High-risk behaviors for transmission of syphilis and human immunodeficiency virus among crack cocaine-using women. A case study from the Midwest.
This study examines the drug use patterns, sexual practices, condom use, knowledge and attitudes toward sexually transmitted diseases (STD)s and AIDS, and seroprevalence of human immunodeficiency virus (HIV) and syphilis among women who use crack in Dayton, Ohio. In 1990, two indigenous outreach workers recruited 150 participants who were not in drug treatment programs, who were 18 years of age or older, and had used crack in the previous 3 months. Structured interviews revealed that 90% of the sample were black, 78% used crack "daily," 93% had multiple sexual partners, and 49% had 10 or more male sexual partners in the last 3 months. A majority (67%) of the women felt they were in need of drug treatment. No reactive syphilis serologies were detected in 138 serum samples; 2 women (1.4%) were HIV seropositive. This case study provides insight into the high-risk sexual behaviors of crack users in a medium-sized, midwestern city. The study demonstrates the value of indigenous outreach prevention and STD screening initiatives in reaching this segment of our society, which has a high risk of acquiring STDs.


Passage-dependent cancerous transformation of human mesenchymal stem cells under carcinogenic hypoxia.
Bone marrow-derived human mesenchymal stem cells (hMSCs) either promote or inhibit cancer progression, depending on factors that heretofore have been undefined. Here we have utilized extreme hypoxia (0.5% O2) and concurrent treatment with metal carcinogen (nickel) to evaluate the passage-dependent response of hMSCs toward cancerous transformation. Effects of hypoxia and nickel treatment on hMSC proliferation, apoptosis, gene and protein expression, replicative senescence, reactive oxygen species (ROS), redox mechanisms, and in vivo tumor growth were analyzed. The behavior of late passage hMSCs in a carcinogenic hypoxia environment follows a profile similar to that of transformed cancer cells (i.e., increased expression of oncogenic proteins, decreased expression of tumor suppressor protein, increased proliferation, decreased apoptosis, and aberrant redox mechanisms), but this effect was not observed in earlier passage control cells. These events resulted in accumulated intracellular ROS in vitro and excessive proliferation in vivo. We suggest a mechanism by which carcinogenic hypoxia modulates the activity of three critical transcription factors (c-MYC, p53, and HIF1), resulting in accumulated ROS and causing hMSCs to undergo cancer-like behavioral changes. This is the first study to utilize carcinogenic hypoxia as an environmentally relevant experimental model for studying the age-dependent cancerous transformation of hMSCs.


Nurse leaders' views on clinical ladders as a strategy in professional development.
To investigate nurse leaders' views on clinical ladders as a strategy in professional development of nursing. Hospitals worldwide have implemented clinical ladders to boost professional development and improve quality of patient care. At ward level good leadership is vital in creating a learning environment and using nurses' new competence. The design was explorative and data were collected in focus groups with 19 nurse leaders at the ward level and 24 executive nurse leaders at hospitals with several years of experience with clinical ladders. Most nurse leaders did not think strategically in promoting clinical ladders at the organizational level. Nurse leaders who considered clinical ladders a tool in developing nursing quality found motivational work challenging and rewarding. Not all nurse leaders managed to utilize clinical specialists' new competence. Further investigation into nurse leaders' actions as strategic managers of development and use of nurses' competence is warranted. Implications for nursing management It is important that managers see the close connection between professional development of individuals and development of quality and high standard in the ward. A prerequisite is therefore to engage in the strategic planning of competence at all levels of decision in the organization.


Effects of h1-calponin ablation on the contractile properties of bladder versus vascular smooth muscle in mice lacking SM-B myosin.
The functional significance of smooth muscle-specific h1-calponin up-regulation in the smooth muscle contractility of SM-B null mice was studied by generating double knockout mice lacking both h1-calponin and SM-B myosin. The double knockout mice appear healthy, reproduce well and do not show any smooth muscle pathology. Loss of h1-calponin in the SM-B null mice bladder resulted in increased maximal shortening velocity (V(max)) and steady-state force generation. The force dilatation pressure, which was decreased in the SM-B null mesenteric vessels, was restored to wild-type levels in the double knockout vessels. In contrast, the half-time to maximal constriction was significantly increased in the double knockout vessels similar to that of SM-B null mice and indicating decreased shortening velocity in the double knockout vessels. Biochemical analyses showed that there is a significant reduction in smooth muscle alpha-actin levels, whereas h-caldesmon levels are increased in the double knockout bladder and mesenteric vessels, suggesting that these changes may also partly contribute to the altered contractile function. Taken together, our studies suggest that up-regulation of h1-calponin in the SM-B null mice may be necessary to maintain a reduced level of cross-bridge cycling over time in the absence of SM-B myosin and play an important role in regulating the smooth muscle contraction.


Prevalence of anti-aquaporin 4 antibody in a diagnostic cohort of patients being investigated for possible neuromyelitis optica spectrum disorder in Western Australia.
To evaluate the prevalence of anti-AQP4 antibody in serum and CSF samples from patients being investigated for possible neuromyelitis optica spectrum disorder (NMOSD) referred to the PathWest State reference laboratory using a sensitive cell-based assay (CBA). NMOSD is an inflammatory CNS disease distinct from MS, which is relatively rare in Western countries. A proportion of patients with NMOSD have detectable serum IgG antibodies that target the water channel aquaporin-4 (AQP4-IgG), but the frequency varies in different populations studied and according to the assay method employed. Sera or CSF from a diagnostic cohort of 196 consecutive patients with possible NMOSD which had previously been screened by indirect immunofluorescence (IIF) on primate cerebellum were re-tested for AQP4-IgG reactivity to the M1 and M23 isoforms of AQP4 using a commercial CBA. A control group of 205 patients with definite MS was also included in the study. Of the 196 patients, only 5 sera were AQP4-IgG positive, representing 2.6% of patients in the diagnostic cohort. All 5 AQP4-IgG positive patients fulfilled the 2015 revised diagnostic criteria for NMOSD and were females of varied ethnic origins, 4 of whom had longitudinally extensive transverse myelitis. The CBA confirmed AQP4-IgG positivity in the four patients previously reported as positive by IIF, and an additional patient with NMOSD who had previously been diagnosed as MS was also identified. None of the 205 MS sera were AQP4-IgG positive. Our study confirms the utility and greater reliability of the M1/M23 CBA for detecting AQP4-IgG in patients with possible NMOSD, and indicates a prevalence of seropositive NMOSD in the Western Australian population similar to that in other Western populations.


The corpus luteum: an ovarian structure with maternal instincts and suicidal tendencies.
The corpus luteum is a unique hormone-regulated, transient reproductive gland that produces progesterone, a required product for the establishment and maintenance of early pregnancy. In the absence of pregnancy the corpus luteum will cease to produce progesterone and the structure itself will regress in size over time. Although the process of luteal regression has been studied for several decades, many of the regulatory mechanisms involved in loss of function and involution of the structure are incompletely understood. More importantly, we are far from understanding how these complex mechanisms function in unison. The factor or factors responsible for initiating and mediating luteolysis are no doubt more complex than originally envisioned. Further, efforts to elucidate the mechanisms responsible for luteolysis have been complicated by different interpretations of what is 'luteolysis', discrepancies between in vitro and in vivo studies, and subsequent biases which are associated with the different methods of analyses. Moreover, the complexity of the mechanisms which regulate the life span of the corpus luteum are compounded by the presence of a heterogeneous population of cells which often respond differentially to the same ligand or stimuli. Attempts to isolate specific luteal cell types for the intention of defining intracellular signaling mechanisms have yielded valuable information. However, studies of a specific cell type taken out of context are often subject to criticism. The most obvious being that the cells are no longer maintained within their three dimensional environment. Evaluation of the corpus luteum in vivo, is not without its criticisms either. A subtle change evoked within a subpopulation of cells can be overlooked if measured in whole tissue or in mixed cell preparations. Furthermore, treatment in vivo with a single agent/ligand (i.e., prostaglandin F2 alpha) may induce a secondary ligand that is ultimately responsible for the biological response. All arguments are valid and cannot be ignored. There are secondary levels of complexity in the corpus luteum brought about by the pleiotropic actions of specific ligands. For example, one ligand can be luteotropic to a steroid producing cell and cytotoxic to a luteal endothelial cell. Furthermore, a specific cell type within the corpus luteum may respond differentially depending on the developmental stage of the luteal phase (i.e., early, mid, or late luteal phase) suggesting that the intracellular signaling pathways are key to defining ligand-induced biological responses. The purpose of this review is to culminate what is known regarding signal transduction pathways activated by initiator(s) and/or mediators of luteolysis. We recognize that an all-inclusive review describing the molecular mechanisms involved in the development, maintenance and regression of the corpus luteum would be impossible within the context of this review. There are a number of recent reviews that discuss luteal development, luteal maintenance and luteolysis with emphasis on neuroendocrine events (1-3). Consequently, we have focused our review primarily on potential intracellular signaling events of proposed regulators and mediators of luteal regression. Where possible we have attempted to incorporate references that represent rodents, domestic farm animals and primates.


Immunological Outcomes of Allergen-Specific Immunotherapy in Food Allergy.
IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.


Evaluation of cerebrospinal fluid proteins as potential biomarkers for early stage Parkinson's disease diagnosis.
Cerebrospinal fluid (CSF) has often been used as the source of choice for biomarker discovery with the goal to support the diagnosis of neurodegenerative diseases. For this study, we selected 15 CSF protein markers which were identified in previously published clinical investigations and proposed as potential biomarkers for PD diagnosis. We aimed at investigating and confirming their suitability for early stage diagnosis of the disease. The current study was performed in a two-fold confirmatory approach. Firstly, the CSF protein markers were analysed in confirmatory cohort I comprising 80 controls and 80 early clinical PD patients. Through univariate analysis we found significant changes of six potential biomarkers (α-syn, DJ-1, Aβ42, S100β, p-Tau and t-Tau). In order to increase robustness of the observations for potential patient differentiation, we developed-based on a machine learning approach-an algorithm which enabled identifying a panel of markers which would improve clinical diagnosis. Based on that model, a panel comprised of α-syn, S100β and UCHL1 were suggested as promising candidates. Secondly, we aimed at replicating our observations in an independent cohort (confirmatory cohort II) comprising 30 controls and 30 PD patients. The univariate analysis demonstrated Aβ42 as the only reproducible potential biomarker. Taking into account both technical and clinical aspects, these observations suggest that the large majority of the investigated CSF proteins currently proposed as potential biomarkers lack robustness and reproducibility in supporting diagnosis in the early clinical stages of PD.


A SARS-CoV-2 antiviral therapy score card.
The COVID-19 pandemic has unleashed an unprecedented effort to identify efficacious treatments for persons infected with SARS-CoV-2. As of September 2020, more than 750 completed, ongoing, or planned clinical trials of drugs intended to inhibit SARS-CoV-2 replication have been registered on the ClinicalTrials.gov or WHO International Clinical Trials Platform websites. Most of the treatments studied in these trials are repurposed licensed or investigational drugs targeting viral proteins or cellular pathways required for virus replication. The use of repurposed compounds is understandable because with the exception of monoclonal antibodies, it will be several months before novel SARS-CoV-2-specific drugs will be available for human testing. This editorial describes those compounds that I believe should be prioritized for clinical testing: i) viral RNA polymerase inhibitors including GS-441524, its prodrug remdesivir, and EIDD-2801; ii) entry inhibitors including monoclonal antibodies, ACE2 molecular decoys, and peptide fusion inhibitors; iii) parenteral and inhalational preparations of interferon β and λ; and iv) inhibitors of host transmembrane protease serine 2 (TMPRSS2), endosomal trafficking, and pyrimidine synthesis. As SARS-CoV-2 is pandemic and as its most severe consequences result from a dysregulated immunological response to infection, the ideal therapies should be inexpensive and should be able to be administered to non-hospitalized persons at the time of their initial diagnosis.


Psychedelics and health behaviour change.
Healthful behaviours such as maintaining a balanced diet, being physically active and refraining from smoking have major impacts on the risk of developing cancer, diabetes, cardiovascular diseases and other serious conditions. The burden of the so-called 'lifestyle diseases'-in personal suffering, premature mortality and public health costs-is considerable. Consequently, interventions designed to promote healthy behaviours are increasingly being studied, e.g., using psychobiological models of behavioural regulation and change. In this article, we explore the notion that psychedelic substances such as psilocybin could be used to assist in promoting positive lifestyle change conducive to good overall health. Psilocybin has a low toxicity, is non-addictive and has been shown to predict favourable changes in patients with depression, anxiety and other conditions marked by rigid behavioural patterns, including substance (mis)use. While it is still early days for modern psychedelic science, research is advancing fast and results are promising. Here we describe psychedelics' proposed mechanisms of action and research findings pertinent to health behaviour change science, hoping to generate discussion and new research hypotheses linking the two areas. Therapeutic models including psychedelic experiences and common behaviour change methods (e.g., Cognitive Behaviour Therapy, Motivational Interviewing) are already being tested for addiction and eating disorders. We believe this research may soon be extended to help promote improved diet, exercise, nature exposure and also mindfulness or stress reduction practices, all of which can contribute to physical and psychological health and well-being.


Emerging Infectious Disease Implications of Invasive Mammalian Species: The Greater White-Toothed Shrew (Crocidura russula) Is Associated With a Novel Serovar of Pathogenic Leptospira in Ireland.
The greater white-toothed shrew (Crocidura russula) is an invasive mammalian species that was first recorded in Ireland in 2007. It currently occupies an area of approximately 7,600 km2 on the island. C. russula is normally distributed in Northern Africa and Western Europe, and was previously absent from the British Isles. Whilst invasive species can have dramatic and rapid impacts on faunal and floral communities, they may also be carriers of pathogens facilitating disease transmission in potentially naive populations. Pathogenic leptospires are endemic in Ireland and a significant cause of human and animal disease. From 18 trapped C. russula, 3 isolates of Leptospira were cultured. However, typing of these isolates by standard serological reference methods was negative, and suggested an, as yet, unidentified serovar. Sequence analysis of 16S ribosomal RNA and secY indicated that these novel isolates belong to Leptospira alstonii, a unique pathogenic species of which only 7 isolates have been described to date. Earlier isolations were limited geographically to China, Japan and Malaysia, and this leptospiral species had not previously been cultured from mammals. Restriction enzyme analysis (REA) further confirms the novelty of these strains since no similar patterns were observed with a reference database of leptospires. As with other pathogenic Leptospira species, these isolates contain lipL32 and do not grow in the presence of 8-azagunaine; however no evidence of disease was apparent after experimental infection of hamsters. These isolates are genetically related to L. alstonii but have a novel REA pattern; they represent a new serovar which we designate as serovar Room22. This study demonstrates that invasive mammalian species act as bridge vectors of novel zoonotic pathogens such as Leptospira.


Partner Meeting Contexts and Risky Behavior in College Students' Other-Sex and Same-Sex Hookups.
We analyzed a sample of 12,065 hookup encounters among college students at 22 colleges and universities in the Online College Social Life Survey (OCSLS) to explore how partner meeting locales may influence college students' risky behavior when hookup partners are met in those contexts. For other-sex encounters, meeting in bars or at parties, through common interest groups or history, and (for women) at dormitories was associated with binge drinking during encounters, while meeting online and (for women) in public was associated with reduced binge drinking during encounters. Unprotected sex during other-sex encounters was more common when partners were met in public and less common with partners met in dormitories. Binge drinking and marijuana use during or just prior to encounters was associated with an increased risk of unprotected sex and other substance use. Marijuana use and unprotected sex during encounters was more common when students knew their hookup partner better or had hooked up with the partner before, while binge drinking was associated with hooking up with less familiar partners. Associations of meeting contexts with behavior were explained by the locale's association with institutional and personal trust, social scripts, and selection into certain contexts by students with a risk-taking personality.


Effects of sand and straw bedding on the lying behavior, cleanliness, and hoof and hock injuries of dairy cows.
This experiment compared the effects of sand and straw bedding in free stalls on resting time, cleanliness, hock injuries, and hoof health of dairy cows and tested whether cow preferences for a bedding material depended on the familiarity with the material. A total of 52 dairy cows were kept either on straw bedded concrete stalls or sand stalls for at least 21 wk. The lying behavior was observed, and hock lesions, hoof health, and cleanliness of the cows and stalls were measured. A 5-d preference test between sand and straw stalls was conducted at the end of the experiment. The total daily duration of lying was longer for cows on straw bedding than on sand bedding (straw 749 +/- 16 vs. sand 678 +/- 19 min). During the preference test, cows that had been kept on straw bedding preferred lying in straw stalls [straw 218.7 (133.4 to 239.7) vs. sand 9.0 min (2.8 to 44.8)]; however, cows that had been kept on sand showed no preference [straw 101.3 (51.7 to 205.9) vs. sand 94.3 min (54.1 to 156.1, median and interquartile range)]. Although there were no differences in the dirtiness of stalls, the cows using straw stalls were dirtier than cows using sand stalls [straw 6.04 (5.39 to 6.28) vs. sand 4.19 (3.62 to 5.16)]. At the end of experiment the severity of hock lesions was lower for cows on sand than for cows on straw [sand 0.5 (0.0 to 1.0) vs. straw 1.0 (1.0 to 2.0)]. The improvement in overall hoof health over the observation period was greater for cows kept on sand compared with cows kept on straw [sand -2.00 (-3.75 to -0.25) vs. straw 0.00 (-2.00 to 2.00)]. Straw bedding increased the time that cows spend lying, and cows preferred straw stalls to sand stalls. However, previous experience with sand reduces avoidance of sand stalls. Sand stalls were advantageous for cow cleanliness and health; hock lesions and claw diseases healed more quickly for cows using sand stalls compared with straw.


Sociodemographic factors associated with sleeping position and location.
Recent research has implicated infant sleeping body position and bed sharing as risk factors in the sudden infant death syndrome. The sociodemographic associations of infant sleeping body position and location were examined in this study. This showed that the majority (86.4%) of New Zealand parents now place their infants to sleep on their sides. The remainder place their infants supine (1.3%), prone (4.8%), or no particular way (7.5%). In the waking position, 57.9% were usually found on their sides, 18.2% supine, and 6.1% prone. Infant sleeping position showed marked sociodemographic variability. These findings are a marked contrast to previous New Zealand studies which showed a reversed pattern, with most infants put to sleep prone. There were also highly significant sociodemographic differences in the place of sleeping. Overall 12.2% of infants shared a bed, with infants of younger less well educated mothers who were of non-European origin, with a parity of five or more, or unmarried significantly more likely to do so. Infants of unemployed and lower socioeconomic group (Elley-Irving groups 5 and 6) fathers were also more likely to share a parental bed.


Smooth muscle cell proliferation and localization of macrophages and T cells in the occlusive intracranial major arteries in moyamoya disease.
Stenosis or occlusion due to fibrocellular intimal thickening in the intracranial major arteries is thought to be the primary lesion in moyamoya disease, but its etiology and pathogenesis are unknown. The present study was designed to analyze cellular components of the lesions and their pathological process. Stenotic or occlusive intracranial arterial lesions were collected from six autopsied patients who died of moyamoya disease. The cellular components were analyzed by immunohistochemical staining using cell-type-specific monoclonal antibodies. The sections were also immunostained for proliferating cell nuclear antigen (PCNA) to detect proliferating cells and for two different types of intermediate filaments, desmin and vimentin, to evaluate phenotypes of the intimal smooth muscle cells. The thickened intima was composed predominantly of smooth muscle cells with an admixture of some macrophages and T cells. Macrophages and T cells were scattered in the superficial layer of the intimal thickening, and these were occasionally associated with organization of fibrin thrombi. Proliferating smooth muscle cells, indicated by PCNA-positive nuclei and muscle actin-positive cytoplasm, were found in the thickened intima in four patients. Immunohistochemical staining for intermediate filaments revealed intimal smooth muscle cells showing positive staining for vimentin and negative staining for desmin, compatible with the phenotype of synthetic smooth muscle cells. The present study provides evidence that smooth muscle cells are proliferating in the occlusive lesions in intracranial major arteries in moyamoya disease. The colocalization of inflammatory cells and PCNA-positive cells suggests that inflammatory stimuli may induce proliferative response of smooth muscle and contribute to the formation of the intracranial occlusive lesions in moyamoya disease.


A fully disposable and integrated paper-based device for nucleic acid extraction, amplification and detection.
Nucleic acid testing (NAT) has been widely used for disease diagnosis, food safety control and environmental monitoring. At present, NAT mainly involves nucleic acid extraction, amplification and detection steps that heavily rely on large equipment and skilled workers, making the test expensive, time-consuming, and thus less suitable for point-of-care (POC) applications. With advances in paper-based microfluidic technologies, various integrated paper-based devices have recently been developed for NAT, which however require off-chip reagent storage, complex operation steps and equipment-dependent nucleic acid amplification, restricting their use for POC testing. To overcome these challenges, we demonstrate a fully disposable and integrated paper-based sample-in-answer-out device for NAT by integrating nucleic acid extraction, helicase-dependent isothermal amplification and lateral flow assay detection into one paper device. This simple device allows on-chip dried reagent storage and equipment-free nucleic acid amplification with simple operation steps, which could be performed by untrained users in remote settings. The proposed device consists of a sponge-based reservoir and a paper-based valve for nucleic acid extraction, an integrated battery, a PTC ultrathin heater, temperature control switch and on-chip dried enzyme mix storage for isothermal amplification, and a lateral flow test strip for naked-eye detection. It can sensitively detect Salmonella typhimurium, as a model target, with a detection limit of as low as 102 CFU ml-1 in wastewater and egg, and 103 CFU ml-1 in milk and juice in about an hour. This fully disposable and integrated paper-based device has great potential for future POC applications in resource-limited settings.


Single port laparoscopy combined with vaginal cervicovaginal reconstruction in a patient with congenital atresia of the cervix.
To introduce an innovation that combines single port laparoscopic and Wharton-Sheares-George cervicovaginal reconstruction using a small intestinal submucosa (SIS) graft in a patient with congenital cervical atresia, absence of vagina, and incomplete uterine septum (U2aC4V4). Video article introducing a new surgical technique. University hospital. A 15-year-old patient with congenital cervical atresia, absence of vagina, and incomplete uterine septum had primary amenorrhea and cyclic lower abdominal pain. The magnetic resonance imaging did not show hematometra and the endometrium was 6 mm when she had lower abdominal pain. A neovagina (depth, 7 cm; width, 2.5 cm) was created using the Wharton-Sheares-George neovaginoplasty. By single laparoscopy, the bladder was separated from the anterior surface of the uterus. With the mold in the neovagina created by the assistant, the apex of neovagina was opened. Then the lower uterine segment was exposed and incised. A T-shaped intrauterine device was connected to an 8-cm-long catheter scissored from a 14-F Foley catheter and was inserted into the uterus to prevent cervical or vaginal stenosis. The upper end of the graft was applied onto the lower uterine segment with delayed absorbable sutures. The lower end was sutured to the high vaginal or vestibular mucosa. The feasibility and effect of combination single port laparoscopic with vaginal cervicovaginal reconstruction in the congenital atresia of cervix. The operation was successful. The operating time was 90 minutes. Hospitalization was 3 days. There were no intraoperative and postoperative complications. The patient had resumption of menses at three cycles postoperatively, and she had no dysmenorrhea. No cervical or vaginal stenosis occurred because of the Foley catheter. Single port laparoscopic combined with vaginal cervicovaginal reconstruction provided a minimally invasive, safe, and effective surgical option for the young patient with congenital atresia of cervix. It was successful and without complications or cervical or vaginal stenosis.


The challenges of caring for children who require complex medical care at home: 'The go between for everyone is the parent and as the parent that's an awful lot of responsibility'.
Increasing numbers of children with complex health-care needs are cared for at home by their family. The aim of this qualitative study was to explore the challenges experienced by families caring for children who need complex medical care at home. We conducted a thematic analysis of eleven in-depth interviews with parents who carry out specialist medical procedures (eg, enteral feeding, bowel washouts and tracheostomy care) for their children at home. Participants were purposely selected from an existing sample of interviews with parents whose child had abdominal surgery in the first year of life. We identified three overarching themes: (a) responsibilities of the parent, (b) impact on daily life and (c) the parent journey over time. Parents have substantial responsibilities, including performing medical procedures, managing emergencies (sometimes life-threatening), co-ordinating care and advocating for their child. Their responsibilities have an enormous impact on the family: going out of the home becomes a challenge, there are constant constraints on time, parents are sleep-deprived and there are wider impacts on siblings. The third theme explores the parent journey over time as parents become experts and make sense of the new normal. The burden of care on families caring for children with complex medical needs is much greater than is generally understood by either multidisciplinary health-care teams or the general public. Families need to be better prepared and supported for the responsibilities they take on and the burden of care needs to be shared by others.


Stereopsis in animals: evolution, function and mechanisms.
Stereopsis is the computation of depth information from views acquired simultaneously from different points in space. For many years, stereopsis was thought to be confined to primates and other mammals with front-facing eyes. However, stereopsis has now been demonstrated in many other animals, including lateral-eyed prey mammals, birds, amphibians and invertebrates. The diversity of animals known to have stereo vision allows us to begin to investigate ideas about its evolution and the underlying selective pressures in different animals. It also further prompts the question of whether all animals have evolved essentially the same algorithms to implement stereopsis. If so, this must be the best way to do stereo vision, and should be implemented by engineers in machine stereopsis. Conversely, if animals have evolved a range of stereo algorithms in response to different pressures, that could inspire novel forms of machine stereopsis appropriate for distinct environments, tasks or constraints. As a first step towards addressing these ideas, we here review our current knowledge of stereo vision in animals, with a view towards outlining common principles about the evolution, function and mechanisms of stereo vision across the animal kingdom. We conclude by outlining avenues for future work, including research into possible new mechanisms of stereo vision, with implications for machine vision and the role of stereopsis in the evolution of camouflage.


The interactive systems framework applied to the strategic prevention framework: the Rhode Island experience.
The Interactive Systems Framework for Dissemination and Implementation (ISF) was introduced as a heuristic systems level model to help bridge the gap between research and practice (Wandersman et al., in Am J Commun Psychol 41:171-181, 2008). This model describes three interacting systems with distinct functions that (1) distill knowledge to develop innovations; (2) provide supportive training and technical assistance for dissemination to; (3) a prevention delivery system responsible for implementation in the field. The Strategic Prevention Framework (SPF) is a major prevention innovation launched by the Center for Substance Abuse Prevention (CSAP) of the Substance Abuse and Mental Health Services Administration (SAMHSA). The SPF offers a structured, sequential, data-driven approach that explicitly targets environmental conditions in the community and aims for change in substance use and problems at the population level. This paper describes how the ISF was applied to the challenges of implementing the SPF in 14 Rhode Island communities, with a focus on the development of a new Training and Technical Assistance Resources Center to support SPF efforts. More specifically, we (1) describe each of the three ISF interacting systems as they evolved in Rhode Island; (2) articulate the lines of communication between the three systems; and (3) examine selected evaluation data to understand relationships between training and technical assistance and SPF implementation and outcomes.


Algiphilus aromaticivorans gen. nov., sp. nov., an aromatic hydrocarbon-degrading bacterium isolated from a culture of the marine dinoflagellate Lingulodinium polyedrum, and proposal of Algiphilaceae fam. nov.
A strictly aerobic, halotolerant, Gram-stain-negative, rod-shaped bacterium, designated strain DG1253(T), was isolated from a laboratory culture of the marine dinoflagellate Lingulodinium polyedrum (CCAP 1121/2). The strain was able to degrade two- and three-ring polycyclic aromatic hydrocarbons. It exhibited a narrow nutritional spectrum, preferring to utilize aliphatic and aromatic hydrocarbon compounds and small organic acids. Cells produced surface blebs and contained a single polar flagellum. The predominant isoprenoid quinone of strain DG1253(T) was Q-8. The fatty acid profile was dominated by C(18:1)ω7c. The mean DNA G+C content of strain DG1253(T) was 63.6 ± 0.25 mol%. 16S rRNA gene sequence analysis placed this organism within the order Xanthomonadales of the class Gammaproteobacteria. Its closest relatives included representatives of the Hydrocarboniphaga-Nevskia-Sinobacter clade (≤ 89.9% 16S rRNA gene sequence similarity) in the family Sinobacteraceae. On the basis of distinct phenotypic and genotypic characteristics, strain DG1253(T) is considered to represent a novel species of a new genus in the class Gammaproteobacteria, for which the name Algiphilus aromaticivorans gen. nov., sp. nov. is proposed. The type strain of the type species, Algiphilus aromaticivorans, is DG1253(T) (=ATCC BAA-2243(T)=DSM 24793(T)). In addition, a new family, Algiphilaceae fam. nov., is proposed to accommodate the genus Algiphilus.


Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial.
The Multiple Outcomes of Raloxifene Evaluation trial studied 7705 postmenopausal women with osteoporosis randomized to placebo, or raloxifene 60 or 120 mg/d [JAMA 282(1999): 637]. This report assesses the efficacy of raloxifene on the long-term cumulative incidence new vertebral fractures through 4 yr. New vertebral fractures was assessed from radiographs taken at baseline, yr 2-4. The primary analysis was the cumulative incidence of new vertebral fractures through 4 yr. A posthoc analysis compared the vertebral fracture risk in yr 4 alone with that observed in the first 3 yr. The 4-yr cumulative relative risks (RR) for one or more new vertebral fractures were 0.64 [95% confidence interval (CI) 0.53, 0.76] with raloxifene 60 mg/d and 0.57 (95% CI 0.48, 0.69) with raloxifene 120 mg/d. In yr 4 alone, raloxifene 60 mg/d reduced the new vertebral fracture risk by 39% [RR 0.61 (95% CI 0.43, 0.88)], which was not found to be significantly different from the RR observed in the first 3 yr in both raloxifene groups, irrespective of prevalent fracture status. The nonvertebral fracture risk was not significantly reduced [RR 0.93 (95% CI 0.81, 1.06)]. The safety profile after 4 yr was similar to that observed after 3 yr. Raloxifene 60 and 120 mg/d through 4 yr decreased the cumulative risk of new vertebral fractures in postmenopausal women with osteoporosis. The decreased vertebral fracture risk in yr 4 alone was not different from that observed in the first 3 yr.


Dissemination of Cognitive Therapy for Panic Disorder in Primary Care.
This study investigated whether brief training in cognitive therapy for panic disorder (Clark et al., 1994) can improve the outcomes that primary care therapists obtain with their patients. Seven primary care therapists treated 36 patients meeting DSM-IV (APA, 1994) criteria for panic disorder with or without agoraphobia in general practice surgeries. Outcomes for the cohort of patients whom the therapists treated with their usual methods (treatment-as-usual) before the training (N = 12) were compared with those obtained with similar patients treated by the same therapists after brief training and ongoing supervision in cognitive therapy (CT) for panic disorder (N = 24). Treatment-as-usual led to significant improvements in panic severity, general anxiety, and depression. However, only a small proportion (17% of the intent-to-treat sample) became panic free and there was no improvement in agoraphobic avoidance. Patients treated with CT achieved significantly better outcomes on all measures of panic attacks, including panic-free rate (54%, intent-to-treat), and showed significantly greater improvements in agoraphobic avoidance and patient-rated general anxiety. In conclusion, cognitive therapy for panic disorder can be successfully disseminated in primary care with a brief therapist training and supervision programme that leads to significant improvements in patient outcomes.


Comparison of Diagnostic Accuracy for TNM Stage Among Whole-Body MRI and Coregistered PET/MRI Using 1.5-T and 3-T MRI Systems and Integrated PET/CT for Non-Small Cell Lung Cancer.
OBJECTIVE. The purpose of this study was to compare diagnostic accuracy of TNM stage for whole-body MRI and coregistered PET/MRI using 1.5-T and 3-T MRI systems and PET/CT in patients with non-small cell lung cancer (NSCLC). SUBJECTS AND METHODS. A total of 104 patients with pathologically diagnosed NSCLC underwent whole-body MRI at 1.5 T and 3T and integrated PET/CT, as well as a combination of surgical, pathologic, or follow-up examinations. Whole-body MR images obtained by the five sequences were combined with the PET part of the PET/CT using proprietary software for the PET/MRI studies. The TNM stage obtained with all methods was visually assessed. Kappa statistics were used to determine agreement between TNM stage assessment and final diagnoses, and the McNemar test was used to compare diagnostic accuracy of all methods. RESULTS. Findings of TNM stage on whole-body MRI using 3-T (κ, 0.87; p < 0.0001) and 1.5-T (κ, 0.83; p < 0.0001) systems and for coregistered PET/MRI using a 3-T system (PET/MRI3T; κ, 0.85; p < 0.0001) were rated as significant and almost perfect, and findings for coregistered PET/MRI using a 1.5-T system (PET/MRI1.5T; κ, 0.80; p < 0.0001) and PET/CT (κ, 0.73; p < 0.0001) were rated significant and substantial. Diagnostic accuracy of whole-body MRI using the 3-T system was 88.5% (92/104; p = 0.0002, and using the 1.5-T system it was 84.6% (88/104; p = 0.004); results for PET/MRI3T and PET/MRI1.5T were 86.5% (90/104; p = 0.001) and 81.7% (85/104; p = 0.03), respectively, which were both significantly better than accuracy of results for PET/CT at 76.0% (79/104). Moreover, diagnostic accuracy of whole-body MRI using a 3-T system was significantly higher than that of PET/MRI using a 1.5-T system (p = 0.02). CONCLUSION. Whole-body MRI and coregistered PET/MRI using 3-T and 1.5-T systems are as accurate or more accurate than PET/CT, whereas differences between 3-T and 1.5-T MRI systems are not considered significant.


Transmembrane protein structure: spin labeling of bacteriorhodopsin mutants.
Transmembrane proteins serve important biological functions, yet precise information on their secondary and tertiary structure is very limited. The boundaries and structures of membrane-embedded domains in integral membrane proteins can be determined by a method based on a combination of site-specific mutagenesis and nitroxide spin labeling. The application to one polypeptide segment in bacteriorhodopsin, a transmembrane chromoprotein that functions as a light-driven proton pump is described. Single cysteine residues were introduced at 18 consecutive positions (residues 125 to 142). Each mutant was reacted with a specific spin label and reconstituted into vesicles that were shown to be functional. The relative collision frequency of each spin label with freely diffusing oxygen and membrane-impermeant chromium oxalate was estimated with power saturation EPR (electron paramagnetic resonance) spectroscopy. The results indicate that residues 129 to 131 form a short water-exposed loop, while residues 132 to 142 are membrane-embedded. The oxygen accessibility for positions 131 to 138 varies with a periodicity of 3.6 residues, thereby providing a striking demonstration of an alpha helix. The orientation of this helical segment with respect to the remainder of the protein was determined.


Effects of posture on peripheral vascular responses to lower body positive pressure.
We tested the hypothesis that peripheral vascular responses (in the lower and upper limbs) to application of lower body positive pressure (LBPP) are dependent on the posture of the subjects. We measured heart rate, stroke volume, mean arterial pressure, leg and forearm blood flow (using the Doppler ultrasound technique), and leg (LVC) and forearm (FVC) vascular conductance in 11 subjects (9 men, 2 women) without and with LBPP (25 and 50 mmHg) in supine and upright postures. Mean arterial pressure increased in proportion to increases in LBPP and was greater in supine than in upright subjects. Heart rate was unchanged when LBPP was applied to supine subjects but was reduced in upright ones. Leg blood flow and LVC were both reduced by LBPP in supine subjects [LVC: 4.8 (SD 4.0), 3.6 (SD 3.5), and 1.4 (SD 1.8) ml.min(-1).mmHg(-1) before LBPP and during 25 and 50 mmHg LBPP, respectively; P < 0.05] but were increased in upright ones [LVC: 2.0 (SD 1.2), 3.4 (SD 3.4), and 3.0 (SD 2.0) ml.min(-1).mmHg(-1), respectively; P < 0.05]. Forearm blood flow and FVC both declined when LBPP was applied to supine subjects [FVC: 1.3 (SD 0.6), 1.0 (SD 0.4), and 0.9 (SD 0.6) ml. min(-1).mmHg(-1), respectively; P < 0.05] but remained unchanged in upright ones [FVC: 0.7 (SD 0.4), 0.7 (SD 0.4), and 0.6 (SD 0.5) ml.min(-1).mmHg(-1), respectively]. Together, these findings indicate that the leg vascular response to application of LBPP is posture dependent and that the response differs in the lower and upper limbs when subjects assume an upright posture.


Extended lateral pharyngotomy for selected squamous cell carcinomas of the lateral tongue base.
In a retrospective review of an inception cohort of 26 patients with an isolated, previously untreated, moderately to well-differentiated invasive squamous cell carcinoma of the lateral tongue base, consecutively managed with an extended lateral pharyngotomy approach at a single tertiary referral care center, the authors review the key surgical points, highlight the potential technical pitfalls, and document the complications and long-term functional and oncological outcomes in terms of survival and local control. The adjunctive measures included induction chemotherapy, ipsilateral neck dissection, and postoperative radiotherapy, used in 96.1%, 96.1%, and 38.5% of patients, respectively. All patients but 2 were followed for at least 5 years or until death (maximum, 158 months). The significant postoperative complications included pharyngocutaneous fistula in 3 patients (11.5%) and hemorrhage requiring reoperation, partial flap necrosis, and pneumonia from aspiration in 1 patient (3.8%) each. In univariate analysis, no significant statistical relationship was noted between the significant postoperative complications noted and the variables under analysis. Overall, successful oral alimentation was achieved in 100% of patients by the first postoperative month without gastrostomy, tracheotomy, or completion total laryngectomy. There were no intraoperative or perioperative deaths. The main causes of death were metachronous second primary tumor, intercurrent disease, and distant metastasis, resulting in 84.6%, 64%, and 46.9% 1-, 3-, and 5-year Kaplan-Meier actuarial survival estimates, respectively. Two patients (7.6%) had local recurrence, resulting in 100%, 86.7%, and 86.7% 1-, 3-, and 5-year Kaplan-Meier actuarial local control estimates, respectively. As a function of T stage, the 3- and 5-year actuarial local control estimates were 100%, 87.5%, and 90.9% in patients with tumors classified as T1, T2, and T3-T4a, respectively. Such results suggest that extended lateral pharyngotomy should be integrated among the various conservative treatment options available to patients with selected carcinomas of the lateral tongue base.


Reference intervals for haematological variables during normal pregnancy and postpartum in 434 healthy Danish women.
To report reference intervals for haematological variables during normal pregnancy and postpartum. The series comprised 434 healthy ethnic Danish women with a normal pregnancy > or =37 wk duration and a normal delivery with newborns weight >2500 g. Blood samples were obtained at 18, 32 and 39 wk gestation and at 8 wk postpartum. The following variables were analysed: Haemoglobin (Hb), haematocrit (Hct), blood erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, white cell count, platelet count, erythrocyte folate, plasma folate, plasma cobalamin, plasma methylmalonic acid, plasma total homocysteine, serum ferritin, serum soluble transferrin receptor and plasma creatinine. Reference intervals were calculated using log(10)-transformed values (which showed normal distributions) as mean +/- 1.96 x SD. The lower reference value for Hb during pregnancy was 6.45 mmol/L (105 g/L) and 7.3 mmol/L (118 g/L) postpartum. The lower reference value for Hct was 0.31 in pregnancy and 0.35 postpartum. There was a gradual decline in the lower reference value for erythrocyte folate during pregnancy and postpartum from 0.46 to 0.29 micromol/L and in plasma folate from 6 to 4 nmol/L. Lower reference value for plasma cobalamin declined during pregnancy from 96 to 71 pmol/L, but increased postpartum to 148 pmol/L. Upper reference value for plasma homocysteine increased gradually during pregnancy and postpartum from 11.0 to 20.6 micromol/L. Geometric mean serum ferritin at 18 wk gestation was 32 microg/L. Plasma creatinine values were low during pregnancy and displayed a significant increase postpartum. The characteristic changes occurring in haematological indices during pregnancy and postpartum are described in this study. The results may be used as reference values in the assessment of health status of pregnant women with a similar socio-economic and racial background.


Haida Gwaii (British Columbia, Canada): a Phanerozoic analogue of a subduction-unrelated Archean greenstone belt.
Understanding the formation and evolution of Precambrian greenstone belts is hampered by gaps in the rock record and the uncertainty of the tectonic regime that was operating at the time. Thus identifying a modern analogue of a Precambrian greenstone belt can be problematic. In this paper we present geological, geochemical and petrological evidence outlining the case for Haida Gwaii (British Columbia, Canada) as a modern example of a greenstone belt. Haida Gwaii is comprised of two rift-related volcano-sedimentary sequences. The older (Early Triassic) Karmutsen volcanic sequence consists of subaqueous ultramafic-mafic volcanic rocks that are capped by marine carbonate and siliciclastic rocks. The younger (Paleogene) Masset bimodal volcanic sequence consists of tholeiitic and calc-alkaline basalt along with calc-alkaline silicic volcanic and intrusive rocks that are capped by epiclastic sandstones. The Karmutsen and Masset volcanic rocks have indistinguishable Sr-Nd-Pb isotopes demonstrating they were derived from a similar mantle source. Some of the Masset calc-alkaline rocks are compositionally similar to magnesian andesites (SiO2 = 56-64 wt%; Mg# = 0.50-0.64) that are typical of subduction-related Archean greenstone belts. We show that the calc-alkaline signature observed in the bimodal sequence of the Masset Formation is likely due to fractional crystallization of a tholeiitic parental magma under relatively oxidizing (ΔFMQ + 0.7) conditions indicating that a calc-alkaline signature is not prima facie evidence of a subduction setting. Given the geological and geochemical evidence, Haida Gwaii represents one of the best analogues of a modern subduction-unrelated Archean greenstone belt.


On cognitive neuroscience.
Abstract Stephen M. Kosslyn is Professor of Psychology at Harvard University and an Associate Psychologist in the Department of Neurology at the Massachusetts General Hospital. He received his B.A. in 1970 from UCLA and his Ph.D. from Stanford University in 1974, both in psychology, and taught at Johns Hopkins, Harvard, and Brandeis Universities before joining the Harvard Faculty as Professor of Psychology in 1983. His work focuses on the nature of visual mental imagery and high-level vision, as well as applications of psychological principles to visual display design. He has published over 125 papers on these topics, co-edited five books, and authored or co-authored five books. His books include Image and Mind (1980), Ghosts in the Mind's Machine (1983), Wet Mind: The New Cognitive Neuroscience (with 0. Koenig, 1992), Elements of Graph Design (1994), and Image and Brain: The Resolution of the Imagery Debate (1994). Dr. Kosslyn has received numerous honors, including the National Academy of Sciences Initiatives in Research Award, is currently on the editorial boards of many professional journals, and has served on several National Research Council committees to advise the government on new technologies.


Stimulus-dependent maximum entropy models of neural population codes.
Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. For large populations, direct sampling of these distributions is impossible, and so we must rely on constructing appropriate models. We show here that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. We introduce the stimulus-dependent maximum entropy (SDME) model-a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. We find that the SDME model gives a more accurate account of single cell responses and in particular significantly outperforms uncoupled models in reproducing the distributions of population codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like average surprise and information transmission in a neural population.


The anticancer compound JTE-607 reveals hidden sequence specificity of the mRNA 3' processing machinery.
JTE-607 is an anticancer and anti-inflammatory compound and its active form, compound 2, directly binds to and inhibits CPSF73, the endonuclease for the cleavage step in pre-messenger RNA (pre-mRNA) 3' processing. Surprisingly, compound 2-mediated inhibition of pre-mRNA cleavage is sequence specific and the drug sensitivity is predominantly determined by sequences flanking the cleavage site (CS). Using massively parallel in vitro assays, we identified key sequence features that determine drug sensitivity. We trained a machine learning model that can predict poly(A) site (PAS) relative sensitivity to compound 2 and provide the molecular basis for understanding the impact of JTE-607 on PAS selection and transcription termination genome wide. We propose that CPSF73 and associated factors bind to the CS region in a sequence-dependent manner and the interaction affinity determines compound 2 sensitivity. These results have not only elucidated the mechanism of action of JTE-607, but also unveiled an evolutionarily conserved sequence specificity of the mRNA 3' processing machinery.


Health benefits of electrically-assisted cycling: a systematic review.
Electrically assisted bicycles (e-bikes) have been highlighted as a method of active travel that could overcome some of the commonly reported barriers to cycle commuting. The objective of this systematic review was to assess the health benefits associated with e-cycling. A systematic literature review of studies examining physical activity, cardiorespiratory, metabolic and psychological outcomes associated with e-cycling. Where possible these outcomes were compared to those from conventional cycling and walking. Seven electronic databases, clinical trial registers, grey literature and reference lists were searched up to November 2017. Hand searching occurred until June 2018. Experimental or observational studies examining the impact of e-cycling on physical activity and/or health outcomes of interest were included. E-bikes used must have pedals and require pedalling for electric assistance to be provided. Seventeen studies (11 acute experiments, 6 longitudinal interventions) were identified involving a total of 300 participants. There was moderate evidence that e-cycling provided physical activity of at least moderate intensity, which was lower than the intensity elicited during conventional cycling, but higher than that during walking. There was also moderate evidence that e-cycling can improve cardiorespiratory fitness in physically inactive individuals. Evidence of the impact of e-cycling on metabolic and psychological health outcomes was inconclusive. Longitudinal evidence was compromised by weak study design and quality. E-cycling can contribute to meeting physical activity recommendations and increasing physical fitness. As such, e-bikes offer a potential alternative to conventional cycling. Future research should examine the long-term health impacts of e-cycling using rigorous research designs.


Characterization of senescence- and apoptosis-dependent forms of terminin as derived from a precursor found in replicating and nonreplicating cells.
Previously we have reported the production of a monoclonal antibody (Mab 1.2) which recognizes a cytoplasmic protein, terminin, in three different molecular weights: 90 (Tp90), 60 (Tp60), and 30 kDa (Tp30) forms. Further characterization shows that Tp90 is found in young growing and nongrowing quiescent fibroblasts, while Tp60 is found in permanently growth-arrested senescent fibroblasts and Tp30 in cells committed to undergo programmed cell death (apoptosis). In tissue, Tp90 is found in embryonic brain; later, in neonatal brain after terminal differentiation is completed, only Tp60 is found. Tp30 is found in crude liver fractions extracted without the protective action of protease inhibitors. In all these circumstances, Tp90 is mostly seen in the detergent-soluble fraction, while Tp60 and Tp30 are detergent-insoluble. We now report that in cultured fibroblasts, as well as in tissues such as brain and liver, Tp60 and Tp30 are derived from the Tp90 polypeptide, indicated by the fact that only the Tp90 species is identified by both immunoblotting and immunoprecipitation assays, when the cell or tissue extracts are prepared in the presence of protease inhibitors. Further evidence shows that immunoprecipitation of in vitro translation products from brain, liver, and cultured fibroblasts also present a single band of Tp90 polypeptide. Pulse-chase experiments show that during apoptosis, Tp90 is processed to Tp60, and eventually to Tp30. However, when the total protein extracts are fractionated, only Tp90 is found in the detergent-soluble fraction, with diminishing quantities during the time course of apoptosis, and Tp30, in contrast, is found as the only protein species in the insoluble fraction, with increasing quantity during the same time course. Newly processed Tp60 is not found in either of the fractions, reflecting its loss during the fractionation procedure. Limited one-dimensional peptide mapping of Tp90 yields three different bands at 30, 28, and 25 kDa, but only the one at 30 kDa is recognized by Mab 1.2. These results lead us to suggest that terminin protein is synthesized in the Tp90 form, and cleaved to lower molecular weight forms depends upon different physiologic conditions, with Tp60 processed in the terminally differentiated or senescent state and rapidly to Tp30 in apoptosis. Our findings further suggest that Tp90's processing to either Tp60 or Tp30 produces insoluble protein forms. Furthermore, the presence of Tp90 in nonapoptotic (either replicating or nonreplicating) cells may reflect the absence of necessary proteolytic action required for the execution of apoptosis. Future experiments will allow us to determine the nature of this proteolytic action, as well as whether this action is due to the autocatalytic action of Tp90 or by other endogenous proteases, and then to determine the significance of this biochemical action in cells.


A medium-firm drug-candidate library of cryptand-like structures on T7 phage: design and selection of a strong binder for Hsp90.
We designed and synthesized a medium-firm drug-candidate library of cryptand-like structures possessing a randomized peptide linker on the bacteriophage T7. From the macrocyclic library with a 109 diversity, we obtained a binder toward a cancer-related protein (Hsp90) with an antibody-like strong affinity (KD = 62 nM) and the binding was driven by the enthalpy. The selected supramolecular ligand inhibited Hsp90 activity by site-specific binding outside of the well-known ATP-binding pocket on the N-terminal domain (NTD).


Self-motion effects on hydrodynamic pressure sensing: part I. forward-backward motion.
In underwater locomotion, extracting meaningful information from local flows is as desirable as it is challenging, due to complex fluid-structure interaction. Sensing and motion are tightly interconnected; hydrodynamic signals generated by the external stimuli are modified by the self-generated flow signals. Given that very little is known about self-generated signals, we used onboard pressure sensors to measure the pressure profiles over the head of a fusiform-shape craft while moving forward and backward harmonically. From these measurements we obtained a second-order polynomial model which incorporates the velocity and acceleration of the craft to estimate the surface pressure within the swimming range up to one body length/second (L s(-1)). The analysis of the model reveals valuable insights into the temporal and spatial changes of the pressure intensity as a function of craft's velocity. At low swimming velocities (<0.2 L s(-1)) the pressure signals are more sensitive to the acceleration of the craft than its velocity. However, the inertial effects gradually become less important as the velocity increases. The sensors on the front part of the craft are more sensitive to its movements than the sensors on the sides. With respect to the hydrostatic pressure measured in still water, the pressure detected by the foremost sensor reaches values up to 300 Pa at 1 L s(-1) swimming velocity, whereas the pressure difference between the foremost sensor and the next one is less than 50 Pa. Our results suggest that distributed pressure sensing can be used in a bimodal sensing strategy. The first mode detects external hydrodynamic events taking place around the craft, which requires minimal sensitivity to the self-motion of the craft. This can be accomplished by moving slowly with a constant velocity and by analyzing the pressure gradient as opposed to absolute pressure recordings. The second mode monitors the self-motion of the craft. It is shown here that distributed pressure sensing can be used as a speedometer to measure the craft's velocity.


Inorganic mercury accumulation in rice (Oryza sativa L.).
To investigate the source and process of inorganic mercury (IHg) accumulation in rice, we monitored the concentrations of IHg in tissues of rice plants (Oryza sativa L.) from four experimental plantation plots. Biweekly during the rice-growing season, tissues of rice plants, corresponding soil, precipitation, and irrigation water samples were collected. The sampling data support the following: (1) the atmosphere is the principal source of IHg to the aboveground parts of the rice plant; (2) both the atmosphere and soil contribute to IHg content in stalks, but the former source tends to be more important; and (3) soil is the major source of root IHg content. These observations and the fact that the gradually increasing concentration and mass of IHg in stalks and leaves during the rice-growing season suggested that atmospheric Hg could be absorbed by and incorporated into the aboveground parts of the rice plant and that limited or no Hg emission to the air or translocation to the soil occurred after deposition of atmospheric Hg. The root surface acted as a potential Hg barrier and consequently reduced the translocation of Hg ion mass through the root system to the aboveground parts. Accumulated IHg in aboveground parts of rice plants cannot be transported to seeds, which is completely different from the case of methylmercury.


Japanese encephalitis virus (JEV): potentiation of lethality in mice by microwave radiation.
The expression of Japanese Encephalitis Virus (JEV) lethality in mice requires entry of the virus into the central nervous system. This entry is presumably through the capillary endothelial cells (CEC), because entry between CECs is inhibited by bands of circumferential tight-junctions. A viremic stage occurs during the first 4 to 5 days after JEV administration in mice, and both microwave radiation (2.45-GHz, continuous wave, 10-min exposure) and hypercarbia were employed to increase CEC permeability to JEV. Exposure to microwaves at power densities of 10-50 mW/cm2 resulted in a dose-dependent increase in JEV-induced lethality. Mice did not become tolerant or sensitized to microwave potentiation of JEV-induced mortality because 4 daily exposures at 10 or 50 mW/cm2 (SARS, approximately 24-98 W/kg) did not alter the lethality pattern to subsequent microwave radiation of JEV-exposed animals. Similarly, hypercarbia (5, 10, and 20% CO2) was observed to produce a dose-dependent increase in JEV-induced lethality. Both microwave radiation and hypercarbia are thought to promote pinocytosis in CNS capillary endothelial cells. This may be one mechanism by which they enhance JEV-induced lethality in adult Swiss-Cox mice.


Design of specific peptide inhibitors of phospholipase A2: structure of a complex formed between Russell's viper phospholipase A2 and a designed peptide Leu-Ala-Ile-Tyr-Ser (LAIYS).
Phospholipase A(2) (EC 188.8.131.52) is a key enzyme of the cascade mechanism involved in the production of proinflammatory compounds known as eicosanoids. The binding of phospholipase A(2) to membrane surfaces and the hydrolysis of phospholipids are thought to involve the formation of a hydrophobic channel into which a single substrate molecule diffuses before cleavage. In order to regulate the production of proinflammatory compounds, a specific peptide inhibitor of PLA(2), Leu-Ala-Ile-Tyr-Ser, has been designed. Phospholipase A(2) from Daboia russelli pulchella (DPLA(2)) and peptide Leu-Ala-Ile-Tyr-Ser (LAIYS) have been co-crystallized. The structure of the complex has been determined and refined to 2.0 A resolution. The structure contains two crystallographically independent molecules of DPLA(2), with one molecule of peptide specifically bound to one of them. The overall conformations of the two molecules are essentially similar except in three regions; namely, the calcium-binding loop including Trp31 (residues 25-34), the beta-wing consisting of two antiparallel beta-strands (residues 74-85) and the C-terminal region (residues 119-133). Of these, the most striking difference pertains to the orientation of Trp31 in the two molecules. The conformation of Trp31 in molecule A was suitable to allow the binding of peptide LAIYS, while that in molecule B prevented the entry of the ligand into the hydrophobic channel. The structure of the complex clearly showed that the OH group of Tyr of the inhibitor formed hydrogen bonds with both His48 N(delta1) and Asp49 O(delta1), while O(gamma)H of Ser was involved in a hydrogen bond with Trp31. Other peptide backbone atoms interact with protein through water molecules, while Leu, Ala and Ile form strong hydrophobic interactions with the residues of the hydrophobic channel.


Interconversion of Yeast Mating Types I. Direct Observations of the Action of the Homothallism (HO) Gene.
The HO gene promotes interconversion between a and alpha mating types. As a consequence, homothallic diploid cells are formed by mating between siblings descended from a single alpha HO or a HO spore. In order to determine the frequency and pattern of the mating-type switch, we have used a simple technique by which the mating phenotype can be assayed without losing the cell to the mating process itself. Specifically, we have performed pedigree analysis on descendants of single homothallic spores, testing these cells for sensitivity to alpha-factor.The switch from alpha to a and vice versa is detectable after a minimum of two cell divisions. 50% of the clones tested showed switching by the four-cell stage. Of the four cells descended from a single cell, only the oldest cell and its immediate daughter are observed to change mating type. This pattern suggests that one event in the switching process has occurred in the first cell division cycle. Restriction of the switched mating-type to two particular cells may reflect the action of the homothallism system followed by nonrandom segregation of DNA strands in mitosis.The mating behavior of cells which have sustained a change in mating type due to the HO gene is indistinguishable from that of heterothallic strains.


Spike--nucleocapsid interaction in Semliki Forest virus reconstructed using network antibodies.
Using in vitro immunization, we have reconstructed three consecutive steps of an idiotype network to show that the nucleocapsid of Semliki Forest virus contains a specific 'receptor' for the cytoplasmic tail of the E2 spike glycoprotein. This interaction could be the basis for the highly selective inclusion of viral glycoproteins--and exclusion of host cell surface proteins--during virus budding.


Subject-specific computer simulation model for determining elbow loading in one-handed tennis backhand groundstrokes.
A subject-specific angle-driven computer model of a tennis player, combined with a forward dynamics, equipment-specific computer model of tennis ball-racket impacts, was developed to determine the effect of ball-racket impacts on loading at the elbow for one-handed backhand groundstrokes. Matching subject-specific computer simulations of a typical topspin/slice one-handed backhand groundstroke performed by an elite tennis player were done with root mean square differences between performance and matching simulations of < 0.5 degrees over a 50 ms period starting from ball impact. Simulation results suggest that for similar ball-racket impact conditions, the difference in elbow loading for a topspin and slice one-handed backhand groundstroke is relatively small. In this study, the relatively small differences in elbow loading may be due to comparable angle-time histories at the wrist and elbow joints with the major kinematic differences occurring at the shoulder. Using a subject-specific angle-driven computer model combined with a forward dynamics, equipment-specific computer model of tennis ball-racket impacts allows peak internal loading, net impulse, and shock due to ball-racket impact to be calculated which would not otherwise be possible without impractical invasive techniques. This study provides a basis for further investigation of the factors that may increase elbow loading during tennis strokes.


Ownership and use of insecticide-treated nets in Oromia and Amhara regional states of Ethiopia two years after a nationwide campaign.
To evaluate the ownership and use of insecticide-treated nets (ITNs) by the local community 2 years after a free distribution campaign in Ethiopia. This is a population-based survey using a two-stage cluster sample design in 115 randomly selected clusters in Oromia and Amhara regional states of Ethiopia, performed in June 2009. Data on the possession and use of ITNs were collected using structured and pre-tested questionnaires through house-to-house visits. Bivariate and multivariate logistic regression analyses were performed to examine the effect of participant's malaria knowledge, location and ITN characteristics on the use of ITNs. A total of 2874 households participated in the study, and 90.6% of the study population was knowledgeable about ITNs. About 49.1% of households reported at least one ITN; 28.4% owned two or more. ITN coverage was significantly lower in Oromia (34.9%) than in Amhara (76.8%, P<0.001). The average number of ITNs per ITN-owning household was 1.8. In all surveyed households, only 21.8% of all family members, 29.4% of all children under the age of 5 years and 23.2% of all pregnant women had slept under an ITN the night preceding the survey. Among ITN-owning households, 63.0% of all children under the age of 5 years and 52.1% of pregnant women had slept under an ITN the night before the survey. Using multivariate analysis, factors significantly associated with ITN use were number of ITNs in the household, number of ITNs hung over the bed in the household, women's knowledge of ITNs and women's lack of problem in using ITNs, whereas region, area of residence and ITN status were not. Household ITN ownership and use remain below the current Roll Back Malaria targets of universal coverage. A replacement strategy is urgently needed to scale-up coverage and use of ITNs.


The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma.
Vasohibin-1 (VASH1) is a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells, and the status of VASH1 expression has been documented in cancer angiogenesis. The aim of this study was to address the prognostic value of VASH1 expression in upper urinary tract urothelial carcinomas (UTUC). We retrospectively analyzed the clinical records of 171 patients with locally advanced UTUC (Ta-3N0M0). The median follow-up period was 3.8 years. We immunohistochemically examined the accomplished microvessels with anti-CD34 as microvessel density (MVD) and the microvessels with activated endothelial cells as VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinical outcomes. Forty-two patients experienced tumor recurrence and of these 34 died of the disease during follow-up. VASH1 density was significantly associated with tumor grade, pathologic T stage, and MVD. The 5-year recurrence-free and cancer-specific survival rates were 66.1% and 72.8% in patients with VASH1 density (≥ 40/mm(2)) and 81.0% and 86.5% in their counterparts, respectively (P < 0.05). MVD was not an independent predictor of tumor recurrence or cancer-specific survival. Multivariate analyses revealed that high VASH1 density was an independent prognostic indicator of both tumor recurrence (P = 0.024, HR = 2.10) and cancer-specific survival (P = 0.031, HR = 2.23) as well as other standard prognostic factors including high tumor grade and lymphovascular invasion. VASH1 density represents a clinically relevant predictor of patient prognosis in UTUC. The results suggest that VASH1 density could become a new biomarker and provide additional prognostic information in patients with UTUC.


Somatic mitochondrial DNA deletions accumulate to high levels in aging human extraocular muscles.
PURPOSE. Mitochondrial function and the presence of somatic mitochondrial DNA (mtDNA) defects were investigated in extraocular muscles (EOMs) collected from individuals covering a wide age range, to document the changes seen with normal aging. METHODS. Cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) histochemistry was performed on 46 EOM samples to determine the level of COX deficiency in serial cryostat muscle sections (mean age, 42.6 years; range, 3.0-96.0 years). Competitive three-primer and real-time PCR were performed on single-fiber lysates to detect and quantify mtDNA deletions. Whole-genome mitochondrial sequencing was also performed to evaluate the contribution of mtDNA point mutations to the overall mutational load. RESULTS. COX-negative fibers were seen in EOMs beginning in the third decade of life, and there was a significant age-related increase: <30 years, 0.05% (n = 17); 30 to 60 years, 1.94% (n = 13); and >60 years, 3.34% (n = 16, P = 0.0001). Higher levels of COX deficiency were also present in EOM than in skeletal muscle in all three age groups (P < 0.0001). Most of the COX-negative fibers harbored high levels (>70%) of mtDNA deletions (206/284, 72.54%) and the mean deletion level was 66.64% (SD 36.45%). The mutational yield from whole mitochondrial genome sequencing was relatively low (1/19, 5.3%), with only a single mtDNA point mutation identified among COX-negative fibers with low deletion levels < or =70%. CONCLUSIONS. The results show an exponential increase in COX deficiency in EOMs beginning in early adulthood, which suggests an accelerated aging process compared with other postmitotic tissues.


Brief report: effect of dietary restraint on fruit and vegetable intake following implementation intentions.
This study explored whether the effects of implementation intentions on increasing fruit and vegetable intake were moderated by dietary restraint. In total, 208 participants were randomly allocated to control or implementation intention conditions where they were asked to write down when, where and how they would increase their fruit and vegetable intake. Implementation intentions increased fruit and vegetable intake but only in participants scoring low (not high) on rigid dietary restraint. Motives underlying fruit and vegetable consumption may be different for restrained and unrestrained eaters. Efforts to increase their intake may need to be tailored, for example, through motivational rather than situational cues.


Experience in the long-term treatment of patients with hirsutism and/or acne with cyproterone acetate-containing preparations: efficacy, metabolic and endocrine effects.
The effects and side effects of long-term treatment with cyproterone acetate (CPA) are described. Hammerstein's reverse sequential regimen (10 days 100 mg CPA, 21 days 50 micrograms ethinylestradiol (EE)) was used in most cases, although postmenopausal and hysterectomized women received 50 mg CPA/day continuously as monotherapy. The degree of androgenization was assessed in 143 of a total group of 188 women treated from 1968 to the present. The results of the treatment were good or very good in about 75% of hirsutism patients and in more than 90% of acne patients. Adverse events were recorded in 23% of cases. Most were mild and transient, and caused discontinuation of the therapy in only 9% of patients. From this population representing all cases treated and analysed retrospectively, a subgroup of patients was selected for a prospective investigation. Thirty-five patients with good response to CPA and longlasting therapy were included into this 2-year follow-up study; of these, 24 had previously received CPA for 5 or more years, 9 for more than 10 years and 2 for more than 15 years. Treatment in these patients consisted of 5 different regimens of various doses of CPA combined with EE and CPA alone in order to evaluate possible effects of concomitant estrogen treatment as well as a possible dose- or time-dependency of potential side effects. Clinicochemical, metabolic and endocrine parameters were determined at the start and end of the study. The hematological and clinicochemical parameters were within the normal ranges. There was a slight decrease of glucose tolerance and a moderate increase of insulin and C peptide after oral glucose loading. The effects of CPA and EE on lipometabolism were slight and apparently dependent on the dose of CPA and the therapeutic regimen. No suppression of adrenal function or of responsiveness to ACTH was seen. Fasting prolactin levels and serum prolactin concentrations after provocation with metoclopramide did not show any gross deviations. Sonography of the breast and liver did not show any abnormalities apart from adenofibrosis or mastopathy in 2 patients. In conclusion, CPA with or without EE was in our hands an effective and safe method of long-term treatment of hirsutism and/or acne in women.


Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.
Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is one avenue toward generating the potentially protective immune responses necessary to inhibit HIV-1 infection of infants through breastfeeding. In the present study, we tested the efficacy of a maternal vaccine regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime-combined intramuscular-intranasal gp120 boost administered during pregnancy and postpartum to confer passive protection on infant rhesus macaques against weekly oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4 (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust systemic envelope (Env)-specific IgG response, as well as durable milk IgA responses, the maternal vaccine did not have a discernible impact on infant oral SHIV acquisition. This study revealed considerable variation in vaccine-elicited IgG placental transfer and a swift decline of both Env-specific antibodies (Abs) and functional Ab responses in the infants prior to the first challenge, illustrating the importance of pregnancy immunization timing to elicit optimal systemic Ab levels at birth. Interestingly, the strongest correlation to the number of challenges required to infect the infants was the percentage of activated CD4+ T cells in the infant peripheral blood at the time of the first challenge. These findings suggest that, in addition to maternal immunization, interventions that limit the activation of target cells that contribute to susceptibility to oral HIV-1 acquisition independently of vaccination may be required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding. This study of rhesus macaque dam-and-infant pairs is the first preclinical study to investigate the protective role of transplacentally transferred HIV-1 vaccine-elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in infant oral virus acquisition. It revealed highly variable placental transfer of potentially protective antibodies and emphasized the importance of pregnancy immunization timing to reach peak antibody levels prior to delivery. While there was no discernible impact of maternal immunization on late infant oral virus acquisition, we observed a strong correlation between the percentage of activated CD4+ T cells in infant peripheral blood and a reduced number of challenges to infection. This finding highlights an important consideration for future studies evaluating alternative strategies to further reduce the vertical HIV-1 transmission risk.


Care-seeking patterns among families that experienced under-five child mortality in rural Rwanda.
Over half of under-five deaths occur in sub-Saharan Africa and appropriate, timely, quality care is critical for saving children's lives. This study describes the context surrounding children's deaths from the time the illness was first noticed, through the care-seeking patterns leading up to the child's death, and identifies factors associated with care-seeking for these children in rural Rwanda. Secondary analysis of a verbal and social autopsy study of caregivers who reported the death of a child between March 2013 to February 2014 that occurred after discharge from the child's birth facility in southern Kayonza and Kirehe districts in Rwanda. Bivariate analyses using Fisher's exact tests were conducted to identify child, caregiver, and household factors associated with care-seeking from the formal health system (i.e., community health worker or health facility). Factors significant at α = 0.10 significance level were considered for backwards stepwise multivariate logistic regression, stopping when remaining factors were significantly associated with care-seeking at α = 0.05 significance level. Among the 516 eligible deaths among children under-five, 22.7% (n = 117) did not seek care from the health system. For those who did, the most common first point of contact was community health workers (45.8%). In multivariate logistic regression, higher maternal education (OR = 3.36, 95% CI: 1.89, 5.98), having diarrhea (OR = 4.21, 95%CI: 1.95, 9.07) or fever (OR = 2.03, 95%CI: 1.11, 3.72), full household insurance coverage (3.48, 95%CI: 1.79, 6.76), and longer duration of illness (OR = 22.19, 95%CI: 8.88, 55.48) were significantly associated with formal care-seeking. Interventions such as community health workers and insurance promote access to care, however a gap remains as many children had no contact with the health system prior to death and those who sought formal care still died. Further efforts are needed to respond to urgent cases in communities and further understand remaining barriers to accessing appropriate, quality care.


The ultrastructure of the peritoneal membrane in chronically dialysed rats.
The model to estimate peritoneal function in chronically dialysed rats was previously presented by us. The aim of the paper is to report the findings obtained in electron microscopy of peritoneal biopsies from Wistar rats dialysed for 1 month with high glucose dialysis solution. In control animals, thin mesothelial cells were covered with microvilli. The submesothelial tissue was composed of sparse bundles of parallelly oriented collagen fibers with a few resting cells. In chronically dialysed rats, mesothelial cell layer was thicker and cells were fully packed with intracellular structures, mainly secretory granules with a homogeneous content. The submesothelial tissue was expanded due to the increased amount of collagen fibers, oedema and increased amount of submesothelial cells which were activated. The use of electron microscopy to study the peritoneum in dialysed rats is an excellent supplement to the chronic functional model of peritoneal dialysis in rats.


The alpha 2 beta 1 integrin regulates collagen-mediated MDCK epithelial membrane remodeling and tubule formation.
Previous studies have demonstrated that incubation of MDCK cell epithelial cysts in collagen gel induced a reversal in cell surface polarity that was regulated by beta 1 integrins. Further experiments were done to identify the specific collagen binding integrin involved by applying collagen gel overlays to the apical membrane of subconfluent MDCK monolayers. Cell surface levels of the apical membrane glycoprotein gp135 were monitored by ELISA to quantitate the extent of collagen-mediated membrane remodeling. After an 8 hour incubation with collagen, there was a 35% reduction in gp135 while the cell surface levels of the alpha 2, alpha 3 and beta 1 integrin subunits were not affected. Immunofluorescence microscopy confirmed the loss of gp135 from selected regions of the apical cell surface while the alpha 2 and beta 1 integrin subunits were distributed in small clusters over the entire apical membrane in both control and collagen-treated monolayers. Collagen-mediated loss of gp135 was inhibited by monoclonal antibodies which recognize either the alpha 2 or beta 1 integrin subunits but not by a monoclonal antibody against the alpha 6 beta 1 integrin. These results demonstrated that remodeling of the apical membrane had occurred, allowing the selective retention of beta 1 integrins but not gp135. They were supported by the observation that collagen-mediated loss of apical membrane microvilli was inhibited by the monoclonal antibody against the alpha 2 integrin subunit. Incubation of confluent monolayers with collagen gel induced the formation of polarized epithelial tubules within 16 hours. Epithelial tubule biogenesis was completely inhibited by monoclonal antibodies against either the alpha 2 or beta 1 integrin subunits, providing strong evidence that the alpha 2 beta 1 integrin is essential for collagen-mediated epithelial membrane remodeling and tubule formation.


CloudLines: compact display of event episodes in multiple time-series.
We propose incremental logarithmic time-series technique as a way to deal with time-based representations of large and dynamic event data sets in limited space. Modern data visualization problems in the domains of news analysis, network security and financial applications, require visual analysis of incremental data, which poses specific challenges that are normally not solved by static visualizations. The incremental nature of the data implies that visualizations have to necessarily change their content and still provide comprehensible representations. In particular, in this paper we deal with the need to keep an eye on recent events together with providing a context on the past and to make relevant patterns accessible at any scale. Our technique adapts to the incoming data by taking care of the rate at which data items occur and by using a decay function to let the items fade away according to their relevance. Since access to details is also important, we also provide a novel distortion magnifying lens technique which takes into account the distortions introduced by the logarithmic time scale to augment readability in selected areas of interest. We demonstrate the validity of our techniques by applying them on incremental data coming from online news streams in different time frames.


Counterstory methodology in a university-high school collaboration to center and humanize Latina/o voices.
Educational environments can often feel hostile and inequitable for Latina/o students and teachers, with limited resources and support to humanize their experiences. Counterstorytelling methodologies can be used by students and teachers to center lived experiences, contest deficit narratives, and uncover community cultural wealth (CCW). Drawing on a CCW lens, situated in critical race theory and Latina/o critical theory, we examine a university-high school service learning collaboration in an urban setting that focused on educational equity and counterstorytelling (5 high school classes, 80 students, and 1 teacher; 1 university class, 29 undergraduates, 1 graduate student, and 1 university professor) using ethnographic observations and reflections. In a context of relationship building and discussions of educational equity across the university-high school partnership, we engaged in a counterstorytelling process that uncovered existing CCW and helped to cultivate positive relational pedagogy (social capital) and college going culture (aspirational and navigational capital) and fostered critical reflection and hope (resistant capital). Centering the unique knowledge of students can allow the teacher to facilitate a more equitable learning environment that acknowledges students' resilience.


Reaching trajectories unravel modality-dependent temporal dynamics of the automatic process in the Simon task: a model-based approach.
The Simon effect represents a phenomenon in which the location of the stimuli affects the speed and accuracy of the response, despite being irrelevant for the task demands. This is believed to be due to an automatic activation of a response corresponding to the location of the stimuli, which conflicts with the controlled decision process based on relevant stimuli features. Previously, differences in the nature of the Simon effect (i.e., the pattern of change of the effect across the distribution of response times) between visual and somatosensory stimuli were reported. We hypothesize that the temporal dynamics of visual and somatosensory automatic and controlled processes vary, thus driving the reported behavioral differences. While most studies have used response times to study the underlying mechanisms involved, in this study we had participants reach out to touch the targets and recorded their arm movements using a motion capture system. Importantly, the participants started their movements before a final decision was made. In this way, we could analyze the movements to gain insights into the competition between the automatic and controlled processes. We used this technique to describe the results in terms of a model assuming automatic activation due to location-based evidence, followed by inhibition. We found that for the somatosensory Simon effect, the decay of the automatic process is significantly slower than for the visual Simon effect, suggesting quantitative differences in this automatic process between the visual and somatosensory modalities.


Gender impact on prognosis of acute coronary syndrome patients treated with drug-eluting stents.
Women have a higher risk of adverse outcomes after percutaneous coronary intervention (PCI) than men. However, in acute coronary syndrome (ACS), long-term outcomes after contemporary PCI with drug-eluting stent (DES) have not been fully investigated. We aimed to test the impact of gender on outcomes in patients with ACS after PCI with DES. We analyzed all patients with ACS from the prospective NOBORI-2 trial who underwent PCI with a Nobori DES from 2008 through 2009 in 125 centers worldwide. End points of the study were target lesion failure, cardiac death, myocardial infarction (MI), and clinically driven target lesion revascularization, and major adverse cardiac events (composite of cardiac death, MI, and target vessel revascularization) at 1 year and yearly up to 5 years. There were 1,640 patients with ACS, 1,268 men (77%) and 372 women (23%). Compared to men, women were 5 years older and more frequently had co-morbidities such as diabetes mellitus and hypertension. There were no gender differences for cardiac death (1.3% vs 2.7%), MI (2.1% vs 3.2%), or target lesion revascularization (2.6% vs 3.8%) at 1 year after the procedure for men and women, respectively. The trend was the same at 2 years (cardiac death 2.0% vs 2.3%, MI 2.5% vs 3.5%, target lesion revascularization 3.2% vs 4.6%). Target lesion failure rates were 4.5% and 5.9% at 1 year and 5.7% and 7.3% at 2 years in men and women, respectively (p = NS). Multivariate analysis, which included age, hypertension, diabetes mellitus, and number of diseased vessels, showed that gender was not a predictor for outcome. There were no differences in bleeding or stent thrombosis rates. Relief from anginal symptoms was similar. The same rate of adherence to dual antiplatelet therapy was observed and reached 73% at 1 year and 31% at 2 years after the ACS event and PCI. In conclusion, although women had worse baseline characteristics, no differences in outcomes were observed between men and women treated for ACS with contemporary DES.


Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease.
The increased incidence of inflammatory bowel disease (IBD) has become a global phenomenon that could be related to adoption of a Western life-style. Westernization of dietary habits is partly characterized by enrichment with the ω-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), which entails risk for developing IBD. Glutathione peroxidase 4 (GPX4) protects against lipid peroxidation (LPO) and cell death termed ferroptosis. We report that small intestinal epithelial cells (IECs) in Crohn's disease (CD) exhibit impaired GPX4 activity and signs of LPO. PUFAs and specifically AA trigger a cytokine response of IECs which is restricted by GPX4. While GPX4 does not control AA metabolism, cytokine production is governed by similar mechanisms as ferroptosis. A PUFA-enriched Western diet triggers focal granuloma-like neutrophilic enteritis in mice that lack one allele of Gpx4 in IECs. Our study identifies dietary PUFAs as a trigger of GPX4-restricted mucosal inflammation phenocopying aspects of human CD.


Otoacoustic Emissions in Young Children with Autism.
The aim of this study is to investigate otoacoustic emissions (OAEs) in young children with autism compared with those in an age-matched control group. Thirty-eight children with autism aged 3-6 years and 27 typically developing (normally developing) control subjects participated in this study. All the participants had normal hearing and middle-ear function. Auditory brainstem responses were used to determine the hearing status in the autism group. Transient-evoked otoacoustic emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) were measured in the two groups. The TEOAE response level was higher in the autism group. Analysis of the DPOAE response showed that the mean emission levels at 1.5, 2 , 3, and 6 kHz and signal/noise ratios at 2, 4, 6, and 8 kHz were higher in the autism group (p<0.05). The greatest between-group differences were observed in the DPOAE signal levels at 2, 3, and 6 kHz (p=0.000). No statistically significant difference was found between the noise levels in the autism and control groups (p>0.05). The emission responses in the autism group were higher than those in the control group. The increase in DPOAEs at high frequencies may be related to the higher outer cell activation in the autism group. Further studies with larger sample sizes comprising younger children are needed to confirm the result and investigate the possible association between the increased OAEs and auditory sensitivity reported in autism.