Treatment of May-Thurner's Syndrome and Associated Complications: A Multicenter Experience.
To assess the treatment options and associated complications in patients with May-Thurner's syndrome (MTS). We retrospectively reviewed the charts of patients diagnosed with MTS. Thorough review was completed and data relevant to methods of diagnosis, treatment, complications, hospital readmission, and mortality were extracted from patient charts. The patients were followed for two years after diagnosis. Of the 47 patients identified as having "MTS", 32 (70%) were diagnosed formally with either magnetic resonance venography, computed tomography venography, or ultrasound. Two patients were excluded for insufficient availability of follow-up records. Mean age of the population included (N = 30) was 50.24 ±15.33 years and 83% (N = 25) had female gender. The majority (40%) of patients were treated with anticoagulation, thrombolysis, and stent placement, and 13.3% received a combination of anticoagulation, antiplatelet agent, thrombolysis, and stent placement. Overall, we found 28 patients (93%) who underwent endovascular stenting. However, 39.3% (11/28) had stent-related complications that included stent thrombosis, stenosis, and migration. One patient underwent open heart surgery for stent retrieval. Duration of anticoagulation therapy ranged from 6 months to lifelong. Two patients (6.7%) suffered major bleeds requiring transfusion. Fourteen patients (46.6%) developed post-thrombotic syndrome. Seven (23.3%) patients required MTS-related readmission within 30 days. No mortality was noted at two-year follow-up. Although our study only included 30 patients, it was evident to us that there is no consensus in the management of MTS. Furthermore, endovascular stenting, which has a major role in the management of MTS, has complication rates that hover close to 40%. Further research is needed to help develop a standardized evidence-based approach in the management of MTS that ensures a decreased risk of immediate and long-term complications.


abYpap: improvements to the prediction of antibody VH/VL packing using gradient boosted regression.
The Fv region of the antibody (comprising VH and VL domains) is the area responsible for target binding and thus the antibody's specificity. The orientation, or packing, of these two domains relative to each other influences the topography of the Fv region, and therefore can influence the antibody's binding affinity. We present abYpap, an improved method for predicting the packing angle between the VH and VL domains. With the large data set now available, we were able to expand greatly the number of features that could be used compared with our previous work. The machine-learning model was tuned for improved performance using 37 selected residues (previously 13) and also by including the lengths of the most variable 'complementarity determining regions' (CDR-L1, CDR-L2 and CDR-H3). Our method shows large improvements from the previous version, and also against other modeling approaches, when predicting the packing angle.


Epidemiology and antibacterial susceptibility patterns of bloodstream infections, 2001-2004: an experience with BACTEC 9240 in Southern Iran.
This study was conducted to determine the prevalence of bacteria recovered from bloodstream samples by Bactec 9240 at our hospital wards and to evaluate their antibacterial susceptibility patterns. During January 2001 through December 2004, 9407 referred blood samples in Bactec bottles from admitted patients at three main wards, neonates, pediatrics and adults at Nemazee Hospital, affiliated to Shiraz University of Medical Sciences in Shiraz were processed. Positive cultures were purified and identified according to standard methods. Sensitivity of bacteria to different antibiotics was determined by Kirby-Bauer disk diffusion method. Staphylococcus aureus 132(25%), Escherichia coli 64(12.1%) and Pseudomonas aeruginosa 52(9.8%) were the most pathogenic bacteria which were recovered from the blood samples. Pathogenic microorganisms were isolated from blood samples of 305 (57.8%) at pediatrics, from 181 (34.2%) at adults and from 42 (8%) at neonates wards. The highest antibiotics activities against gram positive isolates observed for vancomycin (98.4%), chloramphenicol (86.4%) and ciprofloxacin (77.4%), while in gram negative bacteria imipenem (96.1%), ciprofloxacin (83%) and amikacin (77.9%), were effective antibiotics. Frequency of isolated bacteria at pediatrics compared to adults and neonates wards were approximately two and seven folds high, respectively which indicates special attention should be paid to pediatrics patients both in prevention and treatment aspects. Vancomycin and imipenim are the effective antibiotics and could cover majority of gram positive and negative bacteria. Therefore, combined administrations of these antibiotics seems mandatory for empirical therapy.


Beet necrotic yellow vein virus 42 kDa triple gene block protein binds nucleic acid in vitro.
The triple gene block (TGB) of beet necrotic yellow vein virus RNA 2 is required for cell-to-cell movement of the virus RNA. The protein P42 encoded by the 5'-proximal gene of the TGB has consensus sequence motifs characteristic of an ATP/GTP-dependent helicase. P42 was over-expressed in Escherichia coli and shown to bind both single- and double-stranded RNA and DNA by Northwestern blotting. Site-directed mutagenesis located the nucleic acid-binding domain to the N-terminal 24 amino acids of the protein and a point mutation or deletions in the region of P42 containing the helicase consensus sequences did not affect nucleic acid-binding activity of the immobilized protein. Electrophoretic mobility-shift assays revealed that P42 also binds nucleic acids in solution and that deletion of the N-terminal region inhibits this binding. Mutations in both the N-terminal nucleic acid-binding domain and the helicase domain blocked infection of leaves, indicating that both regions of P42 are important for its activity in vivo.


Hormone Modulation of Toll-Like Receptor 5 in Cultured Human Bladder Epithelial Cells.
The effect of hormone levels on the stimulation of Toll-like receptor 5 (TLR5) in the bladder is unknown. We aimed to study the effect of estradiol and progesterone on TLR5 expression and function in human bladder epithelial cells. After growing to near confluence, T24 human urinary bladder (HUB) cells were incubated in hormone-free (HF) media for 72 hours. Human urinary bladder cells were then incubated in (1) HF media, (2) estradiol media, (3) progesterone media, or (4) media containing estradiol and progesterone at physiologic concentrations. Following flagellin exposure, cells and media were collected. Toll-like receptor 5 expression and stimulated cytokine release were analyzed using enzyme-linked immunosorbent assays. Results were normalized with cellular protein assays. A TLR5 antagonist was used to confirm that stimulation from flagellin was mediated by TLR5 signaling. Cultured HUB cells express TLR5 protein. Estradiol and progesterone environments suppress TLR5 expression compared to HF environment. The function of TLR5 was measured by interleukin 6 (IL-6) and monocyte chemoattractant protein 1 production after flagellin exposure. Interleukin 6 production was 75% higher in the estradiol than progesterone environment. The progesterone environment produced IL-6 levels twice that observed in HF and combined estrogen-progesterone environments. Interestingly, higher TLR5 expression was associated with lower IL-6 production. Our study demonstrated that TLR5 expression and functional activity as measured by IL-6 are modulated by hormones. The increase in TLR5-associated IL-6 may play a role in increasing the rate of symptomatic urinary tract infection. Likewise, low TLR5 functional activity may dampen the response of the innate immune system, thereby lessening the likelihood of a symptomatic bladder infection.


Substrate Induced Strain Field in FeRh Epilayers Grown on Single Crystal MgO (001) Substrates.
Equi-atomic FeRh is highly unusual in that it undergoes a first order meta-magnetic phase transition from an antiferromagnet to a ferromagnet above room temperature (Tr ≈ 370 K). This behavior opens new possibilities for creating multifunctional magnetic and spintronic devices which can utilise both thermal and applied field energy to change state and functionalise composites. A key requirement in realising multifunctional devices is the need to understand and control the properties of FeRh in the extreme thin film limit (tFeRh < 10 nm) where interfaces are crucial. Here we determine the properties of FeRh films in the thickness range 2.5-10 nm grown directly on MgO substrates. Our magnetometry and structural measurements show that a perpendicular strain field exists in these thin films which results in an increase in the phase transition temperature as thickness is reduced. Modelling using a spin dynamics approach supports the experimental observations demonstrating the critical role of the atomic layers close to the MgO interface.


Tumor-induced eosinophilia and endocardial fibrosis: evidence for ectopic eosinophilopoietin production and toxic O2 metabolite-mediated endothelial damage.
We have described a patient with the clinical triad of anaplastic pulmonary carcinoma, extreme eosinophilia, and endocardial damage, with resulting fibrosis and mural "thrombosis." Since the "thrombi" consisted mainly of masses of aggregated eosinophils in close approximation to areas of fibrotic cardiac endothelium, it was hypothesized that eosinophils might provoke endothelial damage. Indeed, eosinophils generated large amounts of toxic oxygen species and were highly toxic to cultured endothelial cells in vitro; moreover, high concentrations of corticosteroids inhibited in tandem these phenomena. In addition, from the patient's tumor a 45,000-dalton "eosinophilopoietin" was extracted which stimulated eosinophil colonies without help from T-lymphocytes. We believe our results help explain both the hypereosinophilia which accompanies certain anaplastic carcinomas and the endocardial damage with thrombosis and embolization which may occur in any patient with excessive eosinophils. In this latter regard, our studies suggest that very high doses of corticosteroids--since they decrease generation of toxic oxygen products by, and the numbers of, eosinophils--may be rational therapy in hypereosinophilic syndromes.


Sequential Upregulation of Superoxide Dismutase 2 and Heme Oxygenase 1 by tert-Butylhydroquinone Protects Mitochondria during Oxidative Stress.
Oxidative stress is linked to mitochondrial dysfunction in aging and neurodegenerative conditions. The transcription factor nuclear factor E2-related factor 2 (Nrf2)-antioxidant response element (ARE) regulates intracellular antioxidative capacity to combat oxidative stress. We examined the effect of tert-butylhydroquinone (tBHQ), an Nrf2-ARE signaling pathway inducer, on mitochondrial function during oxidative challenge in neurons. tBHQ prevented glutamate-induced cytotoxicity in an HT-22 neuronal cell line even with an 8-hour exposure delay. tBHQ blocked glutamate-induced intracellular reactive oxygen species (ROS) and mitochondrial superoxide accumulation. It also protected mitochondrial function under glutamate toxicity, including maintaining mitochondrial membrane potential, mitochondrial Ca(2+) hemostasis, and mitochondrial respiration. Glutamate-activated, mitochondria-mediated apoptosis was inhibited by tBHQ as well. In rat primary cortical neurons, tBHQ protected cells from both glutamate and buthionine sulfoximine toxicity. We found that tBHQ scavenged ROS and induced a rapid upregulation of superoxide dismutase 2 (SOD2) expression and a delayed upregulation of heme oxygenase 1 (HO-1) expression. In HT-22 cells with a knockdown of SOD2 expression, delayed treatment with tBHQ failed to prevent glutamate-induced cell death. Briefly, tBHQ rescues mitochondrial function by sequentially increasing SOD2 and HO-1 expression during glutamate-mediated oxidative stress. This study is the first to demonstrate the role of tBHQ in preserving mitochondrial function during oxidative challenge and provides a clinically relevant argument for using tBHQ against acute neuron-compromising conditions.


Muscle-specific TGR5 overexpression improves glucose clearance in glucose-intolerant mice.
TGR5, a G protein-coupled bile acid receptor, is expressed in various tissues and regulates several physiological processes. In the skeletal muscle, TGR5 activation is known to induce muscle hypertrophy; however, the effects on glucose and lipid metabolism are not well understood, despite the fact that the skeletal muscle plays a major role in energy metabolism. Here, we demonstrate that skeletal muscle-specific TGR5 transgenic (Tg) mice exhibit increased glucose utilization, without altering the expression of major genes related to glucose and lipid metabolism. Metabolite profiling analysis by capillary electrophoresis time-of-flight mass spectrometry showed that glycolytic flux was activated in the skeletal muscle of Tg mice, leading to an increase in glucose utilization. Upon long-term, high-fat diet challenge, blood glucose clearance was improved in Tg mice without an accompanying increase in insulin sensitivity in skeletal muscle and a reduction of body weight. Moreover, Tg mice showed improved age-associated glucose intolerance. These results strongly suggest that TGR5 ameliorated glucose metabolism disorder that is caused by diet-induced obesity and aging by enhancing the glucose metabolic capacity of the skeletal muscle. Our study demonstrates that TGR5 activation in the skeletal muscle is effective in improving glucose metabolism and may be beneficial in developing a novel strategy for the prevention or treatment of hyperglycemia.


Biocatalytic cyclization of small macrolactams by a penicillin-binding protein-type thioesterase.
Macrocyclic peptides represent promising scaffolds for chemical tools and potential therapeutics. Synthetic methods for peptide macrocyclization are often hampered by C-terminal epimerization and oligomerization, leading to difficult scalability. While chemical strategies to circumvent this issue exist, they often require specific amino acids to be present in the peptide sequence. Herein, we report the characterization of Ulm16, a peptide cyclase belonging to the penicillin-binding protein-type class of thioesterases that catalyze head-to-tail macrolactamization of nonribosmal peptides. Ulm16 efficiently cyclizes various nonnative peptides ranging from 4 to 6 amino acids with catalytic efficiencies of up to 3 × 106 M-1 s-1. Unlike many previously described homologs, Ulm16 tolerates a variety of C- and N-terminal amino acids. The crystal structure of Ulm16, along with modeling of its substrates and site-directed mutagenesis, allows for rationalization of this wide substrate scope. Overall, Ulm16 represents a promising tool for the biocatalytic production of macrocyclic peptides.


Transcutaneous nerve stimulation for pain relief during chest tube removal following cardiac surgery.
In patients undergoing open heart surgery, chest tubes are removed postoperatively when patients are well awake and stable. Pain during chest tube removal can be moderate to severe and can be the worst experience of hospitalization. Various modalities of pain relief during chest tube removal have been tried with variable results. We sought to examine the effect of transcutaneous electrical nerve stimulation (TENS) as an intervention for pain relief during chest tube removal after cardiac surgery. In a tertiary care center, fifty patients undergoing open heart surgery were randomized into two groups. Group TENS (n = 25) received TENS from 30 min before and continued up to 30 min after chest tube removal. Control Group (n = 25) did not receive TENS. In both the groups, additional analgesic medication was provided on demand, besides the standard analgesic regime which was injection ketorolac 30 mg intramuscularly every 8 h. Patients were studied for pain during chest drain removal and pain related nausea, vomiting, and sense of well-being. Mean visual analog pain score assessed for chest tube removal was significantly less 4.1 ± 1.2 (P < 0.05) in TENS Group as compared to 6.1 ± 0.8 in Control Group. Significantly greater number of patients (n = 14) (P < 0.05) in Control Group demanded additional analgesia as compared to TENS Group (n = 5). Feeling of well-being, improvement in appetite, and sleep was better in TENS Group as compared to Control Group. We conclude that TENS might not replace the conventional analgesics but has definite adjuvant role in decreasing pain scores and improves sense of well-being during chest tube removal after cardiac surgery.


Uncoupling of ATP-mediated calcium signaling and dysregulated interleukin-6 secretion in dendritic cells by nanomolar thimerosal.
Dendritic cells (DCs) , a rare cell type widely distributed in the soma, are potent antigen-presenting cells that initiate primary immune responses. DCs rely on intracellular redox state and calcium (Ca2+) signals for proper development and function, but the relationship between these two signaling systems is unclear. Thimerosal (THI) is a mercurial used to preserve vaccines and consumer products, and is used experimentally to induce Ca2+ release from microsomal stores. We tested adenosine triphosphate (ATP) -mediated Ca2+ responses of DCs transiently exposed to nanomolar THI. Transcriptional and immunocytochemical analyses show that murine myeloid immature DCs (IDCs) and mature DCs (MDCs) express inositol 1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) Ca2+ channels, known targets of THI. IDCs express the RyR1 isoform in a punctate distribution that is densest near plasma membranes and within dendritic processes, whereas IP3Rs are more generally distributed. RyR1 positively and negatively regulates purinergic signaling because ryanodine (Ry) blockade a) recruited 80% more ATP responders, b) shortened ATP-mediated Ca2+ transients > 2-fold, and c) produced a delayed and persistent rise (>/= 2-fold) in baseline Ca2+. THI (100 nM, 5 min) recruited more ATP responders, shortened the ATP-mediated Ca2+ transient (>/= 1.4-fold) , and produced a delayed rise (>/= 3-fold) in the Ca2+ baseline, mimicking Ry. THI and Ry, in combination, produced additive effects leading to uncoupling of IP3R and RyR1 signals. THI altered ATP-mediated interleukin-6 secretion, initially enhancing the rate of cytokine secretion but suppressing cytokine secretion overall in DCs.DCs are exquisitely sensitive to THI, with one mechanism involving the uncoupling of positive and negative regulation of Ca2+ signals contributed by RyR1.


Integrated analysis of gene expression, CpG island methylation, and gene copy number in breast cancer cells by deep sequencing.
We used deep sequencing technology to profile the transcriptome, gene copy number, and CpG island methylation status simultaneously in eight commonly used breast cell lines to develop a model for how these genomic features are integrated in estrogen receptor positive (ER+) and negative breast cancer. Total mRNA sequence, gene copy number, and genomic CpG island methylation were carried out using the Illumina Genome Analyzer. Sequences were mapped to the human genome to obtain digitized gene expression data, DNA copy number in reference to the non-tumor cell line (MCF10A), and methylation status of 21,570 CpG islands to identify differentially expressed genes that were correlated with methylation or copy number changes. These were evaluated in a dataset from 129 primary breast tumors. Gene expression in cell lines was dominated by ER-associated genes. ER+ and ER- cell lines formed two distinct, stable clusters, and 1,873 genes were differentially expressed in the two groups. Part of chromosome 8 was deleted in all ER- cells and part of chromosome 17 amplified in all ER+ cells. These loci encoded 30 genes that were overexpressed in ER+ cells; 9 of these genes were overexpressed in ER+ tumors. We identified 149 differentially expressed genes that exhibited differential methylation of one or more CpG islands within 5 kb of the 5' end of the gene and for which mRNA abundance was inversely correlated with CpG island methylation status. In primary tumors we identified 84 genes that appear to be robust components of the methylation signature that we identified in ER+ cell lines. Our analyses reveal a global pattern of differential CpG island methylation that contributes to the transcriptome landscape of ER+ and ER- breast cancer cells and tumors. The role of gene amplification/deletion appears to more modest, although several potentially significant genes appear to be regulated by copy number aberrations.


Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function.
Lymphangioleiomyomatosis (LAM) is a rare low-grade metastasising disease characterised by cystic lung destruction. The genetic basis of LAM remains incompletely determined, and the disease cell-of-origin is uncertain. We analysed the possibility of a shared genetic basis between LAM and cancer, and LAM and pulmonary function. The results of genome-wide association studies of LAM, 17 cancer types and spirometry measures (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and peak expiratory flow (PEF)) were analysed for genetic correlations, shared genetic variants and causality. Genomic and transcriptomic data were examined, and immunodetection assays were performed to evaluate pleiotropic genes. There were no significant overall genetic correlations between LAM and cancer, but LAM correlated negatively with FVC and PEF, and a trend in the same direction was observed for FEV1. 22 shared genetic variants were uncovered between LAM and pulmonary function, while seven shared variants were identified between LAM and cancer. The LAM-pulmonary function shared genetics identified four pleiotropic genes previously recognised in LAM single-cell transcriptomes: ADAM12, BNC2, NR2F2 and SP5. We had previously associated NR2F2 variants with LAM, and we identified its functional partner NR3C1 as another pleotropic factor. NR3C1 expression was confirmed in LAM lung lesions. Another candidate pleiotropic factor, CNTN2, was found more abundant in plasma of LAM patients than that of healthy women. This study suggests the existence of a common genetic aetiology between LAM and pulmonary function.


Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity.
Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately -24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype.


Fabrication of a mechanically anisotropic poly(glycerol sebacate) membrane for tissue engineering.
Poly(glycerol sebacate) (PGS) has been used successfully as a scaffolding material for soft tissue engineering. PGS scaffolds, however, are usually mechanically isotropic, which may restrict their use in tissue repairs as many soft tissues in the body have anisotropic mechanical behaviors. Although various methods have been used to fabricate anisotropic scaffolds, it remains challenging to make anisotropic scaffolds from thermoset PGS. Here a new, simple method to fabricate an anisotropic PGS membrane which can then be used to construct thicker three-dimensional anisotropic scaffolds was developed. First, an aligned sacrificial poly(vinyl alcohol) fibrous membrane was prepared by electrospinning. The fibrous membrane was then partially immersed in PGS prepolymer solution, resulting in a composite membrane upon drying. After curing, the sacrificial fibers within the membrane were removed by water, supposedly leaving aligned cylindrical pores in the membrane. Both SEM and AFM illustrated aligned grooves on the surface of the resultant PGS membrane, indicating the successful removal of sacrificial fibers. The PGS membrane was validated to be mechanically anisotropic using uniaxial tensile testing along and perpendicular to the predominant pore direction. The in vitro cytocompatibility of the PGS membrane was confirmed. As a demonstration of its potential application in vascular tissue engineering, a tubular scaffold was constructed by wrapping a stack of two axisymmetric pieces of the anisotropic PGS membranes on a mandrel. The compliance of the scaffold was found to depend on the pitch angle of its double helical structure, imitating the anisotropic mechanical behavior of the arterial media. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 760-770, 2018.


[Organic features of mast cells cytochemistry in rats].
The mast cells from small intestine mesentery, brain membrane, skin, uterus, wide uterical ligament, ovaries and peritoneal fluid were studied in rats by hystochemical and immunocytochemical technique. Constitutional and inducible NO-synthase, Ca2+-ATPase, cytochromoxidase, and biogenic amines (histamine, dopamine, serotonin) were revealed in mast xells, localized in different tissues. A great number of mast cells with positive cytochromoxidase reaction was presented in skin, intestine mesentery and peritoneal fluid, while the amount of must cells containing biogenic amines was found to be greater in the organs with a significant deal of Ca2+-ATPase and NO-synthase-active cells. The number of degranulating mast cells was lower in the organs with a lack of such cells (skin, wide uterical ligament).


Analysing Domain Shift Factors between Videos and Images for Object Detection.
Object detection is one of the most important challenges in computer vision. Object detectors are usually trained on bounding-boxes from still images. Recently, video has been used as an alternative source of data. Yet, for a given test domain (image or video), the performance of the detector depends on the domain it was trained on. In this paper, we examine the reasons behind this performance gap. We define and evaluate different domain shift factors: spatial location accuracy, appearance diversity, image quality and aspect distribution. We examine the impact of these factors by comparing performance before and after factoring them out. The results show that all four factors affect the performance of the detectors and their combined effect explains nearly the whole performance gap.


Switching reciprocity on and off in a magneto-optical x-ray scattering experiment using nuclear resonance of α-(57)Fe foils.
Reciprocity is when the scattering amplitude of wave propagation satisfies a symmetry property, connecting a scattering process with an appropriate reversed one. We report on an experiment using nuclear resonance scattering of synchrotron radiation, which demonstrates that magneto-optical materials do not necessarily violate reciprocity. The setting enables us to switch easily between reciprocity and its violation. In the latter case, the exhibited reciprocity violation is orders of magnitude larger than achieved by previous wave scattering experiments.


Fundamental factors determining the nature of parasite aggregation in hosts.
The distribution of parasites in hosts is typically aggregated: a few hosts harbour many parasites, while the remainder of hosts are virtually parasite free. The origin of this almost universal pattern is central to our understanding of host-parasite interactions; it affects many facets of their ecology and evolution. Despite this, the standard statistical framework used to characterize parasite aggregation does not describe the processes generating such a pattern. In this work, we have developed a mathematical framework for the distribution of parasites in hosts, starting from a simple statistical description in terms of two fundamental processes: the exposure of hosts to parasites and the infection success of parasites. This description allows the level of aggregation of parasites in hosts to be related to the random variation in these two processes and to true host heterogeneity. We show that random variation can generate an aggregated distribution and that the common view, that encounters and success are two equivalent filters, applies to the average parasite burden under neutral assumptions but it does not apply to the variance of the parasite burden, and it is not true when heterogeneity between hosts is incorporated in the model. We find that aggregation decreases linearly with the number of encounters, but it depends non-linearly on parasite success. We also find additional terms in the variance of the parasite burden which contribute to the actual level of aggregation in specific biological systems. We have derived the formal expressions of these contributions, and these provide new opportunities to analyse empirical data and tackle the complexity of the origin of aggregation in various host-parasite associations.


Synthesis and biological evaluation of (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: a novel series of PPAR gamma agonists.
A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and biologically evaluated. (S)-2-Benzyl-7-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (10, KY-021) was identified as a novel peroxisome proliferators-activated receptor (PPAR) gamma agonist, which showed potent activity in human PPAR gamma (EC50=11.8 nM). KY-021 reduced plasma glucose and triglyceride levels at 3 mg/kg/d for 7 d in male KK-Ay mice. KY-021 also decreased plasma triglyceride levels at 0.3-3 mg/kg/d for 6 d, and improved oral glucose tolerance at 1 and 3 mg/kg/d for 7 d in male Zucker fatty rats. Maximal plasma concentration of KY-021 after oral administration at 10 mg/kg was 6.6 microg/ml and 2.1 microg/ml in male ICR mice and male SD rats, respectively. Repeated oral administration of KY-021 at 30 mg/kg/d for 10 weeks had little toxicity in male SD rats. These results demonstrated that KY-021 has great potential as an efficacious and safe drug for diabetes.


Influence of needle type on the incidence of intravascular injection during transforaminal epidural injections: a comparison of short-bevel and long-bevel needles.
Vascular penetration and injection of corticosteroids into a vessel during lumbosacral transforaminal epidural injection is a suspected cause of myelopathy. Blunt needles have been suggested to avoid vascular penetration, but they are difficult to navigate. Another alternative to the standard long-bevel sharp needles is the short-bevel needles. Some have postulated that short-bevel needles are the best option for high-risk spine injections because they maintain navigation characteristics while potentially reducing the risk of complications. To date, no studies have been performed to either confirm or refute this. The purpose of this study was to determine if there is a difference in the incidence of vascular penetration during lumbosacral transforaminal epidural injections between short-bevel and long-bevel needles. This is a prospective, observational, in vivo study. The sample comprises patients receiving lumbosacral transforaminal epidural injections at a university-based outpatient spine center. The outcome measure was the incidence of vascular contrast patterns observed under live fluoroscopy. One interventional spine physician recorded contrast patterns observed during 158 fluoroscopically guided lumbosacral transforaminal epidural injections under live fluoroscopy using two different types of needle tips. Vascular injections were observed in 22 of the 158 injections, for an overall incidence of 13.9%. The incidence of vascular injections in the short-bevel group was 15.6% (10/64) and in the long-bevel group was 12.8% (12/94). This difference was not statistically significant (p=.6447). A secondary analysis was performed to determine if the needle gauge influenced the incidence of vascular injections, and again, there were no statistical differences in the overall rates of vascular injection. In comparison with long-bevel needles, short-bevel needles do not reduce the risk of inadvertent vascular injection in lumbosacral transforaminal epidural injections.


A systematic review of the effects of nuts on blood lipid profiles in humans.
The inverse association of nut consumption and risk markers of coronary heart disease (lipids) has sparked the interest of the scientific and lay community. The objective of this study was to conduct a systematic review to investigate the effects of nuts on the lipid profile. Medline and Web of Science databases were searched from the start of the database to August 2004 and supplemented by cross-checking reference lists of relevant publications. Human intervention trials with the objective of investigating independent effects of nuts on lipid concentrations were included. From the literature search, 415 publications were screened and 23 studies were included. These papers received a rating based upon the methodology as it appeared in the publication. No formal statistical analysis was performed due to the large differences in study designs of the dietary intervention trials. The results of 3 almond (50-100 g/d), 2 peanut (35-68 g/d), 1 pecan nut (72 g/d), and 4 walnut (40-84 g/d) studies showed decreases in total cholesterol between 2 and 16% and LDL cholesterol between 2 and 19% compared with subjects consuming control diets. Consumption of macadamia nuts (50-100 g/d) produced less convincing results. In conclusion, consumption of approximately 50-100 g (approximately 1.5-3.5 servings) of nuts > or = 5 times/wk as part of a heart-healthy diet with total fat content (high in mono- and/or polyunsaturated fatty acids) of approximately 35% of energy may significantly decrease total cholesterol and LDL cholesterol in normo- and hyperlipidemic individuals.


High value and low-cost virtual reality healthcare professional education: proceedings of a roundtable workshop.
This article was migrated. The article was marked as recommended. Introduction The following represents proceedings of an online roundtable workshop on high value and low-cost virtual reality healthcare professional education. The purpose of the workshop was to seek the views of professionals from different sectors and different countries on moving toward high value and low-cost virtual reality education. The workshop was comprised of eight delegates with an interest in this subject. The delegates were from Europe, the Middle East, and Australia. They represented different sectors - including clinical medicine, educational economics, health professional education, simulation, technology, evidence-based methodologies, and industry. Themes The following themes emerged from the workshop: the challenge of thinking about the cost of virtual reality from the points of view of the payer and the user; the core need to define the context of use of virtual reality; the absolute need to define the purpose of a virtual reality programme; the recognition of the growing opportunity of multiplayer virtual reality; the need to exploit the unique properties of virtual reality; the importance of realising that there are already various forms of virtual reality available and these can achieve different outcomes at different costs; the need to integrate virtual reality into the rest of the curriculum; and the various forms of cost analysis that might be suitable for evaluating the cost and outcomes of virtual reality. Conclusions In the long-term, a growing body of evidence that is based on original research and systematic reviews will help us decide what is high value and low-cost virtual reality in healthcare professional education. However, a strategic approach is needed to ensure that the original research concentrates on the right topics that will yield the most value to education decision-makers and to other related stakeholders. We feel that non-hierarchical interdisciplinary roundtable discussions are an effective means of planning strategy.


Coronary Microvascular Disease Assessed by 82-Rubidium Positron Emission Tomography Myocardial Perfusion Imaging Is Associated With Small Vessel Disease of the Kidney and Brain.
Background Coronary microvascular disease (CMD) may be part of a systemic small vessel disease that also manifests as neurological impairment and kidney disease. However, clinical evidence supporting a potential link is scarce. We assessed whether CMD is associated with an increased risk of small vessel disease in the kidney and brain. Methods and Results A retrospective multicenter (n=3) study of patients clinically referred to 82-rubidium positron emission tomography myocardial perfusion imaging was conducted between January 2018 and August 2020. Exclusion criterion was reversible perfusion defects >5%. CMD was defined as myocardial flow reserve (MFR) ≤2. The primary outcome, microvascular event, was defined by hospital contact for chronic kidney disease, stroke, or dementia. Among 5122 patients, 51.7% were men, median age 69.0 [interquartile range, 60.0-75.0] years, 11.0% had left ventricular ejection fraction ≤40%, and 32.4% had MFR ≤2. MFR was associated with baseline estimated glomerular filtration rate after multivariable adjustment (β=0.04 [95% CI, 0.03-0.05]; P<0.001). During a median follow-up of 3.05 years, 383 (7.5%) patients suffered an event (253 cerebral and 130 renal), more frequently in patients with MFR ≤2 versus MFR >2 (11.6% versus 5.5%, P<0.001). MFR ≤2 was associated to outcome with a hazard ratio (HR) of 2.30 (95% CI, 1.88-2.81, P<0.001) and an adjusted HR of 1.62 (95% CI, 1.32-2.00, P<0.001). Results were consistent across subgroups defined by presence of irreversible perfusion defects, estimated glomerular filtration rate, diabetes, left ventricular ejection fraction, and previous revascularization. Conclusions This is the first large-scale cohort study to link CMD to microvascular events in the kidney and brain. Data support the hypothesis that CMD is part of a systemic vascular disorder.


Sequential Serum Metabolomic Profiling after Radiofrequency Ablation of Hepatocellular Carcinoma Reveals Different Response Patterns According to Etiology.
Radiofrequency ablation (RFA) is commonly performed as a curative approach in patients with hepatocellular carcinoma (HCC); however, the risk of tumor recurrence is difficult to predict due to a lack of reliable clinical and biological markers, and identification of new biomarkers poses a major challenge for improving prognoses. Metabolomics is a promising technique that may lead to the identification and characterization of new disease fingerprints. The objective of the present study was to explore, preoperatively and at various time points post-RFA, the metabolic profile of serum samples from HCC patients to identify factors associated with treatment response and recurrence. Sequential sera obtained before and after RFA procedures for 120 patients with HCC due to cirrhosis were investigated using nuclear magnetic resonance metabolomics. A multilevel orthogonal projection to latent structure analysis was used to discriminate intraindividual metabolic changes in response to RFA treatment. Recurrence-free survival differed depending on the underlying cause of cirrhosis. The statistical model showed significant differences depending on whether the liver disease had a viral or nonviral etiology before RFA intervention (explained variance of R(2)Y = 0.89 and predictability of Q(2)Y = 0.34). These profiles were also associated with specific and distinct metabolic responses after RFA.


The effect of glycerol supplements on aerobic and anaerobic performance of athletes and sedentary subjects.
The purpose of this study was to evaluate the effect of glycerol supplementation on aerobic and anaerobic exercise performance in sedentary subjects and athletes. The glycerol supplement treatments were as follows: 40 volunteers were selected and divided into two groups, sedentary and exercise groups. These two groups were further subdivided into two groups. The first group, the placebo (S), only consumed water; the second group (GS) consumed glycerol followed by water. Neither of these groups did any exercise for 20 days. The third and fourth groups consisted of the exercise group subjects; they were required to perform a 20-m shuttle run test every day for 20 days. The third group's subjects, the placebo (E), only consumed water. The last group (GE) consumed glycerol followed by water. The Astrand Cycle Ergometer Test (ACET) was performed, and the Cosmed K4b(2) portable gas analysis system was used to determine the aerobic capacity, while the Wingate Anaerobic Power Test (WAPT) was performed to determine the level of anaerobic power. The 20 Meter Shuttle Run Test (20MSRT) was performed after glycerol supplementation throughout the 20 days, and the exercise periods and distances were recorded. The glycerol supplement was found to have an increasing effect on aerobic and anaerobic performance in GS, E and GE. A similar effect was found for the covered distances and time in the same groups. However, an adverse effect was found on body weight.


Effect of solution chemistry and operating conditions on the nanofiltration of acid dyes by a nanocomposite membrane.
A composite nanofiltration membrane was developed by a poly(acrylic acid) in situ ultraviolet (UV) graft polymerization process using an ultrafiltration polysulfone membrane as a porous support, by a phase inversion method. SEM images showed that the PSf membranes had numerous finger-like pores. Atomic force microscopy (AFM) showed that the roughness of the surface was reduced by an increase in UV irradiation times. The rejections of sodium chloride and sodium sulfate were moderate and declined with the increase of concentration. We observed that by increasing UV irradiation time and nanofiltration pressure applied, retention of dyes was enhanced and in the most irradiated membrane (M-4 membrane) at 4 bars, color removal with a high rejection of about 99.80% was achieved. It was found that the separation efficiency of dyes in the mixture of salt and dyes decreased with the salt concentration due to a decrease in the Donnan effect. It was also found that by varying the pH, the membrane surface and the dyes' charges are changed, which meant that the membrane surface and dyes had different interactions at various pHs.


Perceived threat to paternity reduces likelihood of paternal provisioning in house wrens.
Biparental care is a critical and, occasionally, unequally shared obligation that ensures that young survive to maturity. Such care may be complicated in systems in which one parent, typically the male, is unsure of his genetic relatedness to the young. Males may reduce paternal provisioning when full paternity is not assured, as occurs in mating systems in which females engage in extrapair copulations. Moreover, other factors independent of extrapair matings, such as male personality traits, likely also affect the level of paternal care. In this study, we determined the effect of a paternity threat event (i.e., a conspecific or a heterospecific territory intrusion) and male personality (i.e., the level of aggressiveness) on provisioning effort by male house wrens (Troglodytes aedon). Males were more likely to attack a conspecific intruder than a heterospecific intruder. Males that were exposed to a conspecific intruder were less likely to provision young at all. Of those males that did feed the young in their nest, male aggressiveness did not relate to feeding effort. These findings suggest that the likelihood of paternal care is reduced by perceived threats to paternity but that the costs of not feeding potentially multisired young are high and feeding efforts are unrelated to male personality.


Structured variability of steady-speed locomotion in rats.
By examining key locomotor parameters during terrestrial locomotion on a substrate without irregularities, we show that rats frequently accelerate and decelerate between two consecutive steps while maintaining an overall steady speed and that the touchdown order of contralateral limbs significantly influences those speed adjustments. The latter highly correlates with significant adjustments in relative forelimb protraction at touchdown and hindlimb extension at lift-off. We conclude that this remarkable level of variability in limb coordination would clearly be advantageous for the functional flexibility needed during terrestrial locomotion on much more irregular (rough) natural terrain. In addition, its occurrence on a substrate lacking irregularities suggests that much of stable, terrestrial steady-speed locomotion in rats is mechanically controlled.


Niclosamide suppresses renal cell carcinoma by inhibiting Wnt/β-catenin and inducing mitochondrial dysfunctions.
To investigate the effects of anthelminthic drug niclosamide in renal cell carcinoma (RCC) and the underlying mechanisms of its action. The effects of niclosamide on the proliferation and apoptosis of RCC cells were examined in vitro and in vivo by using MTS, colony formation assay, flow cytometry and xenograft cancer mouse model. Mechanism studies were performed by analyzing Wnt/β-catenin signaling and mitochondrial functions in a panel of RCC cell lines. We show that niclosamide effectively targets two RCC cell lines through inhibiting proliferation and anchorage-independent colony formation, and inducing apoptosis. It also enhances the inhibitory effects of chemotherapeutic drug cisplatin in two independent in vivo RCC xenograft mouse models. Mechanistically, niclosamide decreases β-catenin levels and therefore suppresses Wnt/β-catenin activities. Overexpression of β-catenin partially reverses the inhibitory effects of niclosamide in RCC cells, demonstrating that besides β-catenin, other mechanisms are involved in niclosamide's anti-cancer activity. Indeed, we further show that niclosamide induces mitochondrial dysfunctions as shown by the decreased level of mitochondrial membrane potential and respiration, resulting in decreased ATP levels and increased reactive oxygen species (ROS) levels. Our findings support the inhibitory effects of niclosamide in cancer and provide better understanding on its underlying mechanism. Our data suggests that niclosamide is a useful addition to the treatment armamentarium for RCC.


"Like fighting a fire with a water pistol": A qualitative study of the work experiences of critical care nurses during the COVID-19 pandemic.
To understand the experience of critical care nurses during the COVID-19 pandemic, through the application of the Job-Demand-Resource model of occupational stress. Qualitative interview study. Twenty-eight critical care nurses (CCN) working in ICU in the UK NHS during the COVID-19 pandemic took part in semi-structured interviews between May 2021 and May 2022. Interviews were guided by the constructs of the Job-Demand Resource model. Data were analysed using framework analysis. The most difficult job demands were the pace and amount, complexity, physical and emotional effort of their work. Prolonged high demands led to CCN experiencing emotional and physical exhaustion, burnout, post-traumatic stress symptoms and impaired sleep. Support from colleagues and supervisors was a core job resource. Sustained demands and impaired physical and psychological well-being had negative organizational consequences with CCN expressing increased intention to leave their role. The combination of high demands and reduced resources had negative impacts on the psychological well-being of nurses which is translating into increased consideration of leaving their profession. The full impacts of the pandemic on the mental health of CCN are unlikely to resolve without appropriate interventions. Managers of healthcare systems should use these findings to inform: (i) the structure and organization of critical care workplaces so that they support staff to be well, and (ii) supportive interventions for staff who are carrying significant psychological distress as a result of working during and after the pandemic. These changes are required to improve staff recruitment and retention. We used the COREQ guidelines for reporting qualitative studies. Six CCN provided input to survey content and interview schedule. Two authors and members of the study team (T.S. and S.C.) worked in critical care during the pandemic.


Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease.
The amyloid-beta protein (Abeta) is strongly implicated in the pathogenesis of Alzheimer's disease. The final step in the production of Abeta from the amyloid precursor protein (APP) is proteolysis by the unidentified gamma-secretases. This cleavage event is unusual in that it apparently occurs within the transmembrane region of the substrate. Studies with substrate-based inhibitors together with molecular modeling and mutagenesis of the gamma-secretase cleavage site of APP suggest that gamma-secretases are aspartyl proteases that catalyze a novel intramembranous proteolysis. This proteolysis requires the presenilins, proteins with eight transmembrane domains that are mutated in most cases of autosomal dominant familial Alzheimer's disease. Two conserved transmembrane aspartates in presenilins are essential for gamma-secretase activity, suggesting that presenilins themselves are gamma-secretases. Moreover, presenilins also mediate the apparently intramembranous cleavage of the Notch receptor, an event critical for Notch signaling and embryonic development. Thus, if presenilins are gamma-secretases, then they are also likely the proteases that cleave Notch within its transmembrane domain. Another protease, S2P, involved in the processing of the sterol regulatory element binding protein, is also a multipass integral membrane protein which cleaves within or very close to the transmembrane region of its substrate. Thus, presenilins and S2P appear to be members of a new type of polytopic protease with an intramembranous active site.


Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury.
Advanced glycation end products (AGEs) are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation. The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis. Recent studies in basic and translational research have revealed the contributing roles of AGEs in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer. Excessive chronic and/or acute binge consumption of alcohol (ethanol), a widely consumed addictive substance, is known to cause more than 200 diseases, including alcohol use disorder (addiction), alcoholic liver disease, and brain damage. However, despite the considerable amount of research in this area, the underlying molecular mechanisms by which alcohol abuse causes cellular toxicity and organ damage remain to be further characterized. In this review, we first briefly describe the properties of AGEs: their formation, accumulation, and receptor interactions. We then focus on the causative functions of AGEs that impact various aging-related diseases. We also highlight the biological connection of AGE-alcohol-adduct formations to alcohol-mediated tissue injury. Finally, we describe the potential translational research opportunities for treatment of various AGE- and/or alcohol-related adduct-associated disorders according to the mechanistic insights presented.


Tailored porous silicon microparticles: fabrication and properties.
The use of mesoporous silicon particles for drug delivery has been widely explored thanks to their biodegradability and biocompatibility. The ability to tailor the physicochemical properties of porous silicon at the micro- and nanoscale confers versatility to this material. A method for the fabrication of highly reproducible, monodisperse, mesoporous silicon particles with controlled physical characteristics through electrochemical etching of patterned silicon trenches is presented. The particle size is tailored in the micrometer range and pore size in the nanometer range, the shape from tubular to discoidal to hemispherical, and the porosity from 46 to over 80%. In addition, the properties of the porous matrix are correlated with the loading of model nanoparticles (quantum dots) and their three-dimensional arrangement within the matrix is observed by transmission electron microscopy tomography. The methods developed in this study provide effective means to fabricate mesoporous silicon particles according to the principles of rational design for therapeutic vectors and to characterize the distribution of nanoparticles within the porous matrix.


The skeletal muscle VEGF mRNA response to acute exercise in patients with chronic heart failure.
In seven patients with chronic heart failure (CHF) and six controls, we examined (a) resting and post-exercise muscle vascular endothelial growth factor (VEGF) mRNA levels and (b) their relationship with muscle structure and function. Muscle biopsies were taken after 30 min of single-leg knee-extensor exercise at 50% of maximum work rate (50% WR(max)) from both the exercised and rested legs. Muscle blood flow (.Q) and O(2) uptake .VO(2) were measured during exercise. Resting VEGF mRNA levels were not different between patients and controls and both groups upregulated VEGF mRNA equally in response to acute exercise. Patients had lower .Q, .VO(2), and mitochondrial density but similar capillarity and fiber area. These findings reveal a normal basal level of muscle VEGF mRNA, its appropriate upregulation in response to acute exercise and, despite increased vascular resistance during exercise, a normal skeletal muscle vascular structure in patients with CHF.


Analysis of 5-hydroxytryptamine 2c receptor gene promoter variants as alcohol-dependence risk factors.
To examine whether polymorphic variants of the HTR2C gene are associated with diagnosis of alcohol dependence. We compared allele frequencies of five HTR2C promoter polymorphisms in a Nordic population of alcohol dependent individuals (Males: n = 309; Females: n = 127) and ethnically matched controls (Males: n = 83; Females: n = 190) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively. Patients were further subtyped into Type I (late onset) and Type II (early onset) alcoholics. None of the individual polymorphisms indicated significant association with alcohol dependence. A common promoter haplotype (GAGG) exhibited different distribution frequencies between males and females (Type I), however on Bonferroni's multiple-testing correction, this observation proved to be insignificant. Although we report a lack of association between alcohol dependence and five common promoter polymorphisms, and the constituted haplotypes, the analysis tends to indicate gender and sub-type differences. We suggest that a follow up study with larger sample numbers should be performed to improve the power to detect the genetic influences of HTR2C in alcohol dependence.


Evaluation of the effect of bruxism on mandibular cortical bone using radiomorphometric indices on panoramic radiographs.
This prospective study was designed to evaluate the effects of bruxism on mandibular cortical bone using radiomorphometric indices on digital panoramic radiographs. The mandibular cortical index (MCI), mental index (MI), and panoramic mandibular index (PMI) were measured on digital panoramic radiographs and evaluated for 128 bruxers (66 female, 60 male) and 128 control subjects. The data were analyzed statistically using intraclass correlation coefficients (ICC), Kappa statistics, Chi-square test, Kolmogorov-Smirnov test, independent t-test, and Pearson's correlation analysis. There was no difference between the groups in terms of MCI type (P > 0.05). While mean MI values were significantly higher in bruxers than the control group (P = 0.007), the difference between groups in mean PMI values was nonsignificant (P > 0.05). In both groups, the C1 type was more prevalent in females than in males (P = 0.001). Females showed significantly lower mean MI values than males in both groups (P ≤ 0.040). However, the difference between genders in mean PMI values was not significant (P > 0.05). MI measurements may be useful when radiomorphometric indices are to be used for the diagnosis or follow-up of bruxism in the mandible. Among radiomorphometric indices, MI and MCI values are affected by gender differences.


Over-expression of ascorbate oxidase in the apoplast of transgenic tobacco results in altered ascorbate and glutathione redox states and increased sensitivity to ozone.
Transgenic tobacco ( Nicotiana tabacum L. cv. Xanthi) plants expressing cucumber ascorbate oxidase (EC.126.96.36.199) were used to examine the role of extracellular ascorbic acid in mediating tolerance to the ubiquitous air pollutant, ozone (O(3)). Three homozygous transgenic lines, chosen on the basis of a preliminary screen of AO activity in the leaves of 29 lines, revealed up to a 380-fold increase in AO activity, with expression predominantly associated with leaf cell walls. Over-expression of AO resulted in no change in the total ascorbate content recovered in apoplast washing fluid, but the redox state of ascorbate was reduced from 30% in wild-type leaves to below the threshold for detection in transgenic plants. Levels of ascorbic acid and glutathione in the symplast were not affected by AO over-expression, but the redox state of ascorbate was reduced, while that of glutathione was increased. AO over-expressing plants exposed to 100 nmol mol(-1) ozone for 7 h day(-1) exhibited a substantial increase in foliar injury, and a greater pollutant-induced reduction in both the light-saturated rate of CO(2) assimilation and the maximum in vivo rate of ribulose-1,5-bisphosphate carboxylase/oxygenase carboxylation, compared with wild-type plants. Transgenic plants also exhibited a greater decline in CO(2) assimilation rate when exposed to a brief ozone episode (300 nmol mol(-1) for 8 h). Stomatal conductance, hence O(3) uptake, was unaffected by AO over-expression. Our findings illustrate the important role played by ascorbate redox state and sub-cellular compartmentation in mediating the tolerance of plants to ozone-induced oxidative stress.


Group I allergens of grass pollen as cell wall-loosening agents.
Group I allergens are the major allergens of grass pollen, but their biological function is unknown. These proteins are shown here to be structurally related to expansins, which are able to induce extension (creep) of plant cell walls. Extracts of maize pollen possess potent expansin-like activity, as measured in wall extension and wall stress-relaxation assays. This activity is selective for grass cell walls and is, at least partly, due to the action of maize group I allergens. We propose that group I allergens facilitate invasion of the pollen tube into the maternal tissues by loosening the cell walls of the grass stigma and style. Additionally, the presence of related mRNAs in vegetative tissues of rice, Arabidopsis, and soybean implies that allergen homologs may function to loosen walls in growing vegetative tissues as well.


Subunit influenza vaccine and its testing in clinical immunology.
Subunit adsorbed chemical influenza vaccine [ACI] was tested in subcutaneous administration by the needleless and syringe methods. A weak reactogenicity and a high immunogenic activity of the ACI vaccine was demonstrated after a single administration by the needleless and syringe methods [73.0---75.0% of seroconversions with a geometric mean of the titre of 1:91.0---1:169.0 and a relative increase in antibody titre of 8.1---14.9]. Revaccination increased the mentioned indices to 75.0---86.0%, 1:128.0---1:181.0 and 11.3---16.0, respectively. A many-sided comparison of three preparations [ACI vaccine, "Vaxgrip" and "Mutagripe"] permitted to reveal a number of advantages in the Soviet vaccine. However, all the three preparations ensured an expressed protection against influenza virus.


Dynamic Mg2 B8 Cluster: A Nanoscale Compass.
Boron-based binary cluster Mg2 B8 is shown to adopt a compass-like structure via computational global searches, featuring an Mg2 dimer as the needle and a disk-shaped B8 molecular wheel as baseplate. The nanocompass has a diameter of 0.35 nm. Born-Oppenheimer molecular dynamics simulations indicate that Mg2 B8 is structurally fluxional with the needle rotating freely on the baseplate, analogous to a functioning compass. The dynamics is readily initiated via a ultrasoft vibrational mode. The rotational barrier is only 0.1 kcal mol-1 at the single-point CCSD(T) level. Chemical bonding analysis suggests that the cluster compass can be formulated as [Mg2 ]2+ [B8 ]2- ; that is, the baseplate and the needle are held together primarily through ionic interactions. The baseplate is doubly aromatic with π and σ sextets. The bonding pattern provides a dilute, continuous, and delocalized electron cloud, which underlies the dynamics of the nanocompass.


Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats.
The pathophysiology of erectile dysfunction post radical prostatectomy is not clearly clarified, and the low efficacy of traditional PDE5i treatment remains a major complaint in contemporary practice. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, and subsequently validate gene therapy with Myocardin (Mycod) by maintaining a contractile phenotype in corpus cavernosum smooth muscle cells. Initially, 36 male rats were randomly divided into BCNI and negative control (NC) groups for histological and phenotypic molecular measurements at 3, 5, and 7 days. Afterwards, an additional 30 rats received a single intra-cavernous injection of 50 μL PBS, Ad-Myocd (1 × 1011 pfu/ml) or Ad-vector for 10 animals each, namely the NC+PBS, BCNI+Ad-Myocd, and BCNI+Ad-vector groups. Finally, the validity and mechanism of Myocd transfection was explored at 21 days in vivo and 48 h in vitro. Western blotting showed canonical declines in Myocd, α-SMA, and Calponin expression, as well as elevated Osteopontin (OPN) expression, before corporeal morphological and SM-to-collagen ratio changes at day 5 after injury. Overexpression of Myocd maintained the contractile phenotype of corpus cavernosum smooth muscle cells, ameliorated bilateral cavernous nerve injury rat erectile dysfunction, as well as promoted cell contractility and suppressed proliferative capacity. Simultaneously, confocal imaging revealed up-regulation and co-localization of serum response factor in gene-transferred cells. In conclusion, our study is the first to investigate corpus cavernosum smooth muscle cells phenotypes in the early stages of cavernous injury model rats, and Myocd reversed phenotypic modulation by activating serum response factor. The experimental results demonstrated the validity of gene therapy for erectile dysfunction.


Poly(N-isopropylacrylamide-co-acrylamide) cross-linked thermoresponsive microspheres obtained from preformed polymers: Influence of the physico-chemical characteristics of drugs on their release profiles.
Poly(N-isopropylacrylamide-co-acrylamide) copolymer was synthesized as an interesting thermoresponsive material possessing a phase transition temperature of around 36 degrees C in phosphate buffer, pH 7.4 (PB); the concentration was 10%, w/v. The copolymer maintains a sharp phase transition at a relatively high percentage of acrylamide. The lower critical solution temperature (LCST) of the copolymer is influenced by the concentration of copolymer solution in PB. The copolymer was transformed in thermoresponsive microspheres by chemical cross-linking of amide groups with glutaraldehyde. The key factors for the successful preparation of microspheres are the use of a concentrated polymer solution, a temperature (38 degrees C) that is high enough but lower than LCST, and a long reaction time (48h). The microspheres were characterized by optical and scanning electron microscopy, swelling/deswelling kinetics, swelling degree, and PB retention at different temperatures. Finally, the influence of hydrophilicity/hydrophobicity and the molecular weight of the drugs (propranolol, lidocaine, vitamin B(12)) on their release profile from thermoresponsive microspheres were examined. Above LCST the hydrogel matrix is in the dehydrated state and hydrophobic interactions between the hydrophobic drugs and the polymer occur, modulating the release rate of the drugs. For hydrophilic drugs, the release rate is modulated mainly by the steric interaction between the drug molecule and the matrix.


US Adults' Perceptions, Beliefs, and Behaviors towards Plant-Rich Dietary Patterns and Practices: International Food Information Council Food and Health Survey Insights, 2012-2022.
Expert groups recommend that populations adopt dietary patterns higher in whole, plant-based foods and lower in red and processed meat as a high-impact climate action. Yet, there is limited understanding of populations' willingness to adopt plant-rich dietary patterns. This study examined United States (US) adults' perceptions, beliefs, and behaviors towards plant-rich dietary patterns and practices over a decade. Fifteen questions from the International Food Information Council's Food and Health Surveys (2012-2022) were analyzed across four sustainability domains (i.e., human health, environmental, social, and economic domains). Most respondents had favorable perceptions of environmentally sustainable food and beverages, but sustainability influenced less than half of consumers' purchase decisions. Plant-rich dietary pattern adherence increased across survey years (12.1% [2019] to 25.8% [2022], p < 0.001). One-quarter (28.1%) of Americans reported reducing their red meat intake over 12 months (2020-2022). Yet, another 15.5% reported greater red meat intake, and 18.8% reported greater plant-based meat alternative (PBMA) intake over 12 months. The percentage of respondents who reported greater red meat and PBMA consumption in the previous 12 months significantly increased across the years surveyed (2020-2022, p < 0.05). IFIC Survey findings highlight growing US consumer awareness of health, environmental, and social sustainability but low adoption of plant-rich dietary patterns and practices. Government leadership and coordinated actions by health professionals, civil society, and businesses are needed to educate and incentivize Americans to adopt plant-rich dietary behaviors, and greater industry transparency is needed to show how food and beverage products support human and planetary health.


A Scottish cost analysis of interceptive orthodontics for thumb sucking habits.
There is a potential cost saving to be made within the NHS by providing simple interceptive treatment rather than comprehensive treatment at a later date. The focus of this study is to determine the size of this potential cost by looking at the cost to NHS Tayside for the provision of interceptive treatment for cessation of thumb sucking and where this has been unsuccessful (or not provided) the costs of correction of the associated malocclusion. A cost analysis is described, investigating the costs of treatment solely to the NHS, both in the primary and secondary setting. Three potential treatment pathways are identified with the costs calculated for each pathway. The actual cost of providing this treatment in NHS Tayside, and the potential cost saving in Tayside if there was a change in clinical practice are calculated. Both discounting of costs and a sensitivity analysis are performed. The cost to NHS Tayside of current practice was calculated to be between £123,710 and £124,930 per annum. Change in practice to replace use of a removable with a fixed habit breaker for the interceptive treatment of thumb sucking reduced the calculated cost to between £99,581 and £105,017. A saving could be made to the NHS, both locally and nationally, if the provision of a removable habit breaker was changed to a fixed habit breaker. In addition, increasing the proportion receiving active treatment, in the form of a fixed habit breaker, rather than monitoring, would appear to further reduce the cost to the NHS considerably.


L-ascorbic acid biosynthesis in higher plants from L-gulono-1, 4-lactone and L-galactono-1, 4-lactone.
Detached bean (Phaseolus vulgaris) and strawberry (Fragaria) fruits fed l-gulono-1,4-lactone or l-galactono-1,4-lactone convert this compound, in part, to l-ascorbic acid. When l-galactono-1,4-lactone is given as a 0.25% solution to detached bean shoots, the ascorbic acid content is tripled in less than 10 hours. l-Gulono-1,4-lactone is only 5 to 10% as effective as its epimer. Experiments with specifically labeled l-gulono-1,4-lactone and l-galactono-1,4-lactone prove that conversion is direct. Ascorbic acid is labeled at the same carbon as its precursor.A method is described for preparation of l-galactono-1,4-lactone-2-(14)C from myo-inositol-2-(14)C. This method can be extended to the preparation of l-ascorbic acid-2-(14)C on the basis of results obtained in the present study.


Do reactive oxygen species or does oxygen itself confer obligate anaerobiosis? The case of Bacteroides thetaiotaomicron.
Bacteroides thetaiotaomicron was examined to determine whether its obligate anaerobiosis is imposed by endogenous reactive oxygen species or by molecular oxygen itself. Previous analyses established that aerated B. thetaiotaomicron loses some enzyme activities due to a high rate of endogenous superoxide formation. However, the present study establishes that another key step in central metabolism is poisoned by molecular oxygen itself. Pyruvate dissimilation was shown to depend upon two enzymes, pyruvate:formate lyase (PFL) and pyruvate:ferredoxin oxidoreductase (PFOR), that lose activity upon aeration. PFL is a glycyl-radical enzyme whose vulnerability to oxygen is already understood. The rate of PFOR damage was unaffected by the level of superoxide or peroxide, showing that molecular oxygen itself is the culprit. The cell cannot repair PFOR, which amplifies the impact of damage. The rates of PFOR and fumarase inactivation are similar, suggesting that superoxide dismutase is calibrated so the oxygen- and superoxide-sensitive enzymes are equally sensitive to aeration. The physiological purpose of PFL and PFOR is to degrade pyruvate without disrupting the redox balance, and they do so using catalytic mechanisms that are intrinsically vulnerable to oxygen. In this way, the anaerobic excellence and oxygen sensitivity of B. thetaiotaomicron are two sides of the same coin.


Comparing memory skill maintenance across the life span: preservation in adults, increase in children.
The authors examined life-span differences in the maintenance of skilled episodic memory performance by assessing 100 individuals (10 -11, 12-13, 21-26, and 66-79 years old) 11 months after termination of an intensive multisession mnemonic training program (Y. Brehmer, S.-C. Li, V. Müller, T. von Oertzen, & U. Lindenberger, 2007). Skill maintenance was tested in 2 follow-up sessions, the first without and the second with mnemonic reinstruction. Younger and older adults' average performance levels were stable across time. In contrast, both younger and older children's memory performance improved beyond originally attained levels. Older adults' performance improved from the first to the second follow-up session, presumably profiting from instruction-induced skill reactivation. Results suggest that (a) skill maintenance is largely intact in healthy older adults, (b) older adults need environmental support to fully reactivate their former skill levels (cf. F. I. M. Craik, 1983), and (c) children adapt a skill learned 11 months ago to their increasing cognitive capabilities.


[Study of protective activity of Streptococcus pneumoniae protein-containing antigen complex in homologous system].
Study protective activity of S. pneumoniae protein-containing antigen complex obtained from T3No.3 strain against infection by homologous pneumococcus strain. S. pneumoniae T3No.3 (serotype 3) strain obtained from collection of pneumococcus strains of Mechnikov Research Institute of Vaccines and Sera was used in the study. S. pneumoniae protein-containing antigen complex was isolated by precipitation by 2 volumes of acetone of supernatant fraction of cultural medium used for pneumococcus cultivation. Molecular mass of proteins contained in S. pneumoniae antigen complex was determined by SDS electrophoresis in polyacrylamide gel. Protective activity of S. pneumoniae protein-containing antigen complex was studied in BALB/c line mice active protection experiments. Activity of mice immune sera obtained against whole-cell pneumococcus culture (T3No.3 strain) was determined in vitro by solid phase indirect EIA. The data obtained give evidence that the isolated protein-containing antigen complex from S. pneumoniae T3No.3 strain effectively protects mice from consequent infection by a homologous S. pneumoniae strain. S. pneumoniae protein-containing antigen complex sorbed on solid phase at 5 microg dose was established by using EIA to interact with homologous mice immune sera. The results of the carried out studies allow to move to studies of cross-activity of S. pneumoniae protein-containing antigen complex isolated from T3No.3 strain.


[Hemoglobin affinity for oxygen and the reaction of the gas-transport system in rats with acute anemia].
A population of Wistar rats was studied for a few years. The findings revealed a considerable variability of the hemoglobin affinity to oxygen: P50 (oxygen tension at hemoglobin satiation with oxygen for 50 per cent). Two groups of the rats were studied: with P50 = 31.9 +/- 1.0 mm Hg and P50 = 42.3 +/- 1.1 mm Hg. The 2nd group rats (with reduced affinity of hemoglobin to oxygen), in acute profound anemia, revealed an enhanced resistance of gas exchange against anemia, an augmented response of the circulation minute volume, a less obvious metabolic acidosis and a lesser degree of the brain tissue hypoxia.


The Impact of Antithrombin Deficiency on Women's Reproductive Health Experiences and Healthcare Decision-Making.
Women with inherited antithrombin (AT) deficiency are at high risk for venous thromboembolism (VTE), especially during times of estrogen exposure, but little is known about patient-oriented reproductive decision-making in this population. Provider-administered survey of women with AT deficiency. Participants were asked to discuss their diagnosis of AT deficiency and questioned about (1) contraception, (2) pregnancies, and (3) menorrhagia, and the impact of their AT deficiency on each reproductive health experience. Of 31 women with inherited AT deficiency, 18 (58%) were surveyed, 8 (26%) were unreachable, and 5 (16%) were deceased. Twelve (67%) had a VTE, including two which occurred during pregnancy and five during oral contraceptive (OCP) use. Women reported using OCPs, intrauterine device (IUD), and condoms for contraception. Of five women diagnosed with AT deficiency while taking OCPs, three switched to an IUD, one to condoms, and one used no alternative method. Eighteen women reported 42 total pregnancies, with 33 (79%) resulting in live term birth, 3 (7%) in live preterm birth, and 6 (14%) in spontaneous abortion at a median of 12 weeks. Four (22%) women reported the use of anticoagulation during pregnancy. Eleven (61%) women reported menorrhagia and 4 (36%), while on anticoagulation for VTE events. Ten of 18 women (56%) reported that the diagnosis of AT had affected their reproductive health in some way. Women with AT deficiency require careful multidisciplinary management to avoid complications in the setting of contraception and pregnancy. AT deficiency impacts women's reproductive health experiences and patient-oriented reproductive decision-making is key.


WRF-Chem modeling of particulate matter in the Yangtze River Delta region: Source apportionment and its sensitivity to emission changes.
China has been troubled by high concentrations of fine particulate matter (PM2.5) for many years. Up to now, the pollutant sources are not yet fully understood and the control approach still remains highly uncertain. In this study, four month-long (January, April, July and October in 2015) WRF-Chem simulations with different sensitivity experiments were conducted in the Yangtze River Delta (YRD) region of eastern China. The simulated results were compared with abundant meteorological and air quality observations at 138 stations in 26 YRD cities. Our model well captured magnitudes and variations of the observed PM2.5, with the normal mean biases (NMB) less than ±20% for 19 out of the 26 YRD cities. A series of sensitivity simulations were conducted to quantify the contributions from individual source sectors and from different regions to the PM2.5 in the YRD region. The calculated results show that YRD local source contributed 64% of the regional PM2.5 concentration, while outside transport contributed the rest 36%. Among the local sources, industry activity was the most significant sector in spring (25%), summer (36%) and fall (33%), while residential source was more important in winter (38%). We further conducted scenario simulations to explore the potential impacts of varying degrees of emission controls on PM2.5 reduction. The result demonstrated that regional cooperative control could effectively reduce the PM2.5 level. The proportionate emission controls of 10%, 20%, 30%, 40% and 50% could reduce the regional mean PM2.5 concentrations by 10%, 19%, 28%, 37% and 46%, respectively, and for places with higher ambient concentrations, the mitigation efficiency was more significant. Our study on source apportionment and emission controls can provide useful information on further mitigation actions.


Dementia, Comorbidity, and Physical Function in the Program of All-Inclusive Care for the Elderly.
Participants in the Program of All-Inclusive Care for the Elderly (PACE) are a unique clinical population of medically complex and highly disabled older adults who qualify for nursing home level care but receive services in the community. A main goal of PACE programs is to prevent further declines in physical function that may necessitate costly institutionalization. This study evaluates how multimorbidity and dementia impact both self-selected gait speed and Timed Up and Go (TUG) in this population. This study was a cross-sectional design. Sociodemographic information, physical function, comorbidity data, and dementia status on 525 PACE participants were extracted from a quality improvement database. Separate univariable and multivariable linear regression models were used to evaluate the impact of comorbidity status and dementia on gait speed and TUG time. PACE participants overall have a high degree of functional disability, with an average gait speed of 0.66 m/s, an average Short Physical Performance Battery score of 6.0/12, and an average TUG time of nearly 20 s. In the univariable analysis, a higher number of comorbidities and a diagnosis of dementia were associated with greater limitation for gait speed and TUG time. After adjusting for age, sex, strength, and balance, each additional comorbidity was independently associated with 0.015 m/s slower gait speed, as well as a 3.5% increase in TUG time for PACE participants with dementia. Ambulatory PACE participants have average levels of physical function that are dangerously close to thresholds thought to indicate vulnerability for further disability development, hospitalization, and nursing home admission. Both dementia and comorbidity burden are associated with declines in physical function, and the interaction between these risk factors is a telling indicator to functional decline in higher-level ambulatory tasks. PACE program clinicians can use this information to better identify participants at risk for limited physical function. Further research should investigate consequences of functional decline and determine optimal intervention strategies for PACE participants with functional impairments.


Detection and quantification of Phytophthora ramorum, P. kernoviae, P. citricola and P. quercina in symptomatic leaves by multiplex real-time PCR.
SUMMARY New species of Phytophthora such as Phytophthora ramorum, P. kernoviae and P. quercina together with P. citricola are plant pathogens which impact on forest health, natural ecosystem stability and international trade. A real-time multiplex PCR approach based on TaqMan PCR was developed to simultaneously identify and detect these four Phytophthora species. Specific primers and probes labelled with FAM (P. ramorum), Yakima Yellow (P. kernoviae), Rox (P. citricola) and Cy5 (P. quercina) were designed in different regions of the ras-related protein (Ypt1) gene. A new set of Black Hole Quenchers (BHQ), which dissipate energy as heat rather than fluorescence, were utilized. The method proved to be highly specific in tests with target DNA from 72 Phytophthora isolates (35 species). For all pathogens, the detection limit was 100 fg of target DNA and was not improved utilizing a nested approach to provide a first round of amplification with Phytophthora spp.-specific primers. Cycle threshold (Ct) values were linearly correlated with the concentration of the target DNA (correlation coefficients ranged from 0.947 to 0.996) and were not affected by the presence of plant extracts, indicating the appropriateness of the method for qualitative and quantitative analyses. Two universal primers and a TaqMan probe were also developed to evaluate the quality and quantity of extracted DNA and to avoid false negatives. The reliability of the entire procedure was assessed using both artificially and naturally infected leaves of a range of plant species. The method, combined with a rapid procedure for DNA extraction, proved to be rapid, reliable, sensitive and cost effective as multiple pathogens were detected within the same plant extract by using different primer/probe combinations.


Changes in diet quality during a 12 month weight loss randomised controlled trial.
Reductions in energy intake are seen in weight loss trials, but whether this occurs with improvements to diet quality (DQ) is less established. The aim of this study was to evaluate changes in diet quality in a sample of volunteers in a weight loss trial. This was a secondary analysis of dietary data from a lifestyle intervention trial (the HealthTrack study) which advised on dietary guidelines. The trial ran for 12 months with three treatment groups: control (general advice C), intervention (individualised advice, I), and intervention plus a supplement of walnuts (IW). Both the published a priori diet quality score (APDQS, maximum score 164) and a study specific Diet Quality Tracker (DQT, maximum score 44) indicated compliance to dietary advice. DQ scores calculated at 0, 3months and 12months were evaluated using two-way RMANOVA, one-way ANOVA and one-way RMANOVA. Changes in intakes of food groups and nutrients were analysed using Kruskal-Wallis and Friedman's tests. There were no differences between groups at baseline, but at 3months IW recorded higher DQ scores (APDQS:96 ± 10; DQT:22 ± 5, P < 1 × 10-3 for both) compared to I (APDQS:91 ± 13, P < 1 × 10-3; DQT:21 ± 4, P < 1 × 10-2) and C (APDQS:87 ± 12, P < 5 × 10-2; DQT:19 ± 4, P > 5 × 10-2), and a higher consumption of nuts at 3 months (P < 1 × 10-3), and 12months (P < 1 × 10-2). All groups reported decreased intakes of discretionary foods/beverages assessed by the DQT (P < 1 × 10-3 for IW and I; P < 1 × 10-2 for C). The APDQS showed this as reduced intakes of grain based desserts (P < 1 × 10-3 at 3 and 12months), and salty snacks at 12months (P < 1 × 10-3 for IW and I; P < 5 × 10-2 for C). Intakes of monounsaturated and saturated fatty acids were lowest, and polyunsaturated fatty acids highest for IW (P < 1 × 10-3), resulting in a higher dietary polyunsaturated:saturated fat ratio (P < 1 × 10-3). Lifestyle intervention addressing dietary guidelines can lead to significant reductions in consumption of discretionary foods and saturated fat, but individualised advice may have a greater impact on improving overall DQ regardless of DQI used. Providing a healthy food supplement may help assure higher DQ and where the food is walnuts, produce commensurate differences in dietary fatty acid profiles. ANZCTRN 12614000581662. Date of registration: 30th May 2014.


Chronic posttraumatic stress disorder and family functioning of Vietnam veterans and their partners.
This study examines the association between posttraumatic stress disorder (PTSD), in terms of the three main symptom clusters (intrusion, avoidance and arousal), and the self-report of family functioning of Vietnam veterans and the self-report of family functioning of their partners. A second objective was to determine if depression, anger and alcohol abuse mediated between PTSD symptoms and family functioning. Vietnam veterans and their partners completed a series of questionnaires as part of their participation in the inpatient and outpatient PTSD treatment program, in the Veterans Psychiatry Unit, at the Austin and Repatriation Hospital. Data from 270 veterans and partners were used in the final analyses. The PTSD subscales were initially correlated with family functioning for veterans and family functioning for partners. Then two path diagrams were constructed and analyzed using the statistical program AMOS to test for mediating effects between PTSD symptoms and family functioning. For veterans there were significant initial correlations with all three subscales of the PTSD measure. In the path analysis when the mediating variables were included only the avoidance subscale of the PTSD measure remained directly associated with family functioning. The arousal PTSD subscale was mediated by anger. The measures of depression and anger were significantly associated with poor family functioning and the anger and the avoidance subscales were significantly associated with depression. In the second set of analyses conducted on data from partners, the PTSD symptoms of avoidance and arousal were initially correlated with family functioning. When the test for mediation was conducted none of the PTSD subscales remained associated with partners' self-report of family functioning. Posttraumatic stress disorder arousal and alcohol abuse were mediated by anger for partners' self-report of family functioning. Posttraumatic stress disorder symptoms of avoidance for veterans, and comorbid symptoms of anger and depression for veterans, and anger on its own for partners appear to be important in the self-report of family functioning. These findings suggest that veterans and their partners have similar difficulties as couples with distressed relationships in the community.


Variation in bone mineral density in adults in Poland: age and sex differences.
The decline of mineral bone density with age can lead in more extreme cases to osteopenia and osteoporosis, and is therefore one of the aspects of ageing with great medical and social significance. With this idea in mind a study of age changes in the trabecular and, separately, the cortical bone density of the radius was carried out in 1218 females and 405 males, aged 22 to 60 years, all occupationally active inhabitants of the city of Wroclaw, Poland. The technique used was the peripheral Quantitative Computed Tomography (pQCT). It was found that in females bone densities remain relatively stable throughout the period between 22 and 40 years. They then begin to decline slowly, with a rapid decline after the age of 55. A distinctly different pattern was found among males, with bone densities reaching peak values, markedly higher than those in females, in the third decade of life. After this age the bone density values begin to decline at a rapid rate, so that by the age of 60 years mean trabecular and cortical densities in males have decreased to levels almost equivalent to females of equal age. In view of the small size of the male samples, especially in the older age classes, the above results should be treated with caution and confirmed using larger samples.


Postnatal development of Na(+)-K(+)-2Cl(-) co-transporter 1 and K(+)-Cl(-) co-transporter 2 immunoreactivity in multiple brain stem respiratory nuclei of the rat.
Previously, we reported that in rats, GABA(A) and glycine receptor immunoreactivity increased markedly in multiple brain stem respiratory nuclei around postnatal days (P) 12-13, a critical period when abrupt neurochemical, metabolic, ventilatory, and electrophysiological changes occur in the respiratory network and when the system is under greater inhibition than excitation. Since Na(+)-K(+)-2Cl(-) co-transporter 1 (NKCC1) and K(+)-Cl(-) co-transporter 2 (KCC2) play pivotal roles in determining the responses of GABA(A) and glycine receptors, we hypothesized that NKCC1 and KCC2 undergo significant changes during the critical period. An in-depth immunohistochemical and single neuron optical densitometric study of neurons in seven respiratory-related nuclei (the pre-Bötzinger complex [PBC], nucleus ambiguus [Amb], hypoglossal nucleus [XII], ventrolateral subnucleus of solitary tract nucleus [NTS(VL)], retrotrapezoid nucleus/parafacial respiratory group [retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG)], dorsal motor nucleus of the vagus nerve [dorsal motor nucleus of the vagus nerve (DMNX)], and inferior olivary nucleus [IO]) and a non-respiratory cuneate nucleus (CN, an internal control) was undertaken in P0-P21 rats. Our data revealed that (1) NKCC1 immunoreactivity exhibited a developmental decrease from P0 to P21 in all eight nuclei examined, being relatively high during the first 1½ postnatal weeks and decreased thereafter. The decrease was abrupt and statistically significant at P12 in the PBC, Amb, and XII; (2) KCC2 immunoreactivity in these eight nuclei showed a developmental increase from P0 to P21; and (3) the significant reduction in NKCC1 and the greater dominance of KCC2 around P12 in multiple respiratory nuclei of the brain stem may form the basis of an enhanced inhibition in the respiratory network during the critical period before the system stabilizes to a more mature state.


Analysis of gene families encoding acidic and basic beta-1,3-glucanases of tobacco.
Healthy tobacco plants accumulate beta-1,3-glucanases (glucan endo-1,3-beta-glucosidase; EC 188.8.131.52) in their roots and in specific parts of the flowers. After infection with tobacco mosaic virus, acidic and basic beta-1,3-glucanases are induced in the inoculated and virus-free leaves of the plant. An analysis of cDNA clones demonstrated that at least five genes for acidic beta-1,3-glucanases are induced after tobacco mosaic virus infection. Southern blot analysis indicated that the tobacco genome contains approximately eight genes for acidic beta-1,3-glucanases and a smaller number of genes encoding basic beta-1,3-glucanases. Genes from both gene families were cloned and sequenced. The basic isozymes contain a C-terminal extension that is cleaved off during their targeting to the vacuoles. This extension is absent in the acidic isozymes, which accumulate extracellularly. Northern blot hybridization showed that genes encoding acidic and basic beta-1,3-glucanases are strongly induced after tobacco mosaic virus infection or salicylate treatment of tobacco. The cloning of these genes is a first step toward the identification of regulatory elements involved in their coordinate induction.


Monocytic suppressive cells mediate cardiovascular transplantation tolerance in mice.
One of the main unresolved questions in solid organ transplantation is how to establish indefinite graft survival that is free from long-term treatment with immunosuppressive drugs and chronic rejection (i.e., the establishment of tolerance). The failure to achieve this goal may be related to the difficulty in identifying the phenotype and function of the cell subsets that participate in the induction of tolerance. To address this issue, we investigated the suppressive roles of recipient myeloid cells that may be manipulated to induce tolerance to transplanted hearts in mice. Using depleting mAbs, clodronate-loaded liposomes, and transgenic mice specific for depletion of CD11c+, CD11b+, or CD115+ cells, we identified a tolerogenic role for CD11b+CD115+Gr1+ monocytes during the induction of tolerance by costimulatory blockade with CD40L-specific mAb. Early after transplantation, Gr1+ monocytes migrated from the bone marrow into the transplanted organ, where they prevented the initiation of adaptive immune responses that lead to allograft rejection and participated in the development of Tregs. Our results suggest that mobilization of bone marrow CD11b+CD115+Gr1+ monocytes under sterile inflammatory conditions mediates the induction of indefinite allograft survival. We propose that manipulating the common bone marrow monocyte progenitor could be a useful clinical therapeutic approach for inducing transplantation tolerance.


Synthetic myosin filaments.
A stable preparation of myosin filaments was formed in a medium at pH 8.0. The filament length varied from 0.2 to 0.5 micron. Most of the material sedimented at 21S, but there was a minor peak (due to monomer) at 6.8S. The filaments did not taper and had large bulbous irregularities at the ends.


Silencing of the baculovirus Op-iap3 gene by RNA interference reveals that it is required for prevention of apoptosis during Orgyia pseudotsugata M nucleopolyhedrovirus infection of Ld652Y cells.
The Op-iap3 gene from the baculovirus Orgyia pseudotsugata M nucleopolyhedrovirus (OpMNPV) inhibits apoptosis induced by a mutant of Autographa californica MNPV (AcMNPV) that lacks the antiapoptotic gene p35, as well as apoptosis induced by a wide range of other stimuli in both mammalian and insect cells. However, the role of Op-iap3 during OpMNPV infection has not been previously examined. To determine the function of the Op-IAP3 protein during OpMNPV infection, we used RNA interference (RNAi) to silence Op-iap3 expression during OpMNPV infection of Ld652Y cells. Infected cells treated with Op-iap3 double-stranded RNA (dsRNA) did not accumulate detectable Op-iap3 mRNA, confirming that the Op-iap3 gene was effectively silenced. Op-IAP3 protein was found to be a component of the budded virion; however, in OpMNPV-infected cells treated with Op-iap3 dsRNA, the Op-IAP3 protein that was introduced by the inoculum virus decreased to almost undetectable levels by 12 h after dsRNA addition. Apoptosis was observed in infected cells treated with Op-iap3 dsRNA beginning at 12 h, and by 48 h, almost all of the cells had undergone apoptosis. These results show for the first time that Op-IAP3 is necessary to prevent apoptosis during OpMNPV infection. In addition, our results demonstrate that the RNAi technique can be an effective tool for studying baculovirus gene function.


Survival nomogram for curatively resected Korean gastric cancer patients: multicenter retrospective analysis with external validation.
A small number of nomograms have been previously developed to predict the individual survival of patients who undergo curative resection for gastric cancer. However, all were derived from single high-volume centers. The aim of this study was to develop and validate a nomogram for gastric cancer patients using a multicenter database. We reviewed the clinicopathological and survival data of 2012 patients who underwent curative resection for gastric cancer between 2001 and 2006 at eight centers. Among these centers, six institutions were randomly assigned to the development set, and the other two centers were assigned to the validation set. Multivariate analysis using the Cox proportional hazard regression model was performed, and discrimination and calibration were evaluated by external validation. Multivariate analyses revealed that age, tumor size, lymphovascular invasion, depth of invasion, and metastatic lymph nodes were significant prognostic factors for overall survival. In the external validation, the concordance index was 0.831 (95% confidence interval, 0.784-0.878), and Hosmer-Lemeshow chi-square statistic was 3.92 (P = 0.917). We developed and validated a nomogram to predict 5-year overall survival after curative resection for gastric cancer based on a multicenter database. This nomogram can be broadly applied even in general hospitals and is useful for counseling patients, and scheduling follow-up.