Menopausal Symptom Relief and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Conjugated Equine Estrogen and/or Progestin Hormone Replacement Therapy, Part 3.
The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy. A descriptive comparative design was used. Inferential and descriptive statistical procedures including a paired difference t-test, two-sample t-test, and f-tests (percentage, mean, standard deviation, frequency) were run on the Statistical Package for the Social Sciences. The framework used to guide this study was Lenz and Pugh's Theory of Unpleasant Symptoms. Surveys were distributed once to a convenient sample of women aged 35 and older when they dropped off or picked up their prescriptions at a pharmacy. Of the 216 surveys distributed, 70 were returned from those women taking compounded bioidentical hormone replacement therapy and 53 from traditional hormone replacement therapy. The survey contained 15 questions pertaining to age, duration of hormone replacement therapy, type and formulation of hormone replacement therapy, reasons for initiating hormone replacement therapy, symptoms before and one month after hormone replacement therapy, and side effects related to hormone replacement therapy. Included in part 1 of this series of articles was the introduction to the study conducted and the results of the literature review that was conducted for the purpose of examining the current data related to the topic of hormone replacement therapy. Part 2 provided a brief discussion on the significance of this study to nursing and provided the methods used in this study. The results and conclusion of this study are provided within this article.


Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity.
The epidemic of obesity imposes unprecedented challenges on human adipose tissue (WAT) storage capacity that may benefit from adaptive mechanisms to maintain adipocyte functionality. Here, we demonstrate that changes in the regulatory feedback set point control of Insig1/SREBP1 represent an adaptive response that preserves WAT lipid homeostasis in obese and insulin-resistant states. In our experiments, we show that Insig1 mRNA expression decreases in WAT from mice with obesity-associated insulin resistance and from morbidly obese humans and in in vitro models of adipocyte insulin resistance. Insig1 downregulation is part of an adaptive response that promotes the maintenance of SREBP1 maturation and facilitates lipogenesis and availability of appropriate levels of fatty acid unsaturation, partially compensating the antilipogenic effect associated with insulin resistance. We describe for the first time the existence of this adaptive mechanism in WAT, which involves Insig1/SREBP1 and preserves the degree of lipid unsaturation under conditions of obesity-induced insulin resistance. These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress.


A measure of cognitions specific to seasonal depression: Development and validation of the Seasonal Beliefs Questionnaire.
We introduce the Seasonal Beliefs Questionnaire (SBQ), a self-report inventory of maladaptive thoughts about the seasons, light availability, and weather conditions, proposed to constitute a unique cognitive vulnerability to winter seasonal affective disorder (SAD; Rohan, Roecklein, & Haaga, 2009). Potential items were derived from a qualitative analysis of self-reported thoughts during SAD-tailored cognitive-behavioral therapy (CBT-SAD) and subsequently refined based on qualitative feedback from 48 SAD patients. In the psychometric study (N = 536 college students), exploratory and confirmatory factor analyses pruned the items to a 26-item scale with a 5-factor solution, demonstrating good internal consistency, convergent and divergent validity, and 2-week test-retest reliability. In a known groups comparison, the SBQ discriminated SAD patients (n = 86) from both nonseasonal major depressive disorder (MDD) patients (n = 30) and healthy controls (n = 110), whereas a generic measure of depressogenic cognitive vulnerability (the Dysfunctional Attitudes Scale [DAS]) discriminated MDD patients from the other groups. In a randomized clinical trial comparing CBT-SAD with light therapy (N = 177), SBQ scores improved at twice the rate in CBT-SAD than in light therapy. Greater change in SBQ scores during CBT-SAD, but not during light therapy, was associated with a lower risk of depression recurrence 2 winters later. In contrast, DAS scores improved comparably during CBT-SAD and light therapy, and DAS change was unrelated to recurrence following either treatment. These results support using the SBQ as a brief assessment tool for a SAD-specific cognitive vulnerability and as a treatment target in CBT-SAD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Long-Lasting Alterations in Gene Expression of Postsynaptic Density 95 and Inotropic Glutamatergic Receptor Subunit in the Mesocorticolimbic System of Rat Offspring Born to Morphine-Addicted Mothers.
Prenatal exposure to morphine causes altered glutamatergic neurotransmission, which plays an important pathophysiological role for neurobiological basis of opiate-mediated behaviors in such offspring. However, it is still not clear whether such alteration involves gene expression of ionotropic glutamate receptor subunits. In this study, we further studied whether prenatal morphine exposure resulted in long-term changes in the gene expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, N-methyl-d-aspartate (NMDA) receptor, and postsynaptic density 95 in the mesocorticolimbic area (an essential integration circuitry for drug craving behavior), nucleus accumbens (NAc), ventral tegmental area (VTA), and prefrontal cortex (PFC), of rat offspring from morphine-addicted mothers. Experimental results showed that prenatal morphine exposure led to a persistent downregulation of gene expression in the AMPA and NMDA receptor subunit, with a differential manner of decreased magnitudes, at the age of postnatal days 14 (P14) and P30. However, in PFC, the gene expression of the AMPA receptor subunit was not synchronized in observed rat offspring subjected to prenatal morphine exposure. An upregulation of gene expression in the AMPA receptor subunit 3 (GluR3) was persistently observed at P14 and P30. Furthermore, the gene expressions of PSD-95 in NAc, VTA, and PFC were all decreased concurrently. Collectively, the results suggest that prenatal exposure to morphine may initiate molecular mechanisms leading to a long-lasting, differential alteration in gene expression of the inotropic glutamate receptor subunit and PSD-95 in the mesocorticolimbic circuitry in rat offspring. This study raises a possibility in which differential changes in gene expression with a long-lasting manner may play a role for the development of nearly permanent changes in opiate-mediated behaviors, at least in part for the neurobiological pathogenesis in offspring.


Critical Aspects of Person Counting and Density Estimation.
Many scientific studies deal with person counting and density estimation from single images. Recently, convolutional neural networks (CNNs) have been applied for these tasks. Even though often better results are reported, it is often not clear where the improvements are resulting from, and if the proposed approaches would generalize. Thus, the main goal of this paper was to identify the critical aspects of these tasks and to show how these limit state-of-the-art approaches. Based on these findings, we show how to mitigate these limitations. To this end, we implemented a CNN-based baseline approach, which we extended to deal with identified problems. These include the discovery of bias in the reference data sets, ambiguity in ground truth generation, and mismatching of evaluation metrics w.r.t. the training loss function. The experimental results show that our modifications allow for significantly outperforming the baseline in terms of the accuracy of person counts and density estimation. In this way, we get a deeper understanding of CNN-based person density estimation beyond the network architecture. Furthermore, our insights would allow to advance the field of person density estimation in general by highlighting current limitations in the evaluation protocols.


Preliminary Assessment of Resistance Among U.S. Wheat Cultivars to the Triticum Pathotype of Magnaporthe oryzae.
Magnaporthe oryzae is the causal agent of blast disease on several graminaceous plants. The M. oryzae population causing wheat blast has not been officially reported outside South America. Wheat production in the United States is at risk to this pathogen if it is introduced and established. Proactive testing of U.S. wheat cultivars for their reaction to blast and identification of resistance resources is crucial due to the national and global importance of the U.S. wheat industry. In this preliminary study, the phenotypic reaction of 85 U.S. wheat cultivars to M. oryzae (Triticum pathotype) was determined. Although there was a significant correlation in the reaction to blast at the seedling and adult plant stages, only 57% of the head reaction was explained by the seedling reaction. Because of the importance of disease development at the head stage in the field, assessment of all 85 cultivars occurred at the head stage. Among cultivars tested, a continuum in severity to head blast was observed; cultivars Everest and Karl 92 were highly susceptible with more than 90% disease severity, while cultivars Postrock, JackPot, Overley, Jagalene, Jagger, and Santa Fe showed less than 3% infection. No evidence of the presence of physiological races among isolates T-7, T-12, T-22, and T-25 was found.


Antisymmetric spin filtering in one-dimensional electron systems with uniform spin-orbit coupling.
We theoretically analyze the possibility to use a ferromagnetic gate as a spin-polarization filter for one-dimensional electron systems formed in semiconductor heterostructures showing strong Rashba spin-orbit interaction. The proposed device is based on the effect of the breaking time-reversal symmetry due to the presence of weak magnetic fields. For a proper strength and magnetic field orientation there appears an energy interval in the electron energy spectrum at which the orientation of spin states is controlled by the direction of the electron velocity. It leads to the natural spin polarization of the electron current if the Fermi energy falls into this energy interval.


A chemical, morphological, and electrochemical (XPS, SEM/EDX, CV, and EIS) analysis of electrochemically modified electrode surfaces of natural chalcopyrite (CuFeS2) and pyrite (FeS2) in alkaline solutions.
Electrodic surfaces of natural chalcopyrite and natural pyrite minerals (El Teniente mine, Chile) have been studied by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy including microanalysis (SEM/EDX). For comparison, fractured and polished mineral surfaces were also studied by XPS. In both electrodes, the formation of Fe(III) species containing oxygen were detected and Cu(II) species containing oxygen were additionally detected for chalcopyrite at advanced oxidation states. The presence of Cu(II) species containing oxygen was not detected by XPS for the initial oxidation states of the chalcopyrite. For pyrite, the present results do not allow confirmation of the presence of polysulfurs such as have been previously proposed. In both minerals, the measurements of SEM and EDX show relevant alterations in the respective surfaces when different potential values were applied. The chalcopyrite surface shows the formation of protrusions with a high concentration of oxygen. The pyrite surface shows a layer of modified material with high oxygen content. The modifications detected by XPS, SEM, and EDX allowed the explanation of the complexity of the equivalent circuit used to simulate the experimental EIS data. At high oxidation states, both minerals showed a pseudoinductive loop in the equivalent circuit, which was due to the active electrodissolution of the minerals which takes place through a surface film previously formed.


Canine oviductal exosomes improve oocyte development via EGFR/MAPK signaling pathway.
Oviduct cells produce a favorable environment for the development of gametes by generating multiple growth factors. Particularly, in canine species, immature oocytes undergo serial maturation processes in the oviduct, while the other mammals already possess matured oocytes in ovulatory follicles. However, little is known about the potential effect exhibited by the components released from canine oviduct cells (OCs) for modulating the biological function of oocytes. Recently, exosomes are regarded as promising extracellular vesicles because they represent considerable data for molecular cargo. Therefore, we first investigated the effect of canine oviductal exosomes (OC-Exo) on oocyte development via EGFR/MAPK pathway. Our results showed that OC-Exo labeled with PHK67 are successfully incorporated with cumulus cells and oocytes during IVM. Also, OC-Exo markedly increased the proportion of cumulus-oocyte complexes (COCs) exhibiting cumulus expansion as well as cumulus cell proliferation and maturation rate of oocytes (P < 0.05). Furthermore, gene expression patterns related with EGFR/MAPK pathway including EGFR, PKA, TACE/ADAM17, MAPK1/3, MAPK14, PTGS2, TNFAIP6, GDF9, and BMP15 were positively modified in COCs cultured with OC-Exo (P < 0.05). In addition, OC-Exo significantly up-regulated the protein expression levels of p-EGFR, p-MAPK1/3, GDF9 and BMP15 in COCs (P < 0.05). Consequently, the current study provides a model for understanding the roles of OC-Exo as bioactive molecules for canine oocyte maturation via EGFR/MAPK pathway, which would open a new avenue for the application of exosomes to improve assisted reproductive technology in mammals, including humans.


Effect of the Strawberry Genotype, Cultivation and Processing on the Fra a 1 Allergen Content.
Birch pollen allergic patients show cross-reactivity to vegetables and fruits, including strawberries (Fragaria × ananassa). The objective of this study was to quantify the level of the Fra a 1 protein, a Bet v 1-homologous protein in strawberry fruits by a newly developed ELISA, and determine the effect of genotype, cultivation and food processing on the allergen amount. An indirect competitive ELISA using a specific polyclonal anti-Fra a 1.02 antibody was established and revealed high variability in Fra a 1 levels within 20 different genotypes ranging from 0.67 to 3.97 µg/g fresh weight. Mature fruits of red-, white- and yellow-fruited strawberry cultivars showed similar Fra a 1 concentrations. Compared to fresh strawberries, oven and solar-dried fruits contained slightly lower levels due to thermal treatment during processing. SDS-PAGE and Western blot analysis demonstrated degradation of recombinant Fra a 1.02 after prolonged (>10 min) thermal treatment at 99 °C. In conclusion, the genotype strongly determined the Fra a 1 quantity in strawberries and the color of the mature fruits does not relate to the amount of the PR10-protein. Cultivation conditions (organic and conventional farming) do not affect the Fra a 1 level, and seasonal effects were minor.


Summary estimates of cholesterol used to predict coronary heart disease.
The relationships of total cholesterol and the proportion of cholesterol in individual lipoprotein classes to coronary heart disease are complex. To help simplify these relationships, cholesterol values are often combined into one summary estimate to form a single risk factor with a relationship to disease that is more easily described. Although summary estimates result in convenient expressions relating cholesterols to coronary heart disease, there is the potential for sacrificing information by ignoring the joint configuration of cholesterols that make up these estimates. We investigated the extent of this possibility for the ratio of total cholesterol to high-density lipoprotein cholesterol and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol. The findings suggest that the summary estimates are useful expressions for combining cholesterol information and are strong predictors of coronary heart disease. Clinicians who choose to use a summary estimate for screening purposes should recognize that a single ratio estimate is not always as informative as the joint configuration of the cholesterols that make up the estimate. This possibility is most clearly exhibited for the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and it may become more apparent in future studies as the capabilities of exploring lipoprotein cholesterol relationships improve.


Unique lipoprotein phenotype and genotype associated with exceptional longevity.
Individuals with exceptional longevity have a lower incidence and/or significant delay in the onset of age-related disease, and their family members may inherit biological factors that modulate aging processes and disease susceptibility. To identify specific biological and genetic factors that are associated with or reliably define a human longevity phenotype. In a case-control design, 213 Ashkenazi Jewish probands with exceptional longevity (mean [SD] age, 98.2 [5.3] years) and their offspring (n = 216; mean [SD] age, 68.3 [6.7] years) were recruited from 1998 to 2002, while an age-matched control group of Ashkenazi Jews (n = 258) and participants from the Framingham Offspring Study (n = 589) were accepted as control groups. Detailed questionnaires, physical examination, and blood samples were taken, including assessment of lipids and lipoprotein subclass levels and particle sizes by proton nuclear magnetic resonance. Samples were also genotyped for the codon 405 isoleucine to valine (I405V) variation in the cholesteryl ester transfer protein (CETP) gene, which is involved in regulation of lipoprotein and its particle sizes. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) particle sizes were significantly higher in probands compared with both control groups (P =.001 for both), independent of plasma levels of HDL and LDL cholesterol and apolipoprotein A1 and B. This phenotype was also typical of the proband's offspring but not of the age-matched controls. The HDL and LDL particle sizes were significantly larger in offspring and controls without hypertension or cardiovascular disease, (P =.001 and P =.008, respectively). Furthermore, lipoprotein particle sizes, but not plasma LDL levels, were significantly higher in offspring and controls without the metabolic syndrome (P<.001). Probands and offspring had a 2.9- and 3.6-fold (in men) and 2.7- and 1.5-fold (in women) increased frequency, respectively, of homozygosity for the 405 valine allele of CETP (VV genotype), respectively, compared with controls (P<.001 for both). Those probands with the VV genotype had increased lipoprotein sizes and lower serum CETP concentrations. Individuals with exceptional longevity and their offspring have significantly larger HDL and LDL particle sizes. This phenotype is associated with a lower prevalence of hypertension, cardiovascular disease, the metabolic syndrome, and increased homozygosity for the I405V variant in CETP. These findings suggest that lipoprotein particle sizes are heritable and promote a healthy aging phenotype.


Improved methodology to assess modification and completion of landfill gas management in the aftercare period.
Municipal solid waste landfills represent the dominant option for waste disposal in many parts of the world. While some countries have greatly reduced their reliance on landfills, there remain thousands of landfills that require aftercare. The development of cost-effective strategies for landfill aftercare is in society's interest to protect human health and the environment and to prevent the emergence of landfills with exhausted aftercare funding. The Evaluation of Post-Closure Care (EPCC) methodology is a performance-based approach in which landfill performance is assessed in four modules including leachate, gas, groundwater, and final cover. In the methodology, the objective is to evaluate landfill performance to determine when aftercare monitoring and maintenance can be reduced or possibly eliminated. This study presents an improved gas module for the methodology. While the original version of the module focused narrowly on regulatory requirements for control of methane migration, the improved gas module also considers best available control technology for landfill gas in terms of greenhouse gas emissions, air quality, and emissions of odoriferous compounds. The improved module emphasizes the reduction or elimination of fugitive methane by considering the methane oxidation capacity of the cover system. The module also allows for the installation of biologically active covers or other features designed to enhance methane oxidation. A methane emissions model, CALMIM, was used to assist with an assessment of the methane oxidation capacity of landfill covers.


Search for the Higgs boson produced in association with a W boson and decaying to four b-quarks via two spin-zero particles in pp collisions at 13 TeV with the ATLAS detector.
This paper presents a dedicated search for exotic decays of the Higgs boson to a pair of new spin-zero particles, [Formula: see text], where the particle a decays to b-quarks and has a mass in the range of 20-60 GeV. The search is performed in events where the Higgs boson is produced in association with a [Formula: see text] boson, giving rise to a signature of a lepton (electron or muon), missing transverse momentum, and multiple jets from b-quark decays. The analysis is based on the full dataset of pp collisions at [Formula: see text] recorded in 2015 by the ATLAS detector at the CERN Large Hadron Collider, corresponding to an integrated luminosity of 3.2 [Formula: see text]. No significant excess of events above the Standard Model prediction is observed, and a [Formula: see text] confidence-level upper limit is derived for the product of the production cross section for [Formula: see text] times the branching ratio for the decay [Formula: see text]. The upper limit ranges from 6.2 pb for an a-boson mass [Formula: see text] to 1.5 pb for [Formula: see text].


The effectiveness of assertive community treatment for elderly patients with severe mental illness: a randomized controlled trial.
Due to fragmented mental, somatic, and social healthcare services, it can be hard to engage into care older patients with severe mental illness (SMI). In adult mental health care, assertive community treatment (ACT) is an organizational model of care for treating patients with SMI who are difficult to engage. So far all outcome studies of assertive community treatment have been conducted in adults. In a randomized controlled trial design we compared the effectiveness of ACT for elderly patients with that of treatment as usual (TAU). Sixty-two outpatients (60 years and older) with SMI who were difficult to engage in psychiatric treatment were randomly assigned to the intervention or control group (32 to ACT for elderly patients and 30 to TAU). Primary outcomes included number of patients who had a first treatment contact within 3 months, the number of dropouts (i.e. those discharged from care due to refusing care or those who unintentionally lost contact with the service over a period of at least 3 months); and patients' psychosocial functioning (HoNOS65+ scores) during 18 months follow-up. Secondary outcomes included the number of unmet needs and mental health care use. Analyses were based on intention-to-treat. Of the 62 patients who were randomized, 26 were lost to follow-up (10 patients in ACT for elderly patients and 16 in TAU). Relative to patients with TAU, more patients allocated to ACT had a first contact within three months (96.9 versus 66.7%; X2 (df = 1) = 9.68, p = 0.002). ACT for elderly patients also had fewer dropouts from treatment (18.8% of assertive community treatment for elderly patients versus 50% of TAU patients; X2 (df = 1) = 6.75, p = 0.009). There were no differences in the other primary and secondary outcome variables. These findings suggest that ACT for elderly patients with SMI engaged patients in treatment more successfully. NTR1620.


Process-explicit models reveal the structure and dynamics of biodiversity patterns.
With ever-growing data availability and computational power at our disposal, we now have the capacity to use process-explicit models more widely to reveal the ecological and evolutionary mechanisms responsible for spatiotemporal patterns of biodiversity. Most research questions focused on the distribution of diversity cannot be answered experimentally, because many important environmental drivers and biological constraints operate at large spatiotemporal scales. However, we can encode proposed mechanisms into models, observe the patterns they produce in virtual environments, and validate these patterns against real-world data or theoretical expectations. This approach can advance understanding of generalizable mechanisms responsible for the distributions of organisms, communities, and ecosystems in space and time, advancing basic and applied science. We review recent developments in process-explicit models and how they have improved knowledge of the distribution and dynamics of life on Earth, enabling biodiversity to be better understood and managed through a deeper recognition of the processes that shape genetic, species, and ecosystem diversity.


Genetic and toxinological divergence among populations of Tityus trivittatus Kraepelin, 1898 (Scorpiones: Buthidae) inhabiting Paraguay and Argentina.
Envenoming by scorpions in genus Tityus is a public health problem in Tropical America. One of the most medically significant species is Tityus trivittatus, which is known to occur from southwest Brazil to central-northern and eastern Argentina. In this work, we studied the lethality, composition, antigenicity, and enzymatic activity of venom from a T. trivittatus population found further north in urban areas of eastern Paraguay, where it has caused serious envenomation of children. Our results indicate that the population is of medical importance as it produces a potently toxic venom with an LD50 around 1.19 mg/kg. Venom neutralization in preliminary mouse bioassays was complete when using Brazilian anti-T. serrulatus antivenom but only partial when using Argentinean anti-T. trivittatus antivenom. Venom competitive solid-phase enzyme immunoassays and immunoblotting from Argentinean and Paraguayan T. trivittatus populations indicated that antigenic differences exist across the species range. SDS-PAGE showed variations in type and relative amounts of venom proteins between T. trivitattus samples from Argentina and Paraguay. MALDI-TOF mass spectrometry indicated that while some sodium channel toxins are shared, including β-toxin Tt1g, others are population-specific. Proteolytic activity by zymography and peptide identification through nESI-MS/MS also point out that population-specific proteases may exist in T. trivitattus, which are postulated to be involved in the envenoming process. A time-calibrated molecular phylogeny of mitochondrial COI sequences revealed a significant (8.14%) genetic differentiation between the Argentinean and Paraguayan populations, which appeared to have diverged between the mid Miocene and early Pliocene. Altogether, toxinological and genetic evidence indicate that T. trivitattus populations from Paraguay and Argentina correspond to distinct, unique cryptic species, and suggest that further venom and taxonomic diversity exists in synanthropic southern South American Tityus than previously thought.


Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design.
Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.


Evaluation of dose homogenization and radiation carcinogenesis risk in total body irradiation for bone marrow transplantation.
The purpose of this study is to report on the dose homogeneity in total body irradiated patients undergoing Bone Marrow Transplantation (BMT), and carcinogenic risk in surviving patients. Between 1987 and 2001, 105 patients received hyperfractionated (6 fractions in 3 days) 12 Gy Total Body Irradiation (TBI) in our institution with lateral opposed fields. All the patients had measurements with thermoluminiscence dosimetry (TLD100) placed on seven bilateral body sites in vivo, controlled by the randophantom measurements to verify reasonable dose homogeneity achievement. The comorbid effects in the whole TBI conditioning group with at least three months post BMT follow-up were noted and surviving patients who had a minimum 5-year and maximum 14-year follow-up (median 7.8 years) have been evaluated for carcinogenic radiation risk on the basis of tissue weighting factors as defined by ICRP 60. Reasonable dose homogeneity by lateral opposed beam TBI has been obtained in all 105 patients in whom lateral TLD100 measurement means were within +5% of the planned doses. Calculated carcinogenesis risk factor was 11.34% for males and 12.40% for females, and no second-cancer has been detected whilst radiation-induced 5 cataracts and 10 interstitial pneumonia comorbidities were noted. Dose homogenization can be well achieved for hyperfractionated lateral-beam TBI with acceptable comorbidities and estimated second-cancer risk is significant but relatively low compared to the risk from the clinical indications for TBI.


Everything you never wanted to know about circular analysis, but were afraid to ask.
Over the past year, a heated discussion about 'circular' or 'nonindependent' analysis in brain imaging has emerged in the literature. An analysis is circular (or nonindependent) if it is based on data that were selected for showing the effect of interest or a related effect. The authors of this paper are researchers who have contributed to the discussion and span a range of viewpoints. To clarify points of agreement and disagreement in the community, we collaboratively assembled a series of questions on circularity herein, to which we provide our individual current answers in <or=100 words per question. Although divergent views remain on some of the questions, there is also a substantial convergence of opinion, which we have summarized in a consensus box. The box provides the best current answers that the five authors could agree upon.


SU-D-213CD-04: Dosimetric Evaluation of HexaPOD as a Tool for Patient Setup Verification Accuracy.
To quantify the dosimetric accuracy of 6 degrees vs. 3 degrees of motion for patient positioning for cone-beam CT and HexaPOD Evo RT system (Elekta, Inc.) using the ArcCHECK (Sun Nuclear Corporation, software v.6.0) QA phantom. The average absolute values of our daily reported patient hexapod shift data were recorded and averaged for 18 patients. Using the CT scans of ArcCHECK, a QA plan was created in the Pinnacle (v.9.0) treatment planning system. By setting up ArcCHECK according to the QA plan and measuring the dose on Elekta Synergy, the baseline data was established. Next, an artificial shift was introduced in our phantom setup. A cone-beam CT scan of the phantom was obtained and images adjusted. The resulting translational and rotational shifts were recorded. The table was then moved according to the translational shifts only, and another measurement was taken. Next, using hexapod translational and rotational shifts, the table was moved in 6 degrees of motion, and the dose was re-measured. For 18 IMRT patients, the average translational shifts were: x= 0.53 cm, y=0.38 cm and z= 0.516 cm, and average rotational shifts were pitch=0.979°, roll=0.8° and yaw= 0.67°. The ArcCHECK phantom measured results were quantified using 3%, 3mm distance to agreement gamma analysis criteria when comparing measured to planned dose. Our measurements showed that an average 97.3% of the points agreed in plans with no shift. After the artificial shift was introduced, and cone-beam CT translational shifts were applied, 76.3% of points agreed. When both rotational and translational shifts were applied using Hexapod, an average of 93.4% of points agreed. Using hexapod for imaging and patient positioning results in a significantly more accurate dose delivery as compared to using only CBCT, as shown by our ArcCHECK QA phantom results.


Contact precautions: more is not necessarily better.
To determine whether increases in contact isolation precautions are associated with decreased adherence to isolation practices among healthcare workers (HCWs). Prospective cohort study from February 2009 to October 2009. Eleven teaching hospitals. HCWs. One thousand thirteen observations conducted on HCWs. Additional data included the number of persons in isolation, types of HCWs, and hospital-specific contact precaution practices. Main outcome measures included compliance with individual components of contact isolation precautions (hand hygiene before and after patient encounter, donning of gown and glove upon entering a patient room, and doffing upon exiting) and overall compliance (all 5 measures together) during varying burdens of isolation. Compliance with hand hygiene was as follows: prior to donning gowns/gloves, 37.2%; gowning, 74.3%; gloving, 80.1%; doffing of gowns/gloves, 80.1%; after gown/glove removal, 61%. Compliance with all components was 28.9%. As the burden of isolation increased (20% or less to greater than 60%), a decrease in compliance with hand hygiene (43.6%-4.9%) and with all 5 components (31.5%-6.5%) was observed. In multivariable analysis, there was an increase in noncompliance with all 5 components of the contact isolation precautions bundle (odds ratio [OR], 6.6 [95% confidence interval (CI), 1.15-37.44]; P = .03) and in noncompliance with hand hygiene prior to donning gowns and gloves (OR, 10.1 [95% CI, 1.84-55.54]; P = .008) associated with increasing burden of isolation. As the proportion of patients in contact isolation increases, compliance with contact isolation precautions decreases. Placing 40% of patients under contact precautions represents a tipping point for noncompliance with contact isolation precautions measures.


Offspring Microbiomes Differ Across Breeding Sites in a Panmictic Species.
High dispersal rates are known to homogenize host's population genetic structure in panmictic species and to disrupt host local adaptation to the environment. Long-distance dispersal might also spread micro-organisms across large geographical areas. However, so far, to which extent selection mechanisms that shape host's population genetics are mirrored in the population structure of the enteric microbiome remains unclear. High dispersal rates and horizontal parental transfer may homogenize bacterial communities between breeding sites (homogeneous hypothesis). Alternatively, strong selection from the local environment may differentiate bacterial communities between breeding sites (heterogeneous hypothesis). Furthermore, selection from age-specific environmental or physiological factors may differentiate the microbiome between juveniles and adults. Here, we analyzed the cloacal bacterial 16S rRNA gene of fledgling greater flamingos, Phoenicopterus roseus, across nine western Mediterranean breeding sites and four breeding seasons (n = 731) and adult birds (n = 27) from a single site. We found that fledgling cloacal microbiome, as measured by alpha diversity, beta diversity, the relative abundance of assigned sequence variants (ASVs) belonging to a phylum and genus composition within phylum, varied significantly between sampling sites and across time within site despite high adult dispersal rates. The spatio-temporal effects were stronger on individual ASV absence/presence than on ASV abundance (i.e., than on core microbiome composition). Spatial effects had a stronger effect than temporal effects, particularly on ASV abundance. Our study supports the heterogeneous hypothesis whereby local environmental conditions select and differentiate bacterial communities, thus countering the homogenizing effects of high-dispersing host species. In addition, differences in core microbiome between adult vs. fledgling samples suggests that differences in age-specific environmental and/or physiological factors result in differential selection pressure of core enteric microbiome between age classes, even within the same environment. In particular, the genus Corynebacterium, associated with both seasonal fat uptake and migration in previous studies, was much more abundant in high-dispersing fledglings than in more resident adults. To conclude, selection mechanisms that shape the host's genetic structure cannot be extended to the genetic structure of the enteric microbiome, which has important implications regarding our understanding of both host local adaptation mechanisms and enteric microbiome population genetics.


The Rosa genome provides new insights into the domestication of modern roses.
Roses have high cultural and economic importance as ornamental plants and in the perfume industry. We report the rose whole-genome sequencing and assembly and resequencing of major genotypes that contributed to rose domestication. We generated a homozygous genotype from a heterozygous diploid modern rose progenitor, Rosa chinensis 'Old Blush'. Using single-molecule real-time sequencing and a meta-assembly approach, we obtained one of the most comprehensive plant genomes to date. Diversity analyses highlighted the mosaic origin of 'La France', one of the first hybrids combining the growth vigor of European species and the recurrent blooming of Chinese species. Genomic segments of Chinese ancestry identified new candidate genes for recurrent blooming. Reconstructing regulatory and secondary metabolism pathways allowed us to propose a model of interconnected regulation of scent and flower color. This genome provides a foundation for understanding the mechanisms governing rose traits and should accelerate improvement in roses, Rosaceae and ornamentals.


Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion.
Prooxidents can induce reversible inhibition or irreversible inactivation and degradation of the mitochondrial enzyme aconitase. Cardiac ischemia/reperfusion is associated with an increase in mitochondrial free radical production. In the current study, the effects of reperfusion-induced production of prooxidants on mitochondrial aconitase and proteolytic activity were determined to assess whether alterations represented a regulated response to changes in redox status or oxidative damage. Evidence is provided that ATP-dependent proteolytic activity increased during early reperfusion followed by a time-dependent reduction in activity to control levels. These alterations in proteolytic activity paralleled an increase and subsequent decrease in the level of oxidatively modified protein. In vitro data supports a role for prooxidants in the activation of ATP-dependent proteolytic activity. Despite inhibition during early periods of reperfusion, aconitase was not degraded under the conditions of these experiments. Aconitase activity exhibited a decline in activity followed by reactivation during cardiac reperfusion. Loss and regain in activity involved reversible sulfhydryl modification. Aconitase was found to associate with the iron binding protein frataxin exclusively during reperfusion. In vitro, frataxin has been shown to protect aconitase from [4Fe-4S](2+) cluster disassembly, irreversible inactivation, and, potentially, degradation. Thus, the response of mitochondrial aconitase and ATP-dependent proteolytic activity to reperfusion-induced prooxidant production appears to be a regulated event that would be expected to reduce irreparable damage to the mitochondria.


In-line interferometer for direction-sensitive displacement measurements by optical feedback detection.
We demonstrate a compact in-line interferometer for direction-sensitive displacement measurement by optical feedback detection with a semiconductor laser (SL) light source. Two reflected beams from a semitransparent reference mirror and a reflecting test object interfere in the SL medium, causing a variation in its output power. The reference mirror is located between the SL output facet and the test object. The performance of the interferometer is investigated numerically and experimentally to determine its optimal operating conditions. We have verified the operating conditions where the behavior of the SL output power profile could indicate accurately the displacement magnitude and direction of the moving test object. The profile behavior is robust against variations in optical feedback and scale of the interferometer configuration.


Simultaneous detection of ochratoxin A and fumonisin B1 in cereal samples using an aptamer-photonic crystal encoded suspension array.
A simple, new aptamer-photonic crystal encoded suspension array was designed to simultaneously quantify and qualify ochratoxin A(OTA) and fumonisin B1(FB1) in cereal samples. The aptamers of OTA and FB1 were immobilized on the surfaces of photonic crystals by chemical bonding. When the target mycotoxins appear in a sample, the fluorescence-labeled complementary DNA of the aptamer dissociates from their double DNA hybrid and results in an obvious decrease in fluorescence intensity of the microsphere. The difference value of fluorescent intensities for each kind of silica photonic crystal microsphere (SPCM) quantitatively conveys the concentration of mycotoxin, and the structure colors or reflectance peak positions of the SPCMs confirm the kind of mycotoxin detected. The reaction conditions including the immobilization method for aptamers, hybridization, and incubation conditions have been optimized. This developed method displayed a wide linear detection range (0.01-1 ng/mL for OTA and 0.001-1 ng/mL for FB1) and a low limit of detection (0.25 pg/mL for OTA and 0.16 pg/mL for FB1). The recovery rates in the spiked cereal samples ranged from 81.80% to 116.38% for OTA and 76.58%-114.79% for FB1. The positive detection results in the naturally contaminated cereal samples were in agreement with those of classic enzyme-linked immunosorbent assay (ELISA). This simple suspension array scheme displays a great application potential for the high throughput screen assay of mycotoxins.


Self-help materials for anxiety: a randomized controlled trial in general practice.
The efficacy of a self-help package in treating chronic anxiety was evaluated in a randomized controlled trial in which the intervention group received self-help materials in the form of an audiotape and booklet, in addition to their current treatment. The intervention was successful in terms of mean depression scores (P = 0.01), anxiety scores (P = 0.04) and general health questionnaire scores (P = 0.02) which were significantly lower for the intervention group than for the controls. In addition, the depression scores fell faster for the intervention group than for the controls. The overall mean reduction in three months in adjusted depression scores was approximately two points greater for the intervention group than for the controls (P = 0.02). Clinicians welcomed the package as a valuable addition to the therapies available for managing chronic anxiety problems. Further studies should include larger sample sizes, taking into account the non-response to postal questionnaires over time.


Comparison of binding and removal of remnants of triglyceride-rich lipoproteins of intestinal and hepatic origin by rat liver in vitro.
Chylomicrons were isolated from intestinal lymph and very low-density lipoproteins (VLDL) from the perfusate of isolated perfused livers. In vivo the initial phase of clearance of these particles was very rapid. Chylomicrons appeared to be cleared more quickly than VLDL (t1/2 = 3.7 +/- 1.4 vs. 10.6 +/- 4.0 min). Remnants were prepared from these particles in eviscerated rats and isolated using conditions under which contamination of particles from one organ by particles from the other organ was minimal. The removal of these remnant particles by isolated perfused livers was studied. VLDL remnants were removed more rapidly than the nascent VLDL. The removal of 125I-labeled VLDL remnants was inhibited by the presence of unlabeled VLDL remnants or chylomicron remnants in the perfusate. A 15- to 20-fold excess of either particle inhibited about 50% of the uptake of the labeled lipoprotein. The two types of remnants had comparable potency as competitors of uptake. Similarly, the two types of remnants inhibited uptake of a trace of labeled chylomicron remnants. The binding of these particles to rat liver plasma remnants. The binding of these particles to rat liver plasma membranes was also investigated. Both labeled chylomicron remnants and VLDL remnants bound specifically to the membranes, and either type of remnant displaced the binding of the other with equal potency. Taken together, these results indicate that chylomicron and VLDL remnants share the same hepatic removal mechanism and suggest that the rate of removal of a remnant is not a function of the organ of origin of the precursor lipoprotein.


Geodesic lenses for guided optical waves.
Two-dimensional lenses are essential elements in integrated optics. As an alternative to the techniques already suggested and tested to obtain such optical systems, a different method is reported that consists of extending to thin film optics the principle of configuration lenses already studied for application to microwave antennas. The working principle of such lenses is that the propagation occurs along a curved surface in a two-dimensional Riemann space. The rays are the geodesics of the surface. Two optical geodesic lenses having planar input and output have been constructed and tested. They can be easily inserted in planar film circuits. The advantage of these optical systems is that the substrate can be prepared in advance with the accuracy of glass optics. Then the dielectric film can be deposited with the same method used for planar components.


Climate change and epilepsy: Time to take action.
Climate change is the biggest challenge facing humanity today. The associated global warming and humidification, increases in the severity and frequency of extreme climate events, extension of the ranges of vector-borne diseases, and the consequent social and economic stresses and disruption will have major negative consequences on many aspects of health care. People whose resilience to change is already impaired may suffer disproportionately from these environmental changes, which are of unprecedented reach and magnitude. There has been little connection made so far between climate change and epilepsy. We briefly review the history of climate change science and the subsequent response of the global scientific community. We consider how climate change effects might in general affect health and disease. We consider some of the underlying complex interactions that, for example, favor the spread of vector-borne diseases and how climate models operate and may help plan for global and local changes. We then speculate specifically on how these generic ideas may apply specifically to epilepsy. We consider these impacts at levels from molecular to the epidemiological. Data are sparse, and there is undoubtedly a need for more information to enable better estimation of possible effects of climate change on care in epilepsy. We also consider how the professional activities of those involved in epilepsy health care might contribute to global carbon emissions, for example, through flying for conference attendance. Healthcare organizations across the world are already considering, and responding to, many of these issues. We argue for more research in this area, but also for action today. Actions today are likely to generate cobenefits for health care, including care in epilepsy, resulting from efforts to decarbonize, mitigate effects of climate change that has already happened, and plan for adaptation to climate change.


Chemical characterization of etched dentin in non-carious cervical lesions.
Bonding to non-carious cervical lesion (NCCL) sclerotic dentin that involves acid etching continues to be a challenging problem due to its altered chemical structure. In the present study, the objective was to investigate the chemical response of NCCL sclerotic dentin to the different acid etching times. Extracted human premolars affected with NCCLs were selected, and a cavity matching the natural lesion with respect to size and location was prepared on the lingual surface of each tooth to serve as the control. The dentin surfaces were treated for 15 s and 30 s using 37% phosphoric acid and then analyzed by Raman microspectroscopic mapping/imaging. NCCL dentin substrates had dramatic effects on the chemical profile of dentin demineralization. The spectral comparison showed that the demineralized layer generated by the acid treatment was highly irregular in terms of depth and mineral component retained, especially when NCCL sclerotic dentin was etched for 15 s. When the etching time was increased to 30 s, the demineralization of NCCL sclerotic dentin was more effective and comparable to the nonsclerotic control that was treated for 15 s. Different etching times affected the depth, degree, and profile of the dentin demineralization. The shorter etching time (ie, 15 s) might not be adequate for NCCL sclerotic dentin. However, the longer etching time (ie, 30 s) would induce much deeper demineralized dentin for nonsclerotic substrates. Thus, although extended etching times can be used to remove the hypermineralized layer, further studies are required to analyze the impact this might have on the dentin bonding.


Superinfection and the evolution of parasite virulence.
Earlier ideas that parasites evolve toward becoming harmless to their hosts have, in recent years, given way to more analytic studies, focused on the 'basic reproductive rate', R0, of individual parasites. In general, the biology of the parasite life cycle will lead to constraining relations between virulence (parasite-associated host death or reduction in fertility) and transmissibility: the maximum R0 may then be attained by virulence being high, or low, or at some intermediate level, depending on the details of the constraining relations. Such studies have not generally included superinfection (where an already-infected host is infected by another parasite). Here we propose a general, but simple, model of superinfection, which is amenable to analytical treatment. In such models selection does not simply act to maximize R0; superinfection leads to selection for higher levels of virulence, highly polymorphic parasite populations and very complicated dynamics. We calculate the equilibrium distribution of parasite strains and the maximum level of virulence that can be maintained by superinfection. We also note the equivalence between our 'superinfection model' and recent approaches to the study of the meta-population dynamics of multi-species interactions.


A simple approach to ignoring irrelevant variables by population decoding based on multisensory neurons.
Sensory input reflects events that occur in the environment, but multiple events may be confounded in sensory signals. For example, under many natural viewing conditions, retinal image motion reflects some combination of self-motion and movement of objects in the world. To estimate one stimulus event and ignore others, the brain can perform marginalization operations, but the neural bases of these operations are poorly understood. Using computational modeling, we examine how multisensory signals may be processed to estimate the direction of self-motion (i.e., heading) and to marginalize out effects of object motion. Multisensory neurons represent heading based on both visual and vestibular inputs and come in two basic types: "congruent" and "opposite" cells. Congruent cells have matched heading tuning for visual and vestibular cues and have been linked to perceptual benefits of cue integration during heading discrimination. Opposite cells have mismatched visual and vestibular heading preferences and are ill-suited for cue integration. We show that decoding a mixed population of congruent and opposite cells substantially reduces errors in heading estimation caused by object motion. In addition, we present a general formulation of an optimal linear decoding scheme that approximates marginalization and can be implemented biologically by simple reinforcement learning mechanisms. We also show that neural response correlations induced by task-irrelevant variables may greatly exceed intrinsic noise correlations. Overall, our findings suggest a general computational strategy by which neurons with mismatched tuning for two different sensory cues may be decoded to perform marginalization operations that dissociate possible causes of sensory inputs.


DDX54 regulates transcriptome dynamics during DNA damage response.
The cellular response to genotoxic stress is mediated by a well-characterized network of DNA surveillance pathways. The contribution of post-transcriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing radiation (IR). Interestingly, more than 260 proteins, including many nucleolar proteins, showed increased binding to poly(A)+ RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well-defined class of pre-mRNAs that harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Because DDX54 promotes survival after exposure to IR, its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR.


Uptake and correlates of HIV testing among men in Malawi: evidence from a national population-based household survey.
HIV testing is one of the key strategies in the HIV/AIDS prevention and control programmes. However, studies examining utilization of this service by men in Malawi are limited. The aim of this study was to assess the uptake and determinants of HIV testing among men in Malawi. Secondary data analysis was conducted on cross-sectional household data for 7478 men aged 15 to 54 years drawn from the 2015-16 Malawi Demographic and Health Survey. Descriptive statistics, bivariate and multivariable logistic regression analyses were performed to identify the socio-demographic, behavioral and health service related factors that are associated with HIV testing service utilisation by men in Malawi. All analyses were performed using the complex sample analysis procedure of the Statistical Package for the Social Sciences version 22.0 to account for the multistage sampling used in Demographic Health Survey. Overall, 69.9% of the participants had ever been tested for HIV. The results indicate that age, region of residence, marital status, covered by health insurance, education and age at first sexual debut are significant predictors of HIV testing among men in Malawi. In particular, men who were in the age group 30-39 years (AOR = 3.00; 95% CI = 2.35-3.82), married (AOR = 3.03; 95% CI = 2.51-3.65), those with secondary or above education (AOR = 3.02; 95% CI = 2.33-3.91), and those who had health insurance (AOR = 1.66; 95% CI = 1.05-2.63) were likely to utilise HIV testing service than their counterparts. The findings suggest that HIV testing services and programmes need to target younger unmarried men aged 15-19, men with low level or no education and expand HIV testing services to the central and southern regions of Malawi. Targeting the undiagnosed men living with HIV in a timely manner is a crucial and necessary step not only for achieving the UNAIDS' 90-90-90 targets but for individuals to benefit from antiretroviral treatment and to sustainably reduce population-level HIV transmission.


Pifithrin-μ induces necroptosis through oxidative mitochondrial damage but accompanies epithelial-mesenchymal transition-like phenomenon in malignant mesothelioma cells under lactic acidosis.
Heat shock protein 70 (HSP70), a chaperone protein associated with tumorigenesis and chemoresistance, has attracted significant attention as a potential therapeutic target for the development of anticancer drugs. Here, the effects of pifithrin-μ, an effective dual inhibitor of HSP70 and p53, on anticancer activities and epithelial-mesenchymal transition (EMT) were investigated in malignant mesothelioma (MM) cells. MSTO-211HAcT cells, pre-incubated in a medium containing lactic acid, showed more potent resistance to cisplatin and gemcitabine, compared with their acid-sensitive parental MSTO-211H cells. Pifithrin-μ treatment induced both apoptosis and necroptosis, which were accompanied by an EMT-like phenomenon, as evidenced by an elongated cell morphology, decreased levels of epithelial cell markers including E-cadherin, claudin-1, and β-catenin, increased levels of mesenchymal markers including Snail, Slug, and vimentin, and increased cell migratory property. Moreover, pifithrin-μ increased intracellular ROS levels, which is associated with mitochondrial dysfunction and decreased cellular ATP content. A series of changes caused by pifithrin-μ treatment were effectively restored by lowering the ROS level through pretreatment with N-acetylcysteine. Collectively, our results suggest that pifithrin-μ may promote the metastatic behavior of surviving cells by triggering the EMT, despite its effective cell-killing action against MM cells, possibly linked to oxidative mitochondrial dysfunction and ATP depletion.


Cultural practices and medical beliefs in pre-revolutionary Russia compared to modern textbook advice: did Russian women breastfeed the "wrong" way?
Historical accounts of infant feeding practices can inform our understanding of current-day practices and the ways in which cultural traditions are incorporated into infant care. Pre-revolutionary Russian feeding practices have not previously been summarized, to our knowledge. The purpose of this study is to collect information about pre-revolutionary feeding practices. We may then be able to better understand the motivation for suboptimal practices and tailor feeding messages to the specific population. Materials were collected from libraries and from the Internet regarding medical, demographic, and ethnographic literature of the 19(th) century and early 21(st) century, primarily in Russian. Breastfeeding was pervasive in pre-revolutionary Russia, but suboptimal patterns such as withholding colostrum and early introduction of other foods and liquids were common. Breast problems were treated with folk remedies and comfort measures, some of which are similar to modern-day treatments. Around 1906, child rearing and infant feeding recommendations were subsumed by male physicians espousing the "scientific approach." Many of these medical recommendations were detrimental to the previously successful breastfeeding practices that, despite barriers, had allowed Russian women to continue breastfeeding for 2 years or longer.


Deletion polymorphism of glutathione S-transferases M1 and T1 in the Tunisian population.
Glutathione S-transferases (GST) play a vital role in cellular defense against environmentally toxic compounds. These enzymes present a genetic deletion polymorphism, which varies with ethnicity. To evaluate the frequencies of homozygous deletion of GSTM1 and GSTT1 genes in Tunisian population. On the basis of multiplex PCR protocol, the frequency of the deleted genotypes of GSTM1 and GSTT1 genes was evaluated on 145 healthy Tunisian subjects. We found that 34.6% of the individuals had the GSTM1 null genotype, 16.6% had the GSTT1 null genotype and 4.82% had a double deletion of both GSTM1 and GSTT1. The distribution of GSTM1 null in Tunisians is rather in the range of black populations and is lower than that reported in Asians, Arabs and Caucasians. However the frequency of GSTT1 null is in the range of several populations studied except Asians. The double deletion frequency seems lower than that described in different populations.


Photoproduction of proton gradients with pi-stacked fluorophore scaffolds in lipid bilayers.
Rigid p-octiphenyl rods were used to create helical tetrameric pi-stacks of blue, red-fluorescent naphthalene diimides that can span lipid bilayer membranes. In lipid vesicles containing quinone as electron acceptors and surrounded by ethylenediaminetetraacetic acid as hole acceptors, transmembrane proton gradients arose through quinone reduction upon excitation with visible light. Quantitative ultrafast and relatively long-lived charge separation was confirmed as the origin of photosynthetic activity by femtosecond fluorescence and transient absorption spectroscopy. Supramolecular self-organization was essential in that photoactivity was lost upon rod shortening (from p-octiphenyl to biphenyl) and chromophore expansion (from naphthalene diimide to perylene diimide). Ligand intercalation transformed the photoactive scaffolds into ion channels.


Regional Brain Volumes Moderate, but Do Not Mediate, the Effects of Group-Based Exercise Training on Reductions in Loneliness in Older Adults.
Introduction: Despite the prevalence of and negative health consequences associated with perceived loneliness in older adults, few studies have examined interactions among behavioral, psychosocial, and neural mechanisms. Research suggests that physical activity and improvements in perceived social support and stress are related to reductions in loneliness. Yet, the influence of brain structure on these changes is unknown. The present study examined whether change in regional brain volume mediated the effects of changes in social support and stress on change in perceived loneliness after an exercise intervention. We also examined the extent to which baseline brain volumes moderated the relationship between changes in social support, stress, and loneliness. Methods: Participants were 247 older adults (65.4 ± 4.6 years-old) enrolled in a 6-month randomized controlled trial comprised of four exercise conditions: Dance (n = 69), Strength/Stretching/Stability (n = 70), Walk (n = 54), and Walk Plus (n = 54). All groups met for 1 h, three times weekly. Participants completed questionnaires assessing perceived social support, stress, and loneliness at baseline and post-intervention. Regional brain volumes (amygdala, prefrontal cortex [PFC], hippocampus) before and after intervention were measured with automatic segmentation of each participant's T1-weighted structural MRI. Data were analyzed in a latent modeling framework. Results: Perceived social support increased (p = 0.003), while stress (p < 0.001), and loneliness (p = 0.001) decreased over the intervention. Increased social support directly (-0.63, p < 0.01) and indirectly, through decreased stress (-0.10, p = 0.02), predicted decreased loneliness. Changes in amygdala, PFC, and hippocampus volumes were unrelated to change in psychosocial variables (all p ≥ 0.44). However, individuals with larger baseline amygdalae experienced greater decreases in loneliness due to greater reductions in stress (0.35, p = 0.02). Further, individuals with larger baseline PFC volumes experienced greater reductions in stress due to greater increases in social support (-0.47, p = 0.02). No group differences in these pathways were observed. Conclusions: The social support environment and resulting reductions in stress, as opposed to exercise mode, may represent important features of exercise programs for improving older adults' perceived loneliness. As amygdala volume has been linked to anxiety, depression and impaired cognitive control processes in the PFC, moderation findings suggest further investigation in this area is warranted. Trial Registration: ClinicalTrials.gov identifier NCT01472744 (https://clinicaltrials.gov/ct2/show/NCT01472744?term=NCT01472744&rank=1).


Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis.
Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C-C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins' structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2's catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis.


Assessing Mitochondrial DNA Variation and Copy Number in Lymphocytes of ~2,000 Sardinians Using Tailored Sequencing Analysis Tools.
DNA sequencing identifies common and rare genetic variants for association studies, but studies typically focus on variants in nuclear DNA and ignore the mitochondrial genome. In fact, analyzing variants in mitochondrial DNA (mtDNA) sequences presents special problems, which we resolve here with a general solution for the analysis of mtDNA in next-generation sequencing studies. The new program package comprises 1) an algorithm designed to identify mtDNA variants (i.e., homoplasmies and heteroplasmies), incorporating sequencing error rates at each base in a likelihood calculation and allowing allele fractions at a variant site to differ across individuals; and 2) an estimation of mtDNA copy number in a cell directly from whole-genome sequencing data. We also apply the methods to DNA sequence from lymphocytes of ~2,000 SardiNIA Project participants. As expected, mothers and offspring share all homoplasmies but a lesser proportion of heteroplasmies. Both homoplasmies and heteroplasmies show 5-fold higher transition/transversion ratios than variants in nuclear DNA. Also, heteroplasmy increases with age, though on average only ~1 heteroplasmy reaches the 4% level between ages 20 and 90. In addition, we find that mtDNA copy number averages ~110 copies/lymphocyte and is ~54% heritable, implying substantial genetic regulation of the level of mtDNA. Copy numbers also decrease modestly but significantly with age, and females on average have significantly more copies than males. The mtDNA copy numbers are significantly associated with waist circumference (p-value = 0.0031) and waist-hip ratio (p-value = 2.4×10-5), but not with body mass index, indicating an association with central fat distribution. To our knowledge, this is the largest population analysis to date of mtDNA dynamics, revealing the age-imposed increase in heteroplasmy, the relatively high heritability of copy number, and the association of copy number with metabolic traits.


Iron intake and markers of iron status and risk of Barrett's esophagus and esophageal adenocarcinoma.
To investigate the association between iron intake and iron status with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). A total of 220 BE patients, 224 EAC patients, and 256 frequency-matched controls completed a lifestyle and food frequency questionnaire and provided serum and toenail samples between 2002 and 2005. Using multiple logistic regression, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated within quartiles of intake/status. Comparing the fourth to the first quartile, ferritin (OR 0.47; 95% CI: 0.23, 0.97) and transferrin saturation (OR 0.41; 95% CI: 0.20, 0.82) were negatively associated with BE; while total iron binding capacity was positively associated per 50 μg/dl increment (OR 1.47; 95% CI: 1.12, 1.92). Comparing the fourth to the first quartile, iron intake (OR 0.50; 95% CI: 0.25, 0.98), non-heme iron intake per 10 mg/day increment (OR 0.29; 95% CI: 0.08, 0.99), and toenail iron (OR 0.40; 95% CI: 0.17, 0.93) were negatively associated with EAC; while heme iron intake was positively associated (OR 3.11 95% CI: 1.46, 6.61). In contrast to the hypothesis that increased iron intakes and higher iron stores are a risk factor for BE and EAC, this study suggests that higher iron intakes and stores may have a protective association with BE and EAC, with the exception of what was found for heme iron intake.


Prevalence of Complementary and Alternative Medicine and Herbal Remedy Use in Hispanic and Non-Hispanic White Women: Results from the Study of Women's Health Across the Nation.
To investigate the prevalence of complementary and alternative medicine (CAM) use, including botanical/herbal remedies, among Hispanic and non-Hispanic white women from the Study of Women's Health Across the Nation (SWAN), New Jersey site. We also examined whether attitudes toward CAM and communication of its use to providers differed for Hispanic and non-Hispanic women. SWAN is a community-based, multiethnic cohort study of midlife women. At the 13th SWAN follow-up, women at the New Jersey site completed both a general CAM questionnaire and a culturally sensitive CAM questionnaire designed to capture herbal products commonly used in Hispanic/Latina communities. Prevalence of and attitudes toward CAM use were compared by race/ethnicity and demographic characteristics. Among 171 women (average age 61.8 years), the overall prevalence of herbal remedy use was high in both Hispanic and non-Hispanic white women (88.8% Hispanic and 81.3% non-Hispanic white), and prayer and herbal teas were the most common modalities used. Women reported the use of multiple herbal modalities (mean 6.6 for Hispanic and 4.0 for non-Hispanic white women; p = 0.001). Hispanic women were less likely to consider herbal treatment drugs (16% vs. 37.5%; p = 0.005) and were less likely to report sharing the use of herbal remedies with their doctors (14.4% Hispanic vs. 34% non-Hispanic white; p = 0.001). The number of modalities used was similar regardless of the number of prescription medications used. High prevalence of herbal CAM use was observed for both Hispanic and non-Hispanic white women. Results highlight the need for healthcare providers to query women regarding CAM use to identify potential interactions with traditional treatments and to determine whether CAM is used in lieu of traditional medications.


Broadband light generation by noncollinear parametric downconversion.
Broadband light generation is demonstrated by noncollinear spontaneous parametric downconversion with a cw pump laser. By use of a suitable noncollinear phase-matching geometry and a tightly focused pump beam, downconverted signals that feature a bell-shaped spectral distribution with a bandwidth approaching 200 nm are obtained. As an application of the generated broadband light, submicrometer axial resolution in an optical coherence tomography scheme is demonstrated; a free-space resolution down to 0.8 microm was achieved.


Combination of self-harm methods and fatal and non-fatal repetition: A cohort study.
Assessment and aftercare for people who self-harm needs to be related to an understanding of risks of adverse outcomes. We aimed to determine whether self-harm by a combination of methods and its early repetition are associated with adverse outcomes - especially non-fatal repetition and suicide. 10,829 consecutive general hospital attendances due to self-harm in one large English city were monitored, through scrutiny of Emergency Department attendances, over three years and followed up to determine the incidence of non-fatal repetition. Subsequent deaths, by any cause and by suicide, were determined from national statistical records. 6155 patients accounted for the 10,829 episodes: 72% by self-poisoning, 21% self-injury, and 746 episodes (7%) due to a combination of methods. After a combined-methods index episode, non-fatal repetition (P=0.001) and suicide (P=0.002) occurred sooner and more frequently than it did among those who had self-poisoned. Further hospital attendance due to self-harm within a month was associated with a 3.7-fold (95% CI 2.1-6.4) risk of subsequent suicide. The data exclude self-harm episodes that do not result in a hospital attendance. Index episodes in the study are not generally life-time first episodes so follow-up data are based on an arbitrary start-point. Both of these limitations are common to all studies of this kind. At psychosocial assessment and the making of aftercare arrangements, combined methods of self-harm or another recent episode should be considered 'red-flag' indicators for attention to care.


Comparative analysis of RNA-Seq alignment algorithms and the RNA-Seq unified mapper (RUM).
A critical task in high-throughput sequencing is aligning millions of short reads to a reference genome. Alignment is especially complicated for RNA sequencing (RNA-Seq) because of RNA splicing. A number of RNA-Seq algorithms are available, and claim to align reads with high accuracy and efficiency while detecting splice junctions. RNA-Seq data are discrete in nature; therefore, with reasonable gene models and comparative metrics RNA-Seq data can be simulated to sufficient accuracy to enable meaningful benchmarking of alignment algorithms. The exercise to rigorously compare all viable published RNA-Seq algorithms has not been performed previously. We developed an RNA-Seq simulator that models the main impediments to RNA alignment, including alternative splicing, insertions, deletions, substitutions, sequencing errors and intron signal. We used this simulator to measure the accuracy and robustness of available algorithms at the base and junction levels. Additionally, we used reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing to validate the ability of the algorithms to detect novel transcript features such as novel exons and alternative splicing in RNA-Seq data from mouse retina. A pipeline based on BLAT was developed to explore the performance of established tools for this problem, and to compare it to the recently developed methods. This pipeline, the RNA-Seq Unified Mapper (RUM), performs comparably to the best current aligners and provides an advantageous combination of accuracy, speed and usability. The RUM pipeline is distributed via the Amazon Cloud and for computing clusters using the Sun Grid Engine (http://cbil.upenn.edu/RUM). email@example.com; email@example.com The RNA-Seq sequence reads described in the article are deposited at GEO, accession GSE26248.


Lung transplantation for emphysema: impact of age on short- and long-term survival.
Overall, emphysema (EMP) is the most common indication for lung transplantation. The majority of patients present with chronic obstructive pulmonary disease (COPD) and less frequently with alpha-1 antitrypsin deficiency (A1ATD). We analysed the results of lung transplants performed for EMP in order to identify the impact of age on short- and long-term outcome. A retrospective analysis was undertaken of the 108 consecutive lung transplants for EMP performed at our institution from November 1992 to August 2013 (77 COPD, 31 A1ATD). Retransplantations were excluded. The median age was 56 years (range 31-68). Thirty-day mortality rate was 3.7%. One- and 5-year survival rates in COPD and A1ATD recipients were comparable (P = 0.8). The 1- and 5-year survival rates for recipients aged <60 years old were significantly better than the age group of ≥60 years (91 and 79 vs 84 and 54%, P = 0.05). Since 2007, the 1- and 5-year survival for these two age groups were 96 and 92 vs 86 and 44%, respectively, P = 0.04, log-rank test). For the following parameters, we were not able to find any difference to affect survival rates: use of intraoperative extracorporeal membrane oxygenation, waiting list time, sex, graft size reduction, body mass index and diagnosis. In multivariate analysis, age at transplantation (≥60 years old) (HR 2.854; 95% confidence interval (CI) 1.338-6.08, P = 0.008) and unilateral lung transplantation (HR 15.2; 95% CI 3.2-71.9, P = 0.009) were independent risk factors for mortality. COPD and A1ATD recipients have similar overall long-term survival. Recipients aged ≥60 years and unilateral lung transplants were risk factors for mortality.


The Tectonic interaction between the Paramirim aulacogen and the Araçuaí belt, São Francisco craton region, Eastern Brazil.
The Paramirim aulacogen, hosted in the northern part of the São Francisco craton, corresponds to two superimposed and partially inverted rifts of Paleo and Neoproterozoic ages. The Rio Pardo salient of the Araçuaí belt defines the local limit of the craton and interferes with the aulacogen structures. In order to understand the mechanism and timing of the tectonic interaction between these tectonic features during the inversion processes, a structural analysis was undertaken in the southern Paramirim aulacogen and along the Rio Pardo salient. The results obtained indicate that the Rio Pardo salient formed during an early stage of closure of the Neoproterozoic Macaúbas rift system and consequent initiation of the Araçuaí orogen. The orogenic front propagated further northwards into the craton, causing a first stage of inversion in the southern terminus of the aulacogen trough. Subsequently, the Paramirim aulacogen experienced the main stage of inversion, which led to the development of a NNW-oriented basement involved fold-thrust system. These fabric elements overprint the Rio Pardo salient, and the structures of both the first and second stages of inversion affect the Salitre Formation, the youngestNeoproterozoic unit of the area, clearly indicating a Late Neoproterozoic maximum age for all the inversion stages of the Paramirim aulacogen.


[Comparison of Pentacam and OrbscanII systems for the diagnosis of keratoconus suspects].
To compare the sensitivity of Pentacam and OrbscanII and to analyze the morphology characteristic of topography in normal eyes and different stages of keratoconus, to provide the basis for early screening of keratoconus suspects. One hundred and ninety six normal eyes, 50 eyes with keratoconus suspect and 73 eyes with clinical keratoconus were enrolled. The changes of corneal anterior/posterior curvature, best fitting sphere (BFS). Inferior-Superior value (I-S) (3 mm and 5 mm), classification of elevation maps and corneal thickness were measured. There were significant differences including posterior curvature, anterior/posterior BFS, elevation value and corneal thickness in normal eyes between the data measured by these two different instruments, values obtained by Pentacam were less than those by Orbscan. Concerning the elevation maps pattern, the progressively decreasing pattern was dominant in Pentacam with normal eyes and keratoconus suspects, with the progressively increasing pattern accounting for 14.4% (28/196) and 20.0% (10/50) respectively in anterior surface, and 2.0% (41/96) and 26.0% (13/50) in posterior surface. The progressively increasing pattern was in dominant with clinical keratoconus, accounting for 91.7% (67/73) and 94.5% (69/73) respectively in anterior and posterior surface. Progressively increasing pattern in Orbscan was presented in 80.4% (165/196) normal eyes and suspected or clinical stage keratoconus. As to the receiver-operating-characteristic (ROC) curves and cutoff value, Orbscan I-S value (3 mm and 5 mm) of anterior and posterior surface was sensitive for the diagnosis of keratoconus suspects, with the cutoff value of anterior and posterior 5 mm I-S at 1.15 D and 0.65 D, respectively. In addition to the sensitivity of I-S values in Pentacam, the elevation value of anterior and posterior surface also displayed important diagnostic meaning. The cutoff of anterior, posterior elevation values was 4.5 µm and 7.5 µm, respectively. Numerous measured indicators revealed obviously difference between the two instruments in normal eyes, with slightly smaller values in Pentacam. In addition to I-S values, pattern changes and elevation values in elevation map of Pentacam represent remarkable advantages for the screening of keratoconus suspects. There is an incremental risk of corneal ectasia in the increasing pattern of elevation map.


Differentiating selves: middle-aged gay men in Manchester's less visible 'homospaces'.
Scholarship on gay bars/'villages' has overshadowed study of 'homospaces' (gay fields of existence) less available/inaccessible to a wider public - websites, saunas and social/support groups. Based on interviews with 27 men aged 39-61 living in Manchester, this article addresses what middle-aged gay men's accounts of these particular homospaces say about their experiences of age/ageing and how relations of ageism work within them. Specifically, I focus on how study participants use 'ageing capital' in these fields to differentiate themselves from their younger counterparts in three ways. First, ageing capital is implicated in capitulation to gay ageism and a reverse ageism - visible in accounts of differentiation from the 'superficial,' reckless ways of sexualized space that participants associated with younger gay men. Second, it was visible in accounts of resistance to/questioning of gay ageism - strategies that could make sexualized homospaces more habitable. Third, ageing capital was implicated in negotiation with ageing/gay ageism - visible in ambivalent stances hovering between compliance and resistance - towards ageing and ageism, which could reinforce constraints on uses/display of the body. The first and third accounts indicate the multidirectional character of gay ageism, limits on the deployment on ageing capital and show how middle-aged men can undermine their generational claims to represent a more authentic form of gay male embodiment. En route, I also complicate stereotypical thinking that gay social/support groups represent more inclusive, empowering space whilst overtly sexualized spaces of the 'gay scene' represent the opposite.


"When They See a Wheelchair, They've Not Even Seen Me"-Factors Shaping the Experience of Disability Stigma and Discrimination in Kenya.
Disability stigma in many low- and middle-income countries represents one of the most pervasive barriers preventing people with disabilities from accessing equal rights and opportunities, including the uptake of available assistive technology (AT). Previous studies have rarely examined how disability stigma may be shaped through factors endemic to social interactions, including how the use of assistive technology itself may precipitate or alleviate disability stigma. Through two strands of work, we address this gap. Via a series of focus groups with Kenyans without disabilities (Study 1) and secondary data analysis of consultations with Kenyans with disabilities and their allies (Study 2), we identify shared and divergent understandings of what shapes disability stigma and discrimination. Specifically, Kenyans with and without disabilities were cognizant of how religious/spiritual interpretations of disability, conceptions of impairments as "different" from the norm, and social stereotypes about (dis)ability shaped the experience of stigma and discrimination. Moreover, both groups highlighted assistive technology as an influential factor that served to identify or "mark" someone as having a disability. However, whereas participants without disabilities saw assistive technology purely as an enabler to overcome stigma, participants with disabilities also noted that, in some cases, use of assistive technologies would attract stigma from others.


Growth dynamics in the context of pediatric sports injuries and overuse.
The onset and timing of the growth of children and adolescents occurs with considerable variability in cohorts of the same chronological age. The musculoskeletal system changes in proportion over time, and lever-arm changes, altered individual flexibility, and strength lead to age-specific injury patterns in youth sports. In sports, juniors are commonly grouped according to their chronological age. Early- and late-maturing children and adolescents might therefore not routinely be trained in relation to their biology. This not only represents a risk for overuse and injury but might limit their development in sports. To obtain information about the biological age of children is challenging. Numerous methods have been studied and validated. However, the implementation of these methods on a large scale is still to come. This report provides a brief overview of growth dynamics in relation to youth sports injuries and describes a few challenges for the future.


Exhaled aerosol transmission of pandemic and seasonal H1N1 influenza viruses in the ferret.
Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected 'donor' ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa.


Long-term (5 years) efficacy and safety of pancreas transplantation alone in type 1 diabetic patients.
Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate. We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated. Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min. PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.


A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia.
Fasting hyperinsulinemia is a widely used surrogate measure of insulin resistance and predicts type 2 diabetes in various populations. Whether fasting hyperinsulinemia predicts diabetes independent of insulin resistance is unknown. In 319 Pima Indians with normal glucose tolerance, fasting plasma insulin concentration and insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp) were inversely related, but at any given M, there was substantial variation, with some subjects being hyperinsulinemic and others being hypoinsulinemic relative to their degree of insulin sensitivity. In 262 of the 319 subjects followed prospectively over 6.4 +/- 3.9 years, a high fasting plasma insulin concentration was a significant independent predictor of diabetes, in addition to low M and low acute insulin response (AIR) (intravenous glucose challenge). In 161 of the 319 subjects with follow-up measurements of M and AIR (5.1 +/- 3.9 years), a high relative fasting plasma insulin concentration predicted a decline in AIR but not in M before the onset of diabetes. The adjusted fasting plasma insulin concentration was a familial trait (heritability of 0.52) and in a genome-wide scan, there was suggestive evidence of linkage (logarithm of odds score 1.77) to a region on chromosome 3q, which harbors the gene encoding GLUT2. These results provide the first prospective evidence in humans that fasting hyperinsulinemia itself has a primary role in the pathogenesis of diabetes, independent of insulin resistance. Whether amelioration of basal insulin hypersecretion will prevent diabetes remains to be elucidated.


Understanding the dimensions of home that impact on home modification decision making.
The home environment is a multidimensional and personally meaningful place, and the complexity of this environment often impacts on the home modification process and outcomes. Home modifications can appear as a straightforward solution to safety and occupational performance concerns; nevertheless, clients sometimes reject modifications or are unsatisfied with the completed works. To understand this phenomenon, this study aimed to determine what aspects of the home environment impact home modification decision making. In this qualitative descriptive study, 42 in-depth interviews using a semi-structured questionnaire were undertaken and analysed using a template analysis. The interviews explored the experience of the home modification process, including concerns and the decisions made about the modifications. Four dimensions of the home environment were commonly found to affect decision making namely, the personal, societal, physical and temporal dimensions of home as well as social and occupational dimensions. An understanding of the dimensions of home that impact decision making provides occupational therapists with a greater appreciation of the experience of home and allows them to enhance the effectiveness and acceptance of home modifications.


PCR detection of enzyme-encoding genes in Leuconostoc mesenteroides strains of wine origin.
Fifteen isolates of lactic acid bacteria originating from South African grape and wine samples were identified as Leuconostoc mesenteroides subsp. mesenteroides through the taxonomic analysis of their 16S rDNA gene sequences. These isolates were further tested for the presence of genes coding for enzymes of oenological relevance using PCR detection technique. A type strain of Leuc. mesenteroides (NCDO 529(T)) was also incorporated for comparative analysis. From the PCR detection results, the estA, prtP, alsD, alsS, metK, metC and metB genes were present in all the strains tested. The bgl and gshR genes encoding β-glucosidase and glutathione reductase, respectively, were not detected in some strains. On the other hand, none of the tested strains possessed the genes encoding phenolic acid decarboxylase (padA), citrate permease (citP), citrate lyase (citD, citE and citF) and arginine deiminase pathway enzymes (arcA, arcB and arcC). The verification of PCR-generated fragments was performed by sequencing. GenBank database was used to search for homologous DNA sequences. Neighbour-joining trees based on nucleotide sequences of alsS, estA, metK and mleA genes were also constructed in order to study the phylogenetic relationship between Leuc. mesenteroides strains and closely related species. The phylogenetic analyses revealed that there are genetic heterogeneities between strains of Leuc. mesenteroides species. In conclusion, this study has improved our knowledge on the genetics of oenological strains of Leuc. mesenteroides and their genetic potential to contribute to certain wine aroma compounds.


Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy.
Muscle phosphoglycerate mutase activity was decreased (5.7 percent of the lowest control value) in a 52-year-old man with intolerance for strenuous exercise and recurrent pigmenturia since adolescence. All of the other enzymes of glycolysis had normal activities, and glycogen concentration was normal. Electrophoretic, heat lability, and mercury inhibition studies showed that the small residual activity in the patient's muscle was represented by the brain (BB) isoenzyme of phosphoglycerate mutase, suggesting a genetic defect of the M subunit which predominates in normal muscle. The prevalence of the BB isoenzyme in other tissues, including muscle culture, may explain why symptoms were confined to muscle.


General practitioner views about discussing sexual issues with patients with coronary heart disease: a national survey in Ireland.
Sexual problems are common among people with coronary heart disease and can adversely affect patients' quality of life. GPs are ideally placed to deal with these problems. Research suggests that GPs are reluctant to address sexual problems but little is known about what currently takes place in practice. The aim of this study was to examine GPs' self-reported behaviour and attitudes to discussing sexual problems with people with coronary heart disease. A cross-sectional survey which administered 230 postal questionnaires to a nationally representative, stratified random sample of GPs in the Republic of Ireland. GPs were asked about current practice, knowledge, awareness and confidence in dealing with sexual problems, barriers to addressing sexual problems, and about improving services in this area. Responses were available for 61 GPs (27% response rate). Seventy percent of GPs reported that they rarely or never discussed sexual problems with coronary patients. While all GPs believed addressing sexual problems was important, many GPs reported lacking awareness, knowledge and confidence in addressing sexual problems. The main barriers were lack of time, feeling the patient wasn't ready and lack of training in the area. GPs wanted more training and guidelines for practice. There is currently no standardised protocol for GPs for dealing with sexual problems among coronary patients. Awareness of these issues appears to be low among GPs. Services could be improved by developing practice guidelines for brief, effective actions or assessments, providing training in the area and improving information resources and support services for referral.