Small-scale forestry and carbon offset markets: An empirical study of Vermont Current Use forest landowner willingness to accept carbon credit programs.
This study investigates the preferences of small forest landowners regarding forest carbon credit programs while documenting characteristics of potentially successful frameworks. We designed hypothetical carbon credit programs with aggregated carbon offset projects and requirements of existing voluntary and compliance protocols in mind. We administered a mail survey to 992 forest landowners in Vermont's Current Use Program utilizing best-worst choice, a novel preference elicitation technique, to elicit their preferences about these programs. We found that small forest landowners see revenue as the most important factor in a carbon credit program and the duration of the program as the least important factor. Landowners reported that shorter program duration, higher revenue, and lower withdrawal penalties positively impact their willingness to accept forest carbon credit programs. Notably, our study includes carbon credit program implementer as a key program attribute, allowing us to quantify landowners' tradeoffs between non-profit, for-profit, and government organizations. Overall, we found that landowners significantly prefer working with a non-profit organization. Based on monetary estimates of willingness-to-accept compensation, our results suggest that aggregated forest carbon offset projects incorporating small forest landowners could be piloted successfully in Vermont by non-profit organizations while maintaining relatively strict guidelines of existing carbon offset protocols.


Computed tomographic findings of good prognosis for hemiplegia in hypertensive putaminal hemorrhage.
Computed tomography (CT) findings were analyzed in 17 patients with hypertensive putaminal hemorrhage accompanied by hemiplegia which had subsided almost completely by conservative therapy within one month after the onset. In such patients a high density area was not seen at the level of the lateral ventricles on CT scan. To study the reason for this, the relationship between the extent of a hematoma and the level at which the pyramidal tract was destroyed was investigated. From consideration of the process of destruction of the pyramidal tract by a hematoma, it seemed that CT findings at the level of the bodies of the lateral ventricles, rather than at the level of the posterior limb of the internal capsule, were of value in evaluating the prognosis of hemiplegia in putaminal hemorrhage.


Electrode Placement in Transcranial Direct Current Stimulation-How Reliable Is the Determination of C3/C4?
The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. M1 is identified by C3 and C4 of the 10/20 EEG system yet the reliability of 10/20 EEG measurements by novice research raters is unknown. We investigated the reliability of the 10/20 EEG measurements for C3 and C4 in 25 adult participants. Two novice raters were assessed for inter-rater reliability. Both raters received two hours of instruction from a registered neurodiagnostic technician. One of the raters completed the measurements across two testing days for intra-rater reliability. Relative reliability was determined using the intraclass coefficient (ICC) and absolute reliability. We observed a low to fair inter and intra-rater ICC for motor cortex measurements. The absolute reliability was <1.0 cm by different novice raters and on different days. Although a low error was observed, consideration of the integrity of the targeted region of the brain is critical when designing tDCS interventions in clinical populations who may have compromised brain structure, due to a lesion or altered anatomy.


The effect of consensus on demand for voluntary micro health insurance in rural India.
This study deals with examining factors that catalyze demand for community-based micro health insurance (MHI) schemes. We hypothesize that demand for health insurance is a collective decision in the context of informality and poverty. Our hypothesis challenges the classical theory of demand which posits individual expected diminishing utility. We examine factors beyond the traditional exogenous variables. This study uses data collected through a household survey conducted among self-help groups in rural India in the states of Uttar Pradesh and Bihar before the implementation of three community-based MHI schemes. Additional information was extracted from the management information system maintained by the schemes. At the first step, we compared the estimated probability of a household joining the scheme (obtained by applying logistic regression) to the actual uptake. In the next step, we analyzed the role of consensus within groups on demand for health insurance (by applying ordinary least square regressions). The results of the logistic regressions indicated that exogenous household characteristics could not explain the probability of joining health insurance. We observed that group consensus on several critical issues, such as the price of the insurance, perceptions about exposure to adverse health events, and perceptions of the quality of service of local health care providers, was the important determinant of demand for insurance. Based on the analysis, we reject the null hypothesis that demand is an individual decision at the household level. The analysis upholds the assumption that demand is created through a process of consensus building on perceptions of risk exposure, welfare gains from the insurance, and quality of local health care provision. Success in catalyzing demand for health insurance in the informal sector depends on encouraging group dialog.


Lactoferrin and lysozyme levels in synovial fluid: differential indices of articular inflammation and degradation.
Lysozyme and lactoferrin levels were measured in 71 synovial fluids (SF) of patients with traumatic effusions, osteoarthritis, rheumatoid arthritis, pseudogout, septic arthritis, and gout, as well as in 91 synovial fluids graded according to their neutrophil count. Elevated lysozyme levels were found in all the inflammatory arthritides and also in osteoarthritis. Lactoferrin levels were not increased in osteoarthritis but displayed a close correlation to the extent of the inflammatory response as judged by SF neutrophilia. The ratio of lysozyme to lactoferrin decreased progressively with increasing SF neutrophilia. In vitro experiments showed that lactoferrin is released from neutrophils isochronously with lysozyme and beta-glucuronidase. Lactoferrin was not found in hyaline cartilage, a tissue known to contain lysozyme. These results are consistent with belief that SF lysozyme has a major derivation from both cartilage and neutrophils, and that lactoferrin arises only from neutrophils. These findings indicate that the simultaneous measurement of lysozyme and lactoferrin provides a potentially useful index of both joint inflammation and cartilage degradation.


Lack of association between airflow limitation and recurrence of venous thromboembolism among cancer patients with pulmonary embolism.
COPD is a well-known risk factor for venous thromboembolism (VTE) development. However, recent data showed that it was not associated with VTE recurrence risk, which excluded cancer patients. This study investigated the association of airflow limitation and VTE recurrence in cancer patients with pulmonary embolism (PE). This is a retrospective cohort study of cancer patients with newly diagnosed PE at a university hospital. PE was confirmed using contrast-enhanced computed tomography scan. Airflow limitation was defined as pre-bronchodilator forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.7 within 2 years of PE diagnosis. VTE recurrence was defined as a composite of recurrence as PE or deep vein thrombosis or both. Among 401 cancer patients with newly diagnosed PE, spirometry-based airflow limitation was observed in 126 (31.4%) patients. Half of the patients had lung cancer, which was more common in the group with airflow limitation (65.1% vs 42.9%, p < 0.001). Symptomatic PE was present in less than half (45.4%) of the cases, and 62.6% of patients were treated for PE. During the median follow-up period of 9.7 months, VTE recurred in 49 (12.2%) patients. Compared with patients without airflow limitation, those with airflow limitation did not have an increased risk of VTE recurrence in univariate or multivariate analyses (adjusted hazard ratio, 1.29 [95% CI 0.68, 2.45]). The presence of airflow limitation did not increase the risk of VTE recurrence in cancer patients with PE. Prospective studies are needed to validate this finding.


Free-breathing single navigator gated cine cardiac magnetic resonance at 3 T: feasibility study in patients.
Cardiac magnetic resonance imaging (CMRI) is an important tool to assess cardiac function. However, one of the limitations of CMRI is the need for frequent breath-holding (BH) steps. This may be inconvenient to some patients and limit the use of this modality in patients unable to cooperate because of cognitive reasons or physically incapable of performing the required BH steps. The purpose of this study is to overcome the intrinsic timing and computation limitations of dual-navigator cine imaging and demonstrate the feasibility of free-breathing (FB) cine cardiac left ventricular function with a single-respiratory-navigator gating at 3 T. Eight participants underwent cine CMRI with both the conventional 2-dimensional cine BH and FB navigator-gated techniques. Scan parameters were identical, except in the FB technique, in which a respiratory navigator and only 2 signal averages were used. Images were scored for quality. Left ventricular end-systolic volume and end-diastolic volume were calculated. The differences in the end-systolic volume and end-diastolic volume assessed by the BH and FB were not statistically significant with P = 0.9 and 0.2, respectively. There was a good agreement between LV volumes with the limits of agreement (± 2 SD = ± 22.36 mL). Image quality score was not significantly different (P = 0.76). Free-breathing cine imaging utilizing a single-respiratory-navigator gating technique is comparable to conventional BH technique in both qualitative and quantitative imaging measures. Therefore, the FB cine technique can be used as an alternative for children and patients who are unable to hold their breath.


Model for distributed feedback Brillouin lasers.
We present a propagation model for the dynamics of distributed feedback Brillouin lasers. The model is applied to the recently demonstrated DFB Brillouin laser based on a π-phase shifted grating in a highly nonlinear silica fiber. Steady state results agree with the experimental values for threshold and efficiency. We also simulate a DFB Brillouin laser in chalcogenide and find sub-milliwatt thresholds and the possibility of centimeter-long Brillouin-DFB's.


Discovering vesicle traffic network constraints by model checking.
A eukaryotic cell contains multiple membrane-bound compartments. Transport vesicles move cargo between these compartments, just as trucks move cargo between warehouses. These processes are regulated by specific molecular interactions, as summarized in the Rothman-Schekman-Sudhof model of vesicle traffic. The whole structure can be represented as a transport graph: each organelle is a node, and each vesicle route is a directed edge. What constraints must such a graph satisfy, if it is to represent a biologically realizable vesicle traffic network? Graph connectedness is an informative feature: 2-connectedness is necessary and sufficient for mass balance, but stronger conditions are required to ensure correct molecular specificity. Here we use Boolean satisfiability (SAT) and model checking as a framework to discover and verify graph constraints. The poor scalability of SAT model checkers often prevents their broad application. By exploiting the special structure of the problem, we scale our model checker to vesicle traffic systems with reasonably large numbers of molecules and compartments. This allows us to test a range of hypotheses about graph connectivity, which can later be proved in full generality by other methods.


Synergy Effect of Nanocrystalline Cellulose for the Biosensing Detection of Glucose.
Integrating polypyrrole-cellulose nanocrystal-based composites with glucose oxidase (GOx) as a new sensing regime was investigated. Polypyrrole-cellulose nanocrystal (PPy-CNC)-based composite as a novel immobilization membrane with unique physicochemical properties was found to enhance biosensor performance. Field emission scanning electron microscopy (FESEM) images showed that fibers were nanosized and porous, which is appropriate for accommodating enzymes and increasing electron transfer kinetics. The voltammetric results showed that the native structure and biocatalytic activity of GOx immobilized on the PPy-CNC nanocomposite remained and exhibited a high sensitivity (ca. 0.73 μA·mM(-1)), with a high dynamic response ranging from 1.0 to 20 mM glucose. The modified glucose biosensor exhibits a limit of detection (LOD) of (50 ± 10) µM and also excludes interfering species, such as ascorbic acid, uric acid, and cholesterol, which makes this sensor suitable for glucose determination in real samples. This sensor displays an acceptable reproducibility and stability over time. The current response was maintained over 95% of the initial value after 17 days, and the current difference measurement obtained using different electrodes provided a relative standard deviation (RSD) of 4.47%.


Modulation of crayfish retinal sensitivity by 5-hydroxytryptamine.
The responsiveness of crayfish retinal photoreceptors to light was enhanced by exposure to 5-hydroxytryptamine (5-HT), either following injection into whole animals or following topical application to isolated eyestalks or retinas. The effect was measured as an increment in the amplitude of the receptor potential, and was dose-dependent in the range 10(-6)-10(-3) mol l-1 (injected as a 0.1 microliter dose in intact animals). It was more pronounced at low levels of illumination and was reversibly blocked by methysergide. The enhancement was a consequence of a dual effect: (a) retraction of the proximal pigment granules within the photoreceptors, with a corresponding increase in the light-admittance function of the retina; and (b) a direct effect, facilitating a membrane conductance increase which mediated the generation of the receptor potential. A set of axons in the lamina ganglionaris with a 5-HT-like immunoreactivity was found in the vicinity of the photoreceptor axons. 5-HT antagonists were capable of blocking the physiological retraction of pigment granules in photoreceptors at night, suggesting that 5-HT acts as a modulator during the nocturnal phase of the circadian cycle in the crayfish retina.


[Chagas' disease epidemiology in the province of General Paz, Argentina].
The aim of this study was to evaluate triatomine colonization in domestic and peridomestic ecotopes and to assess the seroprevalence of Chagas' disease in rural areas. The study was carried out in the province of General Paz, Corrientes, Argentina. Human dwellings and peridomestic ecotopes were randomly selected. Triatomines were collected using the man/hour/capture method. The insects were taxonomically determined and classified by age and sex. Trypanosoma cruzi infection was detected through direct microscopy of feces and polymerase chain reaction (PCR). Diagnosis of Chagas infection in volunteer residents was performed using indirect hemagglutination (IHA) and immunoenzimatic assay (ELISA). Infestation, density, colonization, natural infection and dispersion indexes were recorded. RESULTS; A total of 42 households and 50 peridomestic areas were examined. Triatoma infestans domestic infestation and infection indexes were 23.8 and 19.4; respectively. Density, colonization and dispersion indexes were 2.1; 47.0 and 50.0; respectively. Of all, 5.9% of peridomiciles were infested by T. infestans and 11.8% by Triatoma sordida. Trypanosoma cruzi infection was observed in 2.0% of T. sordida. The seroprevalence rate obtained from 85 human sera analyzed was 22.3%. The results suggest a halt in T. cruzi transmission in the study area. Nevertheless the presence of seroreactive individuals and infected T. infestans vectors might facilitate the resurgence of the transmission cycle. Control actions with the use of insecticides might be considered in order to eliminate vector populations.


Sustainable implementation of international health cooperation projects while Japanese technical experts cannot go to low- and middle-income countries because of the COVID-19 pandemic travel restrictions.
Due to the COVID-19 pandemic, Japanese technical experts who have been supporting health in low-and middle- income countries (LMICs) are facing unprecedented travel restrictions. As of 11 April 2020, of 195 countries Japan has diplomatic relationship with, 181 countries have entry restrictions and 69 countries have post-entry movement restrictions (self-quarantine) for Japanese nationals or travellers from Japan. In order for technical experts to assist LMICs technically from Japan to meet the increased demand and needs in the health sector due to COVID-19, it is important to prioritize and reorganize the project activities in accordance with the local situation in particular to address three challenges i) to communicate from Japan; ii) to prioritize activities to match to the increased COVID-19 related tasks; and iii) to advocate health workers' rights and working environment.


Conditioning theory: a model for the etiology of public speaking anxiety?
To study the etiology of public speaking anxiety (speech phobia), 30 Ss with the fear of public speaking, and 24 controls without this fear were asked about past public speaking experiences, their beliefs about the main reason for their phobia, and their concerns in the feared situation. All speech phobics met the DSM-III-R criteria for social phobia. Results showed that traumatic external events, vicarious and informational learning--the causes for phobia that fit in best with Rachman's conditioning theory--were notably uncommon among these phobics, who attributed their fear most often to panic attacks. Yet it was not clear whether panic attacks were causes or consequences of phobia.


Accuracy of noninvasive breath methane measurements using Fourier transform infrared methods on individual cows.
Individual methane (CH(4)) production was recorded repeatedly on 93 dairy cows during milking in an automatic milking system (AMS), with the aim of estimating individual cow differences in CH(4) production. Methane and CO(2) were measured with a portable air sampler and analyzer unit based on Fourier transform infrared (FTIR) detection. The cows were 50 Holsteins and 43 Jerseys from mixed parities and at all stages of lactation (mean=156 d in milk). Breath was captured by the FTIR unit inlet nozzle, which was placed in front of the cow's head in each of the 2 AMS as an admixture to normal barn air. The FTIR unit was running continuously for 3 d in each of 2 AMS units, 1 with Holstein and another with Jersey cows. Air was analyzed every 20 s. From each visit of a cow to the AMS, CH(4) and CO(2) records were summarized into the mean, median, 75, and 90% quantiles. Furthermore, the ratio between CH(4) and CO(2) was used as a derived measure with the idea of using CO(2) in breath as a tracer gas to quantify the production of methane. Methane production records were analyzed with a mixed model, containing cow as random effect. Fixed effects of milk yield and daily intake of the total mixed ration and concentrates were also estimated. The repeatability of the CH(4)-to-CO(2) ratio was 0.39 for Holsteins and 0.34 for Jerseys. Both concentrate intake and total mixed ration intake were positively related to CH(4) production, whereas milk production level was not correlated with CH(4) production. In conclusion, the results from this study suggest that the CH(4)-to-CO(2) ratio measured using the noninvasive method is an asset of the individual cow and may be useful in both management and genetic evaluations.


Etiopathology of feline toxic nodular goiter.
We have discussed the etiopathology of feline toxic nodular goiter in the context of human nodular goiter pathogenesis. We have reviewed thyroid heterogeneity, growth regulation, functional and growth autonomy, nodule and tumor formation, and the evolution of toxic nodular goiter in the human being. By addressing toxic nodular goiter of the cat, the history, morphologic findings, xenotransplantation and cell culture studies, evidence for and against circulating thyroid stimulators and epizootiological studies of the feline disease have been summarized. Due to its structure, the thyroid gland offers some unique possibilities to study the mechanisms that are responsible for cellular heterogeneity, the emergence of autonomous nodular growth and function, and, ultimately, the development of tumors. The demonstration of naturally occurring clones of cells with high intrinsic proliferation potential within the follicular epithelium of the thyroid has fostered promising new concepts on the genesis of nodular growth of benign and possibly malignant endocrine tumors. Hyperthyroid cat goiters contain single or multiple, autonomously (i.e., TSH-independently) functioning and growing nodules. Neither hyperfunction nor growth of these nodules depends on extrathyroidal circulating stimulators. The basic lesion appears to be an excessive intrinsic growth capacity of some thyroid cells. The factors enhancing the transformation of a normal thyroid into a nodular hyperfunctioning goiter over many years are still unknown. Immunological, environmental, and nutritional factors are the focus of ongoing studies, but an infectious agent can not yet be excluded.


Host-Specific and Segment-Specific Evolutionary Dynamics of Avian and Human Influenza A Viruses: A Systematic Review.
Understanding the evolutionary dynamics of influenza viruses is essential to control both avian and human influenza. Here, we analyze host-specific and segment-specific Tajima's D trends of influenza A virus through a systematic review using viral sequences registered in the National Center for Biotechnology Information. To avoid bias from viral population subdivision, viral sequences were stratified according to their sampling locations and sampling years. As a result, we obtained a total of 580 datasets each of which consists of nucleotide sequences of influenza A viruses isolated from a single population of hosts at a single sampling site within a single year. By analyzing nucleotide sequences in the datasets, we found that Tajima's D values of viral sequences were different depending on hosts and gene segments. Tajima's D values of viruses isolated from chicken and human samples showed negative, suggesting purifying selection or a rapid population growth of the viruses. The negative Tajima's D values in rapidly growing viral population were also observed in computer simulations. Tajima's D values of PB2, PB1, PA, NP, and M genes of the viruses circulating in wild mallards were close to zero, suggesting that these genes have undergone neutral selection in constant-sized population. On the other hand, Tajima's D values of HA and NA genes of these viruses were positive, indicating HA and NA have undergone balancing selection in wild mallards. Taken together, these results indicated the existence of unknown factors that maintain viral subtypes in wild mallards.


Origins of the Spanish Influenza pandemic (1918-1920) and its relation to the First World War.
The virus which was responsible for the first benign wave of the Spanish Influenza in the spring of 1918, and which was to become extremely virulent by the end of the summer of 1918, was inextricably associated with the soldiers who fought during the First World War. The millions of young men who occupied the military camps and trenches were the substrate on which the influenza virus developed and expanded. Many factors contributed to it, such as: the mixing on French soil of soldiers and workers from the five continents, the very poor quality of life of the soldiers, agglomeration, stress, fear, war gasses used for the first time in history in a massive and indiscriminate manner, life exposed to the elements, cold weather, humidity and contact with birds, pigs and other animals, both wild and domestic. Today, this combination of circumstances is not present and so it seems unlikely that new pandemics, such as those associated with the avian influenza or swine influenza, will emerge with the virulence which characterized the Spanish Influenza during the autumn of 1918.


Zebrafish high-throughput screening to study the impact of dissolvable metal oxide nanoparticles on the hatching enzyme, ZHE1.
The zebrafish is emerging as a model organism for the safety assessment and hazard ranking of engineered nanomaterials. In this Communication, the implementation of a roboticized high-throughput screening (HTS) platform with automated image analysis is demonstrated to assess the impact of dissolvable oxide nanoparticles on embryo hatching. It is further demonstrated that this hatching interference is mechanistically linked to an effect on the metalloprotease, ZHE 1, which is responsible for degradation of the chorionic membrane. The data indicate that 4 of 24 metal oxide nanoparticles (CuO, ZnO, Cr2 O3 , and NiO) could interfere with embryo hatching by a chelator-sensitive mechanism that involves ligation of critical histidines in the ZHE1 center by the shed metal ions. A recombinant ZHE1 enzymatic assay is established to demonstrate that the dialysates from the same materials responsible for hatching interference also inhibit ZHE1 activity in a dose-dependent fashion. A peptide-based BLAST search identifies several additional aquatic species that express enzymes with homologous histidine-based catalytic centers, suggesting that the ZHE1 mechanistic paradigm could be used to predict the toxicity of a large number of oxide nanoparticles that pose a hazard to aquatic species.


Elevated carbon dioxide alters the plasma composition and behaviour of a shark.
Increased carbon emissions from fossil fuels are increasing the pCO2 of the ocean surface waters in a process called ocean acidification. Elevated water pCO2 can induce physiological and behavioural effects in teleost fishes, although there appear to be large differences in sensitivity between species. There is currently no information available on the possible responses to future ocean acidification in elasmobranch fishes. We exposed small-spotted catsharks (Scyliorhinus canicula) to either control conditions or a year 2100 scenario of 990 μatm pCO2 for four weeks. We did not detect treatment effects on growth, resting metabolic rate, aerobic scope, skin denticle ultrastructure or skin denticle morphology. However, we found that the elevated pCO2 group buffered internal acidosis via [Formula: see text] accumulation with an associated increase in Na(+), indicating that the blood chemistry remained altered despite the long acclimation period. The elevated pCO2 group also exhibited a shift in their nocturnal swimming pattern from a pattern of many starts and stops to more continuous swimming. Although CO2-exposed teleost fishes can display reduced behavioural asymmetry (lateralization), the CO2-exposed sharks showed increased lateralization. These behavioural effects may suggest that elasmobranch neurophysiology is affected by CO2, as in some teleosts, or that the sharks detect CO2 as a constant stressor, which leads to altered behaviour. The potential direct effects of ocean acidification should henceforth be considered when assessing future anthropogenic effects on sharks.


Diet quality, measured by fruit and vegetable intake, predicts weight change in young women.
This study investigates the relationship between diet quality and weight gain in young women. Young women (n = 4,287, with 1,356 women identified as plausible subsample aged 27.6 ± 1.5 years at baseline) sampled from the Australian Longitudinal Study on Women's Health study completed food frequency questionnaires in 2003, which were used to evaluate diet quality using three indices: Australian Recommended Food Score (ARFS), Australian Diet Quality Index (Aus-DQI), and Fruit and Vegetable Index (FAVI). Weight was self-reported in 2003 and 2009. Multivariate linear regression was used to examine the association between tertiles of each diet quality index and weight change from 2003 to 2009. The ARFS and FAVI were significant predictors of 6-year weight change in this group of young women, while Aus-DQI did not predict weight change (P > 0.05). In the fully adjusted model, those who were in the top tertile of the ARFS significantly gained lower weight gain compared with the lower tertile for the plausible TEI sub-sample (β = -1.6 kg (95% CI: -2.67 to -0.56), P = 0.003). In the fully adjustment model, young women were classified in the highest FAVI tertile and gained significantly less weight than those in the lowest tertile for the plausible TEI (β = -1.6 kg (95% CI: -2.4 to -0.3) P = 0.01). In conclusion, overall diet quality measured by the ARFS and the frequency and variety of fruit and vegetable consumption may predict long-term weight gain in young women. Therefore, health promotion programs encouraging frequent consumption of a wide variety of fruits and vegetables are warranted.


Development of a LAMP assay for detection of Leishmania infantum infection in dogs using conjunctival swab samples.
Leishmania infantum infections in dogs play a crucial role in the transmission of pathogens causing visceral leishmaniasis to humans in the Gansu province, northwest China. To be able to control zoonotic transmission of the parasite to humans, a non-invasive loop-mediated isothermal amplification (LAMP) assay to specifically detect L. infantum infections in dogs was developed. The primers used in the LAMP assay were designed to target kinetoplast DNA minicircle sequences of the L. infantum isolate MCAN/CN/90/SC and tested using DNA isolated from promastigotes of different Leishmania species. The LAMP assay was evaluated with conjunctional swab samples obtained from 111 and 33 dogs living in an endemic and a non-endemic region of zoonotic visceral leishmaniasis in the Gansu province, respectively. The LAMP assay was also compared with conventional PCR, ELISA and microscopy using conjunctional swab, serum and bone marrow samples from the dogs, respectively. The LAMP assay detected 1 fg of L. infantum DNA purified from cultured promastigotes which was 10-fold more sensitive than a conventional PCR test using Leishmania genus-specific primers. No cross reaction was observed with DNA isolated from promastigotes of L. donovani, L. major, L. tropica, and L. braziliensis, and the L. infantum reference strain MHOM/TN/80/IPT1. The L. infantum-positive rates obtained for field-collected samples were 61.3%, 58.6%, 40.5% and 10.8% by LAMP, PCR, ELISA and microscopy, respectively. As only one out of the 33 samples from control dogs from the non-endemic region of zoonotic visceral leishmaniasis was positive by the LAMP assay and the PCR test, the observed true negative rate (specificity) was 97% for both methods. This study has shown that the non-invasive, conjunctional swab-based LAMP assay developed was more sensitive in the detection of leishmaniasis in dogs than PCR, ELISA and microscopy. The findings indicate that the LAMP assay is a sensitive and specific method for the field surveillance of domestic dogs, particularly of asymptomatic canines, in ZVL-endemic areas in western China.


What is a planning model? An introduction to PRECEDE-PROCEED.
Planning models exist at a macroscopic level; they serve as an organizing framework for an entire health promotion effort aimed at fostering reduction in a given disease. A particularly useful, widely applied, and easy-to-follow example of a planning model is the PRECEDE-PROCEED planning model (PPM). The PPM is very much an ecological approach to health promotion. The PPM is actually quite simple to understand once one realizes that it embodies two key aspects of intervention: a) planning, and (b) evaluation. The PPM guides the program planner to think logically about the desired end point and work "backwards" to achieve that goal. Through community participation, the planning process is broken down into objectives, step 3 sub-objectives, and step 4 sub-objectives. Conceptually, this approach to health promotion provides context to the use of theory, with theory being applied at the fourth step. This observation teaches a vital lesson, namely that program planning is larger and is a more comprehensive task compared to the subservient function of theory selection and application.


Assessment of endocrine disruptors - DDTs and DEHP (plasticizer) in source water: a case study from Selangor, Malaysia.
The presence of endocrine disruptors in source water is of great concern because of their suspected adverse effects on humans, even when present at very low levels. As the main source of potable water supply, rivers in Malaysia are highly susceptible to contamination by various endocrine disruptors originating from anthropogenic activities. In this study, the contamination levels of 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT) and its metabolites and di-(2-ethylhexyl) phthalate (DEHP) in rivers of Selangor were examined using gas chromatography-mass spectrometry. Samples were collected from sites representing source water for 18 drinking water treatment plants in Selangor between July 2008 and July 2009. DDT and its metabolites were detected in only 14% of the 192 samples analysed at levels ranging from 0.6 to 14.6 ng/L. Meanwhile DEHP was detected in 96.8% of the samples at levels ranging from below quantitation level (18 ng/L) to 970 ng/L. The detected levels of DDTs and DEHP were lower than the WHO and Malaysian Guidelines for Drinking Water Quality. Data obtained from this study should also serve as a reference point for future surveillance on these endocrine disruptors.


KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors.
No therapies for targeting KRAS mutations in cancer have been approved. The KRAS p.G12C mutation occurs in 13% of non-small-cell lung cancers (NSCLCs) and in 1 to 3% of colorectal cancers and other cancers. Sotorasib is a small molecule that selectively and irreversibly targets KRASG12C. We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was safety. Key secondary end points were pharmacokinetics and objective response, as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. A total of 129 patients (59 with NSCLC, 42 with colorectal cancer, and 28 with other tumors) were included in dose escalation and expansion cohorts. Patients had received a median of 3 (range, 0 to 11) previous lines of anticancer therapies for metastatic disease. No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma. Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effects occurred in 11.6% of the patients. (Funded by Amgen and others; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).


Melanopsin-dependent photoreception provides earliest light detection in the mammalian retina.
The visual system is now known to be composed of image-forming and non-image-forming pathways. Photoreception for the image-forming pathway begins at the rods and cones, whereas that for the non-image-forming pathway also involves intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin. In the mouse retina, the rod and cone photoreceptors become light responsive from postnatal day 10 (P10); however, the development of photosensitivity of the ipRGCs remains largely unexplored. Here, we provide direct physiological evidence that the ipRGCs are light responsive from birth (P0) and that this photosensitivity requires melanopsin expression. Interestingly, the number of ipRGCs at P0 is over five times that in the adult retina, reflecting an initial overproduction of melanopsin-expressing cells during development. Even at P0, the ipRGCs form functional connections with the suprachiasmatic nucleus, as assessed by light-induced Fos expression. The findings suggest that the non-image-forming pathway is functional long before the mainstream image-forming pathway during development.


In vivo evaluation of a novel 'diastole-patching' algorithm for the estimation of pulse transit time: advancing the precision in pulse wave velocity measurement.
Carotid-to-femoral pulse wave velocity (PWV) is the gold standard for the assessment of aortic stiffness. It is calculated by the ratio of pulse transit time (PTT) between two arterial sites and the distance between them. The precision of PTT estimation depends upon the algorithm that determines characteristic points at the foot of the pulse waveforms. Different algorithms yield variable PTT values thus affecting the precision of PWV and subsequently its diagnostic and prognostic accuracy. Our aim was to apply in vivo a new 'diastole-patching' algorithm and investigate whether it improves the precision of PWV measurement. Two repeated PWV measurements were performed in a general population (340 subjects) by a reference apparatus (SphygmoCor) which uses the tangential method for PTT estimation. PTT was re-estimated by the 'diastole-patching' algorithm. We computed statistical parameters of agreement, consistency, precision and variability between the two PWV measurements. The 'diastole-patching' method yielded more precise and reproducible measurements of PWV compared to the tangential method at the total population. In those cases where the reference method provided PWV measurements with difference >1 m s(-1), the 'diastole-patching' algorithm further improved the precision of PWV. These findings may have direct implications concerning the enhancement of the diagnostic and prognostic value of PWV.


Genome-wide polymorphisms from RNA sequencing assembly of leaf transcripts facilitate phylogenetic analysis and molecular marker development in wild einkorn wheat.
A survey of genome-wide polymorphisms between closely related species is required to understand the molecular basis of the evolutionary differentiation of their genomes. Two wild diploid wheat species, namely Triticum monococcum ssp. aegilopoides and T. urartu, are closely related and harbour the Am and A genomes, respectively. The A-genome donor of tetraploid and common wheat is T. urartu, and T. monococcum ssp. monococcum is the cultivated form derived from the wild einkorn wheat subspecies aegilopoides. Although subspecies aegilopoides has been a useful genetic resource in wheat breeding, genome-wide molecular markers for this subspecies have not been sufficiently developed. Here, we describe the detection of genome-wide polymorphisms such as single-nucleotide polymorphisms (SNPs) and insertions/deletions (indels) from RNA sequencing (RNA-seq) data of leaf transcripts in 15 accessions of the two diploid wheat species. The SNPs and indels, detected using the A genome of common wheat as the reference genome, covered the entire chromosomes of these species. The polymorphism information facilitated a comparison of the genetic diversity of einkorn wheat with that of two related diploid Aegilops species, namely, Ae. tauschii and Ae. umbellulata. Cleaved amplified polymorphic sequence (CAPS) markers converted from the SNP data were efficiently developed to confirm the addition of aegilopoides subspecies chromosomes to tetraploid wheat in nascent allohexaploid lines with AABBAmAm genomes. In addition, the CAPS markers permitted linkage map construction in mapping populations of aegilopoides subspecies accessions. Therefore, these RNA-seq data provide information for further breeding of closely related species with no reference genome sequence data.


Clinical outcome of Turkish metastatic breast cancer patients with currently available treatment modalities--single center experience.
Breast cancer is the most common malignancy and the second leading cause of cancer-related death among women in the developed countries. Despite advances in screening, improved local therapies and adjuvant systemic treatments, median survival of metastatic breast cancer patients (MBC) is in the range of 2-3 years at most. We aimed to investigate whether the prognostic factors and therapeutic responses of our Turkish patients are similar to those in the literature. We reviewed the medical records of MBC patients who had been treated in our institution between 1999-2009 and analyzed their clinicopathological features and survival outcomes retrospectively. A hundred and sixty patients were included. Median age was 47 (23-82), median follow up was 24 (2-186) months. At the time of diagnosis 59% of patients were under the age of 50 and 46% were postmenopausal. The majority (37%) had multiple sites of metastases. Forty percent received endocrine therapy and 40% chemotherapy as first line metastatic treatment. Thirty (20%) patients were treated with molecular targeting agents like trastuzumab, lapatinib and sunitinib, frequently combined with a chemotherapy agent. Five-year overall survival (OS) was 32% and median OS was 38 months for the whole group. Five year progression free survival (PFS) was 10% and median PFS was 10 months. Menopausal status, hormone receptor expression and disease free status had a significant impact on overall survival in the multivariate analysis (p 0.018, p 0.018 and p:0.003, respectively). All our patients were treated with the modern oncologic therapies recommended by the international guidelines. From our data, MBC patients live up to 3-4 years, indicating that further improvement beyond that requires development of new treatment modalities. The survival outcomes of our patients were consistent with the data reported in the literature.


Clinical effectiveness and cost minimisation model of Alpha-Stim cranial electrotherapy stimulation in treatment seeking patients with moderate to severe generalised anxiety disorder.
Cranial electrotherapy stimulation (CES) is a well-tolerated neuromodulation treatment with demonstrated trial efficacy in anxiety disorders. The aim of the current study was to demonstrate its clinical and cost effectiveness during and after CES in people with generalised anxiety disorder (GAD) who had not responded to low intensity psychological treatment in a routine health service. Consecutive sample of eligible patients with GAD waiting for individual cognitive behaviour therapy (CBT) selected from two publicly funded services in England. They received 60 min per day Alpha-Stim CES for 6-12 weeks. Primary outcome was remission on the GAD-7 scale at 12 and 24 weeks. Cost effectiveness was examined using a cost minimisation model of direct health costs. Of 161 patients recruited, 72 (44.7%) and 77 (47.8%) achieved remission on the GAD-7 at 12 and 24 weeks respectively with 122 (75.8%) receiving at least 6 weeks CES. Mean (sd) GAD-7 score at baseline significantly improved from 15.77 (3.21) to 8.92 (5.42) and 8.99 (6.18) at 12 and 24 weeks respectively (p < 0.001). 80 (49.7%) participants required further individual CBT. CES provided a saving of £540.88 per patient (95% CI -£327.12, £648.69). Participants were not randomised and there was no control group. Only 48 (29.9%) participants completed every assessment. In patients with generalised anxiety disorder not responding to low intensity psychological treatment, 6-12 weeks daily Alpha Stim CES may be effective after treatment and 3 months later, thereby reducing the need for individual CBT and saving health costs.


Differential mRNA translation and meiotic progression require Cdc2-mediated CPEB destruction.
Translational activation of several dormant mRNAs in vertebrate oocytes is mediated by cytoplasmic polyadenylation, a process controlled by the cytoplasmic polyadenylation element (CPE) and its binding protein CPEB. The translation of CPE-containing mRNAs does not occur en masse at any one time, but instead is temporally regulated. We show here that in Xenopus, partial destruction of CPEB controls the temporal translation of CPE-containing mRNAs. While some mRNAs, such as the one encoding Mos, are polyadenylated at prophase I, the polyadenylation of cyclin B1 mRNA requires the partial destruction of CPEB that occurs at metaphase I. CPEB destruction is mediated by a PEST box and Cdc2-catalyzed phosphorylation, and is essential for meiotic progression to metaphase II. CPEB destruction is also necessary for mitosis in the early embryo. These data indicate that a change in the CPEB:CPE ratio is necessary to activate mRNAs at metaphase I and drive the cells' entry into metaphase II.


Living on soup: macropinocytic feeding in amoebae.
Macropinocytosis is used by a variety of amoebae for feeding on liquid medium. The amoebae project cups and ruffles from their plasma membrane, driven by actin polymerization, and eventually fuse these back to the membrane, entrapping droplets of medium into internal vesicles. These vesicles are of up to several microns in diameter and are processed through the lysosomal digestive system to extract nutrients. Recognizably the same process is used in metazoan cells for a number of medically important purposes, including the pathological growth of cancer cells. We describe the discovery of macropinocytosis in Dictyostelium amoebae, its genetic regulation by the NF1 RasGAP, and the tools available for its investigation. Work on Dictyostelium over the last 30 years has identified many genes that may be important for macropinocytosis, which are listed at dictyBase, and give a basis for mechanistic studies. We argue that the actin cytoskeleton is organized for macropinocytosis by a signalling patch of PIP3 and active Ras and Rac, together with their regulatory proteins and effectors, including the protein kinases Akt and SGK. The Scar/WAVE complex is recruited to the periphery of this patch, triggering the formation of a hollow ring of protrusive actin polymerization, and eventually a macropinocytic cup. Major problems to be addressed include: the dynamics sustaining macropinocytic patches and the mechanism of Scar/WAVE recruitment; the mechanisms of cup closure and of membrane fusion; the ecological situations where amoebae feed by macropinocytosis; and the evolutionary relationship between macropinocytosis and growth factor signalling.


A health survey of granite workers in Finland: radiographic findings, respiratory function, hearing, electric sensory thresholds of the fingers and subjective symptoms.
Results from a health survey of 777 granite workers, exposed to quartz dust, noise and/or machine vibration, and 122 unexposed "controls" are reported. The survey included chest X-rays, pulmonary function tests, a hearing examination, the determination of the electric sensory thresholds of the fingers, and questionnaires on the subjective symptoms of the respiratory system and upper limbs. The exposed workers' radiographic findings (except for a 2.6 % rate of silicosis), respiratory functions, and sensory thresholds did not differ significantly from those of the controls. Granite drillers had a high prevalence of hearing defects. Respiratory symptoms were common among drillers and sandblasters, and subjective symptoms of the upper limbs due to vibration occurred among the granite dressing workers who used pneumatic hammers. Both primary and secondary measures of prevention are strongly recommended for the granite industry, primarlily for quartz dust exposure and its health effects.


Nonreciprocity and magnetic-free isolation based on optomechanical interactions.
Nonreciprocal components, such as isolators and circulators, provide highly desirable functionalities for optical circuitry. This motivates the active investigation of mechanisms that break reciprocity, and pose alternatives to magneto-optic effects in on-chip systems. In this work, we use optomechanical interactions to strongly break reciprocity in a compact system. We derive minimal requirements to create nonreciprocity in a wide class of systems that couple two optical modes to a mechanical mode, highlighting the importance of optically biasing the modes at a controlled phase difference. We realize these principles in a silica microtoroid optomechanical resonator and use quantitative heterodyne spectroscopy to demonstrate up to 10 dB optical isolation at telecom wavelengths. We show that nonreciprocal transmission is preserved for nondegenerate modes, and demonstrate nonreciprocal parametric amplification. These results open a route to exploiting various nonreciprocal effects in optomechanical systems in different electromagnetic and mechanical frequency regimes, including optomechanical metamaterials with topologically non-trivial properties.


Criteria used for diagnosis of adhesive capsulitis of the shoulder: a scoping review protocol.
The objective of this scoping review is to locate and summarize the current criteria used in the diagnosis of adhesive capsulitis of the shoulder in recent academic literature. Furthermore, we aim to explore differences, if any, in the criteria used across treating professions, study country of origin and study level of evidence.


HFE Cys282Tyr homozygotes with serum ferritin concentrations below 1000 microg/L are at low risk of hemochromatosis.
Hemochromatosis gene (HFE)-associated hereditary hemochromatosis (HH) is a genetic predisposition to iron overload and subsequent signs and symptoms of disease that potentially affects approximately 80,000 persons in Australia and almost 1 million persons in the United States. Most clinical cases are homozygous for the Cys282Tyr (C282Y) mutation in the HFE gene, with serum ferritin (SF) concentration >1000 microg/L as the strongest predictor of cirrhosis. The optimal treatment regimen for those with SF concentrations above the normal range but <1000 microg/L is unknown. We assessed HFE mutations in a prospective cohort of 31,192 participants of northern European descent, aged 40-69 years. An HFE-stratified random sample of 1438 participants including all C282Y homozygotes with iron studies 12 years apart were examined by physicians blinded to participants' HFE genotype. All previously undiagnosed C282Y homozygotes (35 male, 67 female) and all HFE wild-types (131 male, 160 female) with baseline and follow-up SF concentrations <1000 microg/L were assessed for HH-associated signs and symptoms including abnormal second/third metacarpophalangeal joints (MCP2/3), raised liver enzymes, hepatomegaly, and self-reported liver disease, fatigue, diabetes mellitus, and use of arthritis medication. The prevalence of HH-associated signs and symptoms was similar for C282Y homozygotes and HFE wild-types for both normal and moderately elevated SF concentrations. The maximum prevalence difference between HFE genotype groups with moderately elevated SF was 11% (MCP2/3, 95% confidence interval = -6%, 29%; P = 0.22) and for normal SF was 6% (arthritis medicine use, 95% confidence interval = -3%, 16%; P = 0.11). Previously undiagnosed C282Y homozygotes with SF concentrations that remain below 1000 microg/L are at low risk of developing HH-associated signs and symptoms at an age when disease would be expected to have developed. These observations have implications for the management of C282Y homozygotes.


Synthesis and crystal structures of a novel layered silicate SSA-1 and its microporous derivatives by topotactic transformation.
The synthesis of a novel layered silicate SSA-1 (SSA: silicate synthesized with a quaternary amine) was achieved in the SiO2-H2O-TEAOH (TEAOH: tetraethylammonium hydroxide - as an organic structural directing agent) system. The crystal structure of SSA-1 involved two silicate layers composed of bre [10T]-type CBU (Composite Building Unit) and TEAOH in interlayers. The topotactic transformation of SSA-1 by calcination was examined, resulting in a porous material (PML-1: porous material transformed from a layered silicate) with a 108 m2 g-1 BET surface area and 0.035 cm3 g-1 pore volume. PML-1 is a siliceous microporous material with silanols in the framework and possesses unique properties, such as hydrophilicity, in spite of all its silica composition. The most reasonable crystal structure of PML-1 was successfully determined on the basis of the crystal structure of SSA-1 by a combination of manual modelling, PXRD pattern simulation, DFT optimization and Rietveld analysis. Additionally, an interlayer expanded siliceous zeolite SSA-1 (IEZ-SSA-1) was also successfully prepared by silylation using trichloro(methyl)silane under acidic conditions. IEZ-SSA-1 showed hydrophilicity or hydrophobicity properties by changing the functional group of the pillar part in the interlayer. Additionally, IEZ-SSA-1 showed a large gas adsorption property (537 m2 g-1 and 0.21 cm3 g-1).


Sorption Constant of Bisphenol A and Octylphenol Onto Size-Fractioned Dissolved Organic Matter Using a Fluorescence Method.
Dissolved organic matter (DOM) is a complex and heterogeneous mixture ubiquitously present in aquatic systems. DOM affects octylphenol (OP) and bisphenol A (BPA) distribution, transport, bioavailability, and toxicity. This study investigated OP and BPA sorption constants, log KCOC, with three size-fractioned DOM. The molecular weights of the sized fractions were low molecular weight DOM (LDOM, <1 kDa), middle molecular weight DOM (MDOM, 1-10 kDa), and high molecular weight DOM (HDOM, 10 kDa-0.45 μm). The log KCOC ranged from 5.34 to 6.14 L/kg-C for OP and from 5.59 to 6.04 L/kg-C for BPA. The OP and BPA log KCOC values were insignificantly different (p = 0.37) and had a strong positive correlation (r = 0.85, p < 0.001). The OP and BPA LDOM log KCOC was significantly higher than the HDOM and MDOM log KCOC (p = 0.012 for BPA, p = 0.023 for OP). The average specific ultraviolet absorption (SUVA254) values were 32.0 ± 5.4, 13.8 ± 1.0, and 17.9 ± 2.8 L/mg-C/m for LDOM, MDOM, and HDOM, respectively. The log KCOC values for both OP and BPA had a moderately positive correlation with the SUVA254 values (r = 0.79-0.84, p < 0.002), which suggested the aromatic group content in the DOM had a positive impact on sorption behavior.


Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study.
Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006-2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.


Adjuvant chemoradiation for resected gallbladder cancer: Treatment strategies for one of the leading causes of cancer death in Chilean women.
Gallbladder cancer (GBC) is the second leading cause of cancer death in women in Chile. Even after curative surgery, prognosis is grim. To evaluate acute and late toxicity and efficacy of adjuvant chemoradiation (CRT) after curatively resected GBC. We retrospectively analyzed the cohort of patients diagnosed between January 1999 and December 2009, treated with adjuvant CRT at our institution. Treatment protocol considered external beam radiation (RT) (45-54 Gy) to tumor bed and regional lymph nodes with or without concurrent 5-fluorouracil (5-FU) (500 mg/m2/day by 120-hours continuous infusion on days 1-5 and 29-33). Data was obtained from medical records, mortality from death certificates. Survival was estimated by Kaplan- Meier curves. 46 patients with curatively resected GBC received adjuvant CRT. Median age was 57 years (range 33-76); 39 patients were female. After diagnosis, a second surgery was performed in 42 patients. Cholecystectomy with hepatic segmentectomy and lymphadenectomy was the curative surgery in 41 patients. All patients received RT with a planned dose of 45 Gy in 25 fractions, 11 patients received a boost to the tumor bed up to 54 Gy and 34 patients had concurrent 5-FU. Therapy was well tolerated. Five patients experienced grade 3 toxicities. No grade 4 or 5 toxicity was observed. No grade >2 late toxicity was observed. Three- and 5-year overall survival (OS) were 57% and 51%, respectively. Adjuvant chemoradiation is well tolerated and might impact favorably on survival in patients with curatively resected GBC.


Dispersion-corrected energy decomposition analysis for intermolecular interactions based on the BLW and dDXDM methods.
As the simplest variant of the valence bond (VB) theory, the block-localized wave function (BLW) method defines the intermediate electron-localized state self-consistently at the DFT level and can be used to explore the nature of intermolecular interactions in terms of several physically intuitive energy components. Yet, it is unclear how the dispersion interaction affects such a kind of energy decomposition analysis (EDA) as standard density functional approximations neglect the long-range dispersion attractive interactions. Three electron densities corresponding to the initial electron-localized state, optimal electron-localized state, and final electron-delocalized state are involved in the BLW-ED approach; a density-dependent dispersion correction, such as the recently proposed dDXDM approach, can thus uniquely probe the impact of the long-range dispersion effect on EDA results computed at the DFT level. In this paper, we incorporate the dDXDM dispersion corrections into the BLW-ED approach and investigate a range of representative systems such as hydrogen-bonding systems, acid-base pairs, and van der Waals complexes. Results show that both the polarization and charge-transfer energies are little affected by the inclusion of the long-range dispersion effect, which thus can be regarded as an independent energy component in EDA.


Frequency and characteristics of breast lymphomas presenting to a tertiary care hospital, Pakistan.
To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms. All NHLs (nodal and extra nodal) diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients (n=30) diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information. A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs (Nodal and extra Nodal) was 2632. Thirty (n=30) patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was 13.5:1; age range was 12-92 years with a median age of 43 years (Mean age 46.5 years and Standard deviation of age was 16.88 years). The sites of the lesions were the right breast in 11 cases (37.93%), left breast in 9 cases (31.03%) and both breasts in 2 cases (6.89%), while the location of 8 masses (27.58%) was unknown. Immunohistochemical studies were negative for cytokeratins (MNF and Cam 5.2) in all cases. All cases of DLBCL expressed B cell lineage antigens and were positive for LCA and Pan B (CD20 and 79a). We concluded that breast lymphomas represent 1.13% of all NHL and 0.5% of all breast malignancies in this study. The most frequent morphologic type was diffuse large B-cell lymphoma. As patients with primary breast lymphoma have a better prognosis than those with carcinoma of the breast or patients with extranodal lymphomas, a multidisciplinary approach including surgery, radiotherapy, and chemotherapy when needed would result in a more favourable outcome.


Geophagy in Northern Uganda: Perspectives from Consumers and Clinicians.
The etiology and health consequences of geophagy are still poorly understood. The consumed soil, individual motives, consumption habits, and the clinical perspective of geophagy in northern Uganda were examined. A total of 50 semistructured interviews (17 pregnant, eight nonpregnant women, 10 men, and 15 health-care professionals) were conducted. Our results suggest that geophagy is not limited to pregnancy and can also be found among nonpregnant women and men. During gestation, excessive amounts of various soil types are consumed and can replace food at times. Nonpregnant women and men consume less soil and stick to one type. When pregnant, craving and alleviating gastrointestinal upset are the main motives. In men, the main reasons for geophagy were craving, hypersalivation, and natural stimulants. If soil is craved, it can show similarities to a dependency syndrome. When picked up in childhood, geophagy is more likely to be continued throughout life. The consumption habits differ and thereby vary in their possible implications on health. Our findings suggest that men should be included in further studies. Especially nurses from the antenatal care are exposed to geophagists; however, no national guidelines exist for geophagy. Further research is necessary to create guidelines to be included in medical training and practice.


Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells.
There is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. The vast history of experience of traditional Chinese medicine (TCM) with medicinal plants may facilitate the identification of novel antileukemic compounds. In the present investigation, we tested 22 drugs for their activity toward CCRF-CEM cell lines: artesunate, artemisinin, baicalein, baicalin, berberine, bufalin, cantharidin, cephalotaxine, curcumin, daidzein, daidzin, diallyl disulfide, ginsenoside Rh2, glycyrrhizic acid, isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin, quercetin, tannic acid, and tetrahydronardosinon. As compounds from folk medicinal remedies are sometimes looked upon as alternative medicine with some hesitation or criticism, we investigated only chemically pure compounds and tested the drugs independently in two different laboratories in Germany and Australia. We used CCRF-CEM parental cells and doxorubicin-selected P-glycoprotein (P-gp)/MDR1-expressing CEM/ADR5000, vinblastine-selected P-gp/MDR1-expressing CEM/VLB(100), and epirubicin-selected multidrug resistance-related protein 1 (MRP1)-expressing CEM/E1000 sublines thereof. While CEM/ADR5000, CEM/VLB(100), and CEM/E1000 cells were highly resistant to the corresponding selecting agents, no or only minimal degrees of cross-resistance were observed to TCM drugs in both growth inhibition assay and MTT assay (range from 0.4- to 8-fold). Homoharringtonine, artesunate, and bufalin were most active among this panel of compounds. As shown by flow cytometry, artesunate significantly increased daunorubicin accumulation in CEM/E1000 cells, but not in CEM/VLB(100) or CCRF-CEM parental cells. Bufalin caused a small, but significant increase in daunorubicin accumulation in CEM/VLB(100) and CEM/E1000 cells. As artesunate and bufalin showed both antileukemic activity if applied alone and modulation activity in combination with daunorubicin in multidrug-resistant (MDR) cells, these two drugs may be suitable for novel combination treatment regimens to improve leukemia cell killing.


Racial/Ethnic Disparities in Mortality Across the Veterans Health Administration.
Purpose: Equal-access health care systems such as the Veterans Health Administration (VHA) reduce financial and nonfinancial barriers to care. It is unknown if such systems mitigate racial/ethnic mortality disparities, such as those well documented in the broader U.S. population. We examined racial/ethnic mortality disparities among VHA health care users, and compared racial/ethnic disparities in VHA and U.S. general populations. Methods: Linking VHA records for an October 2008 to September 2009 national VHA user cohort, and National Death Index records, we assessed all-cause, cancer, and cardiovascular-related mortality through December 2011. We calculated age-, sex-, and comorbidity-adjusted mortality hazard ratios. We computed sex-stratified, age-standardized mortality risk ratios for VHA and U.S. populations, then compared racial/ethnic disparities between the populations. Results: Among VHA users, American Indian/Alaskan Natives (AI/ANs) had higher adjusted all-cause mortality, whereas non-Hispanic Blacks had higher cause-specific mortality versus non-Hispanic Whites. Asians, Hispanics, and Native Hawaiian/Other Pacific Islanders had similar, or lower all-cause and cause-specific mortality versus non-Hispanic Whites. Mortality disparities were evident in non-Hispanic-Black men compared with non-Hispanic White men in both VHA and U.S. populations for all-cause, cardiovascular, and cancer (cause-specific) mortality, but disparities were smaller in VHA. VHA non-Hispanic Black women did not experience the all-cause and cause-specific mortality disparity present for U.S. non-Hispanic Black women. Disparities in all-cause and cancer mortality existed in VHA but not in U.S. population AI/AN men. Conclusion: Patterns in racial/ethnic disparities differed between VHA and U.S. populations, with fewer disparities within VHAs equal-access system. Equal-access health care may partially address racial/ethnic mortality disparities, but other nonhealth care factors should also be explored.


Lack of endosymbiont release by two Lucinidae (Bivalvia) of the genus Codakia: consequences for symbiotic relationships.
Associations between marine invertebrates and chemoautotrophic bacteria constitute a wide field for the study of symbiotic associations. In these interactions, symbiont transmission must represent the cornerstone allowing the persistence of the association throughout generations. Within Bivalvia, in families such as Solemyidae or Vesicomyidae, symbiont transmission is undoubtedly vertical. However, in Lucinidae, symbiont transmission is described in the literature as 'environmental', symbionts being acquired from the environment by the new host generations. Hence, if there is transmission, symbionts should be transmitted from adults to juveniles via the environment. Consequently, we should observe a release of the symbiont by adults. We attempted to detect such a release within two Lucinidae species of the genus Codakia. We sampled 10 Codakia orbicularis and 20 Codakia orbiculata distributed in 10 crystallizing dishes containing filtered seawater. During 1 month of investigation, we analyzed water of the dishes in order to detect any release of a symbiont using catalyzed report deposition-FISH techniques. For 140 observations realized during this period, we did not observe any release of symbionts. This suggests that the idea of host-to-host passage in Lucinidae is inaccurate. We could therefore consider that the transmission mode from generation to generation does not occur within Lucinidae, symbiosis appearing to be advantageous in this case only for the host, and constitutes an evolutionary dead-end for the bacteria.


Direct phosphonation of quinoxalin-2(1H)-ones under transition-metal-free conditions.
A direct C-H bond phosphonation of quinoxalin-2(1H)-ones with H-phosphonates, H-phosphinates or H-phosphine oxides has been developed. A wide variety of heteroaryl phosphonates were obtained in up to 92% yield for 20 examples under transition-metal-free conditions. This protocol tolerates a broad scope of substrates and features practicality, high efficiency, environmental friendliness and atom economy.


Manganese transport via the transferrin mechanism.
Excessive manganese (Mn) uptake by brain cells, particularly in regions like the basal ganglia, can lead to toxicity. Mn(2+) is transported into cells via a number of mechanisms, while Mn(3+) is believed to be transported similarly to iron (Fe) via the transferrin (Tf) mechanism. Cellular Mn uptake is therefore determined by the activity of the mechanisms transporting Mn into each type of cell and by the amounts of Mn(2+), Mn(3+) and their complexes to which these cells are exposed; this complicates understanding the contributions of each transporter to Mn toxicity. While uptake of Fe(3+) via the Tf mechanism is well understood, uptake of Mn(3+) via this mechanism has not been systematically studied. The stability of the Mn(3+)Tf complex allowed us to form and purify this complex and label it with a fluorescent (Alexa green) tag. Using purified and labeled Mn(3+)Tf and biophysical tools, we have developed a novel approach to study Mn(3+)Tf transport independently of other Mn transport mechanisms. This approach was used to compare the uptake of Mn(3+)Tf into neuronal cell lines with published descriptions of Fe(3+) uptake via the Tf mechanism, and to obtain quantitative information on Mn uptake via the Tf mechanism. Results confirm that in these cell lines significant Mn(3+) is transported by the Tf mechanism similarly to Fe(3+)Tf transport; although Mn(3+)Tf transport is markedly slower than other Mn transport mechanisms. This novel approach may prove useful for studying Mn toxicity in other systems and cell types.


Heterogeneous reactions of epoxides in acidic media.
Epoxides have recently been identified as important intermediates in the gas phase oxidation of hydrocarbons, and their hydrolysis products have been observed in ambient aerosols. To evaluate the role of epoxides in the formation of secondary organic aerosols (SOA), the kinetics and mechanism of heterogeneous reactions of two model epoxides, isoprene oxide and α-pinene oxide, with sulfuric acid, ammonium bisulfate, and ammonium sulfate have been investigated using complementary experimental techniques. Kinetic experiments using a fast flow reactor coupled to an ion drift-chemical ionization mass spectrometer (ID-CIMS) show a fast irreversible loss of the epoxides with the uptake coefficients (γ) of (1.7 ± 0.1) × 10(-2) and (4.6 ± 0.3) × 10(-2) for isoprene oxide and α-pinene oxide, respectively, for 90 wt % H(2)SO(4) and at room temperature. Experiments using attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) reveal that diols are the major products in ammonium bisulfate and dilute H(2)SO(4) (<25 wt %) solutions for both epoxides. In concentrated H(2)SO(4) (>65 wt %), acetals are formed from isoprene oxide, whereas organosulfates are produced from α-pinene oxide. The reaction of the epoxides with ammonium sulfate is slow and no products are observed. The epoxide reactions using bulk samples and Nuclear Magnetic Resonance (NMR) spectroscopy reveal the presence of diols as the major products for isoprene oxide, accompanied by aldehyde formation. For α-pinene oxide, organosulfate formation is observed with a yield increasing with the acidity. Large yields of organosulfates in all NMR experiments with α-pinene oxide are attributed to the kinetic isotope effect (KIE) from the use of deuterated sulfuric acid and water. Our results suggest that acid-catalyzed hydrolysis of epoxides results in the formation of a wide range of products, and some of the products have low volatility and contribute to SOA growth under ambient conditions prevailing in the urban atmosphere.


Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells.
Desipramine (DP) is a tricyclic antidepressant used for treating depression and numerous other psychiatric disorders. Recent studies have shown that DP can promote neurogenesis and improve the survival rate of hippocampal neurons. However, whether DP induces neuroprotection or promotes the differentiation of neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs derived from the hippocampal tissues of adult rats as an in vitro model to evaluate the modulation effect of DP on NSCs. First, we demonstrated that the expression of Bcl-2 mRNA and nestin in 2 microM DP-treated NSCs were up-regulated and detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The results of Western blotting and immunofluorescent study confirmed that Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs. Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed that DP protects the lipopolysaccharide (LPS)-induced apoptosis in NSCs, in part by activating the expression of Bcl-2. Furthermore, DP treatment significantly inhibited the induction of proinflammatory factor interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in the culture medium of LPS-treated NSCs mediated by Bcl-2 modulation. The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that DP significantly increased the functional production of serotonin (26+/-3.5 microM, DP-treated 96 h) and noradrenaline (50+/-8.9 microM, DP-treated 96 h) in NSCs through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In conclusion, the present results indicate that DP can increase neuroprotection ability by inhibiting the LPS-induced inflammatory process in NSCs via the modulation of Bcl-2 expression, as confirmed by the siRNA method.


Risk factors of impairment of shoulder function after axillary dissection for breast cancer.
Postoperative shoulder joint dysfunction has been observed at a certain rate after breast cancer surgery with axillary lymph node dissection. The purposes of this study were to verify the feasibility and effects of home-based exercise using a DVD and clarify the target of intensive intervention with physiotherapy by identifying the factors that cause postoperative shoulder dysfunction. The study comprised 237 female patients who underwent breast cancer surgery with axillary lymph node dissection, whose data were acquired until 3 months postoperatively. All patients were instructed to exercise at home using a DVD. Range of motion (ROM) of shoulder flexion and abduction and the disability of the arm, shoulder, and hand (DASH) score were measured before surgery, 1 week and 1, 2, and 3 months after surgery. As factors influencing the recovery of shoulder ROM at 3 months after surgery, the presence or absence of radiation and factors up to 1 month after surgery (age, body mass index, the relationship between operated side and dominant side of the hand, treatment modalities, and complications). Shoulder ROM and DASH scores had gradually recovered from 1 week to 3 months postoperatively. As the results of the multivariate analysis, the factors that were associated with the recovery of ROM of shoulder flexion at 3 months were the side of surgery corresponding to the dominant hand (negative factor) and the presence of paresthesia at 1 week postoperatively (positive factor) (p < 0.05). Radiation therapy and the side of surgery corresponding to the dominant hand were negative factors for the recovery of shoulder abduction (p < 0.01). Regarding the feasibility of the home exercise, 214/229 (93.4%), 172/210 (81.9%), and 139/206 (67.5%) of patients performed exercise at least once a day at 1, 2, and 3 months after surgery, respectively. Our result indicated that the side of surgery corresponding to the dominant hand was the inhibiting factor for recovery for both shoulder flexion and abduction at 3 months after surgery. Home-based exercise with DVD was considered feasible. For the verification of this effectiveness, a randomized control study should be planned in the future.


A Multiobjective Evolutionary Approach for Solving Large-Scale Network Reconstruction Problems via Logistic Principal Component Analysis.
Currently, the problem of uncovering complex network structure and dynamics from time series is prominent in many fields. Despite the recent progress in this area, reconstructing large-scale networks from limited data remains a tough problem. Existing works treat connections of nodes as continuous values, leaving a challenge of setting a proper cut-off value to distinguish whether the connections exist or not. Besides, their performances on large-scale networks are far from satisfactory. Considering the reconstruction error and sparsity as two objectives, this article proposes a subspace learning-based evolutionary multiobjective network reconstruction algorithm, called SLEMO-NR, to solve the aforementioned problems. In the evolutionary process, we assume that binary-coded individuals obey the Bernoulli distribution and can use the probability and natural parameter as alternative representations. Moreover, our approach utilizes the logistic principal component analysis (LPCA) to learn a subspace containing the features of the network structure. The offspring solutions are generated in the learned subspace and then can be mapped back to the original space via LPCA. Benefitting from the alternative representations, a preference-based local search operator (PLSO) is proposed to concentrate on finding solutions approximate to the true sparsity. The experimental results on synthetic networks and six real-world networks demonstrate that, due to the well-learned network structure subspace and the preference-based strategy, our approach is effective in reconstructing large-scale networks compared to six existing methods.


EX-vivo whole blood stimulation with A2E does not elicit an inflammatory cytokine response in patients with age-related macular degeneration.
Age-related macular degeneration (AMD) is a highly prevalent degenerative disease and a leading cause of vision loss worldwide. Evidence for an inflammatory component in the development of AMD exists, yet the exact mechanisms remain unclear. Bisretinoid N-retinylidene-N-retinylethanolamine (A2E) in retinal pigmental epithelial (RPE) cells, and in extracellular deposits constitutes a hallmark of AMD, but its role in the pathology of AMD is elusive. Here, we tested the hypothesis that A2E is responsible for the heightened inflammatory activity in AMD. To this end, we measured ex vivo mRNA expression of the cytokines TNF-α, IL-6, and IL-10 in whole blood samples after stimulation with A2E in a clinical sample of 27 patients with neovascular AMD and 24 patients with geographic atrophy secondary to AMD. Patients' spouses (n = 30) were included as non-affected controls. After stimulation with A2E, no statistical differences were found in the median expression level of TNF-α, IL-6, IL-10 between the control group, and the neovascular AMD and the geographic atrophy group. Our findings do not support evidence for the hypothesis, that A2E per se contributes to heightened inflammatory activity in AMD.


A case of acquired Brown syndrome after surgical repair of a medial orbital wall fracture.
A case of acquired Brown syndrome caused by surgical repair of medial orbital wall fracture is reported in the present paper. A 23-year-old man presented at the hospital with right periorbital trauma. Although the patient did not complain of any diplopia, the imaging study revealed a blow-out fracture of the medial orbital wall. Surgical repair with a calvarial bone autograft was performed at the department of plastic surgery. The patient was referred to the ophthalmologic department due to diplopia that newly developed after surgery. The prism cover test at distant fixation showed hypotropia of the right eye, which was 4 prism diopters (PD) in primary gaze, 20 PD in left gaze, while orthophoric in right gaze. Eye movement of the right eye was markedly limited on elevation in adduction with normal elevation in abduction with intorsion in the right eye present. Forced duction test of the right eye showed restricted elevation in adduction. Computerized tomography scan of the orbits showed the right superior oblique muscle was entrapped between the autografted bone fragment and posterior margin of the fracture. When repairing medial orbital wall fracture that causes Brown syndrome, surgeons should always be careful of entrapment of the superior oblique muscle if the implant is inserted without identifying the superior and posterior margin of the orbital fracture site.


Gaeumannomyces graminis, the take-all fungus and its relatives.
SUMMARY Take-all, caused by the fungus Gaeumannomyces graminis var. tritici, is the most important root disease of wheat worldwide. Many years of intensive research, reflected by the large volume of literature on take-all, has led to a considerable degree of understanding of many aspects of the disease. However, effective and economic control of the disease remains difficult. The application of molecular techniques to study G. graminis and related fungi has resulted in some significant advances, particularly in the development of improved methods for identification and in elucidating the role of the enzyme avenacinase as a pathogenicity determinant in the closely related oat take-all fungus (G. graminis var. avenae). Some progress in identifying other factors that may be involved in determining host range and pathogenicity has been made, despite the difficulties of performing genetic analyses and the lack of a reliable transformation system.


Burkholderia insulsa sp. nov., a facultatively chemolithotrophic bacterium isolated from an arsenic-rich shallow marine hydrothermal system.
Enrichment cultures inoculated with hydrothermally influenced nearshore sediment from Papua New Guinea led to the isolation of an arsenic-tolerant, acidophilic, facultatively aerobic bacterial strain designated PNG-April(T). Cells of this strain were Gram-stain-negative, rod-shaped, motile and did not form spores. Strain PNG-April(T) grew at temperatures between 4 °C and 40 °C (optimum 30-37 °C), at pH 3.5 to 8.3 (optimum pH 5-6) and in the presence of up to 2.7% NaCl (optimum 0-1.0%). Both arsenate and arsenite were tolerated up to concentrations of at least 0.5 mM. Metabolism in strain PNG-April(T) was strictly respiratory. Heterotrophic growth occurred with O2 or nitrate as electron acceptors, and aerobic lithoautotrophic growth was observed with thiosulfate or nitrite as electron donors. The novel isolate was capable of N2-fixation. The respiratory quinones were Q-8 and Q-7. Phylogenetically, strain PNG-April(T) belongs to the genus Burkholderia and shares the highest 16S rRNA gene sequence similarity with the type strains of Burkholderia fungorum (99.8%), Burkholderia phytofirmans (98.8%), Burkholderia caledonica (98.4%) and Burkholderia sediminicola (98.4%). Differences from these related species in several physiological characteristics (lipid composition, carbohydrate utilization, enzyme profiles) and DNA-DNA hybridization suggested the isolate represents a novel species of the genus Burkholderia, for which we propose the name Burkholderia insulsa sp. nov. The type strain is PNG-April(T) ( = DSM 28142(T) = LMG 28183(T)).


Inhaled corticosteroids and the beneficial effect of deep inspiration in asthma.
Deep inspiration-induced bronchoprotection and bronchodilation are impaired in asthma. We evaluated the effect of inhaled glucocorticosteroids on these phenomena. Two groups of subjects with asthma, 9 with moderate/severe hyperresponsiveness to methacholine, and 12 with mild/borderline hyperresponsiveness to methacholine, received inhaled fluticasone (880 microg daily) for 12 weeks. Serial bronchoprovocations were performed at Weeks 0, 6, and 12. The impact of deep inspirations on the airway response to methacholine was evaluated on the basis of inspiratory vital capacity and FEV(1). Fluticasone produced a wide spectrum of changes in the beneficial effects of deep inspiration, but the mean changes were not significant. The magnitude of the steroid-induced changes in bronchoprotection by deep inspiration correlated with baseline log PC(20) (the provocative concentration of methacholine causing a 20% fall in FEV(1); higher log PC(20) predicted improvement of the deep inspiration effect). The steroid-induced changes led to the emergence of strong positive correlations between the effects of deep inspiration and the methacholine log PC(20) that did not exist at baseline. We conclude that deep inspiration-induced bronchoprotection can be restored by inhaled glucocorticosteroids only in individuals with mild hyperresponsiveness. After steroid treatment, the beneficial effects of deep inspiration become significant determinants of the magnitude of airway hyperresponsiveness.


Does measuring body weight impact subsequent response to eating behavior questions?
If being weighed impacts perceptions of eating behavior, it is important that the order of questionnaires and weighing be considered in research and practice. A quasi-experimental study was performed to examine whether being weighed immediately prior to completing a questionnaire affects responses to eating behavior questions. It was hypothesized that being weighed would serve as a priming stimulus and increase measures of dietary restraint, disinhibition, and hunger. Trained researchers collected a sample of volunteers (n = 355) in 8 locations in the United States on two Saturdays in the summer of 2011. Half of the participants were weighed immediately prior to completing the Three Factor Eating Questionnaire (TFEQ), with the remaining half weighed immediately after TFEQ completion. A priori hypotheses were not supported despite replicating known relationships between weight, dietary restraint and disinhibition. Results indicated that being weighed first produced a difference in differences on disinhibition scores between low restraint score (95% CI = 4.65-6.02) and high restraint score (95% CI = 6.11-7.57) compared to being weighed after questionnaire completion (p = 0.003). However, this relationship was not significant when modeling restraint as a continuous variable, questioning the use of dichotomization. Being weighed is unlikely to be a strong enough prime to significantly change scores on eating behavior questionnaires for everyone, but may allow differences in restraint status to become more evident. Researchers assessing dietary restraint should be wary of the possibility of producing different results when treating restraint as continuous or dichotomous, which could lead to different interpretations.


Quantification of human bone microarchitecture damage in press-fit femoral knee implantation using HR-pQCT and digital volume correlation.
Primary press-fit fixation of femoral knee prostheses is obtained thanks to the inside dimensions of the implant being undersized with respect to the bone cuts created intra-operatively, dictated by a press-fit specified by the implant design. However, during prostheses press-fit implantation, high compressive and shear stresses at the implant-bone interface are generated, which causes permanent bone damage. The extent of this damage is unknown, but it may influence the implant stability and be a contributing factor to aseptic loosening, a main cause of revisions for knee arthroplasty. The aim of this ex-vivo study was to quantify, using high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging and Digital Volume Correlation (DVC), permanent bone deformation due to press-fit femoral knee implantation of a commonly used implant. Six human cadaveric distal femora were resected and imaged with HR-pQCT (60.7 μm/voxel, isotropic). Femurs were fitted with cementless femoral knee implants (Sigma PFC) and rescanned after implant removal. For each femur, permanent deformation was examined in the anterior, posterior-medial and posterior-lateral condyles for volumes of interest (VOIs) of 10 mm depth. The bone volume fraction (BV/TV) for the VOIs in pre- and post-implantation images was calculated, at increasing depth from the bone surface. DVC was applied on the VOIs pre- and post-implantation, to assess trabecular bone displacements and plastically accumulated strains. The "BV/TVpost/BV/TVpre ratio vs. depth" showed, consistently among the six femurs, three consecutive points of interest at increasing bone depth, indicating: bone removal (ratio<100%), compaction (ratio>100%) and no changes (ratio = 100%). Accordingly, the trabecular bone displacement computed by DVC suggested bone compaction up to 2.6 ± 0.8 mm in depth, with peak third principal strains of -162,100 ± 55,000 με (mean absolute error: 1,000-2,000 με, SD: 200-500 με), well above the yield strain of bone (7,000-10,000 με). Combining 3D-imaging, at spatial resolutions obtainable with clinical HR-pQCT, and DVC, determines the extent of plastic deformation and accumulated compressive strains occurring within the bone due to femoral press-fit implantation. The methods and data presented can be used to compare different implants, implant surface coatings and press-fit values. These can also be used to advance and validate computational models by providing information about the bone-implant interface obtained experimentally. Future studies using these methods can assist in determining the influence of bone damage on implant stability and the subsequent osseointegration.


CD94/NKG2 is the predominant inhibitory receptor involved in recognition of HLA-G by decidual and peripheral blood NK cells.
Prior studies demonstrated that NK cells isolated from adult peripheral blood kill the HLA-A-, HLA-B-, and HLA-C-deficient B lymphoblastoid cell line 721.221, but many are unable to kill 721.221 cells transfected with HLA-G, a molecule expressed preferentially on fetal cytotrophoblasts. To determine the biologic relevance of this recognition, we established NK cell clones from the placenta and demonstrate that these NK cells also were unable to kill 721.221 cells expressing HLA-G. Recognition of HLA-G by NK cells was prevented in the presence of anti-CD94 mAb, implicating CD94/NKG2 as the predominant inhibitory NK cell receptor for HLA-G used by decidual NK cells. In contrast, mAbs against the killer cell inhibitory receptors recognizing HLA-Cw3-related, HLA-Cw4-related, or HLA-Bw4 ligands did not affect NK cell killing of the HLA-G transfectants.


Sustained proliferation of PDX-1+ cells derived from human islets.
Ex vivo expansion of human beta-cells is an important step toward the development of cell-based insulin delivery systems in type 1 diabetes. Here, we report that human pancreatic endocrine cells can be expanded through 15 cell doublings in vitro for an estimated total 30,000-fold increase in cell number. We believe that the cells resulting from these cultures are of beta-cell origin, since they uniformly express the transcription factor PDX-1 (STF-1, IDX-1, IPF-1), which is initially seen only in cells positive for insulin and negative for the ductal cell marker cytokeratin (CK)-19. To rule out the possibility that PDX-1 expression might be induced by the culture conditions used here, cells from isolated human pancreatic ducts were cultured under the same conditions as the islet cells. Cells in these cultures expressed CK-19 but not PDX-1. Although the expanded beta-cells continued to express PDX-1, insulin expression was lost over time. Whether reexpression of islet-specific genes in vitro is essential for successful cell transplantation remains to be determined.


Dynamic changes in gut microbiota under the influence of smoking and TNF-α-blocker in patients with ankylosing spondylitis.
This study aimed to investigate the relationship among smoking, TNF-α-blocker therapy, and the dynamic changes in gut microbiota in patients with ankylosing spondylitis (AS). Using a 16S rRNA sequence, 98 fecal samples of 20 AS patients collected after 0, 1, 3 and 6 months of anti-TNF-α treatment and from 20 matched health controls were examined. The variation in composition, abundance, and diversity of gut microbiota was analyzed. The dynamic effects of smoking and treatment on gut microbiota and therapeutic efficacy in AS patients were studied. The increased relative abundance of microbiota in AS nonsmokers was g_Comamonas and g_Desulfovibrio, while that in AS smokers was g_Actinomyces, g_Collinsella, g_Lachnospiraceae_UCG-008, and g_Paraprevotella. The relative abundance of gut microbiota showed dynamic variation. The improvement rate of ASDAS in AS nonsmokers was higher than that in AS smokers (2.297 vs 1.736) after anti-TNF-α treatment. The β-diversity of gut microbiota in AS smokers was lower than that in AS nonsmokers and improved with treatment. Both smoking and TNF-α-blocker had significant effects on the composition, relative abundance, and diversity of gut microbiota in AS patients. The AS smokers characteristically shared g_Collinsella and g_Dorea. The relative abundance of gut microbiota revealed high variability and was in dynamic fluctuation during treatment. The response of gut microbiota to anti-TNF-α treatment was found to be heterogeneous and selective. AS nonsmokers showed a greater improvement rate of ASDAS-CRP with treatment than AS smokers did. The AS smokers showed a lower β-diversity of gut microbiota, and improved after treatment. Key Points • Characterized the dynamic variation in gut microbiota in AS patients classified as smokers and nonsmokers during treatment with anti-TNF-α. • Confirmed the interaction between smoking, anti-TNF-α therapy, and gut microbiota.


Stimulation of the proliferation of human bone cells in vitro by human monocyte products with interleukin-1 activity.
The process of induction of bone formation, which follows bone resorption during normal and pathological bone turnover, is well documented. However, the mechanisms responsible for this process are unclear. Mononuclear phagocytes present at the sites of bone remodeling could play a role in this "coupling" of bone formation to bone resorption. This study was designed to investigate such a possibility. By measuring both the increase in [3H]thymidine incorporation and in cell number, we found that human monocytes in culture released factors capable of stimulating the proliferation of osteoblast-like cells derived from human bone. Rapidly dividing cells exhibited a greater response to interleukin 1 (IL-1) than confluent cells. The factors are similar to IL-1 in that they exhibited the same molecular weight and isoelectric point, were present in fractions that contained IL-1 activity after gel filtration chromatography and isoelectric focusing, and showed similar dose-response characteristics. Proliferation was more marked when prostaglandin production by the cells, which was also stimulated by these factors, was inhibited by indomethacin. A factor produced by monocytes that affects osteoblast activity may be important in the coupling of osteoclast and osteoblast actions.


Excitation energies of a water-bridged twisted retinal structure in the bacteriorhodopsin proton pump: a theoretical investigation.
The first proton transfer in the bacteriorhodopsin photocycle takes place during the L → M transition. Structural details of the pre proton transfer L intermediate have been investigated using experiments and computations. Here, we assess L-state structural models by performing hybrid quantum mechanical/molecular mechanical molecular dynamics and excitation energy calculations. The computations suggest that a water-bridged twisted retinal structure gives the closest agreement with the experimental L/bR shift in the excitation energy.