Imaging of brain dopamine pathways: implications for understanding obesity.
Obesity is typically associated with abnormal eating behaviors. Brain imaging studies in humans implicate the involvement of dopamine (DA)-modulated circuits in pathologic eating behavior(s). Food cues increase striatal extracellular DA, providing evidence for the involvement of DA in the nonhedonic motivational properties of food. Food cues also increase metabolism in the orbitofrontal cortex indicating the association of this region with the motivation for food consumption. Similar to drug-addicted subjects, striatal DA D2 receptor availability is reduced in obese subjects, which may predispose obese subjects to seek food as a means to temporarily compensate for understimulated reward circuits. Decreased DA D2 receptors in the obese subjects are also associated with decreased metabolism in prefrontal regions involved in inhibitory control, which may underlie their inability to control food intake. Gastric stimulation in obese subjects activates cortical and limbic regions involved with self-control, motivation, and memory. These brain regions are also activated during drug craving in drug-addicted subjects. Obese subjects have increased metabolism in the somatosensory cortex, which suggests an enhanced sensitivity to the sensory properties of food. The reduction in DA D2 receptors in obese subjects coupled with the enhanced sensitivity to food palatability could make food their most salient reinforcer putting them at risk for compulsive eating and obesity. The results from these studies suggest that multiple but similar brain circuits are disrupted in obesity and drug addiction and suggest that strategies aimed at improving DA function might be beneficial in the treatment and prevention of obesity.


Spatial forecasting of switchgrass productivity under current and future climate change scenarios.
Evaluating the potential of alternative energy crops across large geographic regions, as well as over time, is a necessary component to determining if biofuel production is feasible and sustainable in the face of growing production demands and climatic change. Switchgrass (Panicum virgatum L.), a native perennial herbaceous grass, is a promising candidate for cellulosic feedstock production. In this study, current and future (from 2080 to 2090) productivity is estimated across the central and eastern United States using ALMANAC, a mechanistic model that simulates plant growth over time. The ALMANAC model was parameterized for representative ecotypes of switchgrass. Our results indicate substantial variation in switchgrass productivity both within regions and over time. States along the Gulf Coast, southern Atlantic Coast, and in the East North Central Midwest have the highest current biomass potential. However, these areas also contain critical wetland habitat necessary for the maintenance of biodiversity and agricultural lands necessary for food production. The southern United States is predicted to have the largest decrease in future biomass production. The Great Plains are expected to experience large increases in productivity by 2080-2090 due to climate change. In general, regions where future temperature and precipitation are predicted to increase are also where larger future biomass production is expected. In contrast, regions that show a future decrease in precipitation are associated with smaller future biomass production. Switchgrass appears to be a promising biofuel crop for the central and eastern United States, with local biomass predicted to be high (>10 Mg/ha) for approximately 50% of the area studied for each climate scenario. In order to minimize land conversion and loss of biodiversity, areas that currently have and maintain high productivity under climate change should be targeted for their long-term growth potential.


Plasminogen associates with phosphatidylserine-exposing platelets and contributes to thrombus lysis under flow.
The interaction of plasminogen with platelets and their localization during thrombus formation and fibrinolysis under flow are not defined. Using a novel model of whole blood thrombi, formed under flow, we examine dose-dependent fibrinolysis using fluorescence microscopy. Fibrinolysis was dependent upon flow and the balance between fibrin formation and plasminogen activation, with tissue plasminogen activator-mediated lysis being more efficient than urokinase plasminogen activator-mediated lysis. Fluorescently labeled plasminogen radiates from platelet aggregates at the base of thrombi, primarily in association with fibrin. Hirudin attenuates, but does not abolish plasminogen binding, denoting the importance of fibrin. Flow cytometry revealed that stimulation of platelets with thrombin/convulxin significantly increased the plasminogen signal associated with phosphatidylserine (PS)-exposing platelets. Binding was attenuated by tirofiban and Gly-Pro-Arg-Pro amide, confirming a role for fibrin in amplifying plasminogen binding to PS-exposing platelets. Confocal microscopy revealed direct binding of plasminogen and fibrinogen to different platelet subpopulations. Binding of plasminogen and fibrinogen co-localized with PAC-1 in the center of spread platelets. In contrast, PS-exposing platelets were PAC-1 negative, and bound plasminogen and fibrinogen in a protruding "cap." These data show that different subpopulations of platelets harbor plasminogen by diverse mechanisms and provide an essential scaffold for the accumulation of fibrinolytic proteins that mediate fibrinolysis under flow.


Digital subtraction arteriography in the diagnosis of renovascular hypertension.
Renal digital subtraction arteriography (RDSA) is a relatively safe, simple, and inexpensive means of detecting the presence of renovascular disease in hypertensive patients. We report our own 15-month experience with RDSA, performed on 166 patients because of hypertension, and review the literature. Twenty-eight of the patients had arteriography. Using this as a measure, the sensitivity of RDSA was 83% and its specificity 96%. RDSA findings are usually conclusive. Addition of plain films following the procedure permits evaluation of renal parenchyma, collecting systems, ureters, and bladder. Arteriography should be reserved for those patients with positive RDSA to be treated by surgery or angioplasty, and for the small number of patients who have a non-diagnostic RDSA. If renal vein renin sampling is done first, RDSA may be performed at the same time. As RDSA becomes more available there will be little place for rapid sequence urography in the investigation of hypertension. In patients suspected of having renovascular hypertension, the primary mode of investigation should be renal DSA.


The National Emphysema Treatment Trial (NETT): a study in agency collaboration.
The National Emphysema Treatment Trial (NETT) was a multicenter, randomized, controlled clinical trial, comparing the efficacy of lung volume reduction surgery (LVRS) plus medical management with rehabilitation to medical management with rehabilitation in 1,218 patients with severe emphysema. The NETT was a precedent-setting collaborative effort of three government agencies: the Centers for Medicare and Medicaid Services (CMS); the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH); and the Agency for Healthcare Research and Quality (AHRQ). NETT provided Medicare beneficiaries with controlled access to a promising but unproven procedure, while scientifically valid data on the efficacy and costs were collected to guide future use, coverage decisions, and policy. NETT demonstrates that collaboration among federal agencies and among health plans, researchers, and providers can successfully fulfill their differing missions simultaneously and is a productive approach to evaluating new treatments of mutual interest.


Development and temperament in very low birth weight infants--the second year.
This article reports findings from the second year of a two-year longitudinal study designed to assess the VLBW infant in the areas of temperament, development, and the home environment. Data were obtained from 20 of the original 26 infants who participated in the study. During a home visit the Denver Developmental Screening Test (DDST), the Toddler Temperament Questionnaire (TTQ), and the Home Observation Measurement for Evaluation Inventory (HOME) were completed. Twenty percent of the toddlers were at-risk for developmental delay when assessed at the corrected gestational age. This compares to 42% who were deemed to be at-risk during the first year of life. No relationship was found between developmental-risk status and the quality of the home environment. The VLBW toddlers' temperaments were not significantly different from the standardization population. However, there were fewer easy toddlers than would be expected. During the second year the percentage of difficult children decreased from 38% to 10%. The VLBW toddler's behavioral style was characterized by arrhythmicity and low persistence. There was a moderate correlation between home environment and the toddler's activity level. High activity was negatively correlated with maternal involvement and provision of appropriate play things. The families of the 20 toddlers scored on the upper 25th percentile on the HOME Inventory. The high quality of the childrearing environment was stable over the two years.


Are Changes in Heart Rate Variability During Hypoglycemia Confounded by the Presence of Cardiovascular Autonomic Neuropathy in Patients with Diabetes?
We have recently shown how the combination of information from continuous glucose monitor (CGM) and heart rate variability (HRV) measurements can be used to construct an algorithm for prediction of hypoglycemia in both bedbound and active patients with type 1 diabetes (T1D). Questions remain on how cardiovascular autonomic neuropathy (CAN) influences these measurable changes. This study aims to examine if changes in HRV during hypoglycemia are confounded by the presence of CAN. Twenty-one adults (hereof 13 men) with T1D prone to hypoglycemia were recruited and monitored with CGM and a Holter device while they performed normal daily activities. CAN was diagnosed using two cardiac reflex tests: (1) deep breathing and (2) orthostatic hypotension and end organ symptoms. Early CAN was defined as the presence of one abnormal reflex test and severe CAN was defined as two abnormal tests or one abnormal test combined with symptoms of autonomic neuropathy. A total of 19 hypoglycemic and corresponding euglycemia periods were identified among the 21 patients. Eleven patients were diagnosed with CAN, hereof five with severe CAN. The HRV parameter low frequency (LF) was significantly (P = 0.029) reduced during hypoglycemia. Changes in LF during hypoglycemia were not different between patients with and without CAN, -0.64 versus -0.48 log(LF) (P = 0.74). Our data show that there are measurable changes in HRV during hypoglycemia, and present in both patients with and without CAN.


Radiosynthesis and evaluation of 4-(6-[18F]Fluoro-4-(5-isopropoxy-1H-indazol-3-yl)pyridin-2-yl)morpholine as a novel radiotracer candidate targeting leucine-rich repeat kinase 2.
Mutations that increase leucine-rich repeat kinase 2 (LRRK2) activity in the brain are associated with Parkinson's disease. Here, we synthesized a novel compound 4-(6-fluoro-4-(5-isopropoxy-1H-indazol-3-yl)pyridin-2-yl)morpholine (FIPM) and labeled it with fluorine-18 (18F), to develop a positron emission tomography (PET) tracer for in vivo visualization of LRRK2 in the brain. FIPM showed high in vitro binding affinity for LRRK2 (IC50 = 8.0 nM). [18F]FIPM was prepared in 5% radiochemical yield (n = 5), by inserting 18F into a pyridine ring, followed by removal of the protecting group. After HPLC separation and formulation, [18F]FIPM was acquired with >97% radiochemical purity and 103-300 GBq μmol-1 of molar activity at the end of radiosynthesis. Biodistribution and small-animal PET studies in mice indicated a low in vivo specific binding of [18F]FIPM. While [18F]FIPM presented limited potential as an in vivo PET tracer for LRRK2, we suggested that it can be used as a lead compound for developing new radiotracers with improved in vivo brain properties.


Characterization of vanadium bromoperoxidase from Macrocystis and Fucus: reactivity of vanadium bromoperoxidase toward acyl and alkyl peroxides and bromination of amines.
Vanadium bromoperoxidase (V-BrPO) has been isolated and purified from the marine brown algae Fucus distichus and Macrocystis pyrifera. V-BrPO catalyzes the oxidation of bromide by hydrogen peroxide, resulting in the bromination of certain organic acceptors or the formation of dioxygen. V-BrPO from F. distichus and M. pyrifera have subunit molecular weights of 65,000 and 74,000, respectively, and specific activities of 1580 units/mg (pH 6.5) and 1730 units/mg (pH 6) for the bromination of monochlorodimedone, respectively. As isolated, the enzymes contain a substoichiometric vanadium/subunit ratio; the vanadium content and specific activity are increased by addition of vanadate. V-BrPO (F. distichus, M. pyrifera, and Ascophyllum nodosum) also catalyzes the oxidation of bromide using peracetic acid. In the absence of an organic acceptor, a mixture of oxidized bromine species (e.g., hypobromous acid, bromine, and tribromide) is formed. Bromamine derivatives are formed from the corresponding amines, while 5-bromocytosine is formed from cytosine. In all cases, the rate of the V-BrPO-catalyzed reaction is much faster than that of the uncatalyzed oxidation of bromide by peracetic acid, at pH 8.5, 1 mM bromide, and 2 mM peracetic acid. In contrast to hydrogen peroxide, V-BrPO does not catalyze formation of dioxygen from peracetic acid in either the presence or absence of bromide. V-BrPO also uses phenylperacetic acid, m-chloroperoxybenzoic acid, and p-nitroperoxybenzoic acid to catalyze the oxidation of bromide; dioxygen is not formed with these peracids. V-BrPO does not catalyze bromide oxidation or dioxygen formation with the alkyl peroxides ethyl hydroperoxide, tert-butyl hydroperoxide, and cuminyl hydroperoxide.


Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta.
Recently we reported that second-trimester amniotic fluid (AF) is an abundant source of fetal mesenchymal stem cells (MSCs). In this study, we analyze the origin of these MSCs and the presence of MSCs in human-term AF. In addition, different parts of the human placenta were studied for the presence of either fetal or maternal MSCs. We compared the phenotype and growth characteristics of MSCs derived from AF and placenta. Cells from human second-trimester (mean gestational age, 19(+2) [standard deviation, +/- 1(+3)] weeks, n = 10) and term third-trimester (mean gestational age, 38(+4) [standard deviation, +/- 1] weeks, n = 10) AF, amnion, decidua basalis, and decidua parietalis were cultured in M199 medium supplemented with 10% fetal calf serum and endothelial cell growth factor. Cultured cells were immunophenotypically characterized, the adipogenic and osteogenic differentiation capacity was tested, and the growth kinetics were analyzed. The origin of fetal and maternal cells was determined by molecular human leukocyte antigen typing. We successfully isolated MSCs from second-trimester AF, amnion, and decidua basalis as well as term amnion, decidua parietalis, and decidua basalis. In contrast, MSCs were cultured from only 2 out of 10 term AF samples. The phenotype of MSCs cultured from different fetal and maternal parts of the placenta was comparable. Maternal MSCs from second-trimester and term decidua basalis and parietalis showed a significantly higher expansion capacity than that of MSCs from adult bone marrow (p < .05). Our results indicate that both fetal and maternal MSCs can be isolated from the human placenta. Amnion is a novel source of fetal MSCs, likely contributing to the presence of MSCs in AF. Decidua basalis and decidua parietalis are sources for maternal MSCs. The expansion potency from both fetal and maternal placenta-derived MSCs was higher compared with adult bone marrow-derived MSCs.


Measuring synthesis rates of nitrogen-containing polymers by using stable isotope tracers.
The major N-containing polymer compounds in the body include protein, RNA, and DNA. The endogenous gastrointestinal secretions as well as the portal-drained visceral and peripheral immune responses are basic physiological functions. Elevated endogenous secretions and immune activities, as affected by developmental stages, diets, and management factors, decrease the availability of dietary nutrients for peripheral muscle synthesis and deposition. Measurements of in vivo protein, RNA, and DNA synthesis rates associated with the viscera, peripheral immune cells, and skeletal muscles should, in principle, be the sensitive biochemical and cellular endpoints for studying factors affecting nonruminant nutrition, metabolism, and growth. The selection of stable isotope tracers for precursors, routes of tracer delivery, and mass spectrometric analyses of tracer enrichments are the major methodological considerations. To measure in vivo protein, RNA, and DNA synthesis rates, oral feeding with heavy water (2H2O), and continuous infusion of [U-13C]glucose and [15N]Gly intravenously for labeling the sugar moieties ribose and deoxyribose and de novo purine base synthesis have been established. Flooding doses of tracer Phe, for example, L-[ring-2H5]Phe, via the i.p. route are reliable and cost-effective for measuring in vivo protein synthesis rates, especially for the viscera in small nonruminants. Therefore, measurements of the major N-containing polymer synthesis rates in the viscera, the peripheral immune cells, and muscles through oral feeding with 2H2O and/or i.p. flooding doses of Phe tracers are the emerging tools for studying nonruminant nutrition, metabolism, and growth under research and field test conditions.


Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections.
Previous studies have shown that there is considerable variation in the methods and media used to determine the susceptibility of Neisseria meningitidis to antimicrobial agents in different countries. In this study, national and regional reference laboratories used a standardized methodology to determine the MICs of antibiotics used in the management of meningococcal infection. Fourteen laboratories participated in the study, determining the susceptibility to penicillin G, rifampin, cefotaxime, ceftriaxone, ciprofloxacin, and ofloxacin of a collection of 17 meningococci, of which 11 strains were previously defined as having intermediate resistance to penicillin (Pen(I)) by sequencing and restriction fragment length polymorphism analysis of the penA gene. The MIC was determined by agar dilution and Etest with Mueller-Hinton agar (MH), MH supplemented with sheep blood (MH+B), and MH supplemented with heated (chocolated) blood. Several laboratories encountered problems obtaining confluent growth with unsupplemented MH. MH+B was considered to give the most congruent and reproducible results among the study laboratories. The modal MIC for MH+B for each antibiotic and method was calculated to define the MIC consensus, allowing assessment of each individual laboratory's data in relation to the others. The agreement in each antibiotic/method/medium combination was defined as the percentage of laboratories with a result within one dilution of the modal result. For the whole study, an agreement of 90.6% was observed between agar dilution and Etest methods. The agreement in each laboratory/antibiotic/method combination ranged from 98.2% to 69.7%, with six laboratories demonstrating agreement higher than 90% and 11 more than 80%. The ability of the laboratories to detect the Pen(I) isolates ranged from 18.2% to 100%. The apparent difficulty in interpreting susceptibility to rifampin, particularly with the Etest method, is very interesting.


Postoperative morbidity and mortality in type-2 diabetics after fast-track primary total hip and knee arthroplasty.
Diabetes is a risk factor for postoperative morbidity, which includes total hip and knee arthroplasty. However, no previous studies have been done in a fast-track setting with optimized perioperative care, including spinal anesthesia, multimodal opioid-sparing analgesia, early mobilization, and discharge to home, which improved postoperative outcome. We performed an observational cohort study using prospective data in primary total hip and total knee arthroplasty with a standardized fast-track approach. Eight hundred ninety type 2 diabetics were successfully propensity matched with 7165 nondiabetics. Subanalyses on antihyperglycemic treatment were done using the Danish National Database of Reimbursed Prescriptions for information on dispensed prescriptions 6 months preoperatively. Length of hospital stay (LOS), 90-day readmissions, and mortality were found through the Danish National Health Registry and medical charts. Multiple logistic regression analyses on LOS > 4 days and readmissions were used to further adjust for demographics, comorbidity, and department of surgery. To further evaluate the clinical relevance of type 2 diabetes, we estimated the number of surgical type 2 diabetics needed for 1 more occurrence of LOS > 4 days or readmissions (adjusted number needed to harm [NNH]). Although more type 2 diabetics (11.3%) than nondiabetics (8.1%) had LOS > 4 days (unadjusted P = 0.001), there was no association between type 2 diabetes and LOS > 4 days when adjusting for covariates (odds ratio: 1.19 [0.93-1.54]; P = 0.172). Correspondingly, the NNH was 78 but ranged between 31 and infinity. Type 2 diabetes was not associated with 30- (1.02 [0.75-1.39]; P = 0.897) or 90-day readmissions (1.22 [0.87-1.71]; P = 0.254), and with an NNH of 957 (59-∞) and 115 (35-∞), respectively. Insulin-treated type 2 diabetes was associated with increased risk of specific "diabetes-related" morbidity (1.95 [1.13-3.35]; P = 0.016). Type 2 diabetes per se has limited influence on postoperative morbidity in fast-track total hip and knee arthroplasty.


Bilateral dimorphism of Loewenthal's gland in young male albino rats: an ultrastructural investigation.
This study represents a further contribution to our knowledge about the structure of Loewenthal's gland. There are several divergences in the available literature on the topic, concerning both the histological and ultrastructural findings. However, in these studies, the authors did not take into account the potential influence of a putative side-dependent dimorphism previously reported by us. We therefore carried out histological and electronmicroscopic observations specifically aimed at evaluating the importance of the gland shape for its structure. In particular, in male albino rats aged 70-120 days, we compared the structure of the left and right glands. Depending on the side undergoing morphological investigation, we observed differences in the acini, cells, nuclei, endoplasmic reticulum, Golgi apparatus and granular content. Apart from slight individual differences, we found that structural variations were most frequently observed in glands displaying a more evident macroscopic side-specific dimorphism. Our findings demonstrate that several conflicting data in the literature dealing with the structure of Loewenthal's glands might be explained by the morphofunctional side-dependent dimorphism of the organ.


Alanine in HI: a silent mutation cries out!
It is a widely held paradigm in molecular biology that a change in the third base of a codon is silent in terms of expression. In this investigation, results are presented that challenge that paradigm, at least in terms of one polymorphism in KCNJ11, which is one of five genes that have been implicated in the disorder Hyperinsulinism of Infancy. In two cohorts of Australian patients, an uneven distribution of KCNJ11 SNP's was observed. A silent polymorphism at codon 190 was over-represented in the patients who responded well to medical treatment and under-represented in those that required radical surgical intervention. In an attempt to investigate this polymorphism, it was expressed in vitro and western blot analysis showed that there were virtually no bands from the homozygous variant samples, while strong bands were seen in normal controls. The human genome is highly redundant in terms of tRNA species for each amino acids but enigmatically under-represents a number of specific codons. The polymorphism in question occurs within one such codon. We propose that the presence of a base change at the third position of codon that is not represented by a corresponding anti-codon within the human nuclear tRNA leads to a decreased rate of expression of the protein.


Dynamic macroecology and the future for biodiversity.
Reliable projections of climate-change impacts on biodiversity are vital in formulating conservation and management strategies that best retain biodiversity into the future. While recent modelling has focussed largely on individual species, macroecology has the potential to add significant value to these efforts, by incorporating important community-level constraints and processes. Here we show how a new dynamic macroecological approach can project climate-change impacts collectively across all species in a diverse taxonomic group, overcoming shortfalls in our knowledge of biodiversity, while incorporating the key processes of dispersal and community assembly. Our approach applies a recently published technique (DynamicFOAM) to predict the present composition of every community, which form the initial conditions for a new metacommunity model (M-SET) that projects changes in composition over time, under specified climate and habitat scenarios. Applying this approach at fine resolution to plant biodiversity in Tasmania (2,051 species; 1,157,587 communities), we project high average turnover in community composition from 2010 to 2100 (mean Sorensen's dissimilarity = 0.71 (±7.0 × 10-5 )), with major reductions in species richness (32.9 (±0.02) species lost per community) and no plant species benefitting from climate change in the long term. We also demonstrate how our modelling approach can identify habitat likely to be of high value for retaining rare and poorly reserved species under climate change. Our analyses highlight the potential value of this dynamic macroecological approach, that incorporates key ecological processes in projecting climate change impacts for all species simultaneously and uses simple macroecological inputs that can be derived even for highly diverse and poorly studied taxa.


Nurse Leader Attitudes and Beliefs Regarding Medical Errors.
This study aimed to explore nurse leader attitudes and beliefs about medical errors. The perfectibility model suggests errors are avoidable if nurses are trained and follow safety guidelines. This impacts how nurse leaders approach medical errors. Nurse leaders (NLs) may be the first person to whom a nurse reports an error. Leaders support nurses through the investigation process and subsequent recovery. A cross-sectional quantitative study was conducted to determine NL attitudes toward medical errors using the Medical Error Attitude Scale (MEAS). MEAS scores were high in all categories. Medical error perception was significant for NLs with institutional support programs and when compared with job titles. Medical error approach and perception were significant for NLs with direct reports who had committed a medical error. This study provides insight into NLs' views on medical errors, awareness of NLs who have had nurses involved in medical errors, and formal caregiver support programs.


The epidemiology of schistosomiasis in Egypt: Fayoum Governorate.
Health questionnaires and parasitologic examinations of urine and stool were performed upon a stratified random sample of 7,710 individuals from 1,109 households in 21 rural communities in Fayoum Governorate, Egypt in 1992 to investigate the prevalence of, risk factors for, and changing pattern of, infection with Schistosoma sp. in the governorate. A subset, every fifth household, or 1,038 subjects, had physical and ultrasound examinations to investigate prevalence of, and risk factors for, morbidity. The prevalence of S. haematobium ranged from 0% to 27.1% and averaged 13.7%. The geometric mean egg count (GMEC) was 10.0 eggs/10 ml of urine. Age-stratified prevalence and intensity of infection were 18-25% and 10-15 eggs/10 ml of urine in those 5-25 years of age. Schistosoma mansoni were detected in inhabitants of 13 communities, but 78.5% of the infections were focally present in a group of 4 satellite hamlets around a single village. The overall prevalence of S. mansoni in the governorate was 4.3% and the GMEC was 44.0 ova/g of stool. Risk factors for infection with either species were male gender, an age <20 years, living in smaller communities, and exposures to canal water by males. Histories of burning micturation, blood in the urine, or prior schistosomiasis and reagent strip-detected hematuria and proteinuria were risks for S. haematobium, but not for S. mansoni. Both urinary tract and higher grades of hepatic morbidity were rare. Obstructive uropathy was present in 6.3% of the subjects and was more common in males and older people. Ultrasonography-detected bladder lesions were present in 5.2% and correlated with S. haematobium only in younger subjects and in those with hematuria and proteinuria. The prevalences of hepatomegaly, splenomegaly, and periportal fibrosis (PPF) were associated with each other and increased with age and in males. Ultrasonography-detected hepatomegaly and splenomegaly were weakly associated with S. mansoni infections only in children. The prevalence of PPF was greater in the 4 communities with >25% S. mansoni infection rates in comparison with the 17 other villages and ezbas. Transmission of S. mansoni is focally well established in Fayoum, which also has the highest prevalence of S. haematobium in the governorates surveyed by the Epidemiology 1, 2, 3 Project. However, both urinary tract and hepatic morbidity are relatively rare in the governorate. This probably results from the long-standing schistosomiasis control program in Fayoum, which suppressed intensity more than prevalence of infection, leading to less community morbidity.


Comparative Mapping Combined With Map-Based Cloning of the Brassica juncea Genome Reveals a Candidate Gene for Multilocular Rapeseed.
Multilocular traits exist in a variety of plants and exert important effects on plant yield. Previous genetic studies have shown that multilocular trait of the Brassica juncea cultivar Duoshi is controlled by two recessive genes, Bjln1 and Bjln2. In previous studies, the Bjln1 gene is located on chromosome A07, and the Bjln1 candidate gene is BjuA07.CLV1. In this study, a BC4 mapping population for the Bjln2 gene was generated. This population was used to construct genetic linkage maps of the Bjln2 gene using amplified fragment length polymorphism (AFLP), intron length polymorphism (IP) and simple sequence repeat (SSR) methodology. The results showed that the Bjln2 gene was restricted to a 0.63 cM interval. BLAST alignment with B. juncea revealed the Bjln2 gene was located within a 11.81-16.65 Mb region on chromosome B07. Moreover, the candidate gene BjuB07.CLV1 (equivalent to Bjln2) was cloned by comparing mapping and map-based cloning, and BjuB07.CLV1 gene was shown to have the ability to restore the bilocular traits in a genetic complementation experiment. The sequencing revealed that a 4961 bp insertion interrupted the coding sequence of the BjuB07.CLV1 gene, resulting in an increase in locule number. Expression analysis revealed that BjuB07.CLV1 was expressed in all tissues and the expression level in bilocular plants was significantly higher than that in multilocular plants. In addition, markers closely linked to the Bjln2 gene were developed and used for molecular marker-assisted breeding of multilocular traits.


Scalp Cooling: A Patient's Experience.
CASE STUDY Ms. X is a 23-year-old female who presented to clinic with stage 2A endometrial cancer of the ovary. At her first visit, Ms. X was prescribed paclitaxel and carboplatin on day 1 for 6 cycles. During the visit, the nurse noted Ms. X could not keep her hands out of her hair; she continually played with it. The nurse, judging by Ms. X's body language, suspected she valued her hair. Ms. X revealed she had been doing some research and wanted to use a cold cap to try and prevent alopecia during her treatment. On the first day of chemotherapy, Ms. X came to the clinic with her mother. They brought a manual cap for scalp cooling and a cooler of dry ice. Her mother was to serve as a "capper" and change the cap at 20- to 30-minute intervals during treatment to keep her scalp cool. Ms. X was made comfortable in an infusion bed, and the cap was applied 30 minutes prior to the start of therapy. Ms. X's mother changed the dry ice caps every 20 minutes throughout the infusion. Ms. X then left it on for 90 minutes following her chemotherapy. After 6 cycles of chemotherapy, Ms. X still had all her hair. She appeared to have retained 100% of her hair, although she estimates that she lost about 5% of her hair. During therapy, she followed the instructions outlined in Table 1. Ms. X reported that she rented the cap for $500 per month and paid $45 per week for the dry ice. Her mother also had to miss work to be the "capper," and this added to the out-of-pocket costs of scalp cooling.


Tamara Dembo's European years: working with Lewin and Buytendijk.
In this paper early work of the American rehabilitation psychologist Tamara Dembo (1902-1993) is brought to light. She was highly influenced by the concepts of Kurt Lewin's topological psychology, and she used the framework of topological psychology to analyze her investigations on animal behavior carried out with the Dutch zoopsychologist Frederik J. J. Buytendijk. These investigations have so far been ignored and are being described for the first time making use of archival materials.


Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States.
Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.


Immunoprevention of Friend leukaemia virus-induced erythroleukaemia by vaccination with aggregated gp70.
Vaccines prepared from Friend leukaemia virus envelope and core polypeptides were compared for their efficiency in preventing erythroleukaemia in mice. High doses (100 micrograms) of gp85, the micellar complex of the envelope polypeptides gp70 and p15E, completely protected STU mice. The same dose of purified gp70 still protected about 80% of the animals, while p15E did not affect the cumulative mortality. The internal viral polypeptide p30 was ineffective. Serological examination indicated that immunity against death from leukaemia was mediated by specific antibodies. These leukaemia-preventing antibodies were predominantly induced by immunization with the gp70 env gene product, since p15E showed only minor protection. Glycoprotein gp70, however, was more effective when given as the gp85 micellar complex. An even more potent vaccine was obtained when gp70 was coupled to keyhole limpet haemocyanin (KLH) by glutaraldehyde. Ten micrograms gp70 coupled to KLH was enough to save more than 90% of Friend leukaemia virus-infected mice from erythroleukaemia. KLH may also be a suitable experimental carrier for subunits of gp70 or synthetic oligopeptides for viral vaccines.


Improved growth of Lactobacillus bulgaricus and Streptococcus thermophilus as well as Increased antioxidant activity by biotransforming litchi pericarp polysaccharide with Aspergillus awamori.
This study was conducted to increase the bioactivity of litchi pericarp polysaccharides (LPPs) biotransformed by Aspergillus awamori. Compared to the non-A. awamori-fermented LPP, the growth effects of A. awamori-fermented LPP on Lactobacillus bulgaricus and Streptococcus thermophilus were four and two times higher after 3 days of fermentation, respectively. Increased 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity and DNA protection activity of litchi pericarp polysaccharides were also achieved after A. awamori fermentation. Moreover, the relative content of glucose and arabinose in LPP after fermentation decreased from 58.82% to 22.60% and from 18.82% to 10.09%, respectively, with a concomitant increase in the relative contents of galactose, rhamnose, xylose, and mannose. Furthermore, lower molecular weight polysaccharides were obtained after A. awamori fermentation. It can be concluded that A. awamori was effective in biotransforming LPP into a bioactive mixture with lower molecular weight polysaccharides and higher antioxidant activity and relative galactose content.


Platelet Reduction after Aortic Bioprosthesis Implantation: Results from the PORTRAIT Study.
Background: Platelet count reduction (PR) is a common but unclear phenomenon that occurs after aortic bioprosthesis valve implantation (bio-AVR). This study aimed to investigate the occurrence and clinical impact of PR in patients receiving stented, rapid deployment (RDV), or stentless bioprostheses. Methods: 1233 adult bio-AVR patients were enrolled. Platelet count variation, early post-operative adverse events, and in-hospital mortality were analysed. Results: 944 patients received a stented valve, an RDV was implanted in 218 patients, and 71 patients had a stentless bioprosthesis. In all groups, the platelet count at discharge was lower than the baseline values (p < 0.001). The percentage of PR was 27% in the stented group, 56% in the RDV group, and 55% in the stentless group. A higher platelet reduction, reaching the minimum platelet value, was observed in the RDV (mean: -30.84, standard error (SE): 5.91, p < 0.001) and stentless (mean: 22.54, SE: 9.10, p = 0.03) groups compared to the stented group. A greater PR occurred as the size of the bioprosthesis increased in RDV (p = 0.01), while platelet count variation was not directly proportional to the stented bioprosthesis size (p < 0.001). PR was not affected by cardiopulmonary bypass (mean: -0.00, SE: 0.001, p = 0.635) or cross-clamp (mean: -0.00, SE: 0.002, p = 0.051) times in any of the groups. RDV subjects experienced more in-hospital adverse events. PR was found to be associated with ischemic strokes in the overall population. Conclusions: Bio-AVR is associated with significant but transient PR. RDV patients more likely experience significant PR and related adverse clinical events. PR is associated with ischemic strokes, regardless of the bioprosthesis type.


County lung cancer mortality: a decision tree model for control and prevention.
It is widely accepted that smoking prevalence and poverty predict the occurrence of lung cancer mortality. The question asked in the study was: What are the important factors for counties that are useful to public health professionals? We sought to provide an answer, using a recursive partitioning approach applied to county-level indicators. Classification and regression tree analysis is relatively unexplored for its utility in public health. Using available ecologic data, county lung cancer mortality was modeled by several predictor variables from a larger set of candidates. We constructed a tree on the basis of statistical software, R. Seven groupings were defined. Not surprisingly, smoking prevalence was a major determiner of tree nodes, as were prior coronary heart disease mortality, poverty, and National Air Toxics Assessment excess cancer deaths estimates. Lung cancer mortality groupings ranged from 47 per 100000 in the best 2 groupings (leaves) to 85 per 100000 in the worst grouping of 52 local jurisdictions. Ecologic data portrayed in a classification and regression tree have utility for spurring etiologic investigation, tracking county outcomes, developing policy at any governmental level, and guiding program design and management. Community by community, improvements are not yet at Healthy People 2010 targets. Individual communities may benefit through efforts to focus attention on aspects such as smoking levels, poverty, air quality, or region, highlighted by this analysis.


Bcl-2 expression in synovial fibroblasts is essential for maintaining mitochondrial homeostasis and cell viability.
The regulation of proliferation and cell death is vital for homeostasis, but the mechanism that coordinately balances these events in rheumatoid arthritis (RA) remains largely unknown. In RA, the synovial lining thickens in part through increased proliferation and/or decreased synovial fibroblast cell death. Here we demonstrate that the anti-apoptotic protein, Bcl-2, is highly expressed in RA compared with osteoarthritis synovial tissues, particularly in the CD68-negative, fibroblast-like synoviocyte population. To determine the importance of endogenous Bcl-2, an adenoviral vector expressing a hammerhead ribozyme to Bcl-2 (Ad-Rbz-Bcl-2) mRNA was employed. Ad-Rbz-Bcl-2 infection resulted in reduced Bcl-2 expression and cell viability in synovial fibroblasts isolated from RA and osteoarthritis synovial tissues. In addition, Ad-Rbz-Bcl-2-induced mitochondrial permeability transition, cytochrome c release, activation of caspases 9 and 3, and DNA fragmentation. The general caspase inhibitor zVAD.fmk blocked caspase activation, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation, but not loss of transmembrane potential or viability, indicating that cell death was independent of caspase activation. Ectopically expressed Bcl-xL inhibited Ad-Rbz-Bcl-2-induced mitochondrial permeability transition and apoptosis in Ad-Rbz-Bcl-2-transduced cells. Thus, forced down-regulation of Bcl-2 does not induce a compensatory mechanism to prevent loss of mitochondrial integrity and cell death in human fibroblasts.


Differences in risk perception, knowledge and protective behaviour regarding COVID-19 by education level among women and men in Germany. Results from the COVID-19 Snapshot Monitoring (COSMO) study.
The main strategy for combatting SARS-CoV-2 infections in 2020 consisted of behavioural regulations including contact reduction, maintaining distance, hand hygiene, and mask wearing. COVID-19-related risk perception and knowledge may influence protective behaviour, and education could be an important determinant. The current study investigated differences by education level in risk perception, knowledge and protective behaviour regarding COVID-19 in Germany, exploring the development of the pandemic over time. The COVID-19 Snapshot Monitoring study is a repeated cross-sectional online survey conducted during the pandemic in Germany from 3 March 2020 (waves 1-28: 27,957 participants aged 18-74). Differences in risk perception, knowledge and protective behaviour according to education level (high versus low) were analysed using linear and logistic regression. Time trends were accounted for by interaction terms for education level and calendar week. Regarding protective behaviour, interaction terms were tested for all risk perception and knowledge variables with education level. The strongest associations with education level were evident for perceived and factual knowledge regarding COVID-19. Moreover, associations were found between low education level and higher perceived severity, and between low education level and lower perceived probability. Highly educated men were more worried about COVID-19 than those with low levels of education. No educational differences were observed for perceived susceptibility or fear. Higher compliance with hand washing was found in highly educated women, and higher compliance with maintaining distance was found in highly educated men. Regarding maintaining distance, the impact of perceived severity differed between education groups. In men, significant moderation effects of education level on the association between factual knowledge and all three protective behaviours were found. During the pandemic, risk perception and protective behaviour varied greatly over time. Overall, differences by education level were relatively small. For risk communication, reaching all population groups irrespective of education level is critical.


Intraocular copper foreign bodies. Use of dexamethasone to suppress inflammation.
In an attempt to prevent the intense inflammatory response to intravitreal copper foreign bodies in the rabbit eye, varying dosages of dexamethasone sodium phosphate were administered daily via the subconjunctival route. The steroid appeared to behave systemically and had similar effects in both the injected and the noninjected eyes. Its effect was similar also regardless of the concentration of copper within the foreign body. Nine days of dexamethasone therapy prevented a substantial number of copper foreign bodies from becoming totally encapsulated during that time. Furthermore, a delay in the onset of the inflammatory response to the foreign body was noted. In a few instances, inflammation was completely suppressed during the entire course of therapy.


Meaning in life: does it play a role in smoking?
The aim of this study was to investigate whether a relationship exists between a decreased level of meaning in life and smoking. In 2006, 341 Hungarian respondents (48.1% males, 51.9% females) completed a questionnaire that included the Purpose in Life test, a shortened version of the Aspiration Index and the Beck Depression Inventory, as well as questions about sociodemographic characteristics, past year alcohol and illicit drug consumption, and smoking behavior. The mean age of the participants was 33.0 years (SD = 14.6), while the average years of education of the respondents was 14.5 (SD = 2.7). According to the results of the regression analysis, meaning in life proved to be significant in differentiating between nonsmokers and daily smokers. With regard to the nonsmoker vs. occasional smoker and the daily vs. occasional smoker relationship, level of life meaning was not a significant predictor. The gender-meaning in life interaction was insignificant in all three relations. Limitations of this explorative investigation are noted.


Contralateral reinnervation in patients with facial nerve palsy.
To demonstrate a phenomenon of contralateral reinnervation in facial nerve palsy patients. Retrospective case review of 9 patients whose facial muscles were electrophysiologically proven to be reinnervated contralaterally. The duration from symptom onset spanned from 3 to 114 months. All subjects had moderate-to-severe facial palsy initially. Contralateral reinnervation was observed in both traumatic and idiopathic causes, also in both complete and incomplete palsies. Cross-innervation is more frequently reported in muscles near the midline; however, this is the first report demonstrating evidence of cross-innervation in muscles far from the midline--the frontalis, the orbicularis oculi, and the zygomaticus. Although contralateral reinnervation after facial nerve palsy is a common observation, it has not gained appropriate attention. Without recognition of this phenomenon, misinterpretation of the electromyography may mislead the proper timing of nerve repair or reanimation procedure. Therefore, routine examination of motor action potential by contralateral stimulation during electromyography, especially in patients with moderate-to-severe palsy, would provide accurate assessment of the injured nerves and would help in appropriate decision making for further treatment.


Predominant nuclear localization of mammalian target of rapamycin in normal and malignant cells in culture.
Mammalian target of rapamycin (mTOR) controls initiation of translation through regulation of ribosomal p70S6 kinase (S6K1) and eukaryotic translation initiation factor-4E (eIF4E) binding protein (4E-BP). mTOR is considered to be located predominantly in cytosolic or membrane fractions and may shuttle between the cytoplasm and nucleus. In most previous studies a single cell line, E1A-immortalized human embryonic kidney cells (HEK293), has been used. Here we show that in human malignant cell lines, human fibroblasts, and murine myoblasts mTOR is predominantly nuclear. In contrast, mTOR is largely excluded from the nucleus in HEK293 cells. Hybrids between HEK293 and Rh30 rhabdomyosarcoma cells generated cells co-expressing markers unique to HEK293 (E1A) and Rh30 (MyoD). mTOR distribution was mainly nuclear with detectable levels in the cytoplasm. mTOR isolated from Rh30 nuclei phosphorylated recombinant GST-4E-BP1 (Thr-46) in vitro and thus has kinase activity. We next investigated the cellular distribution of mTOR substrates 4E-BP, S6K1, and eIF4E. 4E-BP was exclusively detected in cytoplasmic fractions in all cell lines. S6K1 was localized in the cytoplasm in colon carcinoma, HEK293 cells, and IMR90 fibroblasts. S6K1 was readily detected in all cellular fractions derived from rhabdomyosarcoma cells. eIF4E was detected in all fractions derived from rhabdomyosarcoma cells but was not detectable in nuclear fractions from colon carcinoma HEK293 or IMR90 cells.


[Screening of tomato cultivars in cadmium-polluted areas and study on their antioxidant capacity].
To screen the available tomato pollution-safe cultivar varieties and reduce the potential food safety risks in Cd-polluted areas, the differences of Cd accumulation in different tomato (Solanum lycopersicum) varieties in southern China were studied by soil culture and hydroponic experiments. Firstly, the high and low accumulation varieties were selected from 25 tomato varieties under 2.94 mg/kg Cd stress by soil culture test, and then the responses of high and low accumulation tomato varieties to Cd stress were determined by hydroponic experiments. The results of soil culture test show that under 2.94 mg/kg Cd stress, there were significant differences in plant height, total biomass and yield among 25 tomato cultivars, and the Cd contents of fruits of all 25 tomato cultivars exceeded the highest limit value (0.05 mg/kg) of CAC (Codex alimentarius commission). Through cluster analysis, 7, 4 and 14 varieties accumulating relatively high, medium, and low concentrations of Cd in the fruits were screened, among which the highest, the lowest, and the average Cd contents in the fruits were 3.06 mg/kg DW, 1.47 mg/kg DW, and 2.21 mg/kg DW, respectively. The results of hydroponic experiment show that under the same concentration of Cd stress, Qiantangxuri F1, a high Cd accumulating variety, absorbed Cd faster, accumulated more Cd, used shorter oxidative stress response time and had stronger tolerance to Cd than Zhefen 3053, a low Cd accumulating variety. The typical high and low Cd accumulating varieties can provide a reference for agricultural production in heavy metal polluted areas and the development of molecular-assisted breeding methods of PSC. At present, cultivating low Cd accumulating PSC varieties and dynamic monitoring of Cd contents in tomato fruits are feasible methods in medium and light Cd-polluted areas.


Functional foods to promote weight loss and satiety.
Diets that induce negative energy balance continue to be the cornerstone of obesity management. However, long-term volitional reduction in energy intake is challenging. Functional foods that enhance satiety may have an important practical application in increasing compliance to weight loss diets and thereby promoting sustained weight loss. Here, we present recent advances in identifying common foods that increase satiety. Protein induces satiety in the short term. There is no clear evidence to indicate superiority of a specific protein source over the other. Low-fat dairy products, eggs, and legumes enhance satiety. Although energy dense, nuts have some satiety-inducing effect, when included in the diet by isocaloric replacement of usual foods. Satiety induced by dietary fiber sources, such as oats and rye, are well documented, but these sensations do not always translate into reductions in energy intake or body weight. Several foods and food groups show promising potential in inducing satiety. However, it is important to recognize that the short-term effect of a food may not always translate into greater weight loss in the long term. Long-term clinical studies are needed to demonstrate the utility of a food in promoting weight loss.


The acute effects of stretching on presynaptic inhibition and peak power.
Stretching before and after physical activity is a controversial aspect of exercise preparation and recovery. Minimal research has been conducted regarding the neuromuscular effects of stretching including changes in the H-reflex, motor neuron excitability and presynaptic inhibition of muscle. The aim of this study was to examine the effects of static and dynamic stretching on the neuromuscular aspects and power output of the M. Soleus. Twenty-one healthy college students (13 F, 8 M; 19.81±0.75 y; 171±8.40 cm; 70.71±11.32 kg) participated. On separate days, participants completed either static and dynamic stretching protocols. A double electrical stimulus, assessed via electromyography, was used to elicit the H-reflex and M-wave before and after each stretching protocol. Participants performed pre- and post-stretching countermovement jumps to produce power measurements. After a single bout of dynamic stretching, presynaptic inhibition significantly decreased (P<0.001), whereas the static stretching produced no change (P=0.296). There was a slightly significant increase in power post-static stretching (369.03±808.3 W, P=0.049). While dynamic stretching is beneficial in decreasing presynaptic inhibition, it did not lead to the hypothesized increase in power output. This study is the first to compare neurological mechanisms and power output, giving a comprehensive view of how stretching affects muscle.


Bacteria dispersal by hitchhiking on zooplankton.
Microorganisms and zooplankton are both important components of aquatic food webs. Although both inhabit the same environment, they are often regarded as separate functional units that are indirectly connected through nutrient cycling and trophic cascade. However, research on pathogenic and nonpathogenic bacteria has shown that direct association with zooplankton has significant influences on the bacteria's physiology and ecology. We used stratified migration columns to study vertical dispersal of hitchhiking bacteria through migrating zooplankton across a density gradient that was otherwise impenetrable for bacteria in both upward and downward directions (conveyor-belt hypothesis). The strength of our experiments is to permit quantitative estimation of transport and release of associated bacteria: vertical migration of Daphnia magna yielded an average dispersal rate of 1.3 x 10(5) x cells x Daphnia(-1) x migration cycle(-1) for the lake bacterium Brevundimonas sp. Bidirectional vertical dispersal by migrating D. magna was also shown for two other bacterial species, albeit at lower rates. The prediction that diurnally migrating zooplankton acquire different attached bacterial communities from hypolimnion and epilimnion between day and night was subsequently confirmed in our field study. In mesotrophic Lake Nehmitz, D. hyalina showed pronounced diel vertical migration along with significant diurnal changes in attached bacterial community composition. These results confirm that hitchhiking on migrating animals can be an important mechanism for rapidly relocating microorganisms, including pathogens, allowing them to access otherwise inaccessible resources.


The epidemiology and treatment of radial head subluxation.
The incidence and treatment of radial head subluxation were evaluated in emergency room and private office settings. Factors associated with recurrence and with successful reduction were identified, and ways to prevent this common injury were sought. Of 54 reductions during which a click was either felt or heard, all but one reduction resulted in reuse of the arm within 30 minutes. Of 13 reductions in which a click was neither felt nor heard, only four reductions resulted in reuse of the arm within 30 minutes. A supination maneuver resulted in reuse of the arm within 30 minutes in all 27 patients seen two or more hours after injury vs 85% (34/40) of patients seen less than two hours after injury. Remanipulation 12 to 106 hours later resulted in reuse of the arm in all those children who had failed to respond to previous treatment.


Pulmonary embolism associated with canine total hip replacement.
To determine by pulmonary perfusion scans and ultrasonography if embolemia occurs during total hip replacement (THR) surgery in dogs. Prospective clinical study. Forty client-owned dogs that had THR surgery. Thoracic radiographs were taken immediately after THR and immediately after completion of (99m)Tc-MAA lung scans. Scintigraphy was performed in 28 dogs, 48 hours after THR. Intraoperative ultrasonography (intercostal or transesophageal) was performed in another 12 dogs that had THR. The right atrium and ventricle and pulmonary outflow tract were observed during and for 5 to 8 minutes after femoral component insertion into medullary canals prepared by reaming, and lavage and aspiration of debris before filling with polymethylmethacrylate in dough stage. A modified Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) classification system was used to evaluate lung scans. No pulmonary radiographic abnormalities were identified. Segmental and subsegmental perfusion defects occurred in 23 (82%) dogs and were classified as severe in 9 (32%) dogs, moderate in 11, and mild in 3. There was no particular lobe predilection. Patchy mulberry-appearing defects, indicative of fat embolism, were most common. Embolemia was observed by ultrasound in 10 dogs. Variable-sized particles occurred in 8 dogs, particles and bubbles in 2 dogs, and no emboli were observed in 2 dogs. Embolemia was observed within 10 seconds after femoral stem insertion and lasted < 1 minute. Pneumoemboli remained in the right atrium for > 8 minutes before dislodgement. Embolemia of either air, particles, or both occurs in most dogs during THR surgery. Most dogs seemingly spontaneously recover from pulmonary embolism that occurs during THR. The risk of clinical complications from this pulmonary embolism should be taken seriously, even though the exact morbidity and mortality rates are unknown.


A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients.
For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 μg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 μg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.).


[Changes in the reproduction of tick-borne encephalitis virus in cell cultures].
The currently used tick-borne encephalitis virus vaccines are based on the inactivation of tick-borne encephalitis virus (TBEV) of Far Eastern or West European genetic types from the primary cultures of chick embryo fibroblasts. Since the WHO recommends that vaccines should be designed using continuous cell cultures rather than chick embryos as a substrate, this investigation has compared the infection of continuous monolayer SPEV, Vero E6, and vaccine line Vero (B) cell cultures with TBEV strains of the Siberian and Far Eastern genetic types dominating in the endemic regions of Russia. After cell infection with Far Eastern (Sofyin and 205 strains) or Siberian (Aina, 2530, 2689, and 2703 strains) TBEV genetic types, the viable TBEV titers reached 2.8 Ig CPD50 for Vero (B) cells, 5.5 Ig CPD50 for Vero E6 cells, and up to 9 Ig CPD50 for SPEV cells. The quantitative scores of TBEV E antigen in enzyme immunoassay (EIA) and genome equivalents by reverse-transcription polymerase chain reaction (PCR), followed by real-time PCR, permitted one to estimate as high as 108 virions in 1 ml of culture fluid, which corresponded to those of the microscopic observations of CPD for SPEV cells and substantially exceeded the values for Vero E6 cells, and for Vero (B) cells in particular. The data of TBEV strain titration, EIA, and realtime reverse-transcription PCR suggest that the Russian vaccine Vero (B) cell line defined as meeting the WHO requirements, as well as Vero E6 cells may be used to design tick-borne encephalitis vaccine.


Placental and fetal cardiac laminin are targets for cross-reacting autoantibodies from mothers of children with congenital heart block.
The association of congenital heart block (CHB) with maternal autoantibodies to the Ro and La ribonucleoprotein antigens may be due to cross-reactions between maternal anti-La antibodies and fetal cardiac specific antigens. One of the major components of cardiac myocytes, laminin, is accessible for binding by maternal autoantibodies and we have previously reported cross-reactivity of mouse laminin with anti-La antibodies affinity purified from the sera of patients with primary Sjögren's syndrome. Affinity purified anti-La antibodies from ten women who had at some time given birth to a child with CHB were examined for cross-reactivity with human placental laminin, which shares structural similarities with cardiac laminin. All ten anti-La antibodies bound to the surface of cryosections of normal full term placental trophoblasts. Binding could be inhibited by pre-incubation of antibodies with either La or placental laminin. Eight anti-La antibodies also reacted with placental laminin by ELISA and La inhibited up to 82% of binding to laminin while laminin inhibited up to 85% of binding to La in a dose dependent manner. Eight anti-La antibodies also bound to the surface of fetal cardiac myocytes at 10.3 weeks of gestation and five showed lower levels of reactivity with the surface of fetal cardiac myocytes at 16.5 weeks of gestation. None showed any surface staining of normal adult heart. These data confirm the cross-reactivity of anti-La antibodies with laminin and may support a placental role in preventing the majority of potentially pathogenic antibodies from reaching the fetal circulation.


Measurement of quality of life I. A methodological framework.
Despite the widespread acceptance of quality of life (QOL) as the ideal guideline in healthcare and clinical research, serious conceptual and methodological problems continue to plague this area. In an attempt to remedy this situation, we propose seven criteria that a quality-of-life concept must meet to provide a sound basis for investigation by questionnaire. The seven criteria or desiderata are: (1) an explicit definition of quality of life; (2) a coherent philosophy of human life from which the definition is derived; (3) a theory that operationalizes the philosophy by specifying unambiguous, nonoverlapping, and jointly exhaustive questionnaire items; (4) response alternatives that permit a fraction-scale interpretation; (5) technical checks of reproducibility; (6) meaningfulness to investigators, respondents, and users; and (7) an overall aesthetic appeal of the questionnaire. These criteria have guided the design of a validated 5-item generic, global quality-of-life questionnaire (QOL5), and a validated 317-item generic, global quality-of-life questionnaire (SEQOL), administered to a well-documented birth cohort of 7,400 Danes born in 1959-1961, as well as to a reference sample of 2,500 Danes. Presented in outline, the underlying integrative quality-of-life (IQOL) theory is a meta-theory. To illustrate the seven criteria at work, we show the extent to which they are satisfied by one of the eight component theories. Next, two sample results of our investigation are presented: satisfaction with one's sex life has the expected covariation with one's quality of life, and so does mother's smoking during pregnancy, albeit to a much smaller extent. It is concluded that the methodological framework presented has proved helpful in designing a questionnaire that is capable of yielding acceptably valid and reliable measurements of global and generic quality of life.


Salmonella adapts to plants and their environment during colonization of tomatoes.
Humans and animals are considered typical hosts for Salmonella, however, also plants can be colonized. Tomatoes were linked to salmonellosis outbreaks already on several occasions. The aim of this study was, therefore, to establish a comprehensive view on the interaction between Salmonella enterica and tomatoes, and to test the hypothesis that colonization of plants is an interactive process. We assessed the persistence of Salmonella in agricultural soil, the colonization pattern in and on tomatoes, as well as the reciprocal responses of tomatoes to different Salmonella strains and Salmonella to root exudates and tomato-related media. This study revealed that Salmonella can persist in the soil and inside the tomato plant. Additionally, we show that Salmonella strains have particular colonization pattern, although the persistence inside the plant differs between the tested strains. Furthermore, the transcriptome response of tomato showed an up-regulation of several defense-related genes. Salmonella transcriptome analysis in response to the plant-based media showed differentially regulated genes related to amino acid and fatty acid synthesis and stress response, while the response to root exudates revealed regulation of the glyoxylate cycle. Our results indicate that both organisms actively engage in the interaction and that Salmonella adapts to the plant environment.


Patterns of medication use in the RRI-CKD study: focus on medications with cardiovascular effects.
Patients with chronic kidney disease (CKD) stages 2-5 are known to suffer numerous complications and co-morbidities associated with kidney disease. The medication prescription patterns in this population are not well understood. We report on prescription data collected as part of a multicentre longitudinal study in patients with CKD, with a focus on medications with cardiovascular or cardioprotective effects. Patients were recruited from four academic nephrology centres in the USA, with patient recruitment from June 2000 to March 2002. Medication data were captured at the time of first enrollment into the study. Individual medications were classified into medication groups, and those with predominant cardioprotective effects or for prevention of progression of kidney disease (e.g. medications for treatment of anaemia, lipid-lowering agents, antihypertensives, statins, etc.) were recorded for analysis. Descriptive statistics were used for medication prescription according to baseline demographics and co-morbidities. Predictors of epoetin and iron use were determined by logistic regression adjusting for age, race, sex, diabetes, glomerular filtration rate (GFR), haemoglobin and serum albumin. Medication data were available for 619 patients with stages 2-5 CKD. Patients were 60.6+/-16.0 years of age, and were prescribed 8+/-4 (range 1-28) medications. Overall, the proportion of patients prescribed different classes of medications included epoetin (20%), intravenous iron (13%), HMG-CoA reductase inhibitors (16%), angiotensin-converting enzyme (ACE) inhibitors (44%), angiotensin receptor blockers (13%), beta-blockers (46%), calcium channel blockers (52%) and aspirin (37%). There was a low use of epoetin (45%) and iron (20%) in patients with anaemia. Only 24% of patients with coronary artery disease were prescribed statins, and ACE inhibitors and angiotensin receptor blockers were used in only 58 and 23% of diabetic patients with proteinuria. Positive predictors of epoetin and iron therapy included white race and diabetes. Higher GFR and higher serum albumin were associated with lower odds of being prescribed epoetin. White race and diabetics were more likely to be prescribed iron. This study provides an overview of prescription practices in a cohort of CKD patients. Substantial underutilization of certain classes of cardioprotective medications is apparent, and systematic educational efforts in this direction may well prove worthwhile to impact outcomes.


Designing catalysts with deep generative models and computational data. A case study for Suzuki cross coupling reactions.
The need for more efficient catalytic processes is ever-growing, and so are the costs associated with experimentally searching chemical space to find new promising catalysts. Despite the consolidated use of density functional theory (DFT) and other atomistic models for virtually screening molecules based on their simulated performance, data-driven approaches are rising as indispensable tools for designing and improving catalytic processes. Here, we present a deep learning model capable of generating new catalyst-ligand candidates by self-learning meaningful structural features solely from their language representation and computed binding energies. We train a recurrent neural network-based Variational Autoencoder (VAE) to compress the molecular representation of the catalyst into a lower dimensional latent space, in which a feed-forward neural network predicts the corresponding binding energy to be used as the optimization function. The outcome of the optimization in the latent space is then reconstructed back into the original molecular representation. These trained models achieve state-of-the-art predictive performances in catalysts' binding energy prediction and catalysts' design, with a mean absolute error of 2.42 kcal mol-1 and an ability to generate 84% valid and novel catalysts.


[Diagnostic and prognostic value of antibodies to cyclic citrullinated peptide (Anti-CCP) in rheumatoid arthritis].
There is strong evidence that the determination of autoantibodies against filaggrine is a very useful tool for the diagnosis of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide antibodies (Anti-CCP)-ELISA appear to be the most efficient test among those available for the detection of antifilaggrine autoantibodies, as it has the best diagnostic accuracy for the diagnosis of RA. Furthermore, the anti-CCP-ELISA determination in early arthritis is a good predictor of disease persistence and radiographic joint damage. The positivity of Anti-CCP some years before the onset of the RA and the high concentration of autoantibodies in synovial fluid suggest a possible pathogenetic role of citrullination. However, at present, it is unclear whether anti-CCP antibodies have a better diagnostic performance than rheumatoid factor in recent onset synovitis and if they confer any additional value to the prognostic evaluation obtained with validated predictors of outcome (FR, joint count, duration of disease).


Exploring and expanding the research agenda for diabetes in managed care. A report of a Centers for Disease Control and Prevention-Managed Care Workshop.
The objective of this article is to describe the proceedings of a workshop organized by the Centers for Disease Control and Prevention (CDC) to 1) summarize current preventive care practices for people with diabetes in managed care organizations (MCOs) in the U.S., 2) understand the strengths and barriers to diabetes-related health services research in MCOs, and 3) highlight the major research questions and approaches to improve diabetes-related research in these organizations. Review and synthesis of presentations and discussions are provided. MCOs have considerable potential to enhance diabetes health services research because of their access to large diverse populations, novel health service interventions, and availability of data systems that link patients, health care providers, health care use, and health outcomes. Barriers to improved MCO-based research include confounding by concurrent interventions and secular trends, lack of control groups for rigorous evaluation of interventions, and the heterogeneous structures of MCOs. Future research, particularly if conducted in a collaborative environment, has the potential to improve the understanding of trends in health services, improve the understanding of characteristics of MCOs, and evaluate complex interventions directed at patients, health care providers, and systems of care.


Thyroid nodule core needle biopsy - current approach.
Fine needle aspiration biopsy (FNAB) guided by ultrasonography is routinely used to identify thyroid nodules prior to surgery. Although FNAB has great diagnostic accuracy and safety, it is limited by its relatively low diagnostic accuracy in follicular lesions, such as non-diagnostic or atypia of unclear significance (AUS)/follicular lesion of uncertain significance (FLUS). Additional diagnostic tests are required to overcome these challenges in evaluating thyroid nodules. Thyroid nodules can now be diagnosed with spring-activated single- or double-action needles following the introduction of core needle biopsy (CNB). CNB has the ability to address the limitations of FNAB by obtaining a sizeable tissue sample with more details on the histological structure supporting the capsule and fewer non-diagnostic effects brought on by the absence of follicular cells. Compared to repeated FNAB, CNB has been demonstrated to produce fewer ambiguous results, such as non-diagnostic or AUS/FLUS results. The Korean Endocrine Pathology Thyroid CNB Working Group issued its first set of guidelines for "Pathology Reporting of Thyroid Core Needle Biopsy" in 2015. In 2017, the Korean Society of Thyroid Radiology (KSThR) published "Core Needle Biopsy of Thyroid: 2016 Consensus Statement and Recommendations from the Korean Society of Thyroid Radiology". The main objectives of thyroid CNB are to detect individuals with thyroid illness who require surgery and to obtain a significant number of thyroid lesions with low morbidity.


Eosinophilic leukemia in three African pygmy hedgehogs ( Atelerix albiventris) and validation of Luna stain.
Neoplasia is usually encountered in the African pygmy hedgehog at a mean age of 3.5 y, and malignancy is common. Myelogenous leukemias are rarely reported in hedgehogs. We describe 3 cases of eosinophilic leukemia in adult, middle-aged (mean age: 2.3 y) hedgehogs, for which prognosis appears grave. In 1 case, attempted treatment was unsuccessful, and in all 3 cases, the disease course was rapid and all died soon after diagnosis. Blood smear evaluation, along with complete blood count, was critical in making the diagnosis in all cases. Luna stain was validated and used to better visualize eosinophils in cytologic and histologic sections. Electron microscopy confirmed the presence of specific granules in hedgehog eosinophils.


Regulation of single potassium ion channels from apical membrane of rabbit collecting tubule.
The regulation of K+-channel activity from the apical membrane of the rabbit cortical collecting tubule was studied using the patch-clamp technique. Using inside-out patches, channel open probability was determined as a function of calcium and barium concentration and transmembrane potential. Channel open probability was increased by raising bath (cytoplasmic) calcium concentration, with an apparent Ka of 2.4 microM. Mean channel open time also increased during this maneuver. The channel was reversibly inhibited by barium, applied to the cytoplasmic face, with an apparent Ki of 12 microM. Depolarization of the transmembrane potential increased channel open probability. With 1 mM calcium in the bath solution, the open probability was one-half maximal at -55 mV. It is concluded that this channel is the probable route for transcellular K+ secretion by the cortical collecting tubule and that procedures likely to increase intracellular calcium and/or depolarize the apical membrane will cause an increased potassium secretion.


Pressure dependence of the laser-induced breakdown thresholds of gases and droplets.
Laser-induced breakdown threshold intensities for helium, argon, xenon and clean air were measured as a function of pressure (p < 900 Torr) at wavelength lambda = 0.532 microm using the Nd:YAG laser with 6.5-ns pulse duration. Pressure dependence of the breakdown of a 50-microm diam water droplet in these gases was also investigated. For pure gases, different free electron generation processes and electron loss processes dominate in different pressure regions. The water droplets decrease the breakdown thresholds up to 3 orders of magnitude depending on the pressure of the particular gas surrounding the droplet. For the droplet in He, Ar, and clean air for p < 800 Torr, the breakdown at the threshold intensity occurs inside the droplet and is independent of pressure. For the droplet in Xe, the breakdown occurs inside the droplet for p < 140 Torr; however, for p < 140 Torr, the breakdown occurs outside the droplet and is dependent on pressure. Transition from the breakdown inside to outside the droplet takes place in the pressure region where the breakdown thresholds of the bulk liquid and the pure gas are approximately equal.


Factor XIII cross-links fibrin(ogen) independent of fibrin polymerization in experimental acute liver injury.
Intravascular fibrin clot formation follows a well-ordered series of reactions catalyzed by thrombin cleavage of fibrinogen leading to fibrin polymerization and cross-linking by factor XIIIa (FXIIIa). Extravascular fibrin(ogen) deposits are observed in injured tissues; however, the mechanisms regulating fibrin(ogen) polymerization and cross-linking in this setting are unclear. The objective of this study was to determine the mechanisms of fibrin polymerization and cross-linking in acute liver injury induced by acetaminophen (APAP) overdose. Hepatic fibrin(ogen) deposition and cross-linking were measured following APAP overdose in wild-type mice, mice lacking the catalytic subunit of FXIII (FXIII-/-), and in FibAEK mice, which express mutant fibrinogen insensitive to thrombin-mediated fibrin polymer formation. Hepatic fibrin(ogen) deposition was similar in APAP-challenged wild-type and FXIII-/- mice, yet cross-linking of hepatic fibrin(ogen) was dramatically reduced (>90%) by FXIII deficiency. Surprisingly, hepatic fibrin(ogen) deposition and cross-linking were only modestly reduced in APAP-challenged FibAEK mice, suggesting that in the APAP-injured liver fibrin polymerization is not strictly required for the extravascular deposition of cross-linked fibrin(ogen). We hypothesized that the oxidative environment in the injured liver, containing high levels of reactive mediators (eg, peroxynitrite), modifies fibrin(ogen) such that fibrin polymerization is impaired without impacting FXIII-mediated cross-linking. Notably, fibrin(ogen) modified with 3-nitrotyrosine adducts was identified in the APAP-injured liver. In biochemical assays, peroxynitrite inhibited thrombin-mediated fibrin polymerization in a concentration-dependent manner without affecting fibrin(ogen) cross-linking over time. These studies depict a unique pathology wherein thrombin-catalyzed fibrin polymerization is circumvented to allow tissue deposition and FXIII-dependent fibrin(ogen) cross-linking.


Management of limited-stage Hodgkin lymphoma.
Hodgkin lymphoma (HL) is a rare type of B-cell malignancy with bimodal age distribution targeting young adults and elderly. Prognostic models are available to identify risk of recurrence and response to treatment. Currently, positron emission tomography scanning is most useful in optimizing therapy. Outcomes are generally excellent with standard chemotherapy or combined modality therapy. Balancing efficacy and the risk of late effects in Hodgkin lymphoma is essential, including early detection of potential complications. Incorporation of novel therapies such as brentuximab vedotin and checkpoint inhibitors are being explored in the frontline setting, having already demonstrated improved survival and tolerable toxicity in advanced HL. Furthermore, the addition of these agents have the potential to transform treatment paradigms for early-stage HL and may result in improved outcomes with decreased risks of late toxicities that continue to afflict long-term survivors. However, the patient population, sequencing, and combinations with cytotoxic chemotherapy all remain still standing questions as results of current and upcoming randomized trials are awaited. In this article, we discuss the current data on the approach to initial treatment of early-stage classical HL, review toxicity profiles, and examine upcoming novel therapy trials.


Hybrid Sterility in Fish Caused by Mitotic Arrest of Primordial Germ Cells.
Sterility in hybrid animals is widely known to be due to a cytological mechanism of aberrant homologous chromosome pairing during meiosis in hybrid germ cells. In this study, the gametes of four marine fish species belonging to the Sciaenid family were artificially fertilized, and germ cell development was examined at the cellular and molecular levels. One of the intergeneric hybrids had gonads that were testis-like in structure, small in size, and lacked germ cells. Specification of primordial germ cells (PGCs) and their migration toward genital ridges occurred normally in hybrid embryos, but these PGCs did not proliferate in the hybrid gonads. By germ cell transplantation assay, we showed that the gonadal microenvironment in hybrid recipients produced functional donor-derived gametes, suggesting that the germ cell-less phenotype was caused by cell autonomous proliferative defects of hybrid PGCs. This is the first evidence of mitotic arrest of germ cells causing hybrid sterility in animals.


Transient response of aerobic and anoxic activated sludge activities to sudden substrate concentration changes.
The state-of-the-art understanding of activated sludge processes as summarized in activated sludge models (ASMs) predicts an instantaneous increase in the biomass activity (which is measured, e.g., by the corresponding respiration rate OUR, NUR, etc.) under sudden substrate concentration changes. Experimental data (e.g., short-term batch respiration experiments under aerobic or anoxic conditions) collected for the calibration of the dynamic models (ASMs) often exhibit a transient phenomenon while attaining maximum activity, which cannot be explained by the current understanding of the activated sludge process. That transient phenomenon exhibits itself immediately upon addition of a substrate source to an endogenously respiring activated sludge sample and it usually takes a few minutes until the activated sludge reaches its maximum possible rate under given environmental conditions. This discrepancy between the state-of-the-art model and the experimental data is addressed in detail in this investigation. It is shown that the discrepancy is not caused by an error in the experimental set-up/data but it is rather due to model inadequacy. Among the hypotheses proposed, it appears that this transient response of the activated sludge most likely results from the sequence of intracellular reactions involved in substrate degradation by the activated sludge. Results from studies performed elsewhere with pure cultures (S. cerevisae and E. coli) support the hypothesis. The transient phenomenon can be described by a dynamic metabolic network model or by a simple first-order model, as adopted in this study. The transient phenomenon occurring in short-term batch respiration experiments is shown to interfere severely with parameter estimation if not modeled properly (2.8%, 11.5%, and 16.8% relative errors [average of three experiments] on Y(H), micro(maxH), and K(S), respectively). Proper modeling of this transient phenomenon whose time constant is on the order of minutes (1 to 3 min) is expected to contribute fundamentally to a better understanding and modeling of Orbal, carousel, and SBR-type treatment plants with fast-alternating process conditions, although such studies are beyond the scope of this report.


Emotion recognition in preschool children: associations with maternal depression and early parenting.
Emotion knowledge in childhood has been shown to predict social functioning and psychological well-being, but relatively little is known about parental factors that influence its development in early childhood. There is some evidence that both parenting behavior and maternal depression are associated with emotion recognition, but previous research has only examined these factors independently. The current study assessed auditory and visual emotion recognition ability among a large sample of preschool children to examine typical emotion recognition skills in children of this age, as well as the independent and interactive effects of maternal and paternal depression and negative parenting (i.e., hostility and intrusiveness). Results indicated that children were most accurate at identifying happy emotional expressions. The lowest accuracy was observed for neutral expressions. A significant interaction was found between maternal depression and negative parenting behavior: children with a maternal history of depression were particularly sensitive to the negative effects of maladaptive parenting behavior on emotion recognition ability. No significant effects were found for paternal depression. These results highlight the importance of examining the effects of multiple interacting factors on children's emotional development and provide suggestions for identifying children for targeted preventive interventions.


A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis.
Dietary intake of the soy isoflavone genistein is associated with reduced severity of asthma, but the mechanisms responsible for this effect are unknown. To determine whether genistein blocks eosinophil leukotriene C(4) (LTC(4)) synthesis and to evaluate the mechanism of this effect, and to assess the impact of a 4-week period of soy isoflavone dietary supplementation on indices of eosinophilic inflammation in asthma patients. Human peripheral blood eosinophils were stimulated in the absence and presence of genistein, and LTC(4) synthesis was measured. 5-lipoxygenase (5-LO) nuclear membrane translocation was assessed by confocal immunofluorescence microscopy. Mitogen-activated protein (MAP) kinase activation was determined by immunoblot. Human subjects with mild-to-moderate persistent asthma and minimal or no soy intake were given a soy isoflavone supplement (100 mg/day) for 4 weeks. The fraction of exhaled nitric oxide (FE(NO)) and ex vivo eosinophil LTC(4) production were assessed before and after the soy isoflavone treatment period. Genistein inhibited eosinophil LTC(4) synthesis (IC(50) 80 nm), blocked phosphorylation of p38 MAP kinase and its downstream target MAPKAP-2, and reduced translocation of 5-LO to the nuclear membrane. In patients with asthma, following 4 weeks of dietary soy isoflavone supplementation, ex vivo eosinophil LTC(4) synthesis decreased by 33% (N=11, P=0.02) and FE(NO) decreased by 18% (N=13, P=0.03). At physiologically relevant concentrations, genistein inhibits eosinophil LTC(4) synthesis in vitro, probably by blocking p38- and MAPKAP-2-dependent activation of 5-LO. In asthma patients, dietary soy isoflavone supplementation reduces eosinophil LTC(4) synthesis and eosinophilic airway inflammation. These results support a potential role for soy isoflavones in the treatment of asthma.


Determinants of Hypertension amongst Rice Farmers in West Java, Indonesia.
The hypertension rate in Indonesia has increased significantly in the past five years, but there is limited information about the hypertension risk of farmers. Our study assesses the prevalence of hypertension in this population and examines the proportional risk of various work environment and lifestyle factors among farmers. A cross-sectional study was conducted in high and low heat stress agriculture areas of West Java, Indonesia. There were 354 male farmers aged 25 to 73 years old who participated in the study. We measured blood pressure and used a questionnaire on self-reported use of anti-hypertension drugs or diagnosis by a medical professional to define hypertension. We assessed occupational factors including farming methods, heat stress and pesticide use, and personal factors including obesity, food intake, smoking status, alcohol consumption. Multivariate analysis was used to evaluate factors potentially associated with prevalence of hypertension. Forty-six percent of farmers experience hypertension. Farming in a location with higher heat stress (WBGT) was significantly associated with increased risk of hypertension (adjusted prevalence ratio (aPR) 1.41, 95% confidence interval (CI) 1.01, 1.95). Farmers who used pesticide sprayers had an increased risk of hypertension (aPR 1.90, 95% CI 0.93, 3.87). No personal/lifestyle characteristics were significantly associated with hypertension, although ever smoking and ever consuming alcohol had an increased prevalence of hypertension. This study shows the importance of work environmental factors in the prevalence of hypertension and the necessity of public health education, identification and treatment of this "silent killer" among Indonesian farmers.


Implementation of NIAAA College Drinking Task Force recommendations: how are colleges doing 6 years later?
In 2002, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) College Drinking Task Force issued recommendations to reduce heavy drinking by college students, but little is known about implementation of these recommendations. Current discussion about best strategies to reduce student drinking has focused more on lowering the minimum legal drinking age as advocated by a group of college and university presidents called the Amethyst Initiative than the NIAAA recommendations. A nationally representative survey of administrators was conducted at 351 4-year colleges in the United States to ascertain familiarity with and progress toward implementation of NIAAA recommendations. Implementation was compared by enrollment size, public or private status, and whether the school president signed the Amethyst Initiative. Administrators at most colleges were familiar with NIAAA recommendations, although more than 1 in 5 (22%) were not. Nearly all colleges use educational programs to address student drinking (98%). Half the colleges (50%) offered intervention programs with documented efficacy for students at high risk for alcohol problems. Few colleges reported that empirically supported, community-based alcohol control strategies including conducting compliance checks to monitor illegal alcohol sales (33%), instituting mandatory responsible beverage service (RBS) training (15%), restricting alcohol outlet density (7%), or increasing the price of alcohol (2%) were operating in their community. Less than half the colleges with RBS training and compliance checks in their communities actively participated in these interventions. Large colleges were more likely to have RBS training and compliance checks, but no differences in implementation were found across public/private status or whether the college president signed the Amethyst Initiative. Many colleges offer empirically supported programs for high-risk drinkers, but few have implemented other strategies recommended by NIAAA to address student drinking. Opportunities exist to reduce student drinking through implementation of existing, empirically based strategies.


Nicotinic receptor-evoked hippocampal norepinephrine release is highly sensitive to inhibition by isoflurane.
Inhaled anaesthetics (IAs) produce multiple dose-dependent behavioural effects including amnesia, hypnosis, and immobility in response to painful stimuli that are mediated by distinct anatomical, cellular, and molecular mechanisms. Amnesia is produced at lower anaesthetic concentrations compared with hypnosis or immobility. Nicotinic acetylcholine receptors (nAChRs) modulate hippocampal neural network correlates of memory and are highly sensitive to IAs. Activation of hippocampal nAChRs stimulates the release of norepinephrine (NE), a neurotransmitter implicated in modulating hippocampal synaptic plasticity. We tested the hypothesis that IAs disrupt hippocampal synaptic mechanisms critical to memory by determining the effects of isoflurane on NE release from hippocampal nerve terminals. Isolated nerve terminals prepared from adult male Sprague-Dawley rat hippocampus were radiolabelled with [(3)H]NE and either [(14)C]GABA or [(14)C]glutamate and superfused at 37 degrees C. Release evoked by a 2 min pulse of 100 microM nicotine or 5 microM 4-aminopyridine was evaluated in the presence or absence of isoflurane and/or selective antagonists. Nicotine-evoked NE release from rat hippocampal nerve terminals was nAChR- and Ca(2+)-dependent, involved both alpha7 and non-alpha7 subunit-containing nAChRs, and was partially dependent on voltage-gated Na(+) channel activation based on sensitivities to various antagonists. Isoflurane inhibited nicotine-evoked NE release (IC(50)=0.18 mM) more potently than depolarization-evoked NE release (IC(50)=0.27 mM, P=0.014), consistent with distinct presynaptic mechanisms of IA action. Inhibition of hippocampal nAChR-dependent NE release by subanaesthetic concentrations of isoflurane supports a role in IA-induced amnesia.


Identification of a novel C-terminal variant of beta II spectrin: two isoforms of beta II spectrin have distinct intracellular locations and activities.
It is established that variations in the structure and activities of betaI spectrin are mediated by differential mRNA splicing. The two betaI spectrin splice forms so far identified have either long or short C-terminal regions. Are analogous mechanisms likely to mediate regulation of betaII spectrins? Thus far, only a long form of betaII spectrin is reported in the literature. Five human expressed sequence tags indicated the existence of a short splice variant of betaII spectrin. The occurrence and DNA sequence of the short C-terminal variant was confirmed by analysis of human and rat cDNA. The novel variant lacks a pleckstrin homology domain, and has 28 C-terminal residues not present in the previously recognized longer form. Transcripts of the short C-terminal variant (7.5 and 7. 0 kb) were most abundant in tissues originating from muscle and nervous system. Antibodies raised to a unique sequence of short C-terminal variant recognized 240 kDa polypeptides in cardiac and skeletal muscle and in nervous tissue; in cerebellum and forebrain, additional 270 kDa polypeptides were detected. In rat heart and skeletal muscle, both long and short C-terminal forms of betaII spectrin localized in the region of the Z line. The central region of the sarcomere, coincident with the M line, was selectively labeled with antibodies to the short C-terminal form. In cerebellum, the short form was not detectable in parallel fibers, structures in which the long form was readily detected. In cultured cerebellar granule neurons, the long form was dominant in neurites, with the short form being most abundant in cell bodies. In vitro, the short form was found to lack the binding activity for the axonal protein fodaxin, which characterizes the C-terminal region of the long form. Subcellular fractionation of brain revealed that the short form was scarcely detectable in post-synaptic density preparations, in which the long form was readily detected. We conclude that variation in the structure of the C-terminal regions of betaII spectrin isoforms correlates with their differential intracellular targeting.