripotent stem cells (hPSCs). The hPSC-3D-uniHLC-Ss that were produced in 500-μm diameter microwells consistently exhibited high expressions of hepatic marker genes and had no significant signs of cell death. Importantly, a hepatic master gene hepatocyte nuclear factor 4α (HNF4α) was maintained at high levels, and the epithelial-mesenchymal transition was significantly attenuated in hPSC-3D-uniHLC-Ss. Additionally, when compared with 3D-HLC-Ss that were produced in other 3D platforms, hPSC-3D-uniHLC-Ss showed significantly higher hepatic gene expressions and drug-metabolizing activity of the enzyme, CYP3A4. Imaging-based drug toxicity studies demonstrated that hPSC-3D-uniHLC-Ss exhibited enhanced sensitivity to various hepatotoxicants, compared to HLCs, which were differentiated under 2D conditions. Precise prediction of drug-induced hepatotoxicity is a crucial step in the early phases of drug discovery. Thus, the hPSC-3D-uniHLC-Ss produced using our microwell platform could be used as an imaging-based toxicity screening system to predict drug hepatotoxicity.


The association between perceived fatigue and actual level of physical activity in multiple sclerosis.
Both fatigue and reduced physical activity are important consequences of multiple sclerosis (MS). However, their mutual association is poorly understood. The objective of the study was to determine the relation between perceived fatigue and home-based recording of motor activity in patients with MS. Found associations were checked for confounding by age, Expanded Disability Status Scales (EDSS), disease duration, sub-type of MS, anxiety, and depression. Forty-three ambulatory patients with MS were recruited. Ambulatory physical activity was recorded for 24 hours. Fatigue was assessed with the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS) and the Checklist Individual Strength (CIS20R). Linear regression was applied after which potential confounding factors were introduced in a multivariate regression model. No significant associations between physical activity and fatigue scores were found, except for the MFIS sub-scale 'physical activity' (ß(physical_activity) [ß(pa)] = -0.044; SE = 0.020). The association between physical activity and the FSS score was distorted by age, MS-type, anxiety and depression and the association between physical activity and the MFIS score by age and depression. The inverse association between MFIS sub-scale 'physical activity' and physical activity was significantly strengthened by adjusting for age (ß(pa) = - 0.052; SE = 0.019), sub-type of MS (ß(pa) = - 0.048; SE = 0.020), anxiety (ß(pa) = - 0.070; SE = 0.023) and depression (ß(pa) = - 0.083; SE = 0.023). In MS, there is no, or at best a weak association between severity of perceived fatigue and physical activity. Depending on the fatigue questionnaire used, patient characteristics such as age, type of MS, depression and anxiety are factors that may affect this relationship.


Outlier-resilient complexity analysis of heartbeat dynamics.
Complexity in physiological outputs is believed to be a hallmark of healthy physiological control. How to accurately quantify the degree of complexity in physiological signals with outliers remains a major barrier for translating this novel concept of nonlinear dynamic theory to clinical practice. Here we propose a new approach to estimate the complexity in a signal by analyzing the irregularity of the sign time series of its coarse-grained time series at different time scales. Using surrogate data, we show that the method can reliably assess the complexity in noisy data while being highly resilient to outliers. We further apply this method to the analysis of human heartbeat recordings. Without removing any outliers due to ectopic beats, the method is able to detect a degradation of cardiac control in patients with congestive heart failure and a more degradation in critically ill patients whose life continuation relies on extracorporeal membrane oxygenator (ECMO). Moreover, the derived complexity measures can predict the mortality of ECMO patients. These results indicate that the proposed method may serve as a promising tool for monitoring cardiac function of patients in clinical settings.


Situational Awareness: The Effect of Stimulus Type and Hearing Protection on Sound Localization.
The purpose of the current study was to test sound localization of a spoken word, rarely studied in the context of localization, compared to pink noise and a gunshot, while taking into account the source position and the effect of different hearing protection devices (HPDs) used by the listener. Ninety participants were divided into three groups using different HPDs. Participants were tested twice, under with- and no-HPD conditions, and were requested to localize the different stimuli that were delivered from one of eight speakers evenly distributed around them (starting from 22.5°). Localization of the word stimulus was more difficult than that of the other stimuli. HPD usage resulted in a larger mean root-mean-square error (RMSE) and increased mirror image reversal errors for all stimuli. In addition, HPD usage increased the mean RMSE and mirror image reversal errors for stimuli delivered from the front and back, more than for stimuli delivered from the left and right. HPDs affect localization, both due to attenuation and to limitation of pinnae cues when using earmuffs. Difficulty localizing the spoken word should be considered when assessing auditory functionality and should be further investigated to include HPDs with different attenuation spectra and levels, and to further types of speech stimuli.


Acupuncture for Hot Flashes in Cancer Patients: Clinical Characteristics and Traditional Chinese Medicine Diagnosis as Predictors of Treatment Response.
Acupuncture is a recognized integrative modality for managing hot flashes. However, data regarding predictors for response to acupuncture in cancer patients experiencing hot flashes are limited. We explored associations between patient characteristics, including traditional Chinese medicine (TCM) diagnosis, and treatment response among cancer patients who received acupuncture for management of hot flashes. We reviewed acupuncture records of cancer outpatients with the primary reason for referral listed as hot flashes who were treated from March 2016 to April 2018. Treatment response was assessed using the hot flashes score within a modified Edmonton Symptom Assessment Scale (0-10 scale) administered immediately before and after each acupuncture treatment. Correlations between TCM diagnosis, individual patient characteristics, and treatment response were analyzed. The final analysis included 558 acupuncture records (151 patients). The majority of patients were female (90%), and 66% had breast cancer. The median treatment response was a 25% reduction in the hot flashes score. The most frequent TCM diagnosis was qi stagnation (80%) followed by blood stagnation (57%). Older age ( P = .018), patient self-reported anxiety level ( P = .056), and presence of damp accumulation in TCM diagnosis ( P = .047) were correlated with greater hot flashes score reduction. TCM diagnosis and other patient characteristics were predictors of treatment response to acupuncture for hot flashes in cancer patients. Future research is needed to further explore predictors that could help tailor acupuncture treatments for these patients.


Multi-pathogen infections and Alzheimer's disease.
Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD is not fully understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.


A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency.
Both in vitro and in vivo studies established that interleukin 7 (IL-7) is essential for differentiation of immature T cells and B cells but not natural killer (NK) cells in the mouse. In humans, although both T-cell and B-cell progenitors express the functional IL-7 receptor that consists of IL-7R alpha and the gamma common (gamma c) chain, this lymphocyte receptor system is critical for T lineage but not for B lineage development. Indeed, complete gamma c deficiency like IL-7R alpha deficiency results in the arrest of T-cell but not B-cell development (T(-)B(+) SCID). However, partial deficiency of gamma c caused by missense mutations results in a T(+)B(+) phenotype and a delay of clinical presentation. It was therefore plausible to assume that partial deficiency of IL-7R alpha, like partial gamma c deficiency may lead to a milder clinical and immunologic phenotype. A P132S mutation in the IL-7R alpha was identified in 3 patients with severe combined immunodeficiency (SCID) within an extensively consanguineous family. Substitution of proline with serine in the extracellular portion of IL-7R alpha did not affect IL-7R alpha messenger RNA (mRNA) and protein expression, but severely compromised affinity to IL-7, resulting in defective signal transduction. In response to IL-7 stimulation, Jak-3 phosphorylation was markedly reduced in both patient cells as well as in COS cells reconstituted with mutant IL-7R alpha. Surprisingly, this partial deficiency of IL-7R alpha resulted in a severe phenotype, including markedly reduced circulating T cells while sparing B-cell numbers similar to gamma c chain deficiency. However, unlike the previously reported cases, serum immunoglobulins were virtually absent. Further, unlike gamma c deficiency, NK cell numbers and function was preserved. Despite the partial deficiency, clinical presentation was indistinguishable from a complete gamma c deficiency, including severe and persistent viral and protozoal infections and failure to thrive. Unlike partial gamma c deficiency, a partial deficiency of IL-7R alpha results in an arrest of T-cell development, leading to typical severe combined immunodeficiency. This underscores the critical role of IL-7R alpha chain in the differentiation of T cells. (Blood. 2000;96:2803-2807)


A young woman with seizures, visual impairment, and paralysis.
Anti-MOG encephalomyelitis is a recently described demyelinating, autoimmune disease of the central nervous system, identified by antibodies against myelin oligodendrocyte glycoprotein (MOG). A previously healthy 20-year-old woman was admitted to hospital after a seizure. MRI showed leptomeningeal enhancement and lumbar puncture revealed moderate pleocytosis but no evidence of infection. Over the following months, she experienced a series of neurological deficits including bladder dysfunction, loss of sensation in the lower extremities and genital area, impaired motor function of the legs and episodes of visual loss. All symptoms had MRI correlates in the medulla, brainstem, optic tract, thalami and corpus callosum. She responded excellently to corticosteroid treatment, but experienced relapses shortly after discontinuation of treatment. Repeated lumbar puncture revealed pleocytosis up to 475 ∙ 106 cells/l but there were no signs of intrathecal IgG synthesis or infection. Serum anti-MOG antibodies were detected two months after the initial episode. She has been treated with low dose corticosteroids in combination with rituximab for two years, without clinical or radiological relapse. Symptoms and signs mimicking acute demyelinating encephalomyelitis and neuromyelitis optica are typical for anti-MOG encephalomyelitis. This case illustrates that the response to corticosteroids may be excellent but transient, and that the disease can be controlled with moderate immunosuppression.


The feasibility of automated eye tracking with the Early Childhood Vigilance Test of attention in younger HIV-exposed Ugandan children.
Tobii eye tracking was compared with webcam-based observer scoring on an animation viewing measure of attention (Early Childhood Vigilance Test; ECVT) to evaluate the feasibility of automating measurement and scoring. Outcomes from both scoring approaches were compared with the Mullen Scales of Early Learning (MSEL), Color-Object Association Test (COAT), and Behavior Rating Inventory of Executive Function for preschool children (BRIEF-P). A total of 44 children 44 to 65 months of age were evaluated with the ECVT, COAT, MSEL, and BRIEF-P. Tobii ×2-30 portable infrared cameras were programmed to monitor pupil direction during the ECVT 6-min animation and compared with observer-based PROCODER webcam scoring. Children watched 78% of the cartoon (Tobii) compared with 67% (webcam scoring), although the 2 measures were highly correlated (r = .90, p = .001). It is possible for 2 such measures to be highly correlated even if one is consistently higher than the other (Bergemann et al., 2012). Both ECVT Tobii and webcam ECVT measures significantly correlated with COAT immediate recall (r = .37, p = .02 vs. r = .38, p = .01, respectively) and total recall (r = .33, p = .06 vs. r = .42, p = .005) measures. However, neither the Tobii eye tracking nor PROCODER webcam ECVT measures of attention correlated with MSEL composite cognitive performance or BRIEF-P global executive composite. ECVT scoring using Tobii eye tracking is feasible with at-risk very young African children and consistent with webcam-based scoring approaches in their correspondence to one another and other neurocognitive performance-based measures. By automating measurement and scoring, eye tracking technologies can improve the efficiency and help better standardize ECVT testing of attention in younger children. This holds promise for other neurodevelopmental tests where eye movements, tracking, and gaze length can provide important behavioral markers of neuropsychological and neurodevelopmental processes associated with such tests. (PsycINFO Database Record


Method for measuring ATP production in isolated mitochondria: ATP production in brain and liver mitochondria of Fischer-344 rats with age and caloric restriction.
The production of ATP is vital for muscle contraction, chemiosmotic homeostasis, and normal cellular function. Many studies have measured ATP content or qualitative changes in ATP production, but few have quantified ATP production in vivo in isolated mitochondria. Because of the importance of understanding the energy capacity of mitochondria in biology, physiology, cellular dysfunction, and ultimately, disease pathologies and normal aging, we modified a commercially available bioluminescent ATP determination assay for quantitatively measuring ATP content and rate of ATP production in isolated mitochondria. The bioluminescence assay is based on the reaction of ATP with recombinant firefly luciferase and its substrate luciferin. The stabilities of the reaction mixture as well as relevant ATP standards were quantified. The luminescent signals of the reaction mixture and a 0.5 microM ATP standard decreased linearly at rates of 2.16 and 1.39% decay/min, respectively. For a 25 microM ATP standard, the luminescent signal underwent a logarithmic decay, due to intrinsic deviations from the Beer-Lambert law. Moreover, to test the functionality of isolated mitochondria, they were incubated with 1 and 5 mM oligomycin, an inhibitor of oxidative phosphorylation. The rate of ATP production in the mitochondria declined by 34 and 83%, respectively. Due to the sensitivity and stability of the assay and methodology, we were able to quantitatively measure in vivo the effects of age and caloric restriction on the ATP content and production in isolated mitochondria from the brain and liver of young and old Fischer-344 rats. In both tissues, neither age nor caloric restriction had any significant effect on the ATP content or the rate of ATP production. This study introduces a highly sensitive, reproducible, and quick methodology for measuring ATP in isolated mitochondria.


The anatomic location and importance of the tibialis posterior fascicular bundle at the sciatic nerve bifurcation: report of 3 cases.
The authors present the cases of 3 patients with severe injuries affecting the peroneal nerve combined with loss of tibialis posterior function (inversion) despite preservation of other tibial nerve function. Loss of tibialis posterior function is problematic, since transfer of the tibialis posterior tendon is arguably the best reconstructive option for foot drop, when available. Analysis of preoperative imaging studies correlated with operative findings and showed that the injuries, while predominantly to the common peroneal nerve, also affected the lateral portion of the tibial nerve/division near the sciatic nerve bifurcation. Sunderland's fascicular topographic maps demonstrate the localization of the fascicular bundle subserving the tibialis posterior to the area that corresponds to the injury. This has clinical significance in predicting injury patterns and potentially for treatment of these injuries. The lateral fibers of the tibial division/nerve may be vulnerable with long stretch injuries. Due to the importance of tibialis posterior function, it may be important to perform internal neurolysis of the tibial division/nerve in order to facilitate nerve action potential testing of these fascicles, ultimately performing split nerve graft repair when nerve action potentials are absent in this important portion of the tibial nerve.


Longitudinal Associations Between Ambient Air Pollution With Insulin Sensitivity, β-Cell Function, and Adiposity in Los Angeles Latino Children.
Evidence suggests that ambient air pollution (AAP) exposure may contribute to the development of obesity and type 2 diabetes. The objective of this study was to determine whether exposure to elevated concentrations of nitrogen dioxide (NO2) and particulate matter with aerodynamic diameter <2.5 (PM2.5) had adverse effects on longitudinal measures of insulin sensitivity (SI), β-cell function, and obesity in children at high risk for developing diabetes. Overweight and obese Latino children (8-15 years; n = 314) were enrolled between 2001 and 2012 from Los Angeles, CA, and followed for an average of 3.4 years (SD 3.1 years). Linear mixed-effects models were fitted to assess relationships between AAP exposure and outcomes after adjusting for covariates including body fat percent. Higher NO2 and PM2.5 were associated with a faster decline in SI and a lower SI at age 18 years, independent of adiposity. NO2 exposure negatively affected β-cell function, evidenced by a faster decline in disposition index (DI) and a lower DI at age 18 years. Higher NO2 and PM2.5 exposures over follow-up were also associated with a higher BMI at age 18 years. AAP exposure may contribute to development of type 2 diabetes through direct effects on SI and β-cell function.


Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study.
Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995-2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010-14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.


A broadband high spectral brightness fiber-based two-photon source.
After characterizing the Raman scattering in a fused silica polarization-maintaining microstructure optical fiber, we built a fiber-based two-photon light source of high spectral brightness, broad spectral range, and very low noise background at room temperature. The resulting bright low-noise two-photon light can be used for a number of quantum information applications.


Comparative study of four different spherical embolic particles in an animal model: a morphologic and histologic evaluation.
To perform a study in a porcine model comparing four different spherical embolic particles in terms of postembolization patency, deformation, and potential for recanalization, with a focus on a relatively new agent--HepaSphere. Partial embolization of both kidneys was performed in 18 pigs. Nine animals were sacrificed at 48 hours and nine at 4 weeks. In the same animal, the right kidney was embolized with HepaSphere particles ("dry" size, 50-100 microm; presumed final size, 200-300 microm), and the left kidney was alternatively embolized with EmboSphere (100-300 microm), Contour (150-350 microm), or Bead Block (150-350 microm) particles. The authors analyzed the size, deformation, and number of particles in each vessel, their morphologic characteristics, and recanalization. Particle sizes and deformation (1,096 particles) were as follows: HepaSphere, 225.3 microm +/- 67 and 26% +/- 19.7, respectively; EmboSphere, 132.9 microm +/- 36 and 18.1% +/- 14.2; Bead Block, 108.1 microm +/- 38 and 16.5% +/- 13.9; and Contour, 240.8 microm +/- 135 and 55.5% +/- 33. HepaSphere and Bead Block particles were distally located, and EmboSphere and Contour particles were located more proximally. EmboSphere and Bead Block particles were round, HepaSphere particles were round and/or ovoid, and Contour particles had an amorphous aspect. EmboSphere particles had a higher tendency to aggregate. No recanalization was seen with HepaSphere particles, and variable recanalization was observed with the others. Despite similar initial morphologic characteristics, the performance of the agents tested in this study differed in terms of final size, shape, deformation, and luminal recanalization. These differences have potential clinical relevance, and the knowledge of the differing embolic performance may be helpful in choosing agents for specific therapeutic purposes.


An electrochemical DNA sensor based on a layers-film construction modified electrode.
This work developed a relatively inexpensive and layers-film construction electrochemical sensor for DNA recognition and its performance was investigated. The Fe(3)O(4) magnetic nanoparticles-cysteine were immobilized on the carbon paste electrode (CPE) surface using magnetic force. Multiwalled carbon nanotubes (MWCNTs), gold nanoparticles (GNPs), and chitosan (Chi) were used successively to coat on the electrode surface. The thiolated capture probe was assembled and competitively hybridized with the target nucleic acid and biotinylated response probe. The electrochemical behavior was analyzed by cyclic voltammetry and electrochemical impedance spectroscopy. In addition, the sensor performance was also analyzed by introducing the notion of detection efficiency. The experimental results showed that although the electron transfer capability of the CPE is less strong than that of a metal electrode used in the DNA sensor, the materials modified on the CPE could significantly improve the performance. A detection limit of 1 nM of target DNA and a sensitivity of 2.707 × 10(3) mA M(-1) cm(-2) were obtained. Although the resulting detection limit was not remarkable, further experiments could improve it.


[Cancer on the big screen. How and when movies deal with oncological diseases].
Films that feature characters with cancer have become a familiar sight for movie-goers. 148 movies treating tumors were selected, produced all over the world since the Thirties, in which cancer had "prompt", "relevant", or "plot" character. In order to clearly understand each film's peculiar message about cancer, we recollected data such as genealogy, year and country of production, main characters' age and gender, and kind of tumor. Movies deal with cancer through very relevant questions, as well as themes and contexts that have great influence on oncologist's mind and consciousness. Specially in recent years, films have tackled some of the most important issues around cancer, such as his epidemiology and environmental causes; the economic implications of therapies; the management of symptoms and side effects; the psychological dynamics; the care toward the ending of life. The most frequent treatment mentioned in the movies was chemotherapy followed by antalgic therapy. Very often the ill person on the screen doesn't get over the disease and his death is somehow useful to the plot's outcome. This pattern is so strongly standardized that it persists in spite of real progress of treatments. Movies use disease, and other tragedies, as a dramatic device, and since drama is what we expect of the medium, should we be concerned that there is a gap between fiction and reality? Movies represent an essential step of educational process, but their potential has been fully exploited only in recent times. By watching movies on cancer, oncologists could become more conscious of problems they are already facing in the therapeutic setting: cancer and sexuality, the relationship between the ill person and the medical staff, side effects of therapies. Some films simply make us reflect upon the meaning of life and death. This is useful for the sharing of cancer care, from personal or familiar problems to issues of collective relevance.


Investigation of risk factors of psychological acceptance and burnout syndrome among nurses in China.
The objectives of this study were to determine reliability of Chinese version of Acceptance and Action Questionnaire-II (AAQ-II), the relationship between psychological acceptance (PA), and burnout syndrome and their risk factors among nurses in China. The reliability of AAQ-II in Chinese was evaluated first by testing on 111 doctors and 108 nurses in China. On the number of 845 nurses selected from nine city hospitals by using stratified cluster sampling method, the Maslach Burnout Inventory-General Survey was administered to establish the presence of burnout, and the AAQ-II was used to measure their PA. Results showed that the AAQ-II in Chinese had a good test-retest reliability. PA was statistically significantly negatively correlated to the three dimensionalities of burnout among nurses in China. Male and female nurses had a significant difference in PA. Risk factors for burnout were age (25-44 years), marital status (married), gender (male), hospital department (emergency) and position (primary title) as well as PA. The findings provide insights into the risk factors of burnout in Chinese nurses and may have clinical implications in preventing burnout in Chinese nurses.


Disappearance of isocitrate lyase enzyme from cells of Chlorella pyrenoidosa.
1. When acetate-adapted cells of Chlorella are suspended in nitrogen-free medium and supplied with glucose, isocitrate lyase activity disappears from the cells at a rate of about 9%/h. This loss of activity is shown to be accompanied by loss of isocitrate lyase protein. 2. When isocitrate lyase activity is assayed in intact cells after freezing and thawing, the rate of loss of activity after addition of glucose approaches 20%/h. 3. It is shown, by using (35)S, that the rate of turnover of isocitrate lyase protein is somewhat lower than that of other major soluble proteins; general protein turnover during nitrogen starvation, and after glucose addition, is too slow to account for the rate of loss of isocitrate lyase protein. 4. Disappearance of isocitrate lyase activity must result from a mechanism that allows degradation of this specific protein under conditions of limiting nitrogen supply.


A novel function of nuclear nonmuscle myosin regulatory light chain in promotion of xanthine oxidase transcription after myocardial ischemia/reperfusion.
Nuclear myosin regulates gene transcription and this novel function might be modulated through phosphorylation of the myosin regulatory light chain (p-MLC20). Nonmuscle MLC20 (nmMLC20) is also present in the nuclei of cardiomyocytes and a potential nmMLC20 binding sequence has been identified in the promoter of the xanthine oxidase (XO) gene. Thus, we investigated its function in the regulation of XO transcription after myocardial ischemia/reperfusion (IR). In a rat model of myocardial IR and a cardiomyocyte model of hypoxia/reoxygenation (HR) injury, the cardiac or cell injury, myosin light chain kinase (MLCK) content, XO expression and activity, XO-derived products, and level of nuclear p-nmMLC20 were detected. Coimmunoprecipitation (co-IP), chromatin immunoprecipitation, DNA pull-down, and luciferase reporter gene assays were used to decipher the molecular mechanisms through which nmMLC20 promotes XO expression. IR or HR treatment dramatically elevated nuclear p-nmMLC20 level, accompanied by increased XO expression, activity, and products (H2O2 and uric acid), as well as the IR or HR injury; these effects were ameliorated by inhibition of MLCK or knockdown of nmMLC20. Our findings from these experiments demonstrated that nuclear p-nmMLC20 binds to the consensus sequence GTCGCC in the XO gene promoter, interacts with RNA polymerase II and transcription factor IIB to form a transcription preinitiation complex, and hence activates XO gene transcription. These results suggest that nuclear p-nmMLC20 plays an important role in IR/HR injury by transcriptionally upregulating XO gene expression to increase oxidative stress in myocardium. Our findings demonstrate nuclear nmMLC20 as a potential new therapeutic target to combat cardiac IR injury.


Probabilistic White Matter Atlases of Human Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Visual and Visuospatial Networks.
Background: Despite the popularity of functional connectivity analyses and the well-known topology of several intrinsic cortical networks, relatively little is known about the white matter regions (i.e., structural connectivity) underlying these networks. In the current study, we have therefore performed fMRI-guided diffusion tensor imaging (DTI) tractography to create probabilistic white matter atlases for eight previously identified functional brain networks, including the Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Primary Visual, Higher Visual and Visuospatial Networks. Methods: Whole-brain diffusion imaging data were acquired from a cohort of 32 healthy volunteers, and were warped to the ICBM template using a two-stage, high-dimensional, non-linear spatial normalization procedure. Deterministic tractography, with fractional anisotropy (FA) ≥0.15 and deviation angle <50°, was then performed using the Fiber Association by Continuous Tracking (FACT) algorithm, and a multi-ROI approach to identify tracts of interest. Regions-of-interest (ROIs) for each of the eight networks were taken from a pre-existing atlas of functionally defined regions to explore all ROI-to-ROI connections within each network, and all resulting streamlines were saved as binary masks to create probabilistic atlases (across participants) for tracts between each ROI-to-ROI pair. Results: The resulting functionally-defined white matter atlases (i.e., for each tract and each network as a whole) were saved as NIFTI images in stereotaxic ICBM coordinates, and have been added to the UManitoba-JHU Functionally-Defined Human White Matter Atlas (http://www.nitrc.org/projects/uofm_jhu_atlas/). Conclusion: To the best of our knowledge, this work represents the first attempt to comprehensively identify and map white matter connectomes for the Auditory, Basal Ganglia, Language, Precuneus, Sensorimotor, Primary Visual, Higher Visual and Visuospatial Networks. Therefore, the resulting probabilistic atlases represent a unique tool for future neuroimaging studies wishing to ascribe voxel-wise or ROI-based changes (i.e., in DTI or other quantitative white matter imaging signals) to these functional brain networks.


Mycophenolate mofetil and tacrolimus as primary maintenance immunosuppression in simultaneous pancreas-kidney transplantation: initial experience in 50 consecutive cases.
The current study examines the use of mycophenolate mofetil (MMF) and tacrolimus as primary immunosuppression in simultaneous pancreas-kidney (SPK) transplantation. In addition, analyses of the rates of conversion from one immunosuppressive agent to another, and its subsequent consequences with respect to outcomes were determined. Quality of graft function, infections, and effect on preexisting essential hypertension are also described. Immunosuppression consisted of quadruple therapy with antithymocyte globulin induction, tacrolimus, MMF, and prednisone. Patient and graft survival and rejection rates in 50 consecutive SPK recipients, followed for a minimum of 3 months and a mean of 14 months (range: 3-34 months), are described. Thirty-nine of 50 (78%) patients tolerated the MMF/tacrolimus combination long-term (mean duration of follow-up: 14+/-7 months). Nine of 50 patients (18%) were converted to Neoral, and 4 patients were converted to azathioprine as a substitute for MMF. The 2-year actuarial patient, kidney, and pancreas survival rates were 97.7%, 93.3%, and 90.0%, respectively. At 6 months after transplant, the overall incidence of acute rejection was 16%. There was a statistically significant (P< or =0.04, Cox-Mantel test) difference in the rate of rejection associated with conversion to Neoral. The incidence of rejection 6 months after transplant in the group maintained on MMF/tacrolimus was 10.2% vs. 44.4% in the group converted to Neoral (P< or =0.04, Cox-Mantel test). Overall, the 1-year actuarial cumulative incidence of tissue-invasive cytomegalovirus disease was 6.6%. There were no cases of fungal infections or post-transplant lymphoproliferative disorders. One patient developed Kaposi's sarcoma 10 months after transplant. With respect to hypertensive disease, 60% (12/20) of the patients who required pharmacologic control of blood pressure before transplant were off all antihypertensive medications at 1 year after transplant. An additional 20% (4/20) of patients had a reduction in the number of medications required to control blood pressure at 1 year after transplant. We conclude that the combination of MMF and tacrolimus as primary immunosuppression for SPK transplantation results in excellent patient and graft survival rates, a very low rate of acute rejection, and low rates of infection and malignancy.


Incidence of pulmonary embolism in total knee arthroplasty.
The end-tidal carbon dioxide concentration (ETCO2) of 47 patients undergoing prosthetic knee operations was monitored to detect pulmonary embolism during the anthroplasties. The ETCO2 of one patient dropped suddenly following the release of the tourniquet and insertion of the bone cement. Intracardiac aspiration did not reveal any air. At autopsy there was massive pulmonary thromboembolism and the deep veins of the right leg contained old formed thrombi. Patients undergoing such procedures should be investigated to exclude the presence of deep vein thrombosis so that measures to prevent pulmonary thromboembolism must be taken well in advance. As regards the occurrence of air embolism it is believed that insertion of the bone cement is the most important single factor in the prevention of air embolism during knee arthroplasty.


Psychometric evaluation of a decision quality instrument for treatment of lumbar herniated disc.
Retrospective and prospective patient surveys and a physician survey using a sample from American Medical Association master file. To evaluate the performance of a new instrument designed to measure the quality of decisions about treatment of herniated disc. There is growing consensus on the importance of engaging and informing patients to improve the quality of significant medical decisions, yet there are no instruments currently available to measure decision quality. The herniated disc-decision quality instrument (HD-DQI) was developed with input from clinical experts, survey research experts, and patients. The HD-DQI produces 2 scores each scaled to 0% to 100%, with higher scores indicating better quality: (1) a total knowledge score and (2) a concordance score (indicating the percentage of patients who received treatments that matched their goals). We examined hypotheses relating to the acceptability, feasibility, validity, and reliability of the instrument, using data from 3 samples. The HD-DQI survey was feasible to implement and acceptable to patients, with good response rates and low missing data. The knowledge score discriminated between patients who had seen a decision aid or no decision aid (55% vs. 38%, P < 0.001) and between providers and patients (73% vs. 46%, P < 0.001). The knowledge score also had good retest reliability (intraclass correlation coefficient = 0.85). Most patients (78%) received treatments that matched their goals. Patients who received treatments that matched their goals were less likely to regret the decision than those who did not (13% vs. 39%, P = 0.004). The HD-DQI met several criteria for high-quality patient-reported survey instruments. It can be used to determine the quality of decisions for treatment of herniated disc. More work is needed to examine acceptability for use as part of routine patient care.


Crystal structure, coloring problem and magnetism of Gd(5-x)Zr(x)Si4.
Ternary Gd(5-x)Zr(x)Si(4) silicides were synthesized by arc melting of the constituent elements and subsequent heat treatments. The Gd(5-x)Zr(x)Si(4) phases adopt the orthorhombic Gd(5)Si(4)-type (space group Pnma) structure for x≤ 0.25 and the tetragonal Zr(5)Si(4)-type (space group P4(1)2(1)2) structure for x≥ 1.0, respectively. The samples with intermediate compositions contain two phases. Single-crystal X-ray diffraction reveals a preferential site occupancy for Zr on the three metal sites in the order of M3 > M2 > M1. Size arguments based on the local coordination environments suggest that the larger Gd atoms preferentially occupy the larger M1 site, while the smaller Zr atoms tend to occupy the smaller metal sites, M2 and M3. Tight-binding linear-muffin-tin orbital calculations illustrate a role of the metal-silicon bonds in the metal site occupation. An increase in the valence electron concentration through the Zr substitution weakens the Si-Si interactions but enhances the metal-silicon and metal-metal interactions. The Curie temperature of Gd(5-x)Zr(x)Si(4) decreases gradually with the increasing Zr content.


Lactation support and breastfeeding duration in jaundiced infants: a randomized controlled trial.
Neonatal jaundice is the most common problem in full-term infants during the immediate post-natal period. We examined the effect of a lactation support intervention on breastfeeding duration in hospitalized jaundiced infants. We conducted a randomized controlled trial with a qualitative component involving mothers of hospitalized jaundiced breastfed infants <4 weeks of age. Mothers receiving the intervention met with an International Board-Certified Lactation Consultant in hospital and 1-3 times post discharge. Both groups received the standard care for jaundice. The primary outcome was exclusive breastfeeding at 3 months. To the exception of research assistants enrolling participants and completing qualitative interviews, all research staff, investigators and statisticians were blinded to group assignment. Qualitative interviews elicited feedback on breastfeeding experiences for both groups. 99 participants were recruited, and 86 analyzed for primary outcome. There was no difference in exclusive breastfeeding at 3 months between groups (RR 0.84, 95% CI 0.56-1.24, p = 0.40) or in the secondary outcomes. 31 participants were included in the qualitative analysis. Participants in the intervention group described an increase in comfort and confidence levels with breastfeeding. Participants in the control group reported limited lactation support. Our hospital-based lactation support program did not result in a higher proportion of mothers exclusively breastfeeding at 3 months compared to current hospital standard care. Qualitative feedback from the intervention group suggests that mothers' confidence was increased, which is linked to breastfeeding duration. The decision to breastfeed is multifactorial and hospital-based lactation support may be only a small piece of the puzzle in hospitalized jaundiced infants. Further studies may be needed to fully elucidate the impact of an in-hospital lactation support program on successful breastfeeding for these infants. ClinicalTrials.gov NCT00966719 https://www.clinicaltrials.gov/ct2/show/NCT00966719?term=Lactation+Support+and+Breastfeeding+Duration+in+Jaundiced+Infants%3A+a+Randomized+Controlled+Trial&rank=1.


Microbial population shift and metabolic characterization of silver diamine fluoride treatment failure on dental caries.
The objective of this pilot study was to describe the microbial profiles present in the plaque and saliva of children who continued to develop new carious lesions following treatment with silver diamine fluoride ("nonresponders") compared to caries active, caries-free, and children immediately receiving SDF treatment for untreated caries in order to identify potential microbial differences that may relate to a re-incidence of caries. Saliva and plaque samples from infected and contralateral sites were obtained from twenty children who were either caries free, had active carious lesions, were caries active and received SDF treatment immediately before sampling, or had previously received SDF treatment and developed new caries. In total, 8,057,899 Illumina-generated sequence reads from 60 samples were obtained. Reads were processed using the Quantitative Insights Into Microbial Ecology pipeline. Group differences were assessed using Analysis of Variance Models and Tukey Honest Significant Differences. To identify significant taxa between treatment groups, Linear discriminant analysis Effect Size (LefSe) and Analysis of Differential Abundance Taking Sample Variation Into Account were used. Differential abundant analysis indicated that members of the Lachnospiraceae family were significantly enriched in non-responders and the genus Tannerella and species Granulicatella adiances were also highly abundant in this group. LefSe analysis between non-responders and SDF-treated groups revealed that genera Leptotrichia and Granulicatella were enriched in non-responders. We observed the highest abundance of phosphotransferase system and lowest abundance of lipopolysaccharide synthesis in non-responders. The microbiome in dental biofilms is responsible for initiation and progression of dental caries. SDF has been shown to be effective in arresting the progression carious lesions, in part due to its antimicrobial properties. Findings suggest that the differential abundance of select microbiota and specific pathway functioning in individuals that present with recurrent decay after SDF treatment may contribute to a potential failure of silver diamine fluoride to arrest dental caries. However, the short duration of sample collection following SDF application and the small sample size emphasize the need for further data and additional analysis.


Chronic intermittent hypoxia-induced cardiovascular and renal dysfunction: from adaptation to maladaptation.
Chronic intermittent hypoxia (CIH) is the dominant pathological feature of human obstructive sleep apnoea (OSA), which is highly prevalent and associated with cardiovascular and renal diseases. CIH causes hypertension, centred on sympathetic nervous overactivity, which persists following removal of the CIH stimulus. Molecular mechanisms contributing to CIH-induced hypertension have been carefully delineated. However, there is a dearth of knowledge on the efficacy of interventions to ameliorate high blood pressure in established disease. CIH causes endothelial dysfunction, aberrant structural remodelling of vessels and accelerates atherosclerotic processes. Pro-inflammatory and pro-oxidant pathways converge on disrupted nitric oxide signalling driving vascular dysfunction. In addition, CIH has adverse effects on the myocardium, manifesting atrial fibrillation, and cardiac remodelling progressing to contractile dysfunction. Sympatho-vagal imbalance, oxidative stress, inflammation, dysregulated HIF-1α transcriptional responses and resultant pro-apoptotic ER stress, calcium dysregulation, and mitochondrial dysfunction conspire to drive myocardial injury and failure. CIH elaborates direct and indirect effects in the kidney that initially contribute to the development of hypertension and later to chronic kidney disease. CIH-induced morphological damage of the kidney is dependent on TLR4/NF-κB/NLRP3/caspase-1 inflammasome activation and associated pyroptosis. Emerging potential therapies related to the gut-kidney axis and blockade of aryl hydrocarbon receptors (AhR) are promising. Cardiorenal outcomes in response to intermittent hypoxia present along a continuum from adaptation to maladaptation and are dependent on the intensity and duration of exposure to intermittent hypoxia. This heterogeneity of OSA is relevant to therapeutic treatment options and we argue the need for better stratification of OSA phenotypes.


Global programmed switch in neural daughter cell proliferation mode triggered by a temporal gene cascade.
During central nervous system (CNS) development, progenitors typically divide asymmetrically, renewing themselves while budding off daughter cells with more limited proliferative potential. Variation in daughter cell proliferation has a profound impact on CNS development and evolution, but the underlying mechanisms remain poorly understood. We find that Drosophila embryonic neural progenitors (neuroblasts) undergo a programmed daughter proliferation mode switch, from generating daughters that divide once (type I) to generating neurons directly (type 0). This typeI>0 switch is triggered by activation of Dacapo (mammalian p21(CIP1)/p27(KIP1)/p57(Kip2)) expression in neuroblasts. In the thoracic region, Dacapo expression is activated by the temporal cascade (castor) and the Hox gene Antennapedia. In addition, castor, Antennapedia, and the late temporal gene grainyhead act combinatorially to control the precise timing of neuroblast cell-cycle exit by repressing Cyclin E and E2f. This reveals a logical principle underlying progenitor and daughter cell proliferation control in the Drosophila CNS.


[Magnetic resonance imaging in craniopharyngiomas. The differential diagnosis of cystic intra- and suprasellar space-occupying lesions].
Seven patients with confirmed craniopharyngiomas were examined via magnetic resonance imaging. The various tumour components (whether solid, cystic or calcified) were evaluated separately. Three types of cysts were observed that can be distinguished by their signal intensity in various pulse sequences. This could be explained largely by an analysis of the T1 and T2 image contrast. The reason for the various types of cysts is determined by their cholesterol content. MR imaging is not as useful as CT for demonstrating the solid and calcified portions of the tumour and this reduces its value in diagnosing the type of tumour. Against that, it is superior with regard to separating the tumour from its neighbouring structures. The differential diagnosis, which must be considered in using MR, is summarised in a table at the end of the paper.


Comparative aspects of meiotic cell cycle control in mammals.
This review examines the mechanisms of cell cycle control in mammalian germ cells with respect to species-specific variations in reproductive strategies. While sex-specific variants are evidenced at the level of checkpoint controls, the timing of meiotic progression, and the modulation of meiosis by hormonal cues, local somatic cell influences impose a hierarchical order to both the initiation and completion of gametogenesis. In the particular case of meiosis in females the rules governing entry into meiotic prophase during gonadal development are generally conserved. In contrast, the regulation of meiotic arrest in developing ovarian follicles, the reinitiation of meiosis at ovulation, and the completion of meiosis upon fertilization involves changes in both the cell cycle machinery and execution of external cues. The overall efficiency of meiotic progression is determined by inputs, mediated by cell contact and/or growth factor, which coordinate oogenesis with folliculogenesis and ensure appropriate and species-specific ovulatory outputs (monovular or polyovular). How mechanisms of meiotic cell cycle control can be exploited to improve gamete quality or interfere with fertility is discussed.


Variations in the abundance of three Parulidae species in the southern portion of the Brazilian Atlantic Forest, state of Paraná.
We evaluated the distribution of abundance of three species of warblers in the southern portion of the Brazilian Atlantic Forest (BAF): Tropical Parula (Parula pitiayumi), the Golden-Crowned Warbler (Basileuterus culicivorus) and the White-Rimmed Warbler (Basileuterus leucoblepharus). Three types of forests comprise this region of the Atlantic Forest: seasonal semi-deciduous forest (SF), mixed rain forest (MF) and dense rain forest (DF). These forest types occur at different elevations: SF ranging from 200 to 800 m, MF ranging from 800 to 1,200 m and DF ranging from sea level up to 2,000 m. We used point counts in fifteen study areas distributed in the three forest types. The White-Rimmed Warbler and the Tropical Parula had higher abundances in MF, and their abundance was positively correlated with the elevation. The Golden-Crowned Warbler did not present a significant difference in abundance among the forest types, and no correlation between abundance and elevation was found. We suggest that the difference in the occupancy of the forest strata by the Golden-Crowned Warbler is because this species is more generalist and thus less sensitive to variations in the vegetation structure among the forests types when compared to the other two warbler species.


Immunohistochemical evaluation of hormone receptors with predictive value in mammary carcinomas.
AIMS. Immunohistochemical evaluation of hormone receptors (ER, PR) and correlation of immunohistochemical and morpho-clinical data. METHOD. The study was performed on paraffin-embedded and HE stained tissues originating from 100 cases of invasive mammary carcinoma. Monoclonal antibodies anti-estrogen and anti progesterone receptors were used for the immunohistochemical study. The detection system was EnVision HRP and the visualization system was 3-3' diaminobenzidine tetrahydrochloride (DAB). The evaluation of the result was performed using the Allred score. REZULTS. The majority of the studied cases (57%) expressed both types of hormone receptors and in 32% of the cases the hormone receptors were completely absent. The rest of the cases presented a heterogeneous phenotype: 7% presented the ER-/PR+ type and 4%, the ER+/PR- type. Compared with the classical phenotype (ER+/PR-), ER+/PR- tumors were more frequent at patients over 50 years. The tumors with ER+/PR- were larger than the ER+/PR+ and they were of the invasive ductal carcinoma type with an Allred score for ER under 6. CONCLUSION. The predictive value is amplified when the ER status is correlated with the PR status because the heterogeneous phenotypes are identified, especially the ER+/PR- phenotype which have an aggressive behavior and the lowest response to tamoxifen therapy.