Effects of muscle vibration on multi-finger interaction and coordination.
The purpose of this study was to investigate the effects of changes in the proprioceptive signals induced by muscle vibration on multi-finger interaction and coordination. We hypothesized that unintended force production by non-instructed fingers (enslaving) would increase with muscle vibration while synergy indices during steady-state force production would drop. The framework of the uncontrolled manifold hypothesis was used to quantify indices of multi-finger synergies stabilizing total force during steady-state force production and anticipatory changes in these indices (anticipatory synergy adjustments, ASAs) in preparation to a quick force pulse production with and without hand-muscle vibration at 80 Hz. The dominant hands of twelve healthy right-handed subjects were tested under three conditions: no vibration, vibration of the palmar surface of the hand, and vibration of the forearm applied over the flexor muscles. There were no significant effects of vibration on maximal voluntary force. The magnitude of enslaving was larger during vibration of the hand compared to the other two conditions. During steady-state force production, strong synergies stabilizing total force were seen in all three conditions; however, indices of force-stabilizing synergies were lower during vibration of the hand. Prior to the force pulse initiation, the synergy index started to drop earlier and over a larger magnitude without vibration compared to either vibration condition. Effects of vibration on enslaving and synergy index may be due to diffuse reflex effects of the induced afferent activity on alpha-motoneuronal pools innervating the extrinsic flexor compartments. We conclude that multi-finger synergies are not based on signals from muscle receptors. The smaller synergy indices and ASAs may reflect supraspinal effects of the vibration-induced afferent activity, in particular its interactions with trans-thalamic loops.


The NK cell granule protein NKG7 regulates cytotoxic granule exocytosis and inflammation.
Immune-modulating therapies have revolutionized the treatment of chronic diseases, particularly cancer. However, their success is restricted and there is a need to identify new therapeutic targets. Here, we show that natural killer cell granule protein 7 (NKG7) is a regulator of lymphocyte granule exocytosis and downstream inflammation in a broad range of diseases. NKG7 expressed by CD4+ and CD8+ T cells played key roles in promoting inflammation during visceral leishmaniasis and malaria-two important parasitic diseases. Additionally, NKG7 expressed by natural killer cells was critical for controlling cancer initiation, growth and metastasis. NKG7 function in natural killer and CD8+ T cells was linked with their ability to regulate the translocation of CD107a to the cell surface and kill cellular targets, while NKG7 also had a major impact on CD4+ T cell activation following infection. Thus, we report a novel therapeutic target expressed on a range of immune cells with functions in different immune responses.


X-ray crystal structure of the hypothetical phosphotyrosine phosphatase MDP-1 of the haloacid dehalogenase superfamily.
The haloacid dehalogenase (HAD) superfamily is comprised of structurally homologous enzymes that share several conserved sequence motifs (loops I-IV) in their active site. The majority of HAD members are phosphohydrolases and may be divided into three subclasses depending on domain organization. In classes I and II, a mobile "cap" domain reorients upon substrate binding, closing the active site to bulk solvent. Members of the third class lack this additional domain. Herein, we report the 1.9 A X-ray crystal structures of a member of the third subclass, magnesium-dependent phosphatase-1 (MDP-1) both in its unliganded form and with the product analogue, tungstate, bound to the active site. The secondary structure of MDP-1 is similar to that of the "core" domain of other type I and type II HAD members with the addition of a small, 28-amino acid insert that does not close down to exclude bulk solvent in the presence of ligand. In addition, the monomeric oligomeric state of MDP-1 does not allow the participation of a second subunit in the formation and solvent protection of the active site. The binding sites for the phosphate portion of the substrate and Mg(II) cofactor are also similar to those of other HAD members, with all previously observed contacts conserved. Unlike other subclass III HAD members, MDP-1 appears to be equally able to dephosphorylate phosphotyrosine and closed-ring phosphosugars. Modeling of possible substrates in the active site of MDP-1 reveals very few potential interactions with the substrate leaving group. The mapping of conserved residues in sequences of MDP-1 from different eukaryotic organisms reveals that they colocalize to a large region on the surface of the protein outside the active site. This observation combined with the modeling studies suggests that the target of MDP-1 is most likely a phosphotyrosine in an unknown protein rather than a small sugar-based substrate.


Systematic review of health behavioral risks and cognitive health in older adults.
An increasing body of evidence suggests that health behaviors may protect against cognitive impairment and dementia. The purpose of this study was to summarize the current evidence on health behavioral factors predicting cognitive health through a systematic review of the published literature. PubMed, Embase, and PsycINFO databases were searched for studies on community representative samples aged 65 and older, with prospective cohort design and multivariate analysis. The outcome--cognitive health--was defined as a continuum of cognitive function ranging from cognitive decline to impairment and dementia, and health behaviors included physical activity, smoking, alcohol drinking, body mass index, and diet and nutrition. Of 12,105 abstracts identified, 690 relevant full-texts were reviewed. The final yield amounted to 115 articles of which 37 studies were chosen that met the highest standards of quality. Leisure time physical activity, even of moderate level, showed protective effects against dementia, whereas smoking elevated the risk of Alzheimer's disease. Moderate alcohol consumption tended to be protective against cognitive decline and dementia, but nondrinkers and frequent drinkers exhibited a higher risk for dementia and cognitive impairment. Midlife obesity had an adverse effect on cognitive function in later life. Analysis showed vegetable and fish consumption to be of benefit, whereas, persons consuming a diet high in saturated fat had an increased dementia risk. The review demonstrates accumulating evidence supporting health behavioral effects in reducing the risk of cognitive decline and dementia. Results indicate potential benefits of healthy lifestyles in protecting cognitive health in later life.


STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells.
The glucose analog streptozotocin (STZ) has long been used as a tool for creating experimental diabetes because of its relatively specific beta-cell cytotoxic effect, but the mechanism by which systemic injection of STZ causes beta-cell destruction is not well understood. In the current study, we have used insulinoma (RIN) and AtT-20ins cell lines engineered for overexpression of GLUT2 or GLUT1 to investigate the role of glucose transporter isoforms in mediating STZ cytotoxicity. The in vivo effects of STZ were evaluated by implantation of RIN cells expressing or lacking GLUT2 into athymic nude rats. The drug had a potent cytotoxic effect on RIN cells expressing GLUT2, but had no effect on cells lacking GLUT2 expression, as indicated by histological analysis and measurement of the blood glucose levels of treated animals. The preferential cytotoxic effect of STZ on GLUT2-expressing cell lines was confirmed by in vitro analysis of GLUT2-expressing and untransfected RIN cells, as well as GLUT2- and GLUT1-overexpressing AtT-20ins cells. Consistent with these data, only GLUT2-expressing RIN or AtT-20ins cells transported STZ efficiently. We conclude that expression of GLUT2 is required for efficient killing of neuroendocrine cells by STZ, and this effect is related to specific recognition of the drug as a transported substrate by GLUT2 but not GLUT1.


Comparison of video-assisted thoracoscopic talcage for recurrent primary versus persistent secondary spontaneous pneumothorax.
Thoracoscopic talcage (TT) is a safe and effective prophylactic treatment for patients suffering from recurrent primary spontaneous pneumothorax (PSP). Empirically, TT is considered equally effective in the treatment of persistent secondary spontaneous pneumothorax (SSP), although this has not yet been proved. In this study, the efficacy and safety of TT was prospectively evaluated in 28 patients (17 males and 11 females, mean age 27 +/- 8 yrs), with 31 episodes of recurrent PSP, and in 20 patients (13 males and 7 females, mean age 43 +/- 21 yrs) with persistent SSP. TT proved to be equally effective in achieving pleurodesis in both groups; there were 6.5% recurrences in the PSP group and 8.7% in the SSP group during a mean follow-up period of 18 months (p > 0.05). In the SSP group, there were significantly more prolonged postoperative air leaks (26 vs 0%; p = 0.004) and a longer postoperative chest tube drainage time (35.5 +/- 18 vs 24.9 +/- 3.2 hrs; p = 0.002) was necessary. All air leaks, however, ceased spontaneously during drainage. Duration of hospitalization was significantly longer in the SSP group (4.7 +/- 2 vs 3.2 +/- 0.5 days; p < 0.0001). Postoperative pain (90 vs 43%; p < 0.0001) and fever (65 vs 17%; p = 0.001) were more frequent in the PSP group than in the SSP group. There were no major peri- or postoperative complications in either group. We conclude that thoracoscopic talcage is as efficient and safe in achieving pleurodesis in persistent spontaneous pnuemothorax as in recurrent primary spontaneous pneumothorax.


GFPLAIN250m, a global high-resolution dataset of Earth's floodplains.
Identifying floodplain boundaries is of paramount importance for earth, environmental and socioeconomic studies addressing riverine risk and resource management. However, to date, a global floodplain delineation using a homogeneous procedure has not been constructed. In this paper, we present the first, comprehensive, high-resolution, gridded dataset of Earth's floodplains at 250-m resolution (GFPLAIN250m). We use the Shuttle Radar Topography Mission (SRTM) digital terrain model and set of terrain analysis procedures for geomorphic floodplain delineations. The elevation data are processed by a fast geospatial tool for floodplain mapping available for download at https://github.com/fnardi/GFPLAIN. The GFPLAIN250m dataset can support many applications, including flood hazard mapping, habitat restoration, development studies, and the analysis of human-flood interactions. To test the GFPLAIN250m dataset, we perform a consistency analysis with floodplain delineations derived by flood hazard modelling studies in Europe.


Neuroplasticity of dopamine circuits after exercise: implications for central fatigue.
Habitual exercise increases plasticity in a variety of neurotransmitter systems. The current review focuses on the effects of habitual physical activity on monoamine dopamine (DA) neurotransmission and the potential implication of these changes to exercise-induced fatigue. Although it is clear that peripheral adaptations in muscle and energy substrate utilization contribute to this effect, more recently it has been suggested that central nervous system pathways "upstream" of the motor cortex, which initiate activation of skeletal muscles, are also important. The contribution of the brain to exercise-induced fatigue has been termed "central fatigue." Given the well-defined role of DA in the initiation of movement, it is likely that adaptations in DA systems influence exercise capacity. A reduction in DA neurotransmission in the substantia nigra pars compacta (SNpc), for example, could impair activation of the basal ganglia and reduce stimulation of the motor cortex leading to central fatigue. Here we present evidence that habitual wheel running produces changes in DA systems. Using in situ hybridization techniques, we report that 6 weeks of wheel running was sufficient to increase tyrosine hydroxylase mRNA expression and reduce D2 autoreceptor mRNA in the SNpc. Additionally, 6 weeks of wheel running increased D2 postsynaptic receptor mRNA in the caudate putamen, a major projection site of the SNpc. These results are consistent with prior data suggesting that habitually physically active animals may have an enhanced ability to increase DA synthesis and reduce D2 autoreceptor-mediated inhibition of DA neurons in the SNpc compared to sedentary animals. Furthermore, habitually physically active animals, compared to sedentary controls, may be better able to increase D2 receptor-mediated inhibition of the indirect pathway of the basal ganglia. Results from these studies are discussed in light of our understanding of the role of DA in the neurobiological mechanisms of central fatigue.


Cognitive Impairment, Sexual Activity and Physical Tenderness in Community-Dwelling Older Adults: A Cross-Sectional Exploration.
The ability to engage in sexual activity and better cognitive functioning are both associated with better health. However, the association between cognitive functioning and sexual activity is understudied. To examine the association between cognitive functioning with sexual activity and physical tenderness among community-dwelling older adults. From the Rotterdam Study, cognitive impairment and sexual activity were assessed in 4,201 community-dwelling, 60+ year olds between 2008 and 2014 in the Netherlands. Mild cognitive impairment (MCI) was based upon subjective complaints related to age and education-adjusted test scores. Mini-Mental State Examination (MMSE) impairment was defined by a score of < 26. Sexual activity and physical tenderness (e.g., fondling or kissing) in the last 6 months were assessed at an interview. Analyses were stratified by gender and partner status, with prevalence rates for the "no impairment" categories weighted based on age from the cognitive impairment categories. Inter-rater reliability was examined utilising 74 cohabiting couples of opposite gender. It was found that 14% were categorised as having cognitive impairment, and < 1% as dementia (excluded from subsequent analyses). There was strong evidence that the odds of engaging in physical tenderness (observed through MMSE < 26, OR 2.14, 95% CI 1.32-3.48, p = 0.002) and sexual activity (MCI, OR 2.36, 95% CI 1.35-4.12, p = 0.003) among partnered females with no impairment was twice that observed among cognitively impaired partnered females. There was weak evidence that the odds of engaging in physical tenderness (MMSE < 26, OR 1.59, 95% CI 1.04-2.42, p = 0.03) and sexual activity (MMSE < 26, OR 1.51, 95% CI 1.02-2.24, p = 0.04) among partnered males with no impairment was 50% greater than observed among cognitively impaired partnered males. The associations between cognitive functioning and physical tenderness continued to remain after adjustment for physical function, diabetes, cardiovascular disease and cancer. There was no clear evidence of a difference between amnestic and non-amnestic MCI for sexual behaviour. There was moderate to substantial agreement among the coupled adults who had 1 partner categorised with MCI. Having no cognitive impairment was associated with more engagement in sexual activity and physical tenderness among community-dwelling older adults. Sexuality is an important aspect of active aging and our findings illustrate a potential barrier to maintaining or instigating intimate relationships as we age. Longitudinal analyses are required to explore the direction of effect.


Determination of volatile marker compounds of common coffee roast defects.
Coffee beans from the same origin were roasted using six time-temperature profiles, in order to identify volatile aroma compounds associated with five common roast coffee defects (light, scorched, dark, baked and underdeveloped). Thirty-seven volatile aroma compounds were selected on the basis that they had previously been identified as potent odorants of coffee and were also identified in all coffee brew preparations; the relative abundance of these aroma compounds was then evaluated using gas chromatography mass spectrometry (GC-MS) with headspace solid phase micro extraction. Some of the 37 key aroma compounds were significantly changed in each coffee roast defect and changes in one marker compound was chosen for each defect type, that is, indole for light defect, 4-ethyl-2-methoxyphenol for scorched defect, phenol for dark defect, maltol for baked defect and 2,5-dimethylfuran for underdeveloped defect. The association of specific changes in aroma profiles for different roast defects has not been shown previously and could be incorporated into screening tools to enable the coffee industry quickly identify if roast defects occur during production.


Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.
Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10-08, β=7.2). Replication in three independent data sets (N=3612) confirmed the association of Asn396Ser (P-value=7.1 × 10-03, β=2.55) with depressive symptoms. LIPG is predicted to have enzymatic function in steroid biosynthesis, cholesterol biosynthesis and thyroid hormone metabolic processes. The Asn396Ser variant is predicted to have a damaging effect on the function of LIPG. Within the discovery population, carriers also showed an increased burden of white matter lesions (P-value=3.3 × 10-02) and a higher risk of Alzheimer's disease (odds ratio=2.01; P-value=2.8 × 10-02) compared with the non-carriers. Together, these findings implicate the Asn396Ser variant of LIPG in the pathogenesis of depressive symptoms in the general population.


Neonatal piglet survival: impact of sow nutrition around parturition on fetal glycogen deposition and production and composition of colostrum and transient milk.
Piglet survival is a major problem, especially during the first 3 days after birth. Piglets are born deficient of energy, but at the same time they have a very high energy requirement because of high physical activity, high need for thermoregulation (because of their lean body with low insulation) and high heat production in muscle tissues. To be able to survive, newborn piglets may rely upon three different sources of energy, namely, glycogen, colostrum and transient milk, which orchestrate to cover their energy requirements. Piglets are born with limited amounts of energy in glycogen depots in the liver and muscle tissues and these depots are sufficient for normal activity for ∼16 h. Intake and oxidation of fat and lactose from colostrum must supply sufficient amount of energy to cover at least another 18 h until transient milk becomes available in the sow udder ∼34 h after the first piglet is born. Selection for large litters during the last two decades has challenged piglets even further during the critical neonatal phase because the selection programs indirectly decreased birth weight of piglets and because increased litter size has increased the competition between littermates. Different attempts have been made to increase the short-term survival of piglets, that is, survival until day 3 of lactation, by focusing on improving transfer of vital maternal energy to the offspring, either in utero or via mammary secretions. Thus, the present review addresses how sow nutrition in late gestation may favor survival of newborn piglets by increasing glycogen depots, improving colostrum yield or colostrum composition, or by increasing production of transient milk.


Acute mediastinitis due to extravasation of parenteral nutritional formula via a central venous catheter.
Mediastinitis is a complication generally associated with thoracic surgery. Its occurrence after placement of a central venous catheter is uncommon, and only a few cases have been reported. An 83-year-old man who had mediastinitis due to extravasation of parenteral nutritional formula via a central venous catheter is presented. The signs and symptoms, diagnosis, and treatment of this unusual complication are described. This complication should be included in the differential diagnosis of mediastinitis in patients with a central venous catheter in place who have not had thoracic surgery.


Psychosocial development in survivors of childhood differentiated thyroid carcinoma: a cross-sectional study.
The impact of childhood differentiated thyroid carcinoma (DTC) on psychosocial development has not yet been studied. The aim of this study was to evaluate the achievement of psychosocial developmental milestones in long-term survivors of childhood DTC. Survivors of childhood DTC diagnosed between 1970 and 2013 were included. Reasons for exclusion were age <18 or >35 years at follow-up, a follow-up period <5 years or diagnosis with DTC as a second malignant neoplasm. Survivors gathered peer controls of similar age and sex (n = 30). A comparison group non-affected with cancer (n = 508) and other childhood cancer survivors (CCS) were also used to compare psychosocial development. To assess the achievement of psychosocial milestones (social, autonomy and psychosexual development), the course of life questionnaire (CoLQ) was used. We included 39 survivors of childhood DTC (response rate 83.0%, mean age at diagnosis 15.6 years, and mean age at evaluation 26.1 years). CoLQ scores did not significantly differ between survivors of childhood DTC and the two non-affected groups. CoLQ scores of childhood DTC survivors were compared to scores of other CCS diagnosed at similar ages (n = 76). DTC survivors scored significantly higher on social development than other CCS, but scores were similar on autonomy and psychosexual developmental scales. Survivors of childhood DTC showed similar development on social, autonomy, and psychosexual domains compared to non-affected individuals. Social development was slightly more favorable in DTC survivors than in other CCS, but was similar on autonomy and psychosexual domains.


Fluid mixing and the deep biosphere of a fossil Lost City-type hydrothermal system at the Iberia Margin.
Subseafloor mixing of reduced hydrothermal fluids with seawater is believed to provide the energy and substrates needed to support deep chemolithoautotrophic life in the hydrated oceanic mantle (i.e., serpentinite). However, geosphere-biosphere interactions in serpentinite-hosted subseafloor mixing zones remain poorly constrained. Here we examine fossil microbial communities and fluid mixing processes in the subseafloor of a Cretaceous Lost City-type hydrothermal system at the magma-poor passive Iberia Margin (Ocean Drilling Program Leg 149, Hole 897D). Brucite-calcite mineral assemblages precipitated from mixed fluids ca. 65 m below the Cretaceous paleo-seafloor at temperatures of 31.7 ± 4.3 °C within steep chemical gradients between weathered, carbonate-rich serpentinite breccia and serpentinite. Mixing of oxidized seawater and strongly reducing hydrothermal fluid at moderate temperatures created conditions capable of supporting microbial activity. Dense microbial colonies are fossilized in brucite-calcite veins that are strongly enriched in organic carbon (up to 0.5 wt.% of the total carbon) but depleted in (13)C (δ(13)C(TOC) = -19.4‰). We detected a combination of bacterial diether lipid biomarkers, archaeol, and archaeal tetraethers analogous to those found in carbonate chimneys at the active Lost City hydrothermal field. The exposure of mantle rocks to seawater during the breakup of Pangaea fueled chemolithoautotrophic microbial communities at the Iberia Margin, possibly before the onset of seafloor spreading. Lost City-type serpentinization systems have been discovered at midocean ridges, in forearc settings of subduction zones, and at continental margins. It appears that, wherever they occur, they can support microbial life, even in deep subseafloor environments.


Structure-decoupled functional connectome-based brain age prediction provides higher association to cognition.
Brain age prediction as well as the prediction difference has been well examined to be a potential biomarker for brain disease or abnormal aging process. However, less knowledge was reported for the cognitive association within normal population. In this study, we proposed a novel approach to brain age prediction by structure-decoupled functional connectome. The original functional connectome was decomposed and decoupled into a structure-decoupled functional connectome using structural connectome harmonics. Our method was applied to a large dataset of normal aging individuals and achieved a high correlation between predicted and chronological age (r = 0.77). Both the original FC and structure-decoupled FC could be well-trained in a brain age prediction model. Significant remarkable relationships between the brain age prediction difference (predicted age minus chronological age) and cognitive scores were discovered. However, the brain age-predicted difference driven by structure-decoupled FC showed a stronger correction to the two cognitive scores (MMSE: r = -0.27, P -value = 0.002; MoCA: r = -0.32, P -value = 0.0003). Our findings suggest that our structure-decoupled functional connectivity approach could provide a more individual-specific functional network, leading to improved brain age prediction performance and a better understanding of cognitive decline in aging.


A Complex Endomembrane System in the Archaeon Ignicoccus hospitalis Tapped by Nanoarchaeum equitans.
Based on serial sectioning, focused ion beam scanning electron microscopy (FIB/SEM), and electron tomography, we depict in detail the highly unusual anatomy of the marine hyperthermophilic crenarchaeon, Ignicoccus hospitalis. Our data support a complex and dynamic endomembrane system consisting of cytoplasmic protrusions, and with secretory function. Moreover, we reveal that the cytoplasm of the putative archaeal ectoparasite Nanoarchaeum equitans can get in direct contact with this endomembrane system, complementing and explaining recent proteomic, transcriptomic and metabolomic data on this inter-archaeal relationship. In addition, we identified a matrix of filamentous structures and/or tethers in the voluminous inter-membrane compartment (IMC) of I. hospitalis, which might be responsible for membrane dynamics. Overall, this unusual cellular compartmentalization, ultrastructure and dynamics in an archaeon that belongs to the recently proposed TACK superphylum prompts speculation that the eukaryotic endomembrane system might originate from Archaea.


Astroviruses as causative agents of poultry enteritis: genetic characterization and longitudinal studies on field conditions.
Astroviruses (AstVs) are nonenveloped RNA small round viruses (SRVs) with a genome of 6.8-7.9 kb. Known avian AstVs are spread worldwide; they have been associated with poult enteritis and mortality syndrome in the United States and reported in Italy in intensive turkey and guinea fowl flocks. Nevertheless, their real prevalence and their pathogenic role in avian enteritis affecting Italian flocks is far from clear. Negative staining electron microscopy (nsEM) is used for the routine diagnosis of avian enteric SRVs, although it cannot distinguish morphologically similar particles. Enzyme-linked immunosorbent assay (ELISA), reverse-transcription PCR (RT-PCR), and genomic sequencing are now used for this specific purpose. We analyzed 329 samples of chicken, turkey, and guinea fowl intestinal contents from Italian poultry flocks. Most samples were from enteritis outbreaks, but we also included samples from three longitudinal studies (one on 11 broiler flocks and the other two on a guinea fowl flock). We first examined the samples with nsEM. SRVs, including AstVs, are often associated with rotaviruses and were the most commonly detected morphotypes in avian enteric diseases. We then analyzed 124 of the samples with an RT-PCR targeting the open reading frame (ORF)-1b of AstV. This gene codes for an RNA-dependent polymerase. We then sequenced and genetically analyzed the RT-PCR positive samples. Phylogenetic analysis distinguished three defined clusters: the first included guinea fowl AstVs and turkey AstVs-2; the second, chicken AstVs; and the third was formed by avian nephritis viruses (ANVs). No strains clustered with turkey AstVs-1. The results indicate that ORF-1b presents certain genetic variability, even among AstVs from the same species. In longitudinal studies, samples retrieved from the same shed were homogeneous, with some exceptions suggesting possible coexistence of different genetic types in the same unit. The finding of ANV-like viruses in commercial guinea fowls underlines the genetic variability of AstVs and strengthens the hypothesis of a varied intraherd situation.


Ultrasonography in schistosomiasis in Africa.
Approximately 50 publications have become available in the international literature on ultrasonography in schistosomiasis in Africa. Geographically these cover Congo, Egypt, Kenya, Mali, Mauritius, Niger, Senegal, Sudan, Tanzania and East African Islands as well as Zimbabwe. Further studies are ongoing in many countries, such as Burundi, Ghana, Madagaskar and Uganda. It was shown that ultrasonography is useful in the detection of morbidity induced by schistosomiasis on an individual basis and on the community level. There is indication for varying morbidity patterns in different African foci. Post-treatment monitoring has provided evidence for reversibility of pathological lesions induced by Schistosoma (S.) haematobium and S. mansoni, even though evidence for reversibility of periportal fibrosis in adults is not yet satisfactorily substantiated. A standardized set of criteria for ultrasonographical observations has been worked out and is presently in the process of being refined. It is thus hoped that standardization will contribute to render studies in different endemic settings comparable on a global basis.


Portraiture: a methodology through which success and positivity can be explored and reflected.
To present an overview of portraiture. Nursing is increasingly embracing more arts-based approaches as research methodologies. Portraiture has an underlying philosophy and process that enables the illumination of real people in real settings through the 'painting' of their stories. It is a complex methodology in which the researcher attempts to illuminate meaning of personal stories and events presented as narrative. Interview data were collected from nine participants from three nursing settings. Nurses were invited to participate in an interview or conversation designed to elicit data to address the research questions; the aim was to gain insight into the nurses' common shared meanings and shared contemplations of their feelings about resilience. Criteria for inclusion in this study required that all nurse participants were English speaking, registered with the Nurses and Midwives Board of Western Australia and that each had over five years' experience in the Western Australian healthcare environment. This was to enable reflection on significant and ongoing changes within the workplace as a possible source of resilient behaviours. This is a methodological paper. Portraiture blends aesthetics and empiricism while drawing on features of narrative, case study, phenomenology and ethnography. The portraits stand as individual vignettes revealing recognisable themes and enabling patterns of experience to emerge from each topic being studied. Each portrait requires the researcher to constantly reflect on the participant's experiences by incorporating ethnographic observations, interview responses, impressionistic records, the interpretation of context, and the researcher's experiences and insights. It is a methodology that concentrates on success and positivity to immerse the reader in carefully painted and perceptive stories of success and positivity in times of adversity. This paper describes some of the hallmarks of the portraiture method, one of which is to portray success and positivity, and points to the relationship this approach may have with contemporary social science and positive psychology research. The illumination of resilience as a strategy to be learned and fostered in nurses in times of adversity has implications for managers and nursing practice. Resilience education engenders a more resilient workforce and has implications for nurses choosing to or being able to stay in nursing during times of stress and adversity.


Conversion therapy from N3 unresectable lung adenocarcinoma to radical surgery: a case report.
Patients with N3 non-small cell lung cancer (NSCLC) have unresectable tumors. Although significant progress has been made in the past decades for such tumors, the average median survival time remains at 10 months. Equally dismal long-term survival rates were reported with the average 5-year-suvival rate at 9%. Here, we report on a case of a patient with locally advanced disease that was treated with conversion therapy using targeted anti-PD-1 immunotherapy with platinum-based chemotherapy. Following this therapeutic regimen, the tumor showed a reversion to pN0 from pN3 and the patient showed a progression free survival time of at least 33 months.


Discrimination between paralogs using microarray analysis: application to the Yap1p and Yap2p transcriptional networks.
Ohno [Ohno, S. (1970) in Evolution by Gene Duplication, Springer, New York] proposed that gene duplication with subsequent divergence of paralogs could be a major force in the evolution of new gene functions. In practice the functional differences between closely related homologues produced by duplications can be subtle and difficult to separate experimentally. Here we show that DNA microarrays can distinguish the functions of two closely related homologues from the yeast Saccharomyces cerevisiae, Yap1p and Yap2p. Although Yap1p and Yap2p are both bZIP transcription factors involved in multiple stress responses and are 88% identical in their DNA binding domains, our work shows that these proteins activate nonoverlapping sets of genes. Yap1p controls a set of genes involved in detoxifying the effects of reactive oxygen species, whereas Yap2p controls a set of genes over represented for the function of stabilizing proteins. In addition we show that the binding sites in the promoters of the Yap1p-dependent genes differ from the sites in the promoters of Yap2p-dependent genes and we validate experimentally that these differences are important for regulation by Yap1p. We conclude that while Yap1p and Yap2p may have some overlapping functions they are clearly not redundant and, more generally, that DNA microarray analysis will be an important tool for distinguishing the functions of the large numbers of highly conserved genes found in all eukaryotic genomes.


Cognitive complexity of clients and counsellors during motivation-based treatment for smoking cessation: an observational study on occasional smokers in a US college sample.
Motivational interviewing (MI) is a widely used and promising treatment approach for aiding in smoking cessation. The present observational study adds to other recent research on why and when MI works by investigating a new potential mechanism: integrative complexity. The study took place in college fraternity and sorority chapters at one large midwestern university. Researchers transcribed MI counselling sessions from a previous randomised controlled trial focused on tobacco cessation among college students and subsequently scored clients' and counsellors' discussions across four counselling sessions for integrative complexity. This is an observational secondary analysis of a randomised controlled trial that tested the effectiveness of MI. We analysed the relationship between integrative complexity and success at quitting smoking in the trial. Success in quitting smoking:Participants were categorised into two outcome groups (successful quitters vs failed attempters), created based on dichotomous outcomes on two standard variables: (1) self-reported attempts to quit and (2) number of days smoked via timeline follow-back assessment procedures that use key events in participants' lives to prompt their recall of smoking. We found (1) significantly higher complexity overall for participants who tried to quit but failed compared with successful quitters (standardised β=0.36, p<0.001, (Lower Confidence Interval.)LCI=0.16, (Upper Confidence Interval) UCI=0.47) and (2) the predictive effect of complexity on outcome remains when controlling for standard motivational and demographic variables (partial r(102)=-0.23, p=0.022). Taken together, these results suggest that cognitive complexity is uniquely associated with successful quitting in MI controlled trials, and thus may be an important variable to more fully explore during treatment.


Making a hydrophoretic focuser tunable using a diaphragm.
Microfluidic diagnostic devices often require handling particles or cells with different sizes. In this investigation, a tunable hydrophoretic device was developed which consists of a polydimethylsiloxane (PDMS) slab with hydrophoretic channel, a PDMS diaphragm with pressure channel, and a glass slide. The height of the hydrophoretic channel can be tuned simply and reliably by deforming the elastomeric diaphragm with pressure applied on the pressure channel. This operation allows the device to have a large operating range where different particles and complex biological samples can be processed. The focusing performance of this device was tested using blood cells that varied in shape and size. The hydrophoretic channel had a large cross section which enabled a throughput capability for cell focusing of ∼15 000 cells s(-1), which was more than the conventional hydrophoretic focusing and dielectrophoresis (DEP)-active hydrophoretic methods. This tunable hydrophoretic focuser can potentially be integrated into advanced lab-on-a-chip bioanalysis devices.


The genetics of vitamin C loss in vertebrates.
Vitamin C (ascorbic acid) plays important roles as an anti-oxidant and in collagen synthesis. These important roles, and the relatively large amounts of vitamin C required daily, likely explain why most vertebrate species are able to synthesize this compound. Surprisingly, many species, such as teleost fishes, anthropoid primates, guinea pigs, as well as some bat and Passeriformes bird species, have lost the capacity to synthesize it. Here, we review the genetic bases behind the repeated losses in the ability to synthesize vitamin C as well as their implications. In all cases so far studied, the inability to synthesize vitamin C is due to mutations in the L-gulono-γ-lactone oxidase (GLO) gene which codes for the enzyme responsible for catalyzing the last step of vitamin C biosynthesis. The bias for mutations in this particular gene is likely due to the fact that losing it only affects vitamin C production. Whereas the GLO gene mutations in fish, anthropoid primates and guinea pigs are irreversible, some of the GLO pseudogenes found in bat species have been shown to be reactivated during evolution. The same phenomenon is thought to have occurred in some Passeriformes bird species. Interestingly, these GLO gene losses and reactivations are unrelated to the diet of the species involved. This suggests that losing the ability to make vitamin C is a neutral trait.


Influence of T cell receptor V alpha expression on Mlsa superantigen-specific T cell responses.
Recognition of conventional foreign antigen by T cells is determined by the expression of multiple variable regions of both alpha and beta chains of the T cell receptor (TCR) alpha/beta heterodimer. In contrast, there exists a class of antigens that appears to interact with the TCR alpha/beta heterodimer through the variable region on the beta chain (V beta), independent of other TCR components, a property that has led to their designation as superantigens. The goal of the present study was to analyze V alpha use in V beta 6+ T cells responsive to the superantigen, Mlaa. Results indicate that while deletion of T cells expressing V beta 6 in Mlsa-expressing mice is essentially complete and therefore appears to occur regardless of V alpha usage, in vitro Mlsa stimulation of T cells from Mlsa-negative mice results in significant skewing of V alpha use among responding V beta 6+ T cells. This indicates that V alpha expression influences recognition of the superantigen, Mlsa by mature peripheral T cells.


Spectrum and frequency of cardiac channel defects in swimming-triggered arrhythmia syndromes.
Swimming is a relatively genotype-specific arrhythmogenic trigger for type 1 long-QT syndrome (LQT1). We hypothesize that mimickers of concealed LQT1, namely catecholaminergic polymorphic ventricular tachycardia (CPVT), may also underlie swimming-triggered cardiac events. Between August 1997 and May 2003, 388 consecutive, unrelated patients were referred specifically for LQTS genetic testing. The presence of a personal and/or family history of a near-drowning or drowning was determined by review of the medical records and/or phone interviews and was blinded to genetic test results. Comprehensive mutational analysis of the 5 LQTS-causing channel genes, KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6), along with KCNJ2 (Andersen-Tawil syndrome) and targeted analysis of 18 CPVT1-associated exons in RyR2, was performed with the use of denaturing high-performance liquid chromatography and direct DNA sequencing. Approximately 11% (43 of 388) of the index cases had a positive swimming phenotype. Thirty-three of these 43 index cases had a "Schwartz" score (> or =4) suggesting high clinical probability of LQTS. Among this subset, 28 patients (85%) were LQT1, 2 patients (6%) were LQT2, and 3 were genotype negative. Among the 10 cases with low clinical probability for LQTS, 9 had novel, putative CPVT1-causing RyR2 mutations. In contrast to previous studies that suggested universal LQT1 specificity, genetic heterogeneity underlies channelopathies that are suspected chiefly because of a near-drowning or drowning. CPVT1 and strategic genotyping of RyR2 should be considered when LQT1 is excluded in the pathogenesis of a swimming-triggered arrhythmia syndrome.


Diagnosis of Urinary Tract Infections by Urine Flow Cytometry: Adjusted Cut-Off Values in Different Clinical Presentations.
Bacterium and leucocyte counts in urine can be measured by urine flow cytometry (UFC). They are used to predict significant bacterial growth in urine culture and to diagnose infections of the urinary tract. However, little information is available on appropriate UFC cut-off values for bacterium and leucocyte counts in specific clinical presentations. To develop, validate, and evaluate adapted cut-off values that result in a high negative predictive value for significant bacterial growth in urine culture in common clinical presentation subgroups. This is a single center, retrospective, observational study with data from patients of the emergency department of Bern University Hospital, Switzerland, with suspected infections of the urinary tract. The patients presented with different symptoms, and urine culture and urine flow cytometry were performed. For different clinical presentations, the patients were grouped by (i) age (>65 years), (ii) sex, (iii) clinical symptoms (e.g., fever or dysuria), and (iv) comorbidities such as diabetes and immunosuppression. For each group, cut-off values were developed, validated, and analyzed using different strategies, i.e., linear discriminant analysis (LDA) and Youden's index, and were compared with known cut-offs and cut-offs optimized for sensitivity. 613 patients were included in the study. Significant bacterial growth in urine culture depended on clinical presentation and ranged from 32.3% in male patients to 61.5% in patients with urinary frequency. In all clinical presentations, the predictive accuracy of UFC leucocyte and UFC bacterium counts was good for significant bacterial growth in urine culture (AUC ≥ 0.88). The adapted LDA95 equations did not exhibit consistently high sensitivity. However, the in-house cut-offs (test positive if UFC leucocytes > 17/μL or UFC bacteria > 125/μL) were highly sensitive (>90%). In female, younger, and dysuric patients, even higher cut-offs for UFC leucocytes (169/μL, 169/μL, and 205/μL) exhibited high sensitivity. Specificity was insufficient (<0.9) for all tested cut-offs. For various clinical presentations, significant bacterial growth in urine culture can be excluded if flow cytometry measurements give a bacterial count of ≤125/μL or a leucocyte count of ≤17/μL. In female patients, dysuric patients, and patients younger than ≤65 years, the leucocyte cut-off can be increased to 170/μL.


Nucleoside triphosphate pyrophosphatase of rabbit matrix vesicles, a mechanism for the generation of inorganic pyrophosphate in epiphyseal cartilage.
Inorganic pyrophosphate (PPi) may be important in the regulation of mineralisation but its origin in epiphyseal cartilage is ill-defined. Nucleoside triphosphate pyrophosphatase is one potential source, as this enzyme catalyses the formation of PPi from nucleoside triphosphates. This enzyme has been identified in matrix vesicles derived from rabbit epiphyseal cartilage and a method developed to measure the activity using ATP as substrate in intact matrix vesicles under relatively physiological conditions. The enzyme had a high affinity for ATP (Km less than 10 microM) and was also active towards GTP, CTP and UTP. Disruption of the matrix vesicle membrane by sonication failed to alter the activity. Treatment of sonicated matrix vesicles with Triton X-100 increased the activity which may indicate a direct effect of the detergent on the enzyme. Activity towards ATP was inhibited substantially by ADP and AMP and by another potential substrate beta,gamma-methyleneadenosine 5'-triphosphate. Dichloromethylene bisphosphonate, an analogue of the product PPi, inhibited the activity to a lesser extent. Two other potential substrates, NADP+ and thymidine 5'-monophosphate p-nitrophenyl ester were only weakly inhibitory as was 1-hydroxyethylidene 1,1-bisphosphonate. These results imply that nucleoside triphosphates are the substrates in vivo and the inhibitory effects of ADP and AMP suggest mechanisms whereby this activity could be regulated.


Seasonal bone mass of college and senior female field hockey players.
The purpose of the study was to observe the relationship of field hockey playing with bone, muscle and fat in young and older adult women. We measured body composition by dual energy X-ray absorptiometry (DXA) in college players, senior players and controls after a 4-month playing-season and 8-month off-season. Whole body (WB), proximal femur (PF), lumbar spine (LS), right and left forearm (RF, LF) bone mineral density (BMD), percent fat and lean mass of college players (20.6+/-1.1 years; 7.7+/-1 playing years) were compared with those of non-playing controls (19.5+/-1.5 years). BMD of senior players (37.3+/-10.3 years; 19.7+/-9.3 playing years) was compared to normative values. The differences between right and left forearm BMDs during the on and off seasons were also compared. College player BMD was higher than controls at the WB (p=0.02), PF (p=0.00004), RF (p=0.006) and LF (p=0.005), but not the LS. Senior player BMD was higher than age-matched norms at the WB (p=0.001) and PF (p=0.006), but not the LS, RF or LF. There were no differences between on and off-season BMDs for either group. There were no differences between college player RF and LF BMD in either season, nor in the senior players during the off-season, however, during the season, senior players developed greater RF than LF BMD (p=0.02). College players had greater lean mass (p=0.00008) and lower fat mass than controls (p=0.003). Neither changed significantly between seasons. Senior players lost fat (p=0.04) and gained lean mass (p=0.02) in season. Adult female field hockey players have higher than average bone mass that does not change significantly according to seasonal involvement.


Dropout rates in exposure with response prevention for obsessive-compulsive disorder: What do the data really say?
The purposes of this review were to: 1) determine the attrition rates for exposure with response prevention (ERP) for obsessive-compulsive disorder (OCD), 2) compare them to those in other treatments for OCD, and 3) identify predictors of ERP attrition. A systematic literature search of randomized controlled trials for ERP for OCD yielded 21 studies, representing 1400 participants. Attrition data were extracted for individual treatment conditions. The weighted mean dropout rate for ERP was 14.7% (95% CI [11.4%, 18.4%]). This figure was not statistically different from that of comparison conditions (e.g., cognitive therapy; OR=0.67-2.22, all ps>0.15). Only two studies reported refusal rates for ERP (weighted mean=4.0%; 95% CI [0.7%, 9.2%]), which precluded calculation of a reliable refusal rate for ERP. Based on these figures, we estimated an overall attrition rate of 18.7% for ERP. Treatment experience, therapist qualification, and number of treatment sessions did not significantly predict dropout rate. Our review indicates that ERP may have treatment dropout rates similar to other treatments for OCD.


Jockey Falls, Injuries, and Fatalities Associated With Thoroughbred and Quarter Horse Racing in California, 2007-2011.
Despite the popularity of the horse racing industry in the United States and the wide recognition that horse racing is one of the most hazardous occupations, little focused research into the prevention of falls by and injuries to jockeys has been conducted. To describe the incidence rates and characteristics of falls and injuries to Thoroughbred and Quarter Horse racing jockeys in the state of California. Descriptive epidemiology study. Data on race-day falls and injuries were extracted from jockey accident reports submitted to the California Horse Racing Board from January 2007 to December 2011. Denominator data, number of jockey race rides, were obtained from commercial and industry databases. Jockey fall, injury, and fatality incidence rates and ratios in Thoroughbred and Quarter Horse flat races were estimated using Poisson regression. Characteristics of falls and injuries are described and compared. In Thoroughbred races, 184 jockey injuries occurred from 360 reported jockey falls, 180,646 race rides, 23,500 races, and 3350 race meetings. In Quarter Horse races, 85 jockey injuries occurred from 145 jockey falls, 46,106 race rides, 6320 races, and 1053 race meetings. Jockey falls occurred at a rate of 1.99 falls per 1000 rides in Thoroughbred races, with 51% of falls resulting in jockey injury, and 3.14 falls per 1000 rides in Quarter Horse races, with 59% of falls resulting in jockey injury. The majority of falls occurred during a race, with catastrophic injury or sudden death of the horse reported as the most common cause in both Thoroughbred (29%) and Quarter Horse (44%) races. During the period studied, 1 jockey fatality resulted from a fall. Jockey fall rates were lower but injury rates were comparable to those reported internationally. On average, a licensed jockey in California can expect to have a fall every 502 rides in Thoroughbred races and every 318 rides in Quarter Horse races. While jockey fall rates were lower, injury rates were similar to those in other racing jurisdictions. The high proportion of jockey falls caused by horse fatalities should be further investigated.


Usefulness of a Cannula with a Flexible Tip (Swing Tip) for Managing Severe Biliary Stricture.
Biliary stenting for the treatment of biliary stricture is the most common indication of ERCP, but the procedure is sometimes unsuccessful because of severe strictures. The Swing Tip is useful for passing through severe strictures because it has a manually operable tip. The efficacy of using a Swing Tip was retrospectively evaluated. The 2353 patients who underwent ERCP for biliary stenting at our facility between January 2012 and July 2018 were enrolled. In all patients, procedures were begun using tapered tip-catheters, and Swing Tips were used if the procedure was found to be difficult with other devices. The indication for switching to the Swing Tip and the technical success rate were retrospectively evaluated. A total of 99 patients (4.2%) underwent ERCP using the Swing Tip, including 49 patients for the selection of biliary branches and 50 for exchanging guidewires for rigid ones. In these patients, biliary stenting was successful in 22 patients (44.9%) and 45 patients (90%), respectively. The other 32 patients with failed endoscopic biliary drainage were treated via alternative approaches, such as percutaneous procedures, surgeries, or conservative treatments. There were no adverse events associated with the Swing Tip. The Swing Tip was technically feasible especially for exchanging guidewires during ERCP. Percutaneous procedures or surgical treatments can be avoided by using the Swing Tip. This study was approved by the institutional review board of Okayama University. All subjects provided informed consent. The study was registered in the UMIN protocol registration system (identification number UMIN 000033692).


Ecological Assembly Processes Are Coordinated between Bacterial and Viral Communities in Fractured Shale Ecosystems.
The ecological drivers that concurrently act upon both a virus and its host and that drive community assembly are poorly understood despite known interactions between viral populations and their microbial hosts. Hydraulically fractured shale environments provide access to a closed ecosystem in the deep subsurface where constrained microbial and viral community assembly processes can be examined. Here, we used metagenomic analyses of time-resolved-produced fluid samples from two wells in the Appalachian Basin to track viral and host dynamics and to investigate community assembly processes. Hypersaline conditions within these ecosystems should drive microbial community structure to a similar configuration through time in response to common osmotic stress. However, viral predation appears to counterbalance this potentially strong homogeneous selection and pushes the microbial community toward undominated assembly. In comparison, while the viral community was also influenced by substantial undominated processes, it assembled, in part, due to homogeneous selection. When the overall assembly processes acting upon both these communities were directly compared with each other, a significant relationship was revealed, suggesting an association between microbial and viral community development despite differing selective pressures. These results reveal a potentially important balance of ecological dynamics that must be in maintained within this deep subsurface ecosystem in order for the microbial community to persist over extended time periods. More broadly, this relationship begins to provide knowledge underlying metacommunity development across trophic levels.IMPORTANCE Interactions between viral communities and their microbial hosts have been the subject of many recent studies in a wide range of ecosystems. The degree of coordination between ecological assembly processes influencing viral and microbial communities, however, has been explored to a much lesser degree. By using a combined null modeling approach, this study investigated the ecological assembly processes influencing both viral and microbial community structure within hydraulically fractured shale environments. Among other results, significant relationships between the structuring processes affecting both the viral and microbial community were observed, indicating that ecological assembly might be coordinated between these communities despite differing selective pressures. Within this deep subsurface ecosystem, these results reveal a potentially important balance of ecological dynamics that must be maintained to enable long-term microbial community persistence. More broadly, this relationship begins to provide insight into the development of communities across trophic levels.


Entangled epidemics: cocaine use and HIV disease.
Over the past decade, two epidemics have had a severe impact on public health in this country. These health problems involve cocaine abuse and AIDS (or HIV disease). The processes of these two conditions are clearly not independent of each other and may be quite complex. Understanding of this relationship has been hampered by a myriad of social, biological and behavioral variables that are entangled with the basic cocaine-HIV association. This article presents a paradigm for discussion of the interaction between cocaine exposure and HIV disease based on three mechanisms: the relationship between cocaine exposure and increased opportunity for HIV exposure, the direct role that cocaine plays in altering susceptibility to HIV infection, and the influence that cocaine use has on the progression of HIV disease. The goal of this structured approach is to enhance conceptual understanding of the cocaine-HIV relationship while recognizing the complexity of the issue and the limitations of current research efforts. This model will serve as a framework for the discussion of implications for future research, clinical practice, and public policy.


Effects of Ankaferd on anastomotic healing of colon.
Ankaferd (Ankaferd blood stopper®, ABS) is a recently developed topical hemostatic agent. ABS is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. Through its effects on the endothelium, blood cells, angiogenesis, cellular proliferation, vascular dynamics, and cell mediators; Ankaferd plays a part in inflammation and hemostasis processes. The aim of this experimental study is to assess the effects of ABS on the left colonic anastomoses under normal, septic, and ischemic conditions. Forty-eight Wistar Albino male rats were divided into six weight-matched equal groups: A, anastomosis in normal condition (n = 8); AA, anastomosis with ABS in normal condition (n = 8); AS, anastomosis in septic condition (n = 8); AAS, anastomosis with ABS in septic condition (n = 8); AI, anastomosis in ischemic condition (n = 8); and AAI, anastomosis with ABS in ischemic condition (n = 8). Blood and tissue samples were taken for the histopathological and biochemical studies after the anastomotic bursting pressures were measured. Higher hydroxyproline levels (p = .048) and angiogenesis (p = .038) were observed in the sepsis-induced rats compared to the control group. The inflammatory activity, fibrosis, and granulation were comparable in all experimental groups. Ankaferd improved the angiogenesis under septic conditions (AAS) when compared to the control group (AI; p = .038). ABS may support anastomotic healing in septic conditions. Topical ABS application controlling the mucosal bleeding at the cut ends of the colon may also improve the anastomotic wound healing by means of increasing mechanical strength and positively affecting angiogenesis. Further studies shall focus on the clinical importance of those findings.


Evaluation of peristalsis in multiple segments of the guinea-pig isolated small intestine: optimisation of tissue use by refined in vitro methodology.
Peristalsis is the aboral movement by which the intestine propels its contents. Since pharmacological research requires an experimental model with which drug-induced modifications of peristalsis can be reliably quantified, we set out to develop and validate an in vitro method for studying peristalsis in multiple gut segments. In our arrangement, up to four 10cm segments isolated from the guinea-pig jejunum and ileum can be set up in parallel and their lumens perfused. Peristalsis was elicited by pressure-evoked wall distension, and the peristalsis-induced changes in the intraluminal pressure were evaluated with software that determined the peristaltic pressure threshold, the frequency, maximal acceleration and amplitude of the peristaltic waves, and the residual baseline pressure. Validation experiments showed that the peristalsis parameters at baseline and after modification by morphine (0.01-10microM) did not differ between segments from the jejunum and ileum, or between segments examined in a consecutive manner. In conclusion, our work succeeded in optimising the use of the guinea-pig jejunum and ileum for multiple recordings of peristalsis in vitro, and in refining the recording and evaluation of peristaltic motility. This system promises to be particularly useful in the pharmacological screening and testing of drugs which modify peristalsis.


Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.
This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on considerations for the comprehensive care of AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.


Machine learning assisted reflectance spectral characterisation of coronary thrombi correlates with microvascular injury in patients with ST-segment elevation acute coronary syndrome.
We set out to further develop reflectance spectroscopy for the characterisation and quantification of coronary thrombi. Additionally, we explore the potential of our approach for use as a risk stratification tool by exploring the relation of reflectance spectra to indices of coronary microvascular injury. We performed hyperspectral imaging of coronary thrombi aspirated from 306 patients presenting with ST-segment elevation acute coronary syndrome (STEACS). Spatially resolved reflected light spectra were analysed using unsupervised machine learning approaches. Invasive [index of coronary microvascular resistance (IMR)] and non-invasive [microvascular obstruction (MVO) at cardiac magnetic resonance imaging] indices of coronary microvascular injury were measured in a sub-cohort of 36 patients. The derived spectral signatures of coronary thrombi were correlated with both invasive and non-invasive indices of coronary microvascular injury. Successful machine-learning-based classification of the various thrombus image components, including differentiation between blood and thrombus, was achieved when classifying the pixel spectra into 11 groups. Fitting of the spectra to basis spectra recorded for separated blood components confirmed excellent correlation with visually inspected thrombi. In the 36 patients who underwent successful thrombectomy, spectral signatures were found to correlate well with the index of microcirculatory resistance and microvascular obstruction; R 2: 0.80, p < 0.0001, n = 21 and R 2: 0.64, p = 0.02, n = 17, respectively. Machine learning assisted reflectance spectral analysis can provide a measure of thrombus composition and evaluate coronary microvascular injury in patients with STEACS. Future work will further validate its deployment as a point-of-care diagnostic and risk stratification tool for STEACS care.


Efficacy of surgical preparation solutions in shoulder surgery.
Deep infection following shoulder surgery is a rare but devastating problem. The use of an effective skin-preparation solution may be an important step in preventing infection. The purposes of the present study were to examine the native bacteria around the shoulder and to determine the efficacy of three different surgical skin-preparation solutions on the eradication of bacteria from the shoulder. A prospective study was undertaken to evaluate 150 consecutive patients undergoing shoulder surgery at one institution. Each shoulder was prepared with one of three randomly selected solutions: ChloraPrep (2% chlorhexidine gluconate and 70% isopropyl alcohol), DuraPrep (0.7% iodophor and 74% isopropyl alcohol), or povidone-iodine scrub and paint (0.75% iodine scrub and 1.0% iodine paint). Aerobic and anaerobic cultures were obtained prior to skin preparation for the first twenty patients, to determine the native bacteria around the shoulder, and following skin preparation for all patients. Coagulase-negative Staphylococcus and Propionibacterium acnes were the most commonly isolated organisms prior to skin preparation. The overall rate of positive cultures was 31% in the povidone-iodine group, 19% in the DuraPrep group, and 7% in the ChloraPrep group. The positive culture rate for the ChloraPrep group was lower than that for the povidone-iodine group (p < 0.0001) and the DuraPrep group (p = 0.01). ChloraPrep and DuraPrep were more effective than povidone-iodine in eliminating coagulase-negative Staphylococcus from the shoulder region (p < 0.001 for both). No significant difference was detected among the agents in their ability to eliminate Propionibacterium acnes from the shoulder region. No infections occurred in any of the patients treated in this study at a minimum of ten months of follow-up. ChloraPrep is more effective than DuraPrep and povidone-iodine at eliminating overall bacteria from the shoulder region. Both ChloraPrep and DuraPrep are more effective than povidone-iodine at eliminating coagulase-negative Staphylococcus from the shoulder.


Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1.
Cell migration relies on coordinated activity of chemotactic and guidance receptors. Here, we report a specific role for the RNA-binding protein ZFP36L1 in limiting the abundance of molecules involved in the homing of antibody-secreting cells (ASCs) to the bone marrow (BM). In the absence of ZFP36L1, ASCs build up in the spleen and the liver and show diminished accumulation in the BM. ZFP36L1 facilitates migration by directly regulating G protein-coupled receptor kinase 2 (GRK2) and the integrin chains α4 and β1 in splenic ASCs. Expression of CXCR4 and of the integrins α4 and β1 is differentially regulated on ASCs produced at the early and late stages of the immune response. Consequently, deletion of the Zfp36l1 gene has a stronger effect on BM accumulation of high-affinity ASCs formed late in the response. Thus, ZFP36L1 is an integral part of the regulatory network controlling gene expression during ASC homing.


Efficient encoding of motion is mediated by gap junctions in the fly visual system.
Understanding the computational implications of specific synaptic connectivity patterns is a fundamental goal in neuroscience. In particular, the computational role of ubiquitous electrical synapses operating via gap junctions remains elusive. In the fly visual system, the cells in the vertical-system network, which play a key role in visual processing, primarily connect to each other via axonal gap junctions. This network therefore provides a unique opportunity to explore the functional role of gap junctions in sensory information processing. Our information theoretical analysis of a realistic VS network model shows that within 10 ms following the onset of the visual input, the presence of axonal gap junctions enables the VS system to efficiently encode the axis of rotation, θ, of the fly's ego motion. This encoding efficiency, measured in bits, is near-optimal with respect to the physical limits of performance determined by the statistical structure of the visual input itself. The VS network is known to be connected to downstream pathways via a subset of triplets of the vertical system cells; we found that because of the axonal gap junctions, the efficiency of this subpopulation in encoding θ is superior to that of the whole vertical system network and is robust to a wide range of signal to noise ratios. We further demonstrate that this efficient encoding of motion by this subpopulation is necessary for the fly's visually guided behavior, such as banked turns in evasive maneuvers. Because gap junctions are formed among the axons of the vertical system cells, they only impact the system's readout, while maintaining the dendritic input intact, suggesting that the computational principles implemented by neural circuitries may be much richer than previously appreciated based on point neuron models. Our study provides new insights as to how specific network connectivity leads to efficient encoding of sensory stimuli.


Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells.
The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. We report long-term results from three clinical trials to evaluate gammaretroviral vector-engineered T cells for HIV. The vector encoded a chimeric antigen receptor (CAR) composed of CD4 linked to the CD3ζ signaling chain (CD4ζ). CAR T cells were detected in 98% of samples tested for at least 11 years after infusion at frequencies that exceeded average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells; integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells had stable levels of engraftment, with decay half-lives that exceeded 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression before T cell transfer is not required to achieve long-term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient-years of follow-up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long-term delivery of protein-based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases.


Dopaminergic Modulation of Synaptic Integration and Firing Patterns in the Rat Entopeduncular Nucleus.
Dopamine is known to differentially modulate the impact of cortical input to the striatum between the direct and indirect pathways of the basal ganglia (BG). However, the role of extrastriatal dopamine receptors (DRs) in BG information processing is less clear. To investigate the role of extrastriatal DRs, we studied their distribution and function in one of the output nuclei of the BG of the rodent, the entopeduncular nucleus (EP). qRT-PCR indicated that all DR subtypes were expressed by EP neurons, suggesting that both D1-like receptors (D1LRs) and D2-like receptors (D2LRs) were likely to affect information processing in the EP. Whole-cell recordings revealed that striatal inputs to the EP were potentiated by D1LRs whereas pallidal inputs to the EP were depressed by D2LRs. Changes to the paired-pulse ratio of inputs to the EP suggested that dopaminergic modulation of striatal inputs is mediated by postsynaptic receptors, and that of globus pallidus-evoked inputs is mediated by presynaptic receptors. We show that these changes in synaptic efficacy changed the information content of EP neuron firing. Overall, the findings suggest that the dopaminergic system affects the passage of feedforward information through the BG by modulating input divergence in the striatum and output convergence in the EP.SIGNIFICANCE STATEMENT The entopeduncular nucleus (EP), one of the basal ganglia (BG) output nuclei, is an important station in information processing in BG. However, it remains unclear how EP neurons encode information and how dopamine affects this process. This contrasts with the well established role of dopamine in the striatum, which is known to redistribute cortical input between the direct and indirect pathways. Here we show that, in symmetry with the striatum, dopamine controls the rebalancing of information flow between the two pathways in the EP. Specifically, we demonstrate that dopamine regulates EP activity by differentially modulating striatal and pallidal GABAergic inputs. These results call for a reassessment of current perspectives on BG information processing by highlighting the functional role of extrastriatal dopamine receptors.


Volatile atmospheric pressure chemical ionisation mass spectrometry headspace analysis of E. coli and S. aureus.
Identifying the characteristics of bacterial species can improve treatment outcomes and mass spectrometry methods have been shown to be capable of identifying biomarkers of bacterial species. This study is the first to use volatile atmospheric pressure chemical ionisation mass spectrometry to directly and non-invasively analyse the headspace of E. coli and S. aureus bacterial cultures, enabling major biological classification at species level (Gram negative/positive respectively). Four different protocols were used to collect data, three utilising discrete 5 min samples taken between 2 and 96 h after inoculation and one method employing 24 h continuous sampling. Characteristic marker ions were found for both E. coli and S. aureus. A model to distinguish between sample types was able to correctly identify the bacteria samples after sufficient growth (24-48 h), with similar results obtained across different sampling methods. This demonstrates that this is a robust method to analyse and classify bacterial cultures accurately and within a relevant time frame, offering a promising technique for both clinical and research applications.


Ethnic variations in severe maternal morbidity in the UK- a case control study.
Previous studies showed a higher risk of maternal morbidity amongst black and other minority ethnic (BME) groups, but were unable to investigate whether this excess risk was concentrated within specific BME groups in the UK. Our aim was to analyse the specific risks and to investigate reasons for any disparity. Unmatched case-control analysis using data from the United Kingdom Obstetric Surveillance System (UKOSS), February 2005-January 2013. Cases were 1,753 women who experienced severe morbidity during the peripartum period. Controls were 3,310 women who delivered immediately before the cases in the same hospital. Multivariable logistic regression modelling was used to adjust for known confounders and to understand their effects. Compared with white European women, the odds of severe maternal morbidity were 83% higher among black African women (adjusted odds ratio (aOR) = 1.83; 95% Confidence Interval (CI) = 1.39-2.40), 80% higher among black Caribbean (aOR = 1.80; 95% CI = 1.14-2.82), 74% higher in Bangladeshi (aOR = 1.74; 95% CI = 1.05-2.88), 56% higher in other non-whites (non-Asian) (aOR = 1.56; 95% CI = 1.05-2.33) and 43% higher among Pakistani women (aOR = 1.43; 95% CI = 1.07-1.92). There was no evidence of substantial confounding. Anaemia in current pregnancy, previous pregnancy problems, inadequate utilisation of antenatal care, pre-existing medical conditions, parity>3, and being younger and older were independent risk factors but, the odds of severe maternal morbidity did not differ by socioeconomic status, between smokers and non-smokers or by BMI. This national study demonstrates an increased risk of severe maternal morbidity among women of ethnic minority backgrounds which could not be explained by known risk factors for severe maternal morbidity.


Time-frequency mixed-norm estimates: sparse M/EEG imaging with non-stationary source activations.
Magnetoencephalography (MEG) and electroencephalography (EEG) allow functional brain imaging with high temporal resolution. While solving the inverse problem independently at every time point can give an image of the active brain at every millisecond, such a procedure does not capitalize on the temporal dynamics of the signal. Linear inverse methods (minimum-norm, dSPM, sLORETA, beamformers) typically assume that the signal is stationary: regularization parameter and data covariance are independent of time and the time varying signal-to-noise ratio (SNR). Other recently proposed non-linear inverse solvers promoting focal activations estimate the sources in both space and time while also assuming stationary sources during a time interval. However such a hypothesis holds only for short time intervals. To overcome this limitation, we propose time-frequency mixed-norm estimates (TF-MxNE), which use time-frequency analysis to regularize the ill-posed inverse problem. This method makes use of structured sparse priors defined in the time-frequency domain, offering more accurate estimates by capturing the non-stationary and transient nature of brain signals. State-of-the-art convex optimization procedures based on proximal operators are employed, allowing the derivation of a fast estimation algorithm. The accuracy of the TF-MxNE is compared with recently proposed inverse solvers with help of simulations and by analyzing publicly available MEG datasets.


A new technique of myocardial protection during aortic root replacement: antegrade/retrograde coronary perfusion.
Aortic root surgery has traditionally been performed with an arrested and cooled heart using cardioplegia. A new technique of myocardial protection was utilized in the treatment of ascending aortic aneurysm with severe aortic valve regurgitation requiring aortic root replacement with the Cabrol technique. Retrograde and antegrade perfusion of the heart with blood allowed the surgical operation to be performed safely while the heart was beating and eliminated the ischemic reperfusion injury which occurs during cardioplegic arrest and reinstitution of blood perfusion after removal of the aortic cross-clamping required in traditional techniques.


Cross-talk between NFkB and the PI3-kinase/AKT pathway can be targeted in primary effusion lymphoma (PEL) cell lines for efficient apoptosis.
A number of constitutively activated signaling pathways play critical roles in the survival and growth of primary effusion lymphoma cells (PELs) including NFkB and PI3/AKT kinase cascades. NFkBis constitutively activated in a number of malignancies, including multiple myeloma, Burkitt's lymphoma and diffuse large cell B-cell lymphoma. However, its role in primary effusion lymphoma has not been fully explored. We used pharmacological inhibition and gene silencing to define the role of NFkB in growth and survival of PEL cells. Inhibition of NFkB activity by Bay11-7085 resulted in decreased expression of p65 in the nuclear compartment as detected by EMSA assays. In addition, Bay11-7085 treatment caused de-phosphorylation of AKT and its downstream targets suggesting a cross-talk between NFkB and the PI3-kinase/AKT pathway. Importantly, treatment of PEL cells with Bay11-7085 led to inhibition of cell viability and induced apoptosis in a dose dependent manner. Similar apoptotic effects were found when p65 was knocked down using specific small interference RNA. Finally, co-treatment of PEL cells with suboptimal doses of Bay11-7085 and LY294002 led to synergistic apoptotic responses in PEL cells. These data support a strong biological-link between NFkB and the PI3-kinase/AKT pathway in the modulation of anti-apoptotic effects in PEL cells. Synergistic targeting of these pathways using NFKB- and PI3-kinase/AKT-inhibitors may have a therapeutic potential for the treatment of PEL and possibly other malignancies with constitutive activation of these pathways.


Studies on the mechanism of bacterial resistance to complement-mediated killing. VI. IgG increases the bactericidal efficiency of C5b-9 for E. coli 0111B4 by acting at a step before C5 cleavage.
Our previous experiments showed that immune IgG and F(ab')2, but not Fab', mediated serum killing of Escherichia coli 0111B4, strain 12015 (12015), without significantly increasing the extent of terminal complement (C) component attachment to the bacterial surface. We concluded that bactericidal antibody must change either the site or the nature of C5b-9 bacterial attachment. To pursue this possibility, conditions necessary for elution of C5b-9 from the bacterial surface were examined. Forty-two to 44% of 125I-C9 was released from the serum-resistant nonpresensitized 12015 by 1 M NaCl or 0.1% trypsin, compared with the 21 to 24% release from the serum-sensitive presensitized isolate under the same condition. When strain 12015 bearing 125I-C9 was lysed in a French pressure cell, 73.1% of 125I-C9 was released with the capsular fraction if the organisms had not been presensitized. In contrast, on presensitized 12015, 70.2% of 125I-C9 remained associated with the outer membrane after such lysis. These results suggested that C5b-9 was trapped within or underneath the capsule of 12015 in the absence of bactericidal antibody, but that addition of antibody led to C5b-9 insertion into the outer membrane with bacterial killing. The requirement of C components preceding C5 for bacterial killing was next examined. Minimal killing of presensitized 12015 occurred when a terminal C complex was formed by acid activation from purified C5, C6, C7, C8, and C9 in the absence of C3 or earlier components. In contrast, between 1.2 and 3 log killing of nonpresensitized rough Salmonella minnesota and rough E. coli was observed in the same system. Killing of 12015 was examined with bacteria incubated in C5-deficient serum (C5D), followed by washing and the addition of purified C5, C6, C7, C8, and C9 to permit C5b-9 formation. Antibody was added before or after incubation in C5D serum, or after the addition of purified C5-C9. Under conditions of equivalent C3 and C9 binding, significant killing occurred only when antibody was added before incubation in C5D serum. These results show that antibody must be present at or before the time of C5 convertase formation to mediate killing of 12015 by C5b-9. Therefore, antibody is unlikely to be functioning primarily to alter the bacterial surface to expose sites for C5b-9 insertion, nor is the effect of antibody simply to increase C3 and terminal component binding. We postulate that antibody mediates killing of 12015 by localizing C5b-9 around antibody-clustered sites of C3 and C5 convertase formation.


Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls.
Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. We investigated associations of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiethnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6-8 years of age at enrollment (2004-2007). We measured urinary exposure biomarkers at visit 1 and examined associations with breast and pubic hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones. Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with pubic hair development [adjusted PR, 0.94 (95% CI, 0.88-1.00), fifth vs. first quintile]. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed for low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23-1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone. Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.


Neurofilament as Neuronal Injury Blood Marker in Preeclampsia.
Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia. Enrollment started at 21 weeks of gestation, followed up with multiple visits until delivery. Sixty out of 197 women developed preeclampsia (30.5%). NfL (Nf light chain) was measured with a highly sensitive single molecule array (Simoa) assay, in addition to the established preeclampsia markers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor). The most important independent predictors of NfL were maternal age, number of pregnancies, and proteinuria. NfL levels increased during pregnancy and were significantly higher in women developing preeclampsia. The discriminatory accuracy of NfL, PlGF, and sFlt-1 in receiver operating characteristic curves analysis (area under the curve) of the overall group was 0.68, 0.81, and 0.84, respectively, and in women older than 36 years 0.7, 0.62, and 0.79, respectively. We conclude that increased axonal injury serum marker NfL predicts preeclampsia particularly in older women, with an accuracy similar to the established angiogenic factors. NfL may serve as an early indicator of preeclampsia-induced changes in cerebral structure and may help to stratify disease management.


Too wet to exercise? Leaking urine as a barrier to physical activity in women.
Leaking urine is frequently mentioned (anecdotally) by women as a barrier to physical activity. The aim of this paper was to use results from the Australian Longitudinal Study on Women's Health (ALSWH) to explore the prevalence of leaking urine in Australian women, and to ascertain whether leaking urine might be a barrier to participation for women. More than 41,000 women participated in the baseline surveys of the ALSWH in 1996. More than one third of the mid-age (45-50 years) and older (70-75) women and 13% of the young women (18-23) reported leaking urine. There was a cross-sectional association between leaking urine and physical activity, such that women with more frequent urinary leakage were also more likely to report low levels of physical activity. More than one thousand of those who reported leaking urine at baseline participated in a follow-up study in 1999. Of these, more than 40% of the mid-age women (who were aged 48-53 in 1999), and one in seven of the younger (21-26 years) and older (73-79 years) women reported leaking urine during sport or exercise. More than one third of the mid-age women and more than one quarter of the older women, but only 7% of the younger women said they avoided sporting activities because of leaking urine. The data are highly suggestive that leaking urine may be a barrier to physical activity, especially among mid-age women. As current estimates suggest that fewer than half of all Australian women are adequately active for health benefit, health professionals could be more proactive in raising this issue with women and offering help through non-invasive strategies such as pelvic floor muscle exercises.


Generation and characterization of a novel shoulder contracture mouse model.
Frozen shoulder is a relatively common disorder that leads to severe pain and stiffness in the shoulder joint. Although this disorder is self-limiting in nature, the symptoms often persist for years, resulting in severe disability. Recent studies using human specimens and animal models have shown distinct changes in the gene expression patterns in frozen shoulder tissue, indicating that novel therapeutic intervention could be achieved by controlling the genes that are potentially involved in the development of frozen shoulder. To achieve this goal, it is imperative to develop a reliable animal joint contracture model in which gene expression can be manipulated by gene targeting and transgenic technologies. Here, we describe a novel shoulder contracture mouse model. We found that this model mimics the clinical presentation of human frozen shoulder and recapitulates the changes in the gene expression pattern and the histology of frozen shoulder and joint contracture in humans and other larger animal models. The model is highly reproducible, without any major complications. Therefore, the present model may serve as a useful tool for investigating frozen shoulder etiology and for identifying its potential target genes.


Orthopaedic sport biomechanics - a new paradigm.
This article proposes a new paradigm, "Orthopaedic sport biomechanics", for the understanding of the role of biomechanics in preventing and managing sports injury. Biomechanics has three main roles in this paradigm: (1) injury prevention, (2) immediate evaluation of treatment, and (3) long-term outcome evaluation. Related previous studies showing the approach in preventing and managing anterior cruciate ligament rupture and anterior talofibular ligament tear are highlighted. Orthopaedics and biomechanics specialists are encouraged to understand what they could contribute to the current and future practice of sports medicine.


Wall properties of the apolipoprotein E-deficient mouse aorta.
We quantified the dysfunction of the aortic wall, determined structural and elastic properties, and provided histological data of the thoracic aortas of apolipoprotein E (apoE)-deficient mice which are used as model of atherosclerosis. Six young 10-12 week-old (apoE)-deficient mice of both sexes were studied and six age-matched C57BL/6J wild-type mice were used as control group. We performed extension-inflation mechanical tests at three different axial stretches (λ(z) = 1.6, 1.8, and 2.0), under maximally contracted or totally relaxed state of the vascular smooth muscle cells. Classical histology was performed to the arterial segments. Control aortas were generally more distensible than the (apoE)-deficient mouse aortas under both relaxed and contracted smooth muscle. Also, aortas from (apoE)-deficient mice were stiffer (higher incremental elastic modulus) than control aortas. Control aortas exhibited a higher active diameter response compared to (apoE)-deficient mouse aortas, despite the fact that vascular smooth muscle cell density was increased by approximately 15% in the (apoE)-deficient mouse aortas. We found substantial changes in the structural and elastic properties of the wall, in the active diameter response and in the histology of (apoE)-deficient mouse aortas compared to the control group. Our data can be used in the development of constituent-based models of the arterial wall and in studying the changes in arterial wall properties in presence of disease, such as atherosclerosis.


In vitro migration capacity of human adipose tissue-derived mesenchymal stem cells reflects their expression of receptors for chemokines and growth factors.
The homing properties of adipose tissue-derived mesenchymal stem cells (AdMSCs) have stimulated intravenous applications for their use in stem cell therapy. However, the soluble factors and corresponding cellular receptors responsible for inducing chemotaxis of AdMSCs have not yet been reported. In the present study, the migration capacity of human AdMSCs (hAdMSCs) toward various cytokines or growth factors (GFs) and the expression of their receptors were determined. In a conventional migration assay, PDGF-AB, TGF-β1, and TNF-α showed the most effective chemoattractant activity. When AdMSCs were preincubated with various chemokines or GF, and then allowed to migrate toward medium containing 10% FBS, those preincubated with TNF-α showed the highest migratory activity. Next, hAdMSCs were either preincubated or not with TNF-α, and allowed to migrate in response to various GFs or chemokines. Prestimulation with TNF-α increased the migration activity of hAdMSCs compared to unstimulated hAdMSCs. When analyzed by FACS and RT-PCR methods, hAdMSCs were found to express C-C chemokine receptor type 1 (CCR1), CCR7, C-X-C chemokine receptor type 4 (CXCR4), CXCR5, CXCR6, EGF receptor, fibroblast growth factor receptor 1, TGF-β receptor 2, TNF receptor superfamily member 1A, PDGF receptor A and PDGF receptor B at both the protein and the mRNA levels. These results indicate that the migration capacity of hAdMSCs is controlled by various GFs and chemokines. Prior in vitro modulation of the homing capacity of hAdMSCs could stimulate their movement into injured sites in vivo when administered intravenously, thereby improving their therapeutic potential.


Stochastic 3D motion compensation of coronary arteries from monoplane angiograms.
Image-based navigation during percutaneous coronary interventions is highly challenging since it involves estimating the 3D motion of a complex topology using 2D angiographic views. A static coronary tree segmented in a pre-operative CT-scan can be overlaid on top of the angiographic frames to outline the coronary vessels, but this overlay does not account for coronary motion, which has to be mentally compensated by the cardiologist. In this paper, we propose a new approach to the motion estimation problem, where the temporal evolution of the coronary deformation over the cardiac cycle is modeled as a stochastic process. The sequence of angiographic frames is interpreted as a probabilistic evidence of the succession of unknown deformation states, which can be optimized using particle filtering. Iterative and non-rigid registration is performed in a projective manner, and relies on a feature-based similarity measure. Experiments show promising results in terms of registration accuracy, learning capability and computation time.


Daily occupations and well-being in women with limited cutaneous systemic sclerosis.
This study investigated occupational performance, well-being (operationalized as general life satisfaction, domain-specific life satisfaction, and self-rated health), and perceived symptoms in women with limited scleroderma and healthy controls. Interview-based and self-administered questionnaires were used with 36 women with limited scleroderma and 40 healthy women. In the scleroderma group, most of occupation problems were perceived in work and household chores. The women with scleroderma were mainly satisfied with self-care and least satisfied with household chores. Regarding domain-specific life satisfaction, the women were least satisfied with physical health and leisure. General life satisfaction showed the strongest relations to performance of self-defined occupations and satisfaction with leisure, whereas the strongest association with self-rated health was found for satisfaction with work. Fatigue was perceived as a dominant problem and was significantly associated with well-being. Furthermore, the women with scleroderma felt lower satisfaction with daily occupations and well-being than the healthy women. Loss of occupations, low satisfaction with leisure, perceived fatigue, shortness of breath, and pain indicated poorer well-being in women with scleroderma and need to be focused on in occupational therapy interventions.


Testing the Utility of a Data-Driven Approach for Assessing BMI from Face Images.
Several lines of evidence suggest that facial cues of adiposity may be important for human social interaction. However, tests for quantifiable cues of body mass index (BMI) in the face have examined only a small number of facial proportions and these proportions were found to have relatively low predictive power. Here we employed a data-driven approach in which statistical models were built using principal components (PCs) derived from objectively defined shape and color characteristics in face images. The predictive power of these models was then compared with models based on previously studied facial proportions (perimeter-to-area ratio, width-to-height ratio, and cheek-to-jaw width). Models based on 2D shape-only PCs, color-only PCs, and 2D shape and color PCs combined each performed significantly and substantially better than models based on one or more of the previously studied facial proportions. A non-linear PC model considering both 2D shape and color PCs was the best predictor of BMI. These results highlight the utility of a "bottom-up", data-driven approach for assessing BMI from face images.