Expression of LIM-homeodomain transcription factors in the developing and mature mouse retina.
LIM-homeodomain (LIM-HD) transcription factors have been extensively studied for their role in the development of the central nervous system. Their function is key to several developmental events like cell proliferation, differentiation and subtype specification. However, their roles in retinal neurogenesis remain largely unknown. Here we report a detailed expression study of LIM-HD transcription factors LHX9 and LHX2, LHX3 and LHX4, and LHX6 in the developing and mature mouse retina using immunohistochemistry and in situ hybridization techniques. We show that LHX9 is expressed during the early stages of development in the retinal ganglion cell layer and the inner nuclear layer. We also show that LHX9 is expressed in a subset of amacrine cells in the adult retina. LHX2 is known to be expressed in retinal progenitor cells during development and in Müller glial cells and a subset of amacrine cells in the adult retina. We found that the LHX2 subset of amacrine cells is not cholinergic and that a very few of LHX2 amacrine cells express calretinin. LHX3 and LHX4 are expressed in a subset of bipolar cells in the adult retina. LHX6 is expressed in cells in the ganglion cell layer and the neuroblast layer starting at embryonic stage 13.5 (E13.5) and continues to be expressed in cells in the ganglion cell layer and inner nuclear layer, postnatally, suggesting its likely expression in amacrine cells or a subset thereof. Taken together, our comprehensive assay of expression patterns of LIM-HD transcription factors during mouse retinal development will help further studies elucidating their biological functions in the differentiation of retinal cell subtypes.


[Analysis of hospital clinical services to elderly victims of accidents and violence].
The increase of elderly population and more active life allow a greater exposure to accidents and violence in this population. A diagnostic analysis of hospital services for emergency and urgent care to victims of accidents and violence in the elderly population was carried out in five capitals of Brazil. The research was based on the principles of triangulation of methods, including quantitative approaches, through the application of questionnaires to managers and pre-hospital, hospital and rehabilitation service professionals, as well as qualitative, in which interviews were made with managers and professionals and with those in charge of elderly health. Based on the guidelines of the policies studied, it was realized that none of the capitals has met all requirements, with a poor attendance characterized by lack of structure to keep a companion for the elderly, referrals to reference services, specific clinical protocols, reporting sheets, support to the elderly, job training and definition of the flow for this population. The outcome showed that the selected health services do not have the appropriate and integral profile to look after the elderly population, demonstrating the need for adequacy of these services aiming the accomplishment of the guidelines of the policies reviewed.


Cytogenetic survey of Holstein bulls at a commercial artificial insemination company to determine prevalence of bulls with centric fusion and chimeric anomalies.
To determine prevalence of Holstein bulls with chromosomal anomalies, particularly the 1/21 centric fusion (CF), at a commercial artificial insemination (AI) company in the United States. Cross-sectional cytogenetic prevalence study. All 606 Holstein bulls at a commercial AI company were cytogenetically screened to detect CF, chimerism, and other chromosomal abnormalities. Lymphocytes from heparinized blood samples were cultured by standard cytogenetic techniques, and chromosome spreads were prepared for microscopic examination. Chromosomal abnormalities were detected by examining 10 chromosome spreads per bull. Pedigree analysis was performed. None of the bulls had any type of CF. However, 6 bulls were identified as chimeras (i.e., contained lymphocytes with male [XY] and female [XX] chromosomes). One bull was sire or maternal grandsire to 85 of the bulls tested, and 739 of 1,212 (61%) sire and maternal-grandsire possibilities were accounted for by just 18 bulls. Analysis of these results supports previous indications that CF is extremely rare in Holstein bloodlines available commercially via AI in the United States. However, chimeric bulls are more common, and they reportedly have decreased reproductive performance. Therefore, identification of chimeric sires in the AI facility reported here and the possibility of de novo onset of CF at any time indicates that early cytogenetic screening should be encouraged for prospective bulls intended for use in AI programs.


Large variation in predictors of mortality by levels of self-rated health: Results from an 18-year follow-up study.
To analyze the variation in factors associated with mortality risk at different levels of self-rated health (SRH). Retrospective cohort study. Cox regression analysis was used to examine the association between mortality and demographic, socioeconomic and health-related predictors for respondents with good, average, and poor SRH in a longitudinal data set from Estonia with up to 18 years of follow-up time. In respondents with good SRH, male sex, older age, lower income, manual occupation, ever smoking, and heavy alcohol consumption predicted higher mortality. These covariates, together with marital status, illness-related limitations, and underweight predicted mortality in respondents with average SRH. For poor SRH, only being never married and having illness-related limitations predicted mortality risk in addition to older age and male sex. The predictors of all-cause mortality are not universal but depend on the level of SRH. The higher mortality of respondents with poor SRH could to a large extent be attributed to health problems, whereas in the case of average or good SRH, factors other than the presence of illness explained outcome mortality.


Community-applied research of a traditional Chinese medicine rehabilitation scheme on Broca's aphasia after stroke: study protocol for a randomized controlled trial.
Aphasia is a common and severely disabling complication in stroke patients. It usually brings about lower rates of functional recovery, longer rehabilitation length of stay (LOS), and significantly poorer LOS efficiency (LOS-Eff), resulting in higher rehabilitation costs compared to patients without aphasia. It also decreases the quality of life and increases the mortality of stroke patients. The evidence currently available suggests that the effect of acupuncture combined with language training for apoplectic aphasia is statistically better than speech and language therapy (SLT) alone, but there remains a lack of high-quality randomized controlled trials. Acupuncture combined with language training is relatively low-cost and especially suitable for community-based rehabilitation for aphasia patients after stroke, taking its medical and health facilities which are always deficient in manpower and material resources into account. The aim of the present study is to develop an effective standard therapeutic program for apoplectic aphasia in communities. In a randomized controlled clinical trial with blinded assessment, 290 eligible patients with aphasia due to stroke will be randomly allocated into a control group or an experimental group. The course of this trial will comprise a 4-week intervention and a 12-week follow-up period. Five assessment points, including baseline, 2 and 4 weeks after treatment, 6 and 12 weeks after follow-up, are set to dynamically observe the changes of curative effects. Primary outcome measures are the differences in the score on both the China rehabilitation research center aphasia examination (CRRCAE) and Boston diagnostic aphasia examination - Chinese version (BDAE-C) after intervention and follow-up. The Modified Barthel Index (MBI), 36-Item Short Form Health Survey (SF-36), and results of blood oxygen level dependent-functional magnetic resonance imaging (BOLD-fMRI) examination are considered as the secondary outcome measures. Other outcomes will include rate of adverse events and economic effects. If the outcome is positive, this project will offer a low-cost appropriate technology for community health centers (CHCs) in the rehabilitation of aphasia patients after stroke, and could be implemented on a large scale, both in China and worldwide. Chinese Clinical Trial Registry: ChiCTR-TRC-13003703. Registration date: 18 October 2013.


Multiscale methods for macromolecular simulations.
In this article we review the key modeling tools available for simulating biomolecular systems. We consider recent developments and representative applications of mixed quantum mechanics/molecular mechanics (QM/MM), elastic network models (ENMs), coarse-grained molecular dynamics, and grid-based tools for calculating interactions between essentially rigid protein assemblies. We consider how the different length scales can be coupled, both in a sequential fashion (e.g. a coarse-grained or grid model using parameterization from MD simulations), and via concurrent approaches, where the calculations are performed together and together control the progression of the simulation. We suggest how the concurrent coupling approach familiar in the context of QM/MM calculations can be generalized, and describe how this has been done in the CHARMM macromolecular simulation package.


Bismuth sulfide nanoflowers for detection of X-rays in the mammographic energy range.
The increased use of diagnostic x-rays, especially in the field of medical radiology, has necessitated a significant demand for high resolution, real-time radiation detectors. In this regard, the photoresponse of bismuth sulfide (Bi2S3), an n-type semiconducting metal chalcogenide, to low energy x-rays has been investigated in this study. In recent years, several types of nanomaterials of Bi2S3 have been widely studied for optoelectronic and thermoelectric applications. However, photoresponse of Bi2S3 nanomaterials for dosimetric applications has not yet been reported. The photosensitivity of Bi2S3 with nanoscale "flower-like" structures was characterized under x-ray tube-potentials typically used in mammographic procedures. Both dark current and photocurrent were measured under varying x-ray doses, field sizes, and bias voltages for each of the tube potentials - 20, 23, 26 and 30 kV. Results show that the Bi2S3 nanoflowers instantaneously responded to even minor changes in the dose delivered. The photoresponse was found to be relatively high (few nA) at bias voltage as low as +1 V, and fairly repeatable for both short and long exposures to mammographic x-rays with minimal or no loss in sensitivity. The overall dose-sensitivity of the Bi2S3 nanoflowers was found to be similar to that of a micro-ionization chamber.


Expression profiling of estrogenic compounds using a sheepshead minnow cDNA macroarray.
A variety of anthropogenic compounds are capable of binding to the estrogen receptor (ER) of vertebrate species. Binding of these chemicals to the ER can interfere with homeostasis by altering normal gene expression patterns. The purpose of this study was to characterize the expression of 30 genes using a sheepshead minnow (Cyprinodon variegatus) cDNA macroarray. Many of the genes on the array were previously identified by differential display reverse transcriptase-polymerase chain reaction to be upregulated or downregulated in sheepshead minnows treated through aqueous exposure to known or suspected estrogenic chemicals. The results of this study show that 17 beta-estradiol (E2), 17 alpha-ethinyl estradiol (EE2), diethylstilbestrol (DES), and methoxychlor (MXC) have similar genetic signatures for the 30 genes examined. The genetic signature of fish treated with p-nonylphenol was identical in pattern to that in fish treated with E2, EE2, DES, and MXC except for the additional upregulation of a cDNA clone that shares similarity to ubiquitin-conjugating enzyme 9. Endosulfan produced results that resembled the gene expression patterns of untreated control fish with exception of the upregulation of estrogen receptor alpha and the downregulation of a cDNA clone that shares similarity to 3-hydroxy-3-methylglutaryl-coenzyme A reductase. We show that our estrogen-responsive cDNA macroarray can detect dose-dependent changes in gene expression patterns in fish treated with EE2.


Wells syndrome in adults and children: a report of 19 cases.
Wells syndrome, an uncommon inflammatory dermatosis, is characterized by protean cutaneous manifestations, suggestive but not specific histopathologic findings, and usually a recurrent course. Because of its original description as a distinct entity, it has come to be regarded as an abnormal eosinophilic response to a number of causative agents. The medical records of 19 patients (12 adults and 7 children) with Wells syndrome referred to the Institute of Dermatological Sciences from 1990 to 2005 were evaluated for the type and prevalence of skin lesions, clinical course and response to treatment, and possibly associated systemic symptoms, as well as histologic, laboratory, and immunofluorescence findings. The classic plaque-type variant proved to be the most common presentation in children but not in adults, who more frequently had the annular granuloma-like variant. Unilesional forms were found to occur more frequently in children. The course was recurrent, although slowly progressing, with a mean duration of disease of 5 years for adults and 3 years for children. We emphasize the concept that the diagnosis of Wells syndrome is a clinicopathologic diagnosis. Although it should be classified within a spectrum that includes multisystem eosinophilic disorders, such as Churg-Strauss and hypereosinophilic syndromes, Wells syndrome, which has 7 variants, is a distinct cutaneous disease lacking systemic involvement.


Effects of low-dose norethindrone acetate plus ethinyl estradiol (0.5 mg/2.5 microg) in women with postmenopausal symptoms: updated analysis of three randomized, controlled trials.
Based on the potential risks of post-menopausal hormone therapy (HT) found by the Women's Health Initiative, guidelines for HT now recommend use of the lowest effective dose and shortest treatment duration consistent with individual treatment goals. Current (2003) guidance established by the US Food and Drug Administration (FDA) recommends that clinical assessments of HT include women with more frequent and more intense vasomotor symptoms than previously studied. Therefore, this analysis was conducted to further assess the efficacy of a low-dose combination of norethindrone acetate and ethinyl estradiol (NA/EE) previously assessed in dose-ranging studies, while meeting conservative FDA trial design and analysis criteria. The aim of this post hoc analysis and overview was to present data on the efficacy and tolerability of a low-dose combination-NA/EE 0.5 mg/2.5 microg-in the treatment of postmenopausal symptoms, based on data from previously published studies of NA/EE. In addition, the effects of low-dose NA/EE on bone and endometrium are briefly reviewed. Data from 3 previously published randomized, placebo-controlled trials were analyzed using current FDA guidance for the assessment of HT in postmenopausal women. Studies 1 and 2 assessed the efficacy of NA/EE at various doses, including 0.5 mg/2.5 microg, in vasomotor symptom (hot-flush [HF]) relief over 16 and 12 weeks, respectively, using self-reporting of symptom frequency and intensity (scores: 0=none; 1=mild; 2=moderate; and 3=severe) in daily diaries. Study 3 assessed the effects of NA/EE at various doses, including 0.5 mg/2.5 microg, on bone and endometrium, using quantitative computed tomography of the lumbar spine at 12 and 24 months and endometrial biopsy at 6, 12, 18, and 24 months of treatment. In all 3 studies, women were asked to record vaginal bleeding and spotting in diaries. Any adverse events were recorded in diaries and/or at clinic visits. Physical and gynecologic examinations and standard clinical laboratory testing were conducted at baseline and at appropriate follow-up visits in all 3 studies. Studies 1, 2, and 3 enrolled 219, 266, and 1265 women, respectively. Overall, in studies 1 and 2, 91% of women were white, the mean age was approximately 52 years, and mean time since last menstrual period was approximately 24 months. In study 1, NA/EE 0.5 mg/2.5 microg was associated with significant reductions from baseline in mean weekly total HF frequency from week 4 (63.6%) through week 16 (73.7%) (all, P<0.05). In study 2, the frequency of moderate or severe HFs was decreased by 61.1% at week 4 (P<0.05) and by 82.2% at week 12 (P<0.001) with NA/EE 0.5 mg/2.5 microg, and the mean intensity score was significantly lower than that with placebo at weeks 8 and 12 (both, P=0.001). In study 3, cumulative amenorrhea rates were approximately 90% in the NA/EE 0.5-mg/2.5-microg and placebo groups at 12 months. Lumbar spine bone mineral density (BMD) was maintained at 24 months with NA/EE 0.5 mg/2.5 microg but was significantly decreased from baseline, by 7.4%, in the placebo group (P<0.001). Endometrial hyperplasia was not observed in the group receiving NA/EE 0.5 mg/2.5 microg over 24 months. The tolerability of NA/EE was similar to that of placebo. The most common adverse events experienced with NA/EE were headache (15.2%), abdominal pain (10.2%), and breast pain (9.0%). The results from this post hoc analysis and overview of 3 previously published studies suggest that NA/EE 0.5 mg/2.5 microg was associated with decreased frequency and intensity of vasomotor symptoms. This dose of NA/EE was also associated with maintenance of BMD over 24 months, a significant positive effect on BMD compared with placebo. Low-dose NA/EE was also associated with cumulative amenorrhea rates comparable to those of placebo and was not associated with endometrial hyperplasia. This dose was well tolerated, with rates of adverse events generally similar to those of placebo.


Ultra-fast quantum randomness generation by accelerated phase diffusion in a pulsed laser diode.
We demonstrate a high bit-rate quantum random number generator by interferometric detection of phase diffusion in a gain-switched DFB laser diode. Gain switching at few-GHz frequencies produces a train of bright pulses with nearly equal amplitudes and random phases. An unbalanced Mach-Zehnder interferometer is used to interfere subsequent pulses and thereby generate strong random-amplitude pulses, which are detected and digitized to produce a high-rate random bit string. Using established models of semiconductor laser field dynamics, we predict a regime of high visibility interference and nearly complete vacuum-fluctuation-induced phase diffusion between pulses. These are confirmed by measurement of pulse power statistics at the output of the interferometer. Using a 5.825 GHz excitation rate and 14-bit digitization, we observe 43 Gbps quantum randomness generation.


Patterns of Psychological Adaptation to Spousal Bereavement in Old Age.
While the negative effects of spousal bereavement on well-being are well documented in empirical research, the large individual differences in psychological adaptation are still not well understood. This contribution aims to identify patterns of psychological adaptation to spousal loss in old age and to shed light on the role of intra- and interpersonal resources and contextual factors as discriminant variables among these patterns. The data stem from a cross-sectional questionnaire study of 402 widowed individuals (228 women, 174 men) aged between 60 and 89 years (mean age 74.41 years), who lost their partner within the last 5 years, and 618 married individuals, who served as controls (312 women, 306 men; mean age 73.82 years). The exploratory latent profile analysis of the well-being outcomes of depressive symptoms, hopelessness, loneliness, life satisfaction and subjective health revealed three different groups in the widowed sample: 'resilients' (54% of the sample), 'copers' (39%) and 'vulnerables' (7%). The most important variables for group allocation were intrapersonal resources - psychological resilience and the Big Five personality traits - but also the quality of the former relationship and how the loss was experienced. Successful adaptation to spousal loss is primarily associated with high scores in psychological resilience and extraversion and low scores in neuroticism. Our results shed light on the variability in psychological adaptation and underline the important role of intrapersonal resources in facing spousal loss in old age.


The effect of targeting tolerance of children's negative emotions among anxious parents of children with anxiety disorders: A pilot randomised controlled trial.
Following cognitive behavioural therapy for child anxiety a significant minority of children fail to lose their diagnosis status. One potential barrier is high parental anxiety. We designed a pilot RCT to test claims that parental intolerance of the child's negative emotions may impact treatment outcomes. Parents of 60 children with an anxiety disorder, who were themselves highly anxious, received either brief parent-delivered treatment for child anxiety or the same treatment with strategies specifically targeting parental tolerance of their child's negative emotions. Consistent with predictions, parental tolerance of the child's negative emotions significantly improved from pre- to post-treatment. However, there was no evidence to inform the direction of this association as improvements were substantial in both groups. Moreover, while there were significant improvements in child anxiety in both conditions, there was little evidence that this was associated with the improvement in parental tolerance. Nevertheless, findings provide important clinical insight, including that parent-led treatments are appropriate even when the parent is highly anxious and that it may not be necessary to adjust interventions for many families.


Evaluation and use of surveillance system data toward the identification of high-risk areas for potential cholera vaccination: a case study from Niger.
In 2008, Africa accounted for 94% of the cholera cases reported worldwide. Although the World Health Organization currently recommends the oral cholera vaccine in endemic areas for high-risk populations, its use in Sub-Saharan Africa has been limited. Here, we provide the principal results of an evaluation of the cholera surveillance system in the region of Maradi in Niger and an analysis of its data towards identifying high-risk areas for cholera. We evaluated the cholera surveillance data using a standard CDC protocol, through interviews with heads of the system, and a review of cholera data collected between 2006-2009. The surveillance system was found to be sufficiently reliable to be able to utilize the data for the detection of high risk areas for cholera vaccination. Temporal, geographic and socio-demographic analyses of cholera cases indicated that between 2006 and 2009, 433 cholera cases were reported in the Maradi region of Niger. Two deprived neighborhoods of the region's capital city, Bagalam and Yandaka, represented 1% of the regional population and 21% of the cholera cases, reaching a yearly incidence rate of 3 per 1000 in 2006 and 2008, respectively. The results of this evaluation suggest that the reporting sensitivity of the surveillance system is sufficient, to appropriately classify the region as cholera endemic. Additionally, two overcrowded neighborhoods in the regional capital met WHO criteria for consideration for cholera vaccination.


Expression analysis of toll-like receptors of Dengue-infected cornea by real-time polymerase chain reaction.
Toll-like receptors (TLRs) play a significant role based on innate immune mechanism during viral infection. TLR signaling mechanism designates to protect the cells from invading viruses. The expression of TLRs during dengue virus (DENV) infection not yet well explained. This study evaluates the TLR gene expression from DENV-infected patient's cornea. Reverse transcriptase PCR was performed for the detection and genotyping of viral nucleic acid from corneal grafts and DENV-infected cell suspension. TLR expression studies were done on DENV-infected cornea by real-time RT2 Profiler PCR Array. The reverse transcriptase PCR and genotyping confirmed the presence of DENV-3. TLR expression studies revealed the upregulated expression of TLR4, TLR7, TLR9 and TLR10. Molecular testing of DENV reveals that serological positivity induces transmission of the virus through cornea and stimulates the expression of TLR4, TLR7, TLR9 and TLR10, which may lead to up-regulation of innate pro-inflammatory response in the cornea.


The effect of scaffold-cell entrapment capacity and physico-chemical properties on cartilage regeneration.
An important tenet in designing scaffolds for regenerative medicine consists in mimicking the dynamic mechanical properties of the tissues to be replaced to facilitate patient rehabilitation and restore daily activities. In addition, it is important to determine the contribution of the forming tissue to the mechanical properties of the scaffold during culture to optimize the pore network architecture. Depending on the biomaterial and scaffold fabrication technology, matching the scaffolds mechanical properties to articular cartilage can compromise the porosity, which hampers tissue formation. Here, we show that scaffolds with controlled and interconnected pore volume and matching articular cartilage dynamic mechanical properties, are indeed effective to support tissue regeneration by co-cultured primary and expanded chondrocyte (1:4). Cells were cultured on scaffolds in vitro for 4 weeks. A higher amount of cartilage specific matrix (ECM) was formed on mechanically matching (M) scaffolds after 28 days. A less protein adhesive composition supported chondrocytes rounded morphology, which contributed to cartilaginous differentiation. Interestingly, the dynamic stiffness of matching constructs remained approximately at the same value after culture, suggesting a comparable kinetics of tissue formation and scaffold degradation. Cartilage regeneration in matching scaffolds was confirmed subcutaneously in vivo. These results imply that mechanically matching scaffolds with appropriate physico-chemical properties support chondrocyte differentiation.


The evolution of parental care in stochastic environments.
Parental care is of fundamental importance to understanding reproductive strategies and allocation decisions. Here, we explore how parental care strategies evolve in variable environments. Using a set of life-history trait trade-offs, we explore the relative costs and benefits of parental care in stochastic environments. Specifically, we consider the cases in which environmental variability results in varying adult death rates, egg death rates, reproductive rate and carrying capacity. Using a measure of fitness appropriate for stochastic environments, we find that parental care has the potential to evolve over a wide range of life-history characteristics when the environment is variable. A variable environment that affects adult or egg death rates can either increase or decrease the fitness of care relative to that in a constant environment, depending on the specific costs of care. Variability that affects carrying capacity or adult reproductive rate has negligible effects on the fitness associated with care. Increasing parental care across different life-history stages can increase fitness gains in variable environments. Costly investment in care is expected to affect the overall fitness benefits, the fitness optimum and rate of evolution of parental care. In general, we find that environmental variability, the life-history traits affected by such variability and the specific costs of care interact to determine whether care will be favoured in a variable environment and what levels of care will be selected.


Residues of the human metapneumovirus fusion (F) protein critical for its strain-related fusion phenotype: implications for the virus replication cycle.
The paramyxovirus F protein promotes fusion of the viral and cell membranes for virus entry, as well as cell-cell fusion for syncytium formation. Most paramyxovirus F proteins are triggered at neutral pH to initiate membrane fusion. Previous studies, however, demonstrated that human metapneumovirus (hMPV) F proteins are triggered at neutral or acidic pH in transfected cells, depending on the strain origin of the F sequences (S. Herfst et al., J. Virol. 82:8891-8895, 2008). We now report an extensive mutational analysis which identifies four variable residues (294, 296, 396, and 404) as the main determinants of the different syncytial phenotypes found among hMPV F proteins. These residues lie near two conserved histidines (H368 and H435) in a three-dimensional (3D) model of the pretriggered hMPV F trimer. Mutagenesis of H368 and H435 indicates that protonation of these histidines (particularly His435) is a key event to destabilize the hMPV F proteins that require low pH for cell-cell fusion. The syncytial phenotypes were reproduced in cells infected with the corresponding hMPV strains. However, the low-pH dependency for syncytium formation could not be related with a virus entry pathway dependent on an acidic environment. It is postulated that low pH may be acting for some hMPV strains as certain destabilizing mutations found in unusual strains of other paramyxoviruses. In any case, the results presented here and those reported by Schowalter et al. (J. Virol. 83:1511-1522, 2009) highlight the relevance of certain residues in the linker region and domain II of the pretriggered hMPV F protein for the process of membrane fusion.


Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial.
Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; p<0.0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.


Individual US diets show wide variation in water scarcity footprints.
Agriculture accounts for 80% of global freshwater consumption but the environmental impacts of water use are highly localized and depend on water scarcity. The water use impacts of food production should be a key consideration of sustainable diets, yet little is known of the water scarcity demands of diets, especially of individuals. Here we estimate the water scarcity footprint (WSF)-a water use impact metric that accounts for regional scarcity-of individual diets in the United States (n = 16,800) and find a fivefold variation between the highest and lowest quintile of diets ranked by WSF. Larger intakes of some meat, fruit, nuts and vegetables drive these differences. Meat consumption is the greatest contributor (31%) to the WSF of the average diet, and within that, beef contributes about six times that of chicken. Variation between substitutable foods provides insight into diet shifts that can reduce WSF. We introduce a novel, geospatially explicit approach that combines the types and quantities of foods in the diets of individuals, the irrigation water required to produce those foods and the relative scarcity of water where that irrigation occurs.


Despite High Cost, Improved Pneumococcal Vaccine Expected To Return 10-Year Net Savings Of $12 Billion.
In 2010 the US Advisory Committee on Immunization Practices recommended that the seven-valent pneumococcal conjugate vaccine (PCV7) be replaced by the thirteen-valent version (PCV13), which provides protection against six additional serotypes of the bacterium Streptococcus pneumoniae. The higher price of PCV13, compared to PCV7, may be a concern for funding agencies and payers, as has been the case with other new vaccines. This study estimated the budgetary impact on both public and private US insurance payers of the routine use of PCV13 instead of PCV7 from 2010 to 2019. Implementing the PCV13 vaccine is projected to cost public and private payers $3.5 billion and $2.6 billion, respectively, more than PCV7. However, PCV13 is expected to provide net cost savings of $6.1 billion and $4.2 billion, respectively, to those payers during the ten-year period by preventing pneumococcal disease and its associated costs. An additional $1.7 billion in cost savings would be realized for uninsured patients, whose costs ultimately fall on those payers. Despite its higher price, compared to PCV7, this new vaccine is expected to provide payers with substantial net budgetary savings.


Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childhood. Affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. We performed linkage mapping with microsatellite markers in LBSL families and found a candidate region on chromosome 1, which we narrowed by means of shared haplotypes. Sequencing of genes in this candidate region uncovered mutations in DARS2, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals from all 30 families. Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays.


Exogenous application of abscisic acid (ABA) increases root and cell hydraulic conductivity and abundance of some aquaporin isoforms in the ABA-deficient barley mutant Az34.
Background and Aims Regulation of water channel aquaporins (AQPs) provides another mechanism by which abscisic acid (ABA) may influence water flow through plants. To the best of our knowledge, no studies have addressed the changes in ABA levels, the abundance of AQPs and root cell hydraulic conductivity (LpCell) in the same tissues. Thus, we followed the mechanisms by which ABA affects root hydraulics in an ABA-deficient barley mutant Az34 and its parental line 'Steptoe'. We compared the abundance of AQPs and ABA in cells to determine spatial correlations between AQP abundance and local ABA concentrations in different root tissues. In addition, abundance of AQPs and ABA in cortex cells was related to LpCell. Methods Root hydraulic conductivity (LpRoot) was measured by means of root exudation analyses and LpCell using a cell pressure probe. The abundance of ABA and AQPs in root tissues was assessed through immunohistochemical analyses. Isoform-specific antibodies raised against HvPIP2;1, HvPIP2;2 and HvPIP2;5 were used. Key Results Immunolocalization revealed lower ABA levels in root tissues of Az34 compared with 'Steptoe'. Root hydraulic conductivity (LpRoot) was lower in Az34, yet the abundance of HvPIPs in root tissues was similar in the two genotypes. Root hair formation occurred closer to the tip, while the length of the root hair zone was shorter in Az34 than in 'Steptoe'. Application of external ABA to the root medium of Az34 and 'Steptoe' increased the immunostaining of root cells for ABA and for HvPIP2;1 and HvPIP2;2 especially in root epidermal cells and the cortical cell layer located beneath, parallel to an increase in LpRoot and LpCell. Treatment of roots with Fenton reagent, which inhibits AQP activity, prevented the ABA-induced increase in root hydraulic conductivity. Conclusion Shortly after (<2 h) ABA application to the roots of ABA-deficient barley, increased tissue ABA concentrations and AQP abundance (especially the plasma-membrane localized isoforms HvPIP2;1 and HvPIP2;2) were spatially correlated in root epidermal cells and the cortical cell layer located beneath, in conjunction with increased LpCell of the cortical cells. In contrast, long-term ABA deficiency throughout seedling development affects root hydraulics through other mechanisms, in particular the developmental timing of the formation of root hairs closer to the root tip and the length of the root hair zone.


PAT4 levels control amino-acid sensitivity of rapamycin-resistant mTORC1 from the Golgi and affect clinical outcome in colorectal cancer.
Tumour cells can use strategies that make them resistant to nutrient deprivation to outcompete their neighbours. A key integrator of the cell's responses to starvation and other stresses is amino-acid-dependent mechanistic target of rapamycin complex 1 (mTORC1). Activation of mTORC1 on late endosomes and lysosomes is facilitated by amino-acid transporters within the solute-linked carrier 36 (SLC36) and SLC38 families. Here, we analyse the functions of SLC36 family member, SLC36A4, otherwise known as proton-assisted amino-acid transporter 4 (PAT4), in colorectal cancer. We show that independent of other major pathological factors, high PAT4 expression is associated with reduced relapse-free survival after colorectal cancer surgery. Consistent with this, PAT4 promotes HCT116 human colorectal cancer cell proliferation in culture and tumour growth in xenograft models. Inducible knockdown in HCT116 cells reveals that PAT4 regulates a form of mTORC1 with two distinct properties: first, it preferentially targets eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and second, it is resistant to rapamycin treatment. Furthermore, in HCT116 cells two non-essential amino acids, glutamine and serine, which are often rapidly metabolised by tumour cells, regulate rapamycin-resistant mTORC1 in a PAT4-dependent manner. Overexpressed PAT4 is also able to promote rapamycin resistance in human embryonic kidney-293 cells. PAT4 is predominantly associated with the Golgi apparatus in a range of cell types, and in situ proximity ligation analysis shows that PAT4 interacts with both mTORC1 and its regulator Rab1A on the Golgi. These findings, together with other studies, suggest that differentially localised intracellular amino-acid transporters contribute to the activation of alternate forms of mTORC1. Furthermore, our data predict that colorectal cancer cells with high PAT4 expression will be more resistant to depletion of serine and glutamine, allowing them to survive and outgrow neighbouring normal and tumorigenic cells, and potentially providing a new route for pharmacological intervention.


Association of a functional polymorphism in the cholesteryl ester transfer protein (CETP) gene with memory decline and incidence of dementia.
Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up--63 lost to follow-up and 7 new to the study--were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) epsilon4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Memory decline and incident dementia. Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P = .03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P = .02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P = .04). This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.


Alpha lipoic acid attenuates iron induced oxidative acute kidney injury in rats.
Iron has been implicated in oxidative tissue injury owing to its ability to generate reactive oxygen species (ROS). We investigated the reno-protective effects of alpha lipoic acid (ALA) by investigating its effects on the kidney isoform of NADPH oxidase (Nox4) and the specific signaling pathways, p38 MAPK and PI3K/Akt, which participate in apoptosis and survival, respectively. We established four groups of seven rats: control, 100 mg/kg ALA, 80 mg/kg iron sucrose (IS) and IS + ALA. IS and ALA were injected intravenously and rats were sacrificied after 6 h. The mRNA expression of the subunits of NADPH oxidase, Nox4 and p22phox; tumor necrosis factor-alpha (TNF-α); and kidney injury molecule-1 (KIM-1) were measured using quantitative real time polymerase chain reaction (qRT-PCR). Active caspase-3 protein expression was evaluated by immunostaining. Also, p38 MAPK and PI3K/Akt signaling pathways were analyzed using western blot. ALA suppressed the mRNA expression of Nox4, p22phox, TNF-α and KIM-1. Active caspase-3 protein expression induced by IS was decreased by ALA. ALA also suppressed p38 MAPK and activated the PI3K/Akt signaling pathway following IS administration. We found that ALA may be an effective strategy for preventing oxidative acute kidney injury caused by IS.


Assessing the validity of surrogate endpoints in the context of a controversy about the measurement of effectiveness of hepatitis C virus treatment.
Surrogate endpoints are often used in clinical trials, as they allow for indirect measures of outcomes (eg, shorter trials with less participants). Improvements in surrogate endpoints (eg, reduction in low density lipoprotein cholesterol, normalisation of glycated haemoglobin) achieved with an intervention are, however, not always associated with improvements in patient-important outcomes. The common tendency in evidence-based medicine is to view results based on surrogate endpoints as less certain than results based on long term, final patient-important outcomes and rate them as 'lower quality evidence'. However, careful appraisal of the validity of a surrogate endpoint as a measure of the final, patient-important outcome is more useful than an automatic judgement. In this guide, we use a contemporary and currently highly debated example of the surrogate endpoint 'sustained viral response' (ie, viral eradication considered to represent successful treatment) in patients treated for chronic hepatitis C virus. We demonstrate how the validity of a surrogate endpoint can be critically appraised to assess the quality of the evidence (ie, the certainty in estimates) and the implications for decision-making.


Pathogenic polyglutamine tracts are potent inducers of spontaneous Sup35 and Rnq1 amyloidogenesis.
The glutamine/asparagine (Q/N)-rich yeast prion protein Sup35 has a low intrinsic propensity to spontaneously self-assemble into ordered, beta-sheet-rich amyloid fibrils. In yeast cells, de novo formation of Sup35 aggregates is greatly facilitated by high protein concentrations and the presence of preformed Q/N-rich protein aggregates that template Sup35 polymerization. Here, we have investigated whether aggregation-promoting polyglutamine (polyQ) tracts can stimulate the de novo formation of ordered Sup35 protein aggregates in the absence of Q/N-rich yeast prions. Fusion proteins with polyQ tracts of different lengths were produced and their ability to spontaneously self-assemble into amlyloid structures was analyzed using in vitro and in vivo model systems. We found that Sup35 fusions with pathogenic (>or=54 glutamines), as opposed to non-pathogenic (19 glutamines) polyQ tracts efficiently form seeding-competent protein aggregates. Strikingly, polyQ-mediated de novo assembly of Sup35 protein aggregates in yeast cells was independent of pre-existing Q/N-rich protein aggregates. This indicates that increasing the content of aggregation-promoting sequences enhances the tendency of Sup35 to spontaneously self-assemble into insoluble protein aggregates. A similar result was obtained when pathogenic polyQ tracts were linked to the yeast prion protein Rnq1, demonstrating that polyQ sequences are generic inducers of amyloidogenesis. In conclusion, long polyQ sequences are powerful molecular tools that allow the efficient production of seeding-competent amyloid structures.


Cancer related fatigue: A ubiquitous problem yet so under reported, under recognized and under treated.
Cancer related fatigue (CRF) is a problem that is highly under reported, under recognized and thus, under treated. About 80% of patients receiving chemotherapy/radiotherapy experience CRF, making it the most common side effect of cancer treatment. Functional assessment of chronic illness therapy fatigue (FACIT-F) version-4 is a 13 item questionnaire that has been used to measure the level of fatigue of cancer patients during their daily activities over the past 7 days. 92 patients of age 18 years and above attending the oncology Out Patient Department (OPD) of a regional cancer center were recruited in this study and were given FACIT-F questionnaire. The relevant sociodemographic parameters were obtained from the medical records of the patients. The internal consistency of the 13 items was measured using the Cronbach's alpha. The Cronbach alpha coefficient for FACIT-F scale in our study was found to be 0.74. Kendall's coefficient of concordance was estimated to be 0.080. The correlation between Eastern Cooperative Oncology Group (ECOG) performance status and mean score of FACIT-F was studied, Pearson correlation coefficient was estimated to be 0.271 (P = 0.009). FACIT-F is a brief, simple, easy to administer and patient friendly tool to measure the fatigue in last 7 days. CRF should be given adequate attention from the beginning of the treatment to improve the quality of life of cancer patients.


Disruption of barrier function in dermatophytosis and pityriasis versicolor.
Dermatophytes have the ability to form molecular attachments to keratin and use it as a source of nutrients, colonizing keratinized tissues, including the stratum corneum of the skin. Malassezia species also affect the stratum corneum of the skin. Therefore, dermatophytosis and pityriasis versicolor of the skin are thought to be important factors of profound changes in skin barrier structure and function. We aimed to describe the changes in transepidermal water loss (TEWL), stratum corneum hydration, and skin pH in the lesions of the dermatophytosis and pityriasis versicolor. Thirty-six patients with dermatophytosis (14 with tinea cruris, 13 with tinea corporis and nine with tinea pedis or tinea manus) and 11 patients with pityriasis versicolor were included in this study. TEWL, stratum corneum conductance and skin pH were determined by biophysical methods to examine whether our patients exhibited changes in barrier function. Dermatophytosis and pityriasis versicolor except tinea pedis and tinea manus showed highly significant increase in TEWL compared with adjacent infection-free skin. Hydration was significantly reduced in lesional skin compared with adjacent infection-free skin. From this study, infections with dermatophytes and Malassezia species on the body can alter biophysical properties of the skin, especially the function of stratum corneum as a barrier to water loss. On the contrary, infections with dermatophytes on the palms and soles little affect the barrier function of the skin.


Role of social networks in shaping disease transmission during a community outbreak of 2009 H1N1 pandemic influenza.
Evaluating the impact of different social networks on the spread of respiratory diseases has been limited by a lack of detailed data on transmission outside the household setting as well as appropriate statistical methods. Here, from data collected during a H1N1 pandemic (pdm) influenza outbreak that started in an elementary school and spread in a semirural community in Pennsylvania, we quantify how transmission of influenza is affected by social networks. We set up a transmission model for which parameters are estimated from the data via Markov chain Monte Carlo sampling. Sitting next to a case or being the playmate of a case did not significantly increase the risk of infection; but the structuring of the school into classes and grades strongly affected spread. There was evidence that boys were more likely to transmit influenza to other boys than to girls (and vice versa), which mimicked the observed assortative mixing among playmates. We also investigated the presence of abnormally high transmission occurring on specific days of the outbreak. Late closure of the school (i.e., when 27% of students already had symptoms) had no significant impact on spread. School-aged individuals (6-18 y) facilitated the introduction and spread of influenza in households, but only about one in five cases aged >18 y was infected by a school-aged household member. This analysis shows the extent to which clearly defined social networks affect influenza transmission, revealing strong between-place interactions with back-and-forth waves of transmission between the school, the community, and the household.


Purged from the Rolls: A Study of Medicaid Disenrollment in Iowa.
Purpose: To describe the impact of disenrollment from Medicaid because of failure to pay premiums as part of Iowa's Medicaid program's personal responsibility component. Methods: We conducted a mixed method study consisting of in-depth interviews with disenrolled members in 2016 and 2017 (n=72) and a survey of disenrolled members in 2017 (n=225). Results: Many disenrollees did not know why they were disenrolled, were unaware of the personal responsibility component or premium requirement, and were confused by the disenrollment process. Disenrollment had negative effects including stress, financial burden, and engaging in behaviors such as skipping medication and postponing medical or dental care. Furthermore, disenrollees were often unable to enroll in health insurance, and for those who did, many reported it was a difficult process. Conclusions: Disenrollment had numerous, negative impacts on members who failed to pay their premiums. There was confusion about program requirements, which might indicate challenges communicating about a complicated program. Policymakers need to consider how to design and implement personal responsibility programs to achieve their desired outcome and reduce confusion and negative consequences.


Chlorophyll orientation and exciton migration in the photosynthetic membrane.
Measurements of the linear dichroism and of the polarization of the fluorescence with oriented chloroplasts have revealed a definite orientation of the pigment molecules with respect to the membrane plane. The Qy transition moments of the chlorophyll a molecules are more closely inclined with respect to this plane for the forms absorbing at longer wavelengths than for those absorbing at shorter wavelengths. The fluorescence depolarization by energy transfer, determined with magnetically-oriented chloroplasts, indicates that the degree of local order increases with wavelength for the different (absorption wavelength) forms of chlorophyll a in vivo. Laser pulses of either picosecond or microsecond duration have been used to probe the emission spectrum, lifetime and quantum yield of fluorescence of chloroplasts at various temperatures. With single picosecond pulses, singlet-singlet annihilations occur within the light-harvesting chlorophyll molecules. In the case of microsecond pulses, triplet excitions act as efficient quenchers of the singlets. By monitoring both the yield of carotenoid triplets and of the fluorescence during and after a laser flash, one can show that the carotenoid triplets account for part of but not all the fluorescence quenching.


Is it really "panic buying"? Public perceptions and experiences of extra buying at the onset of the COVID-19 pandemic.
Shopping behaviour in response to extreme events is often characterized as "panic buying" which connotes irrationality and loss of control. However, "panic buying" has been criticized for attributing shopping behaviour to people's alleged psychological frailty while ignoring other psychological and structural factors that might be at play. We report a qualitative exploration of the experiences and understandings of shopping behaviour of members of the public at the onset of the COVID-19 pandemic. Through a thematic analysis of semi-structured interviews with 23 participants, we developed three themes. The first theme addresses people's understandings of "panic buying". When participants referred to "panic buying" they meant observed product shortages (rather than the underlying psychological processes that can lead to such behaviours), preparedness behaviours, or emotions such as fear and worry. The second theme focuses on the influence of the media and other people's behaviour in shaping subsequent shopping behaviours. The third theme addresses the meaningful motivations behind increased shopping, which participants described in terms of preparedness; some participants reported increased shopping behaviours as a response to other people stockpiling, to reduce their trips to supermarkets, or to prepare for product shortages and longer stays at home. Overall, despite frequently using the term 'panic', the irrationalist connotations of "panic buying" were largely absent from participants' accounts. Thus, "panic buying" is not a useful concept and should not be used as it constructs expected responses to threat as irrational or pathological. It can also facilitate such behaviours, creating a self-fulfilling prophecy.


rtl-M-MOFs (M = Cu, Zn) with a T-shaped bifunctional pyrazole-isophthalate ligand showing flexibility and S-shaped Type F-IV sorption isotherms with high saturation uptakes for M = Cu.
Two new rtl-MOFs rtl-[Cu(HIsa-az-dmpz)] and rtl-[Zn(HIsa-az-dmpz)] have been synthesized by using the new bifunctional ligand 5-(4-(3,5-dimethyl-1H-pyrazolyl)azo)isophthalic acid (H3Isa-az-dmpz). Both frameworks are potentially porous structures with DMF molecules included in the channels of the as synthesized materials. The flexible MOF rtl-[Cu(HIsa-az-dmpz)] undergoes a reversible phase change into a closed form upon activation. Consequently, rtl-[Cu(HIsa-az-dmpz)] shows S-shaped Type F-IV adsorption profiles or a gate-opening effect at cryogenic temperatures with high saturation uptakes of 360 cm3 g-1 for N2 at 77 K and 310 cm3 g-1 for CO2 at 195 K. These profiles together with the reversibility could be reproduced upon repeated measurements on the same materials. The gravimetric high-pressure CO2 adsorption shows a gate-opening at ∼10 bar with an uptake of 332 mg g-1. rtl-[Zn(HIsa-az-dmpz)] undergoes an irreversible transformation into a non-porous phase upon activation.


Healthy late preterm infants and supplementary artificial milk feeds: effects on breast feeding and associated clinical parameters.
to compare the influence of supplementary artificial milk feeds on breast feeding and certain clinical parameters among healthy late preterm infants given regular supplementary artificial milk feeds versus being exclusively breast fed from birth. a comparative study using quantitative methods. Data were collected via a parental diary and medical records. parents of 77 late preterm infants (34 5/7-36 6/7 weeks), whose mothers intended to breast feed, completed a diary during the infants׳ hospital stay. infants who received regular supplementary artificial milk feeds experienced a longer delay before initiation of breast feeding, were breast fed less frequently and had longer hospital stays than infants exclusively breast fed from birth. Exclusively breast-fed infants had a greater weight loss than infants with regular artificial milk supplementation. A majority of the mothers (65%) with an infant prescribed artificial milk never expressed their milk and among the mothers who used a breast-pump, milk expression commenced late (10-84 hours after birth). At discharge, all infants were breast fed to some extent, 43% were exclusively breast fed. clinical practice and routines influence the initiation of breast feeding among late preterm infants and may act as barriers to the mothers׳ establishment of exclusive breast feeding.


B-cell activation by crosslinking of surface IgM or ligation of CD40 involves alternative signal pathways and results in different B-cell phenotypes.
Treatment of small resting B cells with soluble F(ab')2 fragments of anti-IgM, an analogue of T-independent type 2 antigens, induced activation characterized by proliferation and the expression of surface CD5. In contrast, B cells induced to proliferate in response to thymus-dependent inductive signals provided by either fixed activated T-helper 2 cells or soluble CD40 ligand-CD8 (CD40L) recombinant protein displayed elevated levels of CD23 (Fc epsilon II receptor) and no surface CD5. Treatment with anti-IgM and CD40L induced higher levels of proliferation and generated a single population of B cells coexpressing minimal amounts of CD5 and only a slight elevation of CD23. Anti-IgM- but not CD40L-mediated activation was highly sensitive to inhibition by cyclosporin A and FK520. Sp-cAMPS, an analogue of cAMP, augmented CD40L and suppressed surface IgM-mediated activation. Taken together these results are interpreted to mean that there is a single population of small resting B cells that can respond to either T-independent type 2 (surface IgM)- or T-dependent (CD40)-mediated activation. In response to different intracellular signals these cells are induced to enter alternative differentiation pathways.


Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation.
Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 ± 0.42 vs. PPX[AMIO, DEX] 0.25 ± 0.42, P < 0.001). The PPX[AMIO, DEX] group was similar to native PPX (PPX 0.38 ± 0.48 vs. PPX[AMIO, DEX] 0.25 ± 0.42, P=NS). PPX-Oxd group adhesions were indistinguishable from controls (PPX-Oxd 2.83 ± 0.41 vs. control 2.75 ± 0.42, P=NS). NTF was reduced in the PPX[AMIO, DEX] group (0.80 ± 0.10 mm) compared to control (1.78 ± 0.13 mm, P < 0.001). Total duration of atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 ± 6.8 s vs. 187.6 ± 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 ± 1.2 s vs. 103.2 ± 178 s, p = 0.004). DEX/AMIO-loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications.


A Descriptive, Longitudinal Study of Quality of Life and Perceived Health Needs in Patients With Head and Neck Cancer.
Patients with head and neck cancer have numerous concerns and symptoms in the first year of posttreatment survivorship and are especially vulnerable at the end of treatment and 1 month posttreatment. This article shares the findings of a descriptive, longitudinal study of health-related quality of life (HRQOL) in patients with head and neck cancer from the beginning of treatment through 12 months posttreatment. The primary objective of this study was to describe the symptom experience and health needs of patients receiving radiation for head and neck cancer to support the establishment of an advanced practitioner (AP) clinic for head and neck cancer survivors. Significant findings in this study showed HRQOL at the end of treatment was significantly lower than baseline (p < .001). Low scores persisted through 1 month, with gradual recovery by 12 months. Fatigue and anxiety had the highest mean scores, yet anxiety improved with time, whereas fatigue did not. Positive human papillomavirus status was statistically associated with higher anxiety. Socioeconomic status negatively impacted HRQOL. Themes of perceived health needs were managing oral symptoms, returning to a normal life, and regaining energy. The AP in oncology can play a pivotal role in providing comprehensive assessment, symptom management, health education, and supportive counseling in this population throughout treatment and survivorship.


Spin Current Cross-Correlations as a Probe of Magnon Coherence.
Motivated by the important role of the normalized second-order coherence function, often called g^{(2)}, in the field of quantum optics, we propose a method to determine magnon coherence in solid-state devices. Namely, we show that the cross-correlations of pure spin currents injected by a ferromagnet into two metal leads, normalized by their dc value, replicate the behavior of g^{(2)} when magnons are driven far from equilibrium. We consider two scenarios: driving by ferromagnetic resonance, which leads to the coherent occupation of a single mode, and driving by heating of the magnons, which leads to an excess of incoherent magnons. We find an enhanced normalized cross-correlation in the latter case, thereby demonstrating bunching of nonequilibrium thermal magnons due to their bosonic statistics. Our results contribute to the burgeoning field of quantum magnonics, which seeks to explore and exploit the quantum nature of magnons.


Pain and autonomic dysfunction in patients with sarcoidosis and small fibre neuropathy.
Small fibre neuropathy (SFN) has been demonstrated in sarcoidosis. However, a systematic analysis of neuropathic pain and autonomic symptoms, key features of SFN, has not been performed. Clinimetric evaluation of pain and autonomic symptoms using the neuropathic pain scale (NPS) and the modified Composite Autonomic Symptoms Scale (mCOMPASS) was used in sarcoidosis patients for this study. A total of 91 sarcoidosis patients (n = 23 without SFN symptoms, n = 43 with SFN symptoms but normal intraepidermal nerve fibre density (IENFD), n = 25 with SFN symptoms and reduced IENFD) were examined. NPS and mCOMPASS were assessed twice (reliability studies). Severity of pain was compared between the subgroups. Correlation between NPS and a visual analogue pain scale (VAS) was assessed (validity studies). Healthy controls (n = 105) completed the mCOMPASS for comparison with patients' scores. Patients with sarcoidosis, SFN complaints, and reduced IENFD demonstrated more severe pain scores on the NPS. The mCOMPASS differentiated between subjects with and without SFN symptoms. A significant correlation was obtained between the NPS and VAS, indicating good construct validity. Good reliability values were obtained for all scales. The use of the NPS to evaluate SFN symptoms is suggested, as it shows differences between patients with SFN symptoms with normal or reduced IENFD values. The mCOMPASS might be used to select patients for further testing.


Comparing cost-of-illness estimates from alternative approaches: an application to diabetes.
To compare disease cost estimates from two commonly used approaches. Pooled Medical Expenditure Panel Survey (MEPS) data for 1998-2003. We compared regression-based (RB) and attributable fraction (AF) approaches for estimating disease-attributable costs with an application to diabetes. The RB approach used results from econometric models of disease costs, while the AF approach used epidemiologic formulas for diabetes-attributable fractions combined with the total costs for seven conditions that result from diabetes. We used SAS version 9.1 to create a dataset that combined data from six consecutive years of MEPS. The RB approach produced higher estimates of diabetes-attributable medical spending ($52.9 billion in 2004 dollars) than the AF approach ($37.1 billion in 2004 dollars). RB model estimates may in part be higher because of the challenges of implementing the two approaches in a similar manner, but may also be higher because they capture the costs of increased treatment intensity for those with the disease. We recommend using the RB approach for estimating disease costs whenever individual-level data on health care spending are available and when the presence of the disease affects treatment costs for other conditions, as in the case of diabetes.


Ethical and Regulatory Issues for Embedded Pragmatic Trials Involving People Living with Dementia.
Embedded pragmatic clinical trials (ePCTs) present an opportunity to improve care for people living with dementia (PLWD) and their care partners, but they also generate a complex constellation of ethical and regulatory challenges. These challenges begin with participant identification. Interventions may be delivered in ways that make it difficult to identify who is a human subject and therefore who needs ethical and regulatory protections. The need for informed consent, a core human subjects protection, must be considered but can be in tension with the goals of pragmatic research design. Thus it is essential to consider whether a waiver or alteration of informed consent is justifiable. If informed consent is needed, the question arises of how it should be obtained because researchers must acknowledge the vulnerability of PLWD due in part to diminished capacity and also to increased dependence on others. Further, researchers should recognize that many sites where ePCTs are conducted will be unfamiliar with human subjects research regulations and ethics. In this report, the Regulation and Ethics Core of the National Institute on Aging Imbedded Pragmatic Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory discusses key ethical and regulatory challenges for ePCTs in PLWD. A central thesis is that researchers should strive to anticipate and address these challenges early in the design of their ePCTs as a means of both ensuring compliance and advancing science. J Am Geriatr Soc 68:S37-S42, 2020.


Expression of a folate binding protein in L1210 cells grown in low folate medium.
We have isolated variants of L1210 cells (L1210B) expressing, in addition to the "classical" high affinity/low capacity system for reduced folate uptake, high levels of a membrane-associated folate binding protein. This folate binding protein was expressed in L1210 cells grown at low physiological folate levels (less than 0.5 nM), but down-regulated after transfer in standard high folate (2 microM) medium. The binding capacity of L1210B cells for [3H]folic acid and [3H]-methotrexate was identical (5-11 pmol/10(6) cells) but affinities were different. The affinities relative to folic acid were 0.5 for 5-methyltetrahydrofolate, 0.25 for 5-formyltetrahydrofolate, 0.08 for 10-ethyl-10-deazaaminopterin, and 0.05 for methotrexate, respectively. L1210B cells exposed to low extracellular concentrations of [3H]folic acid (25 nM) accumulated 15 pmol [3H]folic acid/10(7) cells over a 5-h period. [3H]Folic acid accumulation by wild-type L1210 cells could not be demonstrated under these conditions. The folate binding protein in L1210B cells could be specifically and covalently labeled at 4 degrees C with a N-hydroxysuccinimide ester of [3H]-methotrexate or [3H]folic acid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of detergent-solubilized membrane proteins showed a major labeled band with Mr 42,000-44,000.


Bubble CPAP Support after Discontinuation of Mechanical Ventilation Protects Rat Lungs with Ventilator-Induced Lung Injury.
Bubble continuous positive airway pressure (BCPAP) has been used in neonates with respiratory distress for decades, but its lung-protective effect and underlying mechanism has not been investigated. To test the hypothesis that BCPAP use after extubation decreases lung injury and that alterations to lung nitric oxide synthase (NOS) 3 expression may be one of the underlying mechanisms. We compared gas exchange, lung injury severity, and lung NOS expression among rats with ventilator-induced lung injury (VILI) treated with either BCPAP or spontaneous breathing. After high tidal volume ventilation for 30 min, the rats were randomly divided to three groups: a control group underwent spontaneous breathing (n = 7), and two BCPAP groups were treated with the bubble technique with either a 2.5-mm-diameter (n = 7) or a 5.5-mm-diameter (n = 7) expiratory limb for 2 h. The bubble technique (2.5 and 5.5 mm diameter combined) resulted in a significantly higher PaO2, decreased alveolar protein levels (1.01 vs. 1.43 mg/kg, p < 0.05), a lower lung injury score (3.87 vs. 4.86, p < 0.05), and decreased NOS3 expression (1.99 vs. 3.32, p < 0.05) compared to spontaneous breathing in the control group. BCPAP with a 2.5-mm-diameter and with a 5.5-mm-diameter expiratory limb was not different with regard to gas exchange, alveolar protein levels, and lung injury scores, but there was a trend for lower NOS3 expression in the 5.5-mm group (1.41 vs. 2.56, p = 0.052). BCPAP decreases lung injury in rats with VILI after stopping mechanical ventilation. Attenuation of lung NOS3 expression may be one of the underlying mechanisms.


Electronic tuning of self-healing fluorophores for live-cell and single-molecule imaging.
Bright, long-lasting organic fluorophores enable a broad range of imaging applications. "Self-healing" fluorophores, in which intra-molecularly linked protective agents quench photo-induced reactive species, exhibit both enhanced photostability and biological compatibility. However, the self-healing strategy has yet to achieve its predicted potential, particularly in the presence of ambient oxygen where live-cell imaging studies must often be performed. To identify key bottlenecks in this technology that can be used to guide further engineering developments, we synthesized a series of Cy5 derivatives linked to the protective agent cyclooctatetraene (COT) and examined the photophysical mechanisms curtailing their performance. The data obtained reveal that the photostability of self-healing fluorophores is limited by reactivity of the COT protective agent. The addition of electron withdrawing substituents to COT reduced its susceptibility to reactions with molecular oxygen and the fluorophore to which it is attached and increased its capacity to participate in triplet energy transfer. Exploiting these insights, we designed and synthesized a suite of modified COT-fluorophores spanning the visible spectrum that exhibited markedly increased intra-molecular photostabilization. Under ambient oxygen conditions, the photostability of Cy3 and Cy5 fluorophore derivatives increased by 3- and 9-fold in vitro and by 2- and 6-fold in living cells, respectively. We further show that this approach can improve a silicon rhodamine fluorophore. These findings offer a clear strategy for achieving the full potential of the self-healing strategy and its application to the gamut of fluorophore species commonly used for biomedical imaging.


The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues.
In mammalian cells, there are two isoforms of DNA topoisomerase II, designated alpha (170-kDa form) and beta (180-kDa form). Previous studies using cell lines have shown that the topoisomerase IIalpha and beta isoforms are differentially regulated during the cell cycle and in response to changes in growth state. Moreover, both isoforms can act as targets for a range of anti-tumour drugs. Here, we have analysed the normal tissue distribution in humans of topoisomerase IIalpha and beta using isoform-specific antibodies. In addition, we have studied expression of these isoforms in 69 primary tumour biopsies, representative either of tumours that are responsive to topoisomerase II-targeting drugs (breast, lung, lymphoma and seminoma) or of those that show de novo drug resistance (colon). Topoisomerase IIalpha was expressed exclusively in the proliferating compartments of all normal tissues, and was detectable in both the cell nucleus and cytoplasm. In biologically aggressive or rapidly proliferating tumours (e.g. high-grade lymphomas and seminomas), there was a high level of topoisomerase IIalpha, although expression was still detectable in colon tumours, indicating that expression of this isoform is not sufficient to explain the intrinsic drug resistance of colon tumours. Topoisomerase IIbeta was expressed ubiquitously in vivo and was localized in both the nucleoli and the nucleoplasm. This isoform was present in quiescent cell populations, but was expressed at a generally higher level in all tumours and proliferating cells than in normal quiescent tissues. We conclude that topoisomerase IIalpha is a strict proliferation marker in normal and neoplastic cells in vivo, but that topoisomerase IIbeta has a much more general cell and tissue distribution than has topoisomerase IIalpha. The apparent up-regulation of topoisomerase IIbeta in neoplastic cells has implications for the response of patients to anti-tumour therapies that include topoisomerase II-targeting drugs.


Impact of Public Health Responses During a Measles Outbreak in an Amish Community in Ohio: Modeling the Dynamics of Transmission.
We quantified measles transmissibility during a measles outbreak in Ohio in 2014 to evaluate the impact of public health responses. Case incidence and the serial interval (time between symptom onset in primary cases and secondary cases) were used to assess trends in the effective reproduction number R (the average number of secondary cases generated per case). A mathematical model was parameterized using early R values to determine the size and duration of the outbreak that would have occurred if containment measures had not been initiated, as well as the impact of vaccination. As containment started, we found a 4-fold decline in R (from approximately 4 to 1) over the course of 2 weeks and maintenance of R < 1 as control measures continued. Under a conservative scenario, the model estimated 8,472 cases (90% confidence interval (CI): 8,447, 8,489) over 195 days (90% CI: 179, 223) without control efforts and 715 cases (90% CI: 103, 1,338) over 128 days (90% CI: 117, 139) when vaccination was included; 7,757 fewer cases (90% CI: 7,130, 8,365) and 67 fewer outbreak days (90% CI: 48, 98) were attributed to vaccination. Vaccination may not account entirely for transmission reductions, suggesting that changes in community behavior (social distancing) and other control efforts (isolation, quarantining) are important. Our findings highlight the benefits of measles outbreak response and of understanding behavior change dynamics.


Memory T cells specific for murine cytomegalovirus re-emerge after multiple challenges and recapitulate immunity in various adoptive transfer scenarios.
Reconstitution of CMV-specific immunity after transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Because of viral persistence, most CMV-specific CD8(+) T cells become terminally differentiated effector phenotype CD8(+) T cells (TEFF). A minor subset retains a memory-like phenotype (memory phenotype CD8(+) T cells [TM]), but it is unknown whether these cells retain memory function or persist over time. Interestingly, recent studies suggest that CMV-specific CD8(+) T cells with different phenotypes have different abilities to reconstitute sustained immunity after transfer. The immunology of human CMV infections is reflected in the murine CMV (MCMV) model. We found that human CMV- and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. The MCMV-specific TM population was stable over time and retained a proliferative capacity that was vastly superior to TEFF. Strikingly, after transfer, TM established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM could protect Rag(-/-) mice, only TM persisted after transfer into immune replete, latently infected recipients and responded if recipient immunity was lost. Interestingly, transferred TM did not expand until recipient immunity was lost, supporting that competition limits the Ag stimulation of TM. Ultimately, these data show that CMV-specific TM retain memory function during MCMV infection and can re-establish CMV immunity when necessary. Thus, TM may be a critical component for consistent, long-term adoptive immunotherapy success.


Challenges in fabrication of mesoporous carbon films with ordered cylindrical pores via phenolic oligomer self-assembly with triblock copolymers.
Mesoporous phenol formaldehyde (PF) polymer resin and carbon films are prepared by a solution self-assembly of PF oligomers with amphiphilic triblock copolymers. After thermopolymerization of the PF to cross-link the network, the films show an ordered morphology as determined by X-ray diffraction and grazing incidence small-angle X-ray scattering (GISAXS). Our results show that the amphiphilic triblock copolymer template greatly influences the stability of the final porous mesostructures. The pyrolysis of the two-dimensional (2-D) hexagonal films with p6mm symmetry templated by Pluronic F127 yields a disordered porous structure following the template removal. Conversely, films templated by Pluronic P123 can exhibit well-ordered cylindrical pores after the template removal, but the solution composition range to yield ordered cylindrical mesopores is significantly reduced (nearly 70%) for thin films in comparison to bulk powders. We propose two dominant difficulties in fabricating well-ordered cylindrical mesopores in films: first, the stress from contraction during the pyrolysis can lead to a collapse of the mesostructure if the wall thickness is insufficient, and second, the surface wetting behavior in thin films leads to a small compositional range.


Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial.
It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days. A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020). Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs. The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression. Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%). Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment. ClinicalTrials.gov Identifier: NCT04364893.


Patient-reported symptoms improve prediction of acute coronary syndrome in the emergency department.
Early diagnosis is critical in the management of patients with acute coronary syndrome (ACS), particularly ST-elevation myocardial infarction (STEMI), because effective therapies are time-dependent. Aims of this secondary analysis were to determine: (i) the prognostic value of symptoms for an ACS diagnosis in conjunction with electrocardiographic (ECG) and troponin results; and (ii) if any of 13 symptoms were associated with prehospital delay in those presenting to the emergency department (ED) with potential ACS. Patients receiving a cardiac evaluation in the ED were eligible for the study. Thirteen patient-reported symptoms were assessed in triage. Prehospital delay time was calculated as the time from symptom onset until registration in the ED. A total of 1,064 patients were enrolled in five EDs. The sample was 62% male, 70% white, and had a mean age of 60.2 years. Of 474 participants diagnosed with ACS, 118 (25%) had STEMI; 251 (53%) had non-ST elevation myocardial infarction (NSTEMI); and 105 (22%) had unstable angina. Sweating (OR = 1.42 CI [1.01, 2.00]) and shoulder pain (OR = 1.64 CI [1.13, 2.38]) added to the predictive value of an ACS diagnosis when combined with ECG and troponin results. Shortness of breath (OR = 0.71 CI [0.50, 1.00]) and unusual fatigue (OR = 0.60 CI [0.42, 0.84]) were predictive of a non-ACS diagnosis. Sweating predicted shorter prehospital delay (HR = 1.35, CI [1.10, 1.67]); shortness of breath (HR = 0.73 CI [0.60, 0.89]) and unusual fatigue (HR = 0.72, CI [0.57, 0.90]) were associated with longer prehospital delay. Patient-reported symptoms are significantly associated with ACS diagnoses and prehospital delay. Sweating and shoulder pain combined with ECG signs of ischemia may improve the timely detection of ACS in the ED.


Clay Sols versus Clay Gels: Biological Activities Compared.
Clay gels were prepared by extrusion of sodium-Wyoming bentonite pastes through a small orifice. Clay sols were prepared from the gels by rapping on the laboratory bench for disturbance. Lettuce seeds germinated faster, microbes generated more heat, and corn seedlings absorbed more (22)Na in the sols than in the gels. These differences in biological activity are attributable to changes in water properties and ion activities that accompany transformation from gelsol.


Microwave auditory effect- a comparison of some possible transduction mechanisms.
When human subjects are irradiated with pulse modulated microwave energy they report the perception of a sound that appears to originate from within or slightly behing the head. Three of the possible mechanisms are examined using first order mathematical approximations and several simplifying assumptions. The results show that while all three (radiation pressure, strictive force and thermal expansion) are capable of producing the phenomenon, the stress resulting from thermal expansion may be so great that it masks the effect of the others completely.


Neuroimaging and advanced research techniques may lead to improved outcomes in military members suffering from traumatic brain injury.
Recent military conflicts in Iraq and Afghanistan have resulted in the significant increase in blast-related traumatic brain injury (TBI), leading to increased Department of Defense interest in its potential long-term effects ranging from the mildest head injuries termed subconcussive trauma to the most debilitating termed chronic traumatic encephalopathy (CTE). Most patients with mild TBI will recover quickly while others report persistent symptoms called postconcussive syndrome. Repeated concussive and subconcussive head injuries result in neurodegenerative conditions that may hinder the injured for years. Fundamental questions about the nature of these injuries and recovery remain unanswered. Clinically, patients with CTE present with either affective changes or cognitive impairment. Genetically, there have been no clear risk factors identified. The discovery that microglia of the cerebral cortex discharged small extracellular vesicles in the injured and adjacent regions to a TBI may soon shed light on the immediate impact injury mechanisms. The combination of neuroimaging and advanced research techniques may, one day, fill critical knowledge gaps and lead to significant TBI research and treatment advancements.


The Escherichia coli cell division protein and model Tat substrate SufI (FtsP) localizes to the septal ring and has a multicopper oxidase-like structure.
The Escherichia coli protein SufI (FtsP) has recently been proposed to be a component of the cell division apparatus. The SufI protein is also in widespread experimental use as a model substrate in studies of the Tat (twin arginine translocation) protein transport system. We have used SufI-GFP (green fluorescent protein) fusions to show that SufI localizes to the septal ring in the dividing cell. We have also determined the structure of SufI by X-ray crystallography to a resolution of 1.9 A. SufI is structurally related to the multicopper oxidase superfamily but lacks metal cofactors. The structure of SufI suggests it serves a scaffolding rather than an enzymatic role in the septal ring and reveals regions of the protein likely to be involved in the protein-protein interactions required to assemble SufI at the septal ring.


HIV seroconversions among male non-occupational post-exposure prophylaxis service users: a data linkage study.
Despite widespread prescription of non-occupational post-exposure prophylaxis (NPEP) in Victoria, little is known about subsequent HIV acquisition among NPEP users. We linked the Victorian NPEP Service (VNPEPS) database and the Victorian HIV Surveillance Registry to determine the number, incidence rate and predictive factors of HIV seroconversions among users of the VNPEPS. Records from male patients that received NPEP in the VNPEPS database (n = 1420) between January 2001 and February 2008 were linked with all entries in the Victorian HIV Surveillance Registry up to May 2008. Sixty-one men who presented to the VNPEPS were identified as HIV seropositive; 16 of these were diagnosed at initial presentation for NPEP. The incidence of HIV seroconversion in males who were HIV seronegative at first presentation for NPEP was 1.27 (95% confidence interval 0.95-1.70) per 100 person-years. There was no association between HIV seroconversion and number of NPEP presentations or age. The median age of seroconversion was 34.6 years. The incidence of HIV infection among men presenting to the VNPEPS is slightly lower than the HIV incidence in NPEP users in a recent Australian cohort study of men who have sex with men, but higher than HIV incidence in general gay male populations. Frequency of NPEP use was not associated with risk of HIV seroconversion. Examination of risk behaviour before and after NPEP use in this population is required to further assess the impact of NPEP availability and use on HIV incidence rates and risk behaviour in Australia.


Population-based evidence of a strong decline in the prevalence of smokers in Brazil (1989-2003).
To evaluate the evolution in smoking indicators in the adult Brazilian population between 1989 and 2003. We compared age-adjusted prevalence ratios and means for smoking indicators, stratified by age, sex and sociodemographic variables, obtained from two comparable household surveys that used probabilistic sampling of the Brazilian population aged > 18 years (n = 34 808 in 1989 and n = 5000 in 2003). Between 1989 and 2003, there was a substantial decrease in the prevalence of smoking (from 34.8% to 22.4%; age-adjusted prevalence ratio, 0.65; 95% confidence interval, CI, 0.60-0.70) and a modest reduction in the mean number of cigarettes smoked per day (from 13.3 to 11.6; age-adjusted difference, -1.8; 95% CI, -2.6 - -1.0). Reductions in the prevalence and intensity of smoking were greater among males, younger age groups and higher socioeconomic strata. The prevalence of smoking in the adult Brazilian population declined by 35% between 1989 and 2003, or an average of 2.5% per year. This exceptional reduction surpasses those seen in other countries that implemented wide-ranging and rigorous policies for controlling smoking during the same period. The more intense decline in smoking in younger age groups was consistent with the concentration of efforts of the Brazilian tobacco control programme to prevent the onset of smoking among youths and the total prohibition of cigarette advertising. We recommend the intensification of programme initiatives targeting women and less economically favoured population strata.


Surgery for Combined Hamartoma of the Retina and Retinal Pigment Epithelium.
There is no consensus on whether and when surgical treatment is indicated for combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). We aim to discuss the benefits of surgical intervention and techniques that may improve the outcome. A 24-year-old man experienced progressive visual loss for 6 months in his left eye due to CHRRPE. At presentation, visual acuity was 1.3 LogMAR and fundoscopy revealed extensive tractional pre- and epiretinal membranes, subretinal exudation, and a vasoproliferative tumor in the inferior periphery. A complete vitrectomy was performed, while paying special attention to vitreous shaving at the vitreous base and removal of vitreoschisis-induced vitreous cortex remnants (VCR) from the retinal surface posterior to the vitreous base. Tractional membranes and internal limiting membrane were peeled, and the vasoproliferative tumor was excised. Silicone oil tamponade was removed 11 weeks after surgery. No intra- or postoperative complications occurred. Visual acuity improved to 0.8 LogMAR and remained stable for 48-month follow-up. Vitreoretinal surgery can prevent complications that occur with CHRRPE. In addition, visual function may improve even if the initial visual acuity is low. Timely and complete vitrectomy with extensive membranectomy and detection and removal of VCR is recommended to avoid complications in challenging CHRRPE.


Venous thromboembolism in COVID-19: systematic review of reported risks and current guidelines.
Many centres have noticed a high number of venous thromboembolism (VTE) events among critically ill inpatients with COVID-19 pneumonia. The aims of this study were (1) to summarise the reported risk of VTE associated with COVID-19 infections and (2) to summarise guidance documents on thromboprophylaxis in COVID-19 patients, in a systematic review. We systematically searched for peer-reviewed evidence on the risk of VTE in patients with COVID-19, in PubMed, Embase and Twitter, and for guidelines or guidance documents for thromboprophylaxis, from international or national societies relevant to the field of thrombosis and haemostasis, up to April 30 2020. We found 11 studies (1 clinical trial, 7 retrospective cohorts and 3 prospective cohorts), which included a range of 16 to 388 in patients with COVID-19 (total of 1369 inpatients). The diagnoses of COVID-19 and VTE were of high quality, but the follow-up was often unclear. Most studies reported universal in-hospital thromboprophylaxis. Among all inpatients and among intensive care unit (ICU) inpatients with COVID-19, reported risks of VTE were 4.4–8.2% (three studies) and 0–35.3% (six studies), respectively. Two studies at least partially screened for VTE in ICU inpatients with COVID-19, and found risks of 24.7–53.8%. We found 12 guidelines for thromboprophylaxis of COVID-19 patients. The majority suggested universal pharmacological thromboprophylaxis in all COVID-19 inpatients, but there was heterogeneity in the suggested intensity of thromboprophylaxis: seven advised considering intensified doses of heparin according to the clinical or biological severity of the disease, especially in the ICU setting. Venous thromboembolism very commonly complicates the clinical course of inpatients with COVID-19, despite thromboprophylaxis. The risk appears highest among critically ill inpatients. We found no estimates of risks among outpatients. Many questions remain unresolved, as delineated by the heterogeneity of national and international guidelines. This situation calls for fast randomised clinical trials, comparing different schemes of thromboprophylaxis in COVID-19 inpatients.