[Effects of Transcutaneous Electrical Acupoint Stimulation for Depression in Late Pregnancy and Impacts on Inflammatory Cytokines].
To assess the safety and efficacy of transcutaneous electrical acupoint stimulation (TEAS) for depression in late pregnancy and impacts on inflammatory cytokines. A total of 150 pregnant women with depression in late pregnancy were randomized into a high intensity group (n=52), a low intensity group (n=49) and a control group (n=49). TEAS was applied at bilateral Neiguan (PC 6) and Shenmen (HT 7) for 6 weeks. The intensities of TEAS in the high intensity group, the low intensity group and the control group were 10, 5 and 0 mA, respectively. During the process of TEAS, the blood pressure, pulse, uterine contraction and the fetal heart rate were recorded. Depression was evaluated by 24-item Hamilton depression scale (HAMD) before TEAS and after 2-week, 4-week, 6-week treatment. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1 β) and IL-6 were detected by enzyme-linked immunosorbent assay (ELISA) before and after 6-week treatment. Delivery outcomes were observed. The correlation was analyzed between HAMD difference value and the diffe-rence values of TNF-α, IL-1 β and IL-6, respectively. The blood pressure, pulse and fetal heart rate had no statistical significance before and after treatment in the three groups (P>0.05). The HAMD scores at all the time points were lower than that before treatment in the high intensity group (P<0.05), which were lower compared with those in the low intensity group and the control group (P<0.05). The HAMD score in the low intensity group decreased after 6-week treatment compared with that before treatment and was lower than that in the control group (P<0.05). The serum levels of IL-1 β and IL-6 in the high intensity group decreased compared with those before treatment and were lower compared with those in the low intensity group and the control group after 6-week treatment (P<0.05). There was no significant difference in the deliver outcomes among the three groups (P>0.05). The variation of HAMD score did not have significant correlation with those of TNF-α, IL-1 β and IL-6 (P>0.05). TEAS is safe and effective for depression in late pregnancy and can regulate the serum levels of IL-1 β and IL-6 without influencing on delivery outcome.


Clinical risk factors associated with recurrence of ischemic stroke within two years: A cohort study.
To identify the clinical risk factors and investigate the efficacy of a classification model based on the identified factors for predicting 2-year recurrence after ischemic stroke.From June 2017 to January 2019, 358 patients with first-ever ischemic stroke were enrolled and followed up in Shenzhen Traditional Chinese Medicine Hospital. Demographic and clinical characteristics were recorded by trained medical staff. The outcome was defined as recurrence within 2 years. A multivariate logistic regression model with risk factors and their interaction effects was established and evaluated.The mean (standard deviation) age of the participants was 61.6 (12.1) years, and 101 (28.2%) of the 358 patients were female. The common comorbidities included hypertension (286 patients, 79.9%), diabetes (148 patients, 41.3%), and hyperlipidemia (149 patients, 41.6%). The 2-year recurrence rate was 30.7%. Of the 23 potential risk factors, 10 were significantly different between recurrent and non-recurrent subjects in the univariate analysis. A multivariate logistic regression model was developed based on 10 risk factors. The significant variables include diabetes mellitus, smoking status, peripheral artery disease, hypercoagulable state, depression, 24 h minimum systolic blood pressure, 24 h maximum diastolic blood pressure, age, family history of stroke, NIHSS score status. The area under the receiver operating characteristic curve (ROC) was 0.78 (95% confidence interval: 0.726-0.829) with a sensitivity of 0.61 and a specificity of 0.81, indicating a potential predictive ability.Ten risk factors were identified, and an effective classification model was built. This may aid clinicians in identifying high-risk patients who would benefit most from intensive follow-up and aggressive risk factor reduction.The clinical trial registration number: ChiCTR1800019647.


Feed efficiency metrics in growing pigs.
The objective of the present study was to quantify the interrelationships between different feed efficiency measures in growing pigs and characterize pigs divergent for a selection of these measures. The data set included data from 311 growing pigs between 42 and 91 d of age from 3 separate batches. Growth-related metrics available included midtest metabolic BW (BW), energy intake (EI), and ADG. Ratio efficiency traits included energy conversion ratio (ECR), Kleiber ratio (ADG/BW), relative growth rate (RGR), residual EI (REI), and residual daily gain (RDG). Residual intake and gain (RIG; i.e., a dual index of both REI and RDG) and residual midtest metabolic weight (RMW) were also calculated. Simple Pearson correlations were estimated between the growth and feed efficiency metrics. In litters with at least 3 pigs of each sex, pigs were separately stratified on each residual trait as high, medium, and low rank. Considerable interanimal variability existed in all metrics evaluated. Male pigs were superior to females for all metrics ( < 0.001) except for both BW and EI, where no sex differences were evident. Feed efficiency metrics improved as birth BW increased ( < 0.05) except for RGR, where the contrary was observed. Correlations between most growth and feed efficiency metrics were strong to moderate ( < 0.05). Low-REI pigs (i.e., more efficient) had lower EI and ECR and were superior for RIG ( < 0.001) compared with high- and medium-REI pigs. High-RDG pigs (i.e., more efficient) had greater BW gain and better ECR ( < 0.001) compared with medium- and low-RDG pigs. Residual EI and RIG were both superior ( < 0.001) in high-RDG pigs compared with medium- and low-RDG pigs. Energy conversion ratio, REI, and RIG were superior ( < 0.05) in high-RMW pigs (i.e., more efficient) compared with medium-RMW pigs. High-RIG pigs (i.e., more efficient) had lower EI ( < 0.01) and superior ECR for RDG and REI compared with medium- and low-RIG pigs. In general, most of the correlations among the feed efficiency traits investigated in this study were different from unity, indicating that each trait is depicting a different aspect of efficiency in pigs, although the moderate to strong correlations suggest that improvement in one trait would, on average, lead to improvements in the others. Pigs ranked as more efficient on residual traits such as REI consumed less energy for a similar BW gain, which would translate into an economic benefit for pig producers.


A Polymer Physics Model to Dissect Genome Organization in Healthy and Pathological Phenotypes.
Novel technologies revealed a nontrivial spatial organization of the chromosomes within the cell nucleus, which includes different levels of compartmentalization and architectural patterns. Notably, such complex three-dimensional structure plays a crucial role in vital biological functions and its alterations can produce extensive rewiring of genomic regulatory regions, thus leading to gene misexpression and disease. Here, we show that theoretical and computational approaches, based on polymer physics, can be employed to dissect chromatin contacts in three-dimensional space and to predict the effects of pathogenic structural variants on the genome architecture. In particular, we discuss the folding of the human EPHA4 and the murine Pitx1 loci as case studies.


High-Efficiency and Emission-Tunable Inorganic Blue Perovskite Light-Emitting Diodes Based on Vacuum Deposition.
The fabrication of perovskite light-emitting diodes (PeLEDs) with vacuum deposition shows great potential and commercial value in realizing large-area display panel manufacturing. However, the electroluminescence (EL) performance of vacuum-deposited PeLEDs still lags behind the counterparts fabricated by solution process, especially in the field of blue PeLEDs. Here, the fabrication of high-quality CsPbBr3- x Clx film through tri-source co-evaporation is reported to achieve high photoluminescence quantum yield (PLQY). Compared with the conventional traditional dual-source co-evaporation, the tri-source co-evaporation method allows for freely adjustable elemental ratios, enabling the introduction of the lattice-matched Cs4 Pb(Br/Cl)6 phase with the quantum-limited effect into the inorganic CsPb(Br/Cl)3 emitter. By adjusting the phase distribution, the surface defects of the emitter can be effectively reduced, leading to better blue emission and film quality. Further, the effects of Cs/Pb ratio and Br/Cl ratio on the PLQY and carrier recombination dynamics of perovskite films are investigated. By optimizing the deposition rate of each precursor source, spectrally stable blue PeLEDs are achieved with tunable emission ranging from 468 to 488 nm. Particularly, the PeLEDs with an EL peak at 488 nm show an external quantum efficiency (EQE) of 4.56%, which is the highest EQE value for mixed-halide PeLEDs fabricated by vacuum deposition.


Membrane current evoked by mitochondrial Na+-Ca2+ exchange in mouse heart.
The electrogenicity of mitochondrial Na+-Ca2+ exchange (NCXm) had been controversial and no membrane current through it had been reported. We succeeded for the first time in recording NCXm-mediated currents using mitoplasts derived from mouse ventricle. Under conditions that K+, Cl-, and Ca2+ uniporter currents were inhibited, extra-mitochondrial Na+ induced inward currents with 1 μM Ca2+ in the pipette. The half-maximum concentration of Na+ was 35.6 mM. The inward current was diminished without Ca2+ in the pipette, and was augmented with 10 μM Ca2+. The Na+-induced inward currents were largely inhibited by CGP-37157, an NCXm blocker. However, the reverse mode of NCXm, which should be detected as an outward current, was hardly induced by extra-mitochondrial application of Ca2+ with Na+ in the pipette. It was concluded that NCXm is electrogenic. This property may be advantageous for facilitating Ca2+ extrusion from mitochondria, which has large negative membrane potential.


A survey of neural tube defect pregnancies in north-west England.
The preliminary results are reported of the first eighteen months of a three year survey of NTD affected pregnancies in the North Western Region of England. The results are consistent with a general decline in the incidence of NTD. Prenatal screening has been available for 10 years but babies continue to be born with NTD. Supportive services are often lacking for parents having had an affected pregnancy and methods of imparting advice regarding recurrence risks have been shown to be variable and not always efficient.


Safety and Tolerance of Donor-Derived Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation: The MYSTEP1 Study.
Calcineurin inhibitors (CNI) have significantly improved patient and graft survival in pediatric liver transplantation (pLT). However, CNI toxicity leads to significant morbidity. Moreover, CNIs cannot prevent long-term allograft injury. Mesenchymal stem (stromal) cells (MSC) have potent immunomodulatory properties, which may promote allograft tolerance and ameliorate toxicity of high-dose CNI. The MYSTEP1 trial aims to investigate safety and feasibility of donor-derived MSCs in pLT. 7 to 10 children undergoing living-donor pLT will be included in this open-label, prospective pilot trial. A dose of 1 × 106 MSCs/kg body weight will be given at two time points: first by intraportal infusion intraoperatively and second by intravenous infusion on postoperative day 2. In addition, participants will receive standard immunosuppressive treatment. Our primary objective is to assess the safety of intraportal and intravenous MSC infusion in pLT recipients. Our secondary objective is to evaluate efficacy of MSC treatment as measured by the individual need for immunosuppression and the incidence of biopsy-proven acute rejection. We will perform detailed immune monitoring to investigate immunomodulatory effects. Our study will provide information on the safety of donor-derived MSCs in pediatric living-donor liver transplantation and their effect on immunomodulation and graft survival.


[Structural and ultrastructural data on human cutaneous lipids].
The principal function of intercellular lipids of the epidermal horny layer is the constitution of an occlusive barrier and regulation of transepidermal water fluxes. Self-assembly of lipid bilayers and formation of multilayered structures can be observed in the intercellular spaces of the stratum corneum. Progressive organisation of lipids provokes the lateral displacements of hydrophilic compartments, squeezed aside along the lipid layers towards intercellular junctions (corneodesmosomes). Proteolytic enzymes contained in the hydrophilic material are thus delivered to the extracellular portions of cohesive junctional proteins. Consequently, modifications of the composition and structure of the stratum corneum lipids may influence epidermal desquamation through the regulation of corneodesmosome accessibility to extracellular enzymes.


The use of artificial intelligence to detect students' sentiments and emotions in gross anatomy reflections.
Students' reflective writings in gross anatomy provide a rich source of complex emotions experienced by learners. However, qualitative approaches to evaluating student writings are resource heavy and timely. To overcome this, natural language processing, a nascent field of artificial intelligence that uses computational techniques for the analysis and synthesis of text, was used to compare health professional students' reflections on the importance of various regions of the body to their own lives and those of the anatomical donor dissected. A total of 1365 anonymous writings (677 about a donor, 688 about self) were collected from 132 students. Binary and trinary sentiment analysis was performed, as well as emotion detection using the National Research Council Emotion Lexicon which classified text into eight emotions: anger, fear, sadness, disgust, surprise, anticipation, trust, and joy. The most commonly written about body regions were the hands, heart, and brain. The reflections had an overwhelming positive sentiment with major contributing words "love" and "loved." Predominant words such as "pain" contributed to the negative sentiments and reflected various ailments experienced by students and revealed through dissections of the donors. The top three emotions were trust, joy, and anticipation. Each body region evoked a unique combination of emotions. Similarities between student self-reflections and reflections about their donor were evident suggesting a shared view of humanization and person centeredness. Given the pervasiveness of reflections in anatomy, adopting a natural language processing approach to analysis could provide a rich source of new information related to students' previously undiscovered experiences and competencies.


Relations among children's social goals, implicit personality theories, and responses to social failure.
Two studies examined children's thought patterns in relation to their responses to social challenge. In Study 1, 4th and 5th graders tried out for a pen pal club under either a performance goal (stressing the evaluative nature of the tryout) or a learning goal (emphasizing the potential learning opportunities). In their behavior and attributions following rejection, children who were focused on a performance goal reacted with more helplessness, whereas children given a learning goal displayed a more mastery-oriented response. Study 2 found that in response to hypothetical socially challenging situations, 4th, 5th, and 6th graders who believed personality was nonmalleable (entity theorists) vs. malleable (incremental theorists) were more likely to endorse performance goals. Together, these studies indicate that children's goals in social situations are associated with their responses to social failure and are predicted by their implicit theories about their personality.


"We Kind of Met In-Between": A Qualitative Analysis of Young Couples' Relationship Dynamics and Negotiations About Pregnancy Intentions.
The literature on reproductive decision making often focuses on women and neglects the role of men and the importance of relationship context. Research with couples is vital to understanding joint decision making regarding having children at various stages of a couple's relationship and an individual's life course. In-depth, individual interviews were conducted with a socioeconomically, racially and ethnically diverse sample of 50 young heterosexual women and their male partners in northern California in 2015-2016. A dyadic, thematic analytic approach was used to examine whether and how prospective pregnancy intentions and current pregnancy desires are negotiated at the couple level, and how relationship dynamics influence any negotiation and decision-making processes. Twenty-three couples described engaging in joint pregnancy decision making, which required purposeful communication and, for some, compromise and acceptance. For nearly all of these couples, these processes led to aligned prospective pregnancy intentions, even when current pregnancy desires differed. The remaining 27 couples described individual pregnancy decision-making processes; many respondents reported intentions that aligned with their partner's by happenstance, despite some respondents having avoided communicating their desires to their partner. Some of these couples faced relationship difficulties, including poor communication, leading some participants to misinterpret or be unaware of their partner's pregnancy intentions and desires. The relationship context is important in the formulation of prospective pregnancy intentions among young people. Counseling protocols, interventions and policies that attend to the complex factors that influence young couples' pregnancy decision making are needed to better help couples attain their reproductive goals.


Validation of Anthropometric Muscle Cross-Sectional Area Equation after Spinal Cord Injury.
The purposes of this study were to cross-validate a previously derived anthropometric estimation equation specific to the spinal cord injury population and determine the ratios of absolute skeletal muscle cross-sectional area (CSA) for the quadriceps, hamstrings, and adductor muscle groups based on magnetic resonance imaging. The validation cohort consisted of eleven men with chronic (>1 yr. post injury) spinal cord injury (SCI). Ten individuals were classified as AIS A or B and one participant was classified as an AIS C. Significant correlations were found between the anthropometrically predicted CSAs and MRI-derived CSAs for the whole muscle including bone and intramuscular fat (r2=0.72, SEE=10.6 cm2, P<0.001), absolute muscle excluding bone and intramuscular fat (r2=0.60, SEE=10.1 cm2, P=0.005), and absolute quadriceps muscle (r2=0.67, SEE=5.5 cm2, P=0.002). The quadriceps, hamstrings and the adductor muscle groups represented 52±5%, 23±6%, and 20±4%, respectively, of the absolute muscle CSA. Our results suggest that the utilization of a previously developed anthropometric equation is applicable to a different validation cohort with SCI. The equation has the ability to predict whole muscle CSA, absolute muscle CSA excluding bone and intramuscular fat, and absolute muscle CSA of the quadriceps in individuals with chronic SCI.


Prevalence of goitre and autoimmune thyroiditis in schoolchildren in Delhi, India, after two decades of salt iodisation.
Delhi lies in the sub-Himalayan plains and the existence of iodine deficiency is well established. Iodised salt was introduced in Delhi nearly two decades ago. The aim of the present study was to determine the status of iodine nutrition in school-aged children and the prevalence of autoimmune thyroiditis. A total of 4,320 schoolchildren (2,218 [51.3%] boys) aged 10-16 years were studied. Goitre was detected in 396 children, an overall goitre prevalence of 9.2%. Of the 396 children with goitre, 112 (28.3%) had evidence of autoimmune thyroiditis (AIT). The median urinary iodine (UI) excretion in the study population as a whole was 14.6 microg/dl. The median UI in the group of children with goiter was 13.3 microg/dl, whereas UI in children with goiter and evidence of AIT was 16.6 microg/dl (p <0.01). Of the 112 children with AIT, 77 (68.7%) were euthyroid, 23 (20.5%) had subclinical hypothyroidism, eight (7.2%) had hypothyroidism and the remaining four (3.6%) had hyperthyroidism. UI was high in goitrous children with AIT, and in children with thyroid dysfunction. Further studies are needed to clarify whether the higher UI in goitrous children with AIT is causally related to AIT or is due to the inability of the diseased thyroid to trap available iodine efficiently.


Analysis techniques for microarray time-series data.
We address possible limitations of publicly available data sets of yeast gene expression. We study the predictability of known regulators via time-series analysis, and show that less than 20% of known regulatory pairs exhibit strong correlations in the Cho/Spellman data sets. By analyzing known regulatory relationships, we designed an edge detection function which identified candidate regulations with greater fidelity than standard correlation methods. We develop general methods for integrated analysis of coarse time-series data sets. These include 1) methods for automated period detection in a predominately cycling data set and 2) phase detection between phase-shifted cyclic data sets. We show how to properly correct for the problem of comparing correlation coefficients between pairs of sequences of different lengths and small alphabets. Finally, we note that the correlation coefficient of sequences over alphabets of size two can exhibit very counterintuitive behavior when compared with the Hamming distance.


Control of heterogeneous Fe(III) (hydr)oxide nucleation and growth by interfacial energies and local saturations.
To predict the fate of aqueous pollutants, a better understanding of heterogeneous Fe(III) (hydr)oxide nucleation and growth on abundant mineral surfaces is needed. In this study, we measured in situ heterogeneous Fe(III) (hydr)oxide nucleation and growth on quartz, muscovite, and corundum (Al2O3) in 10(-4) M Fe(III) solution (in 10 mM NaNO3 at pH = 3.7 ± 0.2) using grazing incidence small-angle X-ray scattering (GISAXS). Interestingly, both the fastest heterogeneous nucleation and slowest growth occurred on corundum. To elucidate the mechanisms, zeta potential and water contact angle measurements were conducted. Electrostatic forces between the charged Fe(III) (hydr)oxide polymeric embryos and substrate surfaces-which affect local saturations near the substrate surfaces-controlled heterogeneous growth rates. Water contact angles (7.5° ± 0.7, 22.8° ± 1.7, and 44.8° ± 3.7 for quartz, muscovite, and corundum, respectively) indicate that corundum has the highest substrate-water interfacial energy. Furthermore, a comparison of structural mismatches between the substrates and precipitates indicates a lowest precipitate-substrate interfacial energy for corundum. The fastest nucleation on corundum suggests that interfacial energies in the solution-substrate-precipitate system controlled heterogeneous nucleation rates. The unique information provided here bolsters our understanding of nanoparticle-mineral surface interactions, mineral surface modification by iron oxide coating, and pollutant transport.


What are our AIMs? Interdisciplinary Perspectives on the Use of Ancestry Estimation in Disease Research.
Ancestry estimation serves as a tool to identify genetic contributions to disease but may contribute to racial discrimination and stigmatization. We sought to understand user perspectives on the benefits and harms of ancestry estimation to inform research practice and contribute to debates about the use of race and ancestry in genetics. Key informant interviews with 22 scientists were conducted to examine scientists' understandings of the benefits and harms of ancestry estimation. Three main perspectives were observed among key informant scientists who use ancestry estimation in genetic epidemiology research. Population geneticists self identified as educators who controlled the meaning and application of ancestry estimation in research. Clinician-researchers were optimistic about the application of ancestry estimation to individualized risk assessment and personalized medicine. Epidemiologists remained ambivalent toward ancestry estimation and suggested a continued role for race in their research. We observed an imbalance of control over the meaning and application of ancestry estimation among disciplines that may result in unwarranted or premature translation of ancestry estimation into medicine and public health. Differences in disciplinary perspectives need to be addressed if translational benefits of genetic ancestry estimation are to be realized.


Systematic reviews of qualitative evidence: what are the experiences of women with endometriosis?
Just as systematic reviews of quantitative research have developed over the last two decades, the use of a systematic review is also superseding narrative non-systematic reviews in qualitative research in an attempt to bring rigour to reviewing research evidence. Qualitative research is concerned with the subjective world and the way in which people interpret and make sense of the reality of their lives. This paper describes procedures for conducting a systematic review on qualitative research, and the methods for assessing the quality of qualitative research papers, using published qualitative research on endometriosis as an example to demonstrate these. The conclusion from the systematic review carried out is that the values and methods utilised for a systematic review can usefully be applied to qualitative research. The review of endometriosis research revealed that despite the impact of endometriosis on the lives of women sufferers, little qualitative research has been conducted, and much of that which exists lacks rigour in a number of key areas.


Synthetic Simplification of Carolacton Enables Chemical Genetic Studies in Streptococcus mutans.
Understanding the broader biological impact of carolacton, a macrolactone natural product, has been ongoing for the past decade. Multiple studies have shown connections to regulatory systems, acid tolerance mechanisms, biofilm formation, and recently folate dehydrogenase (FolD). Progress elucidating the cause of biofilm-specific activity in Streptococcus mutans has been limited due to low-throughput analyses of carolacton-treated cells. We disclose the discovery of a simplified carolacton-inspired analog that demonstrates inhibitory activity against S. mutans biofilm cells. This discovery permitted a proof of concept chemical genetic screen of S. mutans mutants identifying the carbon catabolite protein A signaling pathway as a putative target.


Acknowledging Errors: Advanced Molecular Replacement with Phaser.
Molecular replacement is a method for solving the crystallographic phase problem using an atomic model for the target structure. State-of-the-art methods have moved the field significantly from when it was first envisaged as a method for solving cases of high homology and completeness between a model and target structure. Improvements brought about by application of maximum likelihood statistics mean that various errors in the model and pathologies in the data can be accounted for, so that cases hitherto thought to be intractable are standardly solvable. As a result, molecular replacement phasing now accounts for the lion's share of structures deposited in the Protein Data Bank. However, there will always be cases at the fringes of solvability. I discuss here the approaches that will help tackle challenging molecular replacement cases.


The use of time-lapse optical coherence tomography to image the effects of microapplied toxins on the retina.
We developed a novel technique for accelerated drug screening and retinotoxin characterization using time-lapse optical coherence tomography (OCT) and a drug microapplication device. Using an ex vivo rabbit eyecup preparation, we studied retinotoxin effects in real-time by microperfusing small retinal areas under a transparent fluoropolymer tube. Known retinotoxic agents were applied to the retina for 5-minute periods, while changes in retinal structure, thickness, and reflectance were monitored with OCT. The OCT images of two agents with dissimilar mechanisms, cyanide and kainic acid, were compared to their structural changes seen histologically. We found the actions of retinotoxic agents tested could be classified broadly into two distinct types: (1) agents that induce neuronal depolarization, such as kainic acid, causing increases in OCT reflectivity or thickness of the inner plexiform and nuclear layers, and decreased reflectivity of the outer retina; and (2) agents that disrupt mitochondrial function, such as cyanide, causing outer retinal structural changes as evidenced by a reduction in the OCT reflectivity of the photoreceptor outer segment and pigment epithelium layers. Retinotoxin-induced changes in retinal layer reflectivity and thickness under the microperfusion tube in OCT images closely matched the histological evidence of retinal injury. Time-lapse OCT imaging of the microperfused local retina has the potential to accelerate drug retinotoxicological screening and expand the use of OCT as an evaluation tool for preclinical animal testing.


The Dbs PH domain contributes independently to membrane targeting and regulation of guanine nucleotide-exchange activity.
Dbl family GEFs (guanine nucleotide-exchange factors) for the Rho GTPases almost invariably contain a PH (pleckstrin homology) domain adjacent to their DH (Dbl homology) domain. The DH domain is responsible for GEF activity, and the PH domain plays a regulatory role that remains poorly understood. We demonstrated previously that Dbl family PH domains bind phosphoinositides with low affinity and cannot function as independent membrane targeting modules. In the present study, we show that dimerization of a Dbs (Dbl's big sister) DH/PH domain fragment is sufficient to drive it to the plasma membrane through a mechanism involving PH domain-phosphoinositide interactions. Thus, the Dbs PH domain could play a significant role in membrane targeting if it co-operates with other domains in the protein. We also show that mutations that prevent phosphoinositide binding by the Dbs PH domain significantly impair cellular GEF activity even in chimaeric proteins that are robustly membrane targeted by farnesylation or by the PH domain of phospholipase C-delta1. This finding argues that the Dbs PH domain plays a regulatory role that is independent of its ability to aid membrane targeting. Thus, we suggest that the PH domain plays dual roles, contributing independently to membrane localization of Dbs (as part of a multi-domain interaction) and allosteric regulation of the DH domain.


Fluorescence in situ hybridization analyses of chromosome band 1p36 in neuroblastoma detect two classes of alterations.
Chromosomal alterations in 1p36 were investigated in 196 neuroblastoma tumors using fluorescence in situ hybridization. Additionally, by using the same technique, it was determined whether MYCN was amplified in 149 of these. The most frequent finding was a deletion in 1p36, leading to monosomy of this region (29 cases, 15%). Furthermore, we found tumors with at least two intact copies of chromosome 1 and additional 1p36-deleted copies. Altogether, 21 tumors (11%) displayed this imbalance of 1p36. Similar to the cases with deletion, imbalances were predominantly found in stage 4 tumors (81%), and they were significantly associated with an increased patient age (P = 0.01). Nearly all 1p-deleted tumors showed amplification of MYCN (24/27 analyzed samples, 89%), whereas only 8 of 21 (38%) with imbalance did. Eight cases with imbalance were investigated for loss of heterozygosity (LOH) using microsatellite markers in 1p35-36. Only 4 displayed 1p36 LOH, whereas the remaining 4 were heterozygous. Both patients with deletion of 1p and with imbalance had a poor outcome [3-year rate of event-free-survival (EFS): 33 +/- 15% and 41 +/- 15%], which was significantly worse compared to the outcome of patients without 1p alterations (3-year EFS: 70 +/- 5%; P = 0.01 and P = 0.0059). We conclude that besides monosomic short arm deletions, imbalance of 1p36 is a strong marker of a poor prognosis in neuroblastoma and not necessarily associated with MYCN amplification and LOH.


Computer Science meets Vascular Surgery: Keeping a pulse on artificial intelligence.
Artificial intelligence (AI)-based technologies have garnered interest across a range of disciplines in the past several years, with an even more recent interest in various health care fields, including Vascular Surgery. AI offers a unique ability to analyze health data more quickly and efficiently than could be done by humans alone and can be used for clinical applications such as diagnosis, risk stratification, and follow-up, as well as patient-used applications to improve both patient and provider experiences, mitigate health care disparities, and individualize treatment. As with all novel technologies, AI is not without its risks and carries with it unique ethical considerations that will need to be addressed before its broad integration into health care systems. AI has the potential to revolutionize the way care is provided to patients, including those requiring vascular care.


A Study on Genetic Distances Among Germplasm Accessions of French Bean.
In a usual hierarchical cluster analysis, the identification of genetic distances among germplasm accessions through morphological data on qualitative as well as quantitative characters recorded using the International Plant Genetic Resources Institute (IPGRI)/ National Bureau of Plant Genetic Resources (NBPGR) descriptors, the high numerical nature of the quantitative data leads to the masking of smaller numerical but very important qualitative characters, leading to a lesser precision. This is true with D2 statistics and also the principal component based vector analysis leading to genetic divergence, restricting the use of highly significant qualitative parameters in germplasm characterization, often resulting in misclassifications even at the species level. Hence, the molecular markers are relied upon for final conclusions. Efficient data transformation systems to arrive at the exact genetic distances by accounting for both the qualitative as well as quantitative characters with equal weightage are being detailed hereunder. Among the models proposed, (value - mean)/SD was proved to be the best and the results are further supported by the factor analysis of principal components derived from the correlation matrix.


The translational termination signal database (TransTerm) now also includes initiation contexts.
The TransTerm database of termination codon contexts has been extended to include sense codon usage, and initiation codon contexts. The database was constructed from 23,721 coding sequences from 93 organisms. The database contains: a) the sequence around the termination codon (-10, +10); b) the sequence around the initiation codon (-20, +10); c) the length, 'G+C%' of the third position of codons (GC3), the 'codon adaptation index' (CAI) and the 'effective number of codons' statistic (Nc); d) summary tables for each organism including total codon usage, stop codon and tetranucleotide stop-signal usage, and matrices tallying base frequencies at each position around the initiation and termination codons. The data are arranged to facilitate investigation of the relationships between the three phases of protein synthesis. The database is available electronically from EMBL.


Structural, dynamic, and electronic properties of liquid tin: An ab initio molecular dynamics study.
We report on a study of several structural, dynamic, and electronic properties of liquid Sn at a thermodynamic state close to the triple point (573 K) and another one at a higher temperature (1273 K). This study has been performed by ab initio molecular dynamics simulations using 205 atoms and around 20 ps of simulation time. The calculated static structures show a good agreement with the available experimental data. The dynamic structure factors fairly agree with their experimental counterparts obtained by inelastic x-ray scattering experiments, which display inelastic side peaks. The calculated dispersion relations exhibit a positive dispersion, although not so marked as suggested by the experiment; moreover, its slope at the long-wavelength limit compares favorably with the experimental sound velocity. Electron densities near selected triplets of atoms are similar to those appearing in the solid phases, but these features have an extremely short lifetime, so they should not be considered as solid remnants in the melt.


Benzophenone-3 sunscreen causes phytotoxicity and cytogenotoxicity in higher plants.
The benzophenone-3 (BP-3) sunscreen is recurrently released into the environment from different sources, however, evaluations of its adverse effects on plants do not exist in the literature. In this study, BP-3 was evaluated, at concentrations 2; 20, and 200 µg/L, regarding phytotoxicity, based on germination and root elongation in seeds, in Lactuca sativa L., Cucumis sativus L. and Allium cepa L., and phytotoxicity, cytogenotoxicity and oxidative stress in A. cepa bulb roots. The BP-3 concentrations, except for the 200 µg/L concentration in L. sativa, caused no significant reduction in seed germination. All concentrations tested significantly reduced the elongation of roots from seeds and roots from bulbs. The 20 and 200 µg/L concentrations caused oxidation in cells, disturbances in the cell cycle, and alterations in prophase and metaphase, as well as the induction of micronuclei, in A. cepa root meristems. Furthermore, the three concentrations induced a high number of prophases in root tips. Such disorders were caused by excess H2O2 and superoxide produced in cells due to exposure to BP-3, which triggered significant phytotoxicity, cytotoxicity, and genotoxicity in root meristems. Thus, the recurrent contamination of agricultural and non-agricultural soils with BP-3, even at a concentration of 2 µg/L, represents an environmental risk for plants. These results point to the impending need to set limits for the disposal of this sunscreen into the environment since BP-3 has been used in industry for several decades.


Spectrophotometric estimation of individual flavone glycosides in three Euphorbia species.
Two spectrophotometric methods (conventional and differential) are carried out for the estimation of flavone glycosides (hyperoside and/or kaempferol-3-beta-glucoside) in Euphorbia paralias L., and Euphorbia helioscopia L. The glycosides are extracted with methanol from the aerial parts of the different Euphorbia species, separated on silica gel chromatoplates, and eluted by refluxing with methanol (80%). The absorbance value (conventional method) and the delta absorbance value (differential method) of the prepared glycosidal solutions are measured. The results of both methods are of conveinent reproducibility.


Boys are victims too? Sexual dating violence and injury among high-risk youth.
Prior research with youth exposed to violence suggests that, in this high-risk population, boys may be victims of sexual teen dating violence (TDV) and injury as frequently as girls. We sought to replicate these findings with a demographically similar sample and to determine whether the findings could be attributed the high-risk nature of the sample by assessing the impact of violence exposure on sex differences. A cross-sectional sample of 2577 youth (ages 11-18, M=15.4, SD=1.9, 52% female, 25% Caucasian) collected in 2004 from a high-risk community reported on history of dating and exposure to multiple forms of violence. We conducted moderation analyses to test whether polyvictimization (PV) and age moderated the potential sex differences in perpetration and victimization of sexual TDV and injury. No significant sex differences in victimization were observed regardless of degree of PV. Boys reported more frequent sexual TDV and injury perpetration relative to girls, but only for youth reporting high degree of PV. There were no sex differences in perpetration among low PV youth. These findings suggest boys from high-risk communities may disproportionately perpetrate severe acts of TDV but at this early age they are equally likely to be victimized. To interrupt the cycle of violence victimization and perpetration, comprehensive violence prevention interventions targeting high-risk youth should be implemented at schools, in homes, and in the community; and they should recognize the potential for girls and boys to be victims of even the most severe forms of TDV.


NMI promotes tumor progression and gemcitabine resistance in pancreatic cancer via STAT3-IFIT3 axis.
N-myc and STAT interactor (NMI) has been reported to interact with several transcription factors, including STATs family, c-Myc, N-Myc, and BRCA1, to indirectly affect transcription events and participate in multiple cellular processes. However, its function in pancreatic ductal adenocarcinoma (PDAC) has seldom been studied. In this study, we investigated the regulation of NMI on PDAC progression and uncovered the underlying molecular mechanisms. We found that NMI expression was significantly upregulated in PDAC and high NMI expression was related to a worse patient survival. Cell proliferation and migration assay, including cell viability, transwell assay, wound healing, and subcutaneous mouse model were utilized to confirm the function of NMI in PDAC progression. Downregulation of NMI abrogates tumor progression of PDAC both in vitro and in vivo. RNA sequencing was utilized to identify the downstream molecules of NMI and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) was confirmed to be regulated by NMI in both mRNA and protein level. The binding function of NMI to STAT3 was essential in regulating the IFIT3 expression. Moreover, the NMI/STAT3-IFIT3 axis was identified to markedly facilitate the gemcitabine resistance in PDAC cells.


Photoreceptors in the rat retina are specifically vulnerable to both hypoxia and hyperoxia.
The current study aims to assess the vulnerability of photoreceptors in rat retina to variations in tissue oxygen levels. Young adult Sprague-Dawley rats were exposed to air with the concentration of oxygen set at 10% (hypoxia), 21% (room air, normoxia), and four levels of hyperoxia (45%, 65%, 70%, and 75%), for up to 3 weeks. Their retinas were then examined for cell death, using the TUNEL technique. Hypoxia (10% oxygen) for 2 weeks caused a limited but significant rise in the frequency of TUNEL+ (dying) cells in the retina, the great majority (>90%) being located in the outer nuclear layer (ONL). Hyperoxia also induced an increase in the frequency of TUNEL+ cells, again predominantly in the ONL. The increase rose with duration of exposure, up to 2 weeks. At 2 weeks exposure, the increase was limited yet significant at 45% oxygen, and maximal at 65%. Where the frequencies of TUNEL+ cells were high, it was evident that photoreceptor death was maximal in the midperipheral retina. The adult retina is vulnerable to maintained shifts in oxygen availability to the retina, both below and above normal. The vulnerability is specific to photoreceptors; other retinal neurons appeared resistant to the exposures tested. Shifts in retinal oxygen levels caused by variations in ambient light, by the persistence of light through the normally dark (night) half of the day-night cycle, or by depletion of the photoreceptor population, may contribute to photoreceptor death in the normal retina.


Is the cloze procedure appropriate to evaluate health literacy in older individuals? Age effects in the test of functional health literacy in adults.
Health literacy has received increasing attention because of its importance for older individuals' health, as studies have shown a close relation between older individuals' health literacy and their health. Research also suggests that older individuals have low levels of health literacy, but this finding is variable and may depend on which health literacy test is used. Older individuals assessed with the Test of Functional Health Literacy (TOFHLA) score lower than younger individuals, but a previous study suggested that this may result from age-related differential item functioning (DIF) on the TOFHLA. The study reported here assessed age-related DIF in a sample of community-dwelling volunteers. Twenty-two percent of items were differentially more difficult for older individuals independent of their overall ability, and when these items were eliminated from the total score, age differences were no longer found. Performance on a working memory task predicted older but not younger individuals' performance on the age-related items. At least part of older individuals' apparent deficits in health literacy when assessed by the TOFHLA may be related to DIF on its items. The TOFHLA, and any measure that employs the cloze procedure to evaluate reading comprehension, should be used cautiously in older individuals.


Dielectric properties of polymer-particle nanocomposites influenced by electronic nature of filler surfaces.
The interface between the polymer and the particle has a critical role in altering the properties of a composite dielectric. Polymer-ceramic nanocomposites are promising dielectric materials for many electronic and power devices, combining the high dielectric constant of ceramic particles with the high dielectric breakdown strength of a polymer. Self-assembled monolayers of electron rich or electron poor organophosphate coupling groups were applied to affect the filler-polymer interface and investigate the role of this interface on composite behavior. The interface has potential to influence dielectric properties, in particular the leakage and breakdown resistance. The composite films synthesized from the modified filler particles dispersed into an epoxy polymer matrix were analyzed by dielectric spectroscopy, breakdown strength, and leakage current measurements. The data indicate that significant reduction in leakage currents and dielectric losses and improvement in dielectric breakdown strengths resulted when electropositive phenyl, electron-withdrawing functional groups were located at the polymer-particle interface. At a 30 vol % particle concentration, dielectric composite films yielded a maximum energy density of ~8 J·cm(-3) for TiO2-epoxy nanocomposites and ~9.5 J·cm(-3) for BaTiO3-epoxy nanocomposites.


Toxicology testing requirements and the U.S.-Japan collaborative study on in vitro tests for chromosomal aberrations.
As part of the U.S.-Japan Agreement on Cooperation in Research and Development in Science and Technology, Japanese and American scientists met in North Carolina to exchange information on toxicology testing requirements and guidelines in the two countries and to review progress in a collaborative study on detection of chemically induced chromosomal aberrations in cultured mammalian cells.


Fontan Circulation Might be Associated with Peripartum Cardiomyopathy: A Review of Mechanistic and Clinical Aspects.
Fontan operation has been defined as a palliative surgery connecting systemic venous return and pulmonary circulation in patients with certain forms of complex congenital heart disease (CHD). Fortunately, it has improved overall survival and chance of successful pregnancies among these patients. However, Fontan circulation (FC), as a potential trade-off, might be associated with specific late or post-gestational complications, including peripartum cardiomyopathy (PPCM) largely through its adverse effects on the placenta and inflammation-oxidation stress. Importantly, diagnosis of superimposed PPCM in women with FC might be a diagnostic challenge, requiring a high index of suspicion. Accordingly, the present paper aims to highlight the potential association of FC with PPCM evolution largely based on certain mechanistic and clinical perspectives.


[Health state of Aral region dwellers].
Studies of birth rate, natural increment and death rate dynamics of Aral region population helped to set major tendencies in demographic processes for dwellers in ecologic disaster area. Morbidity parameters were evaluated via ICD-10 classes with distribution in age and sex, that helped to identify leading classes of diseases in the population of Kyzylorda region. DALY index parameters were estimated through complex evaluation of health losses due to disablement and mortality among adult population of Kyzylorda region. The studies covered 5 districts of Kyzylorda region (Aral, Kazalin, Zhalagash, Karmaksh, Shiely). The parameters were analysed retrospectively over 10 years--from 2004 to 2013.


Perceived direction of gaze from eyes with dark vs. light irises.
Much of the previous research on the perceived direction of gaze has not specified eye color or pupil visibility. This study tests whether the lightness or darkness of a gazer's irises (typically brown vs. blue) affects their perceived direction of gaze. Twenty-five observers judged the direction of horizontal gaze from a model whose LCD-imaged head gazed toward points on the plane of the observer's face. The model's head was displayed with its natural brown irises and also with its irises digitally altered to look blue without pupils, blue with centered pupils, and blue with nasally decentered pupils. True gaze location was compared with the judged gaze location for each type of iris. For all iris types, observers judged that monocular gaze was biased outward from its true direction for all gaze locations, including central, whereas binocular gaze was close to centered and had a greater slope. Blue eyes with no pupil and blue eyes with a centered pupil exaggerated this perceived outward deviation for monocular gaze but binocular gaze remained the same. When the pupils were nasally decentered by a typical amount, straight monocular as well as binocular gaze appeared to be centered. The direction of monocular gaze from eyes that differ in the darkness of their irises is perceived differently, and, within the blue irises, small differences in pupil centration made surprisingly large differences in the perceived directions of gaze.


Relationships between hearing loss and cognition in normally hearing aged persons.
The relationships between mild hearing losses and cognitive functioning were studied for two independently selected samples of aged subjects whose hearing was within normal limits. One group had 47 males of mean age 71.5 (SD 4.8) who were selected for their excellent health status. The second group consisted of 38 females of mean age 75.9 (SD 5.3), all of whom had some significant physical pathology. Hearing losses at various frequency levels (from 125 to 8000 cps) were correlated with performance on cognitive tests such as the WAIS, with age effects then being partialled out. The results reveal substantial associations between hearing losses and scores achieved on the intellectual measures for both samples. Verbal type tests show these relationships much more extensively than the performance tests. The findings imply that aged subjects may be more intellectually capable than their test performances suggest and that hearing is an important variable to be considered in the assessment of their cognitive functioning.


Implementing evidence in an onco-haematology nursing unit: a process of change using participatory action research.
To implement evidence in a nursing unit and to gain a better understanding of the experience of change within a participatory action research. Study design of a participatory action research type was use from the constructivist paradigm. The analytical-methodological decisions were inspired by Checkland Flexible Systems for evidence implementation in the nursing unit. The study was carried out between March and November 2007 in the isolation unit section for onco-haematological patients in a tertiary level general university hospital in Spain. Accidental sampling was carried out with the participation of six nurses. Data were collected using five group meetings and individual reflections in participants' dairies. The participant observation technique was also carried out by researchers. Data analysis was carried out by content analysis. The rigorous criteria were used: credibility, confirmability, dependence, transferability and reflexivity. A lack of use of evidence in clinical practice is the main problem. The factors involved were identified (training, values, beliefs, resources and professional autonomy). Their daily practice (complexity in taking decisions, variability, lack of professional autonomy and safety) was compared with an ideal situation (using evidence it will be possible to normalise practice and to work more effectively in teams by increasing safety and professional recognition). It was decided to create five working areas about several clinical topics (mucositis, pain, anxiety, satisfaction, nutritional assessment, nauseas and vomiting, pressure ulcers and catheter-related problems) and seven changes in clinical practice were agreed upon together with 11 implementation strategies. Some reflections were made about the features of the study: the changes produced; the strategies used and how to improve them; the nursing 'subculture'; attitudes towards innovation; and the commitment as participants in the study and as healthcare professionals. The findings throw light on the process of change in the healthcare sector. The results are useful to modify nursing practice based on evidence.


Endoscopic stenting for chronic recurrent pancreatitis in a child.
Chronic pancreatitis in childhood is a rare but potentially debilitating disorder. Conservative therapy frequently fails, so that recurrent attacks are common. Traditional therapy often culminates in longitudinal pancreaticojejunostomy and distal pancreatectomy with Roux-en-Y pancreaticojejunostomy. We report a 9-year-old girl who had recurrent pancreatitis accompanied by multiple pancreatic cysts with stones in the pancreatic duct. She had been admitted complaining of abdominal pain. Abdominal sonography showed a dilated pancreatic duct and enlarged polycystic kidneys bilaterally. On abdominal computed tomography, there was a suspicion of a calcified shadow in a swollen pancreatic head, along with significant dilatation of the pancreatic duct in the body and the tail. With conservative treatment, the symptoms improved but relapsed 4 months later. Abdominal CT showed progressive abnormalities in the pancreas. ERCP with papillosphincterotomy was performed, resulting in the efflux of pus and stones. A stent was placed in the main pancreatic duct, which dramatically improved the patient's symptoms. We recommend endoscopic stent placement therapy in children with chronic pancreatitis with stones as an alternative to extensive surgery.


High-resolution ultrastructure of amyloid fibrils in familial amyloid polyneuropathy.
The ultrastructure of amyloid fibrils in familial amyloid polyneuropathy (FAP) was clearly demonstrated. Amyloid of three patients with FAP caused by the point mutation of the 30th amino acid of transthyretin (ATTR Val30Met) and one patient with FAP caused by two point mutations of the 30th and 104th amino acid of transthyretin (ATTR Val30Met/Arg104Cys) were partially isolated, stained negatively and examined with an electron microscope. Amyloid fibrils of both types were composed of two protofilaments and twisted at 180 degrees to the right and left alternately with a periodicity of 125-135 nm. This is the first report demonstrating such unique alternating twist structure of amyloid fibrils. There were no ultrastructural differences between the fibrils caused by the ATTR Val30Met and ATTR Val30Met/ Arg104His; therefore, it is suggested that the point mutation of the 30th amino acid of transthyretin might play an important role in the formation of amyloid fibrils. Further biochemical study on the mechanism of this alternating twist formation should be undertaken.


Pediatric vascular anomalies in Austria. Where are we at? A survey among primary care pediatricians.
Vascular anomalies (VAs) are rare conditions and affected patients often experience a difficult patient journey. Timely diagnosis is only possible if primary caregivers are aware of the anomalies and are connected with dedicated specialists. Aim of our survey was to investigate the knowledge about diagnostic and therapeutic possibilities for children with VAs, and the existing networking among primary pediatric caregivers in Austria. Primary care pediatricians in Austria were invited to complete an online questionnaire consisting of 28 questions focusing on pediatric VAs. Out of 373 invited pediatricians 93 (25%) returned the questionnaires, 86 of which were complete. Most physicians (39/93 42%) answered that they see between 15 and 30 patients with infantile hemangiomas per year. Vascular malformations are rarely treated in the primary care setting; most primary care pediatricians (58/86, 67%) reported that they currently treat fewer than 5 patients with such type of VAs. There was unequivocal agreement among the participants (84/86, 98%) on the need to establish a network of specialists and a registry dedicated to pediatric VAs. This survey represents the first study shedding light on the awareness of VAs among Austrian pediatricians and can serve as a basis for future investigations and advances in the management of these conditions in Austria and other countries with a similar healthcare setting.


Wavelet Fuzzy Brain Emotional Learning Control System Design for MIMO Uncertain Nonlinear Systems.
This paper aims to present a novel efficient scheme in order to more effectively control the multiple input and multiple output (MIMO) uncertain nonlinear systems. A wavelet fuzzy brain emotional learning controller (WFBELC) model is proposed, which is comprises the benefit of wavelet function, fuzzy theory and brain emotional neural network. When it is used as the main tracking controller for a MIMO uncertain nonlinear systems, the performances of the system, such as the approximation ability, the learning performance and the convergence rate, will be effectively improved. Meanwhile, the gradient descent method is used to adjust the parameters online of WFBELC and the Lyapunov function is employed to guarantee the rapid convergence of the control systems. For the sake of the further illustrating the superiority of this model, two examples of uncertain nonlinear systems, a Duffing-Holmes chaotic system and a Chua's chaotic circuit, are studied. After compared with other models, the test results show that the proposed model can be applied to obtain more satisfactory control performance and be more suitable to deal with the influence of the uncertainty of the MIMO nonlinear systems.


Cytotoxic activity, tumor accumulation, and tissue distribution of ruthenium-103-labeled bleomycin.
Bleomycin (BLM) was labeled with gamma-emitting 103Ru. Yields of 103Ru-labeled BLM as high as 50.6% were attained. 103Ru-labeled BLM was stable in vitro and the 103ru label was not displaced by large excesses of Cu (II) and Co (II) or Fe (III). Chromatography of the urine following 103Ru-labeled BLM injection indicated no in vivo decomposition. Pharmacokinetic studies in healthy inbred SD and tumor-bearing inbred BUF rats demonstrated tumor accumulations, tissue distributions, and clearance nearly identical with those reported for 3H-labeled BLM. Cytotoxicity studies on a WI-L2 human B-cell line showed that BLM labeled with nonradioactive Ru retained 100% of the activity demonstrated by native BLM. Thus BLM may be labeled with isotopes of Ru to form stable complexes by a simple, rapid reaction without loss of its chemotherapeutic properties or variations in its in vivo distribution. BLM labeled with the proper Ru isotope should prove useful as a gamma-emitting tracer for BLM or a beta-emitting compound capable of providing combination chemotherapy and radiotherapy of tumors.


[Myocardial infarction with nonobstructive coronary arteries].
The review focused on a relatively new issue, myocardial infarction with non-obstructive coronary arteries (MINOCA). According to current ideas, almost 6% of all myocardial infarction (MI) cases may be MINOCA. This term can be used both as a "working diagnosis" at the time of further evaluation and a final diagnosis after establishing a cause for each specific case. Since some variants of cardiac, including non-coronary, pathology may be similar to MI in a number of signs, each individual case of MINOCA requires specification. Among major causes for this condition are vasospasm, CA embolism, spontaneous CA dissection, rupture of an eccentric atherosclerotic plaque in a CA, etc. Diagnostics of MINOCA includes both a set of diagnostic tests for verification of the MI diagnosis according to the Fourth Universal Definition of MI and specific studies for elaboration of the disease etiology. A special role in differential diagnostics belongs to gadolinium-enhanced magnetic-resonance imaging (MRI) of the myocardium, which allows to distinguish between MI and non-ischemic myocardial injury of different genesis. Methods of intravascular visualization, such as optical coherence tomography (OCT) and intravascular ultrasound are also important. Commonly accepted guidelines on the treatment of this pathology consistent with current ideas are not available. However, it is obvious that therapeutic possibilities and prognosis for MINOCA depend on the identified cause in each individual case.


[Long-term survival of a patient with hepatocellular carcinoma with portal vein tumor thrombus treated with interferon-α and 5-fluorouracil combination therapy].
We report a case of long-term survival of a patient with hepatocellular carcinoma( HCC) with portal vein tumor thrombus (PVTT) treated with fluorouracil arterial infusion and interferon therapy (FAIT). A 54-year-old man with severe liver cirrhosis was diagnosed as having HCC in segment 1 and 4 of the liver, with PVTT in the left branch. After 7 courses of FAIT, the main tumor and PVTT were no longer visible on enhanced computed tomography scans. However, recurrent HCC was detected in segment 4. Subsequently, the patient was treated with transarterial chemoembolization (TACE) after confirmation of portal blood flow. At 5 years after the initial treatment, the patient is alive without further recurrence of HCC. Therefore, even if patients have HCC with PVTT in the main branch and severe liver cirrhosis, long-term survival is possible by administration of a combination of FAIT and TACE.


Polymorphism of the human Ig VH4 gene family.
In this study, we analyze the human VH4 gene family and find it to exhibit a level of polymorphism similar to that of the much larger VH3 family. A cloned VH4 probe detected an average of 10 hybridizing BgIII restriction fragments in genomic DNA derived from 75 unrelated individuals and a total of 15 distinct bands. Of these 15 restriction fragments, 12 were polymorphic, as demonstrated by band absence in some individuals. Oligonucleotide probes specific to CDR1 and CDR2 sequences of known VH4 genes detected limited numbers of bands and revealed sequence polymorphisms that correlated with several of the RFLP detected by the cloned probe. The prevalence of the individual polymorphic restriction fragments was highly variable, ranging from 1% to 97%, with a mean prevalence of 51%. These values resemble those previously observed among VH3 elements. Analysis of linkage disequilibrium suggests that most VH4 gene segments are in genetic equilibrium. These results indicate that the VH4 loci, like those of VH3, are dominated by relatively few, perhaps two to four, alleles/locus and further suggest that the haplotype organization of the human VH locus is very complex.


The HIV-1 nucleocapsid protein recruits negatively charged lipids to ensure its optimal binding to lipid membranes.
The HIV-1 Gag polyprotein precursor composed of the matrix (MA), capsid (CA), nucleocapsid (NC), and p6 domains orchestrates virus assembly via interactions between MA and the cell plasma membrane (PM) on one hand and NC and the genomic RNA on the other hand. As the Gag precursor can adopt a bent conformation, a potential interaction of the NC domain with the PM cannot be excluded during Gag assembly at the PM. To investigate the possible interaction of NC with lipid membranes in the absence of any interference from the other domains of Gag, we quantitatively characterized by fluorescence spectroscopy the binding of the mature NC protein to large unilamellar vesicles (LUVs) used as membrane models. We found that NC, either in its free form or bound to an oligonucleotide, was binding with high affinity (∼ 10(7) M(-1)) to negatively charged LUVs. The number of NC binding sites, but not the binding constant, was observed to decrease with the percentage of negatively charged lipids in the LUV composition, suggesting that NC and NC/oligonucleotide complexes were able to recruit negatively charged lipids to ensure optimal binding. However, in contrast to MA, NC did not exhibit a preference for phosphatidylinositol-(4,5)-bisphosphate. These results lead us to propose a modified Gag assembly model where the NC domain contributes to the initial binding of the bent form of Gag to the PM. The NC protein is a highly conserved nucleic acid binding protein that plays numerous key roles in HIV-1 replication. While accumulating evidence shows that NC either as a mature protein or as a domain of the Gag precursor also interacts with host proteins, only a few data are available on the possible interaction of NC with lipid membranes. Interestingly, during HIV-1 assembly, the Gag precursor is thought to adopt a bent conformation where the NC domain may interact with the plasma membrane. In this context, we quantitatively characterized the binding of NC, as a free protein or as a complex with nucleic acids, to lipid membranes and showed that the latter constitute a binding platform for NC. Taken together, our data suggest that the NC domain may play a role in the initial binding events of Gag to the plasma membrane during HIV-1 assembly.


MDMA (3,4-methylenedioxymethamphetamine)-mediated distortion of somatosensory signal transmission and neurotransmitter efflux in the ventral posterior medial thalamus.
MDMA (3,4-methylenedioxymethamphetamine, Ecstasy) is reported to enhance tactile sensory perception, an effect that is believed to contribute to its popularity as a recreational drug. To date, no literature exists that addresses the neurophysiological mechanisms underlying the effects of MDMA on somatosensation. However, MDMA interactions with the serotonin transporter protein (SERT) are well known. The rat trigeminal somatosensory system has been studied extensively and receives serotonergic afferents from the dorsal raphe nucleus. Given that these fibers express SERT, they should be vulnerable to MDMA-induced effects. We found that short-term low-dose MDMA administration (3 mg/kg i.p.) led to a significant increase in 5-hydroxytryptamine (5-HT) efflux in the ventral posterior medial (VPM) thalamus, the main relay along the lemniscal portion of the rodent trigeminal somatosensory pathway. We further evaluated the potential for MDMA to modulate whisker-evoked discharge (WED) of individual neurons in this region. After surgically implanting stainless steel 8-wire multichannel electrode bundles, we recorded spike train activity from single cells of halothane-anesthetized rats while mechanically activating the whisker pathway. We found that short-term low-dose MDMA (3 mg/kg i.p.) increased the spontaneous firing rate but reduced the magnitude and duration of WED in individual VPM thalamic neurons. It is noteworthy that the time course of drug action on neuronal firing patterns was generally consistent with increased 5-HT efflux as shown from our microdialysis studies. Based on these results, we propose the working hypothesis that MDMA may "distort" rather than enhance tactile experiences in humans, in part, by disrupting normal spike firing patterns through somatosensory thalamic relay circuits.


Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies.
Between September 1987 and May 1991, 21 children aged 10 months to 15 years (median 9 years) underwent bone marrow transplantation (BMT) for advanced haematological malignancies using a conditioning regimen consisting of total body irradiation (TBI), etoposide 1.8 g/m2 by continuous infusion, and cyclophosphamide 2 g/m2 on 3 consecutive days. The patients included 14 with acute lymphoblastic leukaemia (ALL), 1 with chronic myeloid leukaemia (CML), 1 with juvenile CML, 4 with non-Hodgkin's lymphoma and 1 with acute nonlymphocytic leukaemia. Eleven had an allogeneic BMT from an HLA-matched sibling, and 1 from an unrelated donor. Nine patients received 4-hydroperoxycyclophosphamide purged autologous marrow. Median time to myeloid engraftment (ANC > 500/microliters) was 19 days in allogeneic BMT patients and 28 days in autologous BMT patients (P < .01). Mucositis was the major regimen-related toxicity (RRT). GI toxicity in the form of diarrhoea affected ten patients and five had veno-occlusive disease of the liver. Two patients had mild bladder toxicity and one died of renal toxicity. There was no CNS or cardiac toxicity. There was no significant difference in the incidence of toxicity according to the type of BMT (autologous or allogeneic), total dose, or sequence of TBI. With a median follow-up of 44 months, ten patients are alive (6/12 allogeneic BMT patients and 4/9 autologous BMT patients). Of the 11 deaths, four were related to toxicity (2 aspergillus, 1 haemorrhage following liver biopsy, and 1 from haemolytic-uraemic syndrome), and 4/12 allogeneic and 4/9 autologous BMT patients died from relapsed disease. This conditioning regimen is well tolerated in children, demonstrating mild and reversible RRT.


Comparison of early outcomes of arthroscopic labral repair or debridement : a study using the UK Non-Arthroplasty Hip Registry dataset.
This study uses prospective registry data to compare early patient outcomes following arthroscopic repair or debridement of the acetabular labrum. Data on adult patients who underwent arthroscopic labral debridement or repair between 1 January 2012 and 31 July 2019 were extracted from the UK Non-Arthroplasty Hip Registry. Patients who underwent microfracture, osteophyte excision, or a concurrent extra-articular procedure were excluded. The EuroQol five-dimension (EQ-5D) and International Hip Outcome Tool 12 (iHOT-12) questionnaires were collected preoperatively and at six and 12 months post-operatively. Due to concerns over differential questionnaire non-response between the two groups, a combination of random sampling, propensity score matching, and pooled multivariable linear regression models were employed to compare iHOT-12 improvement. A total of 2,025 labral debridements (55%) and 1,659 labral repairs (45%) were identified. Both groups saw significant (p < 0.001) EQ-5D and iHOT-12 gain compared to preoperative scores at 12 months (iHOT-12 improvement: labral repair = +28.7 (95% confidence interval (CI) 26.4 to 30.9), labral debridement = +24.7 (95% CI 22.5 to 27.0)), however there was no significant difference between procedures after multivariable modelling. Overall, 66% of cases achieved the minimum clinically important difference (MCID) and 48% achieved substantial clinical benefit at 12 months. Both labral procedures were successful in significantly improving early functional outcome following hip arthroscopy, regardless of age or sex. Labral repair was associated with superior outcomes in univariable analysis, however there was no significant superiority demonstrated in the multivariable model. Level of evidence: III Cite this article: Bone Jt Open 2022;3(4):291-301.


A randomised study of two policies for managing default in out-patients collecting supplies of drugs for pulmonary tuberculosis in a large city in South India.
A randomized controlled study was undertaken to compare 2 policies of default management in out-patients with smear-negative pulmonary tuberculosis attending a large chest clinic in Madras city. All the patients were due to collect monthly supplies of drugs for a year, for daily self-administration at home. In the routine (R) policy, if a patient failed to collect the drug supply on a due date, a reminder letter was posted on the fourth day and, if necessary, a health visitor visited the home a week later. In the intensive (I) policy, a health visitor visited the home on the 4th day and, if necessary, a week later and at 1 and at 2 months. The main analyses concern 150 patients (75 R, 75 I), of whom 16 R and 15 I patients had a positive culture. A total of 29 patients (11 R, 18 I) did not default at any time. For the remaining 64 R and 57 I patients, the mean numbers of defaults were 3.0 and 2.3, and the mean numbers of defaulter retrieval actions were 4.3 and 3.8, respectively. The home visit as the first action (I series) was successful in retrieving defaulters on 65% of 132 occasions, while the reminder letter (R series) was successful in 56% of 193 occasions (P = 0.1). Following the second action, which was a home visit in both the series, these proportions became 80% and 84%, respectively. in the I series, 22 third and 18 fourth actions were taken, but the patient was retrieved in only 4 and 0 instances respectively. The mean number of drug collections during the year was significantly higher in the I series (9.8) than in the R series (8.6). Finally, the proportions of patients who made 12 collections in a 15-month period, a satisfactory target under Indian Programme conditions, were 69% and 52%, respectively (P = 0.07).


Phosphorylation and functional regulation of ClC-2 chloride channels expressed in Xenopus oocytes by M cyclin-dependent protein kinase.
Many dramatic alterations in various cellular processes during the cell cycle are known to involve ion channels. In ascidian embryos and Caenorhabditis elegans oocytes, for example, the activity of inwardly rectifying Cl(-) channels is enhanced during the M phase of the cell cycle, but the mechanism underlying this change remains to be established. We show here that the volume-sensitive Cl(-) channel, ClC-2 is regulated by the M-phase-specific cyclin-dependent kinase, p34(cdc2)/cyclin B. ClC-2 channels were phosphorylated by p34(cdc2)/cyclin B in both in vitro and cell-free phosphorylation assays. ClC-2 phosphorylation was inhibited by olomoucine and abolished by a (632)Ser-to-Ala (S632A) mutation in the C-terminus, indicating that (632)Ser is a target of phosphorylation by p34(cdc2)/cyclin B. Injection of activated p34(cdc2)/cyclin B attenuated the ClC-2 currents but not the S632A mutant channel currents expressed in Xenopus oocytes. ClC-2 currents attenuated by p34(cdc2)/cyclin B were increased by application of the cyclin-dependent kinase inhibitor, olomoucine (100 microM), an effect that was inhibited by calyculin A (5 nM) but not by okadaic acid (5 nM). A yeast two-hybrid system revealed a direct interaction between the ClC-2 C-terminus and protein phosphatase 1. These data suggest that the ClC-2 channel is also counter-regulated by protein phosphatase 1. In addition, p34(cdc2)/cyclin B decreased the magnitude of ClC-2 channel activation caused by cell swelling. As the activities of both p34(cdc2)/cyclin B and protein phosphatase 1 vary during the cell cycle, as does cell volume, the ClC-2 channel could be regulated physiologically by these factors.


Fatal Severe Fever with Thrombocytopenia Syndrome Virus and Pasteurella multocida Coinfection.
We herein report a case of severe fever with thrombocytopenia syndrome (SFTS) with Pasteurella multilocida bacteremia in a 65-year-old man with alcoholic cirrhosis who was admitted to our hospital with anorexia and severe fatigue. Laboratory tests revealed pancytopenia and liver and kidney dysfunction. After admission, he developed impaired consciousness, mucosal hemorrhaging, and septic shock. SFTS virus was detected on polymerase chain reaction testing of blood and throat swabs, and Pasteurella multocida was detected on blood culture. Despite being treated with invasive mechanical ventilation, vasopressors, and antibiotics, the patient's condition progressively deteriorated, and he died four days after admission.


Analysis of short-term outcome after office-based laser-assisted uvulopalatoplasty.
To determine the short-term effectiveness and outcome of office-based laser-assisted uvulopalatoplasty, a prospective statistically controlled study was done at the Department of Otolaryngology, Cleveland Clinic Florida. Thirty-eight consecutive snoring patients underwent a total of 98 laser-assisted uvulopalatoplasties, and data were gathered through examination, interview, and analog scales of snoring, pain, and other morbidity. In addition, a failure analysis was performed. Data were analyzed by descriptive statistics, confidence intervals, and adjusted analysis of variance (p < 0.008). Our results suggest that snoring decreased significantly around each laser-assisted uvulopalatoplasty treatment performed (4 to 8 weeks apart). Postoperative pain diminished after the first two laser-assisted uvulopalatoplasty treatments. The only morbidity in the series was the result of significant pain, causing 77% of laser-assisted uvulopalatoplasty failures.


Prevalence of virulence and resistance to antibiotics in pathogenic enterococci isolated from mastitic cows.
The prevalence of enterococci was examined in 280 milk samples collected from dairy cattle diagnosed with mastitis in three provinces of western China. Sixty strains of enterococci were isolated, and the species were determined based on their biochemical characters and 16S rRNA sequences. Resistance to seven antibiotic agents, frequency of seven virulence genes and pathogenicity in Kunming mice were tested to evaluate biological risks. The correlation between the number of virulence genes and pathogenicity in Kunming mice was also evaluated. The 60 isolates were allocated to Enterococcus hirae (68.3%), E. faecium (25.0%), E. mundtii (3.3%) and E. durans (3.3%). A total of 83.3% of the isolates were resistant to penicillin, whereas 15.0% were resistant to ampicillin, 15.0% to vancomycin, 6.7% to tetracycline and 25.0% to ciprofloxacin. Moreover, isolates exhibited 50.0% and 21.7% resistance to high levels of gentamycin and streptomycin, respectively. The gene asa1 was detected in all enterococcal isolates, whereas 66.7% of strains harbored three or more virulence factors and 56.7% were asa1-ccf-gelE-positive. In pathogenicity tests, isolates harboring numerous virulence factors did not show greater invasiveness than isolates harboring fewer virulence traits against Kunming mice. In conclusion, the number of virulence factors does not appear to predict the risk of enterococcal infection. Isolates were commonly resistant to penicillin and sporadically to ampicillin and vancomycin. These results suggest that the use of gentamycin, streptomycin and ciprofloxacin against enterococci should be avoided in mastitic cows. Additionally, the results demonstrate that the majority of isolates are sensitive to tetracycline.


Detection of Near Falls Using Wearable Devices: A Systematic Review.
Falls among older people are a serious health issue. Remote detection of near falls may provide a new way to identify older people at high risk of falling. This could enable exercise and fall prevention programs to target the types of near falls experienced and the situations that cause near falls before fall-related injuries occur. The purpose of this systematic review was to summarize and critically examine the evidence regarding the detection of near falls (slips, trips, stumbles, missteps, incorrect weight transfer, or temporary loss of balance) using wearable devices. CINAHL, EMBASE, MEDLINE, Compendex, and Inspec were searched to obtain studies that used a wearable device to detect near falls in young and older people with or without a chronic disease and were published in English. Nine studies met the final inclusion criteria. Wearable sensors used included accelerometers, gyroscopes, and insole force inducers. The waist was the most common location to place a single device. Both high sensitivity (≥85.7%) and specificity (≥90.0%) were reported for near-fall detection during various clinical simulations and improved when multiple devices were worn. Several methodological issues that increased the risk of bias were revealed. Most studies analyzed a single or few near-fall types by younger adults in controlled laboratory environments and did not attempt to distinguish naturally occurring near falls from actual falls or other activities of daily living in older people. The use of a single lightweight sensor to distinguish between different types of near falls, actual falls, and activities of daily living is a promising low-cost technology and clinical tool for long-term continuous monitoring of older people and clinical populations at risk of falls. However, currently the evidence is limited because studies have largely involved simulated laboratory events in young adults. Future studies should focus on validating near-fall detection in larger cohorts and include data from (i) people at high risk of falling, (ii) activities of daily living, (iii) both near falls and actual falls, and (iv) naturally occurring near falls.


An observation on the genesis of Münchausen syndrome: a case report.
A case of Münchausen Syndrome diagnosed in an antenatal ward is reported. This patient, while pregnant, presented a variety of factitious obstetric complications to her medical attendants. Examination of the patient's hospital records threw light on the natural history of Münchausen Syndrome, and suggested the possibility that the nature of her interactions with hospitals were of aetiological significance. The implications of this hypothesis are considered.


Modulatory role of protein tyrosine kinase activation in the receptor-induced contractions of the bovine cerebral artery.
Changes in contractile force were measured during isometric contraction of the bovine middle cerebral artery caused by stimulation of various receptors and by application of high K+, caffeine, and protein kinase C (PKC)-activators. The protein tyrosine kinase (PTK)-inhibitors, such as genistein and tyrphostin, were applied before testing the effect on the contractions or during the maximal plateau of the contraction. The contractions induced by serotonin, prostaglandin F2 alpha, endothelin-1, and thromboxane A2 were significantly and dose-dependently depressed by the PTK-inhibitors (IC50 2-15 microM). In contrast, contractions were significantly augmented by 1 microM pervanadate, an inhibitor of phosphoprotein tyrosine phosphatase. Lineweaver-Burk plotting of the dose-response curves with an increase in inhibitor concentration indicated that the receptor affinity for each agonist remained unchanged in spite of marked depression of the responses. Although the effect was not significant, contractions induced by both high K+ and caffeine were also depressed slightly by PTK-inhibitors in the same range of concentrations used for receptor-induced contractions. Contractions induced by PKC-activators, such as 1-oleoyl-2-acetyl-sn-glycerol and phorbol-12,13-diacetate, were significantly depressed by PTK-inhibitors at concentrations similar to those used for receptor-induced contractions. The results suggest that receptor stimulations which produce sequential activation of phospholipase C and PKC can activate PTK and trigger the so-called "PTK-cascade" causing a sustained or long-lasting contraction similar to the cerebral vasospasm observed clinically.


End-stage renal disease in Scotland: outcomes and standards of care.
The number of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) in the United Kingdom rises annually. Patients are increasingly elderly with a greater prevalence of comorbid illness. Unadjusted survival, from the time of starting RRT, is not improving. The United Kingdom Renal Association has published recommended standards of treatment, which all United Kingdom nephrologists strive to attain. This study was devised to define the impact of attaining recommended treatment standards, adjusting for patient age and comorbid illnesses, upon survival on RRT in the United Kingdom population. A prospective, registry based, observational study of all patients starting RRT in Scotland over a 1-year period, followed for the first 2 years of RRT. Of the 523 patients who were studied, 217 (41.5%) had died by 2 years of follow-up, 32% excluding deaths within the first 90 days. Age, comorbidity, weight when starting RRT, and attaining the recommended standards for albumin and hemoglobin had a significant impact upon survival. This study has emphasized the very high mortality of patients starting RRT in Scotland. By paying close attention to the attainment of recommended standards of care for patients with ESRD, it may be possible to improve upon current mortality figures. The monitoring of such success is only possible if correction is made for age and comorbidity.


Service penetration by persons with severe mental illness: how should it be measured?
As performance indicators and outcomes measures become essential parts of doing business, providers of mental health services are developing and using a number of access measures. One that is being used with increasing frequency is service penetration. However, the lack of standard methods for calculating and reporting service penetration has made the comparison of penetration rates cross studies difficult. This article discusses the conceptualization and operationalization of service penetration. In addition, it presents an exploratory study of service penetration using data from the same persons using very different data sources; these data were collected during an evaluation of a Medicaid managed care system in Florida. The article offers recommendations for the use and reporting of service penetration rates.


[Survey on Preparedness, Concerns, and Support Demands for Autonomous Management of Chemical Substances].
The management of workplace chemicals shifted from a regulatory-based to a self-managed approach as of April 2023. To assess readiness, concerns, and necessary support for this change, a free-response questionnaire survey was conducted for the participants of the "Promoting self-management of chemicals in enterprises" seminar held by the Department of Occupational Health, Graduate School of Medicine, University of Occupational and Environmental Health, Japan, in January-February 2023. Text-mining using KH Coder (Ver.3) was conducted to investigate relationships between words that appeared in sentences using a co-occurrence network and hierarchical cluster analysis. From the questionnaire's description text, combinations of the terms "information" and "collection," "small and medium-sized" and "enterprise," and "chemical" and "substance" were extracted. Results suggest a need for "information gathering" and "support for small and medium-sized enterprises."


Involvement of hormones in the swift increase in alcohol metabolism.
The purpose of this study was to determine the time course of changes in blood levels of various hormones in C57BL/6J mice during exposure to ethanol vapor. Groups of adult male mice were given 2.0 g per kg ethanol intraperitoneally or as continuous vapor for four hours and rates of ethanol elimination were measured. In parallel, blood samples were collected at timed intervals over 5.5 hours during and following exposure to ethanol. Blood levels of epinephrine, norepinephrine, corticosterone, and glucagon were elevated two- to four-fold during ethanol treatment and declined to basal values within one hour following termination of treatment. Elevated blood levels of epinephrine, norepinephrine and corticosterone were highly correlated with higher rates of ethanol elimination (r = 0.80, 0.78, and 0.72, respectively). In contrast, thyroxine and insulin levels were not affected by ethanol. These findings are consistent with the idea that acute administration of ethanol causes the release of glycogenolytic hormones which in turn increase rates of ethanol metabolism.


Kinesin light chains are essential for axonal transport in Drosophila.
Kinesin is a heterotetramer composed of two 115-kD heavy chains and two 58-kD light chains. The microtubule motor activity of kinesin is performed by the heavy chains, but the functions of the light chains are poorly understood. Mutations were generated in the Drosophila gene Kinesin light chain (Klc), and the phenotypic consequences of loss of Klc function were analyzed at the behavioral and cellular levels. Loss of Klc function results in progressive lethargy, crawling defects, and paralysis followed by death at the end of the second larval instar. Klc mutant axons contain large aggregates of membranous organelles in segmental nerve axons. These aggregates, or organelle jams (Hurd, D.D., and W.M. Saxton. 1996. Genetics. 144: 1075-1085), contain synaptic vesicle precursors as well as organelles that may be transported by kinesin, kinesin-like protein 68D, and cytoplasmic dynein, thus providing evidence that the loss of Klc function blocks multiple pathways of axonal transport. The similarity of the Klc and Khc (. Cell 64:1093-1102; Hurd, D.D., and W.M. Saxton. 1996. Genetics 144: 1075-1085) mutant phenotypes indicates that KLC is essential for kinesin function, perhaps by tethering KHC to intracellular cargos or by activating the kinesin motor.


Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases.
(1) Oxaliplatin-based chemotherapy for colorectal cancer liver metastasis is associated with sinusoidal injury of liver parenchyma. The effects of oxaliplatin-induced liver injury on the protein level remain unknown. (2) Protein expression in liver tissue was analyzed-from eight patients treated with FOLFOX (combination of fluorouracil, leucovorin, and oxaliplatin) and seven controls-by label-free liquid chromatography mass spectrometry. Recursive feature elimination-support vector machine and Welch t-test were used to identify classifying and relevantly changed proteins, respectively. Resulting proteins were analyzed for associations with gene ontology categories and pathways. (3) A total of 5891 proteins were detected. A set of 184 (3.1%) proteins classified the groups with a 20% error rate, but relevant change was observed only in 55 (0.9%) proteins. The classifying proteins were associated with changes in DNA replication (p < 0.05) through upregulation of the minichromosome maintenance complex and with the innate immune response (p < 0.05). The importance of DNA replication changes was supported by the results of Welch t-test (p < 0.05). (4) Six weeks after FOLFOX treatment, less than 1% of identified proteins showed changes in expression associated with DNA replication, cell cycle entry, and innate immune response. We hypothesize that the changes remain after recovery from FOLFOX treatment injury.


A review on functional ingredients in red meat products.
Meat and meat products are important foods with essential nutritional components such as essential amino acids, fatty acids, vitamins and minerals that form a significant component for the normal physiological and biochemical processes. However, the main drawback of meat and meat products is the absence of dietary fibre and the presence of saturated fat. Value improvement can be done by the incorporation of functional ingredients into the meat products. The use of functional ingredients in meat products offers processors the opportunity to enhance the functional and nutritional value of their products. Vegetable proteins, dietary fibre, cereal by-products, fruits, legumes, spices, herbs, and lactic acid bacteria that have been used alone or in combination for the enhancement of the functional value of meat and meat products were studied. Hence, the current review focuses on the functional ingredients incorporated in meat products.


Application of Machine Learning Algorithms to Classify Peruvian Pisco Varieties Using an Electronic Nose.
Pisco is an alcoholic beverage obtained from grape juice distillation. Considered the flagship drink of Peru, it is produced following strict and specific quality standards. In this work, sensing results for volatile compounds in pisco, obtained with an electronic nose, were analyzed through the application of machine learning algorithms for the differentiation of pisco varieties. This differentiation aids in verifying beverage quality, considering the parameters established in its Designation of Origin". For signal processing, neural networks, multiclass support vector machines and random forest machine learning algorithms were implemented in MATLAB. In addition, data augmentation was performed using a proposed procedure based on interpolation-extrapolation. All algorithms trained with augmented data showed an increase in performance and more reliable predictions compared to those trained with raw data. From the comparison of these results, it was found that the best performance was achieved with neural networks.


Comparative effects of dimethylsulfoxide on metabolism and toxicity of carbon tetrachloride and dichloromethane.
The effects of dimethylsulfoxide (DMSO) on the metabolism and toxicity of chlorinated methanes were examined. Male mice were treated with DMSO (1, 2.5 or 5 ml kg(-1), i.p.) prior to challenge with dichloromethane (CH(2)Cl(2)) or carbon tetrachloride (CCl(4)). Blood carboxyhemoglobin elevation resulting from metabolic conversion of CH(2)Cl(2) to carbon monoxide was inhibited dose-dependently by DMSO pretreatment. The elevation of serum aspartate aminotransferase, alanine aminotransferase and sorbitol dehydrogenase activities induced by CCl(4) (0.1 mmol kg(-1)) was not changed in mice pretreated with DMSO at 1 ml kg(-1), but depressed significantly at a greater dose of DMSO. However, DMSO failed to alter the hepatotoxicity of CCl(4) injected at a dose of 0.2 mmol kg(-1). DMSO induced the microsomal p-nitrophenol hydroxylase and p-nitroanisole O-demethylase activities as early as 2 h following the treatment. Microsomal disposition of CH(2)Cl(2) and CCl(4) was measured using a vial equilibration technique. The disappearance of CH(2)Cl(2) was inhibited competitively by addition of DMSO. But DMSO did not affect the metabolic degradation of CCl(4). The results indicate that DMSO has multiple effects on metabolism and toxicity of xenobiotics. DMSO induces the hepatic metabolizing activity mediated by CYP2E1, but the presence of this solvent in the enzyme site may inhibit directly the enzymatic interaction with a substrate. The toxicological significance of DMSO-induced effects on such an interaction may be variable depending on the properties of each substrate. The invulnerability of CCl(4) metabolism to the effects of DMSO appears to be related to its high affinity for the lipophilic CYP enzyme site.


Preliminary study: Measurement of ion beam energy spreads produced by a Penning ionization gauge-type ion source using electromagnets for a mega-electron volt compact ion microbeam system.
The energy spreads of ion beams generated from a penning ionization gauge-type ion source with electromagnets were measured using a parallel electrostatic analyzer. The ion source was developed to be installed in a mega-electron volt (MeV) compact ion microbeam system. A gaseous ion beam of expectedly high brightness and narrow energy spread was generated from the ion source to form a microbeam. To produce such an ion beam, a high-density plasma with a small volume was generated using a strong magnetic field in the ion source. The beam energy spread width was of particular importance because it forms an ion microbeam by reducing the chromatic aberration at a focusing lens. In this report, the energy spread was investigated by changing the parameters of the ion source, e.g., extraction voltage, excitation current of electromagnets, vacuum, and anode voltage. The investigation showed that spread widths are influenced by the extraction voltage, vacuum, and anode voltage. The minimum width of ∼5.0 ± 0.1 eV was obtained at a beam energy of 200 eV. This value is acceptable for the MeV compact ion microbeam system.


Treat ankylosing spondylitis with methazolamide.
Increased bone resorption and new bone information are two characteristics of ankylosing spondylitis (AS). Much evidence has shown that carbonic anhydrase inhibitors can restrain bone resorption. We had detected increased expression of carbonic anhydrase I (CA1) in synovium of patients with AS. This study aimed to evaluate the effectiveness and safety of methazolamide, an anti-carbonic anhydrase drug, for treating patients with AS. Two patients, called as S and L, were diagnosed with active AS based on BASDAI and BASFI assessments, radiographic data and other clinical indices. They took methazolamide tablets at a dose of 25 mg twice every day. Patient S's BASDAI score fell from 5.4 to 4.4, while patient L's BASDAI fell from 2.4 to 2. Patient S's BASFI score change from 2.7 to 2.9, while patient L's BASFI score fell from 1.2 to 0.2. The ESR values of patient S were considerably reduced, while the ESR value of patient L remained unchanged and in the normal range. The calcium concentration of patient S decreased from 3.05 mmol/L to 2.39 mmol/L. The CT evidence indicates that the articular surfaces of the erosive sacroiliac joints became clearer and the area of the calcium deposits began decreased. No significant systemic side effects were observed in either patient. The above results indicate that methazolamide was effective for active AS. Methazolamide may improve AS symptoms by inhibiting carbonic anhydrase activity during the processes of bone reporption and new bone formation.