Persistence and Suppressiveness of Pasteuria penetrans to Meloidogyne arenaria Race.
The long-term persistence and suppressiveness of Pasteuria penetrans against Meloidogyne arenaria race 1 were investigated in a formerly root-knot nematode suppressive site following 9 years of continuous cultivation of three treatments and 4 years of continuous peanut. The three treatments were two M. arenaria race 1 nonhost crops, bahiagrass (Paspalum notatum cv. Pensacola var. Tifton 9), rhizomal peanut (Arachis glabrata cv. Florigraze), and weed fallow. Two root-knot nematode susceptible weeds commonly observed in weed fallow plots were hairy indigo (Indigofera hirsuta) and alyce clover (Alysicarpus vaginalis). The percentage of J2 with endospores attached reached the highest level of 87% in 2000 in weed fallow, and 63% and 53% in 2002 in bahiagrass and rhizomal peanut, respectively. The percentage of endospore-filled females extracted from peanut roots grown in weed fallow plots increased from nondetectable in 1999 to 56% in 2002, whereas the percentages in bahiagrass and rhizomal peanut plots were 41% and 16%, respectively. Over 4 years, however, there was no strong evidence that endospores densities reached suppressive levels because peanut roots, pods, and pegs were heavily galled, and yields were suppressed. This might be attributed to the discovery of M. javanica infecting peanut in this field in early autumn 2001. A laboratory test confirmed that although the P. penetrans isolate specific to M. arenaria attached to M. javanica J2, no development occurred. In summary, P. penetrans increased on M. arenaria over a 4-year period, but apparently because of infection of M. javanica on peanut at the field site root-knot disease was not suppressed. This was confirmed by a suppressive soil test that showed a higher level of soil suppressiveness than occurred in the field (P </= 0.01).


Imatinib-induced hyperbilirubinemia with UGT1A1 (*28) promoter polymorphism: first case series in patients with gastrointestinal stromal tumor.
Imatinib, an orally administered protein-tyrosine kinase inhibitor (TKI) is indicated for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). Severe hepatotoxicity associated with imatinib is rare, and relationship to polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression and related frequency of hyperbilirubinemia or toxicity are not well known. We present a case series patients who developed hyperbilirubinemia while on oral administration imatinib for treatment of GIST. Genetic testing for polymorphism of UGT1A1 showed the first patient to be homozygous for the UGT1A1 TA7 (*28) polymorphism and the second patient heterozygous for the UGT1A1 TA1 (*28) polymorphism. The first patient had to stop imatinib due to severe and persistent hyperbilirubenemia peaking >3 despite reducing imatininb to only 100 mg every other day while the second patient improved at this dose. Our case series represent the first data associating UGT1A1 polymorphism and imatinib in patients being treated for GIST. Given the prevalence of Gilbert's syndrome and the increasing use of imatinib, we encourage physicians to be aware of this possible toxicity as hepatotoxicity can be fatal if not managed in a timely fashion. This association is also timely due to recent FDA requirement for testing UGT1A1 polymorphism for nilotinib, another TKI.


On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis.
High density mineralised protrusions (HDMP) from the tidemark mineralising front into hyaline articular cartilage (HAC) were first described in Thoroughbred racehorse fetlock joints and later in Icelandic horse hock joints. We now report them in human material. Whole femoral heads removed at operation for joint replacement or from dissection room cadavers were imaged using magnetic resonance imaging (MRI) dual echo steady state at 0.23 mm resolution, then 26-μm resolution high contrast X-ray microtomography, sectioned and embedded in polymethylmethacrylate, blocks cut and polished and re-imaged with 6-μm resolution X-ray microtomography. Tissue mineralisation density was imaged using backscattered electron SEM (BSE SEM) at 20 kV with uncoated samples. HAC histology was studied by BSE SEM after staining block faces with ammonium triiodide solution. HDMP arise via the extrusion of an unknown mineralisable matrix into clefts in HAC, a process of acellular dystrophic calcification. Their formation may be an extension of a crack self-healing mechanism found in bone and articular calcified cartilage. Mineral concentration exceeds that of articular calcified cartilage and is not uniform. It is probable that they have not been reported previously because they are removed by decalcification with standard protocols. Mineral phase morphology frequently shows the agglomeration of many fine particles into larger concretions. HDMP are surrounded by HAC, are brittle, and show fault lines within them. Dense fragments found within damaged HAC could make a significant contribution to joint destruction. At least larger HDMP can be detected with the best MRI imaging ex vivo.


A two-year assessment of particulate air pollution and sources in Kuwait.
Kuwait and the Gulf region have a desert, hyper-arid and hot climate that makes outdoor air sampling challenging. The region is also affected by intense dust storms. Monitoring challenges from the harsh climate have limited data needed to inform appropriate regulatory actions to address air pollution in the region. To compare gravimetric measurements with existing networks that rely on beta-attenuation measurements in a desert climate; determine the annual levels of PM2.5 and PM10 over a two-year period in Kuwait; assess compliance with air quality standards; and identify and quantify PM2.5 sources. We custom-designed particle samplers that can withstand large quantities of dust without their inlet becoming overloaded. The samplers were placed in two populated residential locations, one in Kuwait City and another near industrial and petrochemical facilities in Ali Sabah Al-Salem (ASAS) to collect PM2.5 and PM10 samples for mass and elemental analysis. We used positive matrix factorization to identify PM2.5 sources and apportion their contributions. We collected 2339 samples during the period October 2017 through October 2019. The beta-attenuation method in measuring PM2.5 consistently exceeded gravimetric measurements, especially during dust events. The annual levels for PM2.5 in Kuwait City and ASAS were 41.6 ± 29.0 and 47.5 ± 27.6 μg/m3, respectively. Annual PM2.5 levels in Kuwait were nearly four times higher than the U.S. National Ambient Air Quality Standard. Regional pollution was a major contributor to PM2.5 levels in both locations accounting for 44% in Kuwait City and 46% in ASAS. Dust storms and re-suspended road dust were the second and third largest contributors to PM2.5, respectively. The premise that frequent and extreme dust storms make air quality regulation futile is dubious. In this comprehensive particulate pollution analysis, we show that the sizeable regional anthropogenic particulate sources warrant national and regional mitigation strategies to ensure compliance with air quality standards.


Statin use and risk of primary liver cancer in the Clinical Practice Research Datalink.
Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely prescribed to reduce cholesterol levels. Studies have suggested that statins are associated with reduced risk of liver cancer, but much of the evidence is from regions of the world with high liver cancer incidence rates. The current study examined the statins-liver cancer relationship in a low-rate region and examined the effects of preexisting liver disease and diabetes on that association. A nested case-control study was conducted within the United Kingdom's Clinical Practice Research Datalink (CPRD). Persons diagnosed with primary liver cancer between 1988 and 2011 were matched to controls at a four-to-one ratio. Matches stratified on liver disease and on diabetes were also completed. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations of statins with liver cancer were estimated using conditional logistic regression. In total, 1195 persons with primary liver cancer were matched to 4640 control patients. Statin use was associated with a statistically significantly reduced risk of liver cancer (ORadj = 0.55, 95% CI = 0.45 to 0.69), especially among current users (ORadj = 0.53, 95% CI = 0.42 to 0.66). The reduced risk was statistically significant in the presence (ORadj = 0.32, 95% CI = 0.17 to 0.57) and absence of liver disease (ORadj = 0.65, 95% CI = 0.52 to 0.81) and in the presence (ORadj = 0.30, 95% CI = 0.21 to 0.42) and absence of diabetes (ORadj = 0.66, 95% CI = 0.51 to 0.85). In the current study in a low-rate area, statin use was associated with a statistically significantly reduced risk of liver cancer overall. Risk was particularly reduced among persons with liver disease and persons with diabetes, suggesting that statin use may be especially beneficial in persons at elevated risk of liver cancer.


A Rare Case of Pericardial Decompression Syndrome in a Filipino Female Patient With Suspected Malignant Pericardial Effusion.
Pericardial decompression syndrome (PDS) is a rare, under-reported and potentially fatal complication of pericardial drainage characterized by paradoxical hemodynamic deterioration. The onset ranges from immediate to as long as 48 h post drainage. We present a case of a 51-year-old woman admitted due to progressive dyspnea. She was hemodynamically stable but with signs of cardiac tamponade. On two-dimensional echocardiography (2D-echo) there was a massive pericardial effusion in tamponade physiology. Immediate surgical drainage was done but intra-operatively there was depressed cardiac contractility necessitating inotropic support. Post-operative 2D-echo showed right ventricular (RV) and left ventricular (LV) systolic dysfunction. She was admitted in the intensive care unit (ICU) for 72 h. Repeat 2D-echo showed marked improvement in RV and LV systolic function. She was then discharged improved on the fifth hospital day. The pathophysiology of PDS is still not very clear. The simplest mechanism is that sudden removal of compressing pericardial fluid causes increased venous return with expansion of the RV at the expense of the LV leading to acute heart failure. There are no published studies to propose preventive measures and treatment remains supportive. There has been only one published case reported here in our country. We report this case of a patient who successfully recovered from PDS.


Prolonged C2 spinal hemisection-induced inactivity reduces diaphragm muscle specific force with modest, selective atrophy of type IIx and/or IIb fibers.
The diaphragm muscle (DIAm) is critically responsible for sustaining ventilation. Previously we showed in a commonly used model of spinal cord injury, unilateral spinal cord hemisection at C(2) (SH), that there are minimal changes to muscle fiber cross-sectional area (CSA) and fiber type distribution following 14 days of SH-induced ipsilateral DIAm inactivity. In the present study, effects of long-term SH-induced inactivity on DIAm fiber size and force were examined. We hypothesized that prolonged inactivity would not result in substantial DIAm atrophy or force loss. Adult rats were randomized to control or SH groups (n = 34 total). Chronic bilateral DIAm electromyographic (EMG) activity was monitored during resting breathing. Minimal levels of spontaneous recovery of ipsilateral DIAm EMG activity were evident in 42% of SH rats (<25% of preinjury root mean square amplitude). Following 42 days of SH, DIAm specific force was reduced 39%. There was no difference in CSA for type I or IIa DIAm fibers in SH rats compared with age, weight-matched controls (classification based on myosin heavy chain isoform expression). Type IIx and/or IIb DIAm fibers displayed a modest 20% reduction in CSA (P < 0.05). Overall, there were no differences in the distribution of fiber types or the contribution of each fiber type to the total DIAm CSA. These data indicate that reduced specific force following prolonged inactivity of the DIAm is associated with modest, fiber type selective adaptations in muscle fiber size and fiber type distribution.


Judging Normality and Attractiveness in Faces: Direct Evidence of a More Refined Representation for Own-Race, Young Adult Faces.
Young and older adults are more sensitive to deviations from normality in young than older adult faces, suggesting that the dimensions of face space are optimized for young adult faces. Here, we extend these findings to own-race faces and provide converging evidence using an attractiveness rating task. In Experiment 1, Caucasian and Chinese adults were shown own- and other-race face pairs; one member was undistorted and the other had compressed or expanded features. Participants indicated which member of each pair was more normal (a task that requires referencing a norm) and which was more expanded (a task that simply requires discrimination). Participants showed an own-race advantage in the normality task but not the discrimination task. In Experiment 2, participants rated the facial attractiveness of own- and other-race faces (Experiment 2a) or young and older adult faces (Experiment 2b). Between-rater variability in ratings of individual faces was higher for other-race and older adult faces; reduced consensus in attractiveness judgments reflects a less refined face space. Collectively, these results provide direct evidence that the dimensions of face space are optimized for own-race and young adult faces, which may underlie face race- and age-based deficits in recognition.


Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the preBötzinger complex.
Neurokinin-1 receptor (NK1R) and mu-opioid receptor (muOR) agonists affected respiratory rhythm when injected directly into the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythmogenesis in mammals. These effects were mediated by actions on preBötC rhythmogenic neurons. The distribution of NK1R+ neurons anatomically defined the preBötC. Type 1 neurons in the preBötC, which have rhythmogenic properties, expressed both NK1Rs and muORs, whereas type 2 neurons expressed only NK1Rs. These findings suggest that the preBötC is a definable anatomic structure with unique physiological function and that a subpopulation of neurons expressing both NK1Rs and muORs generate respiratory rhythm and modulate respiratory frequency.


Effect of Single and Combined Expression of Lysophosphatidic Acid Acyltransferase, Glycerol-3-Phosphate Acyltransferase, and Diacylglycerol Acyltransferase on Lipid Accumulation and Composition in Neochloris oleoabundans.
Microalgal lipids are promising feedstocks for food and biofuels. Since lipid production by microalgae is not yet economically feasible, genetic engineering is becoming a promising strategy to achieve higher lipid accumulation and productivities. Enzymes involved in the Kennedy pathway such as glycerol-3-phosphate acyltransferase (GPAT), lysophosphatidic acid acyltransferase (LPAT), and diacylglycerol acyltransferase (DGAT) catalyze key steps in the formation of triacylglycerol, which is the main constituent of lipids in N. oleoabundans. The overexpression of these enzymes in the targeted strain has a great potential to further increase their triacylglycerol content. We overexpressed single and multiple encoding genes for LPAT, GPAT, and DGAT from Acutodesmus obliquus in N. oleoabundans. Strains overexpressing single genes produced up to 52% and 45% g · gDW-1, which corresponds to 1.3- and 1.4-fold increase in total fatty acids and triacylglycerols, respectively. The orchestrated expression of the three genes resulted in 49% and 39% g · gDW-1, which is 1.2-folds increase in total fatty acids and triacylglycerols. Single expression of LPAT, GPAT, and DGAT genes resulted in higher lipid productivities during starvation without a significant effect on growth and photosynthetic activity during replete conditions. On the other hand, the simultaneous expression of LPAT, GPAT, and DGAT genes resulted in 52% lower growth rate, 14% lower photosynthetic activity and 4-folds increase in cell diameter. Moreover, the multigene expressing line showed a decrease in carbohydrates and protein content and an increase in pigments during nitrogen starved condition. The single and multiple expression of heterologous genes LPAT, GPAT, and DGAT showed to significantly enhanced the lipid accumulation in N. oleoabundans. Single gene expression resulted in higher lipid production and productivities without having a significant impact in the physiological status of the strains. This approach shows the potential for the generation of microalgal strains with higher economical potential for the production of lipids.


Acetylator genotype-dependent expression of arylamine N-acetyltransferase and N-hydroxyarylamine O-acetyltransferase in Syrian inbred hamster intestine and colon. Identity with the hepatic acetylation polymorphism.
Human epidemiological studies suggest an association between rapid acetylator phenotype and the incidence of colorectal cancer. Genetic regulation of acetyl coenzyme A-dependent N-acetyltransferase (NAT) and O-acetyltransferase (OAT) enzymatic activities may play a role in the metabolic activation of arylamine chemicals in the intestine and colon. In this study, the inheritance of acetyltransferase activity in the intestine and colon was investigated in the Syrian inbred hamster model. Relatively high levels of both arylamine NAT and N-hydroxyarylamine OAT activities were expressed in hamster intestine and colon cytosols, at levels similar to those in the liver. Acetylator genotype-dependent levels of NAT activity were expressed towards p-aminobenzoic acid and the carbocyclic arylamine carcinogens 2-aminofluorene (AF), 4-aminobiphenyl, and beta-naphthylamine. However, acetylator genotype-independent activity was found with the heterocyclic arylamine carcinogens 2-aminodipyrido[1,2-a:3',2'd]imidazole, 3-amino-1-methyl-5H-pyrido[4,3-b]indole, and 2-amino-9H-pyrido-[2,3,b]indole. F1 hybrid heterozygous acetylator progeny expressed unimodal levels of acetyltransferase activity intermediate between the homozygous rapid and slow acetylator parental strains. F2 generation progeny segregated into three modes (low, intermediate, and high) in a ratio of 1/2/1, and both sets of backcrosses yielded bimodal distributions of low and intermediate or high and intermediate in equal ratios. The genetic data is consistent with simple autosomal Mendelian inheritance of two codominant alleles (rapid and slow) at a single genetic locus, the polymorphic acetyltransferase gene. Levels of N-hydroxy-2-aminofluorene OAT activity were acetylator genotype-dependent in liver, intestine, and colon cytosols, which correlated well with AF NAT activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Arabidopsis male sexual lineage exhibits more robust maintenance of CG methylation than somatic tissues.
Cytosine DNA methylation regulates the expression of eukaryotic genes and transposons. Methylation is copied by methyltransferases after DNA replication, which results in faithful transmission of methylation patterns during cell division and, at least in flowering plants, across generations. Transgenerational inheritance is mediated by a small group of cells that includes gametes and their progenitors. However, methylation is usually analyzed in somatic tissues that do not contribute to the next generation, and the mechanisms of transgenerational inheritance are inferred from such studies. To gain a better understanding of how DNA methylation is inherited, we analyzed purified Arabidopsis thaliana sperm and vegetative cells-the cell types that comprise pollen-with mutations in the DRM, CMT2, and CMT3 methyltransferases. We find that DNA methylation dependency on these enzymes is similar in sperm, vegetative cells, and somatic tissues, although DRM activity extends into heterochromatin in vegetative cells, likely reflecting transcription of heterochromatic transposons in this cell type. We also show that lack of histone H1, which elevates heterochromatic DNA methylation in somatic tissues, does not have this effect in pollen. Instead, levels of CG methylation in wild-type sperm and vegetative cells, as well as in wild-type microspores from which both pollen cell types originate, are substantially higher than in wild-type somatic tissues and similar to those of H1-depleted roots. Our results demonstrate that the mechanisms of methylation maintenance are similar between pollen and somatic cells, but the efficiency of CG methylation is higher in pollen, allowing methylation patterns to be accurately inherited across generations.


Accurate Delineation of Glioma Infiltration by Advanced PET/MR Neuro-Imaging (FRONTIER Study): A Diagnostic Study Protocol.
Glioma imaging, used for diagnostics, treatment planning, and follow-up, is currently based on standard magnetic resonance imaging (MRI) modalities (T1 contrast-enhancement for gadolinium-enhancing gliomas and T2 fluid-attenuated inversion recovery hyperintensity for nonenhancing gliomas). The diagnostic accuracy of these techniques for the delineation of gliomas is suboptimal. To assess the diagnostic accuracy of advanced neuroimaging compared with standard MRI modalities for the detection of diffuse glioma infiltration within the brain. A monocenter, prospective, diagnostic observational study in adult patients with a newly diagnosed, diffuse infiltrative glioma undergoing resective glioma surgery. Forty patients will be recruited in 3 years. Advanced neuroimaging will be added to the standard preoperative MRI. Serial neuronavigated biopsies in and around the glioma boundaries, obtained immediately preceding resective surgery, will provide histopathologic and molecular characteristics of the regions of interest, enabling comparison with quantitative measurements in the imaging modalities at the same biopsy sites. In this clinical study, we determine the diagnostic accuracy of advanced imaging in addition to standard MRI to delineate glioma. The results of our study can be valuable for the development of an improved standard imaging protocol for glioma treatment. We hypothesize that a combination of positron emission tomography, MR spectroscopy, and standard MRI will have a superior accuracy for glioma delineation compared with standard MRI alone. In addition, we anticipate that advanced imaging will correlate with the histopathologic and molecular characteristics of glioma. CHO, [11C-]CholineCRF, case report formsFET, [18F-]Fluoroethyl-tyrosineFLAIR, fluid-attenuated inversion recoveryMETC, Medical Ethical CommitteeMRS, magnetic resonance spectroscopyPET, positron emission tomographyVUmc, VU University Medical Center.


Clinical utility of early improvement to predict response or remission in acute mania: focus on olanzapine and risperidone.
To evaluate early improvement associated with atypical antipsychotic treatment as a predictor of later response or remission among patients experiencing an acute manic or mixed episode without psychotic features. A post hoc analysis was performed on data from a 3-week, randomized, double-blind clinical trial of olanzapine (N = 147) or risperidone (N = 127) to treat inpatients aged 18-70 years meeting DSM-IV criteria for bipolar I disorder. Early improvement, measured as percent change (≥ 25% and ≥ 50% cut points) in the Young Mania Rating Scale (YMRS) total score, was assessed after 2 days and 1 week of treatment. Receiver operating characteristic curves, sensitivity and specificity, and positive and negative predictive values were calculated to determine whether early improvement predicted endpoint (week 3) response or remission. The study was conducted from July 2001 through June 2002. Among 234 patients with ≥ 25% reduction in YMRS total score at week one, 167 (71.4%) responded and 121 (51.7%) remitted at endpoint. Of the 40 patients with < 25% improvement, 25% (n = 10) responded and 5% (n = 2) remitted at endpoint. A total of 157 patients had a ≥ 50% reduction in week 1 YMRS total score, of whom 132 (84.1%) responded and 101 (64.3%) remitted at endpoint. Of the 117 patients with < 50% improvement, 45 (38.5%) responded and 22 (18.8%) remitted at endpoint. Improvement in manic or mixed symptoms at week 1 appears to be a good predictor of treatment outcome. Patients not having sufficient improvement (< 25% reduction in YMRS score) were less likely to reach response or remission by week 3. Patients who achieved response by week 1 (≥ 50% reduction in YMRS score) were likely to remain responders at endpoint. These data suggest the potential to assess benefit in the treatment of manic or mixed symptoms within 1 week of initiating olanzapine or risperidone.


Comparison of power Doppler ultrasound with gray scale transrectal ultrasound in predicting cancer positive prostate biopsy cores.
The aim of this study is to compare the effect of transrectal power Doppler ultrasound (PDUS) and gray scale transrectal ultrasound (TRUS) for the diagnosis of prostate cancer. Seventy-six patients evaluated with transrectal PDUS and TRUS underwent eight systematic TRUS guided core-needle biopsies, with additional cores from abnormal areas. Histologic diagnoses were classified as benign prostatic hyperplasia, chronic prostatitis, intraepithelial neoplasia and adenocarcinoma. TRUS and PDUS findings of the cases were recorded. PDUS sensitivity, specificity, positive predictive value (PPV) and negative predictive values were 81%, 81%, 54% and 94%, respectively. PDUS had a greater sensitivity and specificity than TRUS (43% and 60%, respectively) and identified cancer cases more accurately (Table 2). Hypervascular foci in PDUS signify suitable zones for biopsy. When combined with systematic TRUS guided biopsy, PDUS increases the cancer detection rate with additional biopsies from suspicious hypervascular foci. Transrectal PDUS guided biopsy should be combined with gray scale TRUS guided biopsy to increase accuracy in the diagnosis of prostate cancer.


Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors.
Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels. However, because they inactivate voltage-gated sodium channels by promoting activation of one voltage sensor, we suggest that, despite different effects on the channel gates, the biaryl-sulfonamide motif is a general ion-channel activator motif. Because these compounds block action potential-generating sodium and calcium channels and open an action potential-dampening potassium channel, they should have a high propensity to reduce excitability. This opens up the possibility to build new excitability-reducing pharmaceutical drugs from the biaryl-sulfonamide scaffold.


Phylogeographic Analyses Reveal the Early Expansion and Frequent Bidirectional Cross-Border Transmissions of Non-pandemic HIV-1 Subtype B Strains in Hispaniola.
The human immunodeficiency virus-type 1 (HIV-1) subtype B has probably been circulating on the island of Hispaniola since the 1960s, but information about the early viral history on this Caribbean island is scarce. In this study, we reconstruct the dissemination dynamics of early divergent non-pandemic subtype B lineages (designated BCAR) on Hispaniola by analyzing a country-balanced dataset of HIV-1 BCAR pol sequences from Haiti (n = 103) and the Dominican Republic (n = 123). Phylogenetic analyses supported that BCAR strains from Haiti and the Dominican Republic were highly intermixed between each other, although the null hypothesis of completely random mixing was rejected. Bayesian phylogeographic analyses placed the ancestral BCAR virus in Haiti and the Dominican Republic with the same posterior probability support. These analyses estimate frequent viral transmissions between Haiti and the Dominican Republic since the early 1970s onwards, and the presence of local BCAR transmission networks in both countries before first AIDS cases was officially recognized. Demographic reconstructions point that the BCAR epidemic in Hispaniola grew exponentially until the 1990s. These findings support that the HIV-1 epidemics in Haiti and the Dominican Republic have been connected by a recurrent bidirectional viral flux since the initial phase, which poses a great challenge in tracing the geographic origin of the BCAR epidemic within Hispaniola using only genetic data. These data also reinforce the notion that prevention programs have successfully reduced the rate of new HIV-1 transmissions in Hispaniola since the end of the 1990s.


Using Rates of Low Scores to Assess Agreement between Brief Computerized Neuropsychological Assessment Batteries: A Clinically-based Approach for Psychometric Comparisons.
To assess agreement between four brief computerized neurocognitive assessment tools (CNTs), ANAM, CogState, CNS Vital Signs, and ImPACT, by comparing rates of low scores. Four hundred and six US Army service members (SMs) with and without acute mild traumatic brain injury completed two randomly assigned CNTs with order of administration also randomly assigned. We performed a base rate analysis for each CNT to determine the proportions of SMs in the control and mTBI groups who had various numbers of scores that were 1.0+, 1.5+, and 2.0+ standard deviations below the normative mean. We used these results to identify a hierarchy of low score levels ranging from poorest to least poor performance. We then compared the agreement between every low score level from each CNT pair administered to the SMs. More SMs in the mTBI group had low scores on all CNTs than SMs in the control group. As performance worsened, the association with mTBI became stronger for all CNTs. Most if not all SMs who performed at the worst level on any given CNT also had low scores on the other CNTs they completed but not necessarily at an equally low level. These results suggest that all of the CNTs we examined are broadly similar but still retain some psychometric differences that need to be better understood. Furthermore, the base rates of low scores we present could themselves be useful to clinicians and researchers as a guide for interpreting results from the CNTs.


Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome.
This study investigates the association of psychological symptoms with the distribution of two serotonin transporter gene (SERT) polymorphisms, located in the promoter region (5-HTTLPR) and in intron 2 (STin2 VNTR), in patients with irritable bowel syndrome (IBS). Participants, 21 men and 117 women, were assessed for mental health history and current psychological distress. A blood sample was used for genotyping. Participants who were homozygous for the short allele of 5-HTTLPR or carried a STin2.9 VNTR allele were significantly more likely to have a history of depression. Participants did not differ by genotype in their history of anxiety or suicidal ideation nor in their current levels of depression, anxiety, or general psychological distress. The results support a biopsychosocial model of IBS in which SERT genotype modifies the risk for depressive episodes. Long term, practitioners may individualize treatment of patients with IBS using genotype as one of the factors.


The response of Mucor plumbeus to pentachlorophenol: a toxicoproteomics study.
Pentachlorophenol (PCP) represents a critical concern worldwide due to its toxicity and recalcitrance to degradation. The capacity of Mucor plumbeus to transform PCP into several detoxification metabolites, including tetrachlorohydroquinone and several phase II conjugates, was observed by LC-HRMS. The data obtained support the degradation pathway proposed previously. PCP effects in M. plumbeus, an unsequenced species, were investigated using a proteomics approach (bidimensional gel electrophoresis followed by MALDI TOF/TOF analyses). The mycelial proteins identified in the differentially accumulated spots allowed the identification of PCP responsive proteins. The presence of PCP increased the energy demand, altered the cell wall architecture and cytoskeleton and induced a significant stress response. The latter was emphasised by the up-accumulation of protein species associated with defence mechanisms (e.g. HSP70 and cytochrome c peroxidase). Overall the data produced corroborate the capability of PCP to uncouple oxidative-phosphorylation in mitochondria. Importantly, one of the identified mycelial protein species, a NAD- and Zn-dependent ADH, is likely to be involved in PCP degradation. Amongst the fungal secretome analysed, no putative PCP degradative enzymes were detected. This work constitutes the first toxicoproteomic study involving a Zygomycota fungus and the very first concerning the effect of PCP in a fungal proteome.


"My head is like a bag full of rubbish": concepts of illness and treatment expectations in traumatized migrants.
Traumatized migrants increasingly burden health care services in industrialized countries. These patients usually suffer from a broad range of physical and psychological symptoms, with assessment and treatment being complicated and often unsatisfactory. A large potential for misunderstandings between clinicians and traumatized individuals is not only because of a language barrier; very little is known about the concepts of illness and treatment expectations in these patients. We performed semistructured interviews with 13 traumatized migrants, focusing on their concepts of illness and expectations concerning medical treatment. An analysis of the recorded and transcribed statements revealed that most participants had no clear or defined expectations concerning appropriate treatment. The patients knew very little about psychotherapy, and usually had negative prejudices. Nevertheless, participants firmly believed that medical treatment would help them and considered their current suffering to be the result of a multitude of stressors impacting their lives over long periods of time. The patients did not identify single traumatic events as the causes of their complaints. The prevailing concepts of illness among traumatized migrants can be characterized as multifactorial and psychosocial.


Lysyl oxidase activity in the ocular tissues and the role of LOX in proliferative diabetic retinopathy and rhegmatogenous retinal detachment.
Lysyl oxidase (LOX) cross-links the side chain of collagen and elastin and thereby contributes to extracellular matrix (ECM) integrity. ECM remodeling is seen in various ocular diseases. Until now, there have been no reports on the LOX enzyme's activity in ocular tissues. The purpose of this study was to estimate LOX activity and expression in human donor ocular tissues and to measure the specific activity of LOX in the vitreous of proliferative diabetic retinopathy (PDR) and rhegmatogenous retinal detachment (RRD). Human donor eyeballs obtained from an eye bank were used to study tissue distribution of LOX. Human vitreous specimens were obtained during vitreoretinal surgery from PDR (n = 16) and RRD (n = 10). LOX activity was estimated by N-acetyl-3,7-dihydroxyphenoxazine assay, immunohistochemistry, and real-time polymerase chain reaction (RT-PCR). Matrix metalloprotease (MMP)-2 and -9 were quantified in the vitreous by sandwich enzyme-linked immunosorbent assay (ELISA). The specific activity of LOX in ocular tissues was on the order of vitreous, iris ciliary body, lens, choroid RPE, and retina, which were comparable by mRNA expression and immunolocalization. The vitreous level of LOX activity decreased significantly in PDR and RRD, with an increase in total MMP-2 and -9 levels compared with normal donor vitreous. LOX activity showed a statistically significant decrease in the vitreous of PDR and RRD relative to control specimens. This effect can contribute to the inadequate collagen cross-linking that causes the ECM changes that occur in these diseases.


Imaging CAR T Cell Trafficking with eDHFR as a PET Reporter Gene.
Cell-based therapeutics have considerable promise across diverse medical specialties; however, reliable human imaging of the distribution and trafficking of genetically engineered cells remains a challenge. We developed positron emission tomography (PET) probes based on the small-molecule antibiotic trimethoprim (TMP) that can be used to image the expression of the Escherichia coli dihydrofolate reductase enzyme (eDHFR) and tested the ability of [18F]-TMP, a fluorine-18 probe, to image primary human chimeric antigen receptor (CAR) T cells expressing the PET reporter gene eDHFR, yellow fluorescent protein (YFP), and Renilla luciferase (rLuc). Engineered T cells showed an approximately 50-fold increased bioluminescent imaging signal and 10-fold increased [18F]-TMP uptake compared to controls in vitro. eDHFR-expressing anti-GD2 CAR T cells were then injected into mice bearing control GD2- and GD2+ tumors. PET/computed tomography (CT) images acquired on days 7 and 13 demonstrated early residency of CAR T cells in the spleen followed by on-target redistribution to the GD2+ tumors. This was corroborated by autoradiography and anti-human CD8 immunohistochemistry. We found a high sensitivity of detection for identifying tumor-infiltrating CD8 CAR T cells, ∼11,000 cells per mm3. These data suggest that the [18F]-TMP/eDHFR PET pair offers important advantages that could better allow investigators to monitor immune cell trafficking to tumors in patients.


Greenhouse Gas and Air Pollutant Emissions from Composting.
Composting can divert organic waste from landfills, reduce landfill methane emissions, and recycle nutrients back to soils. However, the composting process is also a source of greenhouse gas and air pollutant emissions. Researchers, regulators, and policy decision-makers all rely on emissions estimates to develop local emissions inventories and weigh competing waste diversion options, yet reported emission factors are difficult to interpret and highly variable. This review explores the impacts of waste characteristics, pretreatment processes, and composting conditions on CO2, CH4, N2O, NH3, and VOC emissions by critically reviewing and analyzing 388 emission factors from 46 studies. The values reported to date suggest that CH4 is the single largest contributor to 100-year global warming potential (GWP100) for yard waste composting, comprising approximately 80% of the total GWP100. For nitrogen-rich wastes including manure, mixed municipal organic waste, and wastewater treatment sludge, N2O is the largest contributor to GWP100, accounting for half to as much as 90% of the total GWP100. If waste is anaerobically digested prior to composting, N2O, NH3, and VOC emissions tend to decrease relative to composting the untreated waste. Effective pile management and aeration are key to minimizing CH4 emissions. However, forced aeration can increase NH3 emissions in some cases.


The frog skin host-defense peptide frenatin 2.1S enhances recruitment, activation and tumoricidal capacity of NK cells.
Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity. A single injection of frenatin 2.1S (100μg) in BALB/c mice increased the presence of peritoneal CD11c+ dendritic cells and CD3+ T cells 24h after administration and there was a significant increase in the number of IL-17 and CXCR3 expressing inflammatory T cells. Frenatin 2.1S treatment also increased the number of TNF-α expressing F4/80+ proinflammatory M1 macrophages. The most striking finding of the study is the marked increase of the number of peritoneal natural killer (NK) cells following frenatin 2.1S injection. Further, frenatin 2.1S administration led to activation of NK cells as evaluated by increased expression of NKG2D, FasL, CD69 and CD107a. The increased ratio of interferon-γ vs. IL-10 producing NK cells is further indication of the proinflammatory action of frenatin 2.1S. Peptide treatment enhanced the tumoricidal action of peritoneal NK cells on 4T1 mouse mammary carcinoma cells as revealed by the real-time automated monitoring of cell status. Our data demonstrate that frenatin 2.1S promotes activation and cytotoxic capacity of NK cells and should be regarded as a candidate for antitumor immunotherapy.


Anti-amyloid activity of neprilysin in plaque-bearing mouse models of Alzheimer's disease.
Abnormally high concentrations of beta-amyloid peptide (Abeta) and amyloid plaque formation in Alzheimer's disease (AD) may be caused either by increased generation or by decreased degradation of Abeta. Therefore, activation of mechanisms that lower brain Abeta levels is considered valuable for AD therapy. Neuronal upregulation of neprilysin (NEP) in young transgenic mice expressing the AD-causing amyloid precursor protein mutations (SwAPP) led to reduction of brain Abeta levels and delayed Abeta plaque deposition. In contrast, a comparable increase of brain NEP levels in aged SwAPP mice with pre-existing plaque pathology did not result in a significant reduction of plaque pathology. Therefore, we suggest that the potential of NEP for AD therapy is age-dependent and most effective early in the course of AD pathophysiology.


Highly sensitive hydrogen sensor based on graphite-InP or graphite-GaN Schottky barrier with electrophoretically deposited Pd nanoparticles.
Depositions on surfaces of semiconductor wafers of InP and GaN were performed from isooctane colloid solutions of palladium (Pd) nanoparticles (NPs) in AOT reverse micelles. Pd NPs in evaporated colloid and in layers deposited electrophoretically were monitored by SEM. Diodes were prepared by making Schottky contacts with colloidal graphite on semiconductor surfaces previously deposited with Pd NPs and ohmic contacts on blank surfaces. Forward and reverse current-voltage characteristics of the diodes showed high rectification ratio and high Schottky barrier heights, giving evidence of very small Fermi level pinning. A large increase of current was observed after exposing diodes to flow of gas blend hydrogen in nitrogen. Current change ratio about 700,000 with 0.1% hydrogen blend was achieved, which is more than two orders-of-magnitude improvement over the best result reported previously. Hydrogen detection limit of the diodes was estimated at 1 ppm H2/N2. The diodes, besides this extremely high sensitivity, have been temporally stable and of inexpensive production. Relatively more expensive GaN diodes have potential for functionality at high temperatures.


Understanding the Reactivity of Layered Transition-Metal Sulfides: A Single Electronic Descriptor for Structure and Adsorption.
Density functional theory is used to investigate the adsorption and structural properties of layered transition-metal sulfide (TMS) catalysts. We considered both the (101̅0) M-edge and (1̅010) S-edge terminations for a wide range of pure and doped TMSs, determined their sulfur coverage under realistic operating conditions (i.e, steady-state structures), and calculated an extensive set of chemisorption energies for several important reactions. On the basis of these results, we show that the d-band center, εd, of the edge-most metal site at 0 ML sulfur coverage is a general electronic descriptor for both structure and adsorption energies, which are known to describe catalytic activity. A negative linear correlation between adsorbate-S binding and S-metal binding allows εd to describe the adsorption of species on both metal and sulfur sites. Our results provide a significant simplification in the understanding of structure-activity relationships in TMSs and provides guidelines for the rational design and large-scale screening of these catalysts for various processes.


Green tea and cancer prevention.
Extracts of green tea and green tea polyphenols have exhibited inhibitory effects against the formation and development of tumors at different organ sites in animals. These include animal models for skin, lung, oral cavity, esophagus, stomach, intestine, colon, liver, pancreas, bladder, mammary gland, and prostate cancers. In addition to suppressing cell proliferation, promoting apoptosis, and modulating signaling transduction, green tea polyphenols, especially (-)-epigallocatechin-3-gallate, also inhibit cell invasion, angiogenesis, and metastasis. This article reviews data on the cancer preventive activities of green tea polyphenols, possible mechanisms involved, and the relationship between green tea consumption and human cancer risk.


Hotspot or blind spot? Historical perspectives on surveillance and response to epidemics in the Central African Republic.
The Central African Republic (CAR), a site of recurrent disease emergence, developed a noteworthy epidemiological surveillance system from the colonial period, but its health measures have remained among the world's lowest. To understand this disparity between surveillance and public health, we examined selected moments in its history of surveillance and changing relations with public health structures. We conducted archival research in CAR and French archives and 18 semi-structured interviews with key researchers working in CAR. We find long-term continuities in privileging surveillance over the health system and population health, making the CAR a "hotspot" for emerging diseases and a "blind spot" of primary health care. From the colonial period, the country attracted considerable support for surveillance, without concomitant investment in public health system. Political disputes and financial constraints have obscured real primary care needs on the ground. As both a hotspot and a blind spot for global health, the CAR signals the need to reorient health interventions to address the long-term health of Central African people.


An application of the SMS method for imaging designs.
The Simultaneous Multiple Surface (SMS) method in planar geometry (2D) is applied to imaging designs, generating lenses that compare well with aplanatic designs. When the merit function utilizes image quality over the entire field (not just paraxial), the SMS strategy is superior. In fact, the traditional aplanatic approach is actually a particular case of the SMS strategy.


Scientific guidance on soil phototransformation products in groundwater - consideration, parameterisation and simulation in the exposure assessment of plant protection products.
This Guidance Document gives recommendations how to consider transformation products from soil photolysis ('phototransformation products') when modelling the predicted environmental concentrations in groundwater. It describes possible parameterisations of the photolytic pathway (i.e. the photolytic half-life and the corresponding reference irradiation) in a tiered approach using the FOCUS-PELMO model. Following the recommendations of the EFSA guidance (2014), separate half-lives can be derived for the surface processes (kfast) and the biodegradation in the soil matrix (kslow) from field dissipation studies by using biphasic models. From field dissipation studies evaluated with biphasic kinetics, the kfast value can be considered representative for the photolytic degradation on soil surface for non-volatile substances. This value should be determined after a time-step normalisation according to irradiance data for the location and period of the field trial, to a reference irradiance of 100 W m-2. In case irradiance values are not available in the study, these values can be derived from databases such as AGRI4CAST or NASA, freely available in the Internet.


Association of Clinical Factors With a Major Pathologic Response Following Preoperative Therapy for Pancreatic Ductal Adenocarcinoma.
We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined. To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma. Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015. Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%). Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression. Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009). Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.


Incidence and Severity of Concussions Among Young Soccer Players Based on Age, Sex, and Player Position.
Previously studied risk factors for sports-related concussion in soccer players include sex, age, and player position. However, prior studies were limited in number, they reported conflicting results, and most did not assess initial concussion severity. The purpose of this study was to conduct an in-depth analysis of soccer players across key demographic groups (sex, age, position) for both concussion incidence and severity. It was hypothesized that concussion incidence and severity would be higher among male players, players aged ≥17 years, and goalkeepers. Cohort study; Level of evidence, 3. The authors analyzed baseline and postinjury ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing) scores for athletes aged 12 to 22 years between July 2009 and June 2019. Players were assigned to an age group based on when they had their most recent baseline test. Concussion incidence and concussion severity index were compared using t tests and multivariate logistic regression. For 1189 individuals who reported soccer as their primary sport, 1032 contributed 1754 baseline ImPACT tests (some individuals had multiple baseline tests), whereas 445 individuals were suspected of sustaining a concussion and then referred for a postinjury 1 test. Of these players, 254 (24.6%) had both a baseline and a postinjury test and were analyzed for concussion severity. Linear regression showed that forwards had a lower incidence of ImPACT-proxied concussions than goalkeepers had (P = .008). Female players had a significantly higher incidence of ImPACT concussions compared with male players (mean, 0.07 [female] vs 0.04 [male] concussions per person-year; P = .05). Players in the ≥17-year age group had a higher incidence of ImPACT concussions than players in the 15- to 16-year age group (P = .04), although the 15- to 16-year age group had more severe concussions than the ≥17-year age group (mean severity index, 2.91 [age 15-16 years] vs 1.73 [age ≥17 years]; P = .001). Female soccer players experienced a higher incidence of concussion than did male players, and goalkeepers experienced a greater incidence of ImPACT concussions than did forwards. Players of both sexes and all positions in the 15- to 16-year age group showed increased initial concussion severity compared with the ≥17-year age group, despite a lower comparative incidence of ImPACT concussions. Further study is needed to understand whether sex and player position affect concussion severity.


What are the important factors in health-related quality of life for people with aphasia? A systematic review.
To determine factors associated with or predictive of poor health-related quality of life (HRQL) in people with aphasia poststroke. Better understanding of these factors can allow better targeting of rehabilitation programs. Electronic databases, covering medical (eg, Medline, Excerpta Medica Database, Evidence-Based Medicine Reviews, Cumulative Index to Nursing and Allied Health Literature, Ovid, Allied and Complementary Medicine Database) and social sciences (eg, PsycINFO) were searched and key experts were approached. Studies including specific information on the HRQL of people with aphasia poststroke using validated HRQL measures or established ways of analyzing qualitative data were included. Two reviewers independently screened studies against the eligibility criteria. This was undertaken independently by 2 reviewers. Discrepancies were resolved by consensus. Quantitative studies were assessed for quality with Counsell and Dennis' critical appraisal tool for systematic review of prognostic models in acute stroke; qualitative studies with the Critical Appraisal Skills Program tool for qualitative research. Fourteen research reports met the eligibility criteria. Because of their high heterogeneity, the data synthesis was narrative. The evidence is not strong enough to determine the main predictors of HRQL in people with aphasia. Still, emotional distress/depression, severity of aphasia and communication disability, other medical problems, activity limitations, and aspects of social network and support were important factors. Emotional distress, aphasia severity, communication and activity limitations, other medical problems, and social factors affect HRQL. Stroke HRQL studies need to include people with aphasia and report separately on them, in order to determine the main predictors of their HRQL and to identify what interventions can best address them.


Purge-and-membrane mass spectrometry, a screening method for analysis of VOCs from soil samples.
Purge-and-membrane mass spectrometry (PAM-MS) is a combination of dynamic headspace sampling and membrane extraction. A new and simple purge-and-membrane sampler is introduced and its basic testing results for the analysis of VOCs in soil samples are reported. Soil moisture had no effect on desorption times in the case of sand, but the desorption times increased when the content of organic matter in the soil sample (garden soil) increased. The longest desorption times were measured with dry garden soil samples. For both types of samples, minor differences in desorption peak areas were observed between 10 and 20% moisture. Detection limits of the VOCs varied in the range 2-150 microg/kg, depending on the soil type. Good linearity (correlation coefficient > 0.990) was observed in the range 0.5-50 mg/kg. Aging of the spiked soil samples had only a slight effect on desorption peak areas for samples stored at 5 degrees C up to two weeks, but after six months of storing, differences were observed between dry sand and moistened garden soil. In both cases, peak areas were diminished. On average, 46% of compounds could be desorbed from the aged sand and 86% from the aged garden soil. The modified vapor fortification method was used in preparing standard soil samples, which were analyzed by static headspace gas chromatography (HSGC) and PAM-MS. Some authentic soil samples were also analyzed using both of these techniques. Many of the vapor fortification samples and the authentic samples were also analyzed in another laboratory by HSGC. The agreement between the methods and the laboratories was generally good.


High rates of unprotected anal intercourse with regular and casual partners and associated risk factors in a sample of ethnic Malay men who have sex with men (MSM) in Penang, Malaysia.
To assess the prevalence of unprotected anal intercourse (UAI) and its correlates among ethnic Malay men who have sex with men (MSM). In 2010, a convenience sample of 350 MSM in Penang were recruited to participate in an anonymous, computerised survey with rapid HIV testing. Participants who were not of Malay ethnicity (n=44) or who did not report sex with another man in the previous 12 months (n=22) were excluded, resulting in 284 participants in the final analysis. Correlates of UAI were examined separately for regular and casual partnerships using bivariate and multivariate logistic regression. Four men (1.9%) tested HIV positive. In the past 12 months, 64.7% of participants had regular sexual partners, 77.1% had casual sexual partners and 41.9% had both. Most participants (83.1%) reported UAI, which was more common in regular partnerships. Over two-thirds of participants had never been tested for HIV. In multivariate analysis, agreement about sexual risk reduction practices was associated with a reduction in UAI with regular partners (adjusted OR (AOR)=0.14, 95% CI 0.05 to 0.40). Reporting difficulty in using condoms was associated with an increase in UAI with casual partners (AOR=9.07, 95% CI 3.35 to 24.5), and any exposure to HIV prevention was associated with a decrease in UAI with casual partners (AOR=0.22, 95% CI 0.09 to 0.54). Despite highly prevalent HIV risk behaviours, HIV seropositivity and prior HIV testing were low. Increasing sexual negotiation skills and access to HIV testing and other prevention services may improve future prevention efforts.


18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels.
To compare the effects of two stereoisomeric forms of glycyrrhetinic acid on different components of Na(+) current, HERG and Kv1.5 channel currents. Wild-type (WT) and long QT syndrome type 3 (LQT-3) mutant ΔKPQ Nav1.5 channels, as well as HERG and Kv1.5 channels were expressed in Xenopus oocytes. In addition, isolated human atrial myocytes were used. Two-microelectrode voltage-clamp technique was used to record the voltage-activated currents. Superfusion of 18β-glycyrrhetinic acid (18β-GA, 1-100 μmol/L) blocked both the peak current (I(Na,P)) and late current (I(Na,L)) generated by WT and ΔKPQ Nav1.5 channels in a concentration-dependent manner, while 18α-glycyrrhetinic acid (18α-GA) at the same concentrations had no effects. 18β-GA preferentially blocked I(Na,L) (IC(50)=37.2 ± 14.4 μmol/L) to I(Na,P) (IC(50)=100.4 ± 11.2 μmol/L) generated by ΔKPQ Nav1.5 channels. In human atrial myocytes, 18β-GA (30 μmol/L) inhibited 47% of I(Na,P) and 87% of I(Na,L) induced by Anemonia sulcata toxin (ATX-II, 30 nmol/L). Superfusion of 18β-GA (100 μmol/L) had no effects on HERG and Kv1.5 channel currents. 18β-GA preferentially blocked the late Na current without affecting HERG and Kv1.5 channels.


Early Supported Discharge by Caregiver-Mediated Exercises and e-Health Support After Stroke: A Proof-of-Concept Trial.
This proof-of-concept trial investigated the effects of an 8-week program of caregiver-mediated exercises commenced in hospital combined with tele-rehabilitation services on patient self-reported mobility and caregiver burden. Sixty-three hospitalized stroke patients (mean age 68.7, 64% female) were randomly allocated to an 8-week caregiver-mediated exercises program with e-health support or usual care. Primary outcome was the Stroke Impact Scale mobility domain. Secondary outcomes included length of stay, other Stroke Impact Scale domains, readmissions, motor impairment, strength, walking ability, balance, mobility, (extended) activities of daily living, psychosocial functioning, self-efficacy, quality of life, and fatigue. Additionally, caregiver's self-reported fatigue, symptoms of anxiety, self-efficacy, and strain were assessed. Assessments were completed at baseline and at 8 and 12 weeks. Intention-to-treat analysis showed no between-group difference in Stroke Impact Scale mobility (P=0.6); however, carers reported less fatigue (4.6, confidence interval [CI] 95% 0.3-8.8; P=0.04) and higher self-efficacy (-3.3, CI 95% -5.7 to -0.9; P=0.01) at week 12. Per-protocol analysis, examining those who were discharged home with tele-rehabilitation demonstrated a trend toward improved mobility (-9.8, CI 95% -20.1 to 0.4; P=0.06), significantly improved extended activities of daily living scores at week 8 (-3.6, CI 95% -6.3 to -0.8; P=0.01) and week 12 (3.0, CI 95% -5.8 to -0.3; P=0.03), a 9-day shorter length of stay (P=0.046), and fewer readmissions over 12 months (P<0.05). Caregiver-mediated exercises supported by tele-rehabilitation show promise to augment intensity of practice, resulting in improved patient-extended activities of daily living, reduced length of stay with fewer readmissions post stroke, and reduced levels of caregiver fatigue with increased feelings of self-efficacy. The current findings justify a larger definite phase III randomized controlled trial. URL: http://www.anzctr.org.au. Unique identifier: ACTRN12613000779774.


Impact metamorphism of lunar surface materials.
Silicate grains from Tranquillity Base have shock-induced features ranging from internal fragmentation through complete disruption of the lattice to thermal melting. Half the crystalline grains with diameters less than 125 micrometers have features of shock equivalent to those produced in the laboratory at pressures greater than about 40 kilobars. One quarter have features indicative of pressures greater than 90 kilobars. These properties together with great quantities of melt glass and aluminum-26 in the fine-grained material are indicative of repeated shock-loading by meteoritic bombardment over long periods of time.


Return to work after stroke: Important aspects shared and contrasted by five stakeholder groups.
Poor co-operation between the various stakeholders underscores the need for reviewing important factors that facilitate return to work (RTW) after stroke. To explore and describe important aspects expressed by Swedish stakeholders in the RTW process for persons post stroke and to contrast the stakeholders' aspects exploring different perspectives that may influence optimal RTW. Data from seven focus group interviews with the stakeholders were analyzed using qualitative content analysis. Three main categories made up the findings; the prolonged RTW process, the need for extended knowledge, and the assessment of work ability in the RTW process. Despite the stakeholders' agreement on these important aspects, they presented divergent views of the categories, representing their diverse agendas. A stroke coordinator may remediate the stakeholders' divergent perspectives. The coordinator should be versed in stroke specific knowledge and in a person centered approach to inform the decision process regarding RTW, while finding optimal solutions within regulatory boundary conditions. A coordinator could increase collaboration of the various stakeholders, provide support and coordinate services for the client with stroke and the employer throughout the whole process facilitating RTW after stroke. Future studies are needed to confirm this proposal.


CD81 expressed on human thymocytes mediates integrin activation and interleukin 2-dependent proliferation.
Lymphocyte recognition of antigen by the antigen-specific T cell receptor (TCR) and coreceptor complexes rapidly alters the cell's adhesive properties facilitating high avidity cell-ligand interactions necessary for lymphocyte development and function. Here, we report the expression of CD81 (target of antiproliferative antigen [TAPA]-1) on human thymocytes and the physical association of CD81 with CD4 and CD8 T cell coreceptors. Antibody ligation of CD81 on thymocytes promotes the rapid induction of integrin-mediated cell-cell adhesion via lymphocyte function-associated molecule-1 (LFA-1). Cross-linking CD81 is also shown to be costimulatory with signaling through the TCR/CD3 complex inducing interleukin 2-dependent thymocyte proliferation. These data suggest that a CD81-mediated pathway in thymocytes is involved in the regulation of both cell adhesion and activation.


Impact of P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) gene dosage on plasma pharmacokinetics and brain accumulation of dasatinib, sorafenib, and sunitinib.
Low brain accumulation of anticancer drugs due to efflux transporters may limit chemotherapeutic efficacy, necessitating a better understanding of the underlying mechanisms. P-glycoprotein (Abcb1a/1b) and breast cancer resistance protein (Abcg2) combination knockout mice often display disproportionately increased brain accumulation of shared drug substrates compared with single transporter knockout mice. Recently developed pharmacokinetic models could explain this phenomenon. To experimentally test these models and their wider relevance for tyrosine kinase inhibitors and other drugs, we selected dasatinib, sorafenib, and sunitinib because of their divergent oral availability and brain accumulation profiles: the brain accumulation of dasatinib is mainly restricted by Abcb1, that of sorafenib mainly by Abcg2, and that of sunitinib equally by Abcb1 and Abcg2. We analyzed the effect of halving the efflux activity of these transporters at the blood-brain barrier by generating heterozygous Abcb1a/1b;Abcg2 knockout mice and testing the plasma and brain levels of the drugs after oral administration at 10 mg/kg. Real-time reverse transcription-polymerase chain reaction analysis confirmed the ∼2-fold decreased expression of both transporters in brain. Interestingly, whereas complete knockout of the transporters caused 24- to 36-fold increases in brain accumulation of the drugs, the heterozygous mice only displayed 1.6- to 1.9-fold increases of brain accumulation relative to wild-type mice. These results are well in line with the predictions of the pharmacokinetic models and provide strong support for their validity for a wider range of drugs. Moreover, retrospective analysis of fetal accumulation of drugs across the placenta in Abcb1a/1b heterozygous knockout pups suggests that these models equally apply to the maternal-fetal barrier.


Ligand-induced folding of a two-component signaling receiver domain.
To survive and adapt to environmental changes, bacteria commonly use two-component signaling systems. Minimally, these pathways use histidine kinases (HKs) to detect environmental signals, harnessing these to control phosphorylation levels of receiver (REC) domains of downstream response regulators that convert this signal into physiological responses. Studies of several prototypical REC domains suggest that phosphorylation shifts these proteins between inactive and active structures that are globally similar and well-folded. However, it is unclear how globally these findings hold within REC domains in general, particularly when they are considered within full-length proteins. Here, we present EL_LovR, a full-length REC-only protein that is phosphorylated in response to blue light in the marine α-proteobacterium, Erythrobacter litoralis HTCC2594. Notably, EL_LovR is similar to comparable REC-only proteins used in bacterial general stress responses, where genetic evidence suggests that their potent phosphatase activity is important to shut off such systems. Size exclusion chromatography, light scattering, and solution NMR experiments show that EL_LovR is monomeric and unfolded in solution under conditions routinely used for other REC structure determinations. Addition of Mg(2+) and phosphorylation induce progressively greater degrees of tertiary structure stabilization, with the solution structure of the fully activated EL_LovR adopting the canonical receiver domain fold. Parallel functional assays show that EL_LovR has a fast dephosphorylation rate, consistent with its proposed function as a phosphate sink that depletes the HK phosphoryl group, promoting the phosphatase activity of this enzyme. Our findings demonstrate that EL_LovR undergoes substantial ligand-dependent conformational changes that have not been reported for other RRs, expanding the scope of conformational changes and regulation used by REC domains, critical components of bacterial signaling systems.


The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance.
Meta-analyses on impact of isoniazid-resistant tuberculosis informed the World Health Organization recommendation of a levofloxacin-strengthened rifampicin-based regimen. We estimated the effect of initial rifampicin resistance (Rr) and/or isoniazid resistance (Hr) on treatment failure or relapse. We also determined the frequency of missed initial and acquired Rr to estimate the impact of true Hr. Retrospective analysis of 7291 treatment episodes with known initial isoniazid and rifampicin status obtained from individual patient databases maintained by the Damien Foundation Bangladesh over 20 years. Drug susceptibility test results were confirmed by the programme's designated supra-national tuberculosis laboratory. To detect missed Rr among isolates routinely classified as Hr, rpoB gene sequencing was done randomly and on a sample selected for suspected missed Rr. Initial Hr caused a large recurrence excess after the 8-month regimen for new cases (rifampicin for two months), but had little impact on rifampicin-throughout regimens: (6 months, new cases; 3.8%; OR 0.8, 95%CI:0.3,2.8; 8 months, retreatment cases: 7.3%, OR 1.8; 95%CI:1.3,2.6). Rr was missed in 7.6% of randomly selected "Hr" strains. Acquired Rr was frequent among recurrences on rifampicin-throughout regimens, particularly after the retreatment regimen (31.9%). It was higher in mono-Hr (29.3%; aOR 3.5, 95%CI:1.5,8.5) and poly-Hr (53.3%; aOR 10.2, 95%CI 4.4,23.7) than in susceptible tuberculosis, but virtually absent after the 8-month new case regimen. Comparing Bangladesh (low Rr prevalence) with a high Rr prevalence setting,true Hr corrected for missed Rr caused only 2-3 treatment failures per 1000 TB cases (of whom 27% were retreatments) in both. Our analysis reveals a non-negligible extent of misclassifying as isoniazid resistance of what is actually missed multidrug-resistant tuberculosis. Recommending for such cases a "strengthened" regimen containing a fluoroquinolone provokes a direct route to extensive resistance while offering little benefit against the minor role of true Hr tuberculosis in rifampicin-throughout first-line regimen.


Plant demographic responses to mycorrhizal symbiosis in tallgrass prairie.
The effects of mycorrhizal symbiosis on seedling emergence, flowering and densities of several grasses and forbs were assessed in native tallgrass prairie and in sown garden populations at the Konza Prairie in northeastern Kansas. Mycorrhizal activity was experimentally suppressed with the fungicide benomyl. Flowering and stem densities of the cool-season grass, Dichanthelium oligosanthes, sedges (Carex spp.), and the forb Aster ericoides were higher in non-mycorrhizal (benomyl-treated) than in mycorrhizal plots and the magnitude of these differences was significantly affected by burning. Mycorrhizae significantly enhanced flowering of the warmseason grasses Andropogon gerardii and Sorghastrum nutans in burned prairie, but not in unburned sites. These patterns suggest that mycorrhizal effects on the dynamics of cool-season graminoid and forb populations are likely to be mediated indirectly through effects of the symbiosis on the competitive dominance of their neighbors. Seedling emergence rates of the cool-season C3 grasses Elymus canadensis and Koeleria cristata were significantly reduced in the benomyl-treated plots, whereas benomyl treatment had no significant effect on seedling emergence of the warm-season C4 grasses A. gerardii and Panicum virgatum. The forbs showed variable responses. Seedling emergence of Liatris aspera was greater under mycorrhizal conditions, but that of Dalea purpurea was unaffected by mycorrhizal treatment. These results show that effects of mycorrhizal symbiosis on the population dynamics of co-occurring prairie plants vary significantly both among species and among different life history stages within species. The results also indicate that mycorrhizas and fire interact to influence competitive interactions and demographic patterns of tallgrass prairie plant populations.


GANGLION CELL LAYER THICKNESS AND VISUAL IMPROVEMENT AFTER EPIRETINAL MEMBRANE SURGERY.
To evaluate the possible prognostic value of preoperative individual retinal layer thicknesses measured by an automated algorithm from spectral domain optical coherence tomography and visual acuity or improvement after epiretinal membrane surgery. Data from 76 eyes with idiopathic epiretinal membrane that underwent pars plana vitrectomy for idiopathic epiretinal membrane removal were analyzed. The preoperative thicknesses of the ganglion cell layer, inner plexiform layer, and other layers were measured using the Iowa Reference Algorithm. Each retinal layer thickness and its ratio of the central foveal thickness were compared between eyes with (Group 1) or without (Group 2) 2 or more Snellen lines of visual improvement at 3, 6, and 12 months after surgery. Higher mean central foveal thickness/ganglion cell layer ratio and symptom duration of ≤1 year were significantly more common in Group 1 (P = 0.03 and 0.04, respectively). After adjusting for age and symptom duration, lens status, and preoperative visual acuity, higher central foveal thickness/ganglion cell layer ratio was associated with ≥2 lines of visual improvement after surgery (odds ratio: 6.57, 95% confidence interval: 1.29-33.40). The preoperative inner retinal layer changes may have a role independent of outer retinal layer parameters in the visual prognosis after epiretinal membrane peeling.


RNase-H-mediated silencing in the CNS proves predictably nontrivial.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily affecting motor neurons. Recently,1 Miller et al. presented phase 3 data for the RNase-H-recruiting antisense oligonucleotide (ASO) targeting superoxide dismutase 1 (SOD1) in ALS, which represents a step forward in the deployment of ASO therapeutics against CNS targets.


Clinical Features of Patients with Concomitant Parkinson's Disease and Progressive Supranuclear Palsy Pathology.
The pathologic changes of Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) have been reported to coexist, but whether PSP pathology modifies the clinical course of those individuals is unknown. The aim of this study was to determine whether clinical features of pathologically confirmed PD subjects with concomitant PSP pathology differ from those with PD alone. Subjects enrolled in the Arizona Study of Aging and Neurodegenerative Disorders had annual movement and cognitive evaluations from enrollment until death/autopsy. All cases between 1997 and 2014 with a final clinicopathological diagnosis of PD with or without PSP at autopsy were analyzed. Overall, 12 of the 125 cases with pathologically confirmed PD had coexisting PSP pathology (9.6%). Those with PD-PSP had more-prominent postural instability, body bradykinesia, difficulty arising from a chair, and falls; asymmetric onset was less common in this group. Downgaze palsy and square wave jerks were infrequent in both groups. Gender, age at death, disease duration, rate of dementia, and presence of rest tremor did not differ between groups. Only 58% of subjects in the PD-PSP group were correctly given a final diagnosis in life of PD, compared to 91% of those with PD alone. The combination of PD and PSP pathology yields a heterogeneous clinical syndrome that often resembles PD, but may be more symmetric at onset and have more-prominent postural instability and falls. Our observations suggest that coexisting PSP pathology may be an important factor contributing to the clinical heterogeneity in PD and a potential confounder in diagnosis.


Adaptive frequency-domain equalization for the transmission of the fundamental mode in a few-mode fiber.
We propose and experimentally demonstrate single-carrier adaptive frequency-domain equalization (SC-FDE) to mitigate multipath interference (MPI) for the transmission of the fundamental mode in a few-mode fiber. The FDE approach reduces computational complexity significantly compared to the time-domain equalization (TDE) approach while maintaining the same performance. Both FDE and TDE methods are evaluated by simulating long-haul fundamental-mode transmission using a few-mode fiber. For the fundamental mode operation, the required tap length of the equalizer depends on the differential mode group delay (DMGD) of a single span rather than DMGD of the entire link.


Comparison of patient outcomes in Magnet® and non-Magnet hospitals.
: This study compared patient outcomes and staffing in Magnet® and non-Magnet hospitals. : The pursuit of Magnet designation is a highly regarded program for improving staff and patient outcomes. Research has confirmed that Magnet hospitals provide positive work environments for nurses. Research related to patient outcomes in Magnet hospitals is scarce, and results vary. : The University Health Systems Consortium provided the clinical and operational databases for the study. Using bivariate and multivariate analyses, a comparison of patient outcomes and nurse staffing in general units and ICUs of Magnet and non-Magnet hospitals was studied. : Non-Magnet hospitals had better patient outcomes than Magnet hospitals. Magnet hospitals had slightly better outcomes for pressure ulcers, but infections, postoperative sepsis, and postoperative metabolic derangement outcomes were worse in Magnet hospitals. Magnet hospitals also had lower staffing numbers. : Magnet hospitals in this study had less total staff and a lower RN skill mix compared with non-Magnet hospitals, which contributed to the outcomes.


Isolation of potent human Fab fragments against a novel highly immunogenic region on human muscle acetylcholine receptor which protect the receptor from myasthenic autoantibodies.
In the autoimmune disease myasthenia gravis (MG), antibodies against the muscle nicotinic acetylcholine receptor (AChR) cause loss of functional AChR in the neuromuscular junction. To isolate AChR-specific human antibody fragments (Fab), a phage-display library was constructed from an MG patient's thymic B lymphocytes. The first Fab isolated had a low affinity for human AChR, but two sequential antibody chain shufflings using the MG donor heavy and light chain gene repertoires resulted in isolating two new Fab with an approximately 30-fold higher binding ability. The selected Fab contained extensively mutated heavy and light chains and probably represent intraclonal variants of a common progenitor having diverged in vivo by somatic hypermutation. Interestingly, the isolated Fab bound to an extracellular highly immunogenic region located either on an alpha-subunit site affected by the gamma/epsilon-subunits or on the interface between alpha- and gamma/epsilon-subunits. This region is not the previously described "main immunogenic region" (MIR), although it seems to be close to it, as one improved Fab and an anti-MIR mAb competed for AChR binding with distinctly different subpopulations of MG sera. Furthermore, this Fab protected surface AChR in cell cultures against MG autoantibody-induced antigenic modulation, suggesting a potential therapeutic use in MG, especially in combination with a human anti-MIR Fab.


Molecularly imprinted polymers with novel functional monomer for selective solid-phase extraction of gastrodin from the aqueous extract of Gastrodia elata.
Molecular imprinted polymers (MIPs) with high selectivity and affinity to gastrodin in water were designed using allyl 2,3,4,6-tetra-O-acetyl-glucopyranoside (TAGL) and 1,2,3,4,5-pentafluoro-6-vinylbenzene (PFVB) as novel functional monomers. Binding characterization of pre-polymerization complexes was researched by nuclear magnetic resonance (NMR) and the MIPs were characterized by scanning electron microscopy (SEM). The properties involving adsorption isotherm, adsorption kinetics and selective recognition capacity were evaluated. The MIPs/TAGL exhibited good site accessibility in which it only took 30min to achieve adsorption equilibrium and highly selective recognition for the template. Furthermore, the performance of the MIPs/TAGL as solid phase extraction material was investigated in detail and hot water at 50°C served as the eluting solvent. Pure gastrodin with the recovery of 76.6% was obtained from the aqueous extract of Gastrodia elata roots.


Anal acoustic reflectometry predicts the outcome of percutaneous nerve evaluation for faecal incontinence.
Sacral nerve stimulation (SNS) is effective for some patients with faecal incontinence. Before insertion of a costly implant, percutaneous nerve evaluation (PNE) is undertaken to identify patients likely to report success from SNS. The aim of this study was to determine whether variables of anal sphincter function measured by anal acoustic reflectometry (AAR) could predict the outcome of PNE for faecal incontinence. Women with faecal incontinence undergoing PNE were recruited. AAR, followed by anal manometry, was performed on the day of surgery, immediately before PNE. The outcome of PNE was determined by bowel diary results and incontinence severity score. Patients with a successful PNE outcome were compared with those with an unsuccessful outcome; logistic regression analysis was used to identify any independent predictors of success. Fifty-two patients were recruited, of whom 32 (62 per cent) had a successful PNE outcome and 20 (38 per cent) an unsuccessful outcome. The AAR variable opening pressure was significantly greater in patients who subsequently had a successful PNE result compared with the pressure in patients who did not (28 versus 17 cmH2 O; P = 0·008). No difference was seen in the manometric equivalent, maximum resting pressure. Opening pressure was an independent predictor of success with an odds ratio of 1·08 (95 per cent confidence interval 1·01 to 1·16; P = 0·018). AAR is a sensitive test of sphincter function and can identify differences between patients who respond to PNE and those who do not. Opening pressure is an independent predictor of success in PNE, and may be of value in the selection of patients for this expensive treatment option.


Effects of feeding level and NDF content of grass-clover silages on chewing activity, fecal particle size and NDF digestibility in dairy heifers.
The objective of this study was to assess effects of feed intake and NDF content of highly digestible grass-clover silage on chewing behavior, fecal particle size distribution and apparent digestibility in restrictively fed heifers. Four grass-clover silages (Lolium perenne, Trifolium pratense and Trifolium repens) were harvested in 2009 at different regrowth stages, resulting in silages with NDF contents of 312, 360, 371 and 446 g/kg dry matter (DM), respectively. Four rumen-fistulated Jersey heifers (343 ± 32 kg BW) were fed silage at 90% of ad libitum levels in a 4 × 4 Latin square design, replicated with further restricted feeding levels (50%, 60%, 70% or 80% of ad libitum) in a balanced 4 × 4 × 4 Greco-Latin square design. Eating activity was estimated from test meal observations, while rumination activity was estimated from jaw movements logged by a jaw recorder system. Total tract digestibility was estimated from chromic oxide marker and fecal spot sampling, and fecal particle size distribution in washed and freeze-dried particulate DM was determined by dry sieving (2.36, 1.0, 0.5, 0.212 and 0.106 mm, and bottom bowl). Higher NDF content of silage stimulated longer eating time per kg DM intake (P<0.001), while reduced feeding level caused a reduction in eating time per kg DM intake (P<0.001) and NDF (P<0.001). Rumination time per kg DM intake (P<0.01) increased with reduced feeding level, with less effect of feeding level at lower NDF contents (P<0.01) and more rumination with greater NDF content (P<0.01). Relative to NDF intake, rumination time increased with greater NDF content (P<0.01), at a higher rate with reduced feeding level (P<0.05). Digestibility of potentially digestible NDF (DNDF) decreased with greater NDF content (P<0.001) and increased with reduced feeding level (P<0.05). Increasing NDF content resulted in more particulate DM in feces (g/kg DM; P<0.05) and larger mean particle size (P<0.001). In conclusion, feeding heifers with grass-clover silages of decreasing NDF content increased chewing time relative to NDF intake, reduced mean fecal particle size, and increased DNDF digestibility. Restricting feeding level made heifers eat for a shorter time period while rumination and total chewing was increased, causing the ratio between eating and rumination time to decrease with lower intake of forage fiber. Particle size reduction and digestibility depended mostly on changes in NDF content, especially the indigestible NDF content.


Central adiposity in children born small and large for gestational age.
To evaluate body composition differences between children that were born small (SGA) or large for gestational age (LGA) compared with their counterparts born adequate for gestational age (AGA). Body composition was assessed in 124 healthy Caucasian children (50% girls) aged 6-10, classified according to their birth weight for gestational age as AGA, SGA and LGA. Fat mass (FM), percentage of FM, lean mass (LM), bone mineral content (BMC) and bone mineral density were measured by dual-energy X-ray absorptiometry (DXA) in the whole body and at different body regions. LM (adjusted for age and sex) and total BMC (adjusted for age, sex and weight) were both significantly higher in LGA children and lower in SGA when compared with those born AGA. After adjustments for height, LM and BMC differences between groups were not significant. In SGA children, truncal (P<0.05) and abdominal fatness (P<0.01) were higher when compared with both AGA and LGA children, after adjustments for age, sex and height. There were no differences in the percentage of total and central FM between children born LGA and AGA. During childhood, children born SGA had higher central adiposity regardless of their body size. Children born LGA seem to have a higher body size but with harmonic body composition and adequate body fat distribution. Small size for gestational age at birth could programme excess abdominal fat deposition in children, which is a major factor for the clustering of cardiovascular disease risk factors defining the metabolic syndrome.


Jejunum: The understudied meeting place of dietary lipids and the microbiota.
Although the jejunum is the main intestinal compartment responsible for lipid digestion and absorption, most of the studies assessing the impact of dietary lipids on the intestinal microbiota have been performed in the ileum, colon and faeces. This lack of interest in the jejunum is due to the much lower number of microbes present in this intestinal region and to the difficulty in accessing its lumen, which requires invasive methods. Recently, several recent publications highlighted that the whole jejunal microbiota or specific bacterial members are able to modulate lipid absorption and metabolism in enterocytes. This information reveals new strategies in the development of bacterial- and metabolite-based therapeutic interventions or nutraceutical recommendations to treat or prevent metabolic-related disorders, including obesity, cardiovascular diseases and malnutrition. This review is strictly focused on the following triad: dietary lipids, the jejunal epithelium and the jejunal microbiota. First, we will describe each member of the triad: the structure and functions of the jejunum, the composition of the jejunal microbiota, and dietary lipid handling by enterocytes and by microorganisms. Then, we will present the mechanisms leading to lipid malabsorption in small intestinal bacterial overgrowth (SIBO), a disease in which the jejunal microbiota is altered and which highlights the strong interactions among this triad. We will finally review the recent literature about the interactions among members of the triad, which should encourage research teams to further explore the mechanisms by which specific microbial strains or metabolites, alone or in concert, can mediate, control or modulate lipid absorption in the jejunum.


Grape seed proanthocyanidin inhibits inflammatory responses in hepatic stellate cells by modulating the MAPK, Akt and NF-κB signaling pathways.
In the present study, we aimed to investigate the molecular mechanisms and prophylactic effects of grape seed proanthocyanidin (GSP) on lipopolysaccharide (LPS)-stimulated human hepatic stellate cells (HSCs). Cell counting and MTT assays were used to assess cell viability in the absence or presence of GSP. Reverse transcription-quantitative PCR (RT-qPCR) was performed for several inflammation-related genes (NOD1, NOD2, TLR2, TLR4, IL-1 β, IL-6, IL-8, iNOS and COX-2). The expression of anti-inflammatory cell signaling molecules, including c-Jun N-terminal kinase (JNK), p38, extracellular signal regulated kinase (ERK), Akt, nuclear factor-κB (NF-κB), inhibitory-κBα (IκBα), iNOS and COX-2, was evaluated by western blot analysis. Finally, IL-8 levels in the culture supernatant of HSCs were measured by ELISA. Pretreatment with GSP before LPS treatment significantly suppressed the mRNA expression of pro-inflammatory cytokines such as IL-1β, IL-6 and IL-8. GSP inhibited mRNA expression of LPS-induced TLR4, NOD2 and COX-2, in addition to inhibiting the expression of iNOS. GSP also inhibited LPS-induced NF-κB activation and IκBα phosphorylation. Concomitantly, GSP dose-dependently suppressed the activation of MAP kinases (JNK, ERK and p38) and Akt in LPS-stimulated HSCs. These data suggest that GSP inhibits inflammatory responses in HSCs by inactivating the NF-κB signaling pathway via MAP kinases. Thus, GSP may be considered as a novel drug for the treatment of hepatic inflammation, infectious diseases and fibrosis.


Understanding adverse events: human factors.
(1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of "upstream" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole.


Is quality free? The relationship between cost and quality across 18 provider groups.
To learn whether the healthcare costs for patients of various care delivery systems are associated with the quality of ambulatory care received. Despite intense interest in the cost and quality of healthcare delivery in the United States, there have been relatively few studies of the relationship between those measures, and none have addressed the relationship for integrated care delivery systems. Results of a retrospective analysis of claims records for overall costs of care for enrollees of 18 care delivery systems were compared with a variety of quality measures for each system. We analyzed the yearly (1996-1998) claims records of 110,000 to 150,000 employees and dependents of member companies of an employer coalition in Minnesota that received all of their medical services from 18 care systems that had at least 1,000 employees and dependents. Overall case-mix and inflation-adjusted costs of care for enrollees of each care system were compared with 21 ambulatory care process-oriented quality indicators covering 3 chronic diseases and 5 preventive services. Regardless of whether the unit of analysis was the care system or the individual enrollee, there was no evidence of a consistent relationship between overall cost of care and quality on any measures. The little association there was tended to suggest that higher quality was provided by the lowest-cost care systems. Although additional confirmatory research is needed, this analysis of the quality-cost relationship provides some reassurance for those who question whether selecting lower-cost sources of medical care might have a negative effect on quality of care.