Potential effectiveness of traditional Chinese medicine for cardiac syndrome X (CSX): a systematic review and meta-analysis.
Treatment of cardiac syndrome X with unknown pathological mechanism remains a big challenge for clinicians. Complementary and alternative medicine may bring a new choice for its management. The aim of this study is to evaluate the clinical effects of traditional Chinese medicine on cardiac syndrome X patients. We systematically searched databases such as Cochrane CENTRAL, PubMed, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), WanFang and VIP, and handsearched relevant journals to identify randomized controlled trials. Following the steps of systematic review recommended by the Cochrane group, we assessed the quality of included studies, extracted valid data and undertook meta-analysis. Twenty one moderate-to low-quality randomized controlled trials involving 1143 patients were included. The results showed that traditional Chinese medicine could improve angina [OR=1.34, 95% CI: 1.2 to 1.50], electrocardiogram (ECG), endothelin-1 (ET-1) levels, prolong exercise duration in treadmill tests, and reduce angina frequency per week compared with routine treatment. No other side effect was reported except two cases of stomach pain. Compared with conventional treatment, traditional Chinese medicine shows the potential of optimizing symptomatic outcomes and improving ECG and exercise duration. The efficacy of TCM may find explanation in its pharmacological activity of adjusting the endothelial function. TCM, as a kind of alternative and complementary medicine, may provide another choice for CSX patients.


Expression and association of vascular endothelial growth factor, vascular endothelial growth factor receptor, and phosphorylated signal transducer and activator of transcription factor 3 in malignant gliomas.
Angiogenesis is one of the main characteristic features of malignant gliomas. Phosphorylated signal transducer and activator of transcription factor 3 (pSTAT3) is not only involved in glioma cell proliferation, anti-apoptosis, and immunosuppression but also plays a key role in cell migration and invasion. Constitutively, activated pSTAT3 induces expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR, leading to endothelial cell proliferation and abnormal microvascular formation causing peritumoral edema (PTE). PTE is one of the significant contributors to mortality in malignant gliomas. Therefore, understanding the molecular mechanism involved in the evolution of gliomas is necessary. This study was to assess the level of expression of pSTAT3, VEGF, and VEGFR in malignant gliomas and analyze the extent of PTE and the extent of expression of one or more of these markers. This study included 84 patients categorized as per the World Health Organization classification of central nervous system tumors into grade IV, III, and II gliomas to investigate the expression of pSTAT3, VEGF, and VEGFR by immunohistochemistry. Furthermore, the presence or absence of PTE was determined using magnetic resonance imaging/computed tomography scans in these patients. The association between the markers (pSTAT3, VEGFR, and VEGF) and the extent of PTE in these patients was statistically significant (P < 0.05). The pSTAT3, VEGF-R, and VEGF signaling pathways could contribute to peritumoral edema and might be a regulatory mechanism during PTE formation during tumorigenesis and progression.


Toward a systems-level understanding of gene regulatory, protein interaction, and metabolic networks in cyanobacteria.
Cyanobacteria are essential primary producers in marine ecosystems, playing an important role in both carbon and nitrogen cycles. In the last decade, various genome sequencing and metagenomic projects have generated large amounts of genetic data for cyanobacteria. This wealth of data provides researchers with a new basis for the study of molecular adaptation, ecology and evolution of cyanobacteria, as well as for developing biotechnological applications. It also facilitates the use of multiplex techniques, i.e., expression profiling by high-throughput technologies such as microarrays, RNA-seq, and proteomics. However, exploration and analysis of these data is challenging, and often requires advanced computational methods. Also, they need to be integrated into our existing framework of knowledge to use them to draw reliable biological conclusions. Here, systems biology provides important tools. Especially, the construction and analysis of molecular networks has emerged as a powerful systems-level framework, with which to integrate such data, and to better understand biological relevant processes in these organisms. In this review, we provide an overview of the advances and experimental approaches undertaken using multiplex data from genomic, transcriptomic, proteomic, and metabolomic studies in cyanobacteria. Furthermore, we summarize currently available web-based tools dedicated to cyanobacteria, i.e., CyanoBase, CyanoEXpress, ProPortal, Cyanorak, CyanoBIKE, and CINPER. Finally, we present a case study for the freshwater model cyanobacteria, Synechocystis sp. PCC6803, to show the power of meta-analysis, and the potential to extrapolate acquired knowledge to the ecologically important marine cyanobacteria genus, Prochlorococcus.


Insulin receptor kinase activity in muscles and white adipose tissue during course of VMH obesity.
Early after lesion of the ventromedial hypothalamus nuclei (VMH), insulin-induced glucose utilization is increased in white adipose tissue (WAT), whereas oxidative and glycolytic muscles are, respectively, normoresponsive or resistant to insulin. Five weeks later, all of the muscles are resistant, whereas WAT returns to normal responsiveness. The aim of this study was to characterize the insulin receptor kinase activity in WAT and muscles 1 and 6 wk after lesion. The number and affinity of insulin receptors were not modified in any of the tissues studied. Autophosphorylation and phosphorylation of an exogenous substrate were similar in oxidative and glycolytic muscles of VMH and control rats both 1 and 6 wk after the lesion. Insulin receptors from WAT of 1-wk VMH rats exhibited a 2.5-fold increase in insulin-stimulated autophosphorylation and phosphorylation. Six weeks after the lesion, both autophosphorylation and phosphorylation returned to normal values. This suggests that insulin receptor tyrosine kinase activity does not play a significant role in the insulin resistance of skeletal muscles but has a crucial role in mediating the variations of insulin action on WAT observed during the development of VMH obesity.


Site-specific spin trapping of tyrosine radicals in the oxidation of metmyoglobin by hydrogen peroxide.
The reaction between metmyoglobin and hydrogen peroxide produces both a ferryl-oxo heme and a globin-centred radical(s) from the two oxidizing equivalents of the hydrogen peroxide. Evidence has been presented for localization of the globin-centred radical on one tryptophan residue and tyrosines 103 and 151. When the spin-trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO) is included in the reaction mixture, a radical adduct has been detected, but the residue at which that adduct is formed has not been determined. Replacement of either tryptophans 7 and 14 or tyrosines 146 and 151 with phenylalanine has no effect on the formation of DMPO adduct in the reaction with hydrogen peroxide. When tyrosine 103 is replaced with phenylalanine, however, only DMPOX, a product of the oxidation of the spin-trap, is detected. Tyrosine-103 is, therefore, the site of radical adduct formation with DMPO. The spin trap 2-methyl-2-nitrosopropane (MNP), however, forms radical adducts with any recombinant sperm whale metmyoglobin that contains either tyrosine 103 or 151. Detailed spectral analysis of the DMPO and MNP radical adducts of isotopically substituted tyrosine radical yield complete structural determinations. The multiple sites of trapping support a model in which the unpaired electron density is spread over a number of residues in the population of metmyoglobin molecules, at least some of which are in equilibrium with each other.


The reforming states group and the promotion of federalism.
Since 1991, leaders in health policy from the legislative and executive branches of state government have come together, with financial support and staff collaboration from the Milbank Memorial Fund, to share their experiences and to work on practical solutions to pressing health care problems. What began with a handful of states at the forefront of health reform is now the Reforming States Group (RSG), a bipartisan, voluntary association that includes leaders from over 40 states. This article describes the origins, history, and future prospects of the RSG.


Effect of ionizing radiation on thymic epithelial cell function. I. Radiation-spared thymic epithelial grafts expedite the recovery of T cell function in lethally irradiated and fetal liver reconstituted mice.
A murine model system was developed to determine whether ionizing radiation has a detrimental influence on thymic epithelium, cell function. Normal mice were lethally irradiated, grafted intracamerally with normal fetal thymic epithelium, and then reconstituted with fetal liver cells. These animals were compared with a group of animals who received their thymic grafts before the irradiation protocol. Analysis of the reconstitution of T cell function in peripheral lymph nodes and spleens at various times post transplantation demonstrated that animals with radiation-spared thymic grafts had superior proliferative responses to T cell mitogens and alloantigens. It was also determined that the capacity of these animals to elicit contact hypersensitivity responses was significantly greater when compared with animals whose thymic grafts had been radiated. The observed difference in T cell function could not be ascribed to a difference in the rate of export of mature T cells from the thymic grafts since the absolute number of Thy-1+, L3T4+, or Lyt-2+ lymphocytes present in the peripheral lymphoid compartment of our two groups of animals was equivalent. Immunohistologic analysis of the thymic grafts demonstrated a marked reduction in the medullary compartment of the repopulated grafts that had been exposed to ionizing radiation. The results of this study suggest: 1) that irradiation of the thymic microenvironment during marrow ablative preparative regimens may be in part responsible for some of the immune alterations observed in marrow transplant recipients, and 2) that our model system may provide a valuable tool for delineating the roles played by medullary and cortical epithelial cells of the thymus on the T cell maturation and education processes.


A silica sol-gel design strategy for nanostructured metallic materials.
Batteries, fuel cells and solar cells, among many other high-current-density devices, could benefit from the precise meso- to macroscopic structure control afforded by the silica sol-gel process. The porous materials made by silica sol-gel chemistry are typically insulators, however, which has restricted their application. Here we present a simple, yet highly versatile silica sol-gel process built around a multifunctional sol-gel precursor that is derived from the following: amino acids, hydroxy acids or peptides; a silicon alkoxide; and a metal acetate. This approach allows a wide range of biological functionalities and metals--including noble metals--to be combined into a library of sol-gel materials with a high degree of control over composition and structure. We demonstrate that the sol-gel process based on these precursors is compatible with block-copolymer self-assembly, colloidal crystal templating and the Stöber process. As a result of the exceptionally high metal content, these materials can be thermally processed to make porous nanocomposites with metallic percolation networks that have an electrical conductivity of over 1,000 S cm(-1). This improves the electrical conductivity of porous silica sol-gel nanocomposites by three orders of magnitude over existing approaches, opening applications to high-current-density devices.


Perceived Stress and Associated Factors Among Pregnant Women Attending Antenatal Care in Urban Thailand.
Perceived stress during pregnancy is associated with adverse obstetric outcomes. Antenatal perceived stress is still unaware and under-diagnosed during routine antenatal care. There has not yet been a study of prevalence and associated factors among pregnant women living in urban areas in Thailand. Understanding antenatal perceived stress is important to improve maternal and neonatal outcomes. To identify the prevalence, associated factors, and predictive factors of perceived stress in pregnant women living in an urban area. This cross-sectional study was conducted from December 1, 2019 to February 29, 2020 among pregnant women attending antenatal care at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital, Bangkok, Thailand. The participants were interviewed using a structured questionnaire which included demographic data, obstetric data, serious life event data, and a Thai language version of the 10-item Perceived Stress Scale (T-PSS-10) to assess perceived stress symptoms. Of a total 403 pregnant women, the prevalence of perceived stress symptoms in antenatal pregnant women was 23.6%. Perceived stress symptoms were significantly associated with divorce (p=0.001), separation from spouse (p=0.005), physical or psychological trauma from family (p=0.005), marital conflict (p<0.001), and family conflict (p<0.001). Results from multiple logistic regression found that significant predictive factors for perceived stress symptoms in pregnant women were marital conflict (AOR 3.10, 95% CI 1.74-5.52, p<0.001) and family conflict (AOR 3.24, 95% CI 1.59-6.60, p=0.001). This study demonstrated that the prevalence of perceived stress symptoms in pregnant women living in an urban area in Thailand was 23.6%. Perceived stress symptoms were significantly associated with divorce, separation from spouse, physical or psychological trauma from family, marital conflict, and family conflict. Predictive factors for perceived stress symptoms were marital conflict and family conflict.


Influence of CYP2D6 and CYP3A4 Phenotypes, Drug Interactions, and Vitamin D Status on Tamoxifen Biotransformation.
In view of the large variability on therapeutic response and the multiple factors associated to tamoxifen (TAM) metabolic activation, this study aimed to evaluate the effect of CYP2D6 and CYP3A4 phenotypes, drug interactions, and vitamin D exposure on TAM metabolism in a group of breast cancer patients. Trough blood samples were collected from 116 patients. TAM and metabolites endoxifen (EDF), N-desmethyltamoxifen, and 4-hydroxytamoxifen (HTF) were measured in plasma by liquid chromatography-tandem mass spectrometry. CYP2D6 and CYP3A4 phenotyping were obtained according to [dextromethorphan]/[dextrorphan] and [omeprazole]/[omeprazole sulfone] metabolic ratios, measured by high-performance liquid chromatography in plasma collected 3 hours after oral administration of 33 mg of dextromethorphan and 20 mg of omeprazole. Vitamin D3 was measured in plasma by high-performance liquid chromatography-ultraviolet. Data on concomitant use of drug considered as CYP2D6 and CYP3A4 inhibitor or inducer and vitamin D supplementation were recorded. About 20% of patients had reduced CYP2D6 metabolic activity and 7% CYP3A4 impaired metabolism. EDF levels diminished proportionally to the reduction of CYP2D6 metabolic activity (poor metabolizer 2.79 ng·mL, intermediate metabolizer (IM) 5.36 ng·mL, and extensive metabolizer 10.65 ng·mL, P < 0.01). Median plasma levels of TAM (161.50 ng·mL) and HTF (1.32 ng·mL) in CYP2D6 IM/CYP3A4 poor metabolizer patients were higher (P < 0.05) than those from CYP2D6 IM/CYP3A4 extensive metabolizer patients (122.07 ng·mL and 0.61 ng·mL, respectively). Seasons contributed to the interpatient variability of EDF and HTF levels; summer concentrations were 24% and 42% higher compared with winter. Vitamin D3 was not associated to CYP3A4 metabolic activity, indicating that other mechanisms might be involved in the relation between TAM metabolism and vitamin D exposure. CYP3A4 contributes to the bioactivation of TAM through formation of HTF and becomes increasingly important in case of reduced or absent CYP2D6 activity. EDF and HTF exposure were associated to seasonal variations, with considerable higher plasma concentrations during summer.


Longitudinal prediction of falls and near falls frequencies in Parkinson's disease: a prospective cohort study.
Several prediction models for falls/near falls in Parkinson's disease (PD) have been proposed. However, longitudinal predictors of frequency of falls/near falls are poorly investigated. Therefore, we aimed to identify short- and long-term predictors of the number of falls/near falls in PD. A prospective cohort of 58 persons with PD was assessed at baseline (mean age and PD duration, 65 and 3.2 years, respectively) and 3.5 years later. Potential predictors were history of falls and near falls, comfortable gait speed, freezing of gate, dyskinesia, retropulsion, tandem gait (TG), pain, and cognition (Mini-Mental State Exam, MMSE). After each assessment, the participants registered a number of falls/near falls during the following 6 months. Multivariate Poisson regression was used to identify short- and long-term predictors of a number of falls/near falls. Baseline median (q1-q3) motor (UPDRS) and MMSE scores were 10 (6.75-14) and 28.5 (27-29), respectively. History of falls was the only significant short-time predictor [incidence rate ratio (IRR), 15.17] for the number of falls/near falls during 6 months following baseline. Abnormal TG (IRR, 3.77) and lower MMSE scores (IRR, 1.17) were short-term predictors 3.5 years later. Abnormal TG (IRR, 7.79) and lower MMSE scores (IRR, 1.49) at baseline were long-term predictors of the number of falls/near falls 3.5 years later. Abnormal TG and MMSE scores predict the number of falls/near falls in short and long term, and may be indicative of disease progression. Our observations provide important additions to the evidence base for clinical fall prediction in PD.


Erythrocyte volume distribution in rainbow trout.
Reference mean corpuscular volume and volume heterogeneity values for erythrocytes of 23 rainbow trout were measured, using an electronic particle counter, and were analyzed, using a particle-size analyzer and microcomputer. The mean (+/- SD) erythrocyte count was 1.5 X 10(6) +/- 0.16 X 10(6) cells/microliter, the mean corpuscular volume was 346 +/- 25 fl, and the mean coefficient of variation of erythrocyte volumes was 29 +/- 2.3%. All erythrogram curves were skewed to the right, representing a mean of 15.6 +/- 3.5% of the total cells counted.


Progress in Polymeric Micelles as Viable Wagons for Brain Targeting.
Polymeric micelles have opened up new horizons for improving drug delivery to brain particularly due to their small size, long circulation time, good stability and targetability. They are used to treat a variety of brain conditions, including glioblastoma, migraine, Alzheimer's, Parkinson's, and other conditions linked to the brain. Micelles are currently underutilised in brain targeting despite having several benefits and spanning a wide variety of brain illnesses. Since most medications are unable to cross the blood brain barrier, scientists are continuously working to discover efficient solutions to the problems. The most pressing issue was thought to be the viability and difficulties of translating micelles into the therapeutic setting. This review describes the role of micellar delivery system in brain diseases treatment along with their route of administration and outcomes. The review also discusses the current state of patents and clinical trials in the relevant fields and their potential future applications.


Analyzing conformational dynamics of single P-glycoprotein transporters by Förster resonance energy transfer using hidden Markov models.
Single-molecule Förster resonance energy (smFRET) transfer has become a powerful tool for observing conformational dynamics of biological macromolecules. Analyzing smFRET time trajectories allows to identify the state transitions occuring on reaction pathways of molecular machines. Previously, we have developed a smFRET approach to monitor movements of the two nucleotide binding domains (NBDs) of P-glycoprotein (Pgp) during ATP hydrolysis driven drug transport in solution. One limitation of this initial work was that single-molecule photon bursts were analyzed by visual inspection with manual assignment of individual FRET levels. Here a fully automated analysis of Pgp smFRET data using hidden Markov models (HMM) for transitions up to 9 conformational states is applied. We propose new estimators for HMMs to integrate the information of fluctuating intensities in confocal smFRET measurements of freely diffusing lipid bilayer bound membrane proteins in solution. HMM analysis strongly supports that under conditions of steady state turnover, conformational states with short NBD distances and short dwell times are more populated compared to conditions without nucleotide or transport substrate present.


The Role of the Away Rotation in Otolaryngology Residency.
Objective To determine the availability and purpose of away rotations during otolaryngology residency. Study Design Cross-sectional survey. Setting Otolaryngology residency programs. Subjects and Methods An anonymous web-based survey was sent to 98 allopathic otolaryngology training program directors, of which 38 programs responded. Fisher exact tests and nonparametric correlations were used to determine statistically significant differences among various strata of programs. A P value of <.05 was considered statistically significant. Results Thirty-nine percent (n = 38) of queried programs responded. Mandatory away rotations and elective away rotations were both present in 6 of 38 programs (16%). Neither number of faculty ( P = .119) nor residents ( P = .88) was predictive of away rotation. Away rotations were typically >151 miles from the home institution and typically used to address deficiencies in clinical exposure (67%) or case volume (50%). Participants of mandatory away rotations were universally provided housing, with other consideration such as stipend (33%), relocation allowance (33%), or food allowance (16%) sometimes offered. In contrast to mandatory rotations, half of elective rotations were to obtain a unique international mission trip experience. Nearly one-third of surveyed program directors (29%) would consider adding an away rotation to their curriculum in the next 3 years. Conclusions Mandatory and elective away rotations play a role in a small, but not insignificant, number of training programs. The rationale for these rotations is variable. Given that nearly one-third of program directors would consider adding an away rotation in the near future, further research into components of a meaningful away rotation and how to optimize the away rotation experience is warranted.


[Enterocolic phlebitis. Description of a case and review of the literature].
To report about a case of enterocolic phlebitis, a rare cause of ischemic intestinal necrosis. The patient, a 71 year-old male, presented with signs of acute abdomen. A right hemicolectomy was performed, which revealed a tubulovillous adenoma with high grade dysplasia located in the ascending colon, and a diffuse ischemic colitis. A localized lymphocytic and granulomatous phlebitis was present in the resected colon. The arteries were spared by the inflammatory process. The patient is alive and well 7 years after surgery. The literature concerning enterocolic phlebitis, a peculiar form of localized intestinal vasculitis, is briefly summarized.


GDNF availability determines enteric neuron number by controlling precursor proliferation.
To clarify the role of Ret signaling components in enteric nervous system (ENS) development, we evaluated ENS anatomy and intestinal contractility in mice heterozygous for Ret, GFRalpha1 and Ret ligands. These analyses demonstrate that glial cell line-derived neurotrophic factor (GDNF) and neurturin are important for different aspects of ENS development. Neurturin is essential for maintaining the size of mature enteric neurons and the extent of neuronal projections, but does not influence enteric neuron number. GDNF availability determines enteric neuron number by controlling ENS precursor proliferation. However, we were unable to find evidence of programmed cell death in the wild type ENS by immunohistochemistry for activated caspase 3. In addition, enteric neuron number is normal in Bax(-/-) and Bid(-/-) mice, suggesting that, in contrast to most of the rest of the nervous system, programmed cell death is not important for determining enteric neuron numbers. Only mild reductions in neuron size and neuronal fiber counts occur in Ret(+/-) and Gfra1(+/-) mice. All of these heterozygous mice, however, have striking problems with intestinal contractility and neurotransmitter release, demonstrating that Ret signaling is critical for both ENS structure and function.


Changes in the Occurrence, Severity, and Distress of Symptoms in Patients With Gastrointestinal Cancers Receiving Chemotherapy.
Studies on multiple dimensions of the symptom experience of patients with gastrointestinal cancers are extremely limited. Purpose was to evaluate for changes over time in the occurrence, severity, and distress of seven common symptoms in these patients. Patients completed Memorial Symptom Assessment Scale, six times over two cycles of chemotherapy (CTX). Changes over time in occurrence, severity, and distress of pain, lack of energy, nausea, feeling drowsy, difficulty sleeping, and change in the way food tastes were evaluated using multilevel regression analyses. In the conditional models, effects of treatment group (i.e., with or without targeted therapy), age, number of metastatic sites, time from cancer diagnosis, number of prior cancer treatments, cancer diagnosis, and CTX regimen on enrollment levels, as well as the trajectories of symptom occurrence, severity, and distress were evaluated. Although the occurrence rates for pain, lack of energy, feeling drowsy, difficulty sleeping, and change in the way food tastes declined over the two cycles of CTX, nausea and numbness/tingling in hands/feet had more complex patterns of occurrence. Severity and distress ratings for the seven symptoms varied across the two cycles of CTX. Demographic and clinical characteristics associated with differences in enrollment levels as well as changes over time in occurrence, severity, and distress of these seven common symptoms were highly variable. These findings can be used to identify patients who are at higher risk for more severe and distressing symptoms during CTX and to enable the initiation of preemptive symptom management interventions.


Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.
I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 μg/l, and 17·9 % of children showed UI<100 μg/l. The median UI was higher in males (180·8 v. 153·6 μg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.


[Fate of lentinan (antitumor polysaccharide) II : - fast of methyl lentinan in rats (author's transl)].
3H-labeled lentinan was prepared by methylation with 3H-dimethyl-sulfate. Blood level, distribution and excretion were studied in rats. After intravenous injection of [methyl-3H] -methyl lentinan, radioactivity rapidly disappeared from blood, lung and kidney, distributed mainly in liver, spleen and mesenteric lymph nodes. There was urinary excretion, but expiratory excretion was a small proportion. In the case of multi-injection of [methyl-3H] -methyl lentinan distribution of radioactivity was similar to a single injection, but retention of 3H was less than a single injection. Bile excretion and transport to fetuses and milk were in mere trace amounts. No substantial difference was found between two types of the 3H-labeled lentinan in either the distribution or excretion.


Origin of nanohole formation by etching based on droplet epitaxy.
Creating and manipulating materials at the nanoscale with controllable size, shape and nucleation site is an important task to meet the urgent demands for quantum structures with designed properties. In the last ten years, droplet epitaxy has been emerging as a versatile fabrication method for various complex nanostructures, such as quantum dots, quantum rings, double-rings, and so on. However, there is a lack of understanding of the deep nanohole formation based on droplet epitaxy at a high substrate temperature. Here we fabricate self-organized GaAs nanoholes by Ga droplet etching at high temperature based on droplet epitaxy, and they present good optoelectronic properties and have promising applications in fabrication of nanodevices due to their unique topology. A theoretical model is correspondingly proposed to explain the basic mechanism and simulate the time evolution of the nanohole structures. Our analysis shows that the morphology of the nanohole nanostructures can be well controlled through regulating experimental conditions.


DNAJB1-PRKACA is specific for fibrolamellar carcinoma.
Fibrolamellar carcinoma is a distinct subtype of hepatocellular carcinoma that predominantly affects young patients without underlying cirrhosis. A recurrent DNAJB1-PRKACA fusion has recently been reported in fibrolamellar carcinomas. To determine the specificity of this fusion and to develop routinely available clinical methods of detection, we developed an RT-PCR assay for paraffin-embedded tissues and a FISH probe for detection of the rearrangements of the PRKACA locus. We also developed an RNA in situ hybridization assay to assess expression levels of the total chimeric transcript and wild-type transcripts. A total of 106 primary liver tumors were studied by RT-PCR, including 26 fibrolamellar carcinomas (4 of which were metastases to the abdominal wall or lymph nodes), 25 conventional hepatocellular carcinomas, 25 cholangiocarcinomas, 25 hepatic adenomas, and 5 hepatoblastomas. RT-PCR was successful in 92% of tested fibrolamellar carcinoma cases (24/26) and the DNAJB1-PRKACA fusion transcript was found in all fibrolamellar carcinomas but not in other tumor types. FISH was tested in 19 fibrolamellar carcinomas and in 6 scirrhous hepatocellular carcinomas, which can closely mimic fibrolamellar carcinoma. Rearrangements of the PRKACA locus was seen in all 19 fibrolamellar carcinoma specimens, but in none of the scirrhous hepatocellular carcinomas. Finally, a RNA in situ hybridization strategy was positive in 7/7 successfully hybridized cases, and showed mRNA over-expression in all of the fibrolamellar carcinomas. In addition, the stromal cells embedded in the characteristic intratumoral fibrosis of fibrolamellar carcinomas and the background liver tissues were negative for the DNAJB1-PRKACA fusion by all tested methods. In conclusion, detection of DNAJB1-PRKACA is a very sensitive and specific finding in support of the diagnosis of fibrolamellar carcinoma.


Enterobacterial common antigen and O-specific polysaccharide coexist in the lipopolysaccharide of Yersinia enterocolitica serotype O:3.
Yersinia enterocolitica serotype O : 3 produces two types of lipopolysaccharide (LPS) molecules to its surface. In both types the lipid A (LA) structure is substituted by inner core (IC) octasaccharide to which either outer core (OC) hexasaccharide or homopolymeric O-polysaccharide (OPS) is linked. In addition, enterobacterial common antigen (ECA) can be covalently linked to LPS, however, via an unknown linkage. To elucidate the relationship between ECA and LPS in Y. enterocolitica O : 3 and the effect of temperature on their expression, LPS was isolated from bacteria grown at 22 °C and 37 °C by consequent hot phenol/water and phenol-chloroform-light petroleum extractions to obtain LPS preparations free of ECA linked to glycerophospholipid. In immunoblotting, monoclonal antibodies TomA6 and 898, specific for OPS and ECA, respectively, reacted both with ladder-like bands and with a slower-migrating smear suggesting that the ECA and OPS epitopes coexist on the same molecules. These results were supported by immunoblotting with a monovalent Y. enterocolitica O : 3 ECA-specific rabbit antiserum. Also, two or three 898-positive (and monovalent-positive) TomA6-negative bands migrated at the level of the LA-IC band in LPS samples from certain OC mutants, most likely representing LA-IC molecules carrying 1-3 ECA repeat units but no OPS. These bands were also present in Y. enterocolitica O : 9 OC mutants; however, coexistence of ECA and OPS in the same molecules could not be detected. Finally, the LA-IC-ECA bands were missing from LPS of bacteria grown at 37 °C and also the general reduction in wild-type bacteria of ECA-specific monovalent-reactive material at 37 °C suggested that temperature regulates the expression of ECA. Indeed, RNA-sequencing analysis showed significant downregulation of the ECA biosynthetic gene cluster at 37 °C.


Hypertension update, JNC8 and beyond.
Hypertension is the most preventable major risk factor for cardiovascular morbidity and mortality. The etiology of elevated blood pressure is a complex process involving the interaction of genetics, demographics, comorbid disorders, and environmental influences. Effective hypertensive therapy has been shown to reduce cardiovascular morbidity and mortality. JNC reports have served as a valuable source of guidelines, and JNC 8 is the most recently updated guideline for the prevention, diagnosis, and treatment of hypertension. It includes modification of JNC 7 regarding the threshold for therapy, therapeutic goals, and medications or combinations of medications that differ in benefits for certain patient populations. However, JNC 8 generated a significant degree of controversy. This review will evaluate JNC 7 versus JNC 8 guidelines and discuss the most controversial aspects of JNC 8 through a therapeutic perspective. This review will also discuss the most recently available evidence that has an impact on the JNC 8 recommendations. Despite the nuance of clinical guidelines, blood pressure control rates remains suboptimal. We will explore potential reasons and solutions for this dilemma including pharmacogenomics, novel risk-stratification strategies, lifestyle interventions, and integrative care.


Nonadiabatic deactivation of 9H-adenine: a comprehensive picture based on mixed quantum-classical dynamics.
Mixed quantum-classical dynamics simulations at the multireference configuration interaction (MR-CIS) level were performed for 9 H-adenine in order to understand its ultrafast nonradiative decay process. Dynamics simulations were also performed for the model system 6-aminopyrimidine. MR-CIS and complete active space perturbation theory (CASPT2) have been employed to characterize a large variety of qualitatively different conical intersections, the branches of the crossing seam connecting them, and the reaction paths from the Franck-Condon region for 9 H-adenine. The results show a two-step process consisting of ultrashort deactivation from S 3 to S 1 and a longer exponential decay step corresponding to the conversion from S 1 to S 0.


[Prospects of the development of probiotic preparations on the basis of the "quorum sensing" in bacteria].
The regulation of definite bacterial genes is known to occur, depending on the density of cell population, on the principle of autoinduction named "quorum sensing". The characteristic sign of all regulatory systems working on the principle of "quorum sensing" is the presence of two regulatory proteins: Luxl-like, responsible for the binding of its autoinductor, which makes it possible for the newly formed complex to bind with the promoter of the specific target gene and activate its transcription. The phenomenon of a rise in the concentration of the secreted autoinductor, depending on the increase of the density of cell culture which forms the basis of the "quorum sensing" systems, is analyzed with a view to the development of new therapeutic remedies.


Benzodiazepines in the treatment of schizophrenia: an updated survey.
Reports on the effects of benzodiazepines in schizophrenia have appeared since the early 1960s. Conclusions drawn from these studies, most of which have been uncontrolled, have ranged from worse than placebo to better than neuroleptics. A critical appraisal of the literature seems to warrant the following main conclusions. Benzodiazepines alone, in conventional doses, have no convincing antipsychotic effect in schizophrenia, although they may reduce anxiety, tension and insomnia. However, very high doses of diazepam, and possibly other benzodiazepines, may have a symptomatic antipsychotic effect, especially in paranoid-hallucinatory schizophrenics, also when given alone. Benzodiazepines, in conventional doses, can enhance the antipsychotic effect of neuroleptics in schizophrenics who have not responded satisfactorily to neuroleptics alone. This effect may be most conspicuous against hallucinations, but improvement may also be obtained from delusions, thought disturbances, some negative symptoms, anxiety and tension. Some benzodiazepines may be more effective than others in schizophrenia, but this has been insufficiently elucidated.


Seabed mlinerals and the law of the sea.
If, as seems likely, a comprehensive law-of-the-sea treaty is successfully concluded, minerals of the continental margins would be almost entirely controlled by coastal nations, and the right to produce minerals of the deep ocean floor would be licensed by an International Seabed Authority. Mineral production from the continental margins is likely to increase and diversify with time. The only minerals from the deep ocean floor for which there are reasonably good prospects of production within the next decade are the metalliferous muds from some of the deeps in the Red Sea (which lie within what is likely to be the jurisdiction of Saudi Arabia and Sudan) and nodules in the northeastern equatorial Pacific that contain recoverable metals, namely nickel, copper, cobalt, and possibly manganese, molybdenum, and vanadium.


An event-related visual occlusion method for examining anticipatory skill in natural interceptive tasks.
This article describes a new automated method for the controlled occlusion of vision during natural tasks. The method permits the time course of the presence or absence of visual information to be linked to identifiable events within the task of interest. An example application is presented in which the method is used to examine the ability of cricket batsmen to pick up useful information from the prerelease movement patterns of the opposing bowler. Two key events, separated by a consistent within-action time lag, were identified in the cricket bowling action sequence-namely, the penultimate foot strike prior to ball release (Event 1), and the subsequent moment of ball release (Event 2). Force-plate registration of Event 1 was then used as a trigger to facilitate automated occlusion of vision using liquid crystal occlusion goggles at time points relative to Event 2. Validation demonstrated that, compared with existing approaches that are based on manual triggering, this method of occlusion permitted considerable gains in temporal precision and a reduction in the number of unusable trials. A more efficient and accurate protocol to examine anticipation is produced, while preserving the important natural coupling between perception and action.


Incompetent misdemeanants--pseudocivil commitment.
Prior to Jackson v. Indiana, psychiatric hospitalization of those found to be incompetent to stand trial often led to an inordinately long confinement, a particularly invidious consequence if the patient had been accused only of a misdemeanor. After a highly publicized murder perpetrated by a patient originally in this category, New York State instituted a rather cumbersome set of procedures designed to assure several layers of review, including involvement of the legal system, prior to increasing privileges or discharging someone committed pursuant to a criminal court order. The effect of this new law on patient care is examined by looking at the hospital course of 52 incompetent misdemeanants at one state facility. They are demographically and clinically quite similar to a control group of persons civilly committed, except for an increased length of inpatient stay. When compared with those sent to the county penitentiary after conviction, the study population differs on several important parameters. Looking like a patient, the incompetent misdemeanant is, however, treated more as a criminal with no indication that public safety is thereby increased or that individual therapeutic objectives are enhanced.


The relationship between the density of alcohol outlets and parental supply of alcohol to adolescents.
This study investigated whether the number of alcohol outlets per 10,000 population in a given area (density) influenced parental supply of alcohol to adolescents; differences in Australian born and acculturating parents were also examined. A state-representative student survey in Victoria identified that the majority of adolescents (55%) reported that they had used alcohol in the past 12months; 34 % of those who had consumed alcohol reported that it had been supplied by their parents. Multilevel modelling identified that there were no overall effects of density, however there were different effects based on parent country of birth and type of license. Specifically, each unit increase in the density of takeaway liquor stores increased the likelihood by 2.03 that children with both Australian-born parents would be supplied alcohol. Adolescents with both migrant parents on the other hand, had a 1.36 increased risk of being supplied alcohol as the density of outlets requiring at-venue consumption increased. The findings of this study suggest that in Australia, alcohol outlet density is associated with parental supply of alcohol to children, with this effect moderated by the cultural background of the parent and type of outlet density. Future research should investigate the association between the density of alcohol outlets and public approval of parents supplying alcohol to adolescents.


Frequency of wrist pain and its associated risk factors in students using mobile phones.
To assess the frequency of wrist pain in students due to mobile phone usage, and impact of usage hours and screen size of mobile phones on pain and disability at wrist joint. A cross-sectional survey was conducted among students studying in different universities of Islamabad and Rawalpindi belonging to both public and private sectors. The study was conducted between May 2018 and March 2019. Sample size was 360 students which were selected through convenience sampling. Data was collected through self-formulated closed ended questionnaire. Patient Rated Wrist Evaluation questionnaire was used to assess pain and disability at wrist joint. Data entry and analysis were done using SPSS 21. Results were analyzed using descriptive statistics. Spearman's and point-biserial correlation coefficients were applied to determine association between different variables. Point, last month, last 3 months, last 6 months, last year and lifetime frequency were found to be 9%, 18.6%, 29%, 33.3%, 42% and 45.3% respectively. Duration of mobile phone usage was found to be of significant association factor that could lead to wrist pain and disability (p=0.004). Wrist pain was not significantly related to mobile phone screen size (p=0.488). It appears that wrist pain is common among mobile phone users and an increase in use of mobile phones increased pain and disability of wrist joint. In addition, it seems that screen size of mobile phone has no significant effect on pain and disability of wrist joint.


Compliance of nursing home residents with a nutrient- and energy-dense oral nutritional supplement determines effects on nutritional status.
Administration of oral nutritional supplements (ONS) is an effective strategy to treat and avoid malnutrition, a persisting issue in nursing homes. However, little is known about compliance in the NH population. This study aimed to analyse the effects of compliance of NH residents with a low-volume, nutrient- and energy-dense ONS on nutritional status and to identify residents' characteristics associated with compliance. Randomized, controlled trial in nursing homes. 87 nursing home residents (87 ± 6y, 91% female) with malnutrition or at risk of malnutrition were randomly allocated to an intervention group (IG) receiving 2 x 125 ml ONS (2.4 kcal/ml)/d for 12 weeks, or the control group (CG) with usual care. ONS intake was recorded daily and compliance calculated. Low and high compliance were defined as ≤ 30% and ≥ 80% of provided ONS actually consumed, respectively. Body weight (BW), BMI, upper-arm (UAC) and calf-circumference (CC) and MNA-SF were assessed at baseline and after 12 weeks. Associations between compliance and changes of nutritional parameters and residents' characteristics were analysed. Compliance was high in 35.7% and low in 28.6% of the IG (n=42). BW change was significantly higher in subjects with high compliance (median +3.0 (interquartile range +2.1;+3.8) kg, n=15) than in those with low compliance (-0.2 (-2.2;+1.6) kg, n=12) and CG (-0.1 (-1.2; +0.6) kg, n=35; p<0.001), and significantly correlated with compliance in IG (r=0.691; p<0.001). Significant differences and correlations were also identified for BMI, UAC and MNA-SF. High compliance was more often observed in residents with malnutrition (66.7 vs. 27.3%) and chewing difficulties (77.8 vs. 24.2%) than in those without these conditions. Low compliance was more prevalent in residents who were immobile (45.0 vs. 13.6%), depressed (33.3 vs. 6.7%) or had gastrointestinal complaints (50.0 vs. 17.9%) (all p<0.05). A high compliance of nursing home residents with a low volume, nutrient- and energy dense ONS was related to a significantly improved nutritional status in comparison to low compliance and therefore enhanced the effectiveness of ONS. A higher compliance may be achieved by consideration of different residents' characteristics.


Costimulation of T cells.
Costimulation is critical to T cell activation. On the antigen-presenting cell the key players are found in the extended family of B7 genes comprising cd80, cd86, B7h/B7RP-1 and B7-H1. cd80 and cd86 encode proteins that bind to CD28 and CTLA4 on T cells. Blocking this pathway with the potent CTLA4-Ig fusion protein shows encouraging potential as a therapeutic agent. While cd80 and cd86 pathways act mainly on naive T cells, B7h/B7RP-1 and B7-H1 seem to exert their effects on antigen-experienced lymphocytes.


[Modeling of the effect of modulated electromagnetic radiation on animal cells].
Frequency-dependent modifications of intracellular free calcium concentration ([Ca2+]i) in neutrophils exposures to modulated extremely high frequency electromagnetic radiation were analyzed using a special mathematical model for [Ca2+]i oscillations. The model took into account the activation of Ca2+ influx into the cell by cytosolic Ca2+ and Ca(2+)-induced Ca2+ release from intracellular stores. The calcium channels of plasma membrane were chosen as a target for the influence of harmonic signal and additive noise in the model. The model simulation showed that in response to modulating signal, the rise in [Ca2+]i, has frequency dependence and phase dependence in relation to the moment of chemical stimulation. The phase-frequency dependence of the effect was observed at a certain sequence of delivery of chemical stimulus and modulating signal to the cell. At intensities of modulating signals exceeding the threshold, a rise in [Ca2+]i, reaching a level of more than 50% of the initial level, was observed at a frequency of about 1 Hz and in the phase range of 0.3-2.5 radians. The effect was found only at high intensities of chemical stimulus. The additive noise introduced into the system modified qualitatively and quantitatively the phase-frequency characteristics of the cell response to the modulating signal. An increase in noise intensity resulted in a displacement of the average frequency of the band of rise in [Ca2+]i, and then the emergence of a set of bands with a greater Q-factors. The analysis of dynamics of the nonlinear system in terms of the stability theory showed that, as the intensity of chemical stimulus increases, the system transits by means of a series of bifurcations from regular driving to chaotic, and then to oscillations, induced by a modulating harmonic signal. The boundary of the transition of oscillations from chaotic to induced ones corresponds to a specific "threshold" of the intensity of chemical stimulus for the significant rise in [Ca2+]i in response to the modulating signal. The results of the model analysis are in good correspondence with the experimental data obtained earlier, namely, with the effects of modulated extremely high-frequency electromagnetic radiation on neutrophils, which were observed only in the presence of Ca2+ in extracellular medium and at high concentrations of calcium ionophore A23187. Thus, as the characteristic frequency of the quasi-periodic process of calcium signalling in the cell coincides with the frequency of external field, a narrow-band rise in [Ca2+]i is observed, which can result in a modification of the functional activity of the cell.


Climate change impacts on the conservation outlook of populations on the poleward periphery of species ranges: A case study of Canadian black-tailed prairie dogs (Cynomys ludovicianus).
Given climate change, species' climatically suitable habitats are increasingly expected to shift poleward. Some imperilled populations towards the poleward edge of their species' range might therefore conceivably benefit from climate change. Interactions between climate and population dynamics may be complex, however, with climate exerting effects both indirectly via influence over food availability and more directly, via effects on physiology and its implications for survival and reproduction. A thorough understanding of these interactions is critical for effective conservation management. We therefore examine the relationship between climate, survival and reproduction in Canadian black-tailed prairie dogs, a threatened keystone species in an imperilled ecosystem at the northern edge of the species' range. Our analyses considered 8 years of annual mark-recapture data (2007-2014) in relation to growing degree days, precipitation, drought status and winter severity, as well as year, sex, age and body mass. Survival was strongly influenced by the interaction of drought and body mass class, and winter temperature severity. Female reproductive status was associated with the interaction of growing degree days and growing season precipitation, with spring precipitation and with winter temperature severity. Results related to body mass suggested that climatic variables exerted their effects via regulation of food availability with potential linked effects of food quality, immunological and behavioural implications, and predation risk. Predictions of future increases in drought conditions in North America's grassland ecosystems have raised concerns for the outlook of Canadian black-tailed prairie dogs. Insights gained from the analyses, however, point to mitigating species management options targeted at decoupling the mechanisms by which climate exerts its negative influence. Our approach highlights the importance of understanding the interaction between climate and population dynamics in peripheral populations whose viability might ultimately determine their species' ability to track climatically suitable space.


Web-browser encryption of personal health information.
Electronic health records provide access to an unprecedented amount of clinical data for research that can accelerate the development of effective medical practices. However it is important to protect patient confidentiality, as many medical conditions are stigmatized and disclosure could result in personal and/or financial loss. We describe a system for remote data entry that allows the data that would identify the patient to be encrypted in the web browser of the person entering the data. These data cannot be decrypted on the server by the staff at the data center but can be decrypted by the person entering the data or their delegate. We developed this system to solve a problem that arose in the context of clinical research, but it is applicable in a range of situations where sensitive information is stored and updated in a database and it is necessary to ensure that it cannot be viewed by any except those intentionally given access. By developing this system, we are able to centralize the collection of some patient data while minimizing the risk that protected health information be made available to study personnel who are not authorized to use it.


Narrowband and tunable optical parametric amplification in Bismuth-Oxide-based highly nonlinear fiber.
The one-pump optical fiber parametric amplification (FOPA) has been well known to be a means for realizing wideband amplification when the group-delay dispersion (beta(2)) is small at the pump wavelength. In this paper, we report one-pump FOPA in short Bismuth-Oxide-based highly nonlinear fiber (Bi-HNLF) that has large normal dispersion at 1550nm, both theoretically and experimentally, for the first time to the best of our knowledge. We found that, due to the large beta(4) along with large beta(2), FOPA in the Bi-HNLF is very narrowband, and its gain peak wavelength is tunable in proportional to the pump wavelength. We achieved the gain bandwidth as narrow as 0.75nm and gain peak as high as 58dB in the experiment using a 2m-long Bi-HNLF.


Digital sampling of acoustic impulse noise: Implications for exposure measurement and damage risk criteria.
Current standards for the measurement of impulse noise (e.g., MIL-STD-1474E) recommend using a sampling rate of at least 200 kHz in order to accurately estimate the risk of hearing damage. The given motivation for this high sampling rate is to ensure a temporal resolution in the impulse waveform fine enough to accurately capture the peak pressure. However, the Nyquist-Shannon sampling theorem specifies that a sampled signal can accurately reconstruct both the amplitude and phase information of a signal given the sampling rate is at least twice the highest frequency present in the original signal. Thus, it is possible to reconstruct a band limited signal with the same temporal resolution as one captured at a higher sampling rate if the contributions of energy above the Nyquist rate can be ignored. In this study, resampling techniques are applied to a signal sampled at 48 kHz to extract A-weighted sound pressure energy estimates within 0.1 dB of those obtained at a higher sampling rate. Our results suggest sampling rates for impulsive noise should be based on the range of frequencies expected to make a contribution to injury risk rather than on concerns about temporal resolution.


Role of glial-like type II cells as paracrine modulators of carotid body chemoreception.
Mammalian carotid bodies (CB) are chemosensory organs that mediate compensatory cardiorespiratory reflexes in response to low blood PO2 (hypoxemia) and elevated CO2/H+ (acid hypercapnia). The chemoreceptors are glomus or type I cells that occur in clusters enveloped by neighboring glial-like type II cells. During chemoexcitation type I cells depolarize, leading to Ca2+-dependent release of several neurotransmitters, some excitatory and others inhibitory, that help shape the afferent carotid sinus nerve (CSN) discharge. Among the predominantly excitatory neurotransmitters are the purines ATP and adenosine, whereas dopamine (DA) is inhibitory in most species. There is a consensus that ATP and adenosine, acting via postsynaptic ionotropic P2X2/3 receptors and pre- and/or postsynaptic A2 receptors respectively, are major contributors to the increased CSN discharge during chemoexcitation. However, it has been proposed that the CB sensory output is also tuned by paracrine signaling pathways, involving glial-like type II cells. Indeed, type II cells express functional receptors for several excitatory neurochemicals released by type I cells including ATP, 5-HT, ACh, angiotensin II, and endothelin-1. Stimulation of the corresponding G protein-coupled receptors increases intracellular Ca2+, leading to the further release of ATP through pannexin-1 channels. Recent evidence suggests that other CB neurochemicals, e.g., histamine and DA, may actually inhibit Ca2+ signaling in subpopulations of type II cells. Here, we review evidence supporting neurotransmitter-mediated crosstalk between type I and type II cells of the rat CB. We also consider the potential contribution of paracrine signaling and purinergic catabolic pathways to the integrated sensory output of the CB during chemotransduction.


Neoplastic effects of oral contraceptives.
The potential association between the use of oral contraceptives (OCs) and certain types of cancer remains an important concern. Epidemiologic studies published over the past decade indicate that the overall risk of breast cancer is not increased among women exposed to OCs. Some studies have suggested an increased risk among younger women with long-term use, and this issue requires further study. OCs confer significant protection against endometrial and ovarian cancers, and the effect is duration-related: longer use is more protective. In the largest study to date, the protection against these two types of cancer persisted for at least 15 years after OCs were discontinued. Several studies have linked long-term OC use with an increased risk of cervical cancer or its precursors, but methodologic difficulties in studying cervical cancer are such that the potential association with OC use may never be clarified. A large international study has found no association between OC use for any duration and liver cancer. Neither malignant melanoma nor pituitary adenoma appears to be linked to OC use. In summary, OCs protect against endometrial and ovarian cancers and have no overall effect on the risk of breast cancer. Women using OCs should have regular Papanicolaou screening.


Two classes of bacterial IMPDHs according to their quaternary structures and catalytic properties.
Inosine-5'-monophosphate dehydrogenase (IMPDH) occupies a key position in purine nucleotide metabolism. In this study, we have performed the biochemical and physico-chemical characterization of eight bacterial IMPDHs, among which six were totally unexplored. This study led to a classification of bacterial IMPDHs according to the regulation of their catalytic properties and their quaternary structures. Class I IMPDHs are cooperative enzymes for IMP, which are activated by MgATP and are octameric in all tested conditions. On the other hand, class II IMPDHs behave as Michaelis-Menten enzymes for both substrates and are tetramers in their apo state or in the presence of IMP, which are shifted to octamers in the presence of NAD or MgATP. Our work provides new insights into the IMPDH functional regulation and a model for the quaternary structure modulation is proposed.


Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted.
In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.


Vibrational spectroscopy and conformational structure of protonated polyalanine peptides isolated in the gas phase.
The conformational structures of protonated polyalanine peptides, Ala(n)H(+), have been investigated in the gas phase for n = 3, 4, 5, and 7 using a combination of resonant-infrared multiphoton dissociation (R-IRMPD) spectroscopy in the NH and OH stretch regions and quantum chemical calculations. Agreement between theoretical IR and experimental R-IRMPD spectral features has enabled the assignment of specific hydrogen-bonded conformational motifs in the short protonated peptides and revealed their conformational evolution under elevated-temperature conditions, as a function of increasing chain length. The shortest peptide, Ala(3)H(+), adopts a mixture of extended and cyclic chain conformations, protonated, respectively, at a backbone carbonyl or the N-terminus. The longer peptides adopt folded, cyclic, and globular charge-solvated conformations protonated at the N-terminus, consistent with previous ion-mobility studies. The longest peptide, Ala(7)H(+), adopts a globular conformation with the N-terminus completely charge-solvated, demonstrating the emergence of "physiologically relevant" intramolecular interactions in the peptide backbone. The computed conformational relative free energies highlight the importance of entropic contributions in these peptides.


Benzene-free synthesis of adipic acid.
Strains of Escherichia coli were constructed and evaluated that synthesized cis,cis-muconic acid from D-glucose under fed-batch fermentor conditions. Chemical hydrogenation of the cis,cis-muconic acid in the resulting fermentation broth has also been examined. Biocatalytic synthesis of adipic acid from glucose eliminates two environmental concerns characteristic of industrial adipic acid manufacture: use of carcinogenic benzene and benzene-derived chemicals as feedstocks and generation of nitrous oxide as a byproduct of a nitric acid catalyzed oxidation. While alternative catalytic syntheses that eliminate the use of nitric acid have been developed, most continue to rely on petroleum-derived benzene as the ultimate feedstock. In this study, E. coli WN1/pWN2.248 was developed that synthesized 36.8 g/L of cis,cis-muconic acid in 22% (mol/mol) yield from glucose after 48 h of culturing under fed-batch fermentor conditions. Optimization of microbial cis,cis-muconic acid synthesis required expression of three enzymes not typically found in E. coli. Two copies of the Klebsiella pneumoniae aroZ gene encoding DHS dehydratase were inserted into the E. coli chromosome, while the K. pneumoniae aroY gene encoding PCA decarboxylase and the Acinetobacter calcoaceticus catA gene encoding catechol 1,2-dioxygenase were expressed from an extrachromosomal plasmid. After fed-batch culturing of WN1/pWN2.248 was complete, the cells were removed from the broth, which was treated with activated charcoal and subsequently filtered to remove soluble protein. Hydrogenation of the resulting solution with 10% Pt on carbon (5% mol/mol) at 3400 kPa of H2 pressure for 2.5 h at ambient temperature afforded a 97% (mol/mol) conversion of cis,cis-muconic acid into adipic acid.


Structural basis for recognition of a kink-turn motif by an archaeal homologue of human RNase P protein Rpp38.
PhoRpp38 in the hyperthermophilic archaeon Pyrococcus horikoshii, a homologue of human ribonuclease P (RNase P) protein Rpp38, belongs to the ribosomal protein L7Ae family that specifically recognizes a kink-turn (K-turn) motif. A previous biochemical study showed that PhoRpp38 specifically binds to two stem-loops, SL12 and SL16, containing helices P12.1/12.2 and P15/16 respectively, in P. horikoshii RNase P RNA (PhopRNA). In order to gain insight into the PhoRpp38 binding mode to PhopRNA, we determined the crystal structure of PhoRpp38 in complex with the SL12 mutant (SL12M) at a resolution of 3.4 Å. The structure revealed that Lys35 on the β-strand (β1) and Asn38, Glu39, and Lys42 on the α-helix (α2) in PhoRpp38 interact with characteristic G•A and A•G pairs in SL12M, where Ile93, Glu94, and Val95, on a loop between α4 and β4 in PhoRpp38, interact with the 3-nucleotide bulge (G-G-U) in the SL12M. The structure demonstrates the previously proposed secondary structure of SL12, including helix P12.2. Structure-based mutational analysis indicated that amino acid residues involved in the binding to SL12 are also responsible for the binding to SL16. This result suggested that each PhoRpp38 binds to the K-turns in SL12 and SL16 in PhopRNA. A pull-down assay further suggested the presence of a second K-turn in SL12. Based on the present results, together with available data, we discuss a structural basis for recognition of K-turn motifs in PhopRNA by PhoRpp38.


A review of dietary selenium intake and selenium status in Europe and the Middle East.
This is a systematic review of existing data on dietary selenium (Se) intake and status for various population groups in Europe (including the United Kingdom (UK)) and the Middle East. It includes English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies obtained through PUBMED searches from January, 2002, to November, 2014, for European data and from 1990 to November 2014, for Middle Eastern data. Reports were selected if they included data on Se intake and status. The search identified 19 European/UK studies and 15 investigations in the Middle East that reported Se intake and Se concentration in water and/or food and 48 European/UK studies and 44 investigations in the Middle East reporting Se status. Suboptimal Se status was reported to be widespread throughout Europe, the UK and the Middle East, and these results agreed with previous reports highlighting the problem. Eastern European countries had lower Se intake than Western European countries. Middle Eastern studies provided varying results, possibly due to varying food habits and imports in different regions and within differing socioeconomic groups. In conclusion, Se intake and status is suboptimal in European and Middle Eastern countries, with less consistency in the Middle East.


Combining top-down and bottom-up routes for fabrication of mesoporous titania films containing ceria nanoparticles for free radical scavenging.
Nanocomposite thin films formed by mesoporous titania layers loaded with ceria nanoparticles have been obtained by combining bottom-up self-assembly synthesis of a titania matrix with top-down hard X-ray lithography of nanocrystalline cerium oxide. At first the titania mesopores have been impregnated with the ceria precursor solution and then exposed to hard X-rays, which triggered the formation of crystalline cerium oxides within the pores inducing the in situ growth of nanoparticles with average size of 4 nm. It has been observed that the type of coordinating agent in the solution plays a primary role in the formation of nanoparticles. Different patterns have been also produced through deep X-ray lithography by spatially controlling the nanoparticle growth on the micrometer scale. The radical scavenging role of the nanocomposite films has been tested using as a benchmark the UV photodegradation of rhodamine 6G. After impregnation with a rhodamine 6G solution, samples with and without ceria have shown a remarkably different response upon exposure to UV light. The dye photodegradation on the surface of nanocomposite films appears strongly slowed down because of the antioxidation effect of ceria nanoparticles.


Freeze-dried cylinders carrying chitosan nanoparticles for vaginal peptide delivery.
Recently nanoparticle-based vaginal drug delivery formulations have been acquiring great attention for the administration of peptide based-vaccines or microbicides to prevent or treat sexually transmitted diseases. In this work, a straightforward and efficient strategy for the vaginal application and release of peptide-loaded mucoadhesive nanoparticles was developed. This essentially consists of chitosan nanoparticles encapsulated in suitable hydrophilic freeze-dried cylinders. Chitosan nanoparticles are responsible for carrying the peptide drug and allowing adhesion to the vaginal mucosal epithelium. Hydrophilic freeze-dried cylinders facilitate the application and quick release of the nanoparticles to the vaginal zone. Upon contact with the aqueous vaginal medium, the excipients constituting these sponge-like systems are quickly dissolved enabling the release of their content. In vitro release studies showed the ability of the sponge-like systems and chitosan nanoparticles to deliver the mucoadhesive nanoparticles and peptide respectively. CLSM micrographs proved the nanoparticles ability promoting the peptide penetration inside the vaginal mucosa.


A Decade of Streptococcus thermophilus Phage Evolution in an Irish Dairy Plant.
Phages of Streptococcus thermophilus present a major threat to the production of many fermented dairy products. To date, only a few studies have assessed the biodiversity of S. thermophilus phages in dairy fermentations. In order to develop strategies to limit phage predation in this important industrial environment, it is imperative that such studies are undertaken and that phage-host interactions of this species are better defined. The present study investigated the biodiversity and evolution of phages within an Irish dairy fermentation facility over an 11-year period. This resulted in the isolation of 17 genetically distinct phages, all of which belong to the so-called cos group. The evolution of phages within the factory appears to be influenced by phages from other dairy plants introduced into the factory for whey protein powder production. Modular exchange, primarily within the regions encoding lysogeny and replication functions, was the major observation among the phages isolated between 2006 and 2016. Furthermore, the genotype of the first isolate in 2006 was observed continuously across the following decade, highlighting the ability of these phages to prevail in the factory setting for extended periods of time. The proteins responsible for host recognition were analyzed, and carbohydrate-binding domains (CBDs) were identified in the distal tail (Dit), the baseplate proteins, and the Tail-associated lysin (Tal) variable regions (VR1 and VR2) of many isolates. This supports the notion that S. thermophilus phages recognize a carbohydrate receptor on the cell surface of their host.IMPORTANCE Dairy fermentations are consistently threatened by the presence of bacterial viruses (bacteriophages or phages), which may lead to a reduction in acidification rates or even complete loss of the fermentate. These phages may persist in factories for long periods of time. The objective of the current study was to monitor the progression of phages infecting the dairy bacterium Streptococcus thermophilus over a period of 11 years in an Irish dairy plant so as to understand how these phages evolve. A focused analysis of the genomic region that encodes host recognition functions highlighted that the associated proteins harbor a variety of carbohydrate-binding domains, which corroborates the notion that phages of S. thermophilus recognize carbohydrate receptors at the initial stages of the phage cycle.


Human values and beliefs and concern about climate change: a Bayesian longitudinal analysis.
The aim of this study was to investigate the influence of human values on beliefs and concern about climate change using a longitudinal design and Bayesian analysis. A sample of 298 undergraduate/master students filled out the same questionnaire on two occasions at an interval of 2 months. The questionnaire included measures of beliefs and concern about climate change (i.e., perceived consequences, risk perception, and skepticism) and human values (i.e., the Portrait Values Questionnaire). After controlling for gender and the respective baseline score, universalism at Time 1 was associated with higher levels of perceived consequences of climate change and lower levels of climate change skepticism. Self-direction at Time 1 predicted Time 2 climate change risk perception and perceived consequences of climate change. Hedonism at Time 1 was associated with Time 2 climate change risk perception. The other human values at Time 1 were not associated with any of the measures of beliefs and concern about climate change at Time 2. The results of this study suggest that a focus on universalism and self-direction values seems to be a more successful approach to stimulate public engagement with climate change than a focus on other human values.


Arctic-adapted dogs emerged at the Pleistocene-Holocene transition.
Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog-specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.


[The study of patients? Opinion about the quality of medical care in the N.I. Pirogov National Medical Surgical Center].
The study covered the consumer group of relatives of 192 patients receiving treatment in the surgery departments of the Saint George National center of thoracic and cardiovascular surgery in 2005 and 2009, after implementation of industrial techniques of medical care quality management. The relatives of 84 patients were polled in 2005 and of 108 patients--in 2007. The questionnaire proceeded the standard algorithm. The final stage of the study included the analysis of proposals of relatives of patients concerning the enhancement of quality of Center functioning.


[Therapeutic function of images].
The aim here searched is to explore the reasons why some systems of psychotherapy choose images as a means for attaining the cure. In one case at least (Roger Desoille's "awake dream"--the production and interpretation of images constitutes the basic procedure. The question arises: which sort of images? It is not dealt here with the oniric ones, but with the consciously created and must be called symbolic images. Almost every image that appears during a therapy session reveals a symbolic nature, but the very concept of symbol is not free from ambiguity some positions originated in different areas of investigation are mentioned, ending with a description of the traits that, according to the writer, bestow a symbolic character to images. These can be sensible ones or linguistic, as they appear in literary productions. Their importance as a factor of the psychotherapeutic change resides in the fact that symbolic images thus created are felt as not real events and at the same time containing subjective meaning. These two traits combine to lessen the anxiety before the confrontation with one's own impulses or feelings and at same time to stimulate towards new ways of behavior, until then desired -perhaps unconsciously- but too frightening to materialize in the real world.


[Recommendations for reducing mortality among workers of mining enterprises].
The authors elaborated measures aimed to lower mortality and higher life expectancy among workers of able-bodied age. The recommendations involve changes in technology of drift mining, improved electric safety of technologic equipment, annual analysis of mortality parameters among miners, accomplishment of prophylactic recommendations on treatment of functional cardiovascular disorders, provision of workers with pectin as a therapeutic and prophylactic nutrient.


Heterogeneity of muscle damage induced by electrostimulation: a multimodal MRI study.
Neuromuscular electrostimulation (NMES) leads to a spatially fixed, synchronous, and superficial motor unit recruitment, which could induce muscle damage. Therefore, the extent of muscle damage and its spatial occurrence were expected to be heterogeneous across and along the quadriceps femoris (QF) muscles. The aim of the present study was to characterize muscle spatial heterogeneity in QF damage after a single bout of isometric NMES using multimodal magnetic resonance imaging (MRI). Twenty-five young healthy males participated in this study. MRI investigations consisted of the assessment of muscle volume, transverse relaxation time (T2), and diffusion tensor imaging (DTI) in muscles positioned near the stimulation electrodes (i.e., vastus lateralis (VL) and vastus medialis (VM)) and muscles located outside the stimulated regions (i.e., vastus intermedius and rectus femoris). These measurements were performed 6 d before, and 2 d and 4 d (D4) after the NMES session. For the muscles placed in direct contact with the stimulation electrodes, volume (VL, +8.5%; VM, +3.8%), T2 (VL, +19.5%; VM, +6.7%) and radial diffusivity (λ3) (VL, + 7.3%; VM, +3.7%) significantly increased at D4. Whereas MRI parameter changes were larger for VL as compared with those for other QF muscles at D4, homogeneous alterations were found along all QF muscles. Isometric NMES induced specific and localized alterations in VL and VM, with heterogeneous damage amplitude among them. Potential effects of unaccustomed intermuscle shear stress during electrically evoked isometric contractions could be a key factor in the spatial occurrence and the extent of damage among QF muscles (especially in VL). The kinetics and extent of MRI changes varied between T2 and diffusion tensor imaging metrics, suggesting the involvement of different physiological processes.


[Cardiac angiosarcoma in a pregnant women].
We present a case of cardiac angiosarcoma in a pregnant women. Clinical manifestations of angiosarcoma were unspecific and progressed rapidly as hemopericardium, cardiac tamponade, heart failure, fever, chest pain. Pregnancy was interrupted at 22-nd week. The patient died in 6 months after appearance of first symptoms.


Risk for Exfoliation Syndrome in Women With Pelvic Organ Prolapse : A Utah Project on Exfoliation Syndrome (UPEXS) Study.
Exfoliation syndrome, an inherited systemic disorder of elastin and extracellular matrix (ECM), is associated with the LOXL1 gene locus. Pelvic organ prolapse is a common connective tissue disorder that affects women. The presence of an association between exfoliation syndrome (exfoliation of the lens capsule) and pelvic organ prolapse was investigated as part of the Utah Project on Exfoliation Syndrome (UPEXS). To examine the association between exfoliation syndrome and pelvic organ prolapse using the Utah Population Database, a comprehensive resource linked to medical records. A 2-pronged approach was used. In substudy A, a cross-sectional analysis was performed to determine the association between pelvic organ prolapse and exfoliation syndrome in women enrolled in Medicare in Utah from calendar year 1992 to 2009 (n = 132 772). In substudy B, the risk of incident exfoliation syndrome from January 1, 1995, to December 31, 2014, was estimated in a cohort of women aged 30 to 65 years at baseline with a diagnosis of pelvic organ prolapse (n = 5130) compared with birth year-matched women serving as controls who did not have pelvic organ prolapse (n = 15 338). Exfoliation syndrome outcome was defined by International Classification of Diseases, Ninth Revision, diagnosis codes for exfoliation syndrome or exfoliation glaucoma (366.11 or 365.52, respectively). In substudy A, odds ratios (ORs) from unconditional logistic regression models were used to estimate the exfoliation syndrome risk in women with pelvic organ prolapse compared with those without pelvic organ prolapse. In substudy B, hazard ratios (HRs) from Cox proportional hazards models were used to estimate incident exfoliation syndrome risk in patients with pelvic organ prolapse (without exfoliation syndrome history) compared with unaffected controls. Models were adjusted for age, years enrolled, parity, and race/ethnicity. Of the 132 772 women enrolled in Utah Medicare from 1992 to 2009, the mean [SD] age at the last enrollment was 82.2 [7.7] years. Pelvic organ prolapse was associated with a 1.56-fold increased risk of exfoliation syndrome in Medicare beneficiaries (OR, 1.56; 95% CI, 1.42-1.72) in substudy A. We observed a 48% increased incident risk of exfoliation syndrome in women aged 30 to 65 years at baseline who had a pelvic organ prolapse diagnosis compared with controls during 20 years of follow-up (HR, 1.48; 95% CI, 1.14-1.91). The diagnosis of exfoliation syndrome was more frequent in women with pelvic organ prolapse in the Utah Population Database, a robust population-based resource, thus supporting an association of exfoliation syndrome with a nonocular systemic condition. Systemic conditions with altered ECM metabolism, such as pelvic organ prolapse, may share common biological pathways with exfoliation syndrome. LOXL1 dysregulation, thought to occur in exfoliation syndrome, may be a contributing factor.


Renal transplantation during the twentieth century: a review.
To provide an overview of the various advancements and problems associated with both live and cadaver donor renal allograft transplantation during the twentieth century. Major published reviews on renal transplantation during the the last five decades of the twentieth century were reviewed using Medline internet search and the Index Medicus. The developments in immunosuppressive therapy associated with renal transplantation, the problem of the shortage of both live and cadaveric organ donors and post-transplant complications were examined. The future of renal transplantation including cross species transplantation (xenotransplantation) is discussed. Renal transplantation has evolved over the years to become a very successful and routine procedure. However, the transplant waiting lists have remained long due to a continuously shrinking kidney donor pool which is due to improved results of neurosurgical procedures, better emergency and intensive care services and the failure to adequately prevent and treat post transplant chronic renal failure.


Carbon-11-methionine PET in focal cortical dysplasia: a comparison with fluorine-18-FDG PET and technetium-99m-ECD SPECT.
Focal cortical dysplasia is one of the known neuronal migration disorders and has recently been recognized as a cause of intractable epilepsy. In this study, we assessed the 11C-methionine (MET) uptake in focal cortical dysplasia by PET, and then compared the results with that of 18F-fluoro-2-deoxy-D-glucose (FDG) PET and 99mTc-ethyl cysteinate dimer (ECD) SPECT. Four patients (3 men, 1 woman; age range 16-68 yr) were examined by PET and SPECT for a presurgical examination of medically intractable seizures. In all 4 patients, 11C-MET PET was performed for 15 min, started 15 min after the administration of 511-662 MBq MET. In 3 of 4 patients, FDG PET was performed for 15 min, and started 20 min after the administration of 185-370 MBq FDG. In all 4 patients, the cerebral blood flow was also evaluated by 99mTc-ECD SPECT for 15 min after the administration of 600 MBq ECD. In MET PET, all 4 lesions were visually recognized to have high MET uptake areas. The MET uptake of the lesions was 1.44 +/- 0.30 for the standardized uptake value (SUV) (ranging from 0.99-1.61). In FDG PET, 2 lesions were demonstrated to have low uptake areas (3.82 in SUV) while 1 had an ictal high uptake (4.74 in SUV). In ECD SPECT, 1 lesion demonstrated hypoperfusion and 1 ictal hyperperfusion while 2 showed no abnormalities. All 4 patients underwent a cortical resection and the microscopic examinations were consistent with those of focal cortical dysplasia but no evidence of a tumor was found. MET PET is useful for identifying focal cortical dysplasia as a high uptake area.


LGBTQ Utilization of a Statewide Tobacco Quitline: Engagement and Quitting Behavior, 2010-2022.
Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) individuals use tobacco at disproportionately high rates but are as likely as straight tobacco users to want to quit and to use quitlines. Little is known about the demographics and geographic distribution of LGBTQ quitline participants, their engagement with services, or their long-term outcomes. Californians (N=333,429) who enrolled in a statewide quitline 2010-2022 were asked about their sexual and gender minority (SGM) status and other baseline characteristics. All were offered telephone counseling. A subset (n=19,431) was followed up at 7 months. Data were analyzed in 2023 by SGM status (LGBTQ vs. straight) and county type (rural vs. urban). Overall, 7.0% of participants were LGBTQ, including 7.4% and 5.4% of urban and rural participants, respectively. LGBTQ participants were younger than straight participants but had similar cigarette consumption. Fewer LGBTQ participants reported a physical health condition (42.1% vs. 48.4%) but more reported a behavioral health condition (71.1% vs. 54.5%; both p's<.001). Among both LGBTQ and straight participants, nearly 9 in 10 chose counseling and both groups completed nearly 3 sessions on average. The groups had equivalent 30-day abstinence rates (24.5% vs. 23.2%; p=.263). Similar patterns were seen in urban and rural subgroups. LGBTQ tobacco users engaged with and appeared to benefit from a statewide quitline even though it was not LGBTQ community-based. A quitline with staff trained in LGBTQ cultural competence can help address the high prevalence of tobacco use in the LGBTQ community and reach members wherever they live. This study describes how participants of a statewide tobacco quitline broke down by sexual orientation and gender. It compares participants both by SGM status and by type of county to provide a more complete picture of quitline participation both in urban areas where LGBTQ community-based cessation programs may exist and in rural areas where they generally do not. To our knowledge, it is the first study to compare LGBTQ and straight participants on their use of quitline services and quitting aids, satisfaction with services received, and rates of attempting quitting and achieving prolonged abstinence from smoking.


Primary Hepatic Osteosarcoma: A Rare Cause of Primary Liver Tumor.
Extraosseous osteosarcomas are rare, accounting for approximately 4% of all osteosarcomas. A literature review yields very few cases of osteosarcoma primarily arising from the hepatic parenchyma. This report describes a case of a man in his 50s with a history of hepatitis C and cirrhosis who presented with 5 days of progressive right upper quadrant pain. Magnetic resonance imaging of the abdomen and pelvis demonstrated a 4.4 cm × 4.8 cm × 4.8 cm right hepatic lobe mass with a large area of necrosis and peripheral enhancement. The subsequent liver biopsy showed few cores of tumor composed of fibroblastic malignant cells producing lace-like osteoid matrix. Osteosarcomatous foci in other parts of the body were excluded by performing extensive physical examination, radiologic imaging, and biopsy. Hence, a primary osteosarcoma was diagnosed. The patient underwent portal vein embolization in preparation for a surgical resection of the right liver lobe. He was admitted six weeks after the embolization for dyspnea and abdominal distension and expired due to abdominal hematoma and pulmonary embolism. Based on the rarity, lack of consensus in treatment, and dismal prognosis, extraosseous osteosarcoma should be considered a separate entity from osseous osteosarcoma. More data and research are needed in this rare and understudied malignancy.


Expression of the receptor for parathyroid hormone-related protein in normal and malignant breast tissue.
Parathyroid hormone-related protein (PTHrP) is the cause of humoral hypercalcaemia of malignancy and interacts with parathyroid hormone (PTH) receptors. Breast cancer cells produce PTHrP in vitro and in vivo. The breast cancer cell line MCF-7, which products PTHrP and expresses PTHrP receptors, proliferates in response to PTHrP. The aim of these studies was to determine the tissue location of PTHrP/PTH receptors (PTHrPR) in primary breast carcinomas and to establish whether they had the potential to respond to PTHrP. The cellular location of mRNA for the PTHrP/PTH receptor was identified using in situ hybridization in primary breast carcinomas and normal breast tissue. Immunohistochemistry for PTHrP was carried out on the same specimens. Tumours were assessed and scored by two observers using the product of intensity of signal and number of positive tumour cells (possible range 0-9). Tumours were also assessed for Ki-67 expression by counting positive nuclei. Non-malignant ductular epithelium expressed mRNA for the PTHrP receptor (mean score 2.6, range 1-4). Breast carcinomas (mean score 4.4, range 0-9) showed variable expression of PTHrP receptor mRNA: eight tumours were negative, 50 had scores similar to normal breast tissue, and 49 had higher scores for the receptor. Levels of expression of the receptor within the primary breast carcinomas were unrelated to immunohistochemical detection of PTHrP or to any standard prognostic factor. There was a significant (P = 0.05) relationship between Ki-67 and PTHrPR expression in individual tumours. The presence of PTHrP and its receptor in normal breast epithelium and breast carcinomas demonstrates that most breast tumours are able to respond to PTHrP. The Ki-67 data suggest that PTHrP is a potential autocrine growth factor in primary breast carcinoma.


When fairness is not enough: The disproportionate contributions of the poor in a collective action problem.
Many of our most pressing challenges, from combating climate change to dealing with pandemics, are collective action problems: situations in which individual and collective interests conflict with each other. In such situations, people face a dilemma about making individually costly but collectively beneficial contributions to the common good. Understanding which factors influence people's willingness to make these contributions is vital for the design of policies and institutions that support the attainment of collective goals. In this study, we investigate how inequalities, and different causes of inequalities, impact individual-level behavior and group-level outcomes. First, we find that what people judged to be fair was not enough to solve the collective action problem: if they acted according to what they thought was fair, they would collectively fail. Second, the level of wealth (rich vs. poor) altered what was judged to be a fair contribution to the public good more than the cause of wealth (merit vs. luck vs. uncertain). Contributions during the game reflected these fairness judgments, with poorer individuals consistently contributing a higher proportion of their wealth than richer participants, which further increased inequality-particularly in successful groups. Finally, the cause of one's wealth was largely irrelevant, mattering most only when it was uncertain, as opposed to resulting from merit or luck. We discuss implications for policymakers and international climate change negotiations. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Hemodynamic effects of nitroglycerin in acute myocardial infarction.
Nitroglycerin (NTG) has recently been suggested to decrease myocardial ischemia and enhance cardiac pump function during acute myocardial infarction (AMI). To evaluate the sublingual agnet in this condition, the hemodynamic effects of 0.4 mg NTG administered to 16 supine patients during the first 72 hours of AMI were determined serially 5, 10 to 15, and 20 to 30 minutes post-NTG. Data were evaluated for the entire group, as well as for six patients with normal pulmonary artery wedge pressure (PAW) (less than or equal to 12 mm Hg; mean 7) who formed group I and for ten patients with elevated PAW (greater than 12 MM Hg; mean 19) who comprised group II. In the 16 patients, NTG resulted in significant decreases in PAW (14 TO 7 MM Hg; P less than .01), mean systemic arterial pressure (MAP) (95 TO 82 MM Hg; P less than .01), cardiac index (CI) (1.79 TO 1.46 L/min/m-2; P less than .02), stroke index (SI) (24 TO 18 CC/M-2; P less than .01) and stroke work index (SWI) (27 TO 20 GM TIMES M/M-2; P less than .01). These alterations were significant in both subgroups, with the decline in PAW greater (P less than .05), while there was no change in group II. There was no significant change in total peripheral vascular resistance (TPVR) for the entire group or in the two subgroups. This study demonstrates that, regardless of initial left ventricular filling pressure, sublingual NTG given in the acute phase of AMI results in rapid fall in PAW, concomitant with decreases in systemic blood pressure, cardiac output and SWI, without changes in TPVR and with little or no effect on heart rate. Since TPVR was unaltered, the decline in MAP was due to fall in cardiac output. Thus, the principal action of sublingual NTG in AMI appears to be systemic venodilation with consequent reduction of ventricular preload. This effect is translated into decline ofpump output even in patients with high initial filling pressures. Although NTG may rapidly relieve pulmonary congestion and lower myocardial oxygen consumption, use of the agent sublingually is limited in AMI because these salutary effects are accomppanied by potentially deleterious fall in cardiac output and systemic blood pressure.


Risks and difficulties of the treatment of aphakia in infancy.
In a clinic where 250 children have been fitted with contact lenses between 1976 and 1982, one hundred and five were bilateral infantile aphakic patients. A review of the data sheets of 43 bilateral infantile aphakic patients in this group implies that the corneal complications of treatment are substantial but surmountable and that the risks and difficulties of contact lens treatment are probably justifiable if the recent reports of improved visual function in these patients are substantiated.


Mathematical modelling of diurnal regulation of carbohydrate allocation by osmo-related processes in plants.
Plants synthesize sucrose in source tissues (mainly mature leafs) and supply it for growth of sink tissues (young leafs). Sucrose is derived from photosynthesis during daytime and from starch at night. Because the diurnal regulation of sucrose fluxes is not completely understood, we built a mathematical model designed to reproduce all key experimental observations. For this, assumptions were made about the molecular mechanisms underlying the regulations, which are all motivated by experimental facts. The key regulators in our model are two kinases (SnRK1 and osmo-sensitive kinase OsmK) under the control of the circadian clock. SnRK1 is activated in the night to prepare for regularly occurring carbon-limiting conditions, whereas OsmK is activated during the day to prepare for water deficit, which often occurs in the afternoon. Decrease of SnRK1 and increase of OsmK result in partitioning of carbon towards sucrose to supply growing sink tissues. Concomitantly, increasing levels of the growth regulator trehalose-6-phosphate stimulates the development of new sink tissues and thus sink demand, which further activates sucrose supply in a positive feedback loop. We propose that OsmK acts as a timer to measure the length of the photoperiod and suggest experiments how this hypothesis can be validated.