Connecting Mobility to Infectious Diseases: The Promise and Limits of Mobile Phone Data.
Human travel can shape infectious disease dynamics by introducing pathogens into susceptible populations or by changing the frequency of contacts between infected and susceptible individuals. Quantifying infectious disease-relevant travel patterns on fine spatial and temporal scales has historically been limited by data availability. The recent emergence of mobile phone calling data and associated locational information means that we can now trace fine scale movement across large numbers of individuals. However, these data necessarily reflect a biased sample of individuals across communities and are generally aggregated for both ethical and pragmatic reasons that may further obscure the nuance of individual and spatial heterogeneities. Additionally, as a general rule, the mobile phone data are not linked to demographic or social identifiers, or to information about the disease status of individual subscribers (although these may be made available in smaller-scale specific cases). Combining data on human movement from mobile phone data-derived population fluxes with data on disease incidence requires approaches that can tackle varying spatial and temporal resolutions of each data source and generate inference about dynamics on scales relevant to both pathogen biology and human ecology. Here, we review the opportunities and challenges of these novel data streams, illustrating our examples with analyses of 2 different pathogens in Kenya, and conclude by outlining core directions for future research.


Two-year clinical, angiographic, and serial optical coherence tomographic follow-up after implantation of an everolimus-eluting bioresorbable scaffold and an everolimus-eluting metallic stent: insights from the randomised ABSORB Japan trial.
We sought to investigate two-year clinical and serial optical coherence tomography (OCT) outcomes after implantation of a fully bioresorbable vascular scaffold (BVS) or a cobalt-chromium everolimus-eluting stent (CoCr-EES). In the ABSORB Japan trial, 400 patients were randomised in a 2:1 ratio to BVS (N=266) or CoCr-EES (N=134). A pre-specified OCT subgroup (N=125, OCT-1 group) underwent angio-graphy and OCT post procedure and at two years. Overall, the two-year TLF rates were 7.3% and 3.8% in the BVS and CoCr-EES arms (p=0.18), respectively. Very late scaffold thrombosis (VLST) beyond one year was observed in 1.6% (four cases: all in non-OCT-1 subgroups) of the BVS arm, while there was no VLST in the CoCr-EES arm. In three cases, OCT at the time of or shortly after VLST demonstrated strut discontinuities, malapposition and/or uncovered struts. However, the vessel healing by two-year OCT was nearly complete in both BVS and CoCr-EES arms with almost fully covered struts, and minimal malapposition. The flow area by two-year OCT was smaller in the BVS arm than in the CoCr-EES arm, mainly due to tissue growth inside the device. However, there were no differences between the BVS and CoCr-EES with regard to the quality of homogenous tissues growing inside the devices. The rate of TLF was numerically higher in the BVS arm than in the CoCr-EES arm, although this difference was not statistically significant. VLST was observed only in the BVS arm at a rate of 1.6% between one and two years. Further studies are mandatory to investigate the risk of BVS relative to metallic stents for VLST, and the underlying mechanisms of BVS VLST.


Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21).
Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of a sex chromosome were more frequent in patients with t(8;21): 15% vs 0.4% for del(9q), 37% vs 0% for loss of X in females, and 44% vs 5% for loss of Y in males. Hyperdiploidy was more frequent in patients with inv(16) (25% vs 9%, whereas hypodiploidy was more frequent in patients with t(8;21) (37% vs 3%. In multivariable analyses (adjusted for age, white blood counts at diagnosis, and KIT mutation status), trisomy 8 was associated with improved overall survival (OS) in inv(16), whereas the presence of other chromosomal abnormalities (not trisomy 8) was associated with decreased OS. In patients with t(8;21), hypodiploidy was associated with improved disease-free survival; hyperdiploidy and del(9q) were associated with improved OS. KIT mutation (either positive or not tested, compared with negative) conferred poor prognoses in univariate analysis only in patients with t(8;21).


Instantaneous center of rotation behavior of the lumbar spine with ligament failure.
The goal of this study was to investigate the effect of ligament failure on the instantaneous center of rotation (ICR) in the lower lumbar spine. A 3D finite element model of the L4-5 segment was obtained and validated. Ligament failure was simulated by reducing ligaments in a stepwise manner from posterior to anterior. A pure bending moment of 7.5 Nm was applied to the model in 3 anatomical planes for the purpose of validation, and a 6-Nm moment was applied to analyze the effect of ligament failure. For each loading case, ligament reduction step, and load increment, the range of motion of the segment and the ICR of the mobile (L-4) vertebra were calculated and characterized. The present model showed a consistent increase in the range of motion as the ligaments were removed, which was in agreement with the literature reporting the kinematics of the L4-5 segment. The shift in the location of the ICR was below 5 mm in the sagittal plane and 3 mm in both the axial and coronal planes. The location of the ICR changed in all planes of motion with the simulation of multiple ligament injury. The removal of the ligaments also changed the load sharing within the motion segment. The change in the center of rotation of the spine together with the change in the range of motion could have a diagnostic value, revealing more detailed information on the type of injury, the state of the ligaments, and load transfer and sharing characteristics of the segment.


Complex repolarization dynamics in ex vivo human ventricles are independent of the restitution properties.
The mechanisms of transition from regular rhythms to ventricular fibrillation (VF) are poorly understood. The concordant to discordant repolarization alternans pathway is extensively studied; however, despite its theoretical centrality, cannot guide ablation. We hypothesize that complex repolarization dynamics, i.e. oscillations in the repolarization phase of action potentials with periods over two of classic alternans, is a marker of electrically unstable substrate, and ablation of these areas has a stabilizing effect and may reduce the risk of VF. To prove the existence of higher-order periodicities in human hearts. We performed optical mapping of explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Signals recorded from the right ventricle endocardial surface were processed to detect global and local repolarization dynamics during rapid pacing. A statistically significant global 1:4 peak was seen in three of six hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of Periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel. We present evidence of complex higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex vivo human hearts. We infer that the oscillation of the calcium cycling machinery is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability and may provide targets for substrate-based ablation of VF.


Occupational therapy assessment and treatment approach in patients with subacute and chronic stroke: A single-blind, prospective, randomized clinical trial.
The aim of this study was to examine the effects of occupational therapy (OT) combined with standard rehabilitation (SR) on the activities of daily living, quality of life, and psychological symptoms of hemiplegic patients. Between August 2014 and February 2016, a total of 35 hemiplegic patients with post-diagnostic periods (19 males, 16 females; mean age 58.3 years; range 37 to 77 years) were included. The patients were randomized into two groups as OT+SR group (n=17) and SR only group (n=18). The study was completed by 16 patients in each group. The patients in the OT group were given 45-min SR five days a week plus 45-min OT three days a week over an eight-week period, while the patients in the SR group received SR only (of the same duration and frequency as the OT group). The patients were assessed at enrolment (pre-treatment), and again after eight weeks of treatment using the Pinch and Grip Strength and the Purdue Pegboard tests, Global Daily Living Activities Scale, Performance Assessment of Self-care Skills (PASS), Nottingham Extended Activities of Daily Living (NEADL) Scale, Quality of Life Short Form (SF-36) Questionnaire, and Hospital Anxiety and Depression Scale (HAD) for their psychological state. Significant improvements were observed in within-group scores for PASS, Pinch and Grip Strength Test, NEADL Scale, and Purdue Pegboard test (p<0.05). After treatment, a significant increase was found in the SF-36 physical function, general health and physical total in-group scores of the OT group, whereas a significant increase was observed only in the physical total scores of the SR group (p<0.05). There was no significant improvement in the HAD scores within both groups (p>0.05). Inter-group comparisons revealed a further significant improvement in PASS instrumental daily activity index-physical subscale and Purdue Pegboard Test scores of the OT group (p<0.05). However, there was no significant difference in PASS activity, self-care and instrumental daily activity cognitive subscale, SF-36, HAD and hand grip and pinch strength scores between the groups (p>0.05). Occupational therapy combined with SR applications has a beneficial impact on certain daily living activities and hand functions. Occupational therapy does not have any additional benefits on the quality of life, pinch and grip strength, and the psychological state.


Comparing terpenes from plant essential oils as pesticides for the poultry red mite (Dermanyssus gallinae).
Resistance to conventional synthetic pesticides has been widely reported in ticks, parasitic mites and other pests of veterinary and medical significance. New and novel approaches to manage these pests are therefore needed to ensure efficient control programmes that can be implemented now and in the future. Recent research in this area has focused on the pesticidal potential of plant essential oils. These products are attractive as pesticide candidates on the grounds of low mammalian toxicity, short environmental persistence and complex chemistries (limiting the development of pest resistance against them). Although issues may exist concerning reliability in efficacy of essential oils, these may be overcome by identifying and developing bioactive oil components for use in pest management. In the current work, three such components (terpenes) found in essential oils (eugenol, geraniol and citral) were tested against the poultry red mite Dermanyssus gallinae. All provided 100% mortality in toxicity tests when undiluted. Even at 1% of this dose, eugenol was 20% effective against experimental pest populations, although the remaining terpenes were largely ineffective at this concentration.


PTEN plasticity: how the taming of a lethal gene can go too far.
PTEN loss drives many cancers and recent genetic studies reveal that often PTEN is antagonised at the protein level without alteration of DNA or RNA expression. This scenario can already cause malignancy, because PTEN is haploinsufficient. We here review normally occurring mechanisms of PTEN protein regulation and discuss three processes where PTEN plasticity is needed: ischaemia, development, and wound healing. These situations demand transient PTEN suppression, whereas cancer exploits them for continuous proliferation and survival advantages. Therefore, increased understanding of PTEN plasticity may help us better interpret tumour development and ultimately lead to drug targets for PTEN supporting cancer therapy.


Mapping biomass with remote sensing: a comparison of methods for the case study of Uganda.
Assessing biomass is gaining increasing interest mainly for bioenergy, climate change research and mitigation activities, such as reducing emissions from deforestation and forest degradation and the role of conservation, sustainable management of forests and enhancement of forest carbon stocks in developing countries (REDD+). In response to these needs, a number of biomass/carbon maps have been recently produced using different approaches but the lack of comparable reference data limits their proper validation. The objectives of this study are to compare the available maps for Uganda and to understand the sources of variability in the estimation. Uganda was chosen as a case-study because it presents a reliable national biomass reference dataset. The comparison of the biomass/carbon maps show strong disagreement between the products, with estimates of total aboveground biomass of Uganda ranging from 343 to 2201 Tg and different spatial distribution patterns. Compared to the reference map based on country-specific field data and a national Land Cover (LC) dataset (estimating 468 Tg), maps based on biome-average biomass values, such as the Intergovernmental Panel on Climate Change (IPCC) default values, and global LC datasets tend to strongly overestimate biomass availability of Uganda (ranging from 578 to 2201 Tg), while maps based on satellite data and regression models provide conservative estimates (ranging from 343 to 443 Tg). The comparison of the maps predictions with field data, upscaled to map resolution using LC data, is in accordance with the above findings. This study also demonstrates that the biomass estimates are primarily driven by the biomass reference data while the type of spatial maps used for their stratification has a smaller, but not negligible, impact. The differences in format, resolution and biomass definition used by the maps, as well as the fact that some datasets are not independent from the reference data to which they are compared, are considered in the interpretation of the results. The strong disagreement between existing products and the large impact of biomass reference data on the estimates indicate that the first, critical step to improve the accuracy of the biomass maps consists of the collection of accurate biomass field data for all relevant vegetation types. However, detailed and accurate spatial datasets are crucial to obtain accurate estimates at specific locations.


Outcomes following prolonged preterm premature rupture of the membranes.
Rupture of the membranes in the second trimester is reported to be associated with high rates of pregnancy loss, neonatal mortality and morbidity. This article describes the outcomes of liveborn infants delivered following a prolonged period of membrane rupture occurring before 24 weeks' gestation. Over a 5-year period, consecutive pregnancies complicated by spontaneous rupture of the membranes before 24 weeks' gestation were identified. Evaluation of short-term outcomes before discharge of liveborn infants delivered, in a tertiary referral centre, following prolonged rupture of membranes of duration greater than 2 weeks. Of 98 pregnancies identified with rupture of the membranes before 24 weeks' gestation, 40 (41%) women progressed to deliver a liveborn infant following a latent period of at least 14 days. Although most liveborn infants required neonatal intensive care including mechanical ventilation (n = 38; 78%), the survival rate to hospital discharge was 70% (n = 28). Airleak occurred in 7 (25%) survivors and 8 (67%) deaths. Among the survivors, 12 (43%) required supplemental oxygen at 36 weeks' postmenstrual age and no infant had grade 3 or 4 intraventricular haemorrhage. One infant had a postmortem diagnosis of pulmonary hypoplasia and nine others had clinical features consistent with this diagnosis. Low liquor volume was not uniformly associated with a poor outcome. With full contemporary neonatal intensive care, the outcome for liveborn infants in the present cohort delivered following membrane rupture occurring before 24 weeks' gestation, of at least 14 days duration, was better than previously reported.


Paper mill residuals and compost effects on soil carbon and physical properties.
Use of organic by-products as soil amendments in agricultural production exemplifies a strategy for converting wastes to resources. The overall objective of this research was to evaluate the short- and intermediate-term effects of repeatedly amending sandy soil with paper mill residuals (PMR) and composted PMR in a vegetable rotation in Wisconsin's Central Sands. Specifically, we investigated the effects of PMR and composted PMR on total soil C and related these to changes in water-holding capacity and plant-available water (PAW). Amendment effects on irrigation requirements were estimated with a simple soil water balance model. The experimental design was replicated five times as a randomized complete block with four organic amendments: raw PMR, PMR composted alone (PMRC), PMR composted with bark (PMRB), and peat applied at two rates and a non-amended control. All amended treatments significantly increased total soil C relative to the nonamended control following applications in 1998 and 1999. One year following the second serial amendment, all PMR treatments increased PAW by 5 to 45% relative to the control. There was a significant positive linear relationship between total soil C and PAW. All amended treatments reduced the average amount of irrigation water required for potato production by 4 to 30% and the number of irrigation events by 10 to 90%. There was a clear trend of greater reduction in irrigation requirements with more carbon added. The cumulative effects of repeated additions of PMRB suggest that certain composts might sustain elevated PAW and reduce irrigation requirements beyond one year.


Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study.
The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration. HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1, 1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy. Of 10,056 patients from 25 cohorts, 9102 (90·5%) had HIV without TDR, 475 (4·7%) had at least one mutation but received fully-active cART, and 479 (4·8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4·2% (95% CI 3·8-4·7) for patients in the no TDR group, 4·7% (2·9-7·5) for those in the TDR and fully-active cART group, and 15·1% (11·9-19·0) for those in the TDR and resistant group (log-rank p<0·0001). The hazard ratio for the difference in virological failure between patients with TDR and resistance to at least one drug and those without TDR was 3·13 (95% CI 2·33-4·20, p<0·0001). The hazard ratio for the difference between patients with TDR receiving fully-active cART and patients without TDR was 1·47 (95% CI 0·19-2·38, p=0·12). In stratified analysis, the hazard ratio for the risk of virological failure in patients with TDR who received fully-active cART that included a non-nucleoside reverse transcriptase inhibitor (NNRTI) compared with those without TDR was 2·0 (95% CI 0·9-4·7, p=0·093). These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients. European Community's Seventh Framework Programme FP7/2007-2013 and Gilead.


Black race and distant recurrence after neoadjuvant or adjuvant chemotherapy in breast cancer.
Black race compared to white race is associated with more advanced stage and biologically aggressive breast cancer. Consequently, black patients are more frequently treated with neoadjuvant chemotherapy (NAC) than white patients. However, it is unclear how distant recurrence-free survival (DRFS) of black patients treated with NAC, compares to DRFS of black patients treated with adjuvant chemotherapy (AC). We evaluated the association between race, distant recurrence, and type of chemotherapy (AC or NAC) in localized or locally advanced breast cancer. We evaluated DRFS in 807 patients, including 473 black, 252 white, 56 Hispanic, and 26 women of other or mixed race. The association between AC or NAC and DRFS was examined using multivariate Cox proportional hazard models that included race, age, stage, estrogen receptor (ER) and triple negative (TN) status. When the black and white subjects were pooled for the analysis the features associated with worse DRFS included stage III disease and age < 50 years, but not ER-negative disease, TN disease, the use of NAC, or black race. However, in the analysis stratified by race NAC was associated with worse DRFS compared to AC in black (HR 2.70; 95% CI 1.73-4.22; p < 0.0001), but not in white women (HR 1.29, 95% CI 0.56-2.95; p = 0.36). Black patients treated with NAC had worse DRFS than black patients treated with AC, or white patients treated with either NAC or AC. These findings need to be validated in a large-scale observational study and the effect of NAC on the breast cancer microenvironment in black women needs to be further evaluated.


'The chicken and egg thing': cognitive representations and self-management of multimorbidity in people with diabetes and depression.
Diabetes with depression is common and can lead to poorer outcomes in both conditions. The existing literature has demonstrated that patients' single condition representations inform self-management, but less is known about the composition and impact of multimorbid representations. This study aimed to explore accounts of multimorbidity with a focus on the content of cognitive representations and reported management of diabetes and depression. Semi-structured qualitative interviews were carried out with 17 people with diabetes and depression. Data were audio-taped, transcribed and analysed using an inductive thematic analysis and elements of grounded theory. The nature of multimorbid representations varied and some participants, in particular those who prioritised other conditions, described diabetes and depression as unrelated and managed each separately. Others saw interactions between conditions, often in terms of causation, and described how diabetes and depression management could be either integrated or conflicting. Problems taking multiple-medications were frequently described, but participants differed in the confidence with which they described representations of multimorbidity. People hold multimorbid representations that appear to impact on their preferred self-management. An awareness of patients' understanding of multimorbidity could have implications for the provision of care and intervention design in this population.


Transfection of human ovarian cancer cells with the HER-2/neu receptor tyrosine kinase induces a selective increase in PTP-H1, PTP-1B, PTP-alpha expression.
Protein tyrosine phosphorylation is a key regulator of cell growth regulation and, when aberrant, is linked with the process of oncogenic transformation. Since tyrosine phosphatases (PTP) reverse phosphorylation mediated by tyrosine kinases (PTK), it has been hypothesized, but insufficiently studied to date, that PTPs function as tumor suppressors. Alternatively, PTPs may augment signal transduction by repriming substrates. To begin to assess the role of PTPs in ovarian cancer cell growth regulation, PTP partial cDNAs were cloned from the OVCA 433 ovarian cancer cell line using RT/PCR and degenerate oligonucleotide primers for the PTP consensus domain. Thirteen partial cDNAs were isolated, the sequences of which, when compared to GenBank, suggested that they were derived from PTP family members. These included PTP-alpha, PTP-gamma, LAR, PTP-delta, T-cell PTP, PTP-2A(1D), PTP-1B, PTP-1C, PTP-H1, PTP-PEST, PTP-Gallus, and two isolates which potentially represent novel PTPs. Steady-state expression analyses revealed that PTP-1B expression was undetectable in normal epithelium but was expressed in four of five ovarian cancer cell lines. In contrast, the expression of two SH2-containing PTPs, PTP-1C and PTP-2A, was detected in the normal ovarian epithelium but lost from one or more ovarian cancer cell lines. Finally, PTP-1B, PTP-alpha, and PTP-H1 expression was increased following HER-2/neu transfection of ovarian cancer cell lines. These results suggest that both normal ovarian epithelial cells and ovarian cancer cells express multiple PTPs. Further, some PTPs are differentially expressed between normal ovarian epithelium and ovarian cancer cells. Intriguingly, the transfection and increased expression of the prognostically significant HER-2/neu PTK induced a selective increase in the expression of the PTP-alpha, PTP-1B, and PTP-H1 tyrosine phosphatases.


Carbohydrate-Free Peach (Prunus persica) and Plum (Prunus salicina) [corrected] Juice Affects Fecal Microbial Ecology in an Obese Animal Model.
Growing evidence shows the potential of nutritional interventions to treat obesity but most investigations have utilized non-digestible carbohydrates only. Peach and plum contain high amounts of polyphenols, compounds with demonstrated anti-obesity effects. The underlying process of successfully treating obesity using polyphenols may involve an alteration of the intestinal microbiota. However, this phenomenon is not well understood. Obese Zucker rats were assigned to three groups (peach, plum, and control, n = 10 each), wild-type group was named lean (n = 10). Carbohydrates in the fruit juices were eliminated using enzymatic hydrolysis. Fecal samples were obtained after 11 weeks of fruit or control juice administration. Real-time PCR and 454-pyrosequencing were used to evaluate changes in fecal microbiota. Over 1,500 different Operational Taxonomic Units at 97% similarity were detected in all rats. Several bacterial groups (e.g. Lactobacillus and members of Ruminococcacea) were found to be more abundant in the peach but especially in the plum group (plum juice contained 3 times more total polyphenolics compared to peach juice). Principal coordinate analysis based on Unifrac-based unweighted distance matrices revealed a distinct separation between the microbiota of control and treatment groups. These changes in fecal microbiota occurred simultaneously with differences in fecal short-chain acids concentrations between the control and treatment groups as well as a significant decrease in body weight in the plum group. This study suggests that consumption of carbohydrate-free peach and plum juice has the potential to modify fecal microbial ecology in an obese animal model. The separate contribution of polyphenols and non-polyphenols compounds (vitamins and minerals) to the observed changes is unknown.


Interfacial rheological properties of self-assembling biopolymer microcapsules.
Tuning the mechanical properties of microcapsules through a cost-efficient route of fabrication is still a challenge. The traditional method of layer-by-layer assembly of microcapsules allows building a tailored composite multi-layer membrane but is technically complex as it requires numerous steps. The objective of this article is to characterize the interfacial rheological properties of self-assembling biopolymer microcapsules that were obtained in one single facile step. This thorough study provides new insights into the mechanics of these weakly cohesive membranes. Firstly, suspensions of water-in-oil microcapsules were formed in microfluidic junctions by self-assembly of two oppositely charged polyelectrolytes, namely chitosan (water soluble) and phosphatidic fatty acid (oil soluble). In this way, composite membranes of tunable thickness (between 40 and 900 nm measured by AFM) were formed at water/oil interfaces in a single step by changing the composition. Secondly, microcapsules were mechanically characterized by stretching them up to break-up in an extensional flow chamber which extends the relevance and convenience of the hydrodynamic method to weakly cohesive membranes. Finally, we show that the design of microcapsules can be 'engineered' in an extensive way since they present a wealth of interfacial rheological properties in terms of elasticity, plasticity and yield stress whose magnitudes can be controlled by the composition. These behaviors are explained by the variation of the membrane thickness with the physico-chemical parameters of the process.


The biology of Frankia sp. strains in the post-genome era.
Progress in understanding symbiotic determinants involved in the N(2)-fixing actinorhizal plant symbioses has been slow but steady. Problems persist with studying the bacterial contributions to the symbiosis using traditional microbiological techniques. However, recent years have seen the emergence of several genomes from Frankia sp. strains and the development of techniques for manipulating plant gene expression. Approaches to understanding the bacterial side of the symbiosis have employed a range of techniques that reveal the proteomes and transcriptomes from both cultured and symbiotic frankiae. The picture beginning to emerge provides some perspective on the heterogeneity of frankial populations in both conditions. In general, frankial populations in root nodules seem to maintain a rather robust metabolism that includes nitrogen fixation and substantial biosynthesis and energy-generating pathways, along with a modified ammonium assimilation program. To date, particular bacterial genes have not been implicated in root nodule formation but some hypotheses are emerging with regard to how the plant and microorganism manage to coexist. In particular, frankiae seem to present a nonpathogenic presence to the plant that may have the effect of minimizing some plant defense responses. Future studies using high-throughput approaches will likely clarify the range of bacterial responses to symbiosis that will need to be understood in light of the more rapidly advancing work on the plant host.


Effect of serum 25-hydroxyvitamin D level on lung, breast, colorectal and prostate cancers: a nested case-control study.
Published studies show that vitamin D deficiency is widespread and it has been suggested that it increases the risk of lung, breast, colorectal and prostate cancers. To investigate prospectively the effect of serum 25-hydroxyvitamin D (25(OH)D) level on lung, breast, colorectal and prostate cancers in people aged 30+ years. In this nested case-control study, the data and collected serum samples from a cohort study, the Balçova Heart Study, during 2007-09, were used. Additional data were collected using a questionnaire in the follow-up. We determined incident lung, breast, colorectal and prostate cancer cases during 2008 and 2013. Serum 25(OH)D levels of 606 persons (179 cases and 427 controls) from the Balçova Heart Study were measured. Odds ratio (OR) and 95% confidence interval (CI) were calculated using logistic regression analysis. Serum 25(OH)D levels did not show a significant association with breast, colorectal and prostate cancers. There was an inverse association between 25(OH)D level and lung cancer risk, where the OR values for the first, second and third quartiles, compared with the fourth quartile (1.00), were 2.92 (CI: 0.82-10.35), 3.76 (CI: 1.14-12.37) and 3.55 (CI: 1.04- 12.08) respectively. It was seen that low 25(OH)D levels were associated with a greater than threefold increased risk of lung cancer; no association was detected for breast, colorectal and prostate cancers. Cohort studies with larger populations are needed to better understand the effect of vitamin D level on cancer risk.


Intraneural stimulation elicits discrimination of textural features by artificial fingertip in intact and amputee humans.
Restoration of touch after hand amputation is a desirable feature of ideal prostheses. Here, we show that texture discrimination can be artificially provided in human subjects by implementing a neuromorphic real-time mechano-neuro-transduction (MNT), which emulates to some extent the firing dynamics of SA1 cutaneous afferents. The MNT process was used to modulate the temporal pattern of electrical spikes delivered to the human median nerve via percutaneous microstimulation in four intact subjects and via implanted intrafascicular stimulation in one transradial amputee. Both approaches allowed the subjects to reliably discriminate spatial coarseness of surfaces as confirmed also by a hybrid neural model of the median nerve. Moreover, MNT-evoked EEG activity showed physiologically plausible responses that were superimposable in time and topography to the ones elicited by a natural mechanical tactile stimulation. These findings can open up novel opportunities for sensory restoration in the next generation of neuro-prosthetic hands.


Modulation of pituitary gonadotropin-releasing hormone receptors during lactation in the rat.
Lactation is associated with a suppression of pituitary GnRH receptors (GnRH-R), and removal of the suckling stimulus for 24 h causes a 4- to 5-fold increase in GnRH-R. These studies were designed to examine the time course of recovery of GnRH-R after pup removal and to determine the roles that GnRH and PRL may play in modulating GnRH-R during lactation and after pup removal. All studies were performed on day 10 postpartum using ovariectomized rats suckling eight or zero pups. GnRH-R had more than doubled by 8 h after pup removal and had increased 4-5 times 16 h after pup removal to reach levels observed in nonsuckled controls. The increase in GnRH-R after pup removal resulted in a significant increase in pituitary responsiveness to GnRH. Maintenance of hyperprolactinemia after pup removal, by injecting ovine PRL, reduced the increase in GnRH-R by about 50%. Simultaneous administration of GnRH with ovine PRL restored GnRH-R to control levels. Administration of a potent antiserum to GnRH at the time of pup removal completely blocked the up-regulation of GnRH-R 24 h later. In the presence of the suckling stimulus and hyperprolactinemia, administration of pharmacological doses of GnRH caused a complete restoration of GnRH-R to levels observed in nonsuckled controls. Inhibition of suckling-induced PRL secretion with CB-154 caused a 2-fold increase in GnRH-R, and this effect could be completely reversed by simultaneous treatment with ovine PRL. These studies show that the suppression of pituitary GnRH-R during lactation appears to be due primarily to inhibition of GnRH secretion. After pup removal, recovery of GnRH-R occurs very rapidly, with recovery (4- to 5-fold increase) being completed by 16 h. Endogenous GnRH secretion is absolutely necessary for the up-regulation of GnRH-R to occur. The decrease in PRL levels after pup removal contributes to this process, most likely by causing an increase in GnRH secretion.


Increased expression level of Hsp70 in the inner ears of mice by exposure to low frequency noise.
Previous studies showed that people in urban areas are possibly exposed to 60-110 dB of low frequency noise (LFN) defined as noise of ≤100 Hz in their daily life. Previous studies also showed increased health risks by exposure to high levels (130-140 dB) of LFN in animals. However, little is known about the health effects of exposure to an ordinary level of LFN. We biochemically and immunohistochemically assessed the effects of exposure to inaudible LFN for mice (12 h/day of 100 Hz LFN at 95 dB for 5 days), at a level to which people are possibly exposed in daily life, on a murine inner ear by targeting 9 stress-reactive molecules. There was more than a 5-fold increased transcript level of heat shock protein 70 (Hsp70) in the whole inner ear exposed to LFN. However, the transcript levels of the other 8 stress-reactive molecules including Hsp27 and Hsp90 were comparable in LFN-exposed and unexposed murine inner ears. Only the transcript level of Cebpβ among the previously reported 4 transcriptional activators for Hsp70 expression was more than 3-fold increased by LFN exposure. Hsp70 transcript expression levels in the inner ears 3 days after LFN exposure were comparable to those in unexposed inner ears. The protein level of Hsp70, but not the levels of Hsp27 and Hsp90, was also increased in the vestibule by LFN exposure. However, hearing levels as well as expression levels of Hsp70 protein in the cochleae were comparable in LFN-exposed mice and unexposed mice. Our results demonstrated that the inner ear might be one of the organs that is negatively affected by stress from inaudible LFN exposure. Moreover, LFN exposure might increase Hsp70 expression level via Cebpβ in the inner ear. Thus, Hsp70 and Cebpβ levels could be candidates of biomarkers for response to LFN exposure.


Significant interactions between maternal PAH exposure and haplotypes in candidate genes on B[a]P-DNA adducts in a NYC cohort of non-smoking African-American and Dominican mothers and newborns.
Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[a]pyrene (B[a]P) is a well-studied PAH that is classified as a probable human carcinogen. Within our New York City-based cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn haplotypes (and in one case, a single-nucleotide polymorphism) in key B[a]P metabolism genes on B[a]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking African-American (n = 132) and Dominican (n = 235) women with available data on maternal PAH exposure, paired cord adducts and genetic data who resided in the Washington Heights, Central Harlem and South Bronx neighborhoods of New York City. We selected seven maternal and newborn genes related to B[a]P metabolism, detoxification and repair for our analyses: CYP1A1, CYP1A2, CYP1B1, GSTM3, GSTT2, NQO1 and XRCC1. We found significant interactions between maternal PAH exposure and haplotype on cord B[a]P-DNA adducts in the following genes: maternal CYP1B1, XRCC1 and GSTM3, and newborn CYP1A2 and XRCC1 in African-Americans; and maternal XRCC1 and newborn NQO1 in Dominicans. These novel findings highlight differences in maternal and newborn genetic contributions to B[a]P-DNA adduct formation, as well as ethnic differences in gene-environment interactions, and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[a]P.


The intestinal parasite Pomphorhynchus laevis (Acanthocephala) interferes with the uptake and accumulation of lead (210Pb) in its fish host chub (Leuciscus cephalus).
Uninfected chub as well as fish experimentally infected with the acanthocephalan parasite Pomphorhynchus laevis were exposed to (210)Pb(2+) for up to 38 days and the uptake and distribution of lead within different fish organs and the parasites was determined at various time points. Highest metal concentrations were detected in the acanthocephalans, followed by intestine, bile, liver, gill and muscle of the fish host. Infected chub had significantly lower (210)Pb levels in the gills on day 17 (P< or =0.01), in the bile on day 24 (P< or =0.05) and in the gills as well as in the intestine on day 38 compared with uninfected fish. A subsequent polynomial regression revealed that lead levels for the infected fish ranged below the levels determined for uninfected fish during most of the exposure period. This is the first proof that P. laevis reduces lead levels in the bile thereby diminishing or even impeding the hepatic intestinal cycling of lead, which may reduce the amount of metals available for the fish organs. This is especially important for ecotoxicological research. For example, organisms used as accumulation indicators may erroneously indicate low levels of pollution if they are infected with parasites which alter their pollutant uptake mechanisms. Additionally, the results gave further experimental evidence for acanthocephalans as accumulation indicators for metals.


Aluminum toxicity in patients with chronic renal failure.
During the past two decades, in association with the commencement of chronic dialysis therapy and prolongation of the uremic state, aluminum toxicity has represented a major cause of morbidity and mortality in uremic patients. The uremic patient has been found to be at higher risk of aluminum loading and toxicity from various sources of parenteral exposure, enhanced gastrointestinal absorption, and compromised ability to eliminate any systemically administered aluminum due to renal impairment. However, the potential sources of aluminum exposure and loading resulting in toxicity in uremic patients have recently been identified. As a result, this toxicity can largely be prevented by eliminating aluminum from the water used to prepare the dialysate, substituting calcium-containing phosphate-binding agents for those containing aluminum, and strict avoidance of the concomitant use of citrate- and aluminum-containing compounds. Thus, in the future, aluminum toxicity should represent a rare and unusual side effect in dialyzed uremic patients.


Health outcomes of continuous positive airway pressure versus oral appliance treatment for obstructive sleep apnea: a randomized controlled trial.
Continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) therapy are commonly used to treat obstructive sleep apnea (OSA). Differences in efficacy and compliance of these treatments are likely to influence improvements in health outcomes. To compare health effects after 1 month of optimal CPAP and MAD therapy in OSA. In this randomized crossover trial, we compared the effects of 1 month each of CPAP and MAD treatment on cardiovascular and neurobehavioral outcomes. Cardiovascular (24-h blood pressure, arterial stiffness), neurobehavioral (subjective sleepiness, driving simulator performance), and quality of life (Functional Outcomes of Sleep Questionnaire, Short Form-36) were compared between treatments. Our primary outcome was 24-hour mean arterial pressure. A total of 126 patients with moderate-severe OSA (apnea hypopnea index [AHI], 25.6 [SD 12.3]) were randomly assigned to a treatment order and 108 completed the trial with both devices. CPAP was more efficacious than MAD in reducing AHI (CPAP AHI, 4.5 ± 6.6/h; MAD AHI, 11.1 ± 12.1/h; P < 0.01) but reported compliance was higher on MAD (MAD, 6.50 ± 1.3 h per night vs. CPAP, 5.20 ± 2 h per night; P < 0.00001). The 24-hour mean arterial pressure was not inferior on treatment with MAD compared with CPAP (CPAP-MAD difference, 0.2 mm Hg [95% confidence interval, -0.7 to 1.1]); however, overall, neither treatment improved blood pressure. In contrast, sleepiness, driving simulator performance, and disease-specific quality of life improved on both treatments by similar amounts, although MAD was superior to CPAP for improving four general quality-of-life domains. Important health outcomes were similar after 1 month of optimal MAD and CPAP treatment in patients with moderate-severe OSA. The results may be explained by greater efficacy of CPAP being offset by inferior compliance relative to MAD, resulting in similar effectiveness. Clinical trial registered with https://www.anzctr.org.au (ACTRN 12607000289415).


The history of adolescent medicine.
The field of adolescent medicine is unique as a subspecialty in that the practice of providing care to teenagers has always been viewed historically as a responsibility of generalists. Scientific advances in subspecialty fields such as endocrinology, gynecology, gastroenterology, infectious disease, and sports medicine were incorporated with considerable success into the general practices of not only pediatricians but also internists and family practitioners. However, societal changes in the past century began to shape the way health professionals thought about adolescents and their families and significantly influenced the practice of providing health care to adolescents. The most notable change, however, was the shift from the traditional role of providing anticipatory guidance to parents toward a reduction of risk-taking behaviors aimed directly at the adolescent. The subspecialty of adolescent medicine thus emerged as an amalgam of researchers, clinicians, and educators, who, through a variety of settings, hoped to advance science, moderate public and social policy, improve health care, and stimulate health promotion to this special population of patients.


On-surface aggregation of α-synuclein at nanomolar concentrations results in two distinct growth mechanisms.
The aggregation of α-synuclein (α-Syn) is believed to be one of the key steps driving the pathology of Parkinson's disease and related neurodegenerative disorders. One of the present hypotheses is that the onset of such pathologies is related to the rise of α-Syn levels above a critical concentration at which toxic oligomers or mature fibrils are formed. In the present study, we find that α-Syn aggregation in vitro is a spontaneous process arising at bulk concentrations as low as 1 nM and below in the presence of both hydrophilic glass surfaces and cell membrane mimicking supported lipid bilayers (SLBs). Using three-dimensional supercritical angle fluorescence (3D-SAF) microscopy, we observed the process of α-Syn aggregation in situ. As soon as α-Syn monomers were exposed to the surface, they started to adsorb and aggregate along the surface plane without a prior lag phase. However, at a later stage of the aggregation process, a second type of aggregate was observed. In contrast to the first type, these aggregates showed an extended structure being tethered with one end to the surface and being mobile at the other end, which protruded into the solution. While both types of α-Syn aggregates were found to contain amyloid structures, their growing mechanisms turned out to be significantly different. Given the clear evidence that surface-induced α-Syn aggregation in vitro can be triggered at bulk concentrations far below physiological concentrations, the concept of a critical concentration initiating aggregation in vivo needs to be reconsidered.


Applications of justification and optimization in medical imaging: examples of clinical guidance for computed tomography use in emergency medicine.
Availability, reliability, and technical improvements have led to continued expansion of computed tomography (CT) imaging. During a CT scan, there is substantially more exposure to ionizing radiation than with conventional radiography. This has led to questions and critical conclusions about whether the continuous growth of CT scans should be subjected to review and potentially restraints or, at a minimum, closer investigation. This is particularly pertinent to populations in emergency departments, such as children and patients who receive repeated CT scans for benign diagnoses. During the last several decades, among national medical specialty organizations, the American College of Emergency Physicians and the American College of Radiology have each formed membership working groups to consider value, access, and expedience and to promote broad acceptance of CT protocols and procedures within their disciplines. Those efforts have had positive effects on the use criteria for CT by other physician groups, health insurance carriers, regulators, and legislators.


Supplementation of Abelmoschus manihot Ameliorates Diabetic Nephropathy and Hepatic Steatosis by Activating Autophagy in Mice.
Diabetic nephropathy (DN) is a diabetic complication marked by albuminuria and a decline of the glomerular filtration rate. Diabetic kidneys are defective in the autophagy process and mitochondrial function and their enhancement of activity alleviates the pathology. In this paper, we developed a mouse model of DN by a combined treatment of a high-fat diet and streptozotocin after unilateral nephrectomy and supplementation with flower or leaf extracts of Abelmoschus manihot (AM) were tested. The preventive effects of the extracts on DN pathology and changes on autophagy and mitochondrial proteins were investigated. DN mice showed a significant increase in fasting blood glucose, plasma creatinine, blood urea nitrogen, and urinary albumin levels. Periodic acid⁻Schiff and Sirius red staining of the diabetic kidney presented a significant change in glomerular and tubular structures that was associated with podocyte loss and fibrotic protein accumulation. These changes were attenuated by AM extract treatment in DN mice. In addition, hepatic injury, proinflammatory cytokines, and lipid accumulation were decreased by AM extracts in DN mice. As a protective mechanism, AM extracts significantly increased the expression of proteins by regulating autophagy and mitochondrial dynamics, which potentially prevented the kidney and liver from accumulating pathogenic proteins and dysfunctional mitochondria, which alleviated the progression of DN.


Long-term renal function outcomes after radical cystectomy.
We evaluated the long-term natural history of renal function after radical cystectomy with urinary diversion and determined factors associated with decreased renal function. We reviewed the records of 1,631 patients who underwent radical cystectomy between 1980 and 2006. The estimated glomerular filtration rate was calculated preoperatively and at various intervals after surgery. A renal function decrease was defined as a greater than 10 ml per minute/1.73 m(2) reduction in the estimated glomerular filtration rate. Multivariate analysis was done to evaluate the association of clinicopathological features, incontinent vs continent diversion type and postoperative complications with decreased renal function. A total of 1,241 patients (76%) underwent incontinent diversion and 390 (24%) underwent continent diversion. Median followup after radical cystectomy in patients alive at last followup was 10.5 years (IQR 7.1, 15.3). The median preoperative estimated glomerular filtration rate was higher in the continent diversion cohort (67 vs 59 ml per minute/1.73 m(2), p <0.0001). This difference was maintained until 7 years postoperatively, after which no difference was noted in renal function by diversion type. By 10 years after radical cystectomy the risk of a renal function decrease was similar for incontinent and continent diversion (71% and 74%, respectively, p = 0.13). On multivariate analysis risk factors associated with decreased renal function included age (HR 1.03, p <0.0001), preoperative estimated glomerular filtration rate (HR 1.05, p <0.0001), chronic hypertension (HR 1.2, p = 0.01), postoperative hydronephrosis (HR 1.2, p = 0.03), pyelonephritis (HR 1.3, p = 0.01) and ureteroenteric stricture (HR 1.6, p <0.0001). Decreased renal function is noted in most patients during long-term followup after radical cystectomy. Postoperative hydronephrosis, pyelonephritis and ureteroenteric stricture represent potentially modifiable factors associated with a decrease. Choice of urinary diversion was not independently associated with decreased renal function.


Simultaneous interactions of anions and cations with cyclohexane and adamantane: aliphatic cyclic hydrocarbons as charge insulators.
With ab initio MP2 computational methods, a theoretical study has been carried out to characterize the interaction between aliphatic cyclic hydrocarbons, as models of molecular hydrocarbon monolayers, with cations (Li(+), Na(+), and K(+)), anions (F(-), Cl(-), and Br(-)), and both simultaneously in opposite faces of the hydrocarbons. In addition, the energetic barrier for the cation crossing through the hydrocarbon ring has been calculated. The hydrocarbons chosen for this study are cyclohexane (C(6)H(12)) and adamantane (C(10)H(16)). The energies obtained for the M(+):hydrocarbon:X(-) complexes indicate positive cooperativity in the cases where the hydrocarbon is cyclohexane while diminutive effects are found in the adamantane complexes. The density functional theory-symmetry adapted perturbation theory analysis of the interaction energies shows that the most important term in the complexes with cations is the induction, while in the complexes with anion and with cations and anions simultaneously the most important term is the repulsion-exchange one. The electron density of the complexes has been analyzed using the atoms in molecules methodology and provides some insight to the electron transfer within the complexes.


The Relationship Between the Implementation of Statutory Preventative Measures, Perceived Susceptibility of COVID-19, and Personality Traits in the Initial Stage of Corona-Related Lockdown: A German and Austrian Population Online Survey.
Background: Particularly during the early and middle stages of the COVID-19 pandemic, a population's compliance with precautionary measures (e.g., hygiene rules, smart working, travel restrictions, and quarantine) is paramount in preventing the virus from spreading. Objective: The investigation and documentation of different socio-demographic and personality-specific factors in regards to preventative measures and consequent specific health behaviors during the COVID-19 pandemic, based on the Health Belief Model. Method: An online survey was conducted on N = 3,006 individuals living in Germany and Austria during the early stages of lockdown. The questionnaire consisted of a self-administered section, exploring the dimensions posited in the Health Belief Model: perceived severity, perceived susceptibility, perceived barriers, perceived benefits of health-promoting measures, and engagement in health-promoting behaviors. Additionally, the following standardized scales were used to record personality determinants: the Stress Coping Style Questionnaire SVF 78 to evaluate coping and processing strategies in stressful circumstances, the Positive and Negative Affect Schedule (PANAS) to assess the emotional state induced by the coronavirus crisis, the UI-18 scale to diagnose the intolerance of uncertainty, and the State-Trait Anxiety Inventory (STAI) to assess anxiety. Results: In line with the Health Belief model, four groups were created based on perceived susceptibility and engagement in health-promoting behaviors, and consequently studied in relation to personality determinants. Those four groups differed significantly in regards to almost all personality dimensions (p ≤ 0.005). Group 1 (n = 450) shows a reduced engagement with protective measures and displays underestimation of the COVID-19-pandemic. Group 2 (n = 984) displays many positive personality variables and high compliance with protective measures. Group 3 (n = 468) perceives the subjective risk of disease as high, but high emotional discomfort and stress caused by the protective measures leads to the activation of a complex fear defense. Group 4 (n = 1,004) is highly anxious and therefore compliant. Conclusion: This typification has implications for establishing the appropriate support systems. This is particularly important to encourage compliance with preventive regulations within the groups, which showed poor abidance for several reasons. For Group 1, further education on the realistic threat and efficient protective measures is as central as the fostering of empathy for others; with its resource-conscious exemplary behavior Group 2 could be used as a positive social role model. Group 3 would benefit from promoting self-care, while Group 4 requires information on psychosocial assistance availability in order to mitigate the high stress to which the group members are subjected.


RNA and protein synthesis in human peripheral blood polymorphonuclear leukocytes.
Polymorphonuclear leukocytes purified from human peripheral blood synthesized RNA and proteins when placed in cell culture. Autoradiography of the cultured cells revealed that a majority of mature PMNs were engaged in macromolecule synthesis, and an analysis of newly synthesized proteins by SDS-polyacrylamide gel electrophoresis showed that many different polypeptide chains were synthesized by these cells. The rate of [3H]uridine incorporation and the pattern of newly synthesized proteins were modulated by Con A and glucocorticoids. These results suggest that in spite of their short lifetime and a large performed enzymatic apparatus, mature PMNs retain a substantial capacity for RNA and protein synthesis; and, further, that modulation of macromolecule synthesis forms part of the mechanism by which PMNs respond to inflammatory and anti-flammatory stimuli.


Radiation dose reduction for CT-guided renal tumor cryoablation.
The purpose of this article is to retrospectively determine the image quality and degree of radiation dose reduction that is clinically acceptable for CT-guided renal tumor cryoablation. A total of 15 patients (17 procedures; mean age, 67 years; range, 38-85 years) undergoing clinically indicated CT-guided renal tumor cryoablation procedures were included in this retrospective study. A previously validated noise-insertion tool was used to simulate reduced-dose scans at 75%, 50%, 25%, and 10% of the original dose at four representative phases of the cryoablation procedure. Images obtained at different dose levels were randomized and reviewed by three radiologists blinded to the level of dose reduction, who scored them independently with a 5-point scale (1-5, with 5 the best). Images with a mean score of 3 or higher were considered diagnostically acceptable. The minimal acceptable dose was that at which 90% of images were considered diagnostically acceptable. Interrater agreement was assessed using the weighted kappa statistic. The weighted kappa value was 0.68, indicating substantial agreement among the reviewers. The averaged percentage of diagnostically acceptable images for the four series was 100% for a full dose, 98-100% for the 75% dose level, 94-98% for the 50% dose level, and less than 90% for images obtained at the 25% and 10% dose levels, which was considered unacceptable. On the basis of results from 15 patients (17 procedures), images obtained from CT acquisitions at 50% (volume CT dose index, 12.2 mGy) of the original dose level (volume CT dose index, 24.4 mGy) were acceptable for the purpose of CT monitoring of renal cryoablation procedures.


Model-based learning for mobile robot navigation from the dynamical systems perspective.
This paper discusses how a behavior-based robot can construct a "symbolic process" that accounts for its deliberative thinking processes using models of the environment. The paper focuses on two essential problems; one is the symbol grounding problem and the other is how the internal symbolic processes can be situated with respect to the behavioral contexts. We investigate these problems by applying a dynamical system's approach to the robot navigation learning problem. Our formulation, based on a forward modeling scheme using recurrent neural learning, shows that the robot is capable of learning grammatical structure hidden in the geometry of the workspace from the local sensory inputs through its navigational experiences. Furthermore, the robot is capable of generating diverse action plans to reach an arbitrary goal using the acquired forward model which incorporates chaotic dynamics. The essential claim is that the internal symbolic process, being embedded in the attractor, is grounded since it is self-organized solely through interaction with the physical world. It is also shown that structural stability arises in the interaction between the neural dynamics and the environmental dynamics, which accounts for the situatedness of the internal symbolic process, The experimental results using a mobile robot, equipped with a local sensor consisting of a laser range finder, verify our claims.


The human HTLV-3 and HTLV-4 retroviruses: new members of the HTLV family.
Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic viruses group (PTLV). HTLV-1 infects 15 to 20million people worldwide, while STLV-1 is endemic in a number of simian or ape species living in Africa or Asia. The high percentage of homologies between HTLV-1 and STLV-1 strains, led to the demonstration that most HTLV-1 subtypes arose from interspecies transmission between monkeys and humans. STLV-3 viruses belong to the third PTLV type and are equally divergent from HTLV-1 than from HTLV-2. They are endemic in several monkey species that live in West, Central, and East Africa. In 2005, we and others reported the discovery of the human homolog (HTLV-3) of STLV-3 in two asymptomatic inhabitants from South Cameroon whose sera exhibited HTLV indeterminate serologies. More recently, we reported a third case of HTLV-3 infection in Cameroon suggesting that this virus is not rare in the human population living in Central Africa. Together with STLV-3, these three human viral strains belong therefore to the PTLV-3 type. A fourth HTLV type (HTLV-4) was also discovered in the same geographical area. Current studies are aimed at determining the prevalence, distribution and modes of transmission of these viruses as well as their possible association with human diseases. Furthermore, molecular characterization of their viral transactivator Tax is ongoing in order to look for possible oncogenic properties.


The sorption of copper on almond shell: optimization and kinetics.
Batch sorption studies using almond shell as an sorbent for the removal of Cu (II) from aqueous solutions, showed that copper removal decreased from 74.9% to 45.6% with increasing its concentration from 10 to 70 ppm. The removal increased with increasing sorbent dose and pH, respectively. Copper removal was obtained equal to 63.7%, 69.6% and 58.6% at 26˚C, 40˚C and 55˚C. The sorption of Cu (II) on almond shell was also optimized by Taguchi method. The optimized conditions were the sorbent mass of 4 g, the ion initial concentration of 10 ppm, pH 7, the temperature of 40˚C and contact time equal to 60 min. The pH and initial Cu (II) concentration with respectively 32.75% and 31.20% contribution had more influence on the removal of Cu (II). The kinetic data fit pseudo-second-order model with correlation coefficients greater than 0.99 and rate constants in the range of 0.26-7.87 g mg(-1) min(-1).


Structure-based optimization of designed Armadillo-repeat proteins.
The armadillo domain is a right-handed super-helix of repeating units composed of three α-helices each. Armadillo repeat proteins (ArmRPs) are frequently involved in protein-protein interactions, and because of their modular recognition of extended peptide regions they can serve as templates for the design of artificial peptide binding scaffolds. On the basis of sequential and structural analyses, different consensus-designed ArmRPs were synthesized and show high thermodynamic stabilities, compared to naturally occurring ArmRPs. We determined the crystal structures of four full-consensus ArmRPs with three or four identical internal repeats and two different designs for the N- and C-caps. The crystal structures were refined at resolutions ranging from 1.80 to 2.50 Å for the above mentioned designs. A redesign of our initial caps was required to obtain well diffracting crystals. However, the structures with the redesigned caps caused domain swapping events between the N-caps. To prevent this domain swap, 9 and 6 point mutations were introduced in the N- and C-caps, respectively. Structural and biophysical analysis showed that this subsequent redesign of the N-cap prevented domain swapping and improved the thermodynamic stability of the proteins. We systematically investigated the best cap combinations. We conclude that designed ArmRPs with optimized caps are intrinsically stable and well-expressed monomeric proteins and that the high-resolution structures provide excellent structural templates for the continuation of the design of sequence-specific modular peptide recognition units based on armadillo repeats.


Effects of microelectrical current on migration of nasal fibroblasts.
Migration of fibroblasts is critical in wound healing. The question of how wounded electric fields guide migration of nasal fibroblasts remains to be elucidated. This study was designed to determine morphology, directedness, and migration rate of nasal fibroblasts during microcurrent application, which is simulated by an endogenous electric field at the vicinity of the wound. Nasal fibroblasts were exposed to a microelectric field at 50, 100, and 250 mV/mm for 3 hours at 37°C. In this experiment, the field polarity was reversed for an additional 3 hours. During in vitro testing, the cells were incubated in a newly developed miniature, microcurrent generating chamber system, with 5% CO(2), at 37°C; the media was circulated by a pump system. A wound was created by scratching a cell-free area (∼150 μm wide) into a confluent monolayer. The average migration speed was calculated as the distance traveled by the cell divided by time. A microelectric field of 100 mV/mm or more induced significant cell migration in the direction of the cathode. Trajectory speeds at 50, 100, and 250 mV/mm were 9.8 ± 0.3, 11.8 ± 0.3, and 13.5 ± 0.9 μm/mm, respectively. A significant difference was observed between migratory rate of controls and that of 50 mV/mm (p < 0.05). Microelectric fields appear to have a crucial role in control of nasal fibroblast activity in the process of wound healing.


Assessing diagnostic value of microRNAs from peripheral blood mononuclear cells and extracellular vesicles in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating multisystemic disease of unknown etiology, affecting thousands of individuals worldwide. Its diagnosis still relies on ruling out medical problems leading to unexplained fatigue due to a complete lack of disease-specific biomarkers. Our group and others have explored the potential value of microRNA profiles (miRNomes) as diagnostic tools for this disease. However, heterogeneity of participants, low numbers, the variety of samples assayed, and other pre-analytical variables, have hampered the identification of disease-associated miRNomes. In this study, our team has evaluated, for the first time, ME/CFS miRNomes in peripheral blood mononuclear cells (PBMCs) and extracellular vesicles (EVs) from severely ill patients recruited at the monographic UK ME biobank to assess, using standard operating procedures (SOPs), blood fractions with optimal diagnostic power for a rapid translation of a miR-based diagnostic method into the clinic. Our results show that routine creatine kinase (CK) blood values, plasma EVs physical characteristics (including counts, size and zeta-potential), and a limited number of differentially expressed PBMC and EV miRNAs appear significantly associated with severe ME/CFS (p < 0.05). Gene enrichment analysis points to epigenetic and neuroimmune dysregulated pathways, in agreement with previous reports. Population validation by a cost-effective approach limited to these few potentially discriminating variables is granted.


Changing pattern of alcoholic liver disease in Great Britain: relation to sex and signs of autoimmunity.
A survey of 293 patients with alcoholic liver disease showed that women, particularly those aged under 45, had a significantly higher incidence of alcoholic hepatitis, with or without superimposed cirrhosis, than men. The long-term prognosis for both women who continued to drink and those who stopped drinking was worse than that for men. Autoantibodies were more common in women, which suggested that immune mechanisms may play a part in the pathogenesis and progression of alcoholic liver disease in women.


Suppression of aggressive strains of 'Candidatus phytoplasma mali' by mild strains in Catharanthus roseus and Nicotiana occidentalis and indication of similar action in apple trees.
To study antagonistic interactions of 'Candidatus Phytoplasma mali' strains, graft inoculation of Catharanthus roseus and Nicotiana occidentalis was performed with mild strains 1/93Vin and 1/93Tab as suppressors and three aggressive strains as challengers. Inoculation of the suppressors was carried out in either the cross-protection modus prior to grafting of the challengers or by co-inoculating suppressors and challengers. Monitoring using multiplex real-time polymerase chain reaction assays revealed that, in long-term cross-protection trials with C. roseus, suppressor 1/93Vin was present in all root and randomly collected stem samples over the entire observation period. In contrast, the challengers were never detected in such stem samples and rarely in the roots. Following simultaneous inoculation, the suppressor successively colonized all stem and root regions whereas detection of challenger AT steadily decreased. However, this strain remained detectable in up to 13 and 27% of stem and root samples, respectively. The cross-protection trials with N. occidentalis yielded results similar to that of the cross-protection experiments with C. roseus. Comparison of the symptomatology of infected apple trees with the presence of putatively suppressive strains indicated that suppression of severe strains also occurs in apple. Phylogenetic analysis using a variable fragment of AAA+ ATPase gene AP460 of 'Ca. P. mali' revealed that suppressors 1/93Vin and 1/93Tab, together with several other mild strains maintained in apple, cluster distantly from obviously nonsuppressive strains that were predominantly highly virulent.


"Artificial intelligence": Which services, which applications, which results and which development today in clinical research? Which impact on the quality of care? Which recommendations?
Artificial intelligence (AI), beyond the concrete applications that have already become part of our daily lives, makes it possible to process numerous and heterogeneous data and knowledge, and to understand potentially complex and abstract rules in a manner human intelligence can but without human intervention. AI combines two properties, self-learning by the successive and repetitive processing of data as well as the capacity to adapt, that is to say the possibility for a scripted program to deal with multiple situations likely to vary over time. Roundtable experts confirmed the potential contribution and theoretical benefit of AI in clinical research and in improving the efficiency of patient care. Experts also measured, as is the case for any new process that people need to get accustomed to, its impact on practices and mindset. To maximize the benefits of AI, four critical points have been identified. The careful consideration of these four points conditions the technical integration and the appropriation by all actors of the life science spectrum: researchers, regulators, drug developers, care establishments, medical practitioners and, above all, patients and the civil society. 1st critical point: produce tangible demonstrations of the contributions of AI in clinical research by quantifying its benefits. 2nd critical point: build trust to foster dissemination and acceptability of AI in healthcare thanks to an adapted regulatory framework. 3rd critical point: ensure the availability of technical skills, which implies an investment in training, the attractiveness of the health sector relative to tech-heavy sectors and the development of ergonomic data collection tools for all health operators. 4th critical point: organize a system of governance for a distributed and secure model at the national level to aggregate the information and services existing at the local level. Thirty-seven concrete recommendations have been formulated which should pave the way for a widespread adoption of AI in clinical research. In this context, the French "Health data hub" initiative constitutes an ideal opportunity.


Following the energy transfer in and out of a polyproline-peptide.
The intramolecular and intermolecular vibrational energy flow in a polyproline peptide with a total number of nine amino acids in the solvent dimethyl sulfoxide is investigated using time-resolved infrared (IR) spectroscopy. Azobenzene covalently bound to a proline sequence containing nitrophenylalanine as a local sensor for vibrational excess energy serves as a heat source. Information on through-space distances in the polyproline peptides is obtained by independent Förster resonance energy transfer measurements. Photoexcitation of the azobenzene and subsequent internal conversion yield strong vibrational excitation of the molecule acting as a local heat source. The relaxation of excess heat, its transfer along the peptide and to the solvent is monitored by the response of the nitro-group in nitrophenylalanine acting as internal thermometer. After optical excitation, vibrational excess energy is observed via changes in the IR absorption spectra of the peptide. The nitrophenylalanine bands reveal that the vibrational excess energy flows in the peptide over distances of more than 20 Å and arrives delayed by up to 7 ps at the outer positions of the peptide. The vibrational excess energy is transferred to the surrounding solvent on a time scale of 10-20 ps. The experimental observations are analyzed by different heat conduction models. Isotropic heat conduction in three dimensions away from the azobenzene heat source is not able to describe the observations. One-dimensional heat dissipation along the polyproline peptide combined with a slower transversal heat transfer to the solvent surrounding well reproduces the observations.


[Correlation between expression of androgen receptors and the degree of cell differentiation in human prostate cancer].
Immunohistochemical examination was carried out to investigate androgen receptor antigen expression in epithelial cells of benign or malignant tumors in the prostate of aged men. The benign tumors were characterized by homogeneous distribution of androgen receptors in all nuclei of secretory epithelial cells. In malignant cells there was partial or complete loss of the androgen receptors to androgens in parallel with decreased cell differentiation.


Antimicrobial Resistant Enteropathogenic Escherichia coli and Salmonella spp. in Houseflies Infesting Fish in Food Markets in Zambia.
Diarrhea is one of the most common diseases and is a leading cause of death in developing countries. This is often caused by contaminated food. Poor food hygiene standards are exacerbated by the presence of flies which can transmit a variety of infectious microorganisms, particularly through animal source foods. This fact becomes especially important in developing countries like Zambia, where fish is a highly valued source of protein. Our interest in this study was to identify if the flies that beset food markets in Zambia carry important pathogenic bacteria on their bodies, and subsequently if these bacteria carry resistance genes to commonly used antibiotics, which would indicate problems in eradicating these pathogens. The present study took into account fish vendors' and consumers' perception of flies and interest in interventions to reduce their numbers. We conducted semi-structured interviews with (1) traders (comprised of randomly selected males and females) and (2) consumers (including randomly selected males and females). Thereafter, we collected flies found on fish in markets in Mongu and Lusaka districts of Zambia. For the entire study, a total of 418 fly samples were analyzed in the laboratory and Salmonella spp. and enteropathogenic Escherichia coli were isolated from the flies. Further laboratory screening revealed that overall, 17.2% (72/418) (95% CI; 43.2%-65.5%) of total samples analyzed contained Extended-Spectrum Beta-Lactamase (ESBL)-producing E. coli. These significant findings call for a strengthening of the antibiotic administering policy in Zambia and the development of sustainable interventions to reduce fly numbers in food markets and improve food safety and hygiene.


Meteorological influence on aerosol extinction in the 0.2-40-microm wavelength range.
The aerosol extinction in various weather situations is calculated from Mie theory by use of an aerosol model which starts from dry particles. The particle size distribution and refractive index are adapted to actual air humidity by use of a growth factor, r/r(o), which is derived according to the theory of the relationship between relative humidity and the equilibrium radius of an aqueous solution droplet. It is shown that the particle number concentration in different size ranges has a dominating influence on the relation between the IR aerosol transmission and the meteorological visibility. Variations in air humidity affect the aerosol extinction mainly through modification of the particle size distribution. The effect on extinction due to the humidity influence on refractive index is proved to be of less importance.


Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: an animal trial.
The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB). Experimental, comparative, animal study. Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test. The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P < 0.05). A higher trans-scleral permeability gradient is obtained with the novel nanoparticles than with the commercial drug, leading to sustained higher levels of carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in the treatment for advanced clinical RB, specifically those with vitreous seeds.


The influence of post-exercise macronutrient intake on energy balance and protein metabolism in active females participating in endurance training.
The purpose of this investigation was to determine the influence of post-exercise macronutrient intake on weight loss, protein metabolism, and endurance exercise performance during a period of increased training volume. Ten healthy young female endurance athletes performed 4 60-min bouts of cycle ergometry at approximately 65% of VO2peak on 4 days (day 1, 3, 4, and 6) during 2 separate 1-week periods. On day 7, participants performed a ride to exhaustion at approximately 75% of VO2peak. One of the 7-day periods served as a control condition, where a placebo beverage was consumed following the exercise bouts on days 1, 3, 4, and 6 (CON). During the other 7-day protocol (POST), participants consumed a predefined formula beverage with added carbohydrate following the exercise bouts on days 1, 3, 4, and 6. Energy intake and macronutrient proportions were the same between the 2 trials; the only difference was the timing at which the macronutrients were consumed. Calculated fat oxidation was greater during exercise on day 6 during POST as compared to CON (p < .05). Glucose and insulin concentrations were significantly higher (p < .05) following exercise during POST as compared to CON. There was a trend (p = .06) for nitrogen balance to be greater on days 5 and 6 with POST as compared to CON. Time to exhaustion during exercise on day 7 was longer during POST as compared to CON (p < .05). POST resulted in a maintenance of body weight during the 7-day protocol, while there was a significant (p < .05) reduction with CON. It was concluded that post-exercise macronutrient intake following endurance exercise can attenuate reductions in body weight and improve nitrogen balance during 7 days of increased energy expenditure. Importantly, post-exercise supplementation improved time to exhaustion during a subsequent bout of endurance exercise.


Sexy gene conversions: locating gene conversions on the X-chromosome.
Gene conversion can have a profound impact on both the short- and long-term evolution of genes and genomes. Here, we examined the gene families that are located on the X-chromosomes of human (Homo sapiens), chimpanzee (Pan troglodytes), mouse (Mus musculus) and rat (Rattus norvegicus) for evidence of gene conversion. We identified seven gene families (WD repeat protein family, Ferritin Heavy Chain family, RAS-related Protein RAB-40 family, Diphosphoinositol polyphosphate phosphohydrolase family, Transcription Elongation Factor A family, LDOC1-related family, Zinc Finger Protein ZIC, and GLI family) that show evidence of gene conversion. Through phylogenetic analyses and synteny evidence, we show that gene conversion has played an important role in the evolution of these gene families and that gene conversion has occurred independently in both primates and rodents. Comparing the results with those of two gene conversion prediction programs (GENECONV and Partimatrix), we found that both GENECONV and Partimatrix have very high false negative rates (i.e. failed to predict gene conversions), which leads to many undetected gene conversions. The combination of phylogenetic analyses with physical synteny evidence exhibits high resolution in the detection of gene conversions.


How reactant polarization can be used to change the effect of interference on reactive collisions.
It is common knowledge that integral and differential cross sections (DCSs) are strongly dependent on the spatial distribution of the molecular axis of the reactants. Hence, by controlling the axis distribution, it is possible to either promote or hinder the yield of products into specific final states or scattering angles. This idea has been successfully implemented in experiments by polarizing the internuclear axis before the reaction takes place, either by manipulating the rotational angular distribution or by the Stark effect in the presence of an orienting field. When there is a dominant reaction mechanism, characterized by a set of impact parameters and angles of attack, it is expected that a preparation that helps the system to reach the transition state associated with that mechanism will promote the reaction, whilst a different preparation would generally impair the reaction. However, when two or more competing mechanisms via interference contribute to the reaction into specific scattering angles and final states, it is not evident which would be the effect of changing the axis preparation. To address this problem, throughout this article we have simulated the effect that different experimental preparations have on the DCSs for the H + D2 reaction at relatively high energies, for which it has been shown that several competing mechanisms give rise to interference that shapes the DCS. To this aim, we have extended the formulation of the polarization dependent DCS to calculate polarization dependent generalized deflection functions of ranks greater than zero. Our results show that interference is very sensitive to changes in the internuclear axis preparation, and that the shape of the DCS can be controlled exquisitely.


Has Toxicity Testing Moved into the 21st Century? A Survey and Analysis of Perceptions in the Field of Toxicology.
Ten years ago, leaders in the field of toxicology called for a transformation of the discipline and a shift from primarily relying on traditional animal testing to incorporating advances in biotechnology and predictive methodologies into alternative testing strategies (ATS). Governmental agencies and academic and industry partners initiated programs to support such a transformation, but a decade later, the outcomes of these efforts are not well understood. We aimed to assess the use of ATS and the perceived barriers and drivers to their adoption by toxicologists and by others working in, or closely linked with, the field of toxicology. We surveyed 1,381 toxicologists and experts in associated fields regarding the viability and use of ATS and the perceived barriers and drivers of ATS for a range of applications. We performed ranking, hierarchical clustering, and correlation analyses of the survey data. Many respondents indicated that they were already using ATS, or believed that ATS were already viable approaches, for toxicological assessment of one or more end points in their primary area of interest or concern (26-86%, depending on the specific ATS/application pair). However, the proportions of respondents reporting use of ATS in the previous 12 mo were smaller (4.5-41%). Concern about regulatory acceptance was the most commonly cited factor inhibiting the adoption of ATS, and a variety of technical concerns were also cited as significant barriers to ATS viability. The factors most often cited as playing a significant role (currently or in the future) in driving the adoption of ATS were the need for expedited toxicology information, the need for reduced toxicity testing costs, demand by regulatory agencies, and ethical or moral concerns. Our findings indicate that the transformation of the field of toxicology is partly implemented, but significant barriers to acceptance and adoption remain. https://doi.org/10.1289/EHP1435.


Corridors increase plant species richness at large scales.
Habitat fragmentation is one of the largest threats to biodiversity. Landscape corridors, which are hypothesized to reduce the negative consequences of fragmentation, have become common features of ecological management plans worldwide. Despite their popularity, there is little evidence documenting the effectiveness of corridors in preserving biodiversity at large scales. Using a large-scale replicated experiment, we showed that habitat patches connected by corridors retain more native plant species than do isolated patches, that this difference increases over time, and that corridors do not promote invasion by exotic species. Our results support the use of corridors in biodiversity conservation.


Inside the ordering room: characteristics of women's in-home sex toy parties, facilitators and sexual communication.
Previous research suggests that adult bookstores are a unique way through which individuals may learn about sexuality or practice sexual communication. Recently, the woman-oriented in-home sex toy party industry has rapidly expanded in several countries. The purpose of this study was to document the characteristics of the parties, the women who run the parties ('facilitators') and facilitator-consumer communication about sexual health topics. Female facilitators for a large in-home sex toy party company in the USA were invited to participate in an anonymous, cross-sectional online survey. A total of 1197 completed surveys were received. Most respondents were white (85.2%), heterosexual (91.6%), had at least some college education (76.3%) and were married (59.4%). Most parties were held in another woman's home (88.3%), lasted 1-2 h (72.2%) and had 10 or fewer women in attendance (65.1%). At their most recent party facilitated, most respondents were asked questions about increasing desire/arousal (75.3%), orgasm (57.8%), desire discrepancy (56.4%), erection and ejaculation (73.8%), and vaginal dryness and lubrication (64.5%). Respondents who encountered sexual health questions or disclosures by consumers (those that were more 'askable') scored significantly higher on the Sexual Opinion Survey, indicating greater erotophilia. Results suggest that female in-home sex toy party facilitators have the potential to provide a diverse group of women with opportunities to access sexuality information, products and communication and that facilitators' 'askability' is related to erotophilia. Implications for sexual health professionals are discussed.


Intracellular responses to frequency modulated tones in the dorsal cortex of the mouse inferior colliculus.
Frequency modulations occur in many natural sounds, including vocalizations. The neuronal response to frequency modulated (FM) stimuli has been studied extensively in different brain areas, with an emphasis on the auditory cortex and the central nucleus of the inferior colliculus. Here, we measured the responses to FM sweeps in whole-cell recordings from neurons in the dorsal cortex of the mouse inferior colliculus. Both up- and downward logarithmic FM sweeps were presented at two different speeds to both the ipsi- and the contralateral ear. Based on the number of action potentials that were fired, between 10 and 24% of cells were selective for rate or direction of the FM sweeps. A somewhat lower percentage of cells, 6-21%, showed selectivity based on EPSP size. To study the mechanisms underlying the generation of FM selectivity, we compared FM responses with responses to simple tones in the same cells. We found that if pairs of neurons responded in a similar way to simple tones, they generally also responded in a similar way to FM sweeps. Further evidence that FM selectivity can be generated within the dorsal cortex was obtained by reconstructing FM sweeps from the response to simple tones using three different models. In about half of the direction selective neurons the selectivity was generated by spectrally asymmetric synaptic inhibition. In addition, evidence for direction selectivity based on the timing of excitatory responses was also obtained in some cells. No clear evidence for the local generation of rate selectivity was obtained. We conclude that FM direction selectivity can be generated within the dorsal cortex of the mouse inferior colliculus by multiple mechanisms.


MicroRNA expression profiles in serous ovarian carcinoma.
Although microRNAs have recently been recognized as riboregulators of gene expression, little is known about microRNA expression profiles in serous ovarian carcinoma. We assessed the expression of microRNA and the association between microRNA expression and the prognosis of serous ovarian carcinoma. Twenty patients diagnosed with serous ovarian carcinoma and eight patients treated for benign uterine disease between December 2000 and September 2003 were enrolled in this study. The microRNA expression profiles were examined using DNA microarray and Northern blot analyses. Several microRNAs were differentially expressed in serous ovarian carcinoma compared with normal ovarian tissues, including miR-21, miR-125a, miR-125b, miR-100, miR-145, miR-16, and miR-99a, which were each differentially expressed in >16 patients. In addition, the expression levels of some microRNAs were correlated with the survival in patients with serous ovarian carcinoma. Higher expression of miR-200, miR-141, miR-18a, miR-93, and miR-429, and lower expression of let-7b, and miR-199a were significantly correlated with a poor prognosis (P < 0.05). Our results indicate that dysregulation of microRNAs is involved in ovarian carcinogenesis and associated with the prognosis of serous ovarian carcinoma.


Cutaneous vasculitis in non Hodgkin's lymphoma.
Cutaneous vasculitis has been described in association with various hematological malignancies, but it seems to be very uncommon among non Hodgkin's lymphomas (NHL). For this reason no attention has been given to the peculiarity of this rare association. We identified 5 cases of cutaneous vasculitis among 315 NHL patients examined at our Institution from 1984 through 1990 and after the appearance of vasculitis, we observed some heterogeneity in either the degree of activity or in the clinical outcome of the NHL. The onset of cutaneous vasculitis appeared to mark two different clinical patterns: a vasculitis present from diagnosis characterized an indolent course of the neoplasia, while a late-appearing vasculitis was followed by rapid lymphoma progression and short survival.


Validation of the WATCH-DM and TRS-HFDM Risk Scores to Predict the Risk of Incident Hospitalization for Heart Failure Among Adults With Type 2 Diabetes: A Multicohort Analysis.
Background The WATCH-DM (weight [body mass index], age, hypertension, creatinine, high-density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS-HFDM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH-DM was developed to predict incident HF, whereas TRS-HFDM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer-based WATCH-DM and TRS-HFDM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer-based WATCH-DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood-Nam-D'Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person-years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer-based WATCH-DM and TRS-HFDM scores had similar discrimination and calibration for predicting 5-year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood-Nam-D'Agostino P>0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood-Nam-D'Agostino P<0.001 for both). In the electronic health record cohort, the integer-based WATCH-DM score demonstrated a concordance index of 0.73 with adequate calibration (Greenwood-Nam-D'Agostino P=0.96). TRS-HFDM score could not be validated in the electronic health record because of unavailability of data on urine albumin/creatinine ratio in most patients in the contemporary clinical practice. Conclusions The WATCH-DM and TRS-HFDM risk scores can discriminate risk of HF among intermediate-risk populations with type 2 diabetes.


Static stretching increases muscle fatigue during submaximal sustained isometric contractions.
The purpose of this study was to examine the acute effects of a static stretching protocol on neuromuscular fatigue of the flexor carpi radialis (FC) and flexor digitorum (FD). Twenty-six healthy and right-handed men with a mean (SD) age of 27.1 (2.9) years volunteered for this study. The fatigue test was performed before (Pre) and after three sets of 50 s stretching (Post) applied to the right hand, and twice (T1 and T2) without stretching to the left hand as a control condition. Isometric handgrip fatigue exercise was maintained for 30s within the range 50-60% of the maximal voluntary contraction. From the electromyography (EMG), root mean squares (RMS) values and mean frequency (MF) were obtained for each 2s consecutive windows of test and normalized by the MVC obtained in 6s tests. From time series, coefficients of linear regression were determined used to compare Pre with Post and T1 with T2 by paired samples t-tests. Higher rate of increase in EMG on Post compared to Pre was found in both FC (P=0.015) and FD (P=0.006). A higher rate of decrease of MF for FC (P=0.004) and FD (P=0.005) was observed with Post compared to Pre. Conversely, the differences between T1 and T2 were not significant (P>0.05). These findings indicate that static stretching performed immediately before submaximal isometric muscle actions may increase neuromuscular fatigue assessed by EMG, suggesting that could reduce muscle's endurance capacity.