Introducing ACASS: An Annotated Character Animation Stimulus Set for Controlled (e)Motion Perception Studies.
Others' movements inform us about their current activities as well as their intentions and emotions. Research on the distinct mechanisms underlying action recognition and emotion inferences has been limited due to a lack of suitable comparative stimulus material. Problematic confounds can derive from low-level physical features (e.g., luminance), as well as from higher-level psychological features (e.g., stimulus difficulty). Here we present a standardized stimulus dataset, which allows to address both action and emotion recognition with identical stimuli. The stimulus set consists of 792 computer animations with a neutral avatar based on full body motion capture protocols. Motion capture was performed on 22 human volunteers, instructed to perform six everyday activities (mopping, sweeping, painting with a roller, painting with a brush, wiping, sanding) in three different moods (angry, happy, sad). Five-second clips of each motion protocol were rendered into AVI-files using two virtual camera perspectives for each clip. In contrast to video stimuli, the computer animations allowed to standardize the physical appearance of the avatar and to control lighting and coloring conditions, thus reducing the stimulus variation to mere movement. To control for low level optical features of the stimuli, we developed and applied a set of MATLAB routines extracting basic physical features of the stimuli, including average background-foreground proportion and frame-by-frame pixel change dynamics. This information was used to identify outliers and to homogenize the stimuli across action and emotion categories. This led to a smaller stimulus subset (n = 83 animations within the 792 clip database) which only contained two different actions (mopping, sweeping) and two different moods (angry, happy). To further homogenize this stimulus subset with regard to psychological criteria we conducted an online observer study (N = 112 participants) to assess the recognition rates for actions and moods, which led to a final sub-selection of 32 clips (eight per category) within the database. The ACASS database and its subsets provide unique opportunities for research applications in social psychology, social neuroscience, and applied clinical studies on communication disorders. All 792 AVI-files, selected subsets, MATLAB code, annotations, and motion capture data (FBX-files) are available online.


Breast cancer: weighing the evidence for a promoting role of dietary fat.
It has been hypothesized that a high-fat diet promotes the development of postmenopausal breast cancer. This contention is supported by data showing high international correlations between fat intake and breast cancer rates, modest positive associations with a high-fat diet in case-control studies, and animal model studies that have consistently demonstrated that dietary fat influences mammary cancer development at several stages in the carcinogenic process. A number of plausible biologic mechanisms have been suggested that may explain such promotional effects. In contrast, dietary fat intake is unrelated to the risk of breast cancer in cohort studies. The conflicting findings from cohort studies have created uncertainty regarding nutritional recommendations and breast cancer prevention. After reviewing key scientific findings that are relevant to this issue, the following conclusion is drawn: In the absence of data from dietary intervention trials, the weight of available evidence suggests that the type and amount of fat in the diet is related to postmenopausal breast cancer and that the inability to detect associations within populations (cohort studies) is because of measurement error and the relative homogeneity of diets measured. It is expected that the results from intervention trials will clarify this issue.


Depression predicts first but not recurrent diabetic foot ulcers.
This study examined the relationship between symptoms of depression and the development of diabetic foot ulcers. Participants were 333 patients (71% male; mean age 62 years; 73% with type 2 diabetes) with diabetic peripheral neuropathy (DPN), but without peripheral vascular disease (PVD). Severity of DPN and the presence of PVD were assessed by clinical examination. Depression, other diabetes complications and foot self-care were assessed by self-report. Cox regression tested whether depression was an independent predictor of foot ulceration over 18 months, whether this relationship was moderated by foot ulcer history, and whether foot self-care mediated this relationship. During follow-up, 63 patients developed a foot ulcer. Those with prior foot ulcers had more than four-fold greater risk of subsequent foot ulceration compared with those without a history of foot ulcer. A significant interaction effect showed that depression was significantly related to the development of first but not recurrent foot ulcers. This relationship was independent of biological risk factors. In the final model, each standard deviation increase in depression symptoms was significantly associated with increased risk of developing first foot ulcers (HR 1.68, 95% CI 1.20-2.35), while foot self-care was associated with lower risk (HR 0.61, 95% CI 0.40-0.94). Foot self-care did not mediate the relationship between depression and foot ulceration. These data suggest that depression is associated with increased risk of first foot ulcers in DPN patients and that this relationship is independent of biological risk factors and foot self-care. Interventions that target depression and foot self-care before the development of foot ulcers may maximise the likelihood of successful prevention of foot ulceration.


Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation.
During virus infection, the adaptor proteins MAVS and STING transduce signals from the cytosolic nucleic acid sensors RIG-I and cGAS, respectively, to induce type I interferons (IFNs) and other antiviral molecules. Here we show that MAVS and STING harbor two conserved serine and threonine clusters that are phosphorylated by the kinases IKK and/or TBK1 in response to stimulation. Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. We further show that TRIF, an adaptor protein in Toll-like receptor signaling, activates IRF3 through a similar phosphorylation-dependent mechanism. These results reveal that phosphorylation of innate adaptor proteins is an essential and conserved mechanism that selectively recruits IRF3 to activate the type I IFN pathway.


Gun Violence on Walkable Routes to and from School: Recommendations for Policy and Practice.
Gun-related violence exposure is a significant public health problem for urban youth. Few studies have implemented methods to estimate the spatial influence of activity spaces on gun violence exposure constrained by the physical configuration of walkable street networks. The present research uses computational network and local indicators of spatial autocorrelation methods to explore gun violence exposure along the walkable streets near schools in Compton, California. Findings demonstrated strong evidence that gun violence is clustered at all distances along the pedestrian network and in proximity to Compton Unified School District (K-12) schools, reaching a maximum between 1.2 and 1.8 mi; thereafter the "attractiveness" of schools to gun violence was inhibiting. Almost all schools had at least one shooting within a 5-min walk (i.e., about 400 m); 37.8% of schools had an average shooting distance of less than 400 m; about 250 incidents occurred within 5 min of schools; and about 30 schools had a shooting within a 5-min walking distance. Determining the spatial extent of violence exposure in proximity to key activity spaces for youth, such as schools, has substantial implications for the health and wellbeing of youth living in violence-prone areas. The public health and legal implications of this study are discussed in context.


A model of effects of narrative as culture-centric health promotion.
Health promotion interventions designed for specific cultural groups often are designed to address cultural values through culturally adapted messages. Recent trends in health promotion incorporate narrative theory, locating culture within the narratives of cultural members, and suggesting that narrative may provide a central, grounded medium for expressing and shaping health behavior. We suggest that culturally grounded narratives are a natural choice for identifying and shaping health messages for specific audiences. A Model of Culture-Centric Narratives in Health Promotion is proposed based on previous persuasion and health promotion research. This model may be used to guide the development and testing of the narrative characteristics and psychosocial mediators of behavior change in a broad range of health interventions. Implications, boundaries, and limitations of the model are discussed.


A planar ion trapping microdevice with integrated waveguides for optical detection.
A planar ion trap with an integrated waveguide was fabricated and characterized. The microdevice, consisting of a 1 mm-diameter one-hole ring trap and multi-mode optical waveguides, was made on a glass wafer using microfabrication techniques. The experimental results demonstrate that the microdevice can trap 1.5 μm- to 150 μm-diameter charged particles in air under an alternating electric field with the amplitude and frequency varying from 100 V to 750 V, and 100 Hz to 700 Hz, respectively. The on-chip waveguide is capable of detecting the presence of a particle in the trap, and the particle secular motion frequency was found to depend on the input alternating signal amplitude and frequency.


Extensive metallosis and necrosis in failed prostheses with cemented titanium-alloy stems and ceramic heads.
We describe three prostheses with cemented titanium-alloy stems and Al2O3 ceramic femoral heads which had to be revised after a mean period of implantation of 78 months. In each case, the neck of the prosthesis had been so severely worn that the profile was elliptical rather than circular. There was severe metallosis of the periprosthetic tissues. Metal particles isolated from the tissues were approximately one nanometre in size and the ratios of titanium, aluminium and vanadium in the particles were the same as in the original alloy. Histologically, the high concentration of metal particles masked the presence of high-density polyethylene (HDP) debris, but again particles about one nanometre in size were isolated from the tissues. The severe necrobiosis and necrosis noted were consistent with other reports of the presence of extensive wear particles in periprosthetic tissues. Wear is presumed to have occurred as a result of mismatch between the shape or size of the taper cone and the femoral head, or to changes in the geometry of loading due to migration of the cup. To facilitate early intervention, patients with this design of prosthesis should be monitored radiologically.


Emerging technologies and their impact on regulatory science.
There is an evolution and increasing need for the utilization of emerging cellular, molecular and in silico technologies and novel approaches for safety assessment of food, drugs, and personal care products. Convergence of these emerging technologies is also enabling rapid advances and approaches that may impact regulatory decisions and approvals. Although the development of emerging technologies may allow rapid advances in regulatory decision making, there is concern that these new technologies have not been thoroughly evaluated to determine if they are ready for regulatory application, singularly or in combinations. The magnitude of these combined technical advances may outpace the ability to assess fit for purpose and to allow routine application of these new methods for regulatory purposes. There is a need to develop strategies to evaluate the new technologies to determine which ones are ready for regulatory use. The opportunity to apply these potentially faster, more accurate, and cost-effective approaches remains an important goal to facilitate their incorporation into regulatory use. However, without a clear strategy to evaluate emerging technologies rapidly and appropriately, the value of these efforts may go unrecognized or may take longer. It is important for the regulatory science field to keep up with the research in these technically advanced areas and to understand the science behind these new approaches. The regulatory field must understand the critical quality attributes of these novel approaches and learn from each other's experience so that workforces can be trained to prepare for emerging global regulatory challenges. Moreover, it is essential that the regulatory community must work with the technology developers to harness collective capabilities towards developing a strategy for evaluation of these new and novel assessment tools.


"It would really support the wider harm reduction agenda across the board": A qualitative study of the potential impacts of drug checking service delivery in Scotland.
Drug checking services (DCS) enable individuals to voluntarily submit a small amount of a substance for analysis, providing information about the content of the substance along with tailored harm reduction support and advice. There is some evidence suggesting that DCS may lead to behaviour and system change, with impacts for people who use drugs, staff and services, and public health structures. The evidence base is still relatively nascent, however, and several evidence gaps persist. This paper reports on qualitative interviews with forty-three participants across three Scottish cities where the implementation of community-based DCS is being planned. Participants were drawn from three groups: professional participants; people with experience of drug use; and affected family members. Findings focus on perceived harm reduction impacts of DCS delivery in Scotland, with participants highlighting the potential for drug checking to impact a number of key groups including: individual service users; harm reduction services and staff; drug market monitoring structures and networks; and wider groups of people who use and sell drugs, in shaping their interactions with the drug market. Whilst continued evaluation of individual health behaviour outcomes is crucial to building the evidence base for DCS, the findings highlight the importance of extending evaluation beyond these outcomes. This would include evaluation of processes such as: information sharing across a range of parties; engagement with harm reduction and treatment services; knowledge building; and increased drug literacy. These broader dynamics may be particularly important for evaluations of community-based DCS serving individuals at higher-risk, given the complex relationship between information provision and health behaviour change which may be mediated by mental and physical health, stigma, criminalisation and the risk environment. This paper is of international relevance and adds to existing literature on the potential impact of DCS on individuals, organisations, and public health structures.


Expression of basic fibroblast growth factor and its receptor in the rat subfornical organ.
Basic fibroblast growth factor (FGF), its mRNA and the mRNA that encodes for its receptor have all been localized in the rat subfornical organ (SFO). Basic FGF is widely distributed throughout the SFO; it is present in neurons, in the vascular basement membrane of lateral blood vessels (but not those within the SFO) and in ependymal cells surrounding the SFO. Results of in situ hybridization show that the expression of basic FGF mRNA is detected throughout the organ. Similarly, the expression of flg, the gene for the putative basic FGF receptor, can also be detected in the SFO. The results all support the possibility that this growth factor may modulate the known physiological functions of the SFO.


Compassion fatigue and psychological distress among social workers: a validation study.
Few studies have focused on caring professionals and their emotional exhaustion from working with traumatized clients, referred to as compassion fatigue (CF). The present study had 2 goals: (a) to assess the psychometric properties of a CF scale, and (b) to examine the scale's predictive validity in a multivariate model. The data came from a survey of social workers living in New York City following the September 11, 2001, terrorist attacks on the World Trade Center. Factor analyses indicated that the CF scale measured multiple dimensions. After overlapping items were eliminated, the scale measured 2 key underlying dimensions--secondary trauma and job burnout. In a multivariate model, these dimensions were related to psychological distress, even after other risk factors were controlled. The authors discuss the results in light of increasing the ability of professional caregivers to meet the emotional needs of their clients within a stressful environment without experiencing CF.


Vibrotactile perception of suprasegmental features of speech: a comparison of single-channel and multichannel instruments.
The recognition of three suprasegmental aspects of speech--the number of syllables in a word, the stress pattern of a word, and rising or falling intonation patterns--through a single-channel tactile device and through a 24-channel tactile vocoder, using two groups of normal-hearing subjects, was compared. All subjects received an initial pretest on three recognition tasks, one for each prosodic feature. Half the subjects from each group then received 12 h of training with feedback on the tasks and stimuli used in the pretest. All subjects received a post-test which contained physically different stimuli from those previously tested. Performance was significantly better on the syllable-number and syllabic stress tasks with the single-channel than with the multichannel device on both the pre- and post-tests; no difference was found for the intonation task. Performance on the post-test was poorer for all trained subjects compared to their final training results, suggesting that cues learned in training were not readily transferable to new stimuli, even those with similar prosodic characteristics. Overall, the results provide support for the notion that certain prosodic features of speech may be conveyed more readily when the waveform envelope is preserved.


Characterization of the Zika virus induced small RNA response in Aedes aegypti cells.
RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25-29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication. Enhanced ZIKV replication was observed in a Dcr2-knockout cell line suggesting that the exo-siRNA pathway is implicated in the antiviral response. Although ZIKV-specific piRNA-sized small RNAs were detected, these lacked the characteristic piRNA ping-pong signature motif and were bound to Ago3 but not Piwi5 or Piwi6. Silencing of PIWI proteins indicated that the knockdown of Ago3, Piwi5 or Piwi6 did not enhance ZIKV replication and only Piwi4 displayed antiviral activity. We also report that the expression of ZIKV capsid (C) protein amplified the replication of a reporter alphavirus; although, unlike yellow fever virus C protein, it does not inhibit the exo-siRNA pathway. Our findings elucidate ZIKV-mosquito RNAi interactions that are important for understanding its spread.


Exposure to 15% oxygen in vivo up-regulates cardioprotective SUR2A without affecting ERK1/2 and AKT: a crucial role for AMPK.
SUR2A is an 'atypical' ABC protein that forms sarcolemmal ATP-sensitive K+ (KATP ) channels by binding to inward rectifier Kir6.2. Manipulation with SUR2A levels has been suggested to be a promising therapeutic strategy against ischaemic heart diseases and other diseases where increased heart resistance to stress is beneficial. Some years ago, it has been reported that high-altitude residents have lower mortality rates for ischaemic heart disease. The purpose of this study was to determine whether SUR2A is regulated by mild-to-severe hypoxic conditions (15% oxygen; oxygen tension equivalent to 3000 m above sea level) and elucidate the underlying mechanism. Mice were exposed to either to 21% (control) or 15% concentration of oxygen for 24 hrs. Twenty-four hours long exposure to 15% oxygen decreased partial pressure of O2 (PO2 ), but did not affect blood CO2 (PCO2 ), haematocrit nor levels of ATP, lactate and NAD+/NADH in the heart. Cardiac SUR2A levels were significantly increased while Kir6.2 levels were not affected. Hypoxia did not induce phosphorylation of extracellular signal-regulated kinases (ERK1/2) or protein kinase B (Akt), but triggered phosphorylation of AMP activated protein kinase (AMPK). AICAR, an activator of AMPK, increased the level of SUR2A in H9c2 cells. We conclude that oxygen increases SUR2A level by activating AMPK. This is the first account of AMPK-mediated regulation of SUR2A.


Sleep disorders in Parkinson's disease.
The nature of sleep is one of the major sources of dissatisfaction with the quality of life among patients with Parkinson's disease (PD). Difficult sleep maintenance (light and fragmented sleep) and difficulties with sleep initiation are the earliest and most frequent sleep disorders observed in these patients. Sleep disorders are also common in the normal elderly population, suggesting that normal aging may play a role in the etiology of sleep disorders in PD. Factor et al. examined the frequency of various sleep disorders in PD and compared them to those of normal elderly subjects. Sleep fragmentation and spontaneous daytime dozing occurred much more frequently in PD patients than in controls. Sleep fragmentation in PD may be due to an increased skeletal muscle activity, disturbed breathing and REM/non-REM variations of the dopaminergic receptor sensitivity. In parkinsonian patients who developed motor fluctuations (on-off phenomenon, wearing-off) during the day, other common sleep-related motor complaints including nocturnal akinesia, dystonia and painful cramps are observed. In a double-blind cross-over study, we compared the efficacy of a single dose of a chronic release formulation of levodopa/carbidopa (Sinemet CR) with that of a placebo in improving sleep-related motor disturbances in a group of 40 fluctuating PD patients. Sinemet CR significantly improved nocturnal akinesia and increased the hours of sleep in this group of patients. Initiation and maintenance of sleep are problems that may not be solved with antiparkinsonian treatment.


The early use of inhaled nitric oxide in premature infants requiring respiratory support.
Background: Earlier studies on the use of inhaled nitric oxide (iNO) for premature infants born at <34 weeks of gestation requiring respiratory support did not provide conclusive evidence of benefit. National guidelines generally discouraged the use in this population. More recent national guidelines endorsed the use of iNO in premature infants with hypoxic respiratory failure (HRF) associated with persistent pulmonary hypertension of the newborn (PPHN).Recent Studies: Two recently published observational studies evaluated the effect of administering iNO on oxygenation in the first week of life. These studies compared premature infants born at the gestational age (GA) of <34 weeks with HRF associated with PPHN to term and late preterm infants born at the GA of ≥34 weeks who received iNO. Both studies showed a similar effect of iNO on oxygenation in the two infant cohorts. The response rate in the premature infant cohort was 59% in the first study and 90% in the second. The mean response time was 9.2 h and 10.3 h, and the mean duration of therapy was 3.5 days and 8.2 days, respectively.Conclusion: The results of these studies support a trial of iNO in premature infants with persistent hypoxia despite optimum respiratory support. Obtaining a timely echocardiogram to exclude cardiac diseases and diagnose PPHN is logistically challenging for many clinicians, thus, a clinical diagnosis of PPHN might have to be made in these situations. Questions remain regarding the optimum dose of iNO and the duration of the initial iNO trial in these patients.KEY MESSAGESIn the most recently published studies, the improvement of oxygenation in iNO-treated infants born at <34 weeks of gestation with HRF and PPHN physiology was as effective as in infants born ≥34 weeks.These studies provide evidence supporting a trial of iNO in the subpopulation of premature infants with HRF associated with PPHN.


Effect of plasma proteins and temperature on echogenicity of blood.
An explanation is proposed for the echogenicity to ultrasound scanning at 5 mHz and above of unclotted blood under conditions of stasis. In vitro experiments using blood from normal subjects and from patients with myeloma revealed that: 1) lysis of red cells prevented echogenicity, 2) echogenicity increased with increasing hematocrit, fibrinogen and other macromolecules, and temperature, and 3) blood from myeloma patients showed increased echogenicity and rouleau formation, a form of aggregation seen on peripheral smears. From these experiments it was concluded that red cell aggregation is a major cause of echogenicity of unclotted blood, requiring both intact red cells and conditions which are known to enhance red cell aggregation, such as the presence of macromolecules and increased temperature.


Growth of Toxoplasma gondii is inhibited by aryloxyphenoxypropionate herbicides targeting acetyl-CoA carboxylase.
Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 microM in 2 days and effectively eliminates the parasite in 2-4 days at 10-100 microM. Clodinafop is not toxic to the host cell even at much higher concentrations. Parasite growth inhibition by different herbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encoding the biotin carboxylase domain of multidomain ACCs of T. gondii, Plasmodium falciparum, Plasmodium knowlesi, and Cryptosporidium parvum were sequenced. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparum ACC, P. knowlesi ACC, and the putative Cyclotella cryptica chloroplast ACC. Another sequence (ACC2) clusters with that of C. parvum ACC, probably the cytosolic form.


Automating data acquisition into ontologies from pharmacogenetics relational data sources using declarative object definitions and XML.
Ontologies are useful for organizing large numbers of concepts having complex relationships, such as the breadth of genetic and clinical knowledge in pharmacogenomics. But because ontologies change and knowledge evolves, it is time consuming to maintain stable mappings to external data sources that are in relational format. We propose a method for interfacing ontology models with data acquisition from external relational data sources. This method uses a declarative interface between the ontology and the data source, and this interface is modeled in the ontology and implemented using XML schema. Data is imported from the relational source into the ontology using XML, and data integrity is checked by validating the XML submission with an XML schema. We have implemented this approach in PharmGKB (http://www.pharmgkb.org/), a pharmacogenetics knowledge base. Our goals were to (1) import genetic sequence data, collected in relational format, into the pharmacogenetics ontology, and (2) automate the process of updating the links between the ontology and data acquisition when the ontology changes. We tested our approach by linking PharmGKB with data acquisition from a relational model of genetic sequence information. The ontology subsequently evolved, and we were able to rapidly update our interface with the external data and continue acquiring the data. Similar approaches may be helpful for integrating other heterogeneous information sources in order make the diversity of pharmacogenetics data amenable to computational analysis.


Biomonitoring approach with mussel Mytilus galloprovincialis (Lmk) and clam Ruditapes philippinarum (Adams and Reeve, 1850) in the Lagoon of Venice.
Transplanted Mytilus galloprovincialis and native Ruditapes philippinarum were deployed in 10 sampling stations with different pollution impact within the Lagoon of Venice to evaluate the temporal variations and the suitability of the following cytochemical and histochemical biomarkers just as indicators of environmental stress: lysosomal membrane stability, lipofuscins, neutral lipids and lysosome to cytoplasm volume ratio. The physiological status of the organisms was also investigated by determining the survival in air capability and the reburrowing rate (clams). The biological parameters were assessed in June and October. Furthermore, for a better definition of the environmental aspects of the study sites, heavy metal, PAH and PCB concentrations were also evaluated in the sediments. As a whole, the biological responses examined in both species from all the sampling sites showed significant differences between the two seasonal campaigns, only lysosomal membrane stability exhibited less variability. Pollutants in sediments generally showed low-intermediate contamination levels, few hotspots persisting mostly in the inner areas of the lagoon, the most influenced by the industrial zone. Transplanted mussels were more responsive than native clams and the biological responses of both species varied temporally. The range of the spatial variability was always narrow and reflected only partially the broader variability shown by the chemical content in the sediments. In this sense, biological responses seemed to be particularly influenced by the high temporal and spatial heterogeneity that characterise the Lagoon of Venice, as well as most of the transitional environments.


Impact of Naturally Contaminated Substrates on Alphitobius diaperinus and Hermetia illucens: Uptake and Excretion of Mycotoxins.
Insects are considered a suitable alternative feed for livestock production and their use is nowadays regulated in the European Union by the European Commission Regulation No. 893/2017. Insects have the ability to grow on a different spectrum of substrates, which could be naturally contaminated by mycotoxins. In the present work, the mycotoxin uptake and/or excretion in two different insect species, Alphitobius diaperinus (Lesser Mealworm, LM) and Hermetia illucens (Black Soldier Fly, BSF), grown on naturally contaminated substrates, was evaluated. Among all the substrates of growth tested, the Fusarium toxins deoxynivalenol (DON), fumonisin 1 and 2 (FB1 and FB2) and zearalenone (ZEN) were found in those based on wheat and/or corn. No mycotoxins were detected in BSF larvae, while quantifiable amount of DON and FB1 were found in LM larvae, although in lower concentration than those detected in the growing substrates and in the residual fractions. Mass balance calculations indicated that BSF and LM metabolized mycotoxins in forms not yet known, accumulating them in their body or excreting in the faeces. Further studies are required in this direction due to the future employment of insects as feedstuff.


Arterial hypertension in school-aged children in western Romania.
To describe the current prevalence of paediatric hypertension and the relationships between body mass index, gender, place of residence, and blood pressure in a population of school-aged children from western Romania. A total of 3626 children from Timisoara and the surrounding regions were examined by medical students from February, 2010 to June, 2011. Children's body mass index was interpreted on the basis of reference guidelines from Centers for Disease Control and Prevention. Blood pressure measurements were taken by the auscultation method. For defining elevated blood pressure, we used the standards published in the Fourth Report. Overall, the prevalence of overweight was 14% and 11.8% for obesity. Boys had a higher prevalence of both overweight and obesity compared with girls. The prevalence of hypertension on our screening was 9.1% higher in boys and urban residence. The prevalence of pre-hypertension was 6.5%. With regard to body mass index, 21.1% of obese, 12.8% of overweight, and 7.1% of normal weight children presented hypertension. The strongest determinant of hypertension was body mass index percentile. Significant odds ratio was found for obesity (3.93; confidence interval: 3.11–4.95), urban residence (1.68; confidence interval: 1.35–2.1), and male gender (1.34; confidence interval: 1.12–1.6). The results confirm a worrisome prevalence of overweight and obesity among children in Romania, accompanied by an alarming prevalence of hypertension. Overweight and obesity, male gender, and urban residence were the major contributing factors for the overall high prevalence of hypertension found. Our results point to the urgent need to adopt strategies aimed at preventing hypertension and obesity in children in Romania.


Corn or sorghum wet distillers grains with solubles in combination with steam-flaked corn: feedlot cattle performance, carcass characteristics, and apparent total tract digestibility.
Two studies were conducted to evaluate the effects of corn (CDG) and sorghum (SDG) wet distillers grains with solubles on feedlot cattle performance, carcass characteristics, and apparent total tract digestion of nutrients. In Exp. 1, 224 steers were used in a randomized complete block design (initial BW 391.1 +/- 9.51 kg) and fed steam-flaked corn (SFC)-based diets consisting of (DM basis) 0% distillers grains (CON), 15% SDG, 30% SDG, 15% CDG, 30% CDG, 15% of a 50:50 blend of SDG and CDG, and 30% of a 50:50 blend of CDG and SDG. Decreased carcass-adjusted final BW and HCW (P < or = 0.05) were noted as the inclusion amount of distillers grains increased in the diet. Body weight gain efficiency did not differ among the CDG, 50:50 SDG and CDG blend, and CON treatments, but G:F was numerically less with either amount of SDG than for CON, and decreased (P < or = 0.05) as distillers grains were increased from 15 to 30%. Cattle fed CON had greater carcass yield grades than those fed the distillers grain diets (P < or = 0.05). In Exp. 2, crossbred beef steers (n = 36; initial BW 567.3 +/- 53.1 kg) were used in a generalized randomized block design and fed SFC-based diets with 0% distillers grains (CON) and 15% (DM basis) CDG or SDG. Digestibility was determined with a pulse dose of Cr(2)O(3). Feeding steers 15% CDG or SDG increased intakes of CP and NDF (P < or = 0.05), but intakes of DM, OM, and starch did not differ among treatments (P >o r = 0.07). Apparent total tract digestibilities of DM, OM, CP, NDF, and starch (P > or = 0.25) did not differ among the 3 treatments. Fecal pH averaged over all sampling times was not affected by treatment, nor were average fecal pH values for prefeeding samples (0, 24, 48, and 72 h after the pulse dose) or for samples taken after feeding (12, 36, and 60 h after the pulse dose; P > or = 0.11). Results suggest that with 15% distillers grains in the DM, G:F was similar for cattle fed the CDG, 50:50 SDG and CDG blend, and CON diets. Feeding 30 vs. 15% distillers grains decreased G:F, but including 15% CDG or SDG in SFC-based diets did not affect apparent total tract digestibilities in feedlot steers.


RNA-binding protein DUS16 plays an essential role in primary miRNA processing in the unicellular alga Chlamydomonas reinhardtii.
Canonical microRNAs (miRNAs) are embedded in duplexed stem-loops in long precursor transcripts and are excised by sequential cleavage by DICER nuclease(s). In this miRNA biogenesis pathway, dsRNA-binding proteins play important roles in animals and plants by assisting DICER. However, these RNA-binding proteins are poorly characterized in unicellular organisms. Here we report that a unique RNA-binding protein, Dull slicer-16 (DUS16), plays an essential role in processing of primary-miRNA (pri-miRNA) transcripts in the unicellular green alga Chlamydomonas reinhardtii In animals and plants, dsRNA-binding proteins involved in miRNA biogenesis harbor two or three dsRNA-binding domains (dsRBDs), whereas DUS16 contains one dsRBD and also an ssRNA-binding domain (RRM). The null mutant of DUS16 showed a drastic reduction in most miRNA species. Production of these miRNAs was complemented by expression of full-length DUS16, but the expression of RRM- or dsRBD-truncated DUS16 did not restore miRNA production. Furthermore, DUS16 is predominantly localized to the nucleus and associated with nascent (unspliced form) pri-miRNAs and the DICER-LIKE 3 protein. These results suggest that DUS16 recognizes pri-miRNA transcripts cotranscriptionally and promotes their processing into mature miRNAs as a component of a microprocessor complex. We propose that DUS16 is an essential factor for miRNA production in Chlamydomonas and, because DUS16 is functionally similar to the dsRNA-binding proteins involved in miRNA biogenesis in animals and land plants, our report provides insight into this mechanism in unicellular eukaryotes.


Induction of Epstein-Barr virus-associated DNA polymerase by 12-O-tetradecanoylphorbol-13-acetate. Purification and characterization.
The diterpene ester promoter of mouse skin tumors, 12-O-tetradecanoylphorbol-13-acetate (TPA), efficiently induces Epstein-Barr virus (EBV)-associated DNA polymerase (DNA nucleotidyltransferase) activity in the EBV-producing lymphoblastoid cell line, P3HR-1. With the use of intervent dilution chromatography followed by sequential DEAE-cellulose and phosphocellulose column chromatography, the virus-associated enzyme has been isolated and purified 300-fold. The partially purified EBV DNA polymerase activity could be distinguished from cellular polymerases by its activation with salt and its degree of sensitivity to N-ethylmaleimide and phosphonoacetic acid. The enzyme showed maximum activity for copying activated calf thymus DNA in the presence of 100 mM ammonium sulfate. In the absence of salt, the enzyme utilized with high efficiency deoxyoligomer-homopolymer templates, but failed to copy poly(rA) . oligo(dT)10 and oligo(dT)10, showing that the enzyme had properties distinct from DNA polymerase gamma, reverse transcriptase, and terminal deoxynucleotidyltransferase. The partially purified enzyme is strongly inhibited by acyclovir triphosphate and thus has properties similar to herpes simplex virus DNA polymerase.


[Venous drainage of the testis and the causes of the development of varicocele in children].
The article discusses the results of angiological examination of 42 children with primary and 13 with recurrent varicocele by the method of ++trans-scrotal antegrade venotesticulography. Three groups of patients were distinguished: I--with drainage of blood into the left testicular vein, II--with drainage into the left cremasteric vein, III--with simultaneous drainage into the two above-indicated veins. Incompetence of the valvular apparatus of the left testicular vein and impaired blood drainage from the left external iliac vein with the development of retrograde flow of blood along the left cremasteric vein are the most frequent causes of varicocele in children.


Sublimable C5A delivery provides sustained and prolonged anti-HIV microbicidal activities.
We have identified a short amphipathic helical peptide, called C5A, which exhibits potent microbicidal activities in vitro and which offers protection from vaginal HIV transmission in vivo in a humanized mouse model. However, there are many obstacles to overcome before C5A can be considered a true microbicidal candidate. First, it must be stabilized against enzymatic degradation in a continuously warm and moist environment. Second, it must be delivered in a controlled manner to achieve long-term and coitally independent efficacy. We demonstrate in this in vitro study that the combination of two matrices with different subliming properties ((hexamethylcyclotrisiloxane [HMCS] and cyclododecane [CDD]) containing 10% labile C5A yielded the best results in terms of controlled release and preserved anti-HIV activity of the peptide when pre-exposed to cell-free medium or cell culture at body temperature for up to 2 months.


A survey of antibiotic resistance of Escherichia Coli isolated from farm animals in Great Britain from 1971 to 1977.
A total of 94,827 Escherichia coli strains isolated from cattle, sheep, pigs and poultry during the years 1971 to 1977 were tested for resistance to six antibiotics using a disc diffusion technique. The percentage of strains resistant to chloramphenicol (10 microgram), streptomycin (10 microgram), tetracycline (10 microgram), neomycin (10 Microgram) and furazolidone (15) were 16.8, 53.9, 42.7, 18 and 10.9 per cent, respectively; 52.2 per cent of strains (1971 and 1972) were resistant to 2 microgram ampicillin and 27.8 per cent of strains (1973 and 1977) were resistant to 10 microgram ampicillin. There was no evidence of an overall increase in antibiotic resistance during the seven year period. The animal species of origin was recorded for each of the 55,494 E coli strains examined during 1974 to 1977; 31,763 strains were isolated from cattle, 15,688 from pigs, 4582 from sheep and 3191 from poultry. Considerable variations in antibiotic resistance were recorded for strains isolated from different species.


A case of primary CNS embryonal rhabdomyosarcoma with PAX3-NCOA2 fusion and systematic meta-review.
Primary central nervous system (CNS) rhabdomyosarcoma is a rare mesenchymal tumor predominantly seen in children and associated with a poor outcome. We report a case of primary CNS rhabdomyosarcoma with PAX3-NCOA2 fusion and present a systematic meta-review of primary CNS rhabdomyosarcoma to characterize this rare tumor. We present the case of a 6-year-old boy with primary CNS rhabdomyosarcoma in the posterior fossa. In a systematic meta-review, we compare the demographic data of primary CNS rhabdomyosarcoma with data of rhabdomyosarcoma at all sites from the SEER database and analyze clinical factors associated with survival outcome. Our patient underwent gross total resection and received vincristine, actinomycin-D, cyclophosphamide with early introduction of concurrent focal radiation and remained alive with no evidence of disease for 2 years after the end of therapy. Histopathological review revealed embryonal-type rhabdomyosarcoma, and whole-transcriptome analysis revealed PAX3 (EX6)-NCOA2 (EX12) fusion. In all, 77 cases of primary CNS rhabdomyosarcoma were identified through the meta-review. The demographic data of primary CNS rhabdomyosarcoma were similar to data of rhabdomyosarcoma at all sites. Overall and event-free survival outcomes were available for 64 and 56 patients, respectively, with a 3-year OS of 29.0% and a 3-year EFS of 25.7%. The group that received trimodal treatment exhibited better survival outcomes, with a 3-year OS of 57.4% and a 3-year EFS of 46.3%. Primary CNS rhabdomyosarcoma shares common histological, molecular, and demographic features with non-CNS rhabdomyosarcoma. A trimodal treatment approach with early introduction of radiation therapy may result in favorable survival outcomes.


Global DNA methylation remodeling during direct reprogramming of fibroblasts to neurons.
Direct reprogramming of fibroblasts to neurons induces widespread cellular and transcriptional reconfiguration. Here, we characterized global epigenomic changes during the direct reprogramming of mouse fibroblasts to neurons using whole-genome base-resolution DNA methylation (mC) sequencing. We found that the pioneer transcription factor Ascl1 alone is sufficient for inducing the uniquely neuronal feature of non-CG methylation (mCH), but co-expression of Brn2 and Mytl1 was required to establish a global mCH pattern reminiscent of mature cortical neurons. Ascl1 alone induced promoter CG methylation (mCG) of fibroblast specific genes, while BAM overexpression additionally targets a competing myogenic program and directs a more faithful conversion to neuronal cells. Ascl1 induces local demethylation at its binding sites. Surprisingly, co-expression with Brn2 and Mytl1 inhibited the ability of Ascl1 to induce demethylation, suggesting a contextual regulation of transcription factor - epigenome interaction. Finally, we found that de novo methylation by DNMT3A is required for efficient neuronal reprogramming.


Raster-scan optoacoustic angiography of blood vessel development in colon cancer models.
Raster-scan optoacoustic angiography at 532 nm wavelength with 50 μm lateral resolution at 2 mm diagnostic depth was used for quantitative characterization of neoangiogenesis in colon cancer models. Two tumor models of human colon adenocarcinoma (HT-29) and murine colon carcinoma (CT26) different in their histology and vascularization were compared. Tumors of both origins showed an inhomogeneous distribution of areas with high and low vascularization. Rapidly growing CT26 tumor demonstrated a higher rate of vessel growth from the periphery to the center. Peculiarities of the vascularity of tumor models revealed by optoacoustic imaging were confirmed by fluorescent microscopy with FITC-dextran and morphological analysis. The obtained results may be important for the investigation of tumor development and for improvement of colon cancer treatment strategies.


Construction of 6-thioguanine and 6-mercaptopurine carriers based on βcyclodextrins and gold nanoparticles.
As a novel strategy to overcome some of the therapeutic disadvantages of 6-thioguanine (TG) and 6-mercaptopurine (MP), we propose the inclusion of these drugs in βcyclodextrin (βCD) to form the complexes βCD-TG and βCD-MP, followed by subsequent interaction with gold nanoparticles (AuNPs), generating the ternary systems: βCD-TG-AuNPs and βCD-MP-AuNPs. This modification increased their solubility and improved their stability, betting by a site-specific transport due to their nanometric dimensions, among other advantages. The formation of the complexes was confirmed using powder X-ray diffraction, thermogravimetric analysis and one and two-dimensional NMR. A theoretical study using DFT and molecular modelling was conducted to obtain the more stable tautomeric species of TG and MP in solution and confirm the proposed inclusion geometries. The deposition of AuNPs onto βCD-TG and βCD-MP via sputtering was confirmed by UV-vis spectroscopy. Subsequently, the ternary systems were characterized by TEM, FE-SEM and EDX to directly observe the deposited AuNPs and evaluate their sizes, size dispersion, and composition. Finally, the in vitro permeability of the ternary systems was studied using parallel artificial membrane permeability assay (PAMPA).


Strong geometrical dependence of the absorption of light in arrays of semiconductor nanowires.
We demonstrate experimentally that arrays of base-tapered InP nanowires on top of an InP substrate form a broad band and omnidirectional absorbing medium. These characteristics are due to the specific geometry of the nanowires. Almost perfect absorption of light (higher than 97%) occurs in the system. We describe the strong optical absorption by finite-difference time-domain simulations and present the first study of the influence of the geometry of the nanowires on the enhancement of the optical absorption by arrays. Cylindrical nanowires present the highest absorption normalized to the volume fraction of the semiconductor. The absolute absorption in layers of conical nanowires is higher than that in cylindrical nanowires but requires a larger volume fraction of semiconducting material. Base-tapered nanowires, with a cylindrical top and a conical base, represent an intermediate geometry. These results set the basis for an optimized optical design of nanowire solar cells.


Use of 4-methylumbelliferyl-6-sulpho-2-acetamido-2-deoxy-beta- D-glucopyranoside for prenatal diagnosis of Tay-Sachs disease using chorionic villi.
Prenatal diagnosis of Tay-Sachs disease was performed using the sulphated substrate 4-methylumbelliferyl-6-sulpho-2-acetamido-2-deoxy-beta-D-glucopyranoside to detect hexosaminidase A in chorionic villi. The presence or absence of hexosaminidase A in villi was detected by both a quantitative enzyme assay, and by a rapid, novel procedure which permitted visual discrimination between normal and affected villi.


Amitriptyline Intoxication in Children: Twenty Years' Experience in a Tertiary Care Center in Turkey.
Amitriptyline ingestion is an important cause of poisoning morbidity and mortality in Turkey and other countries. In contrast to adults, data concerning amitriptyline intoxication in children are limited. The purpose of this study was to investigate amitriptyline intoxication findings in the pediatric population, based on age groups and reported dosages. The medical records of 192 patients admitted to the Karadeniz Technical University Medical Faculty Farabi Hospital Pediatric Emergency Department, Turkey, due to amitriptyline intoxication in 1997-2017 were examined retrospectively. Patients were divided into 6 groups based on amitriptyline doses and 4 groups based on age. Complete blood count, blood glucose, serum electrolytes, renal and liver function tests, coagulation tests (prothrombin time and partial thromboplastin time), and blood gas analysis were studied in all patients. Electrocardiography was performed on all children, and chest radiography and electroencephalography on those with respiratory or central nervous system symptoms. Amitriptyline intoxication was most frequently observed between the ages of 1 and 4 years. The most common signs and symptoms observed at time of hospital admission were lethargy and drowsiness (45.3%), sinus tachycardia (19.2%), and nausea and vomiting (13%). The most common laboratory finding was hyperglycemia (17.7). Six patients were intubated because of respiratory failure, and mechanical ventilation was initiated in these cases. One patient with amitriptyline overdose had persistent supraventricular tachycardia. Four children died due to amitriptyline intoxication. Tricyclic antidepressant intoxication is a leading cause of mortality and morbidity in children. It is therefore particularly important to identify the clinical and laboratory findings that develop with high-dose consumption.


Comparative anatomy of teeth from past to present.
The comparative anatomy of teeth has a long tradition in research, starting more than two thousand years ago in antiquity. In the 19th century, Richard Owen's oeuvre Odontography (1840-45) contributed much to establish odontology as an independent scientific discipline. After a short outline of the historical development of the comparative anatomy of teeth, we describe the contents and importance of Owen's Odontography. Finally, we sketch the contemporary situation of dental morphology, which in the course of the last thirty years has developed into an important and internationally highly recognized multidisciplinary field.


Workflow for Pediatric Midface and Orbital Reconstruction With a Patient-Specific Autogenous Bone Graft.
Extensive midface and orbital reconstruction is challenging, especially in a pediatric population. A 13-year-old patient was diagnosed with fibrous dysplasia of the midface, which required complete resection of the zygomatic bone and orbital floor. The authors present a complete midface and orbital reconstruction, using a patient-specific autologous bone graft, in a growing pediatric patient. Postoperative analysis showed a symmetric orbital floor and good clinical outcome. After 12 months of follow up, no bone resorption was observed. Patient-specific autologous bone grafts have a clear role in the treatment algorithm of patients with large skull bone defects, with emphasis on the pediatric patient. The advantages can be even greater in a pediatric population, because they can benefit more from the minimal invasive approach. Furthermore, this technique allows single-stage complex reconstructive surgeries with a decreased operating time.


Genome degeneration and adaptation in a nascent stage of symbiosis.
Symbiotic associations between animals and microbes are ubiquitous in nature, with an estimated 15% of all insect species harboring intracellular bacterial symbionts. Most bacterial symbionts share many genomic features including small genomes, nucleotide composition bias, high coding density, and a paucity of mobile DNA, consistent with long-term host association. In this study, we focus on the early stages of genome degeneration in a recently derived insect-bacterial mutualistic intracellular association. We present the complete genome sequence and annotation of Sitophilus oryzae primary endosymbiont (SOPE). We also present the finished genome sequence and annotation of strain HS, a close free-living relative of SOPE and other insect symbionts of the Sodalis-allied clade, whose gene inventory is expected to closely resemble the putative ancestor of this group. Structural, functional, and evolutionary analyses indicate that SOPE has undergone extensive adaptation toward an insect-associated lifestyle in a very short time period. The genome of SOPE is large in size when compared with many ancient bacterial symbionts; however, almost half of the protein-coding genes in SOPE are pseudogenes. There is also evidence for relaxed selection on the remaining intact protein-coding genes. Comparative analyses of the whole-genome sequence of strain HS and SOPE highlight numerous genomic rearrangements, duplications, and deletions facilitated by a recent expansion of insertions sequence elements, some of which appear to have catalyzed adaptive changes. Functional metabolic predictions suggest that SOPE has lost the ability to synthesize several essential amino acids and vitamins. Analyses of the bacterial cell envelope and genes encoding secretion systems suggest that these structures and elements have become simplified in the transition to a mutualistic association.


HIV-Associated Histoplasmosis: Current Perspectives.
Histoplasmosis is an endemic mycosis caused by Histoplasma capsulatum. Infection develops by inhalation of microconidia from environmental sites inhabited by birds and bats. Disseminated disease is the usual presentation due to impaired cellular immunity. Common clinical manifestations include fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms. Histoplasma antigen detection is the most sensitive method for diagnosis. The sensitivity of the MVista® Quantitative Histoplasma antigen enzyme immunoassay is 95-100% in urine, over 90% in serum and bronchoalveolar lavage (BAL) antigen and 78% in cerebral spinal fluid (CSF). A proven diagnosis can be established by culture or pathology with sensitivities between 70% and 80%. The sensitivity of antibody detection by immunodiffusion or complement fixation was between 60% and 70%. Diagnosis using molecular methods has not been adequately validated for implementation and FDA cleared assays are unavailable. Liposomal amphotericin B should be used for 1-2 weeks followed by itraconazole for at least one year until CD4 counts are above 150 cells/mm3, HIV viral load is below 400 copies/mL and Histoplasma urine antigen is negative. Serum itraconazole level should be monitored to avoid drug toxicity. Antigen should be measured periodically to establish that treatment is effective and to assist in identifying relapse. The incidence of immune reconstitution inflammatory syndrome is low but it must be considered in patients who are thought to be failing antifungal treatment as it does not respond to changing antifungal agents but rather to initiation of corticosteroid therapy. In this review, we discuss pathogenesis, clinical manifestations, diagnosis and treatment based on personal experience and relevant publications.


Detailed studies of a high-capacity electrode material for rechargeable batteries, Li2MnO3-LiCo(1/3)Ni(1/3)Mn(1/3)O2.
Lithium-excess manganese layered oxides, which are commonly described by the chemical formula zLi(2)MnO(3)-(1-z)LiMeO(2) (Me = Co, Ni, Mn, etc.), are of great importance as positive electrode materials for rechargeable lithium batteries. In this Article, Li(x)Co(0.13)Ni(0.13)Mn(0.54)O(2-δ) samples are prepared from Li(1.2)Ni(0.13)Co(0.13)Mn(0.54)O(2) (or 0.5Li(2)MnO(3)-0.5LiCo(1/3)Ni(1/3)Mn(1/3)O(2)) by an electrochemical oxidation/reduction process in an electrochemical cell to study a reaction mechanism in detail before and after charging across a voltage plateau at 4.5 V vs Li/Li(+). Changes of the bulk and surface structures are examined by synchrotron X-ray diffraction (SXRD), X-ray absorption spectroscopy (XAS), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectroscopy (SIMS). SXRD data show that simultaneous oxygen and lithium removal at the voltage plateau upon initial charge causes the structural rearrangement, including a cation migration process from metal to lithium layers, which is also supported by XAS. This is consistent with the mechanism proposed in the literature related to the Li-excess manganese layered oxides. Oxygen removal associated with the initial charge on the high voltage plateau causes oxygen molecule generation in the electrochemical cells. The oxygen molecules in the cell are electrochemically reduced in the subsequent discharge below 3.0 V, leading to the extra capacity. Surface analysis confirms the formation of the oxygen containing species, such as lithium carbonate, which accumulates on the electrode surface. The oxygen containing species are electrochemically decomposed upon second charge above 4.0 V. The results suggest that, in addition to the conventional transition metal redox reactions, at least some of the reversible capacity for the Li-excess manganese layered oxides originates from the electrochemical redox reaction of the oxygen molecules at the electrode surface.


Insight into the function and evolution of the Wood-Ljungdahl pathway in Actinobacteria.
Carbon fixation by chemoautotrophic microbes such as homoacetogens had a major impact on the transition from the inorganic to the organic world. Recent reports have shown the presence of genes for key enzymes associated with the Wood-Ljungdahl pathway (WLP) in the phylum Actinobacteria, which adds to the diversity of potential autotrophs. Here, we compiled 42 actinobacterial metagenome-assembled genomes (MAGs) from new and existing metagenomic datasets and propose three novel classes, Ca. Aquicultoria, Ca. Geothermincolia and Ca. Humimicrobiia. Most members of these classes contain genes coding for acetogenesis through the WLP, as well as a variety of hydrogenases (NiFe groups 1a and 3b-3d; FeFe group C; NiFe group 4-related hydrogenases). We show that the three classes acquired the hydrogenases independently, yet the carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS) was apparently present in their last common ancestor and was inherited vertically. Furthermore, the Actinobacteria likely donated genes for CODH/ACS to multiple lineages within Nitrospirae, Deltaproteobacteria (Desulfobacterota), and Thermodesulfobacteria through multiple horizontal gene transfer events. Finally, we show the apparent growth of Ca. Geothermincolia and H2-dependent acetate production in hot spring enrichment cultures with or without the methanogenesis inhibitor 2-bromoethanesulfonate, which is consistent with the proposed homoacetogenic metabolism.


Attribution of mortality to the urban heat island during heatwaves in the West Midlands, UK.
The Urban Heat Island (UHI) effect describes the phenomenon whereby cities are generally warmer than surrounding rural areas. Traditionally, temperature monitoring sites are placed outside of city centres, which means that point measurements do not always reflect the true air temperature of urban centres, and estimates of health impacts based on such data may under-estimate the impact of heat on public health. Climate change is likely to exacerbate heatwaves in future, but because climate projections do not usually include the UHI, health impacts may be further underestimated. These factors motivate a two-dimensional analysis of population weighted temperature across an urban area, for heat related health impact assessments, since populations are typically densest in urban centres, where ambient temperatures are highest and the UHI is most pronounced. We investigate the sensitivity of health impact estimates to the use of population weighting and the inclusion of urban temperatures in exposure data. We quantify the attribution of the UHI to heat related mortality in the West Midlands during the heatwave of August 2003 by comparing health impacts based on two modelled temperature simulations. The first simulation is based on detailed urban land use information and captures the extent of the UHI, whereas in the second simulation, urban land surfaces have been replaced by rural types. The results suggest that the UHI contributed around 50 % of the total heat-related mortality during the 2003 heatwave in the West Midlands. We also find that taking a geographical, rather than population-weighted, mean of temperature across the regions under-estimates the population exposure to temperatures by around 1 °C, roughly equivalent to a 20 % underestimation in mortality. We compare the mortality contribution of the UHI to impacts expected from a range of projected temperatures based on the UKCP09 Climate Projections. For a medium emissions scenario, a typical heatwave in 2080 could be responsible for an increase in mortality of around 3 times the rate in 2003 (278 vs. 90 deaths) when including changes in population, population weighting and the UHI effect in the West Midlands, and assuming no change in population adaptation to heat in future.


Effect of noise and reverberation on speech intelligibility for cochlear implant recipients in realistic sound environments.
Previous studies have suggested a strong effect of reverberation on speech intelligibility (SI) in cochlear implant (CI) recipients. In many of them, different reverberation conditions were obtained by altering the acoustic absorption of a single room, thereby omitting the effect of the room volume. In addition, studies that have investigated the combined effects of reverberation and noise on SI have overlooked the effect of reverberation on the modulation of the noise. In the present study, SI was measured unilaterally in 12 CI recipients in quiet and in noise using a three-dimensional loudspeaker array. Target speech was convolved with room impulse responses (RIRs) recorded at three talker-to-listener distances in five physical rooms with distinct reverberation times. Noise consisted of four two-talker dialogues convolved with RIRs measured at fixed positions around the listener. Results in quiet suggest that a significant drop in SI occurs mainly at long talker-to-listener distances, and small reverberant rooms affect SI the most. In noise, the most detrimental type of noise is anechoic as it is the most modulated. Overall, the results suggest that at fixed signal-to-noise ratios the effects of noise and reverberation are smallest at short distances in large rooms or in small rooms with some reverberation.


RhoA influences the nuclear localization of extracellular signal-regulated kinases to modulate p21Waf/Cip1 expression.
The 42/44-kD mitogen-activated protein kinases (extracellular signal-regulated kinases, ERKs) regulate smooth muscle cell (SMC) cell-cycle progression and can either promote or inhibit proliferation depending on the activation status of the small GTPase RhoA. RhoA is involved in the regulation of the actin cytoskeleton and converges on multiple signaling pathways. However, the mechanism by which RhoA modulates ERK signaling is not well defined. The purpose of this investigation was to examine whether RhoA regulates ERK downstream signaling and cellular proliferation through its effects on the cytoskeleton and the nuclear localization of ERK. Treatment of SMCs with Clostridia botulinum C3 exoenzyme, which inhibits RhoA activation, decreased SMC proliferation to 24+/-7% of that of controls and increased p21Waf1/Cip1 transcription and protein levels. These effects of RhoA were reversed by inhibition of ERK phosphorylation. However, inactivation of RhoA did not alter levels of ERK phosphorylation but did increase nuclear localization of phosphorylated ERK. In addition, immunostaining demonstrated that phosphorylated ERK associated with the actin cytoskeleton, which was disrupted by C3 exoenzyme. Leptomycin B, an inhibitor of Crm1 that results in ERK nuclear accumulation, similarly increased p21Waf1/Cip1. RhoA inhibition increased levels of phosphorylated ERK in the cell nucleus. Inhibition of RhoA or pharmacological inhibition of nuclear export resulted in increased p21Waf1/Cip1 expression and decreased SMC proliferation, effects that were partially dependent on ERK. RhoA regulation of the actin cytoskeleton may determine ERK subcellular localization and its subsequent effects on SMC proliferation.


Microcombustion of ng Amounts of Carbon in Non-Volatile Materials for isotope Ratio Evaluation.
Abstract A novel microcombustion technique for carbon isotopic analysis of nanogram amounts of carbon in non-volatile materials based on isotope ratio monitoring (irm) mass spectrometry is described. Liquid or solid samples placed in a quartz sleeve are combusted at 1000°C in a continuous stream of helium and oxygen. CO(2) removed from the carrier gas stream by cryogenic trapping is transferred onto a GC column. Following GC separation, the CO(2) is transferred via an open split to the ion source of a gas isotope ratio mass spectrometer. Reproducibility for samples >25 nmol carbon is <1‰. Problems associated with blanks from various sources and with reproducible deposition of small sample amounts led to variable accuracy, which was dependent on the compound class being analysed. Minimum sample size was in the range from 5 to 10 nmol carbon. Measurements of dissolved organic carbon (DOC) of groundwater from Germany yielded consistent values of δ(13)C = -28.8‰.


Gastro-oesophageal reflux disease in The Netherlands. Results of a multicentre pH study.
Information on the relationships between gastro-oesophageal reflux (GOR), reflux symptoms, hiatal hernia (HH) and oesophagitis, and the response to antisecretory treatment is lacking. In a multicentre study endoscopy, ambulatory 24-h pH monitoring and symptom assessment were carried out in 142 patients with symptomatic reflux disease before and during treatment with ranitidine. Using a randomized, double-blind design, patients took ranitidine 150 mg bid or 300 mg bid. Macroscopic oesophagitis (grade I or II) was found in 85 patients; the remaining 57 patients had normal oesophageal mucosa. A significant correlation was found between the presence of an HH and the presence of oesophagitis. Symptom scores were similar in patients with and without oesophagitis, and in patients with and without HH. Patients with oesophagitis had significantly greater oesophageal acid exposure during the night, and in the total 24-h period, but not during the day. Likewise, patients with HH had greater acid exposure during the night (p < 0.008). Both doses of ranitidine significantly decreased oesophageal acid exposure and the effect was independent of baseline acid exposure. Reflux symptoms cannot be used to differentiate between presence or absence of oesophagitis and/or HH. Reflux patients without oesophagitis have less night-time reflux. Ranitidine dose-dependently decreases oesophageal acid exposure, and the effect is independent of baseline reflux.


Cognitive Rehabilitation for Neurocognitive Late Effects in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Feasibility and Case-Series Study.
Neurocognitive late effects following the diagnosis and treatment of childhood acute lymphoblastic leukemia (ALL) commonly include impaired executive functions (EFs), with negative consequences for one's health-related quality of life and mental health. However, interventions for EF impairments are scarce. Thus, the aims of this study were to (1) explore the feasibility and acceptability of the cognitive rehabilitation program Goal Management Training (GMT) and (2) examine whether GMT is associated with positive outcomes across cases of ALL survivors with EF complaints. Four participants (median age 31.5 years) underwent nine GMT modules in a total of five group sessions. Rehabilitation was focused on compensatory strategies to improve real-life EFs. Participants were evaluated at 2-week and 6-month follow-ups. Evaluation of feasibility and acceptability included adherence, a semi structured interview, self-reports, and safety. Additionally, therapists' experience with implementation was evaluated. Outcome measures included self-reports and neurocognitive tests of attention, EF, and processing speed. All participants completed GMT and rated the intervention as useful, suitable, and satisfactory. The reliable change index showed improved daily life EFs (two participants) and neurocognitive performance (three participants) at 6-month follow-up. Additionally, all participants improved on a "real-life" task involving EF. A future randomized controlled trial is recommended.


Four conserved promoter motifs regulate transcription of the gene encoding human complement component C2.
The early complement components of the classical activation pathway of the complement cascade include the components C1, C4, C2, and C3. These components act in concert to opsonize bacteria, clear immune complexes, and produce inflammatory mediators. They are not structurally homologous nor are they coordinately regulated. The expression of the early complement components is divergent in terms of cytokine responsiveness and tissue specificity. The only pattern of expression shared by the early complement components is inducibility by gamma-IFN and expression in cells of hepatic or monocytic lineage. Nevertheless, four novel conserved promoter motifs were identified in the 5' flanking region of multiple early complement component promoters. Mutation of these four motifs in the C2 promoter decreased transcription in hepatoma cells in transient transfection analyses, and a synthetic promoter consisting of just the four motifs supported transcription in hepatoma cells. Electrophoretic mobility shift assays demonstrate that three of the four conserved elements bind DNA-binding proteins in a tissue-specific manner. One DNA-binding protein is expressed ubiquitously, but the other three are restricted to cells of monocytic or hepatic lineage. Two of the DNA-binding proteins appear to be members of the zinc-finger family of transcription factors. Therefore, these four motifs appear to bind DNA-binding proteins that may function in the tissue-specific expression of C2. Conservation of these four motifs in multiple early complement component genes suggests that these may represent a conserved transcriptional strategy.


Synthetic activation of endogenous PI3K and Rac identifies an AND-gate switch for cell polarization and migration.
Phosphatidylinositol 3-OH kinase (PI3K) has been widely studied as a principal regulator of cell polarization, migration, and chemotaxis. Surprisingly, recent studies showed that mammalian neutrophils and Dictyostelium discoideum cells can polarize and migrate in the absence of PI3K activity. Here we directly probe the roles of PI3K and its downstream effector, Rac, in HL-60 neutrophils by using a chemical biology approach whereby the endogenously present enzymes are synthetically activated in less than one minute. We show that uniform activation of endogenous PI3K is sufficient to polarize previously unpolarized neutrophils and trigger effective cell migration. After a delay following symmetrical phosphatidylinositol (3,4,5)-triphosphate (PIP(3)) production, a polarized distribution of PIP(3) was induced by positive feedback requiring actin polymerization. Pharmacological studies argue that this process does not require receptor-coupled trimeric G proteins. Contrary to the current working model, rapid activation of endogenous Rac proteins triggered effective actin polymerization but failed to feed back to PI3K to generate PIP(3) or induce cell polarization. Thus, the increase in PIP(3) concentration at the leading edge is generated by positive feedback with an AND gate logic with a PI3K-Rac-actin polymerization pathway as a first input and a PI3K initiated non-Rac pathway as a second input. This AND-gate control for cell polarization can explain how Rac can be employed for both PI3K-dependent and -independent signaling pathways coexisting in the same cell.


Analysis of DNA methylation in FFPE tissues using the MethyLight technology.
Novel biomarkers are sought after by mining DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissues. Such tissues offer the great advantage of often having complete clinical data (including survival), as well as the tissues are amenable for laser microdissection targeting specific tissue areas. Downstream analysis of such DNA includes mutational screens and methylation profiling. Screening for mutations by sequencing requires a significant amount of DNA for PCR and cycle sequencing. This is self-inhibitory if the gene screened has a large number of exons. Profiling DNA methylation using the MethyLight technology circumvents this problem and allows for the mining of several biomarkers from DNA extracted from a single microscope slide of the tissue of interest. We describe in this chapter a detailed protocol for MethyLight and its use in the determination of CpG Island Methylator Phenotype status in FFPE colorectal cancer samples.


A theoretical study of multinuclear coupling constants in pyrazoles.
The 243 coupling constants of eight N-R-pyrazoles [R=H, CH3, C6H5, COCH3, NH2, NO2, SO2CF3, Si(CH3)3] have been calculated and compared with 131 experimental values. The agreement is good and can be used to estimate new couplings. The whole collection has been statistically analyzed.


Fatty aldehyde dehydrogenases in Acinetobacter sp. strain HO1-N: role in hexadecanol metabolism.
The role of fatty aldehyde dehydrogenases (FALDHs) in hexadecane and hexadecanol metabolism was studied in Acinetobacter sp. strain HO1-N. Two distinct FALDHs were demonstrated in Acinetobacter sp. strain HO1-N: a membrane-bound, NADP-dependent FALDH activity induced 5-, 15-, and 9-fold by growth on hexadecanol, dodecyl aldehyde, and hexadecane, respectively, and a constitutive, NAD-dependent, membrane-localized FALDH. The NADP-dependent FALDH exhibited apparent Km and Vmax values for decyl aldehyde of 5.0, 13.0, 18.0, and 18.3 microM and 537.0, 500.0, 25.0, and 38.0 nmol/min in hexadecane-, hexadecanol-, ethanol-, palmitate-grown cells, respectively. FALDH isozymes ald-a, ald-b, and ald-c were demonstrated by gel electrophoresis in extracts of hexadecane- and hexadecanol-grown cells. ald-a, ald-b, and ald-d were present in dodecyl aldehyde-grown cells, while palmitate-grown control cells contained ald-b and ald-d. Dodecyl aldehyde-negative mutants were isolated and grouped into two phenotypic classes based on growth: class 1 mutants were hexadecane and hexadecanol negative and class 2 mutants were hexadecane and hexadecanol positive. Specific activity of NADP-dependent FALDH in Ald21 (class 1 mutant) was 85% lower than that of wild-type FALDH, while the specific activity of Ald24 (class 2 mutant) was 55% greater than that of wild-type FALDH. Ald21R, a dodecyl aldehyde-positive revertant able to grow on hexadecane, hexadecanol, and dodecyl aldehyde, exhibited a 100% increase in the specific activity of the NADP-dependent FALDH. The oxidation of [3H]hexadecane byAld21 yielded the accumulation of 61% more fatty aldehyde than the wild type, while Ald24 accumulated 27% more fatty aldehyde, 95% more fatty alcohol, and 65% more wax ester than the wild type. This study provides genetic and physiological evidence for the role of fatty aldehyde as an essential metabolic intermediate and NADP-dependent FALDH as a key enzyme in the dissimilation of hexadecane, hexadecanol, and dodecyl aldehyde in Acinetobactor sp. strain HO1-N.


Interoceptive Abnormalities and Suicidality: A Systematic Review.
Dysfunction of interoception (i.e., difficulties sensing the physiological state of one's own body) is increasingly linked to different mental health disorders and suicidal outcomes. The aim of this study was to systematically review the literature on the association between suicidality and interoception, as well as identify potential confounders and mediators of the relationship. We conducted a systematic review of four databases, allowing for critical examination of the role of different measures of interoception (accuracy, sensibility, awareness, cognitive/emotional evaluation) across the suicide continuum (ideation, plans, attempts, deaths). The search strategy identified 22 studies (14,988 participants). Preliminary but limited evidence was found for impaired interoceptive accuracy among those reporting suicide attempt histories. We found evidence of interoceptive sensibility disturbances across the suicide continuum, including experiences of not trusting one's own body sensations and impaired abilities to sustain and control attention to such sensations. Consistent evidence was also reported for disturbances related to cognitive and emotional evaluations of interoceptive sensations. The latter was particularly pronounced for those reporting suicide attempts, relative to those reporting suicidal thinking or planning alone. Overall, this review's results suggest that interoceptive abnormalities are potentially important indicators of risk for suicidal thinking, intentions, and behaviors. However, due to the inconsistent adjustment for variables of interest, and cross-sectional designs, it is unclear whether interoceptive changes and disturbances have a direct role, or whether the association is explained and mediated by key third variables (e.g. depression, disordered eating, emotional dysregulation). We discuss the implications with respect to suicidal risk and therapeutic interventions.


Synergy between tumor necrosis factor alpha and interleukin 1beta in inducing transcriptional down-regulation of muscarinic M2 receptor gene expression. Involvement of protein kinase A and ceramide pathways.
Stimulation of HEL 299 cells with tumor necrosis factor alpha (TNF-alpha) or interleukin 1beta (IL-1beta) had no effect on M2 muscarinic receptor expression. However, the combination of these two cytokines markedly down-regulated muscarinic M2 receptor protein and mRNA expression and uncoupled M2 receptors from adenylyl cyclase. There was no effect of TNF-alpha and IL-1beta on the m2 muscarinic receptor mRNA stability, and nuclear run-on assays showed reduced m2 receptor gene transcription. Sequential cytokine addition suggests that the synergy involves postreceptor events. Although the cAMP-dependent protein kinase inhibitor H8 provided a significant protection against receptor down-regulation, the protein kinase C inhibitor GF109203X had no effect. The ceramide analog C2-ceramide (N-acetylsphingosine) was without effect on m2 receptor expression. However, a strong synergistic effect was demonstrated when cells were treated with the combination of C2-ceramide and TNF-alpha or IL-1beta. TNF-alpha and/or IL-1beta combination also activated the 46- and 55-kDa c-Jun NH2-terminal protein kinases and to a lesser extent p42 and p44 mitogen-activated protein kinase isoforms. Cycloheximide abolished the TNF-alpha and IL-1beta effect, suggesting that de novo protein synthesis is required for receptor down-regulation. These results suggest that the TNF-alpha and IL-1beta synergize to induce transcriptional down-regulation of the M2 muscarinic receptor, which seems to be mediated through activation of both ceramide and cAMP-dependent protein kinase pathways. Furthermore, these results suggest that M2 receptor expression is under the control of a cytokine network.


Exercise after heart transplantation.
Exercise intolerance in heart transplant recipients (HTR) has a multifactorial origin, involving complex interactions among cardiac, neurohormonal, vascular, skeletal muscle and pulmonary abnormalities. However, the role of these abnormalities may differ as a function of time after transplantation and of many other variables. The present review is aimed at evaluating the role of cardiac, pulmonary and muscular factors in limiting maximal aerobic performance of HTR, and the benefits of chronic exercise. Whereas pulmonary function does not seem to affect gas exchange until a critical value of diffusing lung capacity is attained, cardiac and skeletal muscle function deterioration may represent relevant factors limiting maximal and submaximal aerobic performance. Cardiac function is mainly limited by chronotropic incompetence and diastolic dysfunction, whereas muscle activity seems to be limited by impaired oxygen supply as a consequence of the reduced capillary network. The latter may be due to either immunosuppressive regimen or deconditioning. Endurance and strength training may greatly improve muscle function and maximal aerobic performance of HTR, and may also reduce side effects of immunosuppressive therapy and control risk factors for cardiac allograft vasculopathy. For the above reasons exercise should be considered an important therapeutic tool in the long-term treatment of heart transplant recipients.


Relationship of Preoperative Serum Uric Acid Level with Survival in Colorectal Cancer.
To investigate the prognostic significance of uric acid level in colorectal cancer in addition to conventional factors in terms of survival. Observational Study. At the University of Health Sciences, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, between January 2012 and December 2019. Methodology: A total of selected 332 patients, who underwent surgery for colorectal cancer between 2012 and 2019, were retrospectively reviewed. Patients with a history of neoadjuvant therapy due to rectal cancer, GUT disease, renal failure, stage 4 disease, emergency surgery and severe preoperative infection, were excluded from the study. Peripheral blood samples were collected about a week before the operation. Serum uric acid (SUA) values were measured and recorded. Results: The patients comprised 198 males and 134 females with a mean age 62.2 ±11.7 years (14-91) years in total. Conventional surgery was performed in 228 patients, and laparoscopy in 104 patients. Uric acid level, number of pathological lymph nodes, number of pathological lymph nodes/total number of lymph nodes (LNO), perineural invasion, type of surgery and disease stage were found to be factors affecting the prognosis (p <0.05). Uric acid cut off value of 5.3 or higher was found to be statistically significant in terms of survival. Serum uric acid (SUA) value measured preoperatively was found to be a prognostic factor for colorectal cancer. Key Words: Serum uric acid (SUA), Colon cancer, Rectal cancer, Prognostic factor.


Imaging the dynamics and microstructure of fibrin clot polymerization in cardiac surgical patients using spectrally encoded confocal microscopy.
During cardiac surgery with cardiopulmonary bypass (CPB), altered hemostatic balance may disrupt fibrin assembly, predisposing patients to perioperative hemorrhage. We investigated the utility of a novel device termed spectrally-encoded confocal microscopy (SECM) for assessing fibrin clot polymerization following heparin and protamine administration in CPB patients. SECM is a novel, high-speed optical approach to visualize and quantify fibrin clot formation in three dimensions with high spatial resolution (1.0 μm) over a volumetric field-of-view (165 × 4000 × 36 μm). The measurement sensitivity of SECM was first determined using plasma samples from normal subjects spiked with heparin and protamine. Next, SECM was performed in plasma samples from patients on CPB to quantify the extent to which fibrin clot dynamics and microstructure were altered by CPB exposure. In spiked samples, prolonged fibrin time (4.4 ± 1.8 to 49.3 ± 16.8 min, p < 0.001) and diminished fibrin network density (0.079 ± 0.010 to 0.001 ± 0.002 A.U, p < 0.001) with increasing heparin concentration were reported by SECM. Furthermore, fibrin network density was not restored to baseline levels in protamine-treated samples. In CPB patients, SECM reported lower fibrin network density in protaminized samples (0.055 ± 0.01 A.U. [Arbitrary units]) vs baseline values (0.066 ± 0.009 A.U.) (p = 0.03) despite comparable fibrin time (baseline = 6.0 ± 1.3, protamine = 6.4 ± 1.6 min, p = 0.5). In these patients, additional metrics including fibrin heterogeneity, length and straightness were quantified. Note, SECM revealed that following protamine administration with CPB exposure, fibrin clots were more heterogeneous (baseline = 0.11 ± 0.02 A.U, protamine = 0.08 ± 0.01 A.U, p = 0.008) with straighter fibers (baseline = 0.918 ± 0.003A.U, protamine = 0.928 ± 0.0006A.U. p < 0.001). By providing the capability to rapidly visualize and quantify fibrin clot microstructure, SECM could furnish a new approach for assessing clot stability and hemostasis in cardiac surgical patients.


Pancreas transplantation for type 1 diabetes in Japan: past, present and future prospects.
In Japan, the first pancreas transplantation was performed in 1984 from a brain-dead donor; subsequently, however, the concept of brain death became a social issue. Thereafter, the "Organ Transplant Act", which enables brain-dead transplantation, was enacted in 1997, and then revised in 2010 so that donation after brain death became possible only with the consent of the family. Under the recipient selection and registration system developed after the enactment of the "Organ Transplant Act", more than 400 pancreas transplants have been carried out at facilities certified for brain-dead pancreas transplantation in Japan. Of the 410 total cadaveric pancreas transplants performed by the end of 2019, the patient survival and pancreatic and kidney graft survival rates were considered to be comparable to those in the United States and Europe despite the high frequency of marginal donors. Minimally invasive allogenic islet transplantation came to be covered by national health insurance in 2020 following good outcomes of a recent trial. Furthermore, to overcome the serious donor shortage in Japan, development of xenogeneic islet transplantation and regenerative medicine using stem cells is in progress, with xenotransplantation using porcine islets appearing particularly promising.


Can Anomalous Amplification be Attained without Postselection?
We present a parameter estimation technique based on performing joint measurements of a weak interaction away from the weak-value-amplification approximation. Two detectors are used to collect full statistics of the correlations between two weakly entangled degrees of freedom. Without discarding of data, the protocol resembles the anomalous amplification of an imaginary-weak-value-like response. The amplification is induced in the difference signal of both detectors allowing robustness to different sources of technical noise, and offering in addition the advantages of balanced signals for precision metrology. All of the Fisher information about the parameter of interest is collected. A tunable phase controls the strength of the amplification response. We experimentally demonstrate the proposed technique by measuring polarization rotations in a linearly polarized laser pulse. We show that in the presence of technical noise the effective sensitivity and precision of a split detector is increased when compared to a conventional continuous-wave balanced detection technique.


Computational predictions on the receptive fields and organization of V2 for shape processing.
It has been more than 40 years since the first studies of the secondary visual cortex (V2) were published. However, no concrete hypothesis on how the receptive field of V2 neurons supports general shape processing has been proposed to date. Using a computational model that follows the principle of self-organization, we advance two hypotheses in this letter: (1) typical V2 orientation-selective receptive field contains a primary orientation and a secondary orientation component, forming a corner, a junction, or a cross; and (2) V2 columns with the same primary orientation form contiguous domains, divided into subdomains that prefer different secondary orientations. The first hypothesis is consistent with existing experimental evidence, and both hypotheses can be tested with current techniques in animals. In this manner, computational modeling can be used to provide verifiable predictions that eventually allow us to understand the role of V2 in visual processing.


Multidimensional Functional and Structural Evaluation Reveals Neuroretinal Impairment in Early Diabetic Retinopathy.
To test whether quantitative functional tests and optical coherence tomography (OCT)-defined structure can serve as effective tools to diagnose and monitor early diabetic neuroretinal disease. Fifty-seven subjects with diabetes (23 without diabetic retinopathy [no DR], 19 with mild nonproliferative diabetic retinopathy [mild NPDR], 15 with moderate to severe [moderate NPDR]), and 18 controls underwent full ophthalmic examination, fundus photography, spectral-domain optical coherence tomography (SD-OCT), e-ETDRS (Early Treatment Diabetic Retinopathy Study) acuity, and the quick contrast sensitivity function (qCSF) method. Perimetry testing included short-wavelength automated perimetry (SWAP), standard automated perimetry (SAP), frequency doubling perimetry (FDP), and rarebit perimetry (RBP). ETDRS acuity and RBP were not sensitive for functional differences among subjects with diabetes. AULCSF, a metric of qCSF, was reduced in diabetics with moderate compared to mild NPDR (P = 0.03), and in subjects with no DR compared to controls (P = 0.04). SWAP and SAP mean deviation (MD) and foveal threshold (FT) were reduced in moderate compared to mild NPDR (SWAP, MD P = 0.002, FT P = 0.0006; SAP, MD P = 0.02, FT P = 0.007). FDP 10-2 showed reduced MD in moderate compared to mild NPDR (P = 0.02), and FDP 24-2 revealed reduced pattern standard deviation (PSD) in mild NPDR compared to no DR (P = 0.02). Structural analysis revealed thinning of the ganglion cell layer and inner plexiform layer (GCL+IPL) of moderate NPDR subjects compared to controls. The thinner GCL+IPL correlated with impaired retinal function. This multimodal testing analysis reveals insights into disruption of the neuroretina in diabetes and may accelerate the testing of novel therapies.


Application of analytical performance specifications for urine test strip methods: Importance of reflectance signals.
Urinalysis is essential for diagnosing kidney-related medical conditions. Urine test strip analysis serves as an initial and efficient screening method for reflex testing with accurate quantitative methods. Freshly voided urines (n = 206) were analysed using two urine test strip brands on UC-MAX (Menarini) and cobas u 601 (Roche Diagnostics) instruments. Ordinal scale categories and reflectance signals (if available) were both used for the comparison with reference quantitative methods for glucose, proteins and albumin (cobas 503). Samples were considered positive when glucose > 15 or ≥ 54 mg/dL, proteins ≥ 200 mg/L and albumin ≥ 10 mg/L. Optimized reflectance thresholds were calculated by ROC curve analysis. Analytical performance specifications (APS) for trueness of test strip were gathered from the EFLM guideline (FPD, FNG, FNC). Reflectance signals were significantly lower in urine samples considered positive by the reference method (p < 0.0001). Reflectance signals were also correlated with quantitative measurements, showing strong correlation (0.754 to 0.969). Only the use of optimized reflectance thresholds on cobas u 601 achieved at least the minimum EFLM APS (FPD < 20%, FNG < 50% and FNC < 10%). The use of reflectance signals from urine test strips enhanced accuracy for glucose, proteins, and albumin measurement and may contribute to improve diagnosis of diverse kidney-related conditions.


Fetal protection and potential liability: judicial application of the Pregnancy Discrimination Act and the disparate impact theory.
"Fetal vulnerability programs," which are employer attempts to protect employees' unborn fetuses from harm caused by the mothers' exposure to hazardous material in the workplace, have been challenged as a form of employment discrimination. This Note analyzes the recent judicial application of the Pregnancy Discrimination Act (PDA) and the disparate impact theory to fetal vulnerability cases. The Note also examines the business necessity defense's accommodation of legitimate employer interests. The Note concludes that a more potent business necessity defense, a stricter standard for evaluating alternative protective measures, and a judicial interpretation of the PDA which is more consistent with congressional intent are necessary for fair and reasonable resolution of these cases.


Cochlear function in patients with chronic kidney disease.
To evaluate cochlear functioning in patients (18-45 years old) with varying stages of chronic kidney disease (CKD). Using purposive sampling, 50 participants, 10 in each of the 5 stages of CKD, were selected and underwent pure tone audiometric testing and distortion product otoacoustic emissions (DPOAEs). Significant differences (p < 0.05) were found between pure tone audiometry and DPOAEs in detecting early cochlear dysfunction in the high-frequency range in stages 3 (6,000/5,000 Hz; p = 0.00), 4 (6,000/5,000 Hz; p < 0.03) and 5 (4,000/3,333 Hz; p < 0.01, 8,000/6,667 Hz: p < 0.05) with DPOAEs being more sensitive in identifying early cochlear dysfunction. Patients in stages 1 and 2 presented with normal puretone thresholds and DPOAEs, suggesting that cochlear functioning in these patients was normal. Early cochlear dysfunction, thereby indicating a subclinical hearing loss, was identified in stages 3, 4 and 5 by DPOAE testing. In addition, blood test results, drug intake and concomitant conditions were recorded and analysed which suggested a relationship between reduced cochlear functioning and increased electrolyte levels, treatment regimens and concomitant conditions. Participants in the later stages of CKD presented with early cochlear dysfunction, presenting with subclinical hearing loss. It was postulated that this subclinical hearing loss resulted from a combination of electrolytic, urea and creatinine imbalances, together with concomitant medical conditions and ototoxic drug intake. It was concluded that audiological monitoring be included in the management of patients with CKD and that DPOAEs be introduced as part of the test battery to monitor cochlear function in patients with varying degrees of CKD.


[Effects of Staphylococcus aureus cell-bound protein A on adenosine triphosphate and nitric oxide inhibitory actions in smooth muscles].
Cell-bound protein A (CBPA), an immune-active substance of Staphylococcus aureus was ascertained to depolarize membrane of taenia coli smooth muscle (SM) cells, depress ATP inhibiting action (or uridinetriphosphate (UTP)) and sodium nitroprusside (SNP). ATP or UTP-induced membrane hyperpolarization increased during first minutes of CBPA exposure. Bacterial substance enhanced and then inhibited fast component of nicotine-induced relaxation of histamine-activated smooth muscles. This enhancement was inhibited by N(omega)-nitro-Larginine, a NO-syntase blocker. CBPA decreased ATP inhibiting action upon histamine-induced contraction, but enhanced cholinergic SM excitation. All these processes are reversible.


Pumpkin polysaccharides: Purification, characterization and hypoglycemic potential.
The separation and purification of pumpkin polysaccharide by aqueous two-phase system combined with DEAE cellulose-52 column chromatography. There are two purified polysaccharides, neutral fractions (ATPS-PP-1) (7.67 kDa) and acidic fractions (ATPS-PP-2) (8.83 kDa), were obtained from pumpkin powder which were subsequently characterized structurally. The backbone of ATPS-PP-1 comprised of (1 → 3)-linked-Glcp having branching points at O-3 of (1 → 3,4)-linked-Glcp with terminal Glcp as side chain. ATPS-PP-2, on the other hand, comprised of 1 → Glcp, (1 → 3)-linked-Galp, (1 → 6)-linked-Glcp, (1 → 3,6)-linked-Glcp and (1 → 4)-linked-Glcp as backbone. And ATPS-PP-1with small molecular weight and the backbone consisted of (1 → 3) glycosidic linkages has better hypoglycemic activity. Significant protection was conferred on streptozotocin damaged islet β cells by ATPS-PPs (neutral fractions and acidic fractions). Such protective effect was demonstrated by ATPS-PPs' ability to lower Nitric oxide levels by inhibiting NF-κB mRNA overexpression and afterwards down regulation iNOS mRNA expression, eventually minimizing cell oxidative damage caused by STZ and restoring the normal levels of superoxide dismutase.


Debra-mediated Ci degradation controls tissue homeostasis in Drosophila adult midgut.
Adult tissue homeostasis is maintained by resident stem cells and their progeny. However, the underlying mechanisms that control tissue homeostasis are not fully understood. Here, we demonstrate that Debra-mediated Ci degradation is important for intestinal stem cell (ISC) proliferation in Drosophila adult midgut. Debra inhibition leads to increased ISC activity and tissue homeostasis loss, phenocopying defects observed in aging flies. These defects can be suppressed by depleting Ci, suggesting that increased Hedgehog (Hh) signaling contributes to ISC proliferation and tissue homeostasis loss. Consistently, Hh signaling activation causes the same defects, whereas depletion of Hh signaling suppresses these defects. Furthermore, the Hh ligand from multiple sources is involved in ISC proliferation and tissue homeostasis. Finally, we show that the JNK pathway acts downstream of Hh signaling to regulate ISC proliferation. Together, our results provide insights into the mechanisms of stem cell proliferation and tissue homeostasis control.