A review of design characteristics of cognitive behavioral therapy-informed behavioral intervention technologies for youth with depression and anxiety.
Cognitive behavioral therapy (CBT) has the strongest evidence base for the prevention and treatment of depression and anxiety in youth. Behavioral intervention technologies (BITs) provide an opportunity to overcome access barriers to traditional delivery of CBT. The present review evaluates the design characteristics of CBT-informed BITs for depression and anxiety designed for and tested with youth. A state-of-the-art review of three library databases (PubMed, Scopus, and Web of Science) was conducted to identify papers that evaluated the use of CBT-informed BITs for the prevention and/or treatment of depression and anxiety among youth. Narrative results of design characteristics were organized using the BIT model, which provides a framework for design and evaluation. 219 unique results were retrieved through the search. After review, 14 papers (4 prevention and 10 treatment) met the selection criteria. A broad diversity occurred in reporting the design and methodology of CBT delivered to youth through BITs. Psychoeducation was overwhelmingly utilized as the primary change strategy throughout the interventions, with a heavy use of content delivery elements and linear workflows. The reporting of sample characteristics was minimal and varied. Providing psychoeducation via content delivery was the most utilized BIT change strategy in the interventions, likely limiting the use of multiple BIT elements or flexible workflows. While characterizations could be inferred from the current reports, the high level of variability in reporting is problematic. Generalizability becomes increasingly more difficult to carry out effectively without clear descriptions of the design for evaluated BITs.


Inhibition of Ca2+ release from Trypanosoma brucei acidocalcisomes by 3,5-dibutyl-4-hydroxytoluene: role of the Na+/H+ exchanger.
Acidocalcisomes are acidic vacuoles present in trypanosomatids that contain a considerable fraction of intracellular Ca2+. They possess a vacuolar-type H+-ATPase for H+ uptake, a Ca2+/H+ countertransporting ATPase for Ca2+ uptake and a Ca2+/nH+ antiporter for Ca2+ release. Trypanosoma brucei procyclic trypomastigotes acidocalcisomes possess, in addition, an Na+/H+ antiporter that may participate in Ca2+ release from these organelles. In this work we show that the hydrophobic antioxidant 3,5-dibutyl-4-hydroxy toluene (BHT), at concentrations in the range 1-20 microM, inhibits Na+-induced Ca2+ release from the acidocalcisomes of digitonin-permeabilized procyclic trypomastigotes in a concentration-dependent manner. This effect supports the notion that Ca2+ release from this compartment is regulated by the activity of the Na+/H+ antiporter. In the presence of BHT, Ca2+ release could still be obtained by nigericin-mediated alkalinization of the acidocalcisomes, clearly demonstrating that the action of BHT is not at the level of the Ca2+/nH+ antiporter but on that of the Na+/H+ antiporter. In the same range of concentrations and depending on the preincubation time, BHT had an stimulatory or an inhibitory effect on the vacuolar H+-ATPase present in T. brucei acidocalcisomes. Since these effects of BHT were obtained at concentrations which are commonly used for its antioxidant properties, these results indicate that care should be exercised when attributing effects of BHT to only these properties.


Preface for the special issue of Mathematical Biosciences and Engineering, BIOCOMP 2012.
The International Conference "BIOCOMP2012 - Mathematical Modeling and Computational Topics in Biosciences'', was held in Vietri sul Mare (Italy), June 4-8, 2012. It was dedicated to the Memory of Professor Luigi M. Ricciardi (1942-2011), who was a visionary and tireless promoter of the 3 previous editions of the BIOCOMP conference series. We thought that the best way to honor his memory was to continue the BIOCOMP program. Over the years, this conference promoted scientific activities related to his wide interests and scientific expertise, which ranged in various areas of applications of mathematics, probability and statistics to biosciences and cybernetics, also with emphasis on computational problems. We are pleased that many of his friends and colleagues, as well as many other scientists, were attracted by the goals of this recent event and offered to contribute to its success.


[Elements of comprehensiveness in the professional health practices provided to rural women victims of violence].
The present article refers to a qualitative study that was performed with the objective to identify and analyze the practice of healthcare professionals regarding rural women victims of violence, under the perspective of comprehensive care, in cities located in southern Rio Grande do Sul state. Participants were healthcare professionals and workers from health services who work in rural areas. The information was generated through interviews and analyzed using the thematic mode. In regards to care elements provided to rural women who are victims of violence, the study pointed out not only the relational strategies - welcoming, attachment and dialogue - but also the construction of collective actions through group activities, recognized as supporting health promotion, as well as individual and collective empowerment in the dimension of violent events. It was found that the professionals' care practices are aimed at focusing care on the rural women, establishing a relationship between the worker and client to produce comprehensiveness of care.


The Arabidopsis thaliana trp5 mutant has a feedback-resistant anthranilate synthase and elevated soluble tryptophan.
The first step of tryptophan biosynthesis is catalyzed by anthranilate synthase (AS), which is normally subject to feedback inhibition by tryptophan. Three independent trp5 mutants defective in the Arabidopsis thaliana AS alpha subunit structural gene ASA1 were identified by selection for resistance to the herbicidal compound 6-methylanthranilate. In all three mutants these biochemical changes are caused by a single amino acid substitution from aspartate to asparagine at residue position 341. Compared with the enzyme from wild-type plants, the tryptophan concentration causing 50% inhibition of AS activity in the trp5 mutant increased nearly 3-fold, the apparent Km for chorismate decreased by approximately 50%, and the apparent Vmax increased 60%. As a consequence of altered AS kinetic properties, the trp5 mutants accumulated 3-fold higher soluble tryptophan than wild-type plants. However, even though the soluble tryptophan levels were increased in trp5 plants, the concentrations of five tryptophan biosynthetic proteins remained unchanged. These data are consistent with the hypothesis that the reaction catalyzed by A. thaliana AS is rate limiting for the tryptophan pathway and that accumulation of tryptophan biosynthetic enzymes is not repressed by a 3-fold excess of end product.


Multiscale 3D phenotyping of human cerebral organoids.
Brain organoids grown from human pluripotent stem cells self-organize into cytoarchitectures resembling the developing human brain. These three-dimensional models offer an unprecedented opportunity to study human brain development and dysfunction. Characterization currently sacrifices spatial information for single-cell or histological analysis leaving whole-tissue analysis mostly unexplored. Here, we present the SCOUT pipeline for automated multiscale comparative analysis of intact cerebral organoids. Our integrated technology platform can rapidly clear, label, and image intact organoids. Algorithmic- and convolutional neural network-based image analysis extract hundreds of features characterizing molecular, cellular, spatial, cytoarchitectural, and organoid-wide properties from fluorescence microscopy datasets. Comprehensive analysis of 46 intact organoids and ~ 100 million cells reveals quantitative multiscale "phenotypes" for organoid development, culture protocols and Zika virus infection. SCOUT provides a much-needed framework for comparative analysis of emerging 3D in vitro models using fluorescence microscopy.


[Clinical features of chronic obstructive pulmonary disease course in persons who underwent radiation impact].
Experience of 10-years observation of 164 patients who underwent radiation impact, 38 (23%) afterwards had chronic obstructive pulmonary disease (COPD), is analyzed in the article. It is demonstrated, that timely COPD diagnostics must be based on thorough gathering of anamnestic data, analysis of clinical manifestations and results of annual examination of pulmonary ventilation function. Changes in time of COPD clinical symptoms among COPD patients who underwent radiation influence are considered. It was established, that in patients who underwent radiation influence, COPD began in younger age, coursed more severe, with more frequent aggravations, requiring inpatient treatment. Therapy of this category of persons required all drugs used at COPD treatment.


The ubiquitin-proteasome system plays essential roles in presenting an 8-mer CTL epitope expressed in APC to corresponding CD8+ T cells.
MUT1 is an H-2Kb-restricted 8-mer CTL epitope expressed in Lewis lung carcinoma (3LL) tumor cells derived from C57BL/6 (B6) mice. We constructed a chimeric gene encoding ubiquitin-fused MUT1 (pUB-MUT1). By using a gene gun, B6 mice were immunized with the gene prior to challenge with 3LL tumor cells. Tumor growth and lung metastasis were prominently suppressed in mice immunized with pUB-MUT1 but only slightly in those immunized with the MUT1 gene (pMUT) alone. CD8+ T cells were confirmed to be the final effector by in vitro experiments and in vivo removal of the cells with a corresponding antibody. Anti-tumor immunity was profoundly suppressed in mice deficient in an immuno-subunit of proteasome, LMP7. Furthermore, mice deficient in a proteasome regulator, PA28alpha/beta, failed to acquire protective immunity. Thus, application of the ubiquitin-fusion degradation pathway was useful even in immunization with genes encoding a single CTL epitope for induction of specific and active CD8+ T cells.


Novel non-Joule heating technique: Externally laser-heated diamond anvil cell.
The externally heated diamond anvil cell (EHDAC) conducts high pressure and temperature experiments with spatial uniformity and temporal stability. These are conventionally combined with various spectroscopies and x-ray diffraction measurements. EHDAC techniques perform Joule heating on a heater placed close to or directly in contact with diamond anvils. However, the electrical wiring and heater required for Joule heating complicate EHDAC setups, hindering easy access for the measurement of physical properties. This study proposes an EHDAC technique using laser- instead of Joule-heating. We successfully achieved temperatures reaching 900 K by applying heat to diamond anvils through laser-heating of the gaskets with thermally insulating anvil seats. To test this setup, we measured the melting temperature of H2O ice VII, which was consistent with previous studies. We also measured the high-pressure and temperature impedance of H2O VII and verified the capability of electrical resistivity measurements in this setup. This technique allows various physical property measurements owing to its simple setup required for externally laser-heated diamond anvil cell experiments. The unique characteristics of this heating technique are that (1) no heaters or wiring are required, (2) it exhibits the most efficient heating among EHDAC studies, (3) it maintains the DAC body at room temperature, and (4) diamond anvils do not detach from anvil seats after the EHDAC experiment. This method significantly simplifies the experimental setup, which allows much easier access to various physical property measurements using an EHDAC.


Amblyopia therapy in children with penetrating corneal injuries.
The role of part-time occlusion therapy in children with penetrating ocular injuries has not been studied. The aim of the study is to analyze the role of part-time occlusion therapy in children with penetrating ocular trauma following surgical intervention. This is a retrospective case series with a median follow-up of 17 months (range: 3-105 months). The study was carried out at a tertiary referral center. Consecutive children with penetrating corneal tear injury who underwent surgical intervention were included in the study. These patients were subjected to part-time occlusion, and those with good compliance and follow-up were included in the study. The role of part-time occlusion therapy in children with ocular trauma is studied. There were 26 patients included in the study of which 23 were male and 3 were female, with a median age at presentation of 5 years (range: 1-11 years). The vision following surgical intervention at 6 weeks was 0.85 logMAR units (range: 0.3-2.8). Final median visual acuity was 0.48 logMAR units (range: 0-2). Paired t-test done for improvement in visual outcome before and after amblyopia therapy was statistically significant (P = 0.007). Amblyopia therapy shows promising results for patients following penetrating intraocular injury despite corneal scar in the visual axis in our group. A study on larger population is indicated.


Substitution of Ala for Tyr567 in RB69 DNA polymerase allows dAMP to be inserted opposite 7,8-dihydro-8-oxoguanine .
Accurate copying of the genome by DNA polymerases is challenging due in part to the continuous damage inflicted on DNA, which results from its contact with reactive oxygen species (ROS), producing lesions such as 7,8-dihydro-8-oxoguanine (8-oxoG). The deleterious effects of 8-oxoG can be attributed to its dual coding potential that leads to G --> T transversions. The wild-type (wt) pol alpha family DNA polymerase from bacteriophage RB69 (RB69pol) prefers to insert dCMP as opposed to dAMP when situated opposite 8-oxoG by >2 orders of magnitude as demonstrated using pre-steady-state kinetics (k(pol)/K(d,app)). In contrast, the Y567A mutant of RB69pol inserts both dCMP and dAMP opposite 8-oxoG rapidly and with equal efficiency. We have determined the structures of preinsertion complexes for the Y567A mutant with dATP and dCTP opposite a templating 8-oxoG in a 13/18mer primer-template (P/T) at resolutions of 2.3 and 2.1 A, respectively. Our structures show that the 8-oxoG residue is in the anti conformation when paired opposite dCTP, but it flips to a syn conformation forming a Hoogstein base pair with an incoming dATP. Although the Y567A substitution does not significantly change the volume of the pocket occupied by anti-8-oxoG, it does provide residue G568 the flexibility to move deeper into the minor groove of the P/T to accommodate, and stabilize, syn-8-oxoG. These results support the hypothesis that it is the flexibility of the nascent base pair binding pocket (NBP) in the Y567A mutant that allows efficient insertion of dAMP opposite 8-oxoG.


Menstrual cycle characteristics in women with persistent schizophrenia.
Oestradiol has been implicated in the pathogenesis of schizophrenia. Women with schizophrenia often suffer with menstrual dysfunction, usually associated with low oestradiol levels, but whether menstrual dysfunction has an effect on their psychiatric symptoms is not well researched. The aim of this study is to document the menstrual characteristics of women with chronic schizophrenia with focus upon menstrual regularity, menstrual cycle length and menstrual symptoms. To determine which patient characteristics are associated with irregular menses and whether irregular menses are associated with the severity of psychotic symptoms, menstrual symptoms or depressive symptoms. Cross-sectional analyses using baseline data of women enrolled in a clinical trial. Inclusion criteria include Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective or schizophreniform disorder; aged between 18 and 51 years; residual symptoms of psychosis despite treatment with a stable dose of antipsychotic medication for at least 4 weeks. Menstrual cycle characteristics including regularity, cycle length and menstrual associated symptoms were documented. Symptoms of schizophrenia were measured using Positive and Negative Syndrome Scale, cognition was measured using Repeatable Battery for the Assessment of Neuropsychological Status and depression was assessed using the Montgomery-Asberg Depression Rating Scale. Blood samples were collected at baseline for hormone assays. Of the 139 women, 77 (55.4%) had regular menses, 57 (41%) had irregular menses and 5 (3.6%) women had missing data on their menstrual cycle. Use of atypical antipsychotics associated with hyperprolactinaemia was positively associated with irregular menses (odds ratio = 4.4, 95% confidence interval = [1.8, 10.9], p = 0.001), while age more than 30 years was negatively associated (odds ratio = 0.3, 95% confidence interval = [0.1, 0.6], p = 0.004). Women with irregular cycles had significantly lower oestradiol levels than women with regular cycles (213.2 ± 25.0 vs 299.0 ± 27.3, p = 0.03), but there was no difference in Positive and Negative Syndrome Scale, Montgomery-Asberg Depression Rating Scale or Repeatable Battery for the Assessment of Neuropsychological Status between those with regular and irregular cycles. The most common menstrual associated symptoms were decrease in mood with the menstrual cycle (64.8%), bloating (64.8%), cramps (59.7%), back pain (37.6%) and worsening of psychosis symptoms (32.4%). Regular menses are associated with higher oestradiol levels and higher rates of cyclical mood symptoms but are not associated with Positive and Negative Syndrome Scale scores. Understanding the effect the menstrual cycle can have on psychiatric illness, such as premenstrual exacerbations, is important for the holistic care of women with schizophrenia.


A novel homozygous RIPK4 variant in a family with severe Bartsocas-Papas syndrome.
Bartsocas-Papas syndrome (BPS) is a rare autosomal recessive disorder characterized by popliteal pterygia, syndactyly, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and genital malformations. Most of the BPS cases reported to date are fatal either in the prenatal or neonatal period. Causative genetic defects of BPS were mapped on the RIPK4 gene encoding receptor-interacting serine/threonine kinase 4, which is critical for epidermal differentiation and development. RIPK4 variants are associated with a wide range of clinical features ranging from milder ectodermal dysplasia to severe BPS. Here, we evaluated a consanguineous Turkish family, who had two pregnancies with severe multiple malformations compatible with BPS phenotype. In order to identify the underlying genetic defect, direct sequencing of the coding region and exon-intron boundaries of RIPK4 was carried out. A homozygous transversion (c.481G>C) that leads to the substitution of a conserved aspartic acid to histidine (p.Asp161His) in the kinase domain of the protein was detected. Pathogenicity predictions, molecular modeling, and cell-based functional assays showed that Asp161 residue is required for the kinase activity of the protein, which indicates that the identified variant is responsible for the severe BPS phenotype in the family.


Application of phase modulation to digital data recording by means of superposed diffraction gratings.
Optical phase modulation has been applied to a system for digital data recording based on the photography of a multiplicity of superposed interference fields. When piezoelectrically driven mirrors or electro-optic crystals are placed suitably in the interfering beams and sinusoidally excited to the proper amplitude, the corresponding fringe pattern exposure is effectively spoiled. Since the effect arises from variations in optical path or refractive index, tolerances on optical quality are relatively modest. Extinction ratios in excess of 100:1 are readily obtained.


p27KIP1 in human lung cancers: differential changes in small cell and non-small cell carcinomas.
Small cell lung cancers (SCLCs) and non-small cell lung cancers (NSCLCs), two major categories of human lung cancers, have been shown to exhibit considerably different clinicopathological, biological, and molecular genetic characteristics. Inactivation of cyclin-dependent kinase inhibitors is now thought to play an important part in the pathogenesis of this fatal disease. In the present study, we show that in vitro p27KIP1 expression was associated with cell density-dependent growth inhibition in human lung epithelial cells in vitro, whereas in vivo, p27KIP1 expression in lung cells showed an inverse correlation with proliferative activity in the developing and adult normal lungs. Our immunohistochemical examination of 166 lung tumor specimens also revealed a striking difference in p27KIP1 expression between SCLCs and NSCLCs. Of 149 NSCLCs, 107 (72%) showed reduced p27KIP1 expression, with 8 being virtually negative. Furthermore, p27KIP1 expression status was found to be a significant prognostic factor for patient survival in the analysis of the 149 primary, resected NSCLC cases (P = 0.03 by the log-rank test). In contrast, all SCLC specimens thus far examined exhibited significantly increased staining when compared to the corresponding normal lung epithelium. These findings provide additional evidence for the heterogeneity prevalent in human lung cancers and suggest that p27KIP1 might play distinct biological roles in the pathogenesis of the two major histological categories, warranting additional studies to elucidate the functional consequences of such differences.


Resveratrol protects against doxorubicin-induced cardiotoxicity in aged hearts through the SIRT1-USP7 axis.
Doxorubicin induced functional deteriorations and elevations of USP7-related apoptotic/catabolic signalling in the senescent heart Resveratrol protects against doxorubicin-induced alterations through the restoration of SIRT1 deacetylase activity A compromised cardiac function is often seen in elderly cancer patients receiving doxorubicin therapy. The present study tested the hypothesis that acute intervention with resveratrol, a natural anti-oxidant found in grapes and red wine, reduces the cardiotoxicity of doxorubicin through restoration of sirtuin 1 (SIRT1) deacetylase activity, and attenuation of the catabolic/apoptotic pathways orchestrated by USP7, a p53 deubiquitinating protein, using young (aged 2 months) and old (aged 10 months) senescence-accelerated mice prone 8 (SAMP8). Animals were randomised to receive saline, doxorubicin, and doxorubicin in combination with resveratrol, in the presence or absence of SIRT1 inhibitors, sirtinol or EX527. Resveratrol alone, but not in combination with either of the SIRT1 inhibitors, suppressed the doxorubicin-induced impairment of cardiac systolic function in aged animals. Doxorubicin reduced SIRT1 deacetylase activity, and elevated proteasomal activity and USP7; it also increased the protein level of p300 and ubiquitinated proteins in hearts from aged SAMP8. These doxorubicin-induced alterations were prevented by resveratrol, whereas the protective action of resveratrol was antagonised by sirtinol and EX527. In young SAMP8 hearts, resveratrol attenuated the doxorubicin-induced increases in acetylation of Foxo1 and transactivation of MuRF-1, whereas these mitigations were not found after treatment with SIRT1 inhibitors. However, the protein contents of acetylated Foxo1 and MuRF-1 were not affected by any of the drugs studied in aged SAMP8 hearts. Resveratrol also ameliorated the augmentation of pro-apoptotic markers including p53, Bax, caspase 3 activity and apoptotic DNA fragmentation induced by doxorubicin in hearts from aged animals, whereas these reductions were diminished by combined treatment with SIRT1 inhibitors. These data demonstrate that resveratrol ameliorates doxorubicin-induced cardiotoxicity in aged hearts through the restoration of SIRT1 activity to attenuate USP7-related catabolic/pro-apoptotic signalling.


Evolutionary Ecology of Natural Comammox Nitrospira Populations.
Microbes commonly exist in diverse and complex communities where species interact, and their genomic repertoires evolve over time. Our understanding of species interaction and evolution has increased during the last decades, but most studies of evolutionary dynamics are based on single species in isolation or in experimental systems composed of few interacting species. Here, we use the microbial ecosystem found in groundwater-fed sand filter as a model to avoid this limitation. In these open systems, diverse microbial communities experience relatively stable conditions, and the coupling between chemical and biological processes is generally well defined. Metagenomic analysis of 12 sand filters communities revealed systematic co-occurrence of at least five comammox Nitrospira species, likely promoted by low ammonium concentrations. These Nitrospira species showed intrapopulation sequence diversity, although possible clonal expansion was detected in a few abundant local comammox populations. Nitrospira species showed low homologous recombination and strong purifying selection, the latter process being especially strong in genes essential in energy metabolism. Positive selection was detected for genes related to resistance to foreign DNA and phages. We found that, compared to other habitats, groundwater-fed sand filters impose strong purifying selection and low recombination on comammox Nitrospira populations. These results suggest that evolutionary processes are more affected by habitat type than by species identity. Together, this study improves our understanding of species interaction and evolution in complex microbial communities and sheds light on the environmental dependency of evolutionary processes. IMPORTANCE Microbial species interact with each other and their environment (ecological processes) and undergo changes in their genomic repertoire over time (evolutionary processes). How these two classes of processes interact is largely unknown, especially for complex communities, as most studies of microbial evolutionary dynamics consider single species in isolation or a few interacting species in simplified experimental systems. In this study, these limitations are circumvented by examining the microbial communities found in stable and well-described groundwater-fed sand filters. Combining metagenomics and strain-level analyses, we identified the microbial interactions and evolutionary processes affecting comammox Nitrospira, a recently discovered bacterial type capable of performing the whole nitrification process. We found that abundant and co-occurrent Nitrospira populations in groundwater-fed sand filters are characterized by low recombination and strong purifying selection. In addition, by comparing these observations with those obtained from Nitrospira species inhabiting other environments, we revealed that evolutionary processes are more affected by habitat type than by species identity.


Optimal Thresholds for Fracton Codes and Random Spin Models with Subsystem Symmetry.
Fracton models provide examples of novel gapped quantum phases of matter that host intrinsically immobile excitations and therefore lie beyond the conventional notion of topological order. Here, we calculate optimal error thresholds for quantum error correcting codes based on fracton models. By mapping the error-correction process for bit-flip and phase-flip noises into novel statistical models with Ising variables and random multibody couplings, we obtain models that exhibit an unconventional subsystem symmetry instead of a more usual global symmetry. We perform large-scale parallel tempering Monte Carlo simulations to obtain disorder-temperature phase diagrams, which are then used to predict optimal error thresholds for the corresponding fracton code. Remarkably, we found that the X-cube fracton code displays a minimum error threshold (7.5%) that is much higher than 3D topological codes such as the toric code (3.3%), or the color code (1.9%). This result, together with the predicted absence of glass order at the Nishimori line, shows great potential for fracton phases to be used as quantum memory platforms.


H-2 haplotype-dependent serum IL-12 production in tumor-bearing mice treated with various mycelial extracts.
IL-12 is considered to be one of the most important cytokines in anti-cancer therapy. We have demonstrated that substances derived from Basidiomycetes, such as active hexose-correlated compound (AHCC) and PSK induce the production of IL-12. In this study, the MHC dependency of IL-12 production induced by various mycelial extracts, PSK, AHCC and IL-X, was examined. During tumor-bearing, higher serum IL-12 levels were observed in H-2a and H-2b mice as compared to H-2d mice. Concerning the effect of genetic background of mice on response to mycelial extracts, AHCC administration enhanced the serum IL-12 level in H-2b mice but not in H-2d mice, while PSK administration increased the serum IL-12 level in H-2d mice but not in H-2b mice. IL-X, components derived from the same Basidiomycetes, also enhanced the serum IL-12 level in H-2b mice in the early stage of tumor like AHCC, and maintained serum IL-12 at a level higher than the normal value accompanying tumor growth, whereas AHCC did not restore the lowered serum IL-12 level accompanying tumor growth. These results showed that AHCC or IL-X is effective in a genetically Th1-dominant individual whereas PSK is effective in a genetically Th2-dominant individual or Th2-dominant status in advanced cancer patients. So we propose that the suitable combinations of various mycelial extracts may be effective methods of endogenous IL-12 induction for cancer patients of all stages, which is important as a cancer therapy that is relatively free from adverse reactions and which emphasizes the QOL in individual patients.


[Effect of temperature on structure and functional properties of horseradish peroxidase].
The dynamics of structural and functional changes proceeding in a peroxidase molecule under the effect of temperature was studied. It was shown that peroxidase thermoinactivation proceeds in two consequent stages. Based on the analysis of enzyme peroxidase and oxidase activity and peroxidase spectral and buffer characteristics, it was established that at temperatures from 20 to 55 degrees C reversible conformation there occur changes of the hemoprotein molecule related to consequent unfolding and folding of the protein globule. The influence of temperature of 60 degrees C and above induces the protein globule unfolding and loosing of peroxidase activity.


Cemented or uncemented fixation: Which allows a more acceptable prosthetic femoral version in total hip arthroplasty?
Three-dimensional computed-tomography (3D-CT) planning for primary Total Hip Arthroplasty (THA) typically uses the external femoral surface; as a result, it is difficult to predict the prosthetic femoral version (PFV) for uncemented femoral stems that press-fit to the internal surface of the bone. Cemented fixation allows the surgeon to adjust the version independent of the internal femoral anatomy. We aimed to better understand the effect of the fixation type on PFV. This was a case series study including a total of 95 consecutive patients (106 hips), who underwent uncemented (n = 81 hips) and cemented (n = 25 hips) primary THA using the posterior approach. The surgeon aimed for a PFV of 20°. Our primary objective was to compare PFV in both groups; our secondary objective was to evaluate the clinical outcomes. The mean (± SD) PFV was 13° (± 9°) and 23° (± 8°) for the uncemented and cemented THA groups (P < 0.001), respectively. In the uncemented THA group, 36% of the patients had a PFV of < 10°. In the cemented THA group, this clinically important threshold dropped to 8%. Similarly, the Bland-Altman (BA) plots showed wider 95% limits of agreement for the uncemented group. Satisfactory clinical outcomes were recorded. We found that the PFV was more clinically acceptable, for the posterior surgical approach, in the cemented group when compared to the uncemented group. Both THA groups reported high variability indicating the need to develop surgical tools to guide the PFV closer to the surgical target.


Functional significance of the variations in the geometrical organization of tight junction networks.
Using freeze-fracture techniques, we have examined the morpholog of tight junction networks found along the length of the alimentary tract of Xenopus laevis before and after metamorphosis. We have developed the hypothesis, based on these observations, that the geometrical organization of the network determined by the stress-induced shape changes normally experienced by the cells linked by the network. Consistent with this theory, tight junctions can be classified into two distinct types of network organization which differ in their response normal and experimentally induced stress conditions: (a) loosely interconnected networks which can stretch or compress extensively under tension, thereby adapting to stress changes in the tissue; and (b) evenly cross-linked networks which retain their basic morphology under normal stress conditions. The absorptive cells of the large intestine as well as the mucous cells of the gastrointestine or stomach are sealed by the first, flexible type of tight junction. The second type of junctional organization, the evenly cross-connected network, is found between absorptive cells of the small intestine and ciliated cells of the esophagus, and reflects in its constant morphology the relative stability of the apical region of both of these cell types. Networks intermediate between these two types arise when a cell which would normally form a lossely interconnected network borders a cell which tends to form a more evenly cross-linked network, as is found in the esophagus where ciliated and goblet cells adjoin. Despite the change in the animal's diet during metamorphosis from herbivorous to carnivorous, the basic gemetrical organization of the networks associated with each tissue of the alimentary tract remains the same.


[Erectile dysfunction and obesity].
The review considers the relationship between obesity and erectile dysfunction (ED). Obesity is associated with the high prevalence of ED; however, the pathophysiological link between these conditions has yet to be adequately investigated. Visceral obesity leads to the enhanced activity of inflammatory responses and, thus, endothelial dysfunction and decreased plasma testosterone levels, which favors the development of hypogonadism and increases the risk of vascular diseases. Endothelial dysfunction and androgen deficiency in turn give rise to ED.


Slow progressive popliteal artery insufficiency after neglected proximal tibial physeal fracture: a case report.
Popliteal artery injury is most commonly associated with high-energy trauma, which is easily diagnosed upon initial physical examination. However, in some situations, the diagnosis of arterial injury is delayed because of slow progression of arterial insufficiency, which may lead to limb amputation. We report a rare case of popliteal arterial occlusion with the presence of arterial pulses during initial assessment, resulting from a neglected proximal ibial physis fracture. This case shows that even in the presence of foot pulses, the surgeon must consider the possibility of a popliteal artery damage whenever trauma is seen near the knee joint.


Virtual and Augmented Reality in Interventional Radiology: Current Applications, Challenges, and Future Directions.
Virtual reality (VR) and augmented Reality (AR) are emerging technologies with the potential to revolutionize Interventional radiology (IR). These innovations offer advantages in patient care, interventional planning, and educational training by improving the visualization and navigation of medical images. Despite progress, several challenges hinder their widespread adoption, including limitations in navigation systems, cost, clinical acceptance, and technical constraints of AR/VR equipment. However, ongoing research holds promise with recent advancements such as shape-sensing needles and improved organ deformation modeling. The development of deep learning techniques, particularly for medical imaging segmentation, presents a promising avenue to address existing accuracy and precision issues. Future applications of AR/VR in IR include simulation-based training, preprocedural planning, intraprocedural guidance, and increased patient engagement. As these technologies advance, they are expected to facilitate telemedicine, enhance operational efficiency, and improve patient outcomes, marking a new frontier in interventional radiology.


Use of the Oak Ridge National Laboratory tungsten-188/rhenium-188 generator for preparation of the rhenium-188 HDD/lipiodol complex for trans-arterial liver cancer therapy.
This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ((188)W)/rhenium-188 ((188)Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the (188)Re-perrhenate bolus and preparation of (188)Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The (188)W/(188)Re generator has a long useful shelf-life of several months and is a convenient on-site (188)Re production system. (188)Re has excellent therapeutic and imaging properties (T(1/2) 16.9 hours; E(betamax) 2.12 MeV; 155-keV gamma ray, 15%) and is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of (188)Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of (188)Re, several (188)Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. (188)Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of (188)Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) (188)W/(188)Re generators. The handling of such high levels of (188)Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (ie, "As Low As Reasonably Achievable") principles must be followed. The ORNL generator provides consistently high (188)Re yields (>75%) and low (188)W parent breakthrough (<10(-3)%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require concentration of the (188)Re bolus by postelution passage through silver cation chloride trapping columns used in the cost-effective tandem cation/anion column system. The silver column removes the high levels of chloride anion as insoluble AgCl, thus allowing subsequent specific trapping of the perrhenate anion on the small (QMA SeaPak) anion column. This method permits subsequent elution of (188)Re-perrhenate with a small volume of saline, providing a very high activity-concentration solution. Because the (188)Re-specific volume-activity concentration continually decreases with time, the tandem system is especially effective method for extending the useful generator shelf-life. Low elution flow rates (<1 mL/min) minimize any high back pressure which may be encountered during generator/tandem column elution when using tightly packed, small-particle-size commercial columns. In-house preparation of silver cation columns is recommended since the chloride trapping capacity is essentially unlimited, it is inexpensive and not limited in availability to any one supplier, and back pressure can be eliminated by the use of larger particles. Methods for the preparation of (188)Re-HDD have been optimized and this agent can be obtained in high yield (80%).


Refining the COPES to Measure Social Climate in Therapeutic Residential Youth Care.
Previous studies have shown that social climate in therapeutic residential youth care (TRC) is important to the welfare of residents, staff, and assessing treatment outcomes. The most influential theory on social climate in residential settings is the theory of Moos. The measurement of the concepts and aspects of this theory using the Community Oriented Programs Environment Scale (COPES) has repeatedly been criticized regarding usability, validity, and reliability, especially for TRC. To improve the usability and psychometric quality of the COPES by shortening and refining the original subscale structure for usage in TRC. Four-hundred adolescents living in Norwegian TRC participated. We supplemented confirmatory factor analysis (CFA) with item response theory (IRT) to evaluate model fit, investigate factor loadings, and shorten scales to improve their psychometric qualities and usability in describing social climate in TRC. The original subscales were not acceptable as evaluated by the criteria for CFA and IRT. By removing psychometrically weak items, the instrument was shortened to 40 items within the original ten subscales. This short version showed acceptable psychometric qualities based on both CFA and IRT criteria and the instrument retained its content validity. Finally, the original three higher-order dimensions was not supported. Compared to the original instrument, the refined 40-item version of the COPES represents a more usable instrument for measuring social climate in TRC. Future studies are needed to confirm the multifaceted refined short version in comparable samples of youth and staff to further investigate predictive value and construct validity.


Effect of toxigenic Escherichia coli on myoelectric activity of small intestine.
When exposed to cholera toxin (CT), distal ileal loops of the rabbit small intestine showed an alteration in myoelectric activity. This alteration was defined as the migrating action potential complex (MAPC). The purpose of this study was to determine, using myoelectric recording techniques, the effects of live toxigenic Escherichia coli (TEC) on motility. Live TEC, live nontoxigenic E. coli (NTEC), and culture filtrates of these organisms were studied. Live TEC and its filtrate induced MAPC activity similar to that of CT. Live TEC induced a mean of 3.8 MAPCs/h, significantly greater than induced by live NTEC. TEC filtrate induced a mean of 14.2 MAPCs/h, significantly greater than NTEC filtrate. Heating the TEC filtrate to 100 degrees C before use resulted in a significant decrease of MAPC activity. This experiment demonstrated that live TEC and its culture filtrate altered ileal myoelectric activity. The effect may have been mediated by a heat-labile enterotoxin. This study suggests that alterations in small intestinal motility may be important in the pathogenesis of TEC diarrhea.


Plasma and tissue disposition of non-liposomal DB-67 and liposomal DB-67 in C.B-17 SCID mice.
DB-67 is a silatecan, 7-silyl-modified camptothecin, with enhanced lipophilicity and increased blood stability of the active-lactone ring. The generation of a liposomal formulation of DB-67 may be an attractive method of intravenous (IV) administration and may maintain DB-67 in the active-lactone form. We evaluated the tissue and plasma disposition of DB-67 lactone and hydroxy acid after administration of non-liposomal (NL) and liposomal (L) DB-67 in severe combined immunodeficient (SCID) mice. NL-DB-67 and L-DB-67 10 mg/kg IV x 1 were administered via a tail vein in SCID mice. After dosing, mice (n = 3 per time point) were euthanized and blood ( approximately 1 ml) and tissue were collected from 5 min to 48 h after administration. DB-67 lactone and hydroxy acid concentrations in plasma and DB-67 total (sum of lactone and hydroxyl acid) concentrations in tissues were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. Clearance of DB-67 lactone after administration of NL-DB-67 and L-DB-67 were 1.6 and 3.5 l/h/m(2), respectively; DB-67 lactone half-lives after administration of NL-DB-67 and L-DB-67 were 1.4 and 0.9 h, respectively. The percentages of DB-67 lactone in plasma after administration of NL-DB-67 and L-DB-67 were 92% and 89%, respectively. Liver, kidney, spleen, and lung tissues had longer exposure times to DB-67 after administration of L-DB-67 compared with NL-DB-67. In plasma, the majority of DB-67 remained in the lactone form after administration of NL-DB-67 and L-DB-67. The plasma disposition of DB-67 was similar after administration of NL-DB-67 and L-DB-67, suggesting that most of the DB-67 is immediately released from the L-DB-67 formulation. Following administration of L-DB-67, the higher and longer exposure of DB-67 in the spleen, as compared with NL-DB-67, is consistent with splenic clearance of liposomes by the reticuloendothelial system.


Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis.
Granulocyte and monocyte adsorptive apheresis (GMA) using a column filled with cellulose acetate (CA) beads (carriers) has been associated with a significant clinical efficacy in patients with rheumatoid arthritis and ulcerative colitis. To obtain further understanding on the mechanisms of disease modification by cellulose acetate-carrier-based GMA, in the present study, we investigated the mechanisms of granulocyte and monocyte adhesion to CA beads following exposure of human peripheral blood to the carriers at 37 degrees C for up to 60 min under controlled conditions. Cellulose acetate beads selectively adsorbed granulocytes, monocytes. CD19+ (B cells) and CD56+ (NK cells) lymphocyte subpopulations. The granulocyte and monocyte adsorption was inhibited by heat-inactivated plasma and EDTA, indicating that the adsorption was plasma protein (immunoglobulin, complement) and calcium dependent. Accordingly, granulocyte and monocyte adsorption was markedly enhanced by coating the carriers with IgG. Similarly, C3b was adsorbed onto the CA beads as a marker of complement activation. The results indicated that IgG and active complement fragments mediated leukocyte adhesion to CA beads via the FcgammaR and/or leukocyte complement receptor like CR3. Additionally, CA beads induced loss of expression of TNF receptors on CD16- granulocytes and CD14+ monocytes, but not on CD3+ lymphocytes In conclusion, CA beads might be an appropriate biomaterial for inducing extracorporeal immunomodulation as a treatment for auto-immune diseases which are associated with pathological leukocyte activity.


Effects of Hand Placement Technique on the Video Head Impulse Test (vHIT) in Younger and Older Adults.
To investigate the effects of hand placement techniques on the video head impulse test (vHIT) responses (i.e., gain, velocity) in older and younger adults and to determine intra-rater and inter-rater reliability of the horizontal vHIT. Descriptive, reliability study. University research laboratory. Forty healthy adults grouped by age with negative history of current or previous vestibular diseases between the ages of 20 and 88 years (mean = 46.60, standard deviation 23.20). Three examiners each used two hand placement techniques (chin and head) to elicit the horizontal vHIT responses. Both the examiner and hand placement orders were counterbalanced to account for order and fatigue effects. The outcome measures of interest were vHIT gain and velocity. A two-way between-subject factorial analysis of variance revealed a significant main effect for hand placement technique and gain response. Mean values for vHIT gain were higher for head technique. Significant main effects were observed for the velocity response for hand placement technique and age group. Mean velocity values were higher for chin technique and lower velocities were observed in the older age group. Intra- and inter-rater reliability scores were consistent for gain values; however, poor to fair inter-rater reliability scores were observed for velocity values. It is suggested that clinical sites select one hand placement technique for the measure to provide consistency of protocol. Establishing clinical norms using the one selected method to verify reliability within and across clinicians is suggested before examination with a disordered population.


Nitric oxide synthase inhibition by N(G)-nitro-L-arginine methyl ester inhibits tumor-induced angiogenesis in mammary tumors.
Using a murine breast cancer model, we earlier found a positive correlation between the expression of nitric oxide synthase (NOS) and tumor progression; treatment with inhibitors of NOS, N(G)-methyl-L-arginine (NMMA) and N(G)-nitro-L-arginine methyl ester (L-NAME), had antitumor and antimetastatic effects that were partly attributed to reduced tumor cell invasiveness. In the present study, we used a novel in vivo model of tumor angiogenesis using subcutaneous implants of tumor cells suspended in growth factor-reduced Matrigel to examine the angiogenic role of NO in a highly metastatic murine mammary adenocarcinoma cell line. This cell line, C3L5, expresses endothelial (e) NOS in vitro and in vivo, and inducible (i) NOS in vitro on stimulation with lipopolysaccharide and interferon-gamma. Female C3H/HeJ mice received subcutaneous implants of growth factor-reduced Matrigel inclusive of C3L5 cells on one side, and on the contralateral side, Matrigel alone; L-NAME and D-NAME (inactive enantiomer) were subsequently administered for 14 days using osmotic minipumps. Immediately after sacrifice, implants were removed and processed for immunolocalization of eNOS and iNOS proteins, and measurement of angiogenesis. Neovascularization was quantified in sections stained with Masson's trichrome or immunostained for the endothelial cell specific CD31 antigen. While most tumor cells and endothelial cells expressed immunoreactive eNOS protein, iNOS was localized in endothelial cells and some macrophages within the tumor-inclusive implants. Measurable angiogenesis occurred only in implants containing tumor cells. Irrespective of the method of quantification used, tumor-induced neovascularization was significantly reduced in L-NAME-treated mice relative to those treated with D-NAME. The quantity of stromal tissue was lower, but the quantity of necrotic tissue higher in L-NAME relative to D-NAME-treated animals. The total mass of viable tissue (ie, stroma and tumor cells) was lower in L-NAME relative to D-NAME-treated animals. These data suggest that NO is a key mediator of C3L5 tumor-induced angiogenesis, and that the antitumor effects of L-NAME are partly mediated by reduced tumor angiogenesis.


Infectivity, growth, and development of Echinostoma revolutum (Digenea: Echinostomatidae) in the golden hamster, Mesocricetus auratus.
All 30 female golden hamsters, Mesocricetus auratus, each fed 100 +/- 25 metacercarial cysts of Echinostoma revolutum were found to be infected 2 to 105 days post-infection with 3 to 103 (avg. 38) flukes in the small intestine. Worm wet weights averaged 0.6 mg at 9 days, 3.5 mg at 14 days, and 19 mg at 42 days; average dry weights for the identical days were 0.2, 1.2 and 5.8 mg, respectively. The average body length of worms fixed in hot (80 C) alcohol-formalin-acetic acid was 0.33 mm on day 2, 5.11 mm on day 10, 9.30 mm on day 42 and 8.56 mm on day 105. Body and gonadal area increased rapidly from about day 5 to 15 and then less rapidly. Eggs of E. revolutum were seen in the feces of 10% of the hamsters by day 9, 89% by day 10 and 100% by day 11. Eggs teased from worms, embryonated in tap water, and produced miracidia which infected lab-reared Helisoma trivolvis.


Recovery of Y-cells in the lateral geniculate nucleus of monocularly deprived cats.
Previous studies have demonstrated that removal of inputs from the nondeprived eye of monocularly deprived cats produces a recovery from some of the abnormalities caused by the deprivation. The present experiments examined whether the loss of Y-cells that occurs in the deprived laminae of the lateral geniculate nucleus (LGN) also can be reversed by this manipulation and, if so, what are the necessary and sufficient conditions for reversal to occur. Single cell recordings were made in LGN laminae A and A1 of 31 cats in a variety of rearing conditions, and the cells were classified as X, Y, or mixed on the basis of responses to a battery of tests. In normal cats, a mean of 39.1% of the LGN cells were Y-cells. In agreement with previous studies, monocular deprivation produced a reduction in the proportion of Y-cells encountered (18.1%). Removing the nondeprived eye at 4 months of age did not produce an increase in the proportion of Y-cells if the deprived eye remained closed for 3 months (16.9%). However removing the nondeprived eye at 4 months and opening the deprived eye for 3 months did produce an increase in the proportion of Y-cells (40.2%). Thus, the loss of Y-cells in the LGN that results from rearing with monocular deprivation can be reversed at 4 months of age; however, it is necessary to allow the deprived eye visual experience. In a second experiment, we assessed the age limits and the conditions that are both necessary and sufficient for the recovery of Y-cells. Removing the nondeprived eye at 12 to 16 months of age and allowing the deprived eye 3 months of visual experience still produced a significant increase in the proportion of Y-cells (30.3%). Thus, some reversal can occur well into adulthood. However, opening the deprived eye and simply closing the nondeprived eye (reverse suture) for 3 months in adult monocularly deprived cats did not produce a reversal of the LGN Y-cell loss (14.3%). Thus, it is necessary both to allow the deprived eye visual experience and to remove the inputs from the nondeprived eye to produce a recovery of LGN Y-cells. Simply closing the nondeprived eye is not sufficient, even if the deprived eye is opened. Taken together with previous studies, these results also indicate that there is a dissociation between functional recovery in LGN and striate cortex and between recovery of LGN cell size and the functional class of Y-cells following removal of the nondeprived eye.


Expression of cyclooxygenase-1 and 2 in chronic tonsillitis.
Prostaglandins are critical mediators of inflammation and affect both humoral and cell-mediated immune responses. Recent findings show that T and B cells express COX-2 upon activation. The purpose of this study is to investigate the potential occurrence of COX-1 and COX-2 immunoreactivity in cases of chronic tonsillitis and to determine the sites of their expression. In addition, their expression in adult patients is compared with that in child patients. Immunohistochemical techniques were used to evaluate the expression of the enzymes COX-1 and COX-2, in chronic tonsillitis tissue specimens from adults (n = 15) and children (n = 15). There was no staining in surface epithelium or reticulated crypt epithelium. COX-1 and COX-2 expressions were observed mainly in the intraepithelial lymphoid cells in reticulated crypt epithelium and subepithelial cells. Also, COX-1 and COX-2 stained cells were found in the germinal center. There was no difference of the expressions of COX-1 and COX-2 among adults and children. The only significant difference noted between the adults and children was that, the adults had rich subepithelial plasma cells. Activated B and T cells express COX-1 and COX-2 in paraffin-embedded tissue sections of chronic tonsillitis. Further studies need to be performed to elucidate expression of COX enzymes and their immunologic role in tonsil diseases. They will play an important role in the treatment of chronic tonsillitis. Additional studies are warranted to study the effects of NSAIDs and selective COX-2 inhibitors in chronic tonsillitis.


Naphthoquinone derivatives exert their antitrypanosomal activity via a multi-target mechanism.
Recently, we reported on a new class of naphthoquinone derivatives showing a promising anti-trypanosomatid profile in cell-based experiments. The lead of this series (B6, 2-phenoxy-1,4-naphthoquinone) showed an ED(50) of 80 nM against Trypanosoma brucei rhodesiense, and a selectivity index of 74 with respect to mammalian cells. A multitarget profile for this compound is easily conceivable, because quinones, as natural products, serve plants as potent defense chemicals with an intrinsic multifunctional mechanism of action. To disclose such a multitarget profile of B6, we exploited a chemical proteomics approach. A functionalized congener of B6 was immobilized on a solid matrix and used to isolate target proteins from Trypanosoma brucei lysates. Mass analysis delivered two enzymes, i.e. glycosomal glycerol kinase and glycosomal glyceraldehyde-3-phosphate dehydrogenase, as potential molecular targets for B6. Both enzymes were recombinantly expressed and purified, and used for chemical validation. Indeed, B6 was able to inhibit both enzymes with IC(50) values in the micromolar range. The multifunctional profile was further characterized in experiments using permeabilized Trypanosoma brucei cells and mitochondrial cell fractions. It turned out that B6 was also able to generate oxygen radicals, a mechanism that may additionally contribute to its observed potent trypanocidal activity. Overall, B6 showed a multitarget mechanism of action, which provides a molecular explanation of its promising anti-trypanosomatid activity. Furthermore, the forward chemical genetics approach here applied may be viable in the molecular characterization of novel multitarget ligands.


Transcriptomic and enzymatic analysis reveals the roles of glutamate dehydrogenase in Corynebacterium glutamicum.
Glutamate dehydrogenase (Gdh), catalyzing the reversible conversion between 2-oxoglutarate and glutamate, plays an important role in the connection of nitrogen and carbon metabolism. Yet little is known about these enzymes in the amino acid-manufacturing Corynebacterium glutamicum. In the present study, we firstly identified the enzymatic characteristics of two Gdhs (GdhA and GdhB). The results showed that both GdhA and GdhB prefers NADPH as a coenzyme and have higher affinity for 2-OG than glutamate. The growth characteristics of gdhAΔ mutant and gdhBΔ mutant, gdhABΔ mutant showed GdhA serves as the main conduit for ammonium assimilation, and GdhB is the main glutamate- metabolizing enzyme in C. glutamicum. The full-genome transcriptomic analysis was used to investigate physiological response of C. glutamicum to the glutamate as nitrogen source, and gdh deletion. The results showed that the nitrogen starvation response was elicited when glutamine served as the sole nitrogen source. gdhAΔBΔ double deletion trigger a partially deregulated nitrogen starvation response, in which genes involved in nitrogen assimilation showed obviously upregulated in a certain extent. On the other hand, the genes of phosphotransferase system (PTS) and glycolysis pathway, most genes in pentose phosphate pathway were significantly upregulated, indicating that gdh deficiency initiated the enhancement of the absorption and metabolism of carbon sources. We believed that our results in this study will give new insights on the molecular mechanism of Gdh activity cross-talks with carbon and nitrogen metabolism, also setting a new background for further flux redistribution applied research of biotechnological interest.


iPSC-derived natural killer cells expressing the FcγR fusion CD64/16A can be armed with antibodies for multitumor antigen targeting.
Antibody therapies can direct natural killer (NK) cells to tumor cells, tumor-associated cells, and suppressive immune cells to mediate antibody-dependent cell-mediated cytotoxicity (ADCC). This antigen-specific effector function of human NK cells is mediated by the IgG Fc receptor CD16A (FcγRIIIA). Preclinical and clinical studies indicate that increasing the binding affinity and avidity of CD16A for antibodies improves the therapeutic potential of ADCC. CD64 (FcγRI), expressed by myeloid cells but not NK cells, is the only high affinity IgG Fc receptor and is uniquely capable of stably binding to free monomeric IgG as a physiological function. We have reported on the generation of the FcγR fusion CD64/16A, consisting of the extracellular region of CD64 and the transmembrane and cytoplasmic regions from CD16A, retaining its signaling and cellular activity. Here, we generated induced pluripotent stem cell (iPSC)-derived NK (iNK) cells expressing CD64/16A as a potential adoptive NK cell therapy for increased ADCC potency. iPSCs were engineered to express CD64/16A as well as an interleukin (IL)-15/IL-15Rα fusion (IL-15RF) protein and differentiated into iNK cells. iNK cells and peripheral blood NK cells were expanded using irradiated K562-mbIL21-41BBL feeder cells and examined. NK cells, ovarian tumor cell lines, and therapeutic monoclonal antibodies were used to assess ADCC in vitro, performed by a DELFIA EuTDA assay or in real-time by IncuCyte assays, and in vivo. For the latter, we developed a xenograft mouse model with high circulating levels of human IgG for more physiological relevance. We demonstrate that (1) iNK-CD64/16A cells after expansion or thaw from cryopreservation can be coupled to therapeutic antibodies, creating armed iNK cells; (2) antibody-armed iNK-CD64/16A cells can be redirected by added antibodies to target new tumor antigens, highlighting additional potential of these cells; (3) cytokine-autonomous activity by iNK-CD64/16A cells engineered to express IL-15RF; and that (4) antibody-armed iNK-CD64/16A cells thawed from cryopreservation are capable of sustained and robust ADCC in vitro and in vivo, as determined by using a modified tumor xenograft model with high levels of competing human IgG. iNK cells expressing CD64/16A provide an off-the-shelf multiantigen targeting platform to address tumor heterogeneity and mitigate antigen escape.


Prevalence of cognitive impairment in systemic lupus erythematosus.
We administered a battery of neuropsychological tests to 62 female patients with systemic lupus erythematosus (SLE), 12 female patients with rheumatoid arthritis (RA), and 35 normal control subjects. By applying objective decision rules to individual test protocols, an overall prevalence of cognitive impairment of 66% was obtained in the SLE patient sample. Independent clinical, radiological, and laboratory data were used to determine neuropsychiatric (NP) symptomatology and to group SLE patients as 1) "active" (N = 21), 2) "inactive" (N = 15), and 3) "never" (N = 26) NP-SLE. More than 80% of the patients in groups 1 and 2 and 42% in group 3 showed significant cognitive impairment as compared with 17% of the RA patients and 14% of the normal control subjects. Neither steroid medication nor psychological distress could account for these findings. The unexpectedly high prevalence of cognitive impairment in SLE patients with either inactive or absent neuropsychiatric symptomatology provides evidence for subclinical nervous system involvement in SLE.


Impact of serotonin reuptake inhibitor use on breast milk supply in mothers of preterm infants: a retrospective cohort study.
The aims of the present study were to examine the association between late pregnancy exposure to serotonin reuptake inhibitor (SRI) antidepressants and difficulties in achieving an adequate breast milk supply in women who have given birth to preterm infants, while accounting for the potential impacts of underlying maternal psychiatric illness. A retrospective cohort study was carried out of 3024 women delivering liveborn preterm infants (<37 weeks' gestation) between January 2004 and December 2008. The primary outcome was postnatal domperidone use, considered to be a valid proxy for the presence and pharmacological management of low milk supply. Relative risks adjusted for maternal sociodemographic characteristics and comorbidities (aRRs) were calculated for low milk supply, comparing women with late pregnancy exposure to SRI antidepressants (n = 86), women with a psychiatric illness but no antidepressant use (n = 126) and women with neither antenatal exposures (n = 2812). Compared with non-exposed women, nonmedicated psychiatric illness [aRR 1.64; 95% confidence interval (CI) 1.16, 2.30] but not late pregnancy SRI use (aRR 1.00; 95% CI 0.59, 1.70) was associated with an increased risk of domperidone use, indicative of low milk supply. These findings do not support the previously observed negative impacts of antidepressant use on breastfeeding, instead suggesting that women with an underlying psychiatric illness appear at greatest risk of experiencing low milk supply and could benefit from additional breastfeeding education and support.


Comprehensive study of honey with protected denomination of origin and contribution to the enhancement of legal specifications.
In this study the characterization of a total of 60 honey samples with Protected Denomination of Origin (PDO) collected over three harvests (2009-2011, inclusive), from the Northeast of Portugal was carried out based on the presence of pollen, physicochemical and microbiological characteristics. All samples were found to meet the European Legislation, but some didn't meet the requirements of the PDO specifications. Concerning the floral origin of honey, our results showed the prevalence of rosemary (Lavandula pedunculata) pollen. The microbiological quality of all the analyzed samples was satisfactory, since fecal coliforms, sulfite-reducing clostridia and Salmonella were absent, and molds and yeasts were detected in low counts. Significant differences between the results were studied using one-way analysis of variance (ANOVA), followed by Tukey's HSD test. The samples were submitted to discriminant function analysis, in order to determine which variables differentiate between two or more naturally occurring groups (Forward Stepwise Analysis). The variables selected were in this order: diastase activity, pH, reducing sugars, free acidity and HMF. The pollen spectrum has perfect discriminatory power. This is the first study in which a honey with PDO was tested, in order to assess its compliance with the PDO book of specifications.


Short-term results after aortic valve replacement with stentless xenografts in elderly patients.
Our aim was to chart the short-term results of the first 75 of our patients who had undergone first-time aortic valve replacement (AVR) with stentless xenografts. Our study included a complete follow-up (mean/max. 1.5/3.7 years) of the first 75 patients (42 males, 33 females; mean age 74, range 61-84 years) who underwent a first AVR with stentless xenografts. Forty-three percent of patients were in functional class II and 57% in classes III-IV preoperatively. Coronary artery bypass grafting (CABG) was performed in 33 patients. Early mortality (< or = 30 days) was 6.7%, with no significant relation to CABG or age. Crude survival was 81% (95% confidence interval, CI: 71-91 %) at 3 years. Using a multivariate analysis, we identified a low left ventricular ejection fraction as a predictor of early and late mortality. Late survival (early mortality excluded) was comparable with the survival of a matched Danish background population. There were six embolic events (all cerebral: 3 minor, 1 major, 2 fatal), while two patients underwent redo-AVR because of either endocarditis (fatal) or aortic regurgitation caused by malaligned commissures. There were no other valve-related complications. Cumulative freedom was 89% (95% CI: 79-99%) for embolism and 86% (95% CI: 76-96 %) for all complications at 3 years. At the end of the study, 64% of the survivors were in functional class I, 34% were in class II and 2% in class III. Considering the age composition of our patients, and compared with international results, our early mortality rates were acceptable. The absence of late excess mortality compared with the background population and the functional status at end-of-study may indicate the potential haemodynamic advantages of stentless aortic valves, at least in the short term.


Distribution of gastrin-releasing peptide in the rat trigeminal and spinal somatosensory systems.
Gastrin-releasing peptide (GRP) has recently been identified as an itch-specific neuropeptide in the spinal sensory system in mice, but there are no reports of the expression and distribution of GRP in the trigeminal sensory system in mammals. We characterized and compared GRP-immunoreactive (ir) neurons in the trigeminal ganglion (TG) with those in the rat spinal dorsal root ganglion (DRG). GRP immunoreactivity was expressed in 12% of TG and 6% of DRG neurons and was restricted to the small- and medium-sized type cells. In both the TG and DRG, many GRP-ir neurons also expressed substance P and calcitonin gene-related peptide, but not isolectin B4 . The different proportions of GRP and transient receptor potential vanilloid 1 double-positive neurons in the TG and DRG imply that itch sensations via the TG and DRG pathways are transmitted through distinct mechanisms. The distribution of the axon terminals of GRP-ir primary afferents and their synaptic connectivity with the rat trigeminal sensory nuclei and spinal dorsal horn were investigated by using light and electron microscopic histochemistry. Although GRP-ir fibers were rarely observed in the trigeminal sensory nucleus principalis, oralis, and interpolaris, they were predominant in the superficial layers of the trigeminal sensory nucleus caudalis (Vc), similar to the spinal dorsal horn. Ultrastructural analysis revealed that GRP-ir terminals contained clear microvesicles and large dense-cored vesicles, and formed asymmetric synaptic contacts with a few dendrites in the Vc and spinal dorsal horn. These results suggest that GRP-dependent orofacial and spinal pruriceptive inputs are processed mainly in the superficial laminae of the Vc and spinal dorsal horn.


Detailed clinical features and genotype-phenotype correlation in an OTOF-related hearing loss cohort in Japan.
Mutations in the OTOF gene are a common cause of hereditary hearing loss and the main cause of auditory neuropathy spectrum disorder (ANSD). Although it is reported that most of the patients with OTOF mutations have stable, congenital or prelingual onset severe-to-profound hearing loss, some patients show atypical clinical phenotypes, and the genotype-phenotype correlation in patients with OTOF mutations is not yet fully understood. In this study, we aimed to reveal detailed clinical characteristics of OTOF-related hearing loss patients and the genotype-phenotype correlation. Detailed clinical information was available for 64 patients in our database who were diagnosed with OTOF-related hearing loss. As reported previously, most of the patients (90.6%) showed a "typical" phenotype; prelingual and severe-to-profound hearing loss. Forty-seven patients (73.4%) underwent cochlear implantation surgery and showed successful outcomes; approximately 85-90% of the patients showed a hearing level of 20-39 dB with cochlear implant and a Categories of Auditory Performance (CAP) scale level 6 or better. Although truncating mutations and p.Arg1939Gln were clearly related to severe phenotype, almost half of the patients with one or more non-truncating mutations showed mild-to-moderate hearing loss. Notably, patients with p.His513Arg, p.Ile1573Thr and p.Glu1910Lys showed "true" auditory neuropathy-like clinical characteristics. In this study, we have clarified genotype-phenotype correlation and efficacy of cochlear implantation for OTOF-related hearing loss patients in the biggest cohort studied to date. We believe that the clinical characteristics and genotype-phenotype correlation found in this study will support preoperative counseling and appropriate intervention for OTOF-related hearing loss patients.


Biological aspects of Tiracola grandirena (Herrich-Schäffer, 1868) (Lepidoptera: Noctuidae): a polyphagous armyworm.
We studied the biology of Tiracola grandirena (Herrich-Schäffer, 1868) (Lepidoptera: Noctuidae: Hadeninae) at 25 ± 1 °C, 70 ± 10% RH and 14 hours of photo phase. Three experiments, using 150 larvae each, were conducted for the larval stage. In the first, used to assess the duration and survival of all stages, insects were reared individually and fed an artificial diet (Grenee). In the second, individuals were also reared separately, but were fed leaves of 10 plants from different families. In the third, the larvae were not individualised, the food plants were rotated such as to provide three plant species every 48 hours. In the first experiment, the viability of the eggs, larvae, pupae and prepupae was 91.9, 94.7, 32.49 and 43.5%, respectively. The average duration of the egg, larvae, prepupae, pupae and adult were 6.0, 25.3, 25.7, 21.4 and 12.7 days, respectively. The prolonged prepupal period indicates that T. grandirena can develop larval (prepupal) diapause. The results of the experiments with different host plants showed that T. grandirena is polyphagous at species, population and individual level.


p38 MAP-kinase inhibitor protects against platelet-activating factor-induced death in mice.
Platelet-activating factor (PAF) is a potent inflammatory agonist. In Swiss albino mice, intraperitoneal injection of PAF causes sudden death with oxidative stress and disseminated intravascular coagulation (DIC), characterized by prolonged prothrombin time, thrombocytopenia, reduced fibrinogen content, and increased levels of fibrinogen degradation products. However, the underlying mechanism(s) is unknown. The PAF-R antagonist WEB-2086 protected mice against PAF-induced death by reducing DIC and oxidative stress. Accordingly, general antioxidants such as ascorbic acid, α-tocopherol, gallic acid, and N-acetylcysteine partially protected mice from PAF-induced death. N-acetylcysteine, a clinically used antioxidant, prevented death in 67% of mice, ameliorated DIC characteristics and histological alterations in the liver, and reduced oxidative stress. WEB-2086 suppressed H2O2-mediated oxidative stress in isolated mouse peritoneal macrophages, suggesting that PAF signaling may be a downstream effector of reactive oxygen species generation. PAF stimulated all three (ERK, JNK, and p38) of the MAP-kinases, which were also inhibited by N-acetylcysteine. Furthermore, a JNK inhibitor (SP600125) and ERK inhibitor (SCH772984) partially protected mice against PAF-induced death, whereas a p38 MAP-kinase inhibitor (SB203580) provided complete protection against DIC and death. In human platelets, which have the canonical PAF-R and functional MAP-kinases, JNK and p38 inhibitors abolished PAF-induced platelet aggregation, but the ERK inhibitor was ineffective. Our studies identify p38 MAP-kinase as a critical, but unrecognized component in PAF-induced mortality in mice. These findings suggest an alternative therapeutic strategy to address PAF-mediated pathogenicity, which plays a role in a broad range of inflammatory diseases.


Comparison of Aberrant Behavior Checklist profiles across Prader-Willi syndrome, Down syndrome, and autism spectrum disorder.
Prader-Willi syndrome (PWS, OMIM # 176270) and Down syndrome (DS, OMIM #190685) are neurodevelopmental genetic disorders with higher rates of autism spectrum disorder (ASD). The Aberrant Behavior Checklist (ABC) is a caregiver rating scale that assesses maladaptive behaviors. Overlapping symptoms exist between PWS, DS, and ASD, including maladaptive behaviors. We aimed to evaluate ABC profiles between PWS, DS, and ASD alone (without known genetic syndrome). In addition, we hypothesized PWS and DS with a comorbid ASD positive screen or diagnosis would have similar ABC profiles to ASD alone. ABC data from the following cohorts were analyzed: PWS (Seattle Children's Hospital, n = 28, mean age = 12.8 ± 4.9 years; University of Florida, n = 35, mean age = 9.3 ± 7.1 years), DS (Johns Hopkins, n = 406, mean age = 8.1 ± 2.4 years), and ASD (University of Florida, n = 102, mean age = 10.8 ± 3.5 years). ASD alone had significantly higher ABC scores. Subgroups of PWS and DS with a comorbid ASD positive screen or diagnosis had similarities in scores with the ASD only group, with subscale patterns unique to each syndrome. The ABC indicated worse maladaptive behaviors in children with ASD, including those with genetic syndromes. Although more studies are needed to evaluate the utility and the accuracy of the ABC as a tool to screen for ASD in special populations, it may be a useful adjunct in screening those children with PWS or DS who need more in depth ASD evaluation.


Generalizable brain network markers of major depressive disorder across multiple imaging sites.
Many studies have highlighted the difficulty inherent to the clinical application of fundamental neuroscience knowledge based on machine learning techniques. It is difficult to generalize machine learning brain markers to the data acquired from independent imaging sites, mainly due to large site differences in functional magnetic resonance imaging. We address the difficulty of finding a generalizable marker of major depressive disorder (MDD) that would distinguish patients from healthy controls based on resting-state functional connectivity patterns. For the discovery dataset with 713 participants from 4 imaging sites, we removed site differences using our recently developed harmonization method and developed a machine learning MDD classifier. The classifier achieved an approximately 70% generalization accuracy for an independent validation dataset with 521 participants from 5 different imaging sites. The successful generalization to a perfectly independent dataset acquired from multiple imaging sites is novel and ensures scientific reproducibility and clinical applicability.


Assessment of fish adulteration using SnO2 nanopetal-based gas sensor and machine learning.
The work presents the identification of fish adulteration and quality assessment by incorporating a chemiresistive gas sensor and machine learning (ML) techniques. Highly sensitive SnO2 nanopetals were synthesized chemically and integrated with interdigitated electrodes to fabricate a sensor device. The sensor was calibrated with formaldehyde (37 %) with a theoretical detection limit of 75 ppb and further utilized to detect the vapors emitted from fresh and formalin-adulterated fish. An extensive sensing investigation was conducted with freshly caught Rohu fish samples. The sensing behavior was examined for all the samples at different time intervals to estimate the spoilage level. The classification between fresh and adulterated fish samples was obtained with 100 % accuracy by employing ML tools. Moreover, the storage duration and spoilage level of fish samples were quantified using regression models. This work emphasizes the potential of nanomaterials combined with machine learning for the accurate detection of adulteration in food systems.


SAP increases FynT kinase activity and is required for phosphorylation of SLAM and Ly9.
The free Src homology 2 (SH2) domain protein SAP, encoded by the X-linked lymphoproliferative disease gene SH2D1A, controls signal transduction initiated by engagement of the SLAM-related receptors in T and NK cells. Here we demonstrate that SAP is required for phosphorylation of both SLAM and Ly9 in thymocytes and peripheral T cells. Furthermore, in vitro protein interaction studies and yeast two-hybrid analyses indicated that SAP binds directly to FynT and Lck. While SAP bound to both the SH3 domain and to the kinase domain of FynT, SAP bound solely to the kinase domain of Lck. The existence of a strong interaction between SAP and the SH3 domain of FynT prompted us to study the role of SAP in modulating the activity of FynT. In vitro addition of SAP to the autoinhibited form of FynT caused a large increase in FynT catalytic activity. By contrast, the SAP mutant R78E, which is unable to bind to the FynT SH3 domain, did not increase FynT activity and also displayed a reduced adaptor function upon transfection into T cells. Our results demonstrate that SAP is an adaptor that bridges SLAM and Ly9 with Src-like protein tyrosine kinases (PTKs), and has the ability to activate FynT.


The relationship between glucose tolerance and severity of coronary artery disease using the Gensini score.
Consecutive patients (n = 235) with coronary ischemia were studied; 69 patients (29%) had diabetes. An oral glucose tolerance test (OGTT) was administered to the 166 patients without diabetes; 76 (46%) had normal glucose tolerance (group I = NGT), 68 (41%) had impaired glucose tolerance ([IGT] group II = IGT), and 22 (13%) had diabetic glucose tolerance (DGT). The DGT patients were added to the known diabetics forming (Group III; n = 91). Multivessel disease was significantly more prevalent in group III; 30 patients (43%) in group I, 32 patients (51%) in group II, and 57 patients (69%) in group III (P = .002). Gensini scores were 43.20 ± 24.92 in group I, 54.22 ± 42.61 in group II, and 60.59 ± 38.21 in group III. (P = .037) The severity of coronary artery disease is related to abnormal glucose tolerance. Patients with IGT could be neglected in terms of interventions focused to improve risk factors.


[In vitro study of the fusion products and cell hybrids of mouse oocytes, zygotes and blastomeres].
Several variants of mouse embryos were received by polyethylene glycol-induced fusion of ovulated oocytes, blastomeres from various developmental stages, zygotes and their fragments. Cytological analysis and observation in culture have been carried out. The nuclear dynamics during the process of fusion, onset of mitosis in fusion products, their cleavage and initial morphogenetic processes in developing embryos have been followed. The possibility of directed constitution of embryos with varying quantitative and qualitative combination of nuclei and cytoplasm is, thus, shown. Some aspects of application of these models in studying the controlling mechanisms of early embryogenesis are considered.


Differentiation and Variability in the Rhizosphere and Endosphere Microbiomes of Healthy and Diseased Cotton (Gossypium sp.).
The plant microbiome is a key determinant of health and productivity. However, it is still difficult to understand the structural composition of the bacterial and fungal microbiomes of diseased and healthy plants, especially the spatial dynamics and phylogenies of endophytic and rhizosphere microbial communities. We studied the differentiation and variability in the rhizosphere and endosphere microbiomes of healthy and diseased cotton from north and south of the Tianshan Mountains using the methods of PCR-based high-throughput sequencing and real-time quantitative PCR. The endophytic and rhizosphere bacterial abundances in the diseased plants were greater than those of healthy plants. The numbers of endophytic and rhizosphere fungi associated with diseased plants were greater than those associated healthy plants (p < 0.05). Endophytic and rhizosphere bacteria did not share common OTUs. The dominant rhizosphere bacteria were Proteobacteria (29.70%), Acidobacteria (23.14%), Gemmatimonadetes (15.17%), Actinobacteria (8.31%), Chloroflexi (7.99%), and Bacteroidetes (5.15%). The dominant rhizosphere fungi were Ascomycota (83.52%), Mortierellomycota (7.67%), Basidiomycota (2.13%), Chytridiomycota (0.39%), and Olpidiomycota (0.08%). The distribution of dominant bacteria in different cotton rhizosphere soils and roots differed, with the dominant bacteria Pseudomonas (15.54%) and Pantoea (9.19%), and the dominant fungi Alternaria (16.15%) and Cephalotrichum (9.10%) being present in the greatest numbers. At sampling points in different ecological regions, the total numbers of cotton endophytic and rhizosphere microbiome OTUs from southern to northern Xinjiang showed an increasing trend. There were significant differences in the composition and diversity of rhizosphere microbes and endophytes during the entire cotton growth period and in representative ecological regions (p < 0.01), whereas rhizosphere microbes and endophytes showed no significant differences among the four growth periods and in representative ecological regions. RB41, H16, Nitrospira, and Sphingomonas play important roles in the microbial ecology of cotton rhizosphere soil. Pseudomonas accounted for a large proportion of the microbes in the cotton rhizosphere soil. This study provides an in-depth understanding of the complex microbial composition and diversity associated with cotton north and south of the Tianshan Mountains.


Preoperative templating for the equalization of leg lengths in total hip arthroplasty.
The method and results of preoperative templating for the re-establishment of leg length equality during total hip replacement (THR) are reported. The method is a modification of the technique of Müller and requires an anteroposterior radiograph of the pelvis that includes the proximal third of both femora, appropriate acetabular and femoral templates, and tracing paper. To obtain equalization of leg lengths and tissue tension, a composite drawing is made of the operative plan, with all component sizes and important measurements clearly marked. During THR, the lesser trochanter is identified and the femoral neck is osteotomized after a direct measurement is made. These principles were followed in a prospective, consecutive series of 42 primary THR procedures performed by one surgeon. All the radiographic measurements were performed by a single observer. The leg length discrepancy on the postoperative radiograph averaged 3mm (standard deviation = 3mm, range: -9 to +9mm). The postoperative clinical leg length discrepancy averaged 0mm (range: -10 to +10mm). None of the patients complained of leg length inequality. Preoperative templating allows different alternatives to be traced on paper prior to the actual surgical procedure. This method also helps determine the requirements for special prosthetic implants. Acceptable results for postoperative leg length equality may be reliably achieved using this method.


Prevalence of HIV and STIs and associated risk factors among female sex workers in Guangdong Province, China.
To assess the prevalence of HIV and sexually transmitted infections (STIs) and associated factors among female sex workers (FSWs) in Guangdong, China. Respondent-driven sampling was used to recruit 320 FSWs. The recruited participants were interviewed face-to-face using a structured questionnaire and tested for HIV, syphilis, gonorrhea, and Chlamydia. The prevalence of syphilis, gonorrhea, and Chlamydia were 8.0% (4.6%-12.2%), 9.5% (5.6%-14.3%), and 3.9% (1.7%-6.2%), respectively, and of any STIs was 19.7% (13.9%-26.2%). None of the participants were HIV positive. The median number of clients during the previous week was 5. The proportion of consistent condom use with the clients during the previous week was 58.0% (50.4%-65.5%), use with regular nonpaying partners and nonregular nonpaying partners were much lower than that with clients. Multivariate analysis indicated that years of education and perception of HIV risk were protective factors. Awareness of HIV/AIDS; regular sex partners deciding about condom use when having sex; recruiting clients at hotels, hair/beauty salons, or streets instead of massage parlors; and higher charge for last sexual service were associated with STI infection. Future intervention programs should not only address personal risk factors but also empower FSWs to require condom use by both clients and nonpaying partners.


Nanoparticle-mediated local delivery of Methylprednisolone after spinal cord injury.
Systemic administration of a high-dose of Methylprednisolone (MP) can reduce neurological deficits after acute spinal cord injury (SCI). However, the use of high-dose MP in treating acute SCI is controversial due to significant dose related side effects and relatively modest improvements in neurological function. Here, using a rat model of SCI, we compare the efficacy of controlled, nanoparticle-enabled local delivery of MP to the injured spinal cord with systemic delivery of MP, and a single local injection of MP without nanoparticles. Based on histological and behavioral data, we report that local, sustained delivery of MP via nanoparticles is significantly more effective than systemic delivery. Relative to systemic delivery, MP-nanoparticle therapy significantly reduced lesion volume and improved behavioral outcomes. Nanoparticle-enabled delivery of MP presents an effective method for introducing MP locally after SCI and significantly enhances therapeutic effectiveness compared to bare MP administered either systemically or locally.


Evaluation of the potential effect of transgenic rice expressing Cry1Ab on the hematology and enzyme activity in organs of female Swiss rats.
To assess the safety of transgenic rice expressing Cry1Ab protein to vertebrates, the effect of Cry1Ab rice on broad health indicators in blood and various organs of Swiss rats were analyzed. The 30 and 90 day safety studies of Cry1Ab rice on female Swiss rats revealed that Cry1Ab rice had no significant effect on the several elements of blood lymph including hemogram, calcium ion concentration and apoptosis rate of lymphocytes, indicating that Cry1Ab protein could not affect the blood lymph of Swiss rat. Similarly, Cry1Ab rice had no effect on enzyme activities in a variety of organs of Swiss rat. However, Cry1Ab rice did have significant effects on the blood biochemistry indexes including urea, triglyceride (TG), glutamic oxalacetic transaminase (AST) and alkaline phosphatase (ALP) after the rats were fed with Cry1Ab rice for 30 days, but not after 90 days, indicating that Cry1Ab protein may influence blood metabolism for a short duration. Quantitative real-time PCR (qPCR) analysis of the 6 genes encoding enzymes responsible for the major detoxification functions of liver revealed that Cry1Ab rice exerted no influences on the levels of these transcripts in liver of Swiss rat, indicating that significant differences registered in part of the blood biochemical parameters in the 30 day study might result from other untested organs or tissues in response to the stress of exogenous Cry1Ab protein. The results suggest that Cry1Ab protein has no significant long-term (90 day) effects on female Swiss rat.


How Do Older Patients with End-Stage Osteoarthritis of the Hip Eat Prior to Hip Replacement? A Preliminary Snapshot That Highlights a Poor Diet.
Diet quantity and quality in older adults is critical for the proper functioning of the musculoskeletal system. In view of hip surgery, old patients should consume 1.2-1.5 g of proteins and 27-30 kcal per kilo of body weight daily, and adhere to healthy eating habits. In this analytical study, we studied diet quantity and quality in relation to the clinical chemistry and functional status of 57 older adults undergoing elective hip replacement. Nine in ten patients did not meet suggested protein and energy intakes and only one in ten patients exhibited high adherence to the Mediterranean diet. Legume consumption adjusted for sex, age, body mass index, and health status successfully forecasted haemoglobin levels (p < 0.05), and patients regularly consuming olive oil reported minor hip disability compared to those using it less frequently (p < 0.05). Patients who reported daily ingestion of <1 serving of meat versus those consuming >1.5 servings had greater cumulative comorbidity (p < 0.05), with meat consumption independently predicting walking ability, mobility, and balance in the fully adjusted model (p < 0.01). In conclusion, our patients seem to eat poorly. There is room for improvement in pre-operative pathways to make older adults eat better, but there is a need to plan an interventional study to fully understand the cause-effect of a dietary pattern or specific food in enhancing recovery after surgery.


Multiple time courses of salivary alpha-amylase and dimensions of affect in adolescence.
Previous research has illustrated associations among daily experiences, emotions and stress-responding physiological systems. Recently, investigators have examined salivary alpha-amylase (sAA), a surrogate marker of the autonomic nervous system, and its associations with affect. The current study examined associations among affective valence, arousal and sAA across three different time courses at the momentary, daily and inter-individual level to understand varying influences of adolescents' daily emotional experiences on sAA reactivity and diurnal sAA activity. Adolescents (N=82) provided salivary samples and diary reports of affect and experiences five times a day for three consecutive days. They also completed self-report questionnaires on trait affect. Findings from multilevel growth curves demonstrated that adolescents in our sample displayed typical sAA diurnal rhythms with levels dropping 30 min after waking and then increasing across the day to a peak in the late afternoon. Within person momentary experiences of high arousal positive affect were associated with momentary sAA reactivity. Prior day experiences of high arousal negative affect were associated with a greater amylase awakening response (i.e., greater decrease) and flatter slopes the next day. Trait positive affect was also associated with flatter sAA slopes. Our findings suggest that both affective arousal and valence should be accounted for when examining differences in sAA reactivity and diurnal patterns. Further, our results indicated that emotion-physiology transactions among adolescents occur over varying time scales for salivary alpha-amylase as well as cortisol.


Perceiving and representing both health and the environment: an exploratory investigation.
This article describes an exploratory study that examined the perceptions of both health and environment among men and women in higher and lower status areas in Hamilton, Canada. Situated in the literatures on health perceptions and environmental concerns, it not only describes health and environment perceptions, but also explores their interconnections, arguing that concern for self is more salient than that for any other, including environment, and that this salience is predicated on notions of control and responsibility. The article concludes by speculating on reasons for these findings by suggesting an empirically derived cultural model for representation of health-environment relations and the bases of information processing in this arena.


Action spectrum for phototherapy of psoriasis.
Using a monochromator the action spectrum for ultraviolet phototherapy of psoriasis was determined for radiation between 254 and 313 nm and compared to the action spectrum for erythema of uninvolved adjacent skin. Daily exposures of different doses of 254, 280, 290, 296, 300, 304 and 313 nm radiation were observed. Wavelengths of 254, 280, 290 nm were erythemogenic but not therapeutic even at 10 to 50 times the minimal erythema dose. At the other wavelengths studied, the 2 action spectra were similar. In general, fixed daily doses cleared at lower cumulative dose than did incrementally increased daily doses. The small number of suberythemogenic exposure doses required suggests that monochromatic radiation may have advantages over broadband sources.


Risk factors and complications of hypertension in Yaounde, Cameroon.
To determine the risk factors and complications of hypertension, isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) in Yaounde. Between January and September 1998 we examined 813 consecutive adult patients (46.5% men) in the Yaounde University Teaching Hospital, with special focus on risk factors of hypertension and clinical findings in the cardiovascular system. We measured systolic blood pressure, diastolic blood pressure, body mass index and plasma glucose, and recorded chest X-ray, electrocardiogram and echocardiogram. Hypertension, ISH and IDH were defined using the WHO-ISH 1999 criteria. After controlling for the confounding effects of age and sex, hypertension was significantly associated with obesity, family history of hypertension, alcohol intake, heart failure, stroke and left ventricular hypertrophy (p < 0.01); smoking was significantly associated with ISH (p = 0.04), and no factor was independently associated with IDH. A prevention strategy for hypertension and its resultant complications in Cameroon should include measures aimed at obesity and alcohol consumption, as well as early diagnosis with the institution of effective and affordable therapy.


Estimating Global Visual Field Indices in Glaucoma by Combining Macula and Optic Disc OCT Scans Using 3-Dimensional Convolutional Neural Networks.
To evaluate the accuracy at which visual field global indices could be estimated from OCT scans of the retina using deep neural networks and to quantify the contributions to the estimates by the macula (MAC) and the optic nerve head (ONH). Observational cohort study. A total of 10 370 eyes from 109 healthy patients, 697 glaucoma suspects, and 872 patients with glaucoma over multiple visits (median = 3). Three-dimensional convolutional neural networks were trained to estimate global visual field indices derived from automated Humphrey perimetry (SITA 24-2) tests (Zeiss, Dublin, CA), using OCT scans centered on MAC, ONH, or both (MAC + ONH) as inputs. Spearman's rank correlation coefficients, Pearson's correlation coefficient, and absolute errors calculated for 2 indices: visual field index (VFI) and mean deviation (MD). The MAC + ONH achieved 0.76 Spearman's correlation coefficient and 0.87 Pearson's correlation for VFI and MD. Median absolute error was 2.7 for VFI and 1.57 decibels (dB) for MD. Separate MAC or ONH estimates were significantly less correlated and less accurate. Accuracy was dependent on the OCT signal strength and the stage of glaucoma severity. The accuracy of global visual field indices estimate is improved by integrating information from MAC and ONH in advanced glaucoma, suggesting that structural changes of the 2 regions have different time courses in the disease severity spectrum.