Influence of diet pellet hardness and particle size on food utilization by mice, rats and hamsters.
Increasing hardness of diet pellets reduced food wastage by each species. Also, less wastage occurred when pellets made from finely ground materials were given, an effect that was not related to hardness. The hardest diet reduced growth of the mice by reducing true food consumption and a poorer food conversion efficiency (true food consumption/growth) was obtained. Apparent food consumption increased with the softness of the diet and food utilization (apparent food consumption/growth) of the softest diets was less efficient than those of the others. Grinding of the raw materials prior to pelleting had no effect on food conversion, but food utilization was less efficient because of the greater wastage of pellets from coarsely ground materials and consequent apparent food comsumption.


Musical hallucinations, secondary delusions, and lack of insight: results from a cohort study.
Although musical hallucinations do not tend to be accompanied by delusions, occasionally patients persistently accuse others of being responsible for causing the music they perceive, sometimes with severe social consequences such as frequently calling the police or moving house. In this study we seek to broaden our understanding of this rare type of musical hallucination that comes with secondary delusions and lack of insight, and to explore associations, underlying mechanisms, and treatment possibilities. The present study is part of a cohort study on musical hallucinations carried out in the Netherlands from 2010 through 2023. Participants underwent testing with the aid of the MuHa Questionnaire, Launay-Slade Hallucinations Scale (LSHS), Schizotypal Personality Questionnaire (SPQ), Hamilton Depression Rating Scale (HDRS), and Mini Mental State Examination (MMSE). Additionally, they underwent a brain MRI, electroencephalogram, and audiological testing. Five patients out of a group of N = 81 (6%) lacked insight and presented with secondary delusions regarding the perceived music. They were all female, of advanced age, and hearing-impaired, and were diagnosed with cognitive impairment. In three patients (60%), risperidone was started. This had a positive effect on the hallucinations and secondary delusions. The pathophysiological process underlying musical hallucinations is multifactorial in nature. We consider cognitive impairment the most likely contributing factor of the secondary delusions and lack of insight encountered in our patients, and antipsychotics the most beneficial treatment. On the basis of these small numbers, no definite conclusions can be drawn, so further research is needed to elucidate the underlying mechanisms and to develop evidence-based treatment methods for people experiencing this rare and debilitating combination of symptoms. Since the black box warning of risperidone cautions against the use of this drug in elderly persons with dementia, a proper comparison with the efficacy and safety of other antipsychotics for this group is paramount.


Work-related empowerment of nurse managers: a systematic review.
The present study discusses how nurse managers' work-related empowerment has been investigated, in order to determine the level and relationships of empowerment among them. A systematic review was carried out, and a literature search was conducted with certain electronic databases for the period 1990-2009, using the main key words in various combinations. Only nine empirical studies in English were selected for review, in accordance with the requirements for the methodological quality and inclusion criteria. The most common type of study design was a descriptive survey (n = 5), and included various questionnaires, scales, and interviews. Nurse managers' structural, psychological, and work empowerment was found to be high or moderately high. The empowerment of nurse managers correlated positively with job satisfaction, perceived organizational support, role satisfaction, and managerial self-efficacy, and correlated negatively with emotional exhaustion and own health outcomes. Different theoretical approaches ensure a clear understanding of empowerment, but difficulties arise when the findings are synthesized across studies and settings because of the different theoretical frameworks used to conceptualize empowerment.


Porous cobalt-manganese oxide nanocubes derived from metal organic frameworks as a cathode catalyst for rechargeable Li-O2 batteries.
The development of cathode catalysts with a porous structure is essential to design Li-O2 batteries with a high rate performance and good cycle stability. Herein, spinel-type porous cobalt-manganese oxide (Co-Mn-O) nanocubes derived from metal organic frameworks were employed as an electrocatalyst in a Li-O2 battery. The battery with the porous Co-Mn-O nanocubes electrode showed a low overpotential and enhanced capacity. The synergistic effects of large specific surface area, porous structure, and the high electrocatalytic activity of the porous Co-Mn-O nanocubes electrode endowed the Li-O2 battery with a good rate performance and excellent cycle stability up to 100 cycles.


Loss of vocal culture and fitness costs in a critically endangered songbird.
Cultures in humans and other species are maintained through interactions among conspecifics. Declines in population density could be exacerbated by culture loss, thereby linking culture to conservation. We combined historical recordings, citizen science and breeding data to assess the impact of severe population decline on song culture, song complexity and individual fitness in critically endangered regent honeyeaters (Anthochaera phrygia). Song production in the remaining wild males varied dramatically, with 27% singing songs that differed from the regional cultural norm. Twelve per cent of males, occurring in areas of particularly low population density, completely failed to sing any species-specific songs and instead sang other species' songs. Atypical song production was associated with reduced individual fitness, as males singing atypical songs were less likely to pair or nest than males that sang the regional cultural norm. Songs of captive-bred birds differed from those of all wild birds. The complexity of regent honeyeater songs has also declined over recent decades. We therefore provide rare evidence that a severe decline in population density is associated with the loss of vocal culture in a wild animal, with concomitant fitness costs for remaining individuals. The loss of culture may be a precursor to extinction in declining populations that learn selected behaviours from conspecifics, and therefore provides a useful conservation indicator.


Entire papilla preservation technique in the regenerative treatment of deep intrabony defects: 1-Year results.
This study evaluates the clinical outcomes of a novel tunnel-like surgical technique in the treatment of isolated deep intrabony defects. Twelve patients presenting with at least one isolated deep intrabony defect received regenerative periodontal treatment with "entire papilla preservation (EPP)" technique. Access to the intrabony defect for debridement was provided by a bevelled vertical releasing incision positioned in the buccal gingiva of the neighbouring inter-dental space. Following the elevation of a buccal flap, an inter-dental tunnel was prepared undermining the defect-associated papilla. Granulation tissue was removed, root surfaces were carefully debrided and bone substitutes and enamel matrix derivative were applied. Microsurgical suturing technique was used for optimal wound closure. Early healing was uneventful in all cases, and 100% wound closure was maintained during the entire healing period. At 1-year, there was significant attachment gain of 6.83±2.51 mm (p<0.001). The 7±2.8 mm reduction in probing depth was also significant (p<0.001), which was associated with minimal increase in gingival recession (0.16±0.38 mm, p=0.166). Tunnel-like "EPP" technique may limit the risk of wound failure particularly in the early healing phase, thereby preventing exposure of regenerative biomaterials, possibly enhancing stabilization of blood clot in deep intrabony defects and leading to optimal clinical outcomes.


Genotypic resistance mutations in treatment-naïve and treatment-experienced patients under widespread use of antiretroviral drugs in Thailand: implications for further epidemiologic surveillance.
The aims of this study were to illustrate the prevalence and determinants of mutations associated with antiretroviral drug resistance in a group of antiretroviral-naive and treatment-experienced patients in Thailand, where antiretroviral drugs are widely used. One hundred and thirteen treatment-naive (92 CRF01_AE and 21 subtype B patients) and 1,709 treatment-experienced patients were recruited. Genotypic resistance to antiretroviral drugs was studied by sequencing the isolated viruses. Mutation frequencies in treatment-naive patients were reported along with those for treatment-experienced patients. The results showed that all of the patients with treatment-experienced patients showed the same pattern of genotypic resistance. The results also showed that only 14 drug-naive patients (12.4%) carried HIV-1, with at least one drug-resistant mutation. Moreover, four drug-naive patients were found to carry the marker mutations for transmission of drug resistance. The most commonly found marker in drug-naive patients was M36I/V/L (n=90, 81.1%), which is a common natural polymorphism among HIV-1 subtype CRF01_AE individuals. In order to prevent the rapid emergence of resistant virus strains, a national program to monitor antiretroviral drug resistance should be established. We also recommend routine genotypic testing in treatment-naive patients before starting antiretroviral therapy to prevent subtherapeutic response and viral failure.


Intrinsic magnetoresistance of single-walled carbon nanotubes probed by a noncontact method.
The intrinsic magnetotransport effect of the single-walled carbon nanotube (SWNT) has been observed by the cavity perturbation technique, which is a noncontact method for evaluating transport properties. The inverse Q factor of the cavity resonator, which corresponds to the resistance of the sample, shows a linear increase as a function of the magnetic field. The angular and tube diameter dependence of oriented SWNT thin films, and measurements using sorted SWNTs reveal that the observed positive magnetoresistance is due to the Aharonov-Bohm effect of metallic nanotubes.


Chronobiology and the case for sleep health interventions in the community.
Our sleep-wake cycle is determined by the interaction between our homeostatic sleep drive and circadian rhythm. Each of us has a personalised biological rhythm or chronotype that determines the optimal time to fall asleep and wake up. Chronic sleep deprivation has been linked to the development of several physical and mental health disorders, as well as accidents and occupational errors. Around the world, growing recognition of the importance of sleep has led to the adoption of practices that promote sleep health. Given that Singaporeans were consistently found to be one of the most sleep-deprived populations in the world, we believe that there is an urgent need to pursue the introduction of community-based sleep health interventions here. This includes sleep education and promotion of sleep hygiene, adopting practices to reduce social jetlag and improve sleep health, and enhancing screening and treatment of sleep disorders.


Advanced Noise Indicator Mapping Relying on a City Microphone Network.
In this work, a methodology is presented for city-wide road traffic noise indicator mapping. The need for direct access to traffic data is bypassed by relying on street categorization and a city microphone network. The starting point for the deterministic modeling is a previously developed but simplified dynamic traffic model, the latter necessary to predict statistical and dynamic noise indicators and to estimate the number of noise events. The sound propagation module combines aspects of the CNOSSOS and QSIDE models. In the next step, a machine learning technique-an artificial neural network in this work-is used to weigh the outcomes of the deterministic predictions of various traffic parameter scenarios (linked to street categories) to approach the measured indicators from the microphone network. Application to the city of Barcelona showed that the differences between predictions and measurements typically lie within 2-3 dB, which should be positioned relative to the 3 dB variation in street-side measurements when microphone positioning relative to the façade is not fixed. The number of events is predicted with 30% accuracy. Indicators can be predicted as averages over day, evening and night periods, but also at an hourly scale; shorter time periods do not seem to negatively affect modeling accuracy. The current methodology opens the way to include a broad set of noise indicators in city-wide environmental noise impact assessment.


BreaKmer: detection of structural variation in targeted massively parallel sequencing data using kmers.
Genomic structural variation (SV), a common hallmark of cancer, has important predictive and therapeutic implications. However, accurately detecting SV using high-throughput sequencing data remains challenging, especially for 'targeted' resequencing efforts. This is critically important in the clinical setting where targeted resequencing is frequently being applied to rapidly assess clinically actionable mutations in tumor biopsies in a cost-effective manner. We present BreaKmer, a novel approach that uses a 'kmer' strategy to assemble misaligned sequence reads for predicting insertions, deletions, inversions, tandem duplications and translocations at base-pair resolution in targeted resequencing data. Variants are predicted by realigning an assembled consensus sequence created from sequence reads that were abnormally aligned to the reference genome. Using targeted resequencing data from tumor specimens with orthogonally validated SV, non-tumor samples and whole-genome sequencing data, BreaKmer had a 97.4% overall sensitivity for known events and predicted 17 positively validated, novel variants. Relative to four publically available algorithms, BreaKmer detected SV with increased sensitivity and limited calls in non-tumor samples, key features for variant analysis of tumor specimens in both the clinical and research settings.


Quantification and visualization of glutathione S-transferase omega 1 in cells using inductively coupled plasma mass spectrometry (ICP-MS) and fluorescence microscopy.
We report a novel activity-based and Cu-free click chemistry (CC) mediated methodology for glutathione S-transferase omega 1 (GSTO1) quantification using species-unspecific isotope dilution inductively coupled plasma mass spectrometry (SUID ICP-MS), in which dibenzylcyclooctyne-modified 2-chloroacetamide (DBCO-ChAcA) was designed and synthesized, meanwhile, as a navigator towards GSTO1 for subsequent N3-DOTA-Eu-tagging via Cu-free CC. Using (153)Eu-SUID ICP-MS coupled with size exclusion chromatography (SEC), the LOD (3σ) of GSTO1 reached 6.9 fmol with an RSD of 2.4% at the 0.1 μM level (n = 5) considering the recovery of GSTO1 on the SEC was 96.5 ± 2.4%. The GSTO1 contents in the cells of human hepatocellular carcinoma C7721 and breast carcinoma MCF-7 as well as normal hepatic C7701 without or with cis-platin administration were quantified to be from 1.2 μg/10,000 cells (n = 3, RSD = 4.5%) corresponding to 1.2 × 10(-2) ng per cell to 4.76 μg/10,000 cells (n = 3, RSD = 2.9%) corresponding to 4.76 × 10(-2) ng per cell. For a comparative study, DBCO-ChAcA-fluor 488-based fluorescence microscopy could not alone visualize GSTO1 in the cells but could together with those from the small SH-containing molecules such as GSH and that from extra N3-fluor 488 in the cells. This activity-based CC-mediated tagging/labeling strategy provided an opportunity for ICP-MS-based targeted protein quantification, and is very much expected to find its applications in biological mechanism study and the subsequent drug design.


Parental sensitivity to infant distress: what do discrete negative emotions have to do with it?
Parental sensitivity, a crucial element of attachment theory, refers to the ability to correctly interpret and respond appropriately to infants' signals. The question of whether infants' emotional expressions communicate discrete negative emotions has been widely debated in the literature on infant emotional development, but it has rarely been discussed in the parental sensitivity literature. This article explores how insights from the parental sensitivity literature and from evolutionary and dynamical systems perspectives on infant emotion expressions can be brought together to enhance our understanding of parental responsiveness to infant distress. The current research concludes that sensitivity does not rely on reading discrete negative emotions in infant signals, but rather on an integration of complex, graded distress expressions with contextual factors and iterative interaction processes.


Molecular analysis of homocysteic acid-induced neuronal stress.
Hyperhomocysteinemia is a risk factor for vascular and neuronal lesions often observed with concomitant high levels of homocysteic acid. In contrast to homocysteine, homocysteic acid induces calcium influx into neurons, with characteristics of an excitotoxic glutamatergic agonist at elevated concentrations. On the molecular level this is correlated to fast modifications of proteins (phosphorylation and proteolysis). Within the homocysteic acid induced molecular signature we focused in more detail on phosphorylation of two proteins implicated as risk factors in schizophrenia and neurodegeneration: Dihydropyrimidinase related protein and 14-3-3 protein isoforms. Among the identified proteins there are known chaperones and oxidative metabolism enzymes, but a few are new in context of neuronal stress: Lasp-1, a vitamin D associated factor and an expressed sequence with features of a Rho GDP dissociation inhibitor. Moreover, we detect a specific proteolytic processing of heat shock protein 70 and proteindisulfide isomerase, which is abolished by vitamins (folic acid, vitamin B12, and vitamin B6), which also decrease elevated intracellular calcium levels induced by homocysteic acid.


Sensitive and Quantitative Three-Color Protein Imaging in Fission Yeast Using Spectrally Diverse, Recoded Fluorescent Proteins with Experimentally-Characterized In Vivo Maturation Kinetics.
Schizosaccharomyces pombe is an outstanding model organism for cell biological investigations, yet the range of useful and well-characterized fluorescent proteins (XFPs) is limited. We generated and characterized three recoded fluorescent proteins for 3-color analysis in S.pombe, Super-folder GFP, monomeric Kusabira Orange 2 and E2Crimson. Upon optimization and expression in S. pombe, the three proteins enabled sensitive simultaneous 3-color detection capability. Furthermore, we describe a strategy that combines a pulse-chase approach and mathematical modeling to quantify the maturation kinetics of these proteins in vivo. We observed maturation kinetics in S. pombe that are expected from those described for these proteins in vitro and/or in other cell types, but also unpredicted behaviors. Our studies provide a kinetically-characterized, integrated three-color XFP toolbox for S. pombe.


Prevalence and Predictors of Pressure Injuries From Spine Surgery in the Prone Position: Do Body Morphological Changes During Deformity Correction Increase the Risks?
MINI: Pressure injuries are prevalent in patients undergoing spine surgery while prone. Multiple risk factors exist and should be addressed. We found that patients undergoing spinal deformity correction surgery are at unique risk (odds ratio 3.31, P = 0.010) due to body morphological changes occurring secondary to intraoperative changes in spinal alignment. Review of data and prospective study. To investigate the prevalence and predictive factors of pressure injuries in spine surgery performed in the prone position, and to determine whether morphological changes and truncal shifts occurring during deformity correction predispose to this complication. Spine surgery performed in the prone position presents the risk of developing pressure injuries. This risk is potentially increased in deformity correction, because it tends to involve more extensive procedures, with associated longer operating times. Cases of pressure injuries after spine surgery in the prone position were reviewed to ascertain prevalence and determine risk factors. Data including patient factors (age, sex, height, weight, body mass index, American Society of Anesthesiologists grade, comorbidities, Braden scale, neurological status, spinal pathology) and surgical factors (approach, procedure type, number of screws, operated levels, operative time) were collected. Independent risk factors were identified via multivariate analysis. A subsequent prospective analysis of all patients undergoing spinal deformity correction was conducted by performing intraoperative measurements of body morphological changes and shifts in truncal positions. Statistical correlation was performed to determine whether positional shifts cause pressure injuries. The prevalence of pressure injuries was 23.0%. Previous skin problems (P = 0.034), myelopathy (P = 0.013), operative time >300 minutes (P = 0.005), and more than four operated levels (P = 0.006) were independent predictors of pressure injuries. Being a spinal deformity patient was also an independent risk factor for developing pressure injuries (odds ratio 3.31, P = 0.010). Significant changes in body measurements during deformity correction were predictive of pressure injuries. Pressure injuries are prevalent in patients undergoing spine surgery while prone. Future studies should investigate strategies to prevent this complication based on the multiple risk factors identified in the present study. Patients undergoing spinal deformity correction surgery are particularly at risk due to intraoperative body morphological changes. Improved padding methods should be trialed in future studies. 3.


Ties That Bond: Youth Sport as a Vehicle for Social Identity and Positive Youth Development.
An emerging area of research has focused on understanding how the group dynamics of a sport team influence positive youth development (PYD). The identities that youth form through their membership in sport teams (i.e., social identities) have been found to influence teammate behavior and team performance. Yet, minimal work exists on social identity and PYD in youth sport. The purpose of this study was to investigate the relationship between social identity and PYD in sport. Youth engaged in recreational sport (N = 219; Mage = 11.61 years, SD = 1.39 years) completed measures of social identity and PYD in sport. The social identity measure assessed 3 dimensions including ingroup ties (IGT; perceptions of similarity, bonding, belongingness), cognitive centrality (importance of being a team member), and ingroup affect (IGA; feelings associated with group membership). A regression analysis was performed separately for 4 PYD outcomes (personal and social skills, goal setting, initiative, negative experiences) with the 3 dimensions of social identity entered as predictors. Regression analyses revealed that IGT and IGA were positively associated with personal and social skills (R2 Adj. = .29). Further, IGT predicted initiative (R2 Adj. = .16), whereas IGA was positively associated with goal setting (R2 Adj. = .17) and negatively associated with negative experiences (R2 Adj. = .08). The findings extend previous research highlighting the benefits of social identity on teammate behavior and team performance and demonstrate how social identity may contribute to PYD through sport.


Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial.
Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non-ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non-ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non-ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P =.008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P =.08) and transfusions (17.0% vs 16.0%, P =.16). Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non-ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.


Carbon- and oxygen-centered radicals are equally important haptens of allylic hydroperoxides in allergic contact dermatitis.
Limonene is one of the most commonly used fragrance compounds in western countries today. When exposed to air, it autoxidises, forming hydroperoxides that are strong contact allergens. To cause allergic contact dermatitis (ACD), the hydroperoxides are considered to bind covalently to proteins in the skin via a radical pathway. Consequently, the nature and reactions of the radicals formed from the hydroperoxides are important. We have examined the radical formation from, and sensitizing potential of, three allylic hydroperoxides. Two of these are found in the oxidation mixture of limonene, while the third is a synthetic structural analogue. The identity of the radicals formed from these hydroperoxides has been studied in radical trapping experiments. Chemical trapping experiments were performed using 5,10,15,20-tetraphenyl-21 H,23 H-porphine iron(III) chloride [Fe(III)TPPCl 3] as an initiator and 1,1,3,3-tetramethylisoindolin-2-yloxyl as a radical trapper. Electron paramagnetic resonance experiments using photolysis for initiation were performed with and without 5-diethoxy-phosphoryl-5-methyl-1-pyrroline N-oxide. Our results demonstrate the ability of the studied hydroperoxides to form peroxyl, allyloxyl, and oxiranylcarbinyl radicals. These radicals can potentially react with proteins to form immunogenic hapten-protein complexes relevant for ACD. The sensitizing potency of the hydroperoxides was studied in the murine local lymph node assay. All three hydroperoxides were found to be potent sensitizers with some variations, which can be related to the identity and quantity of the radicals formed. The results indicate that both carbon- and oxygen-centered radicals are important intermediates in the formation of hapten-protein complexes and that the sensitizing potency of the hydroperoxides is related to their structures.


Usability of Smart Home Thermostat to Evaluate the Impact of Weekdays and Seasons on Sleep Patterns and Indoor Stay: Observational Study.
Sleep behavior and time spent at home are important determinants of human health. Research on sleep patterns has traditionally relied on self-reported data. Not only does this methodology suffer from bias but the population-level data collection is also time-consuming. Advances in smart home technology and the Internet of Things have the potential to overcome these challenges in behavioral monitoring. The objective of this study is to demonstrate the use of smart home thermostat data to evaluate household sleep patterns and the time spent at home and how these behaviors are influenced by different weekdays and seasonal variations. From the 2018 ecobee Donate your Data data set, 481 North American households were selected based on having at least 300 days of data available, equipped with ≥6 sensors, and having a maximum of 4 occupants. Daily sleep cycles were identified based on sensor activation and used to quantify sleep time, wake-up time, sleep duration, and time spent at home. Each household's record was divided into different subsets based on seasonal, weekday, and seasonal weekday scales. Our results demonstrate that sleep parameters (sleep time, wake-up time, and sleep duration) were significantly influenced by the weekdays. The sleep time on Fridays and Saturdays is greater than that on Mondays, Wednesdays, and Thursdays (n=450; P<.001; odds ratio [OR] 1.8, 95% CI 1.5-3). There is significant sleep duration difference between Fridays and Saturdays and the rest of the week (n=450; P<.001; OR 1.8, 95% CI 1.4-2). Consequently, the wake-up time is significantly changing between weekends and weekdays (n=450; P<.001; OR 5.6, 95% CI 4.3-6.3). The results also indicate that households spent more time at home on Sundays than on the other weekdays (n=445; P<.001; OR 2.06, 95% CI 1.64-2.5). Although no significant association is found between sleep parameters and seasonal variation, the time spent at home in the winter is significantly greater than that in summer (n=455; P<.001; OR 1.6, 95% CI 1.3-2.3). These results are in accordance with existing literature. This is the first study to use smart home thermostat data to monitor sleep parameters and time spent at home and their dependence on weekday, seasonal, and seasonal weekday variations at the population level. These results provide evidence of the potential of using Internet of Things data to help public health officials understand variations in sleep indicators caused by global events (eg, pandemics and climate change).


Diagnostic Classification of Cystoscopic Images Using Deep Convolutional Neural Networks.
The recognition of cystoscopic findings remains challenging for young colleagues and depends on the examiner's skills. Computer-aided diagnosis tools using feature extraction and deep learning show promise as instruments to perform diagnostic classification. Our study considered 479 patient cases that represented 44 urologic findings. Image color was linearly normalized and was equalized by applying contrast-limited adaptive histogram equalization. Because these findings can be viewed via cystoscopy from every possible angle and side, we ultimately generated images rotated in 10-degree grades and flipped them vertically or horizontally, which resulted in 18,681 images. After image preprocessing, we developed deep convolutional neural network (CNN) models (ResNet50, VGG-19, VGG-16, InceptionV3, and Xception) and evaluated these models using F1 scores. Furthermore, we proposed two CNN concepts: 90%-previous-layer filter size and harmonic-series filter size. A training set (60%), a validation set (10%), and a test set (30%) were randomly generated from the study data set. All models were trained on the training set, validated on the validation set, and evaluated on the test set. The Xception-based model achieved the highest F1 score (99.52%), followed by models that were based on ResNet50 (99.48%) and the harmonic-series concept (99.45%). All images with cancer lesions were correctly determined by these models. When the focus was on the images misclassified by the model with the best performance, 7.86% of images that showed bladder stones with indwelling catheter and 1.43% of images that showed bladder diverticulum were falsely classified. The results of this study show the potential of deep learning for the diagnostic classification of cystoscopic images. Future work will focus on integration of artificial intelligence-aided cystoscopy into clinical routines and possibly expansion to other clinical endoscopy applications.


D-atom products in predissociation of CD2CD2OH from the 202-215 nm photodissociation of 2-bromoethanol.
Experimental observations of D fragments from the predissociation of rovibrationally excited partially deuterated 2-hydroxyethyl radicals, CD(2)CD(2)OH, are reported, and possible dissociation channels are analyzed by theory. The radicals are produced by photolysis of 2-bromoethanol at 202-215 nm, and some of them have sufficient internal energy to predissociate. D fragments are detected by 1 + 1' REMPI and their TOF distributions are determined. They can be associated with vinyl alcohol and/or acetaldehyde cofragments. From analysis of the maximum velocities and kinetic energies of the observed D fragments it is concluded that they originate from the decomposition of CD(2)CD(2)OH, but the experimental resolution is insufficient to distinguish between the two possible channels leading to D products. Theoretical analysis and RRKM calculations of microcanonical dissociation rates and branching ratios for the range of available excess energies (up to 5000-8000 cm(-1) above the OH + C(2)D(4) threshold) indicate that the D-producing channels are minor (about 1%) compared to the predominant OH + C(2)D(4) channel, and the branching ratio for D production is more favorable when the reactant radicals have low rotational energy. The vinyl alcohol channel is strongly favored over the acetaldehyde channel at all excess energies, except near the threshold of these channels.


Disappearance of interfering alkali-metal adducted peaks from matrix-assisted laser desorption/ionization mass spectra of peptides with serine addition to alpha-cyano-4-hydroxycinnamic acid matrix.
It has been described that ion yield in both positive- and negative-ion matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) of peptides is often inhibited by trace amounts of alkali metals and that the MALDI mass spectra are contaminated by the interfering peaks originating from traces of alkali metals, even when sample preparation is carefully performed. Addition of serine to the commonly used MALDI matrix alpha-cyano-4-hydroxycinnamic acid (CHCA) significantly improved and enhanced the signals of both protonated and deprotonated peptides, [M+H](+) and [M-H](-). The addition of serine to CHCA matrix eliminated the alkali-metal ion adducts, [M+Na](+) and [M+K](+), and the CHCA cluster ions from the mass spectra. Serine and serinephosphate as additives to CHCA enhanced and improved the formation of molecular-related ions of phosphopeptides in negative-ion MALDI mass spectra.


Mobility impairment and life satisfaction in the Northern Region of Malawi.
There exist many psychosocial sequelae associated with mobility impairment, especially in low-resource settings where access to mobility assistive devices is limited. This study aims to (1) define the burden and presenting aetiologies of mobility impairment in the rural Northern Region of Malawi and (2) assess the relationship between physical disability, life satisfaction and access to mobility aids. At mobility device donation clinics throughout the Northern Region of Malawi, adults living with mobility impairment were surveyed with a demographic questionnaire and a series of validated surveys to assess their physical activity levels (Global Physical Activity Questionnaire [GPAQ]), degree of mobility impairment (Washington Group Extended Set Questions on Disability) and life satisfaction (patient-reported outcomes measurement information systems satisfaction with participation in social roles and general life satisfaction). There were 251 participants who qualified for inclusion, of which 193 completed all surveys. Higher physical activity scores were positively correlated with increased life satisfaction: (1) satisfaction with participation in social roles (0.481, p < 0.0001) and (2) general life satisfaction (0.230, p < 0.001). Respondents who had previously used a formal mobility device reported 235.5% higher physical activity levels ([139.0%, 333.0%], p = 0.006), significantly higher satisfaction with participation in social roles ([0.21, 6.67], p = 0.037) and equivocally higher general life satisfaction ([-1.77, 3.84], p = 0.470). Disability and mental health do not exist in isolation from one another. Given the positive correlations between formal mobility device usage and both physical activity and life satisfaction, interventions that increase access to mobility-assistive devices in undertreated populations are imperative. This study contributes to the understanding of the complex relationship between physical disability, access to mobility aids, and life satisfaction. Results from this study suggest the potential benefit that increasing access to mobility aids may have in improving the quality of life of mobility impaired persons in resource-limited settings, such as the Northern Region of Malawi.


Expression of maspin in prostate cells is regulated by a positive ets element and a negative hormonal responsive element site recognized by androgen receptor.
Prostate cancer is the most common cancer in men. The molecular mechanisms leading to its development are poorly understood. Maspin is a tumor-suppressing serpin expressed in normal breast and prostate epithelium. We have found that expression of maspin in normal and carcinoma-derived prostate epithelial cells is differentially regulated at the transcriptional level. We have identified two different kinds of cis elements, Ets and hormonal responsive element (HRE), in the maspin promoter. The Ets element is active in regulating maspin expression in normal prostate epithelial cells but inactive in tumor cells. The HRE site is a negative element that is active in both cell types. This negative DNA sequence can repress a heterologous promoter recognized by the androgen receptor. We conclude that expression of maspin is under the influence of both a positive Ets and a negative HRE element. Loss of maspin expression during tumor progression apparently results from both the absence of transactivation through the Ets element and the presence of transcription repression through the negative HRE element recognized by androgen receptor.


Synthesis of ordered macroporous polymers from colloidal silica templates.
Ordered macroporous polymers have been prepared by replication of colloidal crystals made from silica spheres 298 nm in diameter. The colloidal crystals were prepared on a clean indium tin oxide (ITO) glass substrate by sedimentation of a solution of a silica colloidal dispersed solution. The air between the silica spheres was filled by the monomer of poly(methyl methacrylate) (PMMA) that can be subsequently polymerized. After infiltration, the silica spheres were removed by means of etching with hydrofluoric acid (HF) aqueous solution and left a polycrystalline network of interconnected pores. These macroporous ordered structures represent a promising approach for bandgap engineering and can be used as the foundation of various potential applications.


Fluorodeoxyglucose Positron Emission Tomography Can Provide Useful Information for Differentiating Thymic Epithelial Tumors.
We examined the usefulness of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting the World Health Organization (WHO) histologic type and Masaoka stage of thymic epithelial tumors. A total of 73 patients with thymic epithelial tumors who underwent preoperative FDG-PET were included. Relationships between the maximum standardized uptake value (SUVmax) and WHO histologic type and the Masaoka stage of the tumor were examined. Differences in SUVmax between the various groups were calculated. To avoid the effect of the tumor size on SUVmax, the ratio of SUVmax to tumor size (SUVmax/T) was also examined. There was a significant relationship between SUVmax and WHO histologic type. SUVmax of high-risk thymomas (types B2 and B3) was significantly higher than that of low-risk thymomas (types A, AB, and B1). SUVmax of thymic carcinomas was also significantly higher than those of the low-risk and high-risk groups. The relationship between the SUVmax/T and WHO histologic type showed more significant results. SUVmax and SUVmax/T showed higher values in patients with advanced Masaoka stage disease than in those with early-stage disease. FDG-PET can provide useful information for differentiating thymic epithelial tumors. The SUVmax/T is more useful than the SUVmax for differentiating between low-risk and high-risk thymomas.


A cellular, molecular, and pharmacological basis for appendage regeneration in mice.
Regenerative medicine aims to restore normal tissue architecture and function. However, the basis of tissue regeneration in mammalian solid organs remains undefined. Remarkably, mice lacking p21 fully regenerate injured ears without discernable scarring. Here we show that, in wild-type mice following tissue injury, stromal-derived factor-1 (Sdf1) is up-regulated in the wound epidermis and recruits Cxcr4-expressing leukocytes to the injury site. In p21-deficient mice, Sdf1 up-regulation and the subsequent recruitment of Cxcr4-expressing leukocytes are significantly diminished, thereby permitting scarless appendage regeneration. Lineage tracing demonstrates that this regeneration derives from fate-restricted progenitor cells. Pharmacological or genetic disruption of Sdf1-Cxcr4 signaling enhances tissue repair, including full reconstitution of tissue architecture and all cell types. Our findings identify signaling and cellular mechanisms underlying appendage regeneration in mice and suggest new therapeutic approaches for regenerative medicine.


The growth hormone (GH) gene is expressed in the lateral hypothalamus: enhancement by GH-releasing hormone and repression by restraint stress.
Recent studies suggest that GH may modulate emotion, behavior, or stress response by its direct actions on the brain, and possible expression of the GH gene in the brain has been predicted. In this study we have investigated whether and where the GH gene is expressed in the brain and how it is regulated. Ribonuclease protection assay and 5'-rapid amplification of complementary DNA ends-PCR analyses indicated that the GH gene was expressed in rat brain, initiating at the identical transcription start point as that for pituitary GH gene expression. The brain GH messenger RNA was predominantly detected in the lateral hypothalamus (lh) by in situ reverse transcription-PCR analysis. GH gene expression in the brain was significantly enhanced by GH-releasing hormone administration and was rapidly repressed by exposure to restraint stress in the water, whereas the changes in pituitary GH messenger RNA contents in these circumstances were relatively smaller. The results of the present study suggest that the brain GH is predominantly expressed in lh under the control of physiological conditions to play a role in the modulation of brain functions.


Institutional practice in sizing of the hybrid prosthesis in frozen elephant trunk surgery.
The frozen elephant trunk (FET) technique for total arch replacement (TAR) is widely used for repair of aortic arch dissections and aneurysms. Despite its widespread adoption, there are no international or regional guidelines for the sizing of FET prostheses in TAR. We seek to highlight the heterogeneity thereof and pave the way for evidence-based guidelines to advise FET prosthesis sizing in TAR. An online questionnaire was sent to 22 specialist aortic surgeons from 13 different countries across North America, Europe, Asia, and Australia, inquiring about each surgeon's approach to FET prosthesis sizing. The results were then pooled for frequency analysis. All 22 surgeons responded to the questionnaire. Zone 2 is preferred implantation zone for AAD, CAD, and TAA (selected by 72.7%, 72.7%, and 68.2% respectively). The maximal diameter of the true lumen in the DTA is the most common index measurement for AAD and CAD (40.9% and 59.1%, respectively). Stent-graft diameters equal to the index measurement is the most common approach for AAD and CAD (77.3% and 45.5%, respectively) while 59.1% of surgeons oversize the index diameter by 10% for TAA; 100 mm is the preferred length for 50.0%, 27.3%, and 40.9% of surgeons in AAD, CAD, and TAA respectively. There is considerable heterogeneity in sizing practices for FET prostheses internationally, with variable evidence for its impact on clinical outcomes. This issue would be aided by the development of evidence-based guidelines to inform clinical decision making.


Controlled release of corticosteroid with biodegradable nanoparticles for treating experimental autoimmune uveitis.
Noninfectious uveitis is a potentially blinding ocular condition that often requires treatment with corticosteroids to prevent inflammation-related ocular complications. Severe forms of uveitis such as panuveitis that affects the whole eye often require a combination of topical and either regional or systemic corticosteroid. Regional corticosteroids are currently delivered inside the eye by intravitreal injection (e.g. Ozurdex®, an intravitreal dexamethasone implant). Intravitreal injection is associated with rare but potentially serious side effects, including endophthalmitis, retinal and vitreous hemorrhage, and retinal detachment. Subconjunctival (SCT) injection is a less invasive option that is a common route used for post-surgical drug administration and treatment of infection and severe inflammation. However, it is the water soluble form of dexamethasone, dexamethasone sodium phosphate (DSP), that has been demonstrated to achieve high intraocular penetration with subconjunctival injection. It is difficult to load highly water soluble drugs, such as DSP, and achieve sustained drug release using conventional encapsulation methods. We found that use of carboxyl-terminated poly(lactic-co-glycolic acid) (PLGA) allowed encapsulation of DSP into biodegradable nanoparticles (NP) with relatively high drug content (6% w/w) if divalent zinc ions were used as an ionic "bridge" between the PLGA and DSP. DSP-Zn-NP had an average diameter of 210 nm, narrow particle size distribution (polydispersity index ~0.1), and near neutral surface charge (-9 mV). DSP-Zn-NP administered by SCT injection provided detectable DSP levels in both the anterior chamber and vitreous chamber of the eye for at least 3 weeks. In a rat model of experimental autoimmune uveitis (EAU), inflammation was significantly reduced in both the front and back of the eye in animals that received a single SCT injection of DSP-Zn-NP as compared to animals that received either aqueous DSP solution or phosphate buffered saline (PBS). DSP-Zn-NP efficacy was evidenced by a reduced clinical disease score, decreased expression of various inflammatory cytokines, and preserved retinal structure and function. Furthermore, SCT DSP-Zn-NP significantly reduced microglia cell density in the retina, a hallmark of EAU in rats. DSP-Zn-NP hold promise as a new strategy to treat noninfectious uveitis and potentially other ocular inflammatory disorders.


Multiple origins of the cortical γ rhythm.
Gamma rhythms (30-80 Hz) are a near-ubiquitous feature of neuronal population activity in mammalian cortices. Their dynamic properties permit the synchronization of neuronal responses to sensory input within spatially distributed networks, transient formation of local neuronal "cell assemblies," and coherent response patterns essential for intercortical regional communication. Each of these phenomena form part of a working hypothesis for cognitive function in cortex. All forms of physiological gamma rhythm are inhibition based, being characterized by rhythmic trains of inhibitory postsynaptic potentials in populations of principal neurons. It is these repeating periods of relative enhancement and attenuation of the responsivity of major cell groups in cortex that provides a temporal structure shared across many millions of neurons. However, when considering the origins of these repeating trains of inhibitory events considerable divergence is seen depending on cortical region studied and mode of activation of gamma rhythm generating networks. Here, we review the evidence for involvement of multiple subtypes of interneuron and focus on different modes of activation of these cells. We conclude that most massively parallel brain regions have different mechanisms of gamma rhythm generation, that different mechanisms have distinct functional correlates, and that switching between different local modes of gamma generation may be an effective way to direct cortical communication streams. Finally, we suggest that developmental disruption of the endophenotype for certain subsets of gamma-generating interneuron may underlie cognitive deficit in psychiatric illness.


Short-term Outcome of Peroral Endoscopic Myotomy Performed by the Same Endoscopist on Achalasia and Nonachalasia Esophageal Motility Disorders.
Peroral endoscopic myotomy (POEM) is a relatively new but increasingly therapeutic option for achalasia. In recent years, POEM has been used for nonachalasia esophageal motility disorders (NAEMDs), such as diffuse esophageal spasm, esophagogastric junction outlet obstruction, and hypercontractile disorder, with some clinical success. No studies thus far compare the outcomes of these two groups. We perform the first head-to-head comparison of outcomes after POEM in patients with achalasia and NAEMD. A retrospective analysis of all patients undergoing POEM at one university hospital by a single expert endoscopist from July 2021 to December 2022 was performed. All patients were symptomatic, and the presence of esophageal motility disorders was confirmed using multiple diagnostic modalities. These patients were then divided into 2 groups, achalasia and NAEMD, based on the underlying diagnosis. Statistical analysis of different clinical outcomes, including effectiveness and safety, was performed. Thirty-seven patients (mean age: 59.55, females: 22) underwent POEM in the study period. Twenty patients had achalasia and 17 patients had NAEMD. The median myotomy length was 5.5 cm for the achalasia group and 10 cm for the NAEMD group. This excluded patients with esophagogastric junction outlet obstruction in which the median myotomy length was 3 cm. The procedure time, the duration of hospital stays, the rates of same-day discharge, and complications were similar between the two. Short-term outcomes of POEM for the two groups were similar with improvement in 94% of patients in the achalasia group and 93.75% in the NAEMD group. Contrary to prior observations, our study highlights that POEM is equally effective in achieving clinical improvement in patients with NAEMD as achalasia over 6 months of follow-up. In addition, POEM has a comparable safety profile in both patient groups making it a feasible therapeutic option for these debilitating and challenging disorders.


Crystal structure of the major diabetes autoantigen insulinoma-associated protein 2 reveals distinctive immune epitopes.
Insulinoma-associated protein-2 (IA-2) is a major autoantigen in type 1 diabetes that occurs through autoimmune-mediated beta-cell destruction. We present here the crystal structure of the protein tyrosine phosphatase (PTP)-like domain of human IA-2. The structure reveals a canonical PTP domain with the closed WPD loop over the active site pocket, explaining the lack of enzyme activity in the native protein. The structural interpretation of previous mutagenesis studies indicates that the B-cell epitopes are concentrated on two distinctive regions on peripheral loops of the central beta-sheet surrounding T-cell epitopes within the sheet. The detailed structural information on immune epitopes provides a framework for the future development of immune intervention strategies against diabetes.


Evaluation of Annexin A2 as a novel diagnostic serum biomarker for lung cancer.
Annexin A2 (ANXA2) is a 36 kDa protein which orchestrates multiple biologic processes and clinical associations, especially in cancer progression. It is important to establish a specific and sensitive ANXA2 enzyme-linked immunosorbent assay (ELISA) for the study of ANXA2 functions and its clinical application. Therefore, we prepared a polyclonal antibody (PAb) in rabbits and a monoclonal antibody (MAb) in mices immunized with a recombinant ANXA2 protein. Based on our self-made MAb and PAb, highly specific and sensitive ELISA was developed. The detection limitation of ANXA2 was 10 ng/mL and the linear dynamic range was between 10 and 500 ng/mL. Using the established ELISA, we detected ANXA2 protein in human serum. It was found that soluble ANXA2 concentration in serum samples from 42 lung cancer patients was significantly higher than that from 43 healthy individuals (p< 0.01). Our data provides a new approach for detecting soluble ANXA2, especially in large ongoing and future clinical studies.


Integrated screening for tuberculosis and HIV in tuberculosis contact investigations: lessons learned in North Carolina.
Combating the syndemics of tuberculosis (TB) and HIV in the United States will require increasing efficiency as the incidence of TB declines. Fortunately, new tools such as the interferon gamma release assays can be combined with existing strategies such as opt-out HIV testing to facilitate simultaneous, integrated testing for both infections. We describe the lessons learned from our experience with integrated testing for TB and HIV in the setting of TB contact investigations in North Carolina. Integrated testing represents a unique opportunity to leverage TB and HIV program resources to enhance case detection and improve linkages to care. However, joint training in field investigations and diagnostics is critical prior to conducting contact investigations. Furthermore, integrated testing must be tightly coupled to treatment and prevention programs to reduce disease transmission and morbidity from untreated disease in communities.


Carbon Monoxide and Small Hydrocarbon Emissions from Sub-ohm Electronic Cigarettes.
Electronic cigarettes (ECIGs) are routinely advertised as a safer alternative to combustible cigarettes. ECIGs have been shown to emit less toxicants than conventional cigarettes. This study presents for the first time the mouthpiece emissions of carbon monoxide (CO) and small hydrocarbon gases, in addition to carbonyls, from a rebuildable atomizer sub-ohm device (SOD). Because ECIGs do not involve combustion, CO emissions are commonly thought to be a negligible component of ECIG aerosols. CO exposure is a major causative agent of heart disease among smokers. Aerosol generated by vaping a solution of propylene glycol and glycerol was collected in a small chamber. The gas phase was then directed for analysis to a long-path gas cell of a Fourier transform infrared instrument under reduced pressure. The effects of power, ECIG heating coil material, and coil geometry on the generation of small gases were assessed. Results showed that small gases, including CO, carbon dioxide, methane, ethylene, and acetylene, were detected in SOD-emitted gases. Electrical power and material of construction significantly affected the concentrations of the emitted gases. Nickel metal wire was more reactive than kanthal, nichrome, and stainless steel. Depending on use patterns and device operation, users of SOD devices may be exposed daily to similar levels of CO as are cigarette smokers. This finding casts doubt on the validity of CO as a biomarker to distinguish ECIG from tobacco cigarette use and suggests that some subset of ECIG users may be at risk from CO-related heart disease.


Distribution of family history of a disease as a function of mode of inheritance, genetic relative hazard, allele frequency and disease status of the proband, with application to female breast cancer.
This paper aims to determine the family history distribution of a particular disease as a result of its specific genetic aetiology, defined by the mode of inheritance (dominant or recessive), allele frequency, and increased risk in carriers of the genetic risk (genetic relative hazard). Here, 'family history' is the number of affected first-degree relatives of a defined index person (termed the proband), who may be either affected or unaffected with the disease in question. We consider model parameters relevant for female breast cancer in Australia. Breast cancer affects one sex only, although the extension of the model to both sexes is straightforward. Contour plots of the relationships between family history distribution and genetic parameters, for both dominant and recessive inheritance, are displayed for the proband being either affected or unaffected. Under dominant inheritance and an allele frequency of 0.005 (as may be appropriate for mutations in the genes BRCA1 and BRCA2), the proportion of affected probands diagnosed with breast cancer before age 50 years and who have no family history is stable as the genetic relative hazard increases from 5 to 20, decreasing from 89% to 85%. The probability that a proband has a family history is higher when the proband is affected compared with when she is not. For allele frequency 0.005 and relative hazard 10, the ratio of the probability of i (i = 1, 2, 3 or more) affected relatives for an affected proband compared with an unaffected proband is 1.2, 2 and 4.5 respectively, under dominant inheritance. Under recessive inheritance with allele frequency 0.35 and relative hazard 3 (as may be the case for a common polymorphism in the CYP17 gene), the corresponding ratios are 1.1, 1.3 and 1.5, respectively.


Analysis of global Napier grass (Cenchrus purpureus) collections reveals high genetic diversity among genotypes with some redundancy between collections.
Genetic diversity amongst genotypes of several Napier grass collections was analyzed and compared with the diversity in a set of open pollinated progeny plants. A total of 114,881 SNP and 46,293 SilicoDArT genome-wide markers were generated on 574 Napier grass genotypes. Of these, 86% of the SNP and 66% of the SilicoDArT markers were mapped onto the fourteen chromosomes of the Napier grass genome. For genetic diversity analysis, a subset of highly polymorphic and informative SNP markers was filtered using genomic position information, a maximum of 10% missing values, a minimum minor allele frequency of 5%, and a maximum linkage-disequilibrium value of 0.5. Extensive genetic variation, with an average Nei's genetic distance value of 0.23, was identified in the material. The genotypes clustered into three major and eleven sub-clusters with high levels of genetic variation contained both within (54%) and between (46%) clusters. However, we found that there was low to moderate genetic differentiation among the collections and that some overlap and redundancy occurred between collections. The progeny plants were genetically diverse and divergent from the germplasm collections, with an average FST value of 0.08. We also reported QTL regions associated with forage biomass yield based on field phenotype data measured on a subset of the Napier grass collections. The findings of this study offer useful information for Napier grass breeding strategies, enhancement of genetic diversity, and provide a guide for the management and conservation of the collections.


Epidermal growth factor receptor, c-erbB-2 proto-oncogene and estrogen receptor expression in human papillomavirus lesions of the uterine cervix.
The expression of epidermal growth factor receptor (EGF-R), c-erbB-2 proto-oncogene, and estrogen receptor (ER) was studied immunohistochemically in a series of 97 human papillomavirus (HPV) lesions of the uterine cervix, with special emphasis on their association with the HPV type, grade of intraepithelial neoplasia (CIN), and the natural history of the disease. EGF-R expression was found in 95 of 97 (98%) specimens, mainly in basal and parabasal cells. Diffuse nuclear and cytoplasmic staining was detected in 36 of 97 (37%) samples, of which 29 were HPV positive. This staining pattern was most prominent in HPV 18-positive and in CIN lesions. Weak or moderate c-erbB-2 expression was found in 26 of 97 (27%) specimens. Estrogen receptor expression was observed in 28 of 77 (36%) samples, epithelial staining was seen in 11 of 77 (14%), and stromal staining occurred in 24 of 77 (31%) specimens. No clear-cut associations were established between the EGF-R, c-erbB-2, or ER expression and HPV type, nor in CIN or the clinical course of HPV infections. This failure for EGF-R, c-erbB-2, and ER to be associated with the specific HPV types, grade of CIN, or the clinical course of cervical HPV lesions suggests that the assessment of these factors is of limited value in explaining the development of HPV-associated CIN and in predicting the prognosis of this disease.


Elementary steps of the catalytic NO(x) reduction with NH3: cluster studies on reaction paths and energetics at vanadium oxide substrate.
We consider different reaction scenarios of the selective catalytic reduction (SCR) of NO in the presence of ammonia at perfect as well as reduced vanadium oxide surfaces modeled by V2O5(010) without and with oxygen vacancies. Geometric and energetic details as well as reaction paths are evaluated using extended cluster models together with density-functional theory. Based on earlier work of adsorption, diffusion, and reaction of the different surface species participating in the SCR we confirm that at Brønsted acid sites (i.e., OH groups) of the perfect oxide surface nitrosamide, NH2NO, forms a stable intermediate. Here adsorption of NH3 results in NH4 surface species which reacts with gas phase NO to produce the intermediate. Nitrosamide is also found as intermediate of the SCR near Lewis acid sites of the reduced oxide surface (i.e., near oxygen vacancies). However, here the adsorbed NH3 species is dehydrogenated to surface NH2 before it reacts with gas phase NO to produce the intermediate. The calculations suggest that reaction barriers for the SCR are overall higher near Brønsted acid sites of the perfect surface compared with Lewis acid sites of the reduced surface, examined for the first time in this work. The theoretical results are consistent with experimental findings and confirm the importance of surface reduction for the SCR process.


[Incidence of malignant tumors in Slovakia. I. Levels and trends 1968-1989].
In the period from 1968-1989 an increase in the overall incidence of malignant tumors was recorded in men. Of the individual localizations a particularly marked increase was recorded in tumors of the lung, followed by tumors of the oral cavity, pharynx, esophagus, pancreas, urinary bladder, kidney (related to smoking), as well as of the testis and prostate gland. In women the values of overall incidence were lower and the trends were relatively stabilized. This is due to the relatively slow increase in the incidence in cancer of the breast and female reproductive organs and to the slight increase in cancer of the lung. Cancer of the kidney, urinary bladder and pancreas exhibited increased incidence. Low values, stabilized and even decreasing trends were recorded in the incidence of cancer of the oral cavity, pharynx, esophagus, and larynx, as compared to values found in men. In both sexes the incidence of cancer of the stomach showed a pronounced decrease, while the incidence of cancer of the colon and rectum was increasing. A smaller or greater rise was found also in the incidence of tumors of the hematopoietic and lymphatic tissues (except Hodgkins's disease). The trends observed in the incidence of malignant tumors in Slovakia are suggestive of their uncontrolled course, not affected by preventive measures. Yet the findings provide important information for directing the measures so as to aim at localizations of priority. (Tab. 2, Fig. 7, Ref. 20.)


Effects of pulmonary static inflation with 50% xenon on oxygen impairment during cardiopulmonary bypass for stanford type A acute aortic dissection: A pilot study.
The goal of this study was to investigate the effects of pulmonary static inflation with 50% xenon on postoperative oxygen impairment during cardiopulmonary bypass (CPB) for Stanford type A acute aortic dissection (AAD). This prospective single-center nonrandomized controlled clinical trial included 100 adult patients undergoing surgery for Stanford type A AAD at an academic hospital in China. Fifty subjects underwent pulmonary static inflation with 50% oxygen from January 2013 to January 2014, and 50 underwent inflation with 50% xenon from January 2014 to December 2014. During CPB, the lungs were inflated with either 50% xenon (xenon group) or 50% oxygen (control group) to maintain an airway pressure of 5 cm H2O. The primary outcome was oxygenation index (OI) value after intubation, and 10 minutes and 6 hours after the operation. The second outcome was cytokine and reactive oxygen species levels after intubation and 10 minutes, 6 hours, and 24 hours after the operation. Patients treated with xenon had lower OI levels compared to the control group before surgery (P = 0.002); however, there was no difference in postoperative values between the 2 groups. Following surgery, mean maximal OI values decreased by 18.8% and 33.8%, respectively, in the xenon and control groups. After surgery, the levels of interleukin-6 (IL-6), tumor necrosis factor alpha, and thromboxane B2 decreased by 23.5%, 9.1%, and 30.2%, respectively, in the xenon group, but increased by 10.8%, 26.2%, and 26.4%, respectively, in the control group. Moreover, IL-10 levels increased by 28% in the xenon group and decreased by 7.5% in the control group. There were significant time and treatment-time interaction effects on methane dicarboxylic aldehyde (P = 0.000 and P = 0.050, respectively) and myeloperoxidase (P = 0.000 and P = 0.001 in xenon and control groups, respectively). There was no difference in hospital mortality and 1-year survival rate between the 2 groups. Pulmonary static inflation with 50% xenon during CPB could attenuate OI decreases at the end of surgery for Stanford type A AAD. Thus, xenon may function by triggering anti-inflammatory responses and suppressing pro-inflammatory and oxidative effects.


Screening: part 19 of a series on evaluation of scientific publications.
The early detection of cancer and other diseases is generally considered beneficial, yet there is evidence that in some diseases screening may be of limited benefit. To clarify this issue, we present the statistical principles that underlie screening. Methods We define screening and discuss the conditions for its successful use. We give illustrative examples from among the currently recommended types of screening in Germany and from the recent medical literature, particularly with regard to mammography. Certain specific conditions must be fulfilled for screening to be beneficial (usually measured by reduced mortality): The screening procedure must be of high quality, and the screening intervals must be well adapted to the distribution of the sojourn time. Alongside its benefits, screening can also cause harm, particularly to the many patients who are given a false positive test result. According to German law, potential participants are entitled to being given all information necessary to make an informed decision about screening. Just like clinical interventions, screening programs should be evaluated before they are introduced or, at the latest, at the time of their introduction.


Thromboembolic disease.
(1) Thromboembolic disease is a rare condition in physically fit subjects and is, therefore, likely to occur only rarely in aircrew. (2) The clinical diagnosis of both pulmonary embolism and deep venous thrombosis is unreliable. As the occurrence of these conditions has serious implications so far as the future licensing of airmen is concerned, it is of paramount importance to establish the diagnosis beyond doubt. (3) The chance of recurrence after an acute pulmonary embolus is low, particularly in those subjects in whom a definite acute and transient predisposing factor such as recent surgery or trauma can be identified. (4) When there is no definite predisposing factor to an acute pulmonary embolism, careful assessment is needed. The possibility that the embolus was the first sign of some serious sytemic illness, such as malignancy, should be considered and the possibility of rare clotting abnormalities sought. (5) Patients with subacute pulmonary embolism should be regarded as for those with acute pulmonary embolism and no obvious risk factor. A large proportion of these patients will have no predisposing factor and will require long-term oral anticoagulants as part of their routine therapy. Fortunately this condition is very rare. (6) Patients with repeated deep venous thrombosis, usually associated with chronic damage to the venous system of the leg, also may require long-term oral anticoagulants and their condition is likely to be exacerbated by long periods of inactivity.(ABSTRACT TRUNCATED AT 250 WORDS)


Suppression of insulin-like3 receptor reveals the role of β-catenin and Notch signaling in gubernaculum development.
During male development, the testes move from a high intraabdominal position and descend into the scrotum. The gubernaculum, an inguinoscrotal ligament connecting the testis to the lower abdomen, is believed to play a critical role in this process. The first stage of testicular descent is controlled by insulin like3 hormone (INSL3), produced in testicular Leydig cells. Deletion of Insl3 or its receptor, Rxfp2, in mice causes cryptorchidism. We produced Cre/loxP regulated shRNA transgenic mice targeting RXFP2 expression. We have shown that the transgene was able to reduce Rxfp2 gene expression and thus behaved as a hypomorphic allele of Rxfp2. Variable degrees of uni- and bilateral cryptorchidism was detected in males with the activated shRNA transgene on an Rxfp2+/- background. Conditional suppression of Rxfp2 in the gubernaculum led to cryptorchidism. Gene expression analysis of a mutant cremasteric sac using Illumina microarrays indicated abnormal expression of a significant number of genes in Wnt/β-catenin and Notch pathways. We have demonstrated profound changes in the expression pattern of β-catenin, Notch1, desmin, and androgen receptor (AR), in Rxfp2-/- male embryos, indicating the role of INSL3 in proliferation, differentiation, and survival of specific cellular components of the gubernaculum. We have shown that INSL3/RXFP2 signaling is essential for myogenic differentiation and maintenance of AR-positive cells in the gubernaculum. Males with the deletion of β-catenin or Notch1 in the gubernacular ligament demonstrated abnormal development. Our data indicates that β-catenin and Notch pathways are potential targets of INSL3 signaling during gubernacular development.


Phase diagram and universality of the Lennard-Jones gas-liquid system.
The gas-liquid phase transition of the three-dimensional Lennard-Jones particles system is studied by molecular dynamics simulations. The gas and liquid densities in the coexisting state are determined with high accuracy. The critical point is determined by the block density analysis of the Binder parameter with the aid of the law of rectilinear diameter. From the critical behavior of the gas-liquid coexisting density, the critical exponent of the order parameter is estimated to be β = 0.3285(7). Surface tension is estimated from interface broadening behavior due to capillary waves. From the critical behavior of the surface tension, the critical exponent of the correlation length is estimated to be ν = 0.63(4). The obtained values of β and ν are consistent with those of the Ising universality class.


Sex dimorphism and metabolic profiles in management of metabolic-associated fatty liver disease.
Metabolic-associated fatty liver disease (MAFLD) refers to the build-up of fat in the liver associated with metabolic dysfunction and has been estimated to affect a quarter of the population worldwide. Although metabolism is highly influenced by the effects of sex hormones, studies of sex differences in the incidence and progression of MAFLD are scarce. Metabolomics represents a powerful approach to studying these differences and identifying potential biomarkers and putative mechanisms. First, metabolomics makes it possible to obtain the molecular phenotype of the individual at a given time. Second, metabolomics may be a helpful tool for classifying patients according to the severity of the disease and obtaining diagnostic biomarkers. Some studies demonstrate associations between circulating metabolites and early and established MAFLD, but little is known about how metabolites relate to and encompass sex differences in disease progression and risk management. In this review, we will discuss the epidemiological metabolomic studies for sex differences in the development and progression of MAFLD, the role of metabolic profiles in understanding mechanisms and identifying sex-dependent biomarkers, and how this evidence may help in the future management of the disease.


Solid State Structures of Lead Complexes with Relevance for Biological Systems.
Structural information on the interaction between lead ion and its targeting biological substances is important not only for enriching coordination chemistry of lead but for successfully treating lead poisoning that is a present-day problem. This chapter provides structural data, mainly metal binding sites/modes, observed in crystal structures of lead complexes with biorelevant molecules, obtained from the Cambridge Structural Database (the CSD version 5.36 updated to May 2015) and the Protein Data Bank (PDB updated to February 2016). Ligands include (i) amino acids and small peptides, (ii) proteins, (iii) nucleic acid constituents, (iv) nucleic acids, (v) simple saccharides, and (vi) other biorelevant molecules involving lead-detoxification agents. For representative complexes of these ligands, some details on the environment of the metal coordination and structural characteristics are described.


MiR-203 sensitizes glioma cells to temozolomide and inhibits glioma cell invasion by targeting E2F3.
Glioma is the most common malignant and fatal primary tumor in the central nervous system in adults. Recent data has suggested a profound role for microRNAs (miRs) in cancer progression. The present study demonstrated, via quantitative polymerase chain reaction (qPCR) analysis, that miR-203 expression was markedly lower in highly invasive U87MG glioma cells and glioma tissues. Wound healing and Transwell assays demonstrated that restoration of miR-203 expression inhibited U87MG cell migration and invasion. Restoration of miR-203 expression additionally sensitized the cells to temozolomide (TMZ) as determined by MTS assay. By contrast, miR-203 inhibition in A172 cells exerted opposite effects. Bioinformatic analysis combined with experimental analysis revealed that miR-203 directly targeted E2F3 via the conserved miR-203 target site within the E2F3 3'-untranslational region. E2F3 knockdown with specific small hairpin RNA also inhibited U87MG cell migration and invasion, and sensitized them to TMZ. Importantly, miR-203 and E2F3 showed inverse expression patterns in invasive glioma tissues, as demonstrated by qPCR and luciferase assay. These results suggested that miR-203 may function as a tumor suppressor in glioma progression and that the miR-203/E2F3 axis may be a novel candidate in the development of rational therapeutic strategies for glioma.


Life-span retrieval of public events: Reminiscence bump for high-impact events, recency for others.
Although substantial evidence exists showing a reliable reminiscence bump for personal events, data regarding retrieval distributions for public events have been equivocal. The primary aim of the present study was to address life-span retrieval distributions of different types of public events in comparison to personal events, and to test whether the existing accounts of the bump can explain the distribution of public events. We asked a large national sample to report the most important, happiest, and saddest personal events and the most important, happiest, saddest, most proud, most fearful, and most shameful public events. We found a robust bump corresponding to the third decade of life for the happiest and the most important positive but not for the saddest and most important negative personal events. For the most important public events, a bump emerged only for the two most frequently mentioned events. Distributions of public events cued with emotions were marked by recency. These results point to potential differences in retrieval of important personal and public events. While the life-script framework well accounts for the findings regarding important personal events, a chronologically retroactive search seem to guide retrieval of public events. Reminiscence bump observed for the two public events suggest that age-at-event affects recall of public events to the degree that the events are high-impact ones that dominate nation's collective memory. Results provide further evidence that the bump is not unitary and points to importance of event type and memory elicitation method with regard to competing explanations of the phenomenon.


The subjective wellbeing profile of the 'pretiree' demographic: A cross-sectional study.
Pretirees are a demographic interposed between the latter stages of working life and old age. We aimed to characterise subjective wellbeing and lifestyle behaviours for individuals aged in their late-fifties and sixties. Cross-sectional study of 233 men and 229 women aged 55-69 yr from the Geelong Osteoporosis Study. Subjective wellbeing assessed using the World Health Organization Quality of Life questionnaire (WHOQOL-BREF, Australia). Scores below published population norms for Australia for WHOQOL domains (physical, psychological, social, environmental) were considered low. For men, low WHOQOL scores were evident for 78 (33.5%) of participants regarding physical health, 94 (40.3%) for psychological wellbeing, 89 (38.2%) for social relationships, and 99 (42.5%) for the environment; the respective figures for women were 110 (48.0%), 124 (54.1%), 84 (36.7%), and 95 (41.5%). While there were few smokers (men 10.8%; women 6.5%), 42.5% of men and 17.7% of women exceeded recommended alcohol levels; 6.4% of men and 15.2% of women met the recommendation to consume each day at least two portions of fruit and five of vegetables. In multivariable models, being active was consistently associated with high WHOQOL scores, and low socioeconomic status with low WHOQOL scores. Pain and polypharmacy were associated with increased likelihood of poor scores for physical health, living with a partner increased the likelihood of good social relationships, and body mass index, employment, sleep, and alcohol and fruit/vegetable intakes were associated with WHOQOL scores in at least one domain. There is an opportunity for targeting health promotion to pretirees, particularly in socially disadvantaged regions, in order to optimise transition into old age. Our data highlight lifestyle interventions without which many pretirees might progress to old age at increased risk of diminished wellbeing.


Flow cytometric detection of Mycobacterium avium subsp. paratuberculosis-specific antibodies in experimentally infected and naturally exposed calves.
A desirable test to diagnose infections with Mycobacterium avium subsp. paratuberculosis facilitates identification of infected cattle prior to the state of M. avium subsp. paratuberculosis shedding. This study aimed at adjusting a flow cytometry (FC)-based assay, using intact M. avium subsp. paratuberculosis bacteria as the antigen, for diagnosis of M. avium subsp. paratuberculosis infections in calves. Serum samples were collected from experimentally infected (n = 12) and naturally exposed (n = 32) calves. Samples from five calves from positive dams were analyzed to determine the dynamics of maternal antibodies. Samples from adult cattle with defined infection status served as the standard (18 M. avium subsp. paratuberculosis shedders, 22 M. avium subsp. paratuberculosis free). After preadsorption with Mycobacterium phlei, sera were incubated with M. avium subsp. paratuberculosis and M. avium subsp. avium bacterial suspensions, respectively, followed by the separate detection of bovine IgG, IgG1, IgG2, and IgM attached to the bacterial surface. M. avium subsp. paratuberculosis-specific sample/positive (S/P) ratios were compared to enzyme-linked immunosorbent assay (ELISA) S/P ratios. In adult cattle, the FC assay for IgG1 had a sensitivity of 78% at a specificity of 100%. Maternally acquired antibodies could be detected in calves up to 121 days of life. While all but two sera taken at day 100 ± 10 postnatum from naturally exposed calves tested negative, elevated S/P ratios (IgG and IgG1) became detectable from 44 and 46 weeks postinoculation onwards in two calves infected experimentally. Even with the optimized FC assay, M. avium subsp. paratuberculosis-specific antibodies can only occasionally be detected in infected calves less than 12 months of age. The failure to detect such antibodies apparently reflects the distinct immunobiology of M. avium subsp. paratuberculosis infections rather than methodological constraints.


Allelopathic effects of ragweed (Ambrosia artemisiifolia L.) on cultivated plants.
During the past years ragweed has been coming to the forefront of interest in Hungary and in other European countries as well because its serious health risk. Results of the 5th National Weed Survey has proven that ragweed is the most important weed species on Hungarian field lands, its coverage shows a rising tendency in cereals moreover it not only occurs in cultivated plants. Allelopathic effects of aqueous extracts derived from different parts of ragweed plants (air dried leafy stems, seeds) on the germination and growth of other cultivated plants [maize (Zea mays L.), winter wheat (Triticum aestivum L.), rye (Secale cereale L.), oat (Avena sativa L.)] were studied. The extracts made for the trials were prepared with distilled water. Petri dishes were used for the germination experiments and distilled water was used as a control treatment. The seven days long experiment was carried out within a Binder-type thermostat under dark conditions. The germination percentage was checked in every two days and the growth of sprouts was evaluated after a week counting the germinated seeds and measuring the length of the radicle and plumule. The measured data were statistically analysed and the effect of extracts on germinating and length of sprouts were assessed.


A simple simulation model as a tool to assess alternative health care provider payment reform options in Vietnam.
Vietnam is currently considering a revision of its 2008 Health Insurance Law, including the regulation of provider payment methods. This study uses a simple spreadsheet-based, micro-simulation model to analyse the potential impacts of different provider payment reform scenarios on resource allocation across health care providers in three provinces in Vietnam, as well as on the total expenditure of the provincial branches of the public health insurance agency (Provincial Social Security [PSS]). The results show that currently more than 50% of PSS spending is concentrated at the provincial level with less than half at the district level. There is also a high degree of financial risk on district hospitals with the current fund-holding arrangement. Results of the simulation model show that several alternative scenarios for provider payment reform could improve the current payment system by reducing the high financial risk currently borne by district hospitals without dramatically shifting the current level and distribution of PSS expenditure. The results of the simulation analysis provided an empirical basis for health policy-makers in Vietnam to assess different provider payment reform options and make decisions about new models to support health system objectives.


Establishment of reference range of CD4 T-lymphocyte in healthy Nepalese adults.
CD4 T lymphocytes are the most widely used cellular markers to assess the course of HIV infection, clinical staging and, monitoring the effect of antiretroviral therapy. The regional reference range for Eastern, Central and Western development region of Nepal had already been established whereas the same was still lacking in Mid-western and Far-western development region. The objective of this study was to establish reference range of CD4 T lymphocyte in the remaining two development regions and finally the national reference range using data from previous study. The average values (mean ± SD) of CD4 and CD3 T cell in present study was (819 ± 294) cells/μl and (1546 ± 532) cells/μl, respectively. The absolute CD4 T cell (914 ± 303) and CD3 T cell (1671 ± 560) count in female were significantly higher than those from male, CD4 (757 ± 270) and CD3 (1465 ± 499) (p value-0.000). National reference value of CD4 was determined to be (798 ± 335) cells/μl for healthy Nepalese adults.


Structural features of interferon-gamma aggregation revealed by hydrogen exchange.
Using hydrogen-deuterium exchange (HX) and electrospray ionization mass spectrometry, we have investigated the stability and structural changes of recombinant human interferon-gamma (IFN-gamma) during aggregation induced by guanidine hydrochloride (GdnHCl) and potassium thiocyanate. First, HX labeling was initiated after the amorphous aggregates were formed to probe the tertiary structure of the aggregated state. Second, labeling was performed at low protein concentrations to assess stability under aggregation prone conditions. In 1 M GdnHCl, the stability of IFN-gamma was greatly reduced and much less protection from HX in solution was observed. Exchange under these conditions was slower in helix C than in the rest of the protein. Aggregates formed in 1 M GdnHCl showed a HX pattern consistent with a partially unfolded state with an intact helix C. Although aggregates formed in 0.3 M KSCN exhibited a HX pattern similar to those formed in GdnHCl, the solution phase HX pattern in 0.3 M KSCN was surprisingly comparable to that of the native state. Varying the aggregation time before performing HX revealed that KSCN first precipitated native protein and then facilitated partial unfolding of the precipitated protein. These results show that helix C, which forms the hydrophobic core of the IFN-gamma dimer, is highly protected from HX under native conditions, is more stable in GdnHCl than the rest of the protein and remains intact in both GdnHCl- and KSCN-induced aggregates. This suggests that native-state HX patterns may presage regions of the protein susceptible to unfolding during aggregation.


BaxΔ2 Family Alternative Splicing Salvages Bax Microsatellite-Frameshift Mutations.
Mutation or aberrant splicing can interrupt gene expression. Tumor suppressor Bax is one of the susceptible genes prone to microsatellite frameshifting mutations in coding regions. As a result, tumors exhibiting microsatellite instability (MSI) often present a "Bax-negative" phenotype. We previously reported that some Bax-negative cells in fact contain a functional Bax isoform (BaxΔ2), generated when unique alternative splicing "salvages" the shifted reading frame introduced by a microsatellite mutation. Here we compared Bax alternative splicing profiles in a range of cell lines and primary tumors with and without Bax microsatellite mutations. We found that MSI tumors exhibit a high Bax alternative splicing frequency, especially in exon 2, and produce a family of alternatively spliced isoforms that retain many important Bax functional domains. Surprisingly, these BaxΔ2 family isoforms can rescue Bax from all common microsatellite frameshift mutations. Production of BaxΔ2 requires specific cis mutations, while trans components are not cell-type specific. Furthermore, all BaxΔ2 family isoforms are more potent cell death inducers than the parental Bax without directly targeting mitochondria. These results indicate that the BaxΔ2 family can potentially salvage Bax tumor suppressor expression otherwise lost to mutation.


The CFTR gene and regulation of its expression.
The cystic fibrosis transmembrane conductance regulator gene (CFTR) shows clear temporal and developmental regulation of its expression. However, there are few well-defined regulatory elements that control this pattern of expression, and their mechanism of action is poorly understood. We review the structure and organization of the CFTR gene and what is known about its regulation. The CFTR gene promoter is clearly important for maintaining levels of CFTR gene expression, but apparently it does not contain any tissue-specific elements. Thus tissue-specificity is probably controlled by sequences lying elsewhere in this large gene. We discuss data from our group and others implicating additional regions of CFTR in regulatory functions, and evaluate candidate transcription factors that may be involved. Further, we summarize aspects of the regulation of the developmental expression of CFTR. Definition of CFTR gene regulatory elements could be of considerable therapeutic significance, since only a small increase in CFTR expression in the correct cell type could alleviate the disease phenotype.


An improved probabilistic account of counterfactual reasoning.
When people want to identify the causes of an event, assign credit or blame, or learn from their mistakes, they often reflect on how things could have gone differently. In this kind of reasoning, one considers a counterfactual world in which some events are different from their real-world counterparts and considers what else would have changed. Researchers have recently proposed several probabilistic models that aim to capture how people do (or should) reason about counterfactuals. We present a new model and show that it accounts better for human inferences than several alternative models. Our model builds on the work of Pearl (2000), and extends his approach in a way that accommodates backtracking inferences and that acknowledges the difference between counterfactual interventions and counterfactual observations. We present 6 new experiments and analyze data from 4 experiments carried out by Rips (2010), and the results suggest that the new model provides an accurate account of both mean human judgments and the judgments of individuals. (PsycINFO Database Record


[Progress in extracellular vesicle imaging methods].
Extracellular vesicles (EVs), including exosomes and microvesicles, are lipid bilayer-enclosed nanovesicles secreted by cells. These EVs are important mediators of intercellular communication by serving as vehicles for transfer of proteins, mRNA, miRNA and lipids between cells. Various visualization methods have been established to explore the characteristics of EVs and their role in physiological and pathological processes. The nanoscale size and high heterogeneity of EVs hamper the identification of their biological characteristics and functions. This review presents a comprehensive overview of EV imaging methods in light of the origin, separation and dynamic tracking of EVs, and the advantages and disadvantages of different imaging strategies are discussed. We believe that studies at the levels of single vesicles and single cells will become the frontier of future researches of EVs.


Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA.
The reaction of p-isopropylbenzaldehyde thiosemicarbazone [p-is.TSCN], 1, with palladium(II) acetate and potassium tetrachloroplatinate yielded two tetrameric orthopalladated isomers, [Pd(p-is.TSCN)]4 (complexes 2 and 3), and the platinum analogue [Pt(p-is.TSCN)]4 (complex 4), respectively. All of these complexes contain the thiosemicarbazone bonded as a terdentate ligand to the metallic atom, through the thiol sulfur, the azomethinic nitrogen and the ortho carbon of the p-isopropylphenyl ring to which the imine group is attached to as deduced from the study of the IR, NMR, and XRD spectra of complexes 2 and 4. Complexes 2 and 4 crystallize in the centrosymmetric monoclinic space group C2/c, with Z = 8. Unit cell parameters for complex 2 are as follows: a = 25.742(5) A, b = 19.560(4) A, c = 24.199(5) A, beta = 101.70(3)o. Unit cell parameters for complex 4 are as follows: a = 25.8728(19) A, b = 19. 5053(14) A, c = 24.0899(16) A, beta = 101.305(2)o. As can be deduced from the NMR study, the palladated isomers 2 and 3 interconvert in DMSO which may be a consequence of the existence in both complexes of a flexible eight-membered ring with alternating Pd-S atoms. The testing of the cytotoxic activity of these compounds against several human and murine cell lines sensitive and resistant to cisplatin (cis-DDP) suggests that compounds 2, 3, and 4 may be endowed with important anticancer properties since they elicit IC50 values in the microM range as does the clinically used drug cis-DDP, and, moreover, they display cytotoxic activity in tumor lines resistant to cis-DDP. The analysis of the interaction of these novel tetrameric cyclometalated compounds with DNA suggests that they form DNA interhelical cross-links.


Ultraselective electrochemiluminescence biosensor based on locked nucleic acid modified toehold-mediated strand displacement reaction and junction-probe.
Locked nucleic acid (LNA) is applied in toehold-mediated strand displacement reaction (TMSDR) to develop a junction-probe electrochemiluminescence (ECL) biosensor for single-nucleotide polymorphism (SNP) detection in the BRCA1 gene related to breast cancer. More than 65-fold signal difference can be observed with perfectly matched target sequence to single-base mismatched sequence under the same conditions, indicating good selectivity of the ECL biosensor.


Gastroprotective effect of rutin against indomethacin-induced ulcers in rats.
Several reports have indicated that indomethacin-induced gastropathy is mediated through generation of free radicals, neutrophil infiltration and disturbance in nitric oxide production. Rutin is a potent antioxidant flavonoid. Recently, rutin was reported to inhibit neutrophil infiltration and to modulate nitric oxide production in gastric mucosa. Therefore, the aim of this study was to investigate the protective effect of rutin against indomethacin-induced gastric injury. Accordingly, four groups of rats were used. The first three groups were injected orally with vehicle, rutin (200 mg/kg) and indomethacin (48 mg/kg) respectively. The fourth group was injected with rutin 1 hr before indomethacin. Animals were killed after 6 hr of indomethacin administration. Gastric juice acidity and gastric injury were evaluated directly. Moreover, the activities of myeloperoxidase, superoxide dismutase and the contents of reduced glutathione, thiobarbituric acid reactive substance and total nitrite/nitrate (as a marker of nitric oxide production) were determined in mucosal tissues. Indomethacin increased gastric ulcer index, gastric myeloperoxidase activity, gastric acidity and thiobarbituric acid reactive substance contents compared with control. On the other hand, indomethacin decreased glutathione, nitrite/nitrate contents and superoxide dismutase activity. Histopathological examination of the stomachs of indomethacin-treated rats revealed degenerative changes in gastric tissues. Pre-treatment with rutin protected gastric tissues against indomethacin-induced gastropathy as demonstrated from reduction in the ulcer index, attenuation of histopathological changes and amelioration of the altered oxidative stress and biochemical parameters. These results indicate that rutin has a protective effect against indomethacin-induced gastropathy probably through inhibiting neutrophil infiltration, suppression of oxidative stress generation and replenishing nitrite/nitrate levels regardless of gastric acidity.