Chiral stresses in nematic cell monolayers.
Recent experiments on monolayers of spindle-like cells plated on adhesive stripe-shaped domains have provided a convincing demonstration that certain types of collective phenomena in epithelia are well described by active nematic hydrodynamics. While recovering some of the hallmark predictions of this framework, however, these experiments have also revealed a number of unexpected features that could be ascribed to the existence of chirality over length scales larger than the typical size of a cell. In this article we elaborate on the microscopic origin of chiral stresses in nematic cell monolayers and investigate how chirality affects the motion of topological defects, as well as the collective motion in stripe-shaped domains. We find that chirality introduces a characteristic asymmetry in the collective cellular flow, from which the ratio between chiral and non-chiral active stresses can be inferred by particle-image-velocimetry measurements. Furthermore, we find that chirality changes the nature of the spontaneous flow transition under confinement and that, for specific anchoring conditions, the latter has the structure of an imperfect pitchfork bifurcation.


Addressing ethical challenges in HIV prevention research with people who inject drugs.
Despite recent advances in HIV prevention and treatment, high HIV incidence persists among people who inject drugs (PWID). Difficult legal and political environments and lack of services for PWID likely contribute to high HIV incidence. Some advocates question whether any HIV prevention research is ethically justified in settings where healthcare system fails to provide basic services to PWID and where implementation of research findings is fraught with political barriers. Ethical challenges in research with PWID include concern about whether research evidence will be translated into practice; concerns that research might exacerbate background risks; and ethical challenges regarding the standard of HIV prevention in research. While these questions arise in other research settings, for research with PWID, these questions are especially controversial. This paper analyses four ethical questions in determining whether research could be ethically acceptable: (1) Can researchers ensure that research does not add to the burden of social harms and poor health experienced by PWID? (2) Should research be conducted in settings where it is uncertain whether research findings will be translated into practice? (3) When best practices in prevention and care are not locally available, what standard of care and prevention is ethically appropriate? (4) Does the conduct of research in settings with oppressive policies constitute complicity? We outline specific criteria to address these four ethical challenges. We also urge researchers to join the call to action for policy change to provide proven safe and effective HIV prevention and harm reduction interventions for PWID around the world.


Lyme disease.
Lyme disease, a multisystem disorder, has now been reported to the Centers for Disease Control from 43 states of the United States. The disease is a tick-transmitted infectious disorder caused by the spirochete bacterium Borrelia burgdorferi. Lyme disease typically begins with the symptoms of flu associated with a characteristic skin rash, erythema chronicum migrans. The diagnosis of Lyme disease is best made by clinical examination and epidemiologic history, with serologic studies supporting the clinical diagnosis. Prompt diagnosis and early treatment with antibiotics will often lead to the resolution of symptoms and the prevention of late complications, Lyme carditis, neurologic manifestations, and arthritis.


Detection and molecular characterization of swine hepatitis E virus in North Carolina swine herds and their faecal wastes.
Recent findings of almost genetically indistinguishable swine and human strains, have suggested swine play a role in the transmission of hepatitis E virus (HEV). The extent to which HEV may be present and persist in the faecal waste generated from intensive swine operations is largely unknown. The fate of swine waste liquid is often land application, possibly resulting in unintentional seepage into groundwater or run-off into surface waters, hence validating concerns of human exposure risks. Freshly passed swine faeces, barn flush liquid waste, and lagoon liquid from production sites in North Carolina were surveyed periodically for HEV using RT-PCR primers located in ORF2. On three farms where HEV RNA was detected in swine faeces, it was also found in stored liquid waste on several occasions. HEV presence was related to swine age but not to animal management and waste management procedures, which varied amongst the farms. Seasonal patterns of HEV prevalence could not be established as viral RNA was isolated at all time points from two farms. Phylogenetic analysis of 212 bases of the genomic RNA indicated that isolates resembled the known US swine and human strains (percentage nucleic acid homology 91 to 94%), with one amino acid substitution.


Barriers to maternal workforce participation and relationship between paid work and health.
Families of children with disabilities experience extra financial strains, and mothers are frequently unable to participate in paid work because of caregiving obligations. A mailed survey and follow-up phone calls were used to gather data about mother's health, workforce participation and barriers to inclusion in the workplace (n = 152). Verbatim reports of issues that hindered workforce participation were analysed qualitatively to derive themes. Maternal health-related quality of life (HRQoL) was measured using the Short Form Health Survey Version 2 (SF-36v2). Norm-based conversions were used to compare HRQoL between working and non-working mothers and to compare to population norms. Eighty-two per cent of mothers in the sample wanted and needed to work for pay but indicated over 300 issues that prevent their work participation. Data analysis revealed 26 common issues which prevent work participation. These issues fit into three main categories: mother-related reasons (28%), child-related reasons (29%) and service limitations (43%). Mothers who worked (n = 83) reported significantly better HRQoL than mothers who did not work (n = 69) on five of the eight SF-36v2 dimensions and overall mental health. Compared to other working Australians, mothers in this study had higher education yet reported poorer health, lower family income and lower workforce participation. Respondents reported that service system limitations were the main barriers to participation in the paid workforce. Investigation of service changes such as increased respite care, availability of outside hours school care, improved professional competency and family-centred services is recommended in order to improve maternal participation in paid work.


Shape analysis of shark jaws as a tool to identify species involved in incidents with humans.
Shark incidents in Recife, Pernambuco state (Brazil), are registered since 1992. The occurrence of those events is in a relatively small area of urban beaches of about 30 km long, making up one of the world's highest indices of shark incidents per unit of area, totaling 64 casualties, of these 24 were fatal. To mitigate shark incidents, the knowledge on shark species involved is crucial given that each species has specific usage of the habitat and dissimilar feeding strategy. Jaws of five species caught along the Pernambuco coast (Brazil), corresponded to 2 specimens of Carcharhinus acronotus, 4 specimens of C. leucas, 1 of C. limbatus, 4 of Galeocerdo curvier and 3 of Sphyrna lewini. Relative Warps Analysis was applied to enhance possible differences among jaw shapes of the studied species. The consensus configuration from the 14 images was obtained. The first two relative warps components explained 70.17% of the total observed variation. Four distinct groups were clearly observed. Three groups were formed by single species, corresponding to G. curvier, C. leucas and S. lewini, respectively, and one group formed by the combination of C. acronotus and C. limbatus. As expected, due to its peculiar skull shape, S. lewini jaws are very different from other analyzed species, thus all observed individuals of this group were found isolated from the others, considering the horizontal axis. Relative warps and curvature analyses show to be useful tools in the forensic study of shark incidents. In general, jaws shape significantly differed among species.


Genetic correlations for litter weight weaned with growth, prolificacy, and wool traits in Columbia, Polypay, Rambouillet, and Targhee sheep.
Total litter weight weaned at 120 d postpartum per ewe lambing is often believed to be a measure of range ewe productivity. Genetic correlations for litter weight weaned at 120 d with prolificacy, growth, and wool traits for Columbia, Polypay, Rambouillet, and Targhee sheep were estimated using REML with animal models. Observations per breed ranged from 5,140 to 7,083 for litter weight weaned, from 5,140 to 7,095 for prolificacy traits, from 7,750 to 9,530 for growth traits, and from 4,603 to 18,443 for wool traits. Heritability estimates for litter weight weaned were low and ranged from 0.02 to 0.11. Fraction of variance due to permanent environmental effects averaged 0.05 and, due to effects of mates, averaged 0.01. Estimates of genetic correlations with litter weight weaned varied from breed to breed. The ranges were as follows: 0.42 to 0.65 with litter size born, 0.80 to 0.99 with litter size weaned, -0.22 to 0.28 with birth weight, -0.07 to 0.23 with average daily gain to weaning, -0.56 to 0.19 with fleece weight, -0.15 to 0.02 with fleece grade, and -0.11 to 0.08 with staple length. Results suggest that, if selection were practiced on litter weight weaned, the average correlated responses would be expected to be favorable or neutral for prolificacy, growth, and wool traits although responses might vary from breed to breed.


Dairying enabled Early Bronze Age Yamnaya steppe expansions.
During the Early Bronze Age, populations of the western Eurasian steppe expanded across an immense area of northern Eurasia. Combined archaeological and genetic evidence supports widespread Early Bronze Age population movements out of the Pontic-Caspian steppe that resulted in gene flow across vast distances, linking populations of Yamnaya pastoralists in Scandinavia with pastoral populations (known as the Afanasievo) far to the east in the Altai Mountains1,2 and Mongolia3. Although some models hold that this expansion was the outcome of a newly mobile pastoral economy characterized by horse traction, bulk wagon transport4-6 and regular dietary dependence on meat and milk5, hard evidence for these economic features has not been found. Here we draw on proteomic analysis of dental calculus from individuals from the western Eurasian steppe to demonstrate a major transition in dairying at the start of the Bronze Age. The rapid onset of ubiquitous dairying at a point in time when steppe populations are known to have begun dispersing offers critical insight into a key catalyst of steppe mobility. The identification of horse milk proteins also indicates horse domestication by the Early Bronze Age, which provides support for its role in steppe dispersals. Our results point to a potential epicentre for horse domestication in the Pontic-Caspian steppe by the third millennium BC, and offer strong support for the notion that the novel exploitation of secondary animal products was a key driver of the expansions of Eurasian steppe pastoralists by the Early Bronze Age.


The impact of trunk impairment on performance of wheelchair activities with a focus on wheelchair court sports: a systematic review.
Trunk impairment seems to impact significantly on performance in wheelchair court sports, but evidence to support this impression has never been systematically assessed. The objective of this study is to systematically review, describe and synthesise the literature investigating the impact of trunk impairment on wheelchair activities in court sports. This systematic review was performed according to the consensus statement for the meta-analysis of observational studies in epidemiology (MOOSE). The search strategy for original articles comprised Medline (1950- November 2014), Cinahl (1981-November 2014), and Embase (1980- November 2014), using the search terms: trunk, trunk muscles, postural balance, posture and wheelchair. Eligibility criteria for further review were 1) participants included experienced wheelchair users, 2) comparisons were made between a) participants with different levels of trunk impairment or b) between able bodied participants and participants with trunk impairment, or c) between participants with trunk impairment with and without compensatory equipment, and 3) outcome measures were quantitative data on wheelchair activities. For methodological quality assessment, the STROBE (Strengthening the reporting of observational studies in epidemiology) checklist was used. After assessment of 358 potentially relevant studies for the eligibility criteria, 25 studies were appropriate for methodological assessment. Twelve articles fulfilled the predetermined minimum of 15 reported items on the 22-item STROBE checklist. These studies were limited to observational studies with small populations. All but one study were restricted to patients with spinal cord injury (SCI). Limited evidence was found about the impact of trunk impairment on wheelchair activities. Reach to the front and multidirectional reach was further in able bodied persons than in persons with SCI. In a perturbation that equals deceleration in wheelchair court sports, able bodied persons maintain balance, whereas persons with SCI lose balance. No evidence was found to support a difference in acceleration between persons with partial trunk muscle strength and persons with full trunk muscle strength. For future research, there is a need for a test that includes all types of trunk impairment and identification of activities that determine performance in wheelchair court sports. Furthermore, populations of athletes with all trunk impairment types should be included.


The predictive value of the halo sign in color Doppler ultrasonography of the temporal arteries for diagnosing giant cell arteritis.
The diagnosis of giant cell arteritis (GCA) usually requires a temporal artery biopsy. Recently it has been reported that a periluminal dark halo, detected by color Doppler ultrasonography (US) of the temporal arteries, is a characteristic sign of GCA. We evaluated the predictive value of this dark halo sign in diagnosing GCA. During a period of 2 years 69 patients suspected of having GCA were examined by US of both temporal arteries. Temporal artery biopsy was performed in 32 of these patients. The diagnosis of GCA was made if a patient had a biopsy showing arteritis, or met all the following criteria: (1) American College of Rheumatology GCA classification criteria were fulfilled; (2) there was a prompt clinical response to treatment with 40-60 mg/day of prednisone; and (3) no other diagnosis related to the patient's symptoms was made during 6 month followup. Periluminal dark halo was observed in 24 of 69 patients. GCA was diagnosed in 12 of them, giving a positive predictive value (PPV) of only 50%. No halo was detected in 45 cases of which only 2 had GCA, resulting in a high negative predictive value (NPV) of 96%. The sensitivity and specificity of the halo sign for diagnosing GCA were 86% and 78%, respectively. The PPV of the halo sign in US of the temporal arteries is unsatisfactory for diagnosing GCA. However, the NPV is very high. Thus the lack of a halo can practically serve to rule out a diagnosis of GCA, and precludes the need for a biopsy in most instances.


The importance of social support for rural mental health.
While the mentally ill are considered to be vulnerable as a group, those who are mentally ill and reside in rural communities are at a greater disadvantage due to limited access to health care, a scarcity of resources, and traditional cultural belief systems. Social support has been found to have a direct effect on the well-being of families and individuals. Specific strategies are presented which will assist rural health nurses in providing the support systems necessary to help rural residents in managing and coping with stress and mental health problems.


Control of peripheral glial cell proliferation: enteric neurons exert an inhibitory influence on Schwann cell and enteric glial cell DNA synthesis in culture.
Neuronal membranes from rat dorsal root ganglia provide a mitogenic signal to cultured Schwann cells and it has been suggested this is an important factor in regulating Schwann cell numbers during development. In this study, the influence of enteric neurons on the DNA synthesis of both Schwann cells and enteric glia has been investigated as well as the effect of axonal membrane fractions (axolemma) on enteric glia. The proliferation rate of rat Schwann cells and enteric glia was assessed in culture using [3H]thymidine uptake and autoradiography in combination with immunolabelling to identify cell types. When purified rat Schwann cells were co-cultured with guinea pig enteric neurons, their DNA synthesis rate was reduced compared with control cultures of pure Schwann cells or Schwann cells not close to neurites or neuronal cell bodies. Nevertheless, in accordance with previous findings that sensory neurons stimulate Schwann cell division, these Schwann cells increased their DNA synthesis rate when in contact with neurites from purified guinea pig or adult rat dorsal root ganglion neurons and on exposure to bovine axolemmal fractions. The enteric neurons also suppressed the DNA synthesis of enteric glia in co-cultures of purified enteric neurons and enteric glia, while bovine axolemma stimulated their DNA synthesis. These results indicate that a mitotic inhibitory signal is associated with enteric neurons and can exert its effect on both Schwann cells and enteric glia, and that enteric glia, like Schwann cells, are stimulated to divide by axolemmal fractions. It thus seems possible that during development glial cell numbers in the peripheral nervous system may be controlled by both positive and negative regulators of cell growth.


Factors influencing the survival of 451 transient ischemic attack patients.
Four hundred fifty-one patients with transient ischemic attacks (TIA) occurring within 1 month of hospitalization, admitted during 1977-1983, were analyzed to establish the effect on survival of age, race, sex, distribution of TIA, cigarette smoking, previous cerebral infarction or hemorrhage, previous TIA, or history of ischemic heart disease, valvular heart disease, cardiac dysrhythmia, hypertension, and diabetes mellitus. Proportional hazards analysis revealed that decreased survival was associated with increasing age, carotid artery distribution TIAs (compared with vertebrobasilar distribution TIAs), cigarette smoking, previous contralateral stroke, ischemic heart disease, and diabetes mellitus. We found great variation in the estimated survival of TIA patients, ranging from 5-year survivals of greater than 95% for 60-year-old patients with none of these risk factors to less than 25% for patients with all of these risk factors. Although the survival of the strata differed, the average mortality rates for this series of patients was about one-half of that observed for 225 patients accessed and followed by our center during 1961-1973.


A systematic review of soft-to-hard tissue ratios in orthognathic surgery. Part IV: 3D analysis - Is there evidence?
The objective of this study was to determine the soft-to-hard tissue ratio using 3D analysis in different types of orthognathic surgery. A systematic search for relevant studies published in different languages through December 2016 was performed in the Medline, Embase, Lilacs, Scopus, and Science Direct databases. Additional studies were identified by reference analysis. The methodological quality of the included studies was evaluated using the method proposed by the Effective Public Health Practice Project. The level of evidence was assessed using the Level of Evidence (LOE) scale from the Oxford Center for Evidence-Based Medicine. A total of 11 articles with 461 patients were included in the review, comprising 5 retrospective study and 6 prospective studies. The latter included 5 studies that performed anatomical area analyses of postoperative soft tissue results in the context of software-based planned surgeries without regard to hard tissues and 6 articles that presented analyses related to soft tissue in the preoperative and postoperative stage with certain points to be considered in hard tissues. The analysis of bias in the articles revealed a weak methodology in all included studies, which made it impossible to perform any type of comparison. Bias governs many of the published studies related to 3D analysis. There are no data that can be applied to determine the soft-to-hard tissue ratio using 3D analysis in orthognathic surgery.


Do wearable alcohol-based handrub dispensers increase hand hygiene compliance? - a mixed-methods study.
Hand Hygiene (HH) compliance was shown to be poor in several studies. Improving the availability of alcohol-based hand rub (ABHR) is a cornerstone for increasing HH compliance. In this study, we introduced wearable dispensers for ABHR in an Emergency Department (ED) well equipped with mounted ABHR dispensers and accompanied this single-modal intervention by a quasi-experimental mixed-method study. The study was performed in the ED of the University Hospital Zurich, Switzerland, a 950-bed tertiary teaching hospital. During a five-week baseline period and a seven-week intervention period, we observed HH compliance according to the WHO 'Five Moments' concept, measured ABHR consumption, and investigated perceived ABHR availability, self-reported HH compliance and knowledge of HH indications by questionnaire. Multivariable logistic regression was used to identify independent determinants for HH compliance. In addition, semi-structured interviews were conducted and thematically analyzed to assess barriers and facilitators for the use of the newly introduced dispensers. Across 811 observed HH opportunities, the HH compliance for all moments was 56% (95% confidence interval (CI), 51-62%) during baseline and 64% (CI, 59-68%) during intervention period, respectively. In the multivariable analysis adjusted for sex, profession, and WHO HH moment, there was no difference in HH compliance between baseline and intervention (adjusted Odds ratio: 1.22 (0.89-1.66), p = 0.22), No significant changes were observed in consumption and perceived availability of ABHR. During intervention, 7.5% ABHR was consumed using wearable dispensers. HCP perceived wearable dispensers as unnecessary since mounted dispensers were readily accessible. Poor ergonomic design of the wearable dispenser emerged as a main barrier, especially its lid and fastening mechanism. Interviewees identified two ideal situations for wearable dispensers, HCP who accompany patients from ED to other wards, and HCP approaching a patient from a non-patient areas in the ED such as the central working station or the meeting room. The introduction of wearable dispensers did not increase observed hand hygiene compliance or ABHR consumption in an ED already well equipped with mounted dispensers. For broader acceptance and use, wearable dispensers might benefit from an optimized ergonomic design.


Real-Time Imaging of Self-Organization and Mechanical Competition in Carbon Nanotube Forest Growth.
The properties of carbon nanotube (CNT) networks and analogous materials comprising filamentary nanostructures are governed by the intrinsic filament properties and their hierarchical organization and interconnection. As a result, direct knowledge of the collective dynamics of CNT synthesis and self-organization is essential to engineering improved CNT materials for applications such as membranes and thermal interfaces. Here, we use real-time environmental transmission electron microscopy (E-TEM) to observe nucleation and self-organization of CNTs into vertically aligned forests. Upon introduction of the carbon source, we observe a large scatter in the onset of nucleation of individual CNTs and the ensuing growth rates. Experiments performed at different temperatures and catalyst particle densities show the critical role of CNT density on the dynamics of self-organization; low-density CNT nucleation results in the CNTs becoming pinned to the substrate and forming random networks, whereas higher density CNT nucleation results in self-organization of the CNTs into bundles that are oriented perpendicular to the substrate. We also find that mechanical coupling between growing CNTs alters their growth trajectory and shape, causing significant deformations, buckling, and defects in the CNT walls. Therefore, it appears that CNT-CNT coupling not only is critical for self-organization but also directly influences CNT quality and likely the resulting properties of the forest. Our findings show that control of the time-distributed kinetics of CNT nucleation and bundle formation are critical to manufacturing well-organized CNT assemblies and that E-TEM can be a powerful tool to investigate the mesoscale dynamics of CNT networks.


CD16+ monocytes in patients with cancer: spontaneous elevation and pharmacologic induction by recombinant human macrophage colony-stimulating factor.
The small subset of circulating monocytes that express the maturation-associated CD16 antigen has recently been reported to be elevated in patients with bacterial sepsis. We now show that this novel CD16+ monocyte population is also spontaneously expanded in patients with cancer. We studied 14 patients with metastatic gastrointestinal carcinoma enrolled ina clinical trial of recombinant human macrophage colony-stimulating factor (rhMCSF) plus monoclonal antibody D612. We found that before any cytokine treatment, 12 of 14 patients constitutively displayed significant elevations in both the percentage and the absolute number of CD16+ monocytes, as compared with both normal subjects and ill patients with elevated monocyte counts but without malignancy. CD16+ monocytes accounted for 46% +/- 22% of total monocytes in the patients with cancer versus 5% +/- 3% for controls (P < .01). The increase was not attributable to infection or intercurrent illness and appeared to be associated with the underlying malignancy itself. A similar spontaneous elevation of CD16+ monocytes was observed in 35 of 44 additional patients diagnosed with a variety of other solid tumors. When patients with gastrointestinal carcinoma were treated with rhMCSF, there was a marked further increase in the percentage of CD16+ monocytes (to 83% +/- 11%), as well as in the absolute number of CD16+ cells and the level of CD16 antigen expression. In every case, the patients with cancer showed a greater CD16+ monocyte response than the maximal response obtained in normal volunteer subjects treated witha similar regimen of rhMCSF (n = 5, P < .001), suggesting that the presence of malignancy primed patients for enhanced responsiveness to rhMCSF. We hypothesize that spontaneous expansion of the CD16+ monocyte population may represent a novel biologic marker for a widespread and previously unsuspected host immune response to malignancy.


Toward truly optimal IMRT dose distribution: inverse planning with voxel-specific penalty.
To establish an inverse planning framework with adjustable voxel penalty for more conformal IMRT dose distribution as well as improved interactive controllability over the regional dose distribution of the resultant plan. In the proposed coarse-to-fine planning scheme, a conventional inverse planning with organ specific parameters is first performed. The voxel penalty scheme is then "switched on" by allowing the prescription dose to change on an individual voxel scale according to the deviation of the actual voxel dose from the ideally desired dose. The rationale here is intuitive: when the dose at a voxel does not meet its ideal dose, it simply implies that this voxel is not competitive enough when compared with the ones that have met their planning goal. In this case, increasing the penalty of the voxel by varying the prescription can boost its competitiveness and thus improve its dose. After the prescription adjustment, the plan is re-optimized. The dose adjustment/re-optimization procedure is repeated until the resultant dose distribution cannot be improved anymore. The prescription adjustment on a finer scale can be accomplished either automatically or manually. In the latter case, the regions/voxels where a dose improvement is needed are selected visually, unlike in the automatic case where the selection is done purely based on the difference of the actual dose at a given voxel and its ideal prescription. The performance of the proposed method is evaluated using a head and neck and a prostate case. An inverse planning framework with the voxel-specific penalty is established. By adjusting voxel prescriptions iteratively to boost the region where large mismatch between the actual calculated and desired doses occurs, substantial improvements can be achieved in the final dose distribution. The proposed method is applied to a head and neck case and a prostate case. For the former case, a significant reduction in the maximum dose to the brainstem is achieved while the PTV dose coverage is greatly improved. The doses to other organs at risk are also reduced, ranging from 10% to 30%. For the prostate case, the use of the voxel penalty scheme also results in vast improvements to the final dose distribution. The PTV experiences improved dose uniformity and the mean dose to the rectum and bladder is reduced by as much as 15%. Introduction of the spatially non-uniform and adjustable prescription provides room for further improvements of currently achievable dose distributions and equips the planner with an effective tool to modify IMRT dose distributions interactively. The technique is easily implementable in any existing inverse planning platform, which should facilitate clinical IMRT planning process and, in future, off-line/on-line adaptive IMRT.


Psychosocial risk factors for the onset of abdominal pain. Results from a large prospective population-based study.
To determine the psychosocial risk factors for the development of abdominal pain and to determine whether, in those people who consulted, symptoms had been attributed to an organic cause. Prospective population-based postal survey with follow-up survey at 12 months. A mixed sociodemographic suburban area of Manchester, UK. Subjects aged 18-65 years were randomly selected from a population-based primary care register who had responded to a detailed pain questionnaire, which included a pain manikin drawing. They also completed the following psychosocial instruments: General Health Questionnaire, Somatic Symptom Checklist, Fatigue Questionnaire and the Illness Attitude Scales (including the 'health anxiety' and 'illness behaviour' sub-scales). The onset of new abdominal pain. Of the 1953 participants at baseline, 1763 were free of abdominal pain: 1551 were followed up at 12 months (adjusted follow-up rate of 92%) of which 69 subjects reported new abdominal pain (new onset rate 4.6%). New abdominal pain was similar in females (4.9%) and males (4.2%), and did not vary by age group. Baseline factors which predicted onset were high levels of fatigue (odds ratio [OR] = 3.3, 95% CI: 1.9-5.8), psychological distress (OR = 3.4, 95% CI: 1.9-6.0), high scores on the illness behaviour scale (OR = 3.3, 95% CI: 1.7-6.7) and high levels of health anxiety (OR = 2.1, 95% CI: 1.1-3.9). Reporting low back pain at baseline was also associated with an increased risk of reporting abdominal pain (OR = 2.0, 95% CI: 1.2-3.3). On multivariate analysis, high levels of psychological distress and aspects of prior illness behaviour were the major independent predictors of outcome. Of those who sought health care, only one consultation led to a definite diagnosis. In subjects free of abdominal pain, psychological distress, fatigue, health anxiety and illness behaviour are predictors of future onset rather than merely a consequence of symptoms. These results suggest that abdominal pain shares some common features of onset with pain at other sites thought not to be primarily organic in origin.


Reverse genetics based rgH5N2 vaccine provides protection against high dose challenge of H5N1 avian influenza virus in chicken.
An inactivated vaccine was developed using the rgH5N2 virus (6 + 2 reassortant) generated by plasmid based reverse genetics system (RGS) with WSN/33/H1N1 as backbone virus. Following mutation of the basic amino acid cleavage site RRRKKR*GLF to IETR*GLF, the H5-HA (haemagglutinin) gene of the selected donor H5N1 virus (A/chicken/West Bengal/80995/2008) of antigenic clade 2.2 was used along with the N2-NA gene from H9N2 field isolate (A/chicken/Uttar Pradesh/2543/2004) for generation of the rgH5N2 virus. A single dose (0.5 ml/bird) of the inactivated rgH5N2 vaccine protected 100% of the vaccinated chickens (n = 10) on 28(th) dpv (early challenge) and 90% of the vaccinated chickens (n = 10) on 200(th) dpv (late challenge) against high dose challenge with HPAI virus (10(9) EID50/bird). Challenge virus shedding via oropharynx and cloaca of the vaccinated chickens was detectable by realtime RT-PCR during 1-5 dpc and 1-9 days dpc in the early and the late challenge, respectively. The protective level of antibodies (mean HI titre > 128) was maintained without booster vaccination for 200 days. The present study provides the experimental evidence about the extent of protection provided by a reverse genetics based vaccine for clade 2.2 H5N1 viruses against challenge with high dose of field virus at two different time points (28 dpv and 200 dpv). The challenge study is uniquely different from the previous similar experiments on account of 1000 times higher dose of challenge and protection at 200 dpv. The protection and virus shedding data of the study may be useful for countries planning to use H5 vaccine in poultry especially against the clade 2.2 H5N1 viruses.


Cellular glutathione level does not predict ovarian cancer cells' resistance after initial or repeated exposure to cisplatin.
Cisplatin resistance development is a major obstacle in ovarian cancer treatment. One of the most important mechanisms underlying cisplatin resistance is drug detoxification by glutathione. In the present study, the importance of initial or repeated exposure to cisplatin in glutathione dependent resistance was investigated. To this purpose, some cisplatin sensitive and resistant variants of human ovarian cancer cell lines providing an appropriate range of cisplatin sensitivity were selected. Clonogenic survival assay was performed to evaluate cisplatin resistance and intracellular contents of reduced (GSH) and oxidized (GSSG) glutathione were analyzed using an HPLC method. Our results indicated that the intracellular GSH and GSSG concentrations were nearly equal in A2780 and A2780CP cells, while the A2780CP cells showed 14 times more resistance than the A2780 cells after initial exposure to cisplatin. A2780-R1 and A2780-R3 cells which have been repeatedly exposed to cisplatin also showed no significant difference in glutathione content, even though A2780-R3 was about two times more resistant than A2780-R1. Moreover, intracellular GSH/GSSG ratio decreased in the resistant cells, reflecting a shift towards a more oxidizing intracellular environment indicative of oxidative stress. As a conclusion, it seems that although the intracellular glutathione concentration increases after repeated exposure to cisplatin, there is no clear correlation between the intracellular GSH content in ovarian cancer cells and their resistance to cisplatin neither after initial nor after repeated exposure to this drug.


Diagnostic accuracy of rK28-based immunochromatographic rapid diagnostic tests for visceral leishmaniasis: a prospective clinical cohort study in Sudan.
Rapid diagnostic tests (RDTs) for visceral leishmaniasis (VL) based on rK39 antigen showed suboptimal sensitivity in East Africa. A prospective clinical cohort study in Sudan was designed to validate a novel rK28-based RDT for Leishmania donovani VL. Patients (n=285) suspected of VL by residency, fever for ≥2 weeks, splenomegaly with no prior reported VL, and negative for malaria were consecutively enrolled at three Sudanese sites in 2012-2013 and informed consent obtained. Two human readers, who were blinded to the clinical status and other RDT results, evaluated patient whole blood (WB) and serum on the rK28 RDT. Based on Leishmania parasite detection in lymph node or bone marrow aspirates (Giemsa-stained smears or culture in Novy-MacNeal-Nicolle medium), patients were categorized as VL cases (n=200) or VL controls (n=85). The rK28 RDT had high specificity using either WB (100% [85/85]) or serum (97.6% [83/85]) and exhibited greater sensitivity (WB, 92.5% [185/200]; serum, 94.5% [189/200]) than a direct agglutination test performed with the same sera (92.9% [79/85] and 83.5% [167/200] for specificity and sensitivity, respectively). Two blinded readers scored a given WB or serum sample the same on the rK28 RDT 99.6% and 100% of the time, respectively. A reader scored each individual donor's paired WB and serum rK28 RDT results the same 97.2% of the time. An inexpensive rK28 RDT that performs robustly with WB or serum will be valuable for diagnosing cases of VL in East Africa.


An evaluation of Comparative Genome Sequencing (CGS) by comparing two previously-sequenced bacterial genomes.
With the development of new technology, it has recently become practical to resequence the genome of a bacterium after experimental manipulation. It is critical though to know the accuracy of the technique used, and to establish confidence that all of the mutations were detected. In order to evaluate the accuracy of genome resequencing using the microarray-based Comparative Genome Sequencing service provided by Nimblegen Systems Inc., we resequenced the E. coli strain W3110 Kohara using MG1655 as a reference, both of which have been completely sequenced using traditional sequencing methods. CGS detected 7 of 8 small sequence differences, one large deletion, and 9 of 12 IS element insertions present in W3110, but did not detect a large chromosomal inversion. In addition, we confirmed that CGS also detected 2 SNPs, one deletion and 7 IS element insertions that are not present in the genome sequence, which we attribute to changes that occurred after the creation of the W3110 lambda clone library. The false positive rate for SNPs was one per 244 Kb of genome sequence. CGS is an effective way to detect multiple mutations present in one bacterium relative to another, and while highly cost-effective, is prone to certain errors. Mutations occurring in repeated sequences or in sequences with a high degree of secondary structure may go undetected. It is also critical to follow up on regions of interest in which SNPs were not called because they often indicate deletions or IS element insertions.


Rare and unusual glycosylation of peptides and proteins.
Glycosylation represents the most complex co- and post-translational modification of proteins. In addition to N- and O-glycans, almost all combinations, including the nature of the carbohydrate moiety and the amino-acid involved, but also the type of the chemical linkage, can be isolated from natural glycoconjugates. This diversity correlates with the importance and the variety of the biological processes (and consequently the diseases) glycosides are involved in. This review focuses on rare and unusual glycosylation of peptides and proteins.


Transport, fate and speciation of heavy metals (Pb, Zn, Cu, Cd) in mine drainage: geochemical modeling and anodic stripping voltammetric analysis.
The maximum concentrations (ppb) of heavy metals in the mine drainage (pH: down to 3.3) of Chonam-ri creek in the abandoned Kwangyang gold-silver mine, South Korea, are 22600 Zn, 2810 Cu, 182 Cd, and 109 Pb. A small, limestone-infused retention pond, about 440 meters downstream from the waste dump, plays an important role in the removal of heavy metals: the factors of reduction for Zn, Cu, Cd, and Pb are 12, 24, 14, and 14, respectively. This is due to the pH increase (up to >5.4) accompanying adsorption onto and/or coprecipitation with Fe- and Al-hydroxides (goethite and gibbsite). From the waste dump to the pond, heavy metal concentrations also progressively decrease due to pH increase. Geochemical modeling (using the computer code WATEQ4F) predicts that free aqueous metal ions are dominant (mostly >70% for Cu and Zn, and >60% for Pb and Cd) in samples collected upstream from the pond, whereas complexing with sulfate, carbonate and hydroxyl ions becomes important in the samples collected downstream. The comparison between the concentrations of electrochemically labile species (determined by Anodic Stripping Voltammetry) and the result of computer modeling shows that Cd and Zn are present predominantly as labile inorganic species throughout the whole range of the creek. However, Cu and Pb in the samples collected downstream from the pond largely form electrochemically inert species (possibly, metal-organic complexes). The above results indicate that the retention pond is effective in reducing the toxicity of heavy metals, especially Cu and Pb.


Ru/ITO: a carbon-free cathode for nonaqueous Li-O2 battery.
Ru nanoparticles deposited on a conductive support indium tin oxide (Ru/ITO) were applied as a carbon-free cathode in a nonaqueous Li-O2 battery. The Li-O2 battery with Ru/ITO showed much lower charging overpotentials and better cycling performance at 0.15 mA/cm(2) than those with Super P (SP) and SP loaded with Ru nanoparticles (Ru/SP) as the cathodes. The carbon-free cathode Ru/ITO can effectively reduce formation of Li2CO3 or other Li carbonates in a discharging process, which cannot be completely decomposed upon charging, in comparison with the carbon based cathode. The improved performance of Ru/ITO can be attributed to the superior catalytic activity of Ru nanoparticles toward oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) and the absence of carbon that has been reported to react with Li2O2 to form Li2CO3.


Colonization, Baker's law, and the evolution of gynodioecy in Hawaii: implications from a study of Lycium carolinianum.
As Baker's law suggests, the successful colonization of oceanic islands is often associated with uniparental reproduction (self-fertility), but the high incidence of dimorphism (dioecy, gynodioecy) on islands complicates this idea. Lycium carolinianum is widespread, occurring on the North American mainland and the Hawaiian Islands. We examined Baker's ideas for mainland and island populations of L. carolinianum and examined inbreeding depression as a possible contributor to the evolution of gynodioecy on Maui. Controlled crosses were conducted in two mainland populations and two populations in Hawaii. Treatments included self and cross pollination, unmanipulated controls, and autogamy/agamospermy. Alleles from the self-incompatibility S-RNase gene were isolated and compared between mainland and island populations. Given self-compatibility in Hawaii, we germinated seeds from self- and cross- treatments and estimated inbreeding depression using seven traits and a measure of cumulative fitness. Mainland populations of Lycium carolinianum are predominately self-incompatible with some polymorphism for self-fertility, whereas Hawaiian populations are self-compatible. Concordantly, S-RNase allelic diversity is reduced in Hawaii compared to the mainland. Hawaiian populations also exhibit significant inbreeding depression. Self-compatibility in Hawaii and individual variation in self-fertility in mainland populations suggests that a colonization filter promoting uniparental reproduction may be acting in this system. Comparison of S-RNase variation suggests a collapse of allelic diversity and heterozygosity at the S-RNase locus in Hawaii, which likely contributed to mate limitation upon arrival to the Pacific. Inbreeding depression coupled with autonomous self-fertilization may have led to the evolution of gynodioecy on Maui.


Extremely fast pRF mapping for real-time applications.
Population receptive field (pRF) mapping is a popular tool in computational neuroimaging that allows for the investigation of receptive field properties, their topography and interrelations in health and disease. Furthermore, the possibility to invert population receptive fields provides a decoding model for constructing stimuli from observed cortical activation patterns. This has been suggested to pave the road towards pRF-based brain-computer interface (BCI) communication systems, which would be able to directly decode internally visualized letters from topographically organized brain activity. A major stumbling block for such an application is, however, that the pRF mapping procedure is computationally heavy and time consuming. To address this, we propose a novel and fast pRF mapping procedure that is suitable for real-time applications. The method is built upon hashed-Gaussian encoding of the stimulus, which tremendously reduces computational resources. After the stimulus is encoded, mapping can be performed using either ridge regression for fast offline analyses or gradient descent for real-time applications. We validate our model-agnostic approach in silico, as well as on empirical fMRI data obtained from 3T and 7T MRI scanners. Our approach is capable of estimating receptive fields and their parameters for millions of voxels in mere seconds. This method thus facilitates real-time applications of population receptive field mapping.


Respiratory symptoms in Swiss farmers: an epidemiological study of risk factors.
The study was undertaken to assess the prevalence and risk factors of self-reported asthma, symptoms of chronic bronchitis, hay fever, and work-related respiratory symptoms in Swiss farmers as well as to compare the prevalence rates of respiratory symptoms with the Swiss population (SAPALDIA-Study). An epidemiological study was performed with a representative sample of 1,542 Swiss farmers using a self-administered questionnaire. To investigate the effect of the type of farming on reported symptoms, the farmers were subdivided into seven groups according to the time farmers spent in different animal confinement buildings. A multivariate analysis was performed by the methods of binary and multivariate logistic regression adjusted for age and smoking habits. In farmers the prevalence rate was 16.0% for chronic bronchitis, 15.4% for asthma symptoms, and 42.0% for reporting at least one work-related symptom. Using logistic regression analysis, it was established that poultry farming and pig/cattle farming was a risk factor for reporting nasal irritation at work [OR 5.33, (1.57-18.0), OR 3.37 (1.04-10.87)]. Poultry farmers experienced the highest symptom rates. In crop farmers, the prevalence for chronic bronchitis was increased [OR 2.32 (1.03-5.23)]. Over 4 hr spent per day in animal confinement buildings more than doubled the risk for reporting chronic bronchitis [OR 2.61 (1.01-6.76)] and phlegm [OR 2.3 (0.99-5.4)] independent of the type of farming. The comparison of Swiss farmers with the Swiss population showed a twofold elevated risk of reporting chronic bronchitis [OR 1.89 (1.32-2.95)] and a 4.5-fold elevated risk for bringing up phlegm regularly [OR 4.5 (3.25-6.69)] in farmers. In contrast, the risk of farmers to report nasal allergies was less than half as high [OR 0.40 (0.29-0.56)] as that of the general population. This study shows that agricultural work in Switzerland is associated with an elevated risk for reporting symptoms of chronic bronchitis and chronic phlegm compared with the general Swiss population. These main results most likely indicate occupational disorders as the exposure-response relationship (hours spent in animal confinements) was particularly obvious for these symptoms.


Stakeholder views on the impact of nurse prescribing on dermatology services.
To explore stakeholder views on the impact of nurse prescribing on dermatology services. Nurse led care enhances the services that dermatology patients receive. Research indicates that care delivered by nurse prescribers can improve efficiency and access to medicines. There is no evidence exploring the impact of nurse prescribing on the configuration of dermatology services. Case study. A collective case study of 10 practice settings across England where nurses prescribed medicines for dermatology patients. A thematic analysis of semi-structured interview data collected during 2006 and 2007. Participants were qualified nurse prescribers, administrative staff, doctors and non-nurse prescribers. Nurse prescribing was reported to support and facilitate the modernisation of dermatology services. It enabled nurses to make effective use of their knowledge and skills, overcome delays in treatment and provide faster access to medicines. However several organisational issues restricted the success of the initiative. Nurse prescribing is successfully being used to support and deliver a range of services to dermatology patients. Stakeholders reported that both patients and staff had benefited by the adoption of this role by nurses. However issues over support and access to CPD and capacity of the workforce were identified as potential barriers which could affect the contribution of nurse prescribing to dermatology patients. Nurse prescribing contributes to the services provided to dermatology patients; Nurse supplementary prescribing contributes to the ability of dermatology nurse specialists to work in teams and prescribe complex medicines; Provision of adequate support and strategic planning are essential if the impact of nurse prescribing is to be fully realised.


Determinants of breast self-examination among women of lower income and lower education.
This study investigated breast self-examination (BSE) frequency and quality and determinants of BSE practice in two samples of women: (a) women of childbearing age who were of lower income and lower education and (b) women of childbearing age who were of higher income and higher education. Mothers recruited from a pediatric practice completed a questionnaire addressing BSE frequency and quality and factors derived from the Health Belief Model that might influence performance. Results indicated that there were no differences in mean BSE frequency or quality between the two samples. Regression analyses revealed that the perceived barriers index, consisting of forgetting, exclusive reliance on medical personnel for breast exams, and low confidence in ability to perform BSE, was the single best predictor of BSE frequency, accounting for 67% of the variance in each sample of women. When quality of BSE was examined, knowledge of BSE was the best predictor.


First report of Basidiolum fimbriatum since 1861, with comments on its development, occurrence, distribution and relationship with other fungi.
An obscure parasitic fungus, Basidiolum fimbriatum, was found on Amoebidium parasiticum (Amoebidiales) associated with Caenis sp. (mayfly) nymphs, during a survey of gut fungi (Trichomycetes) from a small stream in northeastern Kansas, USA. The hindguts of the nymphs harboured a species of Legeriomycetaceae and Paramoebidium sp. This is the first report of the ectocommensal protozoan, A. parasiticum, associated with the gills of Caenidae (Ephemeroptera), and of B. fimbriatum in the 142 years since its original documentation from Wiesbaden, Germany. B. fimbriatum is recorded from two midwestern USA states (Kansas and Iowa) and the morphological and developmental features of the parasite on its host are compared with Cienkowski's original observations and interpretation. B. fimbriatum is characterized as a parasitic fungus possessing merosporangia that from on a simple pyriform thallus that penetrates and consumes its host via a haustorial network. The hypothesis that B. fimbriatum is most closely related to members of the order Zoopagales sensu Benjamin (1979) is proposed. The importance of future collections and molecular-based phylogenetic approaches to place this parasitic fungus within a current system of classification are highlighted.


Melanoma cell expression of CD200 inhibits tumor formation and lung metastasis via inhibition of myeloid cell functions.
CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1⁻/⁻C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1⁻/⁻C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1⁺ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1⁺ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy.


Asymmetric bead aggregation for microfluidic immunodetection.
We report an asymmetric immunoaggregation assay for rapid, label-free, and sub-picomolar protein detection. Asymmetric immunoaggregated beads (AIBs) are formed when binding occurs between 1 μm magnetic (MG) and 2.8 μm polystyrene (PS) beads coated with specific antibodies for a target antigen. Detection of such aggregation is achieved by optical monitoring of AIBs in a flow under an external magnetic field. AIBs are attracted to the upper surface of the microchannel by a magnetic field and made to slide along the surface by a flow drag force. This sliding behavior is in contrast with other particles such as MG and PS beads; while attracted MG beads hardly slide due to their small size, PS beads quickly move with the flow due to the lack of magnetism. Sliding AIBs are optically monitored in a designated sensing area in the microchannel. A custom-built program code is used for counting the AIBs and further analysis of parameters such as velocity and number distributions that are correlated with target concentrations. The detection range from 54 pg mL-1 to 54 ng mL-1 is demonstrated for the influenza type A H1N1 nucleoprotein (NP). This immunosensing system is simple, highly sensitive, and capable of quantitative detection of antigens in a single test without fluorescent or enzyme labeling, hence is useful for the rapid detection of biomarkers in clinical and biomedical applications.


[Dietary fat intake and incidence of cataracts: The SUN Prospective study in the cohort of Navarra, Spain].
To evaluate prospectively the association between dietary fat intake and the incidence of cataracts in participants from the SUN cohort. Among 12308 men and women, initially free of cataracts and followed-up for up to 6 years, we identified 182 incident cases of cataracts. Fatty acids intake was assessed by a validated 136-item semiquantitative food frequency questionnaire. Socio-demographic and anthropometric characteristics, lifestyle, health-related habits and information about medical conditions were also collected. Incident cases of cataract were ascertained by self-reports using a biennale questionnaire. Participants belonging to the highest category of omega-6 fatty acids intake had a non-significantly reduced risk of cataracts in the model adjusted for potential confounders but not for other fatty acids (adjusted OR: 0.58; 95% CI: 0.33, 1.03). When all types of fatty acids (saturated, monounsaturated, polyunsaturated omega-6 and polyunsaturated omega-3) were included simultaneously in the same multivariable model, this inverse association became significant (adjusted OR: 0.54 95%CI: 0.29, 0.99). There were no significant associations between other dietary fats and the risk of cataracts. High intake of omega-6 fatty acids showed a modest but significant inverse association with the development of cataracts.


An expert system for performance-based direct delivery of published clinical evidence.
To develop a system for clinical performance improvement through rule-based analysis of medical practice patterns and individualized distribution of published scientific evidence. The Quality Feedback Expert System (QFES) was developed by applying a Level-5 expert system shell to generate clinical direct reports for performance improvement. The system comprises three data and knowledge bases: 1) a knowledge base of measurable clinical practice parameters; 2) a practice pattern database of provider-specific numbers of patients and clinical activities; and 3) a management rule base comprising "redline rules" that identify providers whose practice styles vary significantly. Clinical direct reports consist of a table of practice data highlighting individual utilization vs recommendation and selected pertinent statements from medical literature. The QFES supports integration of recommendations from several guidelines into a comprehensive and measurable quality improvement plan, analysis of actual practice patterns and comparison with accepted recommendations, and generation of a confidential individualized direct report to those who significantly deviate from clinical recommendations. The feasibility of the practice pattern analysis by the QFES was demonstrated in a sample of 182 urinary tract infection cases from a primary care clinic. In a set of clinical activities, four questions/procedures were associated with significant (p < 0.001) and unexplained variation. The QFES provides a flexible tool for the implementation of clinical practice guidelines in diverse and changing clinical areas without the need for special program development. Preliminary studies indicate utility in the analysis of clinical practice variation and deviations. Using data obtained through a retrospective chart audit, the QFES was able to detect overutilization, and to identify nonrandom differences in practice patterns.


Evaluation of compressive strength of hydraulic silicate-based root-end filling materials.
Hydraulic silicate cements such as mineral trioxide aggregate (MTA) have many clinical advantages. Newer hydraulic silicate materials have been developed that improve on the limitations of mineral trioxide aggregate such as the long setting time and difficult handling characteristics. The purpose of this study was to examine the effect of saline and fetal bovine serum (FBS) on the setting and compressive strength of the following hydraulic silicate cements: ProRoot MTA (white WMTA; Dentsply International, Tulsa Dental Specialties, Johnson City, TN), EndoSequence Root Repair Material (Brasseler USA, Savannah, GA), MTA Plus (MTAP; Avalon Biomed Inc, Bradenton, FL), and QuickSet (QS; Avalon Biomed Inc, Bradenton, FL). Samples of root-end filling materials were compacted into polyethylene molds. Samples were exposed to FBS or saline for 7 days. A universal testing machine was used to determine the compressive strengths. QS had significantly lower compressive strength than all other materials (P < .001). White MTA and MTAP mixed with liquid had lower compressive strengths after exposure to FBS compared with saline (P = .003). ERRM, MTAP mixed with gel, and QS were not affected by the exposure to FBS. New silicate-based root-end filling materials, other than QS, have compressive strength similar to MTA. Within the limits of this study, premixed materials and those mixed with antiwashout gel maintain their compressive strength when exposed to biological fluids.


Hydrolysates of Fish Skin Collagen: An Opportunity for Valorizing Fish Industry Byproducts.
During fish processing operations, such as skinning and filleting, the removal of collagen-containing materials can account for up to 30% of the total fish byproducts. Collagen is the main structural protein in skin, representing up to 70% of dry weight depending on the species, age and season. It has a wide range of applications including cosmetic, pharmaceutical, food industry, and medical. In the present work, collagen was obtained by pepsin extraction from the skin of two species of teleost and two species of chondrychtyes with yields varying between 14.16% and 61.17%. The storage conditions of the skins appear to influence these collagen extractions yields. Pepsin soluble collagen (PSC) was enzymatically hydrolyzed and the resultant hydrolysates were ultrafiltrated and characterized. Electrophoretic patterns showed the typical composition of type I collagen, with denaturation temperatures ranged between 23 °C and 33 °C. In terms of antioxidant capacity, results revealed significant intraspecific differences between hydrolysates, retentate, and permeate fractions when using β-Carotene and DPPH methods and also showed interspecies differences between those fractions when using DPPH and ABTS methods. Under controlled conditions, PSC hydrolysates from Prionace glauca, Scyliorhinus canicula, Xiphias gladius, and Thunnus albacares provide a valuable source of peptides with antioxidant capacities constituting a feasible way to efficiently upgrade fish skin biomass.


Comprehensive paternity assignment: genotype, spatial location and social status in song sparrows, Melospiza Melodia.
Comprehensive, accurate paternity assignment is critical to answering numerous questions in evolutionary ecology. Yet, most studies of species with extra-pair paternity (EPP) fail to assign sires to all offspring. Common limitations include incomplete and biased sampling of offspring and males, particularly with respect to male location and social status, potentially biasing estimated patterns of paternity. Studies that achieve comprehensive sampling and paternity assignment are therefore required. Accordingly, we genotyped virtually all males and >99% of 6-day-old offspring over 16 years in a song sparrow (Melospiza melodia) population and used three complementary statistical methodologies to attempt complete paternity assignment for all 2207 offspring. Assignments were highly consistent across maximum likelihood methods that used solely genotype data, and heuristic and integrated Bayesian analyses that included data describing individual locations. Sires were assigned to >99% of all genotyped offspring with ≥95% confidence, revealing an EPP rate of c. 28%. Extra-pair sires primarily occupied territories neighbouring their extra-pair offspring; spatial location was therefore highly informative for paternity assignment. EPP was biased towards paired territorial males, although unpaired territorial and floater males sired c. 13% of extra-pair offspring. Failing to sample and include unpaired males as candidate sires would therefore substantially reduce assignment rates. These analyses demonstrate the integration of genetic and ecological information to achieve comprehensive paternity assignment and direct biological insight, illustrate the potential biases that common forms of incomplete sampling could have on estimated patterns of EPP, and provide an essential basis for understanding the evolutionary causes and consequences of EPP.


The influence of Parachlorella beyerinckii CK-5 on the absorption and excretion of methylmercury (MeHg) in mice.
Chlorella (Parachlorella beyerinckii CK-5), previously identified as Chlorella vulgaris CK-5, is a unicellular green algae that has for many years been used as a nutritional supplement. In order to investigate the effects of methylmercury (MeHg) detoxification by Chlorella, we examined the absorption and excretion of MeHg in mice. Female C57BL/6N mice were randomly divided into three groups of five, and were housed in metabolism cages. Mice were orally administered MeHg chloride at doses of 5 mg (4 mg Hg)/kg body weight with or without 100 mg/mouse of P. beyerinckii powder (BP), and were assigned to either a MeHg group or MeHg + BP group, accordingly. Twenty-four hr after oral administration, feces and urine were collected, and blood, liver, and kidney samples were obtained. Total mercury contents in the samples obtained were determined using an atomic absorption method. The amounts of Hg excreted in feces and urine of the MeHg + BP group were increased nearly 1.9 and 2.2-fold compared with those of the MeHg group. On the other hand, blood and organ Hg levels were not significantly different between two groups. These results suggest that the intake of BP may induce the excretion of Hg both in feces and urine, although it does not affect MeHg absorption from the gastrointestinal tract. The effect of BP on the tissue mercury accumulation may become evident in a long-term experiment.


Cranial nerve dysfunction following Gamma Knife surgery for pituitary adenomas: long-term incidence and risk factors.
Gamma Knife surgery (GKS) has become a significant component of neurosurgical treatment for recurrent secretory and nonsecretory pituitary adenomas. Although the long-term risks of visual dysfunction following microsurgical resection of pituitary adenomas has been well studied, the comparable risk following radiosurgery is not well defined. This study evaluates the long-term risks of ophthalmological dysfunction following GKS for recurrent pituitary adenomas. An analysis of 217 patients with recurrent secretory (n = 131) and nonsecretory (n = 86) pituitary adenomas was performed to determine the incidence of and risk factors for subsequent development of visual dysfunction. Patients underwent ophthalmological evaluation as part of post-GKS follow-up to assess for new or worsened cranial nerve II, III, IV, or VI palsies. The median follow-up duration was 32 months. The median maximal dose was 50 Gy, and the median peripheral dose was 23 Gy. A univariate analysis was performed to assess for risk factors of visual dysfunction post-GKS. Nine patients (4%) developed new visual dysfunctions, and these occurred within 6 hours to 34 months following radiosurgery. None of these 9 patients had tumor growth on post-GKS neuroimaging studies. Three of these patients had permanent deficits whereas in 6 the deficits resolved. Five of the 9 patients had prior GKS or radiotherapy, which resulted in a significant increase in the incidence of cranial nerve dysfunction (p = 0.0008). An increased number of isocenters (7.1 vs 5.0, p = 0.048) was statistically related to the development of visual dysfunction. Maximal dose, margin dose, optic apparatus dose, tumor volume, cavernous sinus involvement, and suprasellar extension were not significantly related to visual dysfunction (p >0.05). Neurological and ophthalmological assessment in addition to routine neuroimaging and endocrinological follow-up are important to perform following GKS. Patients with a history of radiosurgery or radiation therapy are at higher risk of cranial nerve deficits. Also, a reduction in the number of isocenters delivered, along with volume treated, particularly in the patients with secretory tumors, appears to be the most reasonable strategy to minimize the risk to the visual system when treating recurrent pituitary adenomas with stereotactic radiosurgery.


Effects of white-nose syndrome on regional population patterns of 3 hibernating bat species.
Hibernating bats have undergone severe recent declines across the eastern United States, but the cause of these regional-scale declines has not been systematically evaluated. We assessed the influence of white-nose syndrome (an emerging bat disease caused by the fungus Pseudogymnoascus destructans, formerly Geomyces destructans) on large-scale, long-term population patterns in the little brown myotis (Myotis lucifugus), the northern myotis (Myotis septentrionalis), and the tricolored bat (Perimyotis subflavus). We modeled population trajectories for each species on the basis of an extensive data set of winter hibernacula counts of more than 1 million individual bats from a 4-state region over 13 years and with data on locations of hibernacula and first detections of white-nose syndrome at each hibernaculum. We used generalized additive mixed models to determine population change relative to expectations, that is, how population trajectories differed with a colony's infection status, how trajectories differed with distance from the point of introduction of white-nose syndrome, and whether declines were concordant with first local observation of the disease. Population trajectories in all species met at least one of the 3 expectations, but none met all 3. Our results suggest, therefore, that white-nose syndrome has affected regional populations differently than was previously understood and has not been the sole cause of declines. Specifically, our results suggest that in some areas and species, threats other than white-nose syndrome are also contributing to population declines, declines linked to white-nose syndrome have spread across large geographic areas with unexpected speed, and the disease or other threats led to declines in bat populations for years prior to disease detection. Effective conservation will require further research to mitigate impacts of white-nose syndrome, renewed attention to other threats to bats, and improved surveillance efforts to ensure early detection of white-nose syndrome.


Clinical Implications of Decreased Computed Tomography Value after Ramucirumab in Advanced Gastric Cancer.
This study aimed to evaluate whether a decrease of computed tomography (CT) value for tumors serves as a predictive marker in patients with advanced gastric cancer (aGC) who have undergone chemotherapy with vascular epithelial growth factor receptor 2 inhibitor (ramucirumab). We retrospectively analyzed 44 patients with aGC who received taxane alone (TAX arm; n = 33), ramucirumab alone, or ramucirumab in combination with taxane (RAM arm; n = 11) as second-line or later chemotherapy between July 2010 and October 2016. In all patients, tumor size and tumor CT value were evaluated at two timepoints: pretreatment and first evaluation. We calculated the change of the tumors' CT value. The associations of these factors with tumor response, progression-free survival (PFS), and overall survival were investigated. Ten (90.9%) of 11 patients in the RAM arm and 18 (54.5%) of 33 patients in the TAX arm showed decreased CT values. The rate of CT value change in the RAM arm (median -32.80%, range -53.63 to 6.84%) was higher than that in the TAX arm (median -0.44%, range -37.47 to 40.64%; p = 0.0005). When using the median value of CT value change as a cut-off, PFS was significantly longer in patients with a high rate of CT value change (decrease ≥32.80%) than in those with a low rate (decrease <32.80%) in the RAM arm (median 292 and 112 days; p = 0.045), while no significant difference of this kind was found in the TAX arm (median 91 and 125 days; p = 0.45). Patients with aGC treated with ramucirumab experienced a significant decrease of CT value of tumors and had an association between the rate of CT value change and PFS. Our study suggests that CT value changes of tumors may be a predictor for the efficacy of ramucirumab in aGC.


Early and late changes in markers of aortic stiffness with breast cancer therapy.
Anthracyclines and trastuzumab are well recognised to cause cardiac toxicity. Further to their effects on left ventricular (LV) function, anthracyclines in particular are considered to cause negative arterial remodelling. Whether these changes reverse is unknown. In addition, whether trastuzumab causes specific effects on arterial remodelling is yet undetermined. Patients receiving these agents for treatment of breast cancer and healthy volunteers prospectively underwent clinical evaluation and cardiovascular magnetic resonance (CMR) imaging at baseline, 1, 4 and 14 months post-therapy, including functional assessment, measurement of aortic pulse wave velocity (PWV) using velocity encoded imaging and distensibility at ascending aorta (AA) and proximal descending aorta (PDA). Twenty-nine patients pretherapy and 12 volunteers demonstrated no differences in PWV, distensibility and LV function. Among cancer subjects, PWV increased acutely, P = 0.002 (4 months), then decreased by 14 months (P < 0.001). In addition, a decrease was observed in distensibility at the AA within 1 (P = 0.001) and 4 months (P < 0.001) of commencing therapy. At the PDA, only significant reduction was observed at 14 month distensibility when compared with baseline, P < 0.001. Patients with anthracycline exposure only had a greater reduction in aortic distensibility in the AA with time, P = 0.005 at 1 month, P < 0.001 at 4 months and P = 0.009 at 14 months. Acute changes are observed in PWV and distensibility at the AA following contemporary breast cancer chemotherapy and partially reverse a year after therapy is discontinued, with more severe effects seen with anthracyclines.


Using Multiple Outcomes of Sexual Behavior to Provide Insights Into Chlamydia Transmission and the Effectiveness of Prevention Interventions in Adolescents.
Mathematical models are important tools for assessing prevention and management strategies for sexually transmitted infections. These models are usually developed for a single infection and require calibration to observed epidemiological trends in the infection of interest. Incorporating other outcomes of sexual behavior into the model, such as pregnancy, may better inform the calibration process. We developed a mathematical model of chlamydia transmission and pregnancy in Minnesota adolescents aged 15 to 19 years. We calibrated the model to statewide rates of reported chlamydia cases alone (chlamydia calibration) and in combination with pregnancy rates (dual calibration). We evaluated the impact of calibrating to different outcomes of sexual behavior on estimated input parameter values, predicted epidemiological outcomes, and predicted impact of chlamydia prevention interventions. The two calibration scenarios produced different estimates of the probability of condom use, the probability of chlamydia transmission per sex act, the proportion of asymptomatic infections, and the screening rate among men. These differences resulted in the dual calibration scenario predicting lower prevalence and incidence of chlamydia compared with calibrating to chlamydia cases alone. When evaluating the impact of a 10% increase in condom use, the dual calibration scenario predicted fewer infections averted over 5 years compared with chlamydia calibration alone [111 (6.8%) vs 158 (8.5%)]. While pregnancy and chlamydia in adolescents are often considered separately, both are outcomes of unprotected sexual activity. Incorporating both as calibration targets in a model of chlamydia transmission resulted in different parameter estimates, potentially impacting the intervention effectiveness predicted by the model.


Chromatin Regulation by the NuA4 Acetyltransferase Complex Is Mediated by Essential Interactions Between Enhancer of Polycomb (Epl1) and Esa1.
Enzymes that modify and remodel chromatin act in broadly conserved macromolecular complexes. One key modification is the dynamic acetylation of histones and other chromatin proteins by opposing activities of acetyltransferase and deacetylase complexes. Among acetyltransferases, the NuA4 complex containing Tip60 or its Saccharomyces cerevisiae ortholog Esa1 is of particular significance because of its roles in crucial genomic processes including DNA damage repair and transcription. The catalytic subunit Esa1 is essential, as are five noncatalytic NuA4 subunits. We found that of the noncatalytic subunits, deletion of Enhancer of polycomb (Epl1), but not the others, can be bypassed by loss of a major deacetylase complex, a property shared by Esa1 Noncatalytic complex subunits can be critical for complex assembly, stability, genomic targeting, substrate specificity, and regulation. Understanding the essential role of Epl1 has been previously limited, a limitation now overcome by the discovery of its bypass suppression. Here, we present a comprehensive in vivo study of Epl1 using the powerful tool of suppression combined with transcriptional and mutational analyses. Our results highlight functional parallels between Epl1 and Esa1 and further illustrate that the structural role of Epl1 is important for promotion of Esa1 activity. This conclusion is strengthened by our dissection of Epl1 domains required in vivo for interaction with specific NuA4 subunits, histone acetylation, and chromatin targeting. These results provide new insights for the conserved, essential nature of Epl1 and its homologs, such as EPC1/2 in humans, which is frequently altered in cancers.


Altered expression of protein tyrosine phosphatase, non-receptor type 22 isoforms in systemic lupus erythematosus.
A C-to-T single nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase, non-receptor type 22 (PTPN22) complementary DNA (cDNA) is associated with an increased risk of systemic lupus erythematosus (SLE). How the overall activity of PTPN22 is regulated and how the expression of PTPN22 differs between healthy individuals and patients with lupus are poorly understood. Our objectives were to identify novel alternatively spliced forms of PTPN22 and to examine the expression of PTPN22 isoforms in healthy donors and patients with lupus. Various human PTPN22 isoforms were identified from the GenBank database or amplified directly from human T cells. The expression of these isoforms in primary T cells and macrophages was examined with real-time polymerase chain reaction. The function of the isoforms was determined with luciferase assays. Blood samples were collected from 49 subjects with SLE and 15 healthy controls. Correlation between the level of PTPN22 isoforms in peripheral blood and clinical features of SLE was examined with statistical analyses. Human PTPN22 was expressed in several isoforms, which differed in their level of expression and subcellular localization. All isoforms except one were functionally interchangeable in regulating NFAT activity. SLE patients expressed higher levels of PTPN22 than healthy individuals and the levels of PTPN22 were negatively correlated with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-DI). The overall activity of PTPN22 is determined by the functional balance among all isoforms. The levels of PTPN22 isoforms in peripheral blood could represent a useful biomarker of SLE.


Comparison of Chicken Cecal Microbiota after Metaphylactic Treatment or Following Administration of Feed Additives in a Broiler Farm with Enterococcal Spondylitis History.
Minimizing the clinical signs of Enterococcus cecorum infections causing enterococcal spondylitis in broiler herds is successful when initiated as metaphylaxis in the first week of life. Mechanistically, either the Enterococcus species present at that time are reduced by antibiotic treatment or antibiotic treatment might induce changes in intestinal microbiota composition with an indirect and subsequent influence. The aim of the present study was to examine the cecal microbiota of chickens after administering lincospectin or different additives to evaluate whether these additives have lincospectin-like effects on microbiota. Therefore, 157,400 broiler chickens were reared in four chicken houses (~40,000 birds each) on a broiler farm with history of enterococcal spondylitis. Each flock was treated either with lincospectin or water soluble esterified butyrins, Bacillus (B.) licheniformis or palm oil was added via drinking water during the first days of life. Ten birds per house were dissected at days 11, 20 and 33 of life and cecal microbiota were analyzed (16S rRNA gene sequencing). Lincospectin treatment elicited significant changes in the cecal microbiota composition until slaughter age. Among the tested additives, effects of B. licheniformis on cecal microbiota composition were most similar to those seen after the treatment with lincospectin at day 11.


Prevalence of Toxoplasma gondii antibodies in stray dogs in Taipei, Taiwan.
From October 2005 through September 2006, blood samples collected from 1,412 (768 male, 644 female) 1-yr-old and older stray dogs in Taipei City, Taiwan, were tested for antibodies to Toxoplasma gondii using the latex agglutination test (LAT). Antibodies (LAT titers >1:32) to T. gondii were found in 284 (20.1%) of the animals. Seroprevalences were not affected by the sex or density of dogs. The prevalence was highest in dogs from the eastern part of the city.


Principled network extraction from images.
Images of natural systems may represent patterns of network-like structure, which could reveal important information about the topological properties of the underlying subject. However, the image itself does not automatically provide a formal definition of a network in terms of sets of nodes and edges. Instead, this information should be suitably extracted from the raw image data. Motivated by this, we present a principled model to extract network topologies from images that is scalable and efficient. We map this goal into solving a routing optimization problem where the solution is a network that minimizes an energy function which can be interpreted in terms of an operational and infrastructural cost. Our method relies on recent results from optimal transport theory and is a principled alternative to standard image-processing techniques that are based on heuristics. We test our model on real images of the retinal vascular system, slime mould and river networks and compare with routines combining image-processing techniques. Results are tested in terms of a similarity measure related to the amount of information preserved in the extraction. We find that our model finds networks from retina vascular network images that are more similar to hand-labelled ones, while also giving high performance in extracting networks from images of rivers and slime mould for which there is no ground truth available. While there is no unique method that fits all the images the best, our approach performs consistently across datasets, its algorithmic implementation is efficient and can be fully automatized to be run on several datasets with little supervision.


Surveillance of anti-tuberculosis drug resistance in the world: an updated analysis, 2007-2010.
To present a global update of drug-resistant tuberculosis (TB) and explore trends in 1994-2010. Data on drug resistance among new and previously treated TB patients, as reported by countries to the World Health Organization, were analysed. Such data are collected through surveys of a representative sample of TB patients or surveillance systems based on routine drug susceptibility testing. Associations between multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection and sex were explored through logistic regression. In 2007-2010, 80 countries and 8 territories reported surveillance data. MDR-TB among new and previously treated cases was highest in the Russian Federation (Murmansk oblast, 28.9%) and the Republic of Moldova (65.1%), respectively. In three former Soviet Union countries and South Africa, more than 10% of the cases of MDR-TB were extensively drug-resistant. Globally, in 1994 to 2010 multidrug resistance was observed in 3.4% (95% confidence interval, CI: 1.9-5.0) of all new TB cases and in 19.8% (95% CI: 14.4-25.1) of previously treated TB cases. No overall associations between MDR-TB and HIV infection (odds ratio, OR: 1.4; 95% CI: 0.7-3.0) or sex (OR: 1.1; 95% CI: 0.8-1.4) were found. Between 1994 and 2010, MDR-TB rates in the general population increased in Botswana, Peru, the Republic of Korea and declined in Estonia, Latvia and the United States of America. The highest global rates of MDR-TB ever reported were documented in 2009 and 2010. Trends in MDR-TB are still unclear in most settings. Better surveillance or survey data are required, especially from Africa and India.


Fiberoptic Endoscopic Evaluation of Swallowing in children: feeding outcomes related to diagnostic groups and endoscopic findings.
Fiberoptic Endoscopic Evaluation of Swallowing (FEES) is used as an adjunct to assess swallowing function in children with complex feeding disorders. We report the feeding outcomes of patients who underwent FEES to determine whether associations exist between clinical diagnoses or FEES findings and feeding outcomes. Retrospective review of children who underwent FEES for dysphagia or aspiration from 2003 to 2009. The clinical diagnoses and initial FEES findings were compared to follow up feeding status for associations. 79 patients were included (44 males and 35 females). The change from initial to final status: total oral feeding (42-67%), NPO ± minimal tastes (39-21%) and oral feeding with tube feeding (19-12%). Of the clinical diagnoses, tonsillar hypertrophy was associated with ultimately obtaining total oral feeding status (p = 0.046) while the inability to obtain total oral feeding status was associated with neurologic (p < 0.001). The initial FEES findings showed no significant associations with long-term feeding status. Many children overcome their dysphagia but those with neurologic disorders are less likely to achieve total oral feeding status. In children with dysphagia evaluated by FEES, the long-term feeding status is not significantly associated with the initial FEES findings.


Phosphorylation of Ser158 regulates inflammatory redox-dependent hepatocyte nuclear factor-4alpha transcriptional activity.
In IL-1beta (interleukin 1beta)-stimulated rat hepatocytes exposed to superoxide, we have previously identified an IRX (inflammatory redox)-sensitive DR1 [direct repeat of RG(G/T)TCA with one base spacing] cis-acting activator element (nt -1327 to -1315) in the iNOS (inducible nitric oxide synthase) promoter: AGGTCAGGGGACA. The corresponding transcription factor was identified to be HNF4alpha (hepatocyte nuclear factor-4alpha). HNF4alpha DNA binding activity and transactivation potential are tightly regulated by its state of phosphorylation. However, the functional consequences of IRX-mediated post-translational phosphorylation of HNF4alpha have not been well characterized. In the setting of IL-1beta+H2O2, HNF4alpha functional activity is associated with a unique serine/threonine phosphorylation pattern. This indicates that an IRX-sensitive serine/threonine kinase pathway targets HNF4alpha to augment hepatocyte iNOS transcription. In the present study, following identification of phosphorylated residues in HNF4alpha, serial mutations were performed to render the target residues phosphorylation-resistant. Electrophoretic mobility-shift assays and transient transfection studies utilizing the iNOS promoter showed that the S158A mutation ablates IRX-mediated HNF4alpha DNA binding and transactivation. Gain-of-function mutation with the S158D phosphomimetic HNF4alpha vector supports a critical role for Ser158 phosphorylation. In vitro phosphorylation and kinase inhibitor studies implicate p38 kinase activity. Our results indicate that p38 kinase-mediated Ser158 phosphorylation is essential for augmentation of the DNA binding and transactivation potential of HNF4alpha in the presence of IL-1beta+H2O2. This pathway results in enhanced iNOS expression in hepatocytes exposed to pro-inflammatory cytokines and oxidative stress.


Porous coordination polymer hybrid device with quartz oscillator: effect of crystal size on sorption kinetics.
A new strategy to synthesize monodispersed porous coordination polymer (PCP) nanocrystals at room temperature was developed and utilized for the formation of PCP thin films on gold substrates with fine control over the crystal sizes using the coordination modulation method. Hybridization of these PCP thin films with an environment-controlled quartz crystal microbalance system allowed determining the adsorption properties for organic vapors (methanol and hexane). In the case of high sensitivity (at the low-concentration dosing of analytes), the sensor response depended on the crystal size but not on the type of analyte. In contrast, at the high-concentration dosing, a clear dependence of the sorption kinetics on the analyte was observed due to significant sorbate-sorbate interaction.


An In vivo Immunohistochemical Study on MacroH2A.1 in Lung and Lymph-Node Tissues Exposed to an Asbestiform Fiber.
The aim of this study was to investigate MacroH2A.1 immunoexpression in tissues of sheep exposed to FE. The correlation between asbestiform fibers, lung cancer, pleural mesothelioma, and other lung diseases is already well established as the pathophisiological pathophysiological respiratory mechanisms involved by inhalation of Fluoro-edenite (FE). The latter is represented by cell proliferation and inducing the release of growth factors, cytokines, and reactive oxygen and nitrite species, with DNA damage that causes chronic inflammation and carcinogenesis. MacroH2A.1, and histone variant, seems to play a role in sensing the metabolic state of the cell and linking it with chromatin. Physiologically, MacroH2A.1 is expressed at low levels in stem cells and it became upregulated during differentiation, preventing reprogramming of induced pluripotent stem cells and after nuclear transfer. In particular, MacroH2A.1 has been shown to explicate a potent antitumor mechanism in vivo as it results upregulated in senescent cells determining a permanent growth-arrest. Evaluate the possible role of the histone variant in the organism in response to deep insight understanding the mechanisms of toxicity and the cellular response to FE. Lung and lymph nodes of exposed sheep were selected. Samples were processed for histological and immunihistochemical immunohistochemical evaluations. Densitometric, morphometric, and statistical analysis analyses were conducted. Tissue sections of FE exposed sheep demonstrated overexpression of MacroH2A.1 vs unexposed samples. The data suggest an involvement of these this molecule in the cellular response triggered by FE directed exposure. In this contest, MacroH2A.1 overexpression supports its function as an epigenetic stabilizer that helps to establish and maintain differentiated states.


Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers.
The amount and quality of dietary fatty acids can modulate the fat metabolism. This dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial beta-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal beta-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes. In a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25-30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile. The plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (> or = C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05). Combined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.


Requirement for tyrosine residues 315 and 319 within zeta chain-associated protein 70 for T cell development.
Engagement of the T cell antigen receptor (TCR) induces the transphosphorylation of the zeta chain-associated protein of 70,000 Mr (ZAP-70) protein tyrosine kinase (PTK) by the CD4/8 coreceptor associated Lck PTK. Phosphorylation of Tyr 493 within ZAP-70's activation loop results in the enzymatic activation of ZAP-70. Additional tyrosines (Tyrs) within ZAP-70 are phosphorylated that play both positive and negative regulatory roles in TCR function. Phosphorylation of Tyr residues (Tyrs 315 and 319) within the Interdomain B region of the ZAP-70 PTK plays important roles in the generation of second messengers after TCR engagement. Here, we demonstrate that phosphorylation of these two Tyr residues also play important roles in mediating the positive and negative selection of T cells in the thymus.


Hematopoietic progenitor stem cell homing in mice lethally irradiated with ionizing radiation at differing dose rates.
It has recently been shown that specific lineage-depleted murine hematopoietic stem cells that home to the bone marrow 2 days after transplantation of ablated primary recipients are capable of long-term engraftment and repopulation of secondary recipients. We were interested in determining whether the rate at which the ablating radiation dose was delivered to the mice affected the homing of lineage-depleted stem cells to the bone marrow and/or sites of tissue damage. Fractionated, lineage-depleted donor marrow cells were isolated and labeled with the membrane dye PKH26. Recipient mice were lethally irradiated with 11 Gy ionizing radiation using varying dose rates and were immediately injected with PKH26-labeled progenitor stem cells. With the exception of the lowest dose-rate group, all irradiated mice had an approximately fivefold (P = 0.014 to 0.025) reduction in stem cell homing to the bone marrow compared to unirradiated control animals. A fivefold reduction of stem cell homing to the spleen compared to unirradiated animals was also observed, though this was not statistically significant for any dose-rate group (P = 0.072 to 0.233). This difference in homing could not be explained by increased stem cell apoptosis/necrosis or non-marrow tissue homing to the intestine, lung or liver. We show that the dose rate at which a lethal dose of total-body radiation is delivered does not augment hematopoietic progenitor stem cell homing to the bone marrow, spleen or sites of early radiation-mediated tissue damage at either 2 or 5 days postirradiation/transplantation. The observation that greater homing was seen in unirradiated control mice calls into question the concept that adequate bone marrow stem cell homing requires radiation-induced "space" to be made in the marrow, certainly for the enriched early progenitor hematopoietic stem cells used for this set of experiments. Further experiments will be needed to determine whether these homed cells are as capable of giving rise to long-term engraftment/repopulation of the marrow of secondary recipients as they are in irradiated recipients.


Comparing eye trackers by correlating their eye-metric data.
Up to now, the potential of eye tracking in science as well as in everyday life has not been fully realized because of the high acquisition cost of trackers. Recently, manufacturers have introduced low-cost devices, preparing the way for wider use of this underutilized technology. As soon as scientists show independently of the manufacturers that low-cost devices are accurate enough for application and research, the real advent of eye trackers will have arrived. To facilitate this development, we propose a simple approach for comparing two eye trackers by adopting a method that psychologists have been practicing in diagnostics for decades: correlating constructs to show reliability and validity. In a laboratory study, we ran the newer, low-cost EyeTribe eye tracker and an established SensoMotoric Instruments eye tracker at the same time, positioning one above the other. This design allowed us to directly correlate the eye-tracking metrics of the two devices over time. The experiment was embedded in a research project on memory where 26 participants viewed pictures or words and had to make cognitive judgments afterwards. The outputs of both trackers, that is, the pupil size and point of regard, were highly correlated, as estimated in a mixed effects model. Furthermore, calibration quality explained a substantial amount of individual differences for gaze, but not pupil size. Since data quality is not compromised, we conclude that low-cost eye trackers, in many cases, may be reliable alternatives to established devices.


Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer.
Over 100 years have passed since the first observation of the notched wing phenotype in Drosophila melanogaster, and significant progress has been made to characterize the role of the Notch receptor, its ligands, downstream targets, and cross-talk with other signaling pathways. The canonical Notch pathway with four Notch receptors (Notch1-4) and five ligands (DLL1, 3-4, Jagged 1-2) is an evolutionarily conserved cell signaling pathway that plays critical roles in cell-fate determination, differentiation, development, tissue patterning, cell proliferation, and death. In cancer, these roles have a critical impact on tumor behavior and response to therapy. Because the role of Notch remains tissue and context dependent, alterations within this pathway may lead to tumor suppressive or oncogenic phenotypes. Although no FDA-approved therapies currently exist for the Notch pathway, multiple therapeutics (e.g., demcizumab, tarextumab, GSI MK-0752, R04929097, and PF63084014) have been developed to target different aspects of this pathway for both hematologic and solid malignancies. Understanding the context-specific effects of the Notch pathway will be important for individualized therapies targeting this pathway.