Human NDUFB9 gene: genomic organization and a possible candidate gene associated with deafness disorder mapped to chromosome 8q13.
Human NADH dehydrogenase (ubiquinone) 1beta-subcomplex, 9 (NDUFB9) is a nuclear encoded mitochondrial protein with the respiratory electron transport chain. It has been physically mapped to a 1-Mb deletion at chromosome 8q13 which also contains the gene for branchio-oto-renal (BOR) syndrome. BOR syndrome is characterized by branchial and renal abnormalities with hearing impairment. Since several hereditary deafness disorders have been associated with mitochondrial mutations, NDUFB9 was considered a candidate gene for BOR syndrome. Recently, EYA1 gene has been identified in the region which underlies the BOR syndrome but majority of BOR families did not show mutations in the EYA1 gene. Here we have determined the genomic structure of the NDUFB9 gene, including the nucleotide sequence, organization and the boundaries of the four coding exons. PCR primers were designed from the adjacent intron sequences that allow amplification of the four exons that encode the complete open reading frame. To identify whether mutations in NDUFB9 are involved in causing the BOR syndrome, we screened 9 BOR families which did not show mutations in the EYA1 gene by heteroduplex analysis; however, no mutations were found.


The embryonic development of the main lymphatics in man.
A study of microscopical serial sections of 40 well-preserved human embryos, ranging in age from about 40 to 65 days (8-33 mm C.-R. length), revealed that the prevertebral main lymphatics develop from a number of separate primordia, all derived from venous walls. These primordia are: paired jugular and axillary lymph sacs and paratracheal, internal throacic, lumbar and iliac lymph plexuses, and single subtracheal and mesenteric lymph plexuses. Probably, the thoracic ducts develop from a series of small additional primordia. All these primordia, except the jugulo-axillary lymph sacs, lose their connections with the veins. They rapidly enlarge, fuse with one another and send out sprouts into peripheral regions, so that soon the definitive pattern of the major lymphatics can be recognized. During development some variations may occur, in particular in the area where the lower extensions of the two throacic ducts meet the lumbar lymph plexuses. Usually, the right thoracic duct primarily comes into contact with the jugulo-axillary lymph sac. The conclusion is drawn that on an embryological basis in the prevertebral region additional lymphatico-venous communications might be expected, but that possible lymphatico-venous communications elsewhere in the body always point to developmental aberrations or to pathology.


Joint study of extracranial arterial occlusion. X. Internal carotid artery occlusion.
One cannot now predict with accuracy the degree of deficit that may be anticipated following a carotid occlusion even when the condition of the opposite artery is known. When symptoms and signs occur, they are most likely related to the hemisphere or eye on the side of the occlusion. In patients with carotid occlusion, a higher rate of severe complications and mortality was encountered following arteriography than in the general study population. Among randomized patients with a carotid occlusion and a contralateral carotid stenosis, 63% of medically treated patients were alive at the end of a 66-month follow-up, whereas only 34% of surgically treated patients were still living. Surgical mortality was extremely high in patients with a carotid occlusion. Sixty-seven percent mortality occurred in patients undergoing surgery within one week of a cerebral infarction.


Repair bond strength of a resin composite to alumina-reinforced feldspathic ceramic.
This study compared the microtensile bond strength of a repair resin to an alumina-reinforced feldspathic ceramic (Vitadur-alpha, Vita) after 3 surface conditioning methods: Group 1, etching with 9.6% hydrofluoric acid for 1 minute plus rinsing and drying, followed by application of silane for 5 minutes; group 2, airborne particle abrasion with 110-mm aluminum oxide using a chairside air-abrasion device followed by silane application for 5 minutes; group 3, chairside tribochemical silica coating with 30-microm SiOx followed by silane application for 5 minutes (N = 30). Group 1 presented the highest mean bond strength (19.7 +/- 3.8 MPa), which was significantly higher than those of groups 2 (10 +/- 2.6 MPa) and 3 (10.4 +/- 4 MPa) (P < .01). Scanning electron microscope analysis of the failure modes demonstrated predominantly mixed types of failures, with adhesive and/or cohesive failures in all experimental groups.


Immune enhancing effect of a growth hormone secretagogue.
Growth hormone (GH) has been known to enhance immune responses, whether directly or through the insulin like growth factor-1, induced by GH. Recently a nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to induce the production of GH by the pituitary gland. In this study, we examined the effect of GHS in immunological functions of 5- to 6-wk-old and 16- to 24-month-old mice. In young mice, we observed a significant increase in PBLs, but T and B cell-proliferative responses were not consistently enhanced. The old mice, treated with GHS for 3 wk, did not show increases in peripheral lymphocytes, but they exhibited a statistically significant increase in thymic cellularity and differentiation. When inoculated with a transplantable lymphoma cell line, EL4, the treated old mice showed statistically significant resistance to the initiation of tumors and the subsequent metastases. Generation of CTL to EL4 cells was also enhanced in the treated mice, suggesting that GHS has a considerable immune enhancing effect, particularly in the old mice. We have also found that GHS promoted better thymic engraftment in bone marrow transplant of SCID mice. We found more cycling cells in the spleens of treated mice, suggesting that GHS may exert its immune enhancing effect by promoting cell division in lymphoid cells. These observations ascribe to GHS a novel therapy possible for aging, AIDS, and transplant individuals, whose immune functions are compromised.


Behavior change techniques used to promote walking and cycling: a systematic review.
Evidence on the effectiveness of walking and cycling interventions is mixed. This may be partly attributable to differences in intervention content, such as the cognitive and behavioral techniques (BCTs) used. Adopting a taxonomy of BCTs, this systematic review addressed two questions: (a) What are the behavior change techniques used in walking and cycling interventions targeted at adults? (b) What characterizes interventions that appear to be associated with changes in walking and cycling in adults? Previous systematic reviews and updated database searches were used to identify controlled studies of individual-level walking and cycling interventions involving adults. Characteristics of intervention design, context, and methods were extracted in addition to outcomes. Intervention content was independently coded according to a 26-item taxonomy of BCTs. Studies of 46 interventions met the inclusion criteria. Twenty-one reported a statistically significant effect on walking and cycling outcomes. Analysis revealed substantial heterogeneity in the vocabulary used to describe intervention content and the number of BCTs coded. "Prompt self-monitoring of behavior" and "prompt intention formation" were the most frequently coded BCTs. Future walking and cycling intervention studies should ensure that all aspects of the intervention are reported in detail. The findings lend support to the inclusion of self-monitoring and intention formation techniques in future walking and cycling intervention design, although further exploration of these and other BCTs is required. Further investigation of the interaction between BCTs and study design characteristics would also be desirable.


[Some fundamental notions of oncomorphology in the light of modern molecular biology advances].
Introduction of molecular biological studies into oncomorphology has made investigators reconsider many fundamental notions of the histogenesis, morphogenesis, and microscopic structure of human neoplasms. Tumor cell differentiation is a more dynamic process, a less fixed concept; hence it is necessary to do away with the rigid frameworks of cancer nosological entities and with a number of postulates on tumor histogenesis, including the rudiments of blastemic tissue changed during embryogenesis. The morphogenesis of a tumor has proven to be frequently determined by the variants of the specific translocations that may, in addition to its miscroscopic structure, affect a great variety of the clinical manifestations of disease. The molecular portrait of a tumor, the result of gene expression peculiarities can substitute for traditional cancer nosological entities although new classifications should be based on advances in oncomorphology.


Perspective: Framework for Developing Recommended Intakes of Bioactive Dietary Substances.
Dietary bioactives are food substances that promote health but are not essential to prevent typical deficiency conditions. Examples include lutein and zeaxanthin, omega-3 fatty acids, and flavonoids. When quality evidence is available, quantified intake recommendations linking dietary bioactives with specific health benefits will enable health professionals to provide evidence-based information to consumers. Without evidence-based recommendations, consumers use information from available sources that often lack standards and rigor. This article describes a framework to develop guidance based on quality evidence fully vetted for efficacy and safety by qualified experts, and designed to communicate the amounts of specific dietary bioactive compounds with identified health benefits. The 4-step Framework described here can be adapted by credible health organizations to work within their guideline development process. Standards of practice used in clinical guidelines are adapted to quantify dietary bioactive intake recommendations from foods consumed by the general public, by taking into account that side effects and trade-offs are often needed for medical treatments but are not acceptable for dietary bioactives. In quantifying dietary bioactive recommendations, this Framework establishes 4 decision-making steps: 1) characterize the bioactive, determine amounts in specific food sources, and quantify intakes; 2) evaluate safety; 3) quantify the causal relation between the specific bioactive and accepted markers of health or normal function via systematic evidence reviews; and 4) translate the evidence into a quantified bioactive intake statement. This Framework provides a working model that can be updated as new approaches are advanced.


Genetic evidence for bidirectional effects of early lexical and grammatical development.
This article addresses the autonomy hypothesis of vocabulary and grammar and bootstrapping mechanisms in early language development. Two birth cohorts of 1,505 and 1,049 same-sex twin pairs from the UK were assessed at 2 and 3 years on grammar and vocabulary, using adapted versions of the MacArthur Communicative Development Inventory. Vocabulary and grammar correlate strongly at both 2 and 3 years in both cohorts. Multivariate genetic modeling reveals a consistently high genetic correlation between vocabulary and grammar at 2 and 3 years. This finding suggests the same genetic influences operate for both vocabulary and grammar, a finding incompatible with traditional autonomy hypothesis, at least in early acquisition. Crosslagged longitudinal genetic models indicate both lexical and syntactical bootstrapping operate from 2 to 3 years.


Compressive Behaviour of Lattice Structures Manufactured by Polyjet Technologies.
Additive manufacturing (AM) techniques can help to reduce the time and cost for manufacturing complex shaped parts. The main goal of this research was to determine the best strength structure of six different types of lattice cells, manufactured using the Poly Jet AM technology. In order to perform the tests, six samples with the same structure were created for each lattice type. For testing the samples in compression, an electromechanical test machine was used. finite element analysis (FEA) analysis was used in order to determine the area where the greatest stresses occured and to estimate the maximal compressive strength. The strongest structure was determined by obtaining the maximal compressive strength. This was calculated in two ways: as a ratio between the maximal supported force and the mass of the sample (N/g) and as a ratio between the maximal supported force and the critical section of the sample (MPa).


Physical Fitness Is Longitudinally Associated With Academic Performance During Childhood and Adolescence, and Waist Circumference Mediated the Relationship.
The current investigation aimed to investigate the longitudinal association between physical fitness and academic performance over 3 years in adolescents. A secondary aim was to determine to what extent waist circumference mediated the association between physical fitness and academic performance. For the current study, 1020 students from first grade [mean age: 7.87 (0.34) y] to fifth grade [mean age: 11.87 (0.37) y] were monitored annually for 3 years (2010-2013). Physical fitness was assessed using the Andersen test, 5 × 5-m shuttle run, jump height, and grip strength tests and by constructing a composite score combining all 4 fitness tests. Academic performance was assessed by national standardized tests in Danish language and math. Generalized structural equation modeling was used to evaluate the relationships between these variables. The Andersen test (standardized β = 0.15 SD), shuttle run (β = -0.18 SD), jump height (β = 0.10 SD), and the fitness composite score (β = 0.23 SD) were positively associated with academic performance over 3 years. In addition, waist circumference partially mediated the association between physical fitness and academic performance. Thus, physical fitness abilities should be stimulated during childhood and early adolescence because of their positive association with academic performance.


Surface-bonded antimicrobial activity of an organosilicon quaternary ammonium chloride.
The hydrolysis product of 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride exhibited antimicrobial activity against a broad range of microorganisms while chemically bonded to a variety of surfaces. The chemical was not removed from surfaces by repeated washing with water, and its antimicrobial activity could not be attributed to a slow release of the chemical, but rather to the surface-bonded chemical.


Pulmonary Mycobacterium tuberculosis in acquired immune deficiency syndrome.
A case of pulmonary infection with Mycobacterium tuberculosis in a patient with the acquired immune deficiency syndrome (AIDS) was studied. Diagnosis of AIDS was confirmed by the finding of pulmonary M tuberculosis with oral and oesophageal candidiasis accompanied by characteristic immunological changes with evidence of infection with human T cell lymphotropic virus III. Treatment of this patient was complicated by an unusual drug interaction between rifampicin and ketoconazole, leading to subtherapeutic serum concentrations and poor clinical response to treatment. Intravenous treatment was more effective than oral treatment. This drug interaction should be studied in greater detail as ketoconazole and rifampicin may be used together to treat patients with candidiasis and infection with M tuberculosis.


More crop for drop - climate change and wine: an economic evaluation of a new drought-resistant rootstock.
The current paper presents the results of an economic evaluation of a new drought-resistant rootstock (M4), capable to maintain in adverse environmental conditions high photosynthetic activity, to accumulate osmotic compounds and to compensate for the accumulation of sodium and chlorine in the grapevines, in two core Italian grapevine growing areas: the North-East and Sicily. After collecting data on quantitative (yield per plant in kg) and qualitative parameters (°Brix, anthocyanins, pH) of experimental vineyards (Cabernet Sauvignon variety) planted using the traditional rootstock 1103P and the innovative M4 rootstock, over a seven-year period, a cost-benefit analysis calculated the effects of replacing the traditional rootstock. The results show that M4 rootstock yields higher net revenues compared to the best situation of 1103P rootstock, roughly in 40% of North-East vineyards and in more than 80% of their Sicilian counterparts. In addition, 14% of North-East vineyards and more than 94% of Sicilian vineyards are currently exposed to drought risk, and these areas are expected to increase in the coming years. Thus the M4 rootstock, as other related innovations [51-53], could significantly improve watersaving strategies, which are gaining increasing attention from both public bodies and wine companies.


Co-designing a telepractice journey map with disability customers and clinicians: Partnering with users to understand challenges from their perspective.
Telepractice has the potential to align with the directive to reduce inequalities by United Nations Sustainable Development Goal 10. Telepractice additionally addresses a national digital health strategic plan for accessible digitally enabled models of care. To plan improvements, it is essential to understand the experience of telepractice for people with disability, which may be achieved through an approach such as journey mapping. The current article provides both a disability-specific case study and a methodological guide for the inclusion of customers and clinicians in the meaningful redevelopment of services. The Perth, Australia-based case study aimed to gain insights into the experience of telepractice for people with disability. The methodological aim describes using co-design to produce a journey map in collaboration with customers and clinicians, for potential replication in a wide range of health and social care contexts. Interview transcripts gathered from a cohort of customer participants (n = 17) were used to inform the journey map. A group of customers (n = 5) and clinicians plus one manager (n = 5) distributed the findings onto a customer experience journey map during a co-design workshop. The journey map describes the emotional experience and actions taken, along five phases of a timeline through telepractice service interactions: (1) before, (2) selecting telepractice, (3) telepractice preparation, (4) during telepractice sessions and (5) after. A journey map visualisation of customer experiences was produced that identified strengths of telepractice service delivery (flexibility) while noting challenges (with technology) as opportunities for improvement. The consensus of participants was the desire to have access to telepractice currently and in the future, in addition to in-person delivery. These findings are valuable in the context of advocating for the incorporation of customers and clinicians through co-design workshops in the content analysis and creation of a journey map that is representative of the lived experience of accessing telepractice services. The paper forms part of a larger co-design process that included customer participants throughout the design and planning of the project, inclusion of a peer researcher and the co-designers in the workshops, journey map and this article production.


An epitope in human immunodeficiency virus 1 reverse transcriptase recognized by both mouse and human cytotoxic T lymphocytes.
T-cell-mediated cytotoxicity may play an important role in control of infection by the human immunodeficiency virus (HIV). In this study, we have identified and characterized a relatively conserved epitope in the HIV-1 reverse transcriptase recognized by murine and human cytotoxic T cells. This epitope was identified using a murine antigen-specific CD8+ class I major histocompatibility complex-restricted cytotoxic T-cell (CTL) line, a transfected fibroblast cell line expressing the HIV-1 pol gene, recombinant vaccinia viruses containing different truncated versions of the pol gene, and overlapping synthetic peptides. The optimal antigenic site was identified as residues 203-219 by synthesizing extended or truncated peptide analogs of the antigenic fragment. The optimal peptide was then tested for sensitization of autologous Epstein-Barr virus-transformed B-cell targets for killing by fresh human peripheral blood mononuclear cells. It was recognized by CTLs from several HIV-seropositive patients but not from any seronegative donor. Therefore, this peptide is a good candidate for inclusion in an AIDS vaccine. This study demonstrates that the same CTL epitope can be seen by murine and human CD8+ CTLs, as previously demonstrated for epitopes recognized by CD4+ helper T cells, and suggests the utility of screening for immunodominant CTL epitopes in mice prior to carrying out studies in humans.


The role of health impact assessment in Phase V of the Healthy Cities European Network.
Health impact assessment (HIA) is a prospective decision-making aid tool that aims to improve the quality of policies, programmes or projects through recommendations that promote health. It identifies how and through which pathways a decision can impact a wide range of health determinants and seeks to define the distribution of effects within populations, thereby raising the issue of equity. HIA was introduced to the WHO European Healthy Cities Network as one of its four core themes during the Phase IV (2004-08). Here we present an evaluation of the use of HIA during Phase V (2009-13), where HIA was linked with the overarching theme of health and health equity in all local policies and a requirement regarding capacity building. The evaluation was based on 10 case studies contributed by 9 Healthy Cities in five countries (France, Hungary, Italy, Spain and the UK). A Realist Evaluation framework was used to collect and aggregate data obtained through three methods: an HIA factors analysis, a case-study template analysis using Nvivo software and a detailed questionnaire. The main conclusion is that HIA significantly helps promote Health in All Policies (HiAP) and sustainability in Healthy Cities. It is recommended that all Healthy City candidates to Phase VI (2014-18) of the WHO Healthy Cities European Network effectively adopt HIA and HiAP.


Prognostic Factors of COVID-19 Infection in Elderly Patients: A Multicenter Study.
The outbreak of the COVID-19 pandemic is a substantial threat to the health of all populations worldwide, and old age is a robust risk factor for poor prognosis of COVID-19 infection. To reduce the fatality rate of COVID-19 infection, further understanding of elderly patients with COVID-19 is necessary. We aimed to investigate the prognostic factors in elderly patients with COVID-19. This was a multicenter and retrospective study. Overall, 340 elderly patients with COVID-19 were enrolled in 3 hospitals in Daegu, South Korea. Death and severe pneumonia requiring oxygen treatment were defined as poor clinical outcomes. Of the patients studied, 15% died and 35.2% were classified as having severe pneumonia. In binary logistic regression analysis, activities of daily living (ADL) impairment, fever during hospitalization, initial infiltration on chest radiograph, and initial increased C-reactive protein (CRP) were significantly associated with severe pneumonia (OR = 5.33, p < 0.001; OR = 3.2, p = 0.002; OR = 2.32, p = 0.044; and OR = 1.33, p < 0.001, respectively). ADL impairment, comorbidity, fever during hospitalization, and initial increased CRP were significantly associated with death (OR = 7.13, p < 0.001; OR = 3.28, p = 0.005; OR = 3.15, p = 0.032, and OR = 1.18, p < 0.001, respectively). ADL impairment, fever, and initial CRP were poor prognostic factors in elderly patients with COVID-19. Understanding these poor prognostic factors is necessary to control the disease in elderly patients.


Ethnobotanical study of plants used in management of livestock health problems by Afar people of Ada'ar District, Afar Regional State, Ethiopia.
The great majority of the Afar people of Ethiopia are pastoralists, highly dependent on livestock and livestock products. Livestock productivity is, however, frequently affected by different diseases. Although many districts in the Region have veterinary clinics, they lack basic facilities. As a result, the Afar people are still dependent on local materials, mainly plants, and traditional knowledge to manage livestock health problems. However, there is a serious threat to such local resources mainly due to recurrent drought and influence of modernization. Hence there is a need for proper documentation and evaluation of the existing ethnoveterinary knowledge in the Region. This study was aimed at documenting and analysing ethnoveterinary knowledge of people in Ada'ar District of the Afar Region associated with the use of plants. The study involved interviewing selected knowledgeable Afar people in Ada'ar District on the use of plants to manage livestock ailments. Fidelity Level (FL) values were calculated for the reported medicinal plant to estimate their healing potentials. Specimens of reported medicinal plant were collected, identified and deposited at the National Herbarium, Addis Ababa University. The study revealed 49 medicinal plants as being used by the Afar people of Ada'ar District for the treatment of various livestock ailments, the majority of which (67.3%) were shrubs. Highest number of medicinal plants was used to treat blackleg, contagious caprine pleuropneumonia (CCPP), sudden sickness and pneumonia. Leaf was the most frequently sought plant part, accounting for 47% of the reported plants. All the medicnal plants used in the District were uncultivated ones growing in semi-disturbed and disturbed habitats as remnant plants and weeds. Cissus quadrangularis and Solanum incanum were the plants scoring the highest fidelity level values for their use to treat blackleg and respiratory tract problems, respectively. The study revealed that there is still rich knowledge of ethnoveterinary medicine in Ada'ar District. There was no habit of cultivating medicinal plants by people in the study area. Efforts, should, therefore, be made to protect these medicinal plants from further depletion, especially those that are scarcely available. Better attention should be given to medicinal plants with the highest fidelity level values as such values could indicate potencies of the plants.


An Open-label, Single-center, Safety and Efficacy Study of Eyelash Polygrowth Factor Serum.
Objective: We sought to evaluate the efficacy of a polygrowth factor serum for increasing length, luster, thickness, and volume of eyelashes in a group of healthy Indian women. Design: This was a 90-day, open-label, single-center safety and efficacy study. Thirty Indian female participants, aged 15 to 45 years old, were enrolled in the study; 29 of these subjects completed the study. There were four assessment visits: at baseline (Day 0) and on Days 30, 60, and 90. Subjects were instructed on the application of the test product uniformly to both eyes on the upper and lower eyelid margins. Subjects applied the product once nightly for 90 days. Measurements: At each visit, subjects underwent ophthalmological and dermatological assessments and digital image photographs using Visia CR imaging system. Improvement in eyelash length, density/volume, luster, and curl were evaluated using imaging and software technologies. Results: Improvement in test parameters was observed 30 days after initiation of product usage. Among the 29 subjects who completed the study, improvements in length (10.52%), volume (9.3%), luster (11.43%), thickness (35%), and curl (50.83%), compared to baseline, were recorded. Conclusion: The study demonstrated efficacy in improving eyelash length, luster, thickness, and curl. The results were observed as early as 30 days of product usage and persisted until the last visit following 90 days of product usage. There were no adverse events associated with the product. We concluded that the polygrowth factor serum was well tolerated and effectively improved eye lash length, luster, thickness, and volume in our patient sample. Additional randomized, controlled studies with larger samples are needed to confirm our findings.


ICF from an occupational therapy perspective in adult care: an integrative literature review.
Since its launch there has been increasing interest in the International Classification of Functioning, Disability and Health (ICF) within occupational therapy (OT). The aim of this study was to perform an integrative literature review, in order to present an overview of knowledge, where the ICF constitutes a significant part in relation to OT. A systematic literature search, covering the period 2001-2008, was performed in the databases MEDLINE, AMED, and CINAHL. A total of 112 articles were included and the majority had exploratory and descriptive designs. The results showed that ICF was valuable for research, clinical practice, and education. ICF was used to link existing instruments and to construct new outcome measures. Occupational therapists have been members of expert groups involved in the development of Core Sets for certain health conditions. Several positive aspects were described, e.g. an effective medium for communication at different levels. Many limitations were mentioned, such as unclear concepts and lack of subjective experiences. Suggestions for improvements were described. The conclusion was that the ICF has been used for a broad spectrum of purposes. The results indicated that further research is needed concerning application of the ICF in clinical practice and education.


High-resolution human cervical spinal cord imaging at 7 T.
We present high-resolution anatomical imaging of the cervical spinal cord in healthy volunteers at the ultrahigh field of 7 T with a prototype four-channel radiofrequency coil array, in comparison with 3-T imaging of the same subjects. Signal-to-noise ratios at both field strengths were estimated using the rigorous Kellman method. Spinal cord cross-sectional area measurements were performed, including whole-cord measurements at both fields and gray matter segmentation at 7 T. The 7-T array coil showed reduced sagittal coverage, comparable axial coverage and the expected significantly higher signal-to-noise ratio compared with equivalent 3-T protocols. In the cervical spinal cord, the signal-to-noise ratio was found by the Kellman method to be higher by a factor of 3.5 with the 7-T coil than with standard 3-T coils. Cervical spine imaging in healthy volunteers at 7 T revealed not only detailed white/gray matter differentiation, but also structures not visualized at lower fields, such as denticulate ligaments, nerve roots and rostral-caudal blood vessels. Whole-cord cross-sectional area measurements showed good agreement at both field strengths. The measurable gray/white matter cross-sectional areas at 7 T were found to be comparable with reports from histology. These pilot data demonstrate the use of higher signal-to-noise ratios at the ultrahigh field of 7 T for significant improvement in anatomical resolution of the cervical spinal cord, allowing the visualization of structures not seen at lower field strength, particularly for axial imaging.


A brief history of "Alzheimer disease": Multiple meanings separated by a common name.
The field of Alzheimer disease (AD) has a nosologic problem: The diagnostic label "Alzheimer disease" has several distinctive meanings. The term probable AD was introduced in 1984 to designate a clinically diagnosed acquired and progressive amnestic dementia for which there was no evidence for another etiology. Probable AD represented a clinicopathologic entity that assumed a specific and sensitive linkage between amnestic dementia and the neuropathology of β-amyloid-containing neuritic plaques and tau-containing neurofibrillary tangles. The clinicopathologic model represented by probable AD was adapted in abbreviated form for population-based studies and general clinical practice, although the uncertainty connoted by "probable" was often overlooked. Representing the growing public awareness of later life cognitive impairment, a vernacular meaning of AD arose out of the clinicopathologic model in which AD represented all dementia not due to another clinically apparent cause. In contrast, by the 1990s, neuropathologists settled on a definition of AD based entirely on a sufficient burden of neuritic plaques and neurofibrillary tangles at postmortem examination, regardless of antemortem clinical status. In the last decade, the availability of fluid and imaging biomarkers that measure β-amyloid and tau abnormalities has enabled antemortem pathobiological diagnoses, highlighting the divide between the clinicopathologic model, the vernacular usage, and the pathobiological models. Each definition has value. However, the meanings of AD as defined by each of these models are not interchangeable. The pathobiological one is the only one that is unambiguous.


High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival.
Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P < 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis.


Clinical experiences with desmopressin for long-term treatment of nocturia.
To our knowledge we report the first long-term use of desmopressin for nocturia. Patients previously responding to desmopressin in short-term studies were enrolled in this long-term open label study. Patients received treatment for 10 or 12 months with the optimal desmopressin dose (0.1, 0.2 or 0.4 mg orally at bedtime). Patients were followed a further month without treatment. Of the patients completing the short-term study 132 males (92%) and 117 females (83%) were recruited, and 95 (72%) and 87 (75%), respectively, completed long-term treatment. The mean number of nocturnal voids was decreased in males and females throughout the study (1.3 to 1.6 and 1.2 to 1.3) compared with baseline (3.1 and 2.9, respectively). After followup the number of voids increased after treatment cessation. From baseline to 12 months the mean duration of the first sleep period gradually increased in males (157 to 288 minutes) and females (142 to 310 minutes). After followup the mean duration of the first sleep period decreased, confirming that it was a treatment related benefit. Desmopressin was well tolerated with few males (14%) or females (10%) withdrawing due to adverse events. Most adverse events were mild (44%) or moderate (44%) in severity. Four males experienced serious drug related adverse events, namely dizziness in 1, cardiac failure, headache and vomiting in 2, and chest pain and hypertension in 1. A female experienced 4 serious drug related adverse events, that is hyponatremia, headache, nausea and vertigo. Two patients had clinically significant hyponatremia. This long-term study shows that desmopressin is a generally well tolerated and effective treatment for nocturia.


The Frank-Starling mechanism is not mediated by changes in rate of cross-bridge detachment.
We tested the hypothesis that the Frank-Starling relationship is mediated by changes in the rate of cross-bridge detachment in cardiac muscle. We simultaneously measured isometric force development and the rate of ATP consumption at various levels of Ca2+ activation in skinned rat cardiac trabecular muscles at three sarcomere lengths (2.0, 2.1, and 2.2 microns). The maximum rate of ATP consumption was 1.5 nmol.s-1.microliter fiber vol-1, which represents an estimated adenosinetriphosphatase (ATPase) rate of approximately 10 s-1 per myosin head at 24 degrees C. The rate of ATP consumption was tightly and linearly coupled to the level of isometric force development, and changes in sarcomere length had no effect on the slope of the force-ATPase relationships. The average slope of the force-ATPase relationships was 15.5 pmol.mN-1.mm-1. These results suggest that the mechanisms that underlie the Frank-Starling relationship in cardiac muscle do not involve changes in the kinetics of the apparent detachment step in the cross-bridge cycle.


Thiol/disulfide redox states in signaling and sensing.
Rapid advances in redox systems biology are creating new opportunities to understand complexities of human disease and contributions of environmental exposures. New understanding of thiol-disulfide systems have occurred during the past decade as a consequence of the discoveries that thiol and disulfide systems are maintained in kinetically controlled steady states displaced from thermodynamic equilibrium, that a widely distributed family of NADPH oxidases produces oxidants that function in cell signaling and that a family of peroxiredoxins utilize thioredoxin as a reductant to complement the well-studied glutathione antioxidant system for peroxide elimination and redox regulation. This review focuses on thiol/disulfide redox state in biologic systems and the knowledge base available to support development of integrated redox systems biology models to better understand the function and dysfunction of thiol-disulfide redox systems. In particular, central principles have emerged concerning redox compartmentalization and utility of thiol/disulfide redox measures as indicators of physiologic function. Advances in redox proteomics show that, in addition to functioning in protein active sites and cell signaling, cysteine residues also serve as redox sensors to integrate biologic functions. These advances provide a framework for translation of redox systems biology concepts to practical use in understanding and treating human disease. Biological responses to cadmium, a widespread environmental agent, are used to illustrate the utility of these advances to the understanding of complex pleiotropic toxicities.


Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study.
We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.


Fluid administration and the kidney.
Intravenous fluids are widely administered in the ICU with the intention of preventing or ameliorating acute kidney injury (AKI). This review focuses on recent studies examining fluid administration and renal function in critical illness to critically examine conventional justifications for fluid administration. Early, targeted, resuscitation of inadequate cardiac output in shock may have a beneficial effect on organ function and patient outcome. However, experimental evidence suggests the relationship between fluid administration and an increase in renal oxygen delivery is weak, whereas any beneficial effects from fluid administration can be short lived. Conversely, evidence associating fluid overload and adverse outcomes is strengthening, whereas more restrictive fluid administration does not seem to predispose to clinically significant AKI in many situations. Furthermore, concerns persist that some colloid or high chloride concentration solutions may directly impair renal function independent of volume overload. Adequate volume resuscitation remains a cornerstone to the emergent treatment of critical illness. However, continued fluid administration and positive fluid balances have not been shown to improve renal outcomes and may worsen overall prognosis in AKI. Concerns about renal dysfunction should not deter clinicians from adopting more restrictive approaches to fluid administration.


NAFTNet retrospective report on the treatment of anti-Ro/SSA mediated fetal heart block with dexamethasone.
Complete atrioventricular block (CAVB) is a complication of maternal antibody positivity and treatment of fetal disease is controversial in terms of efficacy and safety. We hypothesized that dexamethasone treatment for fetal anti-Ro/SSA antibody-mediated cardiac disease leads to better pregnancy outcomes than expectant management. A retrospective multi-center cohort study of anti-Ro/SSA antibody positive pregnancies with fetal conduction disease reported by participating North American Fetal Therapy Network (NAFTNet) centers between January 2010 and December 2018. The primary outcomes included: fetal death, oligohydramnios, growth restriction, preterm delivery, and new maternal comorbidities. Secondary outcomes included: pacemaker prior to 28 days, transplantation, and neonatal death in maternal/fetal dyads treated with dexamethasone versus not. In 127 anti-Ro/SSA positive pregnancies, 98 were treated with dexamethasone and 29 were not. Of those treated, 61/96 (63.5%) met the primary outcome including 45/91 (49.4%) premature deliveries; 20 mothers developed comorbidities during treatment (fetal death 5, 10 growth restriction, 14 oligohydramnios, two new/worsening gestational diabetes). In the untreated group, 15/25 (60%) met the primary outcome including 11/22 (50%) premature deliveries and four mothers developing comorbidities during their pregnancy (fetal death 3, one growth restriction, one new onset maternal hypertension). Regarding secondary outcomes, 37/96 (43%) treated fetuses required a pacemaker or died by 28 days, while untreated 13/25 (52%) required pacemaker placement, died prior to 28 days or required listing for transplantation. Excluding terminations, survival without transplant was 17 (68%) in untreated and 85 (89%) in treated patients (p<.01). While the use of dexamethasone in anti-Ro/SSA positive pregnancies is associated with a high rate of poor pregnancy outcomes, there was an unexpected similarly high rate in untreated positive pregnancies. This suggests that the maternal disease itself is influencing pregnancy complications independent of dexamethasone. Our data, which show that treatment decreases neonatal morbidity and overall mortality without increasing overall pregnancy complications, warrant further study.


Single-cell analysis of Rohon-Beard neurons implicates Fgf signaling in axon maintenance and cell survival.
Peripheral sensory neurons are a critical part of the nervous system that transmit a multitude of sensory stimuli to the central nervous system. During larval and juvenile stages in zebrafish, this function is mediated by Rohon-Beard somatosensory neurons (RBs). RBs are optically accessible and amenable to experimental manipulation, making them a powerful system for mechanistic investigation of sensory neurons. Previous studies provided evidence that RBs fall into multiple subclasses; however, the number and molecular make up of these potential RB subtypes have not been well defined. Using a single-cell RNA sequencing (scRNA-seq) approach, we demonstrate that larval RBs in zebrafish fall into three, largely non-overlapping classes of neurons. We also show that RBs are molecularly distinct from trigeminal neurons in zebrafish. Cross-species transcriptional analysis indicates that one RB subclass is similar to a mammalian group of A-fiber sensory neurons. Another RB subclass is predicted to sense multiple modalities, including mechanical stimulation and chemical irritants. We leveraged our scRNA-seq data to determine that the fibroblast growth factor (Fgf) pathway is active in RBs. Pharmacological and genetic inhibition of this pathway led to defects in axon maintenance and RB cell death. Moreover, this can be phenocopied by treatment with dovitinib, an FDA-approved Fgf inhibitor with a common side effect of peripheral neuropathy. Importantly, dovitinib-mediated axon loss can be suppressed by loss of Sarm1, a positive regulator of neuronal cell death and axonal injury. This offers a molecular target for future clinical intervention to fight neurotoxic effects of this drug.


A lipidic mesophase with tunable release properties for the local delivery of macromolecules: the apoferritin nanocage, a case study.
Lipid mesophases are able to incorporate and release a plethora of molecules, spanning from hydrophobic drugs to small hydrophilic proteins and therefore they have been widely used as drug delivery systems. However, their 3-5 nm water channels do not allow the release of large hydrophilic molecules such as monoclonal antibodies and therapeutic proteins. To overcome this major geometrical constraint, we designed a gel by mixing monoacylglycerol lipids, generally recognized as safe for human and/or animal use by FDA, and phospholipids, to obtain a material with swollen water channels suitable to host and further release macromolecules. Apoferritin, a 12 nm nanocage protein with intrinsic tumor-targeting properties able to incorporate several molecules, was selected here as the hydrophilic model protein to be embedded in the biocompatible gel. When immersed completely in the release media, mesophases with a swollen water channel of 22 nm, composed of monoolein and doped with 5 mole% of DOPS and 10 mole% of Chol allowed us to achieve a protein release of 60%, which is 120 times higher with respect to that obtained by employing non swollen-LMPs composed only of monoolein. Thus, the formulation can be administered locally to the rectal or vaginal mucosa, reducing the drawbacks often associated with the parenteral administration of bio-therapeutics. This approach would pave the way for the local application of other biomacromolecules (including human ferritin, monoclonal antibodies and antibody drug-conjugates) in those diseases easily reachable by a local application such as rectal or vaginal cancer.


New lower-limb gait asymmetry indices based on a depth camera.
Various asymmetry indices have been proposed to compare the spatiotemporal, kinematic and kinetic parameters of lower limbs during the gait cycle. However, these indices rely on gait measurement systems that are costly and generally require manual examination, calibration procedures and the precise placement of sensors/markers on the body of the patient. To overcome these issues, this paper proposes a new asymmetry index, which uses an inexpensive, easy-to-use and markerless depth camera (Microsoft Kinect™) output. This asymmetry index directly uses depth images provided by the Kinect™ without requiring joint localization. It is based on the longitudinal spatial difference between lower-limb movements during the gait cycle. To evaluate the relevance of this index, fifteen healthy subjects were tested on a treadmill walking normally and then via an artificially-induced gait asymmetry with a thick sole placed under one shoe. The gait movement was simultaneously recorded using a Kinect™ placed in front of the subject and a motion capture system. The proposed longitudinal index distinguished asymmetrical gait (p < 0.001), while other symmetry indices based on spatiotemporal gait parameters failed using such Kinect™ skeleton measurements. Moreover, the correlation coefficient between this index measured by Kinect™ and the ground truth of this index measured by motion capture is 0.968. This gait asymmetry index measured with a Kinect™ is low cost, easy to use and is a promising development for clinical gait analysis.


Menstrual hygiene management amongst schoolgirls in the Rukungiri district of Uganda and the impact on their education: a cross-sectional study.
An increasing number of studies have found that girls in low-income settings miss or struggle at school during menstruation if they are unable to manage their menstrual hygiene effectively. This study explores the menstrual hygiene practices and knowledge of girls at rural government primary schools in the Rukungiri district in Uganda and assesses the extent to which poor menstrual hygiene management (MHM) affects their education. A self-administered questionnaire was completed by schoolgirls in six government-run primary schools in the Rukungiri district. Focus groups were held with girls from each school and semi-structured interviews were conducted with headteachers and female teachers from the participating schools. A toilet assessment was also conducted in each school. One hundred and forty schoolgirls completed the questionnaire. The girls reported a lack of access to adequate resources, facilities and accurate information to manage their menstrual hygiene effectively at school. They reported that, as a result, during menstruation they often struggle at school or miss school. Eighty-six girls (61.7%) reported missing school each month for menstrual-related reasons (mean 1.64, range 0-10, SD. 1.84). It is common for girls who attend government-run primary schools in the Rukungiri district to miss school or struggle in lessons during menstruation because they do not have access to the resources, facilities, or information they need to manage for effective MHM. This is likely to have detrimental effects on their education and future prospects. A large-scale study is needed to explore the extent of this issue.


Comparing physiological responses during cognitive tests in virtual environments vs. in identical real-world environments.
Immersive virtual environments (VEs) are increasingly used to evaluate human responses to design variables. VEs provide a tremendous capacity to isolate and readily adjust specific features of an architectural or product design. They also allow researchers to safely and effectively measure performance factors and physiological responses. However, the success of this form of design-testing depends on the generalizability of response measurements between VEs and real-world contexts. At the current time, there is very limited research evaluating the consistency of human response data across identical real and virtual environments. Rendering tools were used to precisely replicate a real-world classroom in virtual space. Participants were recruited and asked to complete a series of cognitive tests in the real classroom and in the virtual classroom. Physiological data were collected during these tests, including electroencephalography (EEG), electrocardiography (ECG), electrooculography (EOG), galvanic skin response (GSR), and head acceleration. Participants' accuracy on the cognitive tests did not significantly differ between the real classroom and the identical VE. However, the participants answered the tests more rapidly in the VE. No significant differences were found in eye blink rate and heart rate between the real and VR settings. Head acceleration and GSR variance were lower in the VE setting. Overall, EEG frequency band-power was not significantly altered between the real-world classroom and the VE. Analysis of EEG event-related potentials likewise indicated strong similarity between the real-world classroom and the VE, with a single exception related to executive functioning in a color-mismatch task.


Herbal medications for surgical patients: a systematic review protocol.
Postoperative nausea and vomiting (PONV) affect approximately 80% of surgical patients and is associated with increased length of hospital stay and systemic costs. Preoperative and postoperative pain, anxiety and depression are also commonly reported. Recent evidence regarding their safety and effectiveness has not been synthesised. The aim of this systematic review is to evaluate the efficacy and safety of herbal medications for the treatment and prevention of anxiety, depression, pain and PONV in patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgical procedures. The following electronic databases will be searched up to 1 October 2016 without language or publication status restrictions: CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science and LILACS. Randomised clinical trials enrolling adult surgical patients undergoing laparoscopic, obstetrical/gynaecological and cardiovascular surgeries and managed with herbal medication versus a control group (placebo, no intervention or active control) prophylactically or therapeutically will be considered eligible. Outcomes of interest will include the following: anxiety, depression, pain, nausea and vomiting. A team of reviewers will complete title and abstract screening and full-text screening for identified hits independently and in duplicate. Data extraction, risk of bias assessments and evaluation of the overall quality of evidence for each relevant outcome reported will be conducted independently and in duplicate using the Grading of Recommendations Assessment Development and Evaluation classification system. Dichotomous data will be summarised as risk ratios; continuous data will be summarised as standard average differences with 95% CIs. This is one of the first efforts to systematically summarise existing evidence evaluating the use of herbal medications in laparoscopic, obstetrical/gynaecological and cardiovascular surgical patients. The findings of this review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO CRD42016042838.


Does supplementary health insurance play a role in the switching behaviour of citizens in the Netherlands?
Several healthcare systems have elements of managed competition in which citizens can choose between multiple insurers. In order for this principle to function properly, all citizens should have equal opportunities to switch insurer. Studies, conducted around 2015, have shown that the supplementary insurance policy is perceived by citizens as a barrier to switching, which could have negative consequences for the intended goals of the system.. We aim to explore whether a supplementary insurance policy still has a restraining role on the opportunity to switch among citizens in the Netherlands from 2015 to 2020. Furthermore, we will examine if the extensiveness of the supplementary insurance policy relates to the switching behaviour of citizens. This element has not been addressed in previous studies. We obtained information on the role of the supplementary health insurance policy in the switching behaviour of citizens by sending questionnaires, yearly in February from 2015-2020, to 1,500 members of the Dutch Health Care Consumer Panel (DHCCP) each year. As such, we were able to examine whether having a supplementary insurance policy plays a role in the decision of Dutch citizens to switch insurer. The response rates were consecutively from 2015 to 2020: 60% (n = 896), 47% (n = 703), 44% (n = 659), 50% (n = 751), 48% (n = 715), and 54% (n = 806). Citizens with a supplementary insurance policy switch less often than citizens without one. The extensiveness of the supplementary insurance policy is significantly associated with the decision of citizens to switch insurer; the more extensive citizens are insured, the less often they switch. Additionally, our results show that every year a small group of citizens does not switch insurer because they are concerned that they will not be accepted for a supplementary insurance policy. Our results indicate that having a supplementary insurance policy holds citizens back from using their opportunity to switch. This contributes to the idea that having a supplementary insurance policy could be experienced by citizens as a barrier to switch. This raises questions about the extent to which the principle of managed competition in the Dutch healthcare system works as intended.


Trophoblast specialisations during pregnancy in the tammar wallaby, Macropus eugenii: a morphological and lectin histochemical study.
The tammar wallaby has a short gestation (26.5 days) and vascular modifications to expedite transport during that brief pregnancy. Here we examine trophoblast structural attributes that would facilitate materno-fetal exchange. Four specimens of Macropus eugenii between days 23 and 26 gestation were examined using electron microscopy and 24 lectins to characterise glycosylated secretions and their internalisation. Two trophoblast phenotypes were found, flattened cells generally in contact with the underlying uterine epithelium and giant cells associated with histiotrophe. The latter appeared to penetrate uterine clefts, occasionally detach and become necrotic. Lectin histochemistry and ultrastructure indicated the presence of many lysosomes and residual bodies especially in trophoblast giant cells; these contained glycans, mainly apically, which were also detected in secretions and cell debris. Trophoblast basal membranes bore extensive filopodia. Giant cells were less common in vascular trilaminar areas and here the trophoblast barrier became thinner near term. Loss of Maackia amurensis agglutinin binding suggested cleavage of terminal sialic acid residues as an early post-internalisation event in the trophoblast. Lectin staining indicated degradation occurred in an apical-basal direction, and the heavily glycosylated basal membrane appeared specialised for transport out of the cell. Granules seen ultrastructurally and histochemically, particularly in giant trophoblast cells of the bilaminar area, suggest that internalised histiotrophe is broken down here and nutrients transferred to the embryo via the specialised basal plasma membrane. The trilaminar vascular area contained mostly flattened trophoblast cells, supporting the suggestion that gaseous exchange is its primary function.


[Analysis of isozyme and RAPD for the germplasm lines from G. hirsutum x G. bickii].
To study the effectiveness of Gossypium interspecific hybrid breeding on molecular level, the six germplasm lines from interspecific hybrids between G. hirsutum and G. bickii were analysed by the techniques of RAPD and isozyme electrophoresis. The main results were summarized as follows: (1) The basic zymograms of peroxidase isozyme of the six germplasm lines were similar to their G. hirsutum parent, but two out of the germplasm lines showed one specific band of the wild parent of G. bickii (pI 4.85); (2) The RAPD fingerprint showed distinct difference of genomic DNA among the germplasm lines; (3) The four specific DNA fragments of G. bickii were observed in RAPD patters of four out of the six germplasm lines.


Physical activity, inflammation, and muscle loss.
Sarcopenia is the degenerative loss of skeletal muscle that occurs naturally in individuals as they age. Although many factors underlie sarcopenia, epidemiological and experimental evidence suggests that low-grade chronic inflammation is an important contributor to its progression. Still, few healthcare professionals have a clear understanding of the profound effects of cytokines on sarcopenia, or how these effects may be counteracted. Interestingly, mounting evidence suggests that along with good diet and vitamin supplementation, this muscle damage can be mitigated with regular physical activity. Without a doubt, exercise is an intervention that reliably counteracts the loss of muscle mass, strength, and power common in our increasingly aged, and pervasively sedentary, population.


Non-Coding RNA in Brain Development and Disorder.
Although up to 90% of the eukaryotic genome can be transcribed, only 1-2% of the resultant transcripts encode for proteins, while the remaining can be classified as non-coding RNAs (ncRNAs) which mostly consist of long ncRNAs (lncRNAs) and small ncRNAs. In overall, they have been suggested to target specific regions in the genome and play multi-faceted roles in many important biological processes. Recent evidence has shown that ncRNAs are abundantly expressed in the brain and many of them are aberrantly regulated in neural disorders. Yet their functional relevance in related physiological and pathological processes has not been adequately understood. Thus, the elucidation of the role of ncRNAs in the brain would greatly enhance the current understanding of neural development and ultimately lead to novel strategies to treat neural diseases. In this report, we reviewed the structure and mechanism of lncRNAs and various classes of small ncRNAs in brain development and neural disorders. We hope that extensive studies of these ncRNAs would unravel and characterize novel molecular circuits in the brain, and facilitate the development of RNA-based therapeutics for people suffering from neural disorders.


Management of violent patients: a training approach.
With the increased occurrence of violence in hospitals, this article provides information on how to resolve violence in the hospital and how to help heal the emotional scars of health care practitioners involved in job-related violent acts. Techniques of conflict management include preventive methods such as observing various cues of possible violence, safety procedures when approaching a violent incident, and various appeals when attempting to persuade the violent person to follow a safer course of action. The process of dealing with the aftermath of a violent act includes establishing a Crisis Aftermath Plan (CAP).


A replacement for methoxyflurane (Metofane) in open-circuit anaesthesia.
Methoxyflurane (Metofane) has been widely used as an open-circuit anaesthetic in small laboratory animals for several decades. Its low vapour pressure and high blood solubility have permitted its use in convenient and simple drop-chamber/nose-cone setups. Recently, following the decision by the primary manufacturer to discontinue production, it has become increasingly difficult to obtain methoxyflurane. We describe here a simple and effective adaptation of isoflurane, an excellent inhalation anaesthetic, to open-circuit drop-chamber/nose-cone anaesthesia. It was found that the vapour concentration of isoflurane could be continuously varied by dissolving the anaesthetic in propylene glycol and that a 20% solution produced effective anaesthesia such that in adult mice, 2 ml of 20% isoflurane in propylene glycol induced anaesthesia within 2 min in a one-litre drop chamber. Furthermore, anaesthesia maintenance with 20% isoflurane was tested in two sets of mice. In one set, surgical plane anaesthesia was maintained for 10 min in a head chamber. After removal of the chamber, the animals awoke within one minute and recovered without any indication of post-anaesthetic distress. The second set contained pregnant mice; here anaesthesia was maintained for between 10 and 12 min, during which laparotomy, exposure of one uterine horn, intrauterine injection and wound closure were completed. The recovery from anaesthesia was also within a minute and with no signs of distress. Healthy litters were delivered after a normal gestation. This isoflurane/propylene glycol procedure is simple, effective and humane, and is a good substitute for methoxyflurane.


[Citizen security observatories: tools for decision making and governability].
The need for good governability to promote countries development has been becoming the focus of governments. Latin America has political systems in crisis of governability caused by the inability of strategic actors to solve conflicts based on rules and procedures. The present review aims to describe how the creation of violence surveillance systems (observatories) contributes to strengthening governability and the creation of effective public policies. It was developed an analysis of the required components for the existence of governability and its relationship with the role of observatories in cities to provide reliable, timely and representative information that allows the formulation of strategies and policies. Governability is enriched with the legitimacy granted by the public from the results obtained by the governments in the formulation, implementation, evaluation of public policies and the evidence-based decisions in public health.


Tangram solved? Prefrontal cortex activation analysis during geometric problem solving.
Recent neuroimaging studies have implicated prefrontal and parietal cortices for mathematical problem solving. Mental arithmetic tasks have been used extensively to study neural correlates of mathematical reasoning. In the present study we used geometric problem sets (tangram tasks) that require executive planning and visuospatial reasoning without any linguistic representation interference. We used portable optical brain imaging (functional near infrared spectroscopy--fNIR) to monitor hemodynamic changes within anterior prefrontal cortex during tangram tasks. Twelve healthy subjects were asked to solve a series of computerized tangram puzzles and control tasks that required same geometric shape manipulation without problem solving. Total hemoglobin (HbT) concentration changes indicated a significant increase during tangram problem solving in the right hemisphere. Moreover, HbT changes during failed trials (when no solution found) were significantly higher compared to successful trials. These preliminary results suggest that fNIR can be used to assess cortical activation changes induced by geometric problem solving. Since fNIR is safe, wearable and can be used in ecologically valid environments such as classrooms, this neuroimaging tool may help to improve and optimize learning in educational settings.


Absence of intraocular infections after hematopoietic stem cell transplantation at a single center: the experience with current preventive regimens.
To investigate the prevalence of intraocular infections after allogeneic stem cell transplantation (allo-SCT). The study design was a single institutional retrospective noncomparative cohort of 135 consecutive patients in 2006 and 2007 who underwent allo-SCT for hematological malignancy. The primary outcome was the development of intraocular infections after allo-SCT and secondary outcome consisted of development of other ocular disorders during follow-up. The most frequent ocular sequel to allo-SCT included ocular graft-versus-host disease (GvHD), which developed in 37/135 patients (27%). Intraocular infection occurred in 1 of 135 patients (0.7%). This patient developed infectious chorioretinitis together with osteomyelitis, endocarditis, and brain abscess with fungus Scedosporium and was successfully treated with a combination of voriconazole, amphotericine B, and surgical interventions. Viral and/or bacterial intraocular infections were not observed at all. Intraocular infections after allo-SCT are currently uncommon due to systematic use of preemptive treatment regimens, frequent controls, and early treatment of systemic infections.


Genetic Variation of the Endangered Neotropical Catfish Steindachneridion scriptum (Siluriformes: Pimelodidae).
Steindachneridion scriptum is an important species as a resource for fisheries and aquaculture; it is currently threatened and has a reduced occurrence in South America. The damming of rivers, overfishing, and contamination of freshwater environments are the main impacts on the maintenance of this species. We accessed the genetic diversity and structure of S. scriptum using the DNA barcode and control region (D-loop) sequences of 43 individuals from the Upper Uruguay River Basin (UUR) and 10 sequences from the Upper Paraná River Basin (UPR), which were obtained from GenBank. S. scriptum from the UUR and the UPR were assigned in two distinct molecular operational taxonomic units (MOTUs) with higher inter-specific K2P distance than the optimum threshold (OT = 0.0079). The COI Intra-MOTU distances of S. scriptum specimens from the UUR ranged from 0.0000 to 0.0100. The control region indicated a high number of haplotypes and low nucleotide diversity, compatible with a new population in recent expansion process. Genetic structure was observed, with high differentiation between UUR and UPR basins, identified by BAPS, haplotype network, AMOVA (FST = 0.78, p < 0.05) and Mantel test. S. scriptum from the UUR showed a slight differentiation (FST = 0.068, p < 0.05), but not isolation-by-distance. Negative values of Tajima's D and Fu's Fs suggest recent demographic oscillations. The Bayesian skyline plot analysis indicated possible population expansion from beginning 2,500 years ago and a recent reduction in the population size. Low nucleotide diversity, spatial population structure, and the reduction of effective population size should be considered for the planning of strategies aimed at the conservation and rehabilitation of this important fisheries resource.


Living in the "land of no"? Consumer perceptions of healthy lifestyle portrayals in direct-to-consumer advertisements of prescription drugs.
Direct-to-consumer advertising (DTCA) of prescription drugs is the most common form of health communication Americans are exposed to. The effects of DTCA on prescription requests and utilization are well established, but little is known about the effects of advertisements on health behaviors. Many advertisements, especially those promoting drugs to prevent or treat cardiovascular disease, refer to lifestyle change as a way to improve health. However, no studies have examined how consumers interpret these frequently ambiguous messages. We used in-depth interviews with 45 participants, recruited in Los Angeles, USA between April 2007 and July 2008, to explore perceptions of 5 advertisements for drugs that prevent or treat cardiovascular disease (Lipitor(®), Vytorin(®), Zetia(®), Caduet(®), Plavix(®)). We found that participants interpreted advertising messages within their own life context and identified four trajectories for enacting behavior change versus taking prescription drugs: Negotiators, Avoiders, Embracers and Jumpstarters. Underlying these four typologies were beliefs about whether lifestyle change was something an individual could do or was willing to do. Our results also show how an advertisement narrative could potentially shift perceptions of causality by suggesting that high cholesterol is primarily hereditary, thereby obviating the need for lifestyle change. Some participants stated that they would prefer lifestyle change to a particular prescription drug, but felt that others would be more likely to embrace taking a prescription drug. This "Third Person Effect" may be masking participants' intentions by identifying a more socially desirable route to therapeutic change. These findings raise questions about how the typologies are distributed in the population and how advertising may shift consumers' beliefs over time, thereby contributing to new forms of medicalization. Effective regulation of DTCA may require expanding scrutiny beyond the accuracy of claims about benefits and risks, to also considering the broader narratives in which these claims are made.


[Space-time organization of neuronal activity in the frog tectum and its transformation in response to different visual stimuli].
The space and time organization of neuronal activity was studied in the frog tectum opticum under the action of different visual stimuli. It is shown that inhibition plays an important role in neuronal reactions. It is suggested that differences in the space time parameters of neuronal activity reflect differences in visual signals which bring optic information from the retina.


Mast cells mediate hyperoxia-induced airway hyper-reactivity in newborn rats.
Premature infants are at increased risk of developing airway hyper-reactivity (AHR) after oxidative stress and inflammation. Mast cells contribute to AHR partly by mediator release, so we sought to determine whether blocking mast cell degranulation or recruitment prevents hyperoxia-induced AHR, mast cell accumulation, and airway smooth muscle (ASM) changes. Rats were exposed at birth to air or 60% O2 for 14 d, inducing significantly increased AHR in the latter group, induced by nebulized methacholine challenge and measured by forced oscillometry. Daily treatment (postnatal d 1-14) with intraperitoneal cromolyn prevented hyperoxia-induced AHR, as did treatment with imatinib on postnatal d 5-14, compared with vehicle treated controls. Cromolyn prevented mast cell degranulation in the trachea but not hilar airways and blocked mast cell accumulation in the hilar airways. Imatinib treatment completely blocked mast cell accumulation in tracheal/hilar airway tissues. Hyperoxia-induced AHR in neonatal rats is mediated, at least in part, via the mast cell.


Role of regulatory non-coding RNAs in traumatic brain injury.
Traumatic brain injury (TBI) is a potentially fatal health event that cannot be predicted in advance. After TBI occurs, it can have enduring consequences within both familial and social spheres. Yet, despite extensive efforts to improve medical interventions and tailor healthcare services, TBI still remains a major contributor to global disability and mortality rates. The prompt and accurate diagnosis of TBI in clinical contexts, coupled with the implementation of effective therapeutic strategies, remains an arduous challenge. However, a deeper understanding of changes in gene expression and the underlying molecular regulatory processes may alleviate this pressing issue. In recent years, the study of regulatory non-coding RNAs (ncRNAs), a diverse class of RNA molecules with regulatory functions, has been a potential game changer in TBI research. Notably, the identification of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other ncRNAs has revealed their potential as novel diagnostic biomarkers and therapeutic targets for TBI, owing to their ability to regulate the expression of numerous genes. In this review, we seek to provide a comprehensive overview of the functions of regulatory ncRNAs in TBI. We also summarize regulatory ncRNAs used for treatment in animal models, as well as miRNAs, lncRNAs, and circRNAs that served as biomarkers for TBI diagnosis and prognosis. Finally, we discuss future challenges and prospects in diagnosing and treating TBI patients in the clinical settings.


Direct conversion of fibroblasts into stably expandable neural stem cells.
Recent advances have suggested that direct induction of neural stem cells (NSCs) could provide an alternative to derivation from somatic tissues or pluripotent cells. Here we show direct derivation of stably expandable NSCs from mouse fibroblasts through a curtailed version of reprogramming to pluripotency. By constitutively inducing Sox2, Klf4, and c-Myc while strictly limiting Oct4 activity to the initial phase of reprogramming, we generated neurosphere-like colonies that could be expanded for more than 50 passages and do not depend on sustained expression of the reprogramming factors. These induced neural stem cells (iNSCs) uniformly display morphological and molecular features of NSCs, such as the expression of Nestin, Pax6, and Olig2, and have a genome-wide transcriptional profile similar to that of brain-derived NSCs. Moreover, iNSCs can differentiate into neurons, astrocytes, and oligodendrocytes. Our results demonstrate that functional NSCs can be generated from somatic cells by factor-driven induction.


[Plastic closure of wounds and trophic ulcers in patients with diabetic foot syndrome by relief autoshred].
This article describes the features of the surgical treatment of patients with diabetes mellitus complicated with diabetic foot syndrome. Results of autodermoplasty of acute and chronic skin damages with ripped and flat skin graft in 185 patients who were treated in the clinic of general surgery of I.Ya. Horbachevsky Ternopil State Medical University, Ukraine, in the period from 2007 to 2012 Using of this method leads to improved cosmetic and functional results in 81.7% of patients with reducing of treatment duration up to 12 days.


Flow Mediated Dilation in Systemic Sclerosis: Association with clinical findings, capillaroscopic patterns and endothelial circulating markers.
Endothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns. 57 SSc patients and 37 healthy subjects were recruited. All included subjects underwent radial artery FMD test and Nailfold Video-Capillaroscopy; serum levels of Vascular Endothelial Growth Factor (VEGF), Vascular Cell Adhesion Molecule-1 (VCAM-1) and angiopoietin-2 were evaluated. Compared to healthy subjects, in SSc patients lower FMD and higher time needed to obtain the maximal FMD responsewere observed, whereas serum levels of VEGF, VCAM-1, and angiopoietin-2 were significantly higher. The impairment of FMD values was associated with disease duration, pulmonary arterial hypertension, and digital ulcers and correlates with greater microvascular damage evaluated by Nailfold Video-Capillaroscopy… An inverse relationship between VEGF, angiopoietin-2, VCAM-1 levels and FMD was observed, but only VEGF and angiopoietin-2 were significantly higher in patients with digital ulcers and pulmonary arterial hypertension. FMD ultrasound test and circulating levels of endothelial dysfuncion markers could be useful as biomarkers of vasculopathy and could be a helpful tool in the overall assessment of vascular injury in Systemic Sclerosis patients.


Complicated airway due to unexpected lingual tonsil hypertrophy.
We report an unexpected failed laryngeal mask airway in a patient with unrecognized lingual tonsil hypertrophy (LTH). A 19-year-old obese woman presented for extraction of multiple teeth via intravenous general anesthesia. Surgery was interrupted due to a laryngospasm midway through the procedure. The laryngospasm required the existing laryngeal mask airway to be removed so the patient could be suctioned. Although it is unclear the extent of obstruction caused by LTH, the surgery had to be postponed due to the discovery of enlarged lingual tonsils, which prevented endotracheal intubation. One reason for unexpected difficult airways is attributed to LTH. It is recognized that LTH is more common in patients with obstructive sleep apnea; however, LTH also has an increased prevalence in obese children with prior palatine tonsillectomies or adenoidectomies. Unexpected LTH can complicate general anesthesia by making placement of a laryngeal mask airway difficult. Thus, further research needs to be conducted to gain a deeper understanding on how to reduce the risks presented by LTH during sedation surgeries.


Combined therapeutic application of botulinum toxin type A, low-frequency rTMS, and intensive occupational therapy for post-stroke spastic upper limb hemiparesis.
For spastic upper limb hemiparesis after stroke, we developed triple-element protocol of botulinum toxin type A (BoNTA) injection, low-frequency repetitive transcranial magnetic stimulation (LF-rTMS), and intensive occupational therapy (OT). Aim. To investigate the safety and feasibility of the protocol. Design. A preliminary study. Setting. At a university hospital. Population. Fourteen post-stroke patients with spastic upper limb hemiparesis (mean age: 54.9±9.2 years, time after onset: 87.1±48.2 months, ±SD). In all patients, BoNTA was injected into spastic muscles of the affected upper limb (maximum total dose: 240 units). Four weeks later, they were hospitalized to receive 22 sessions of 20-min LF-rTMS and 120-min intensive OT daily over 15 days. Motor function of the affected upper limb was evaluated mainly using Fugl-Meyer Assessment (FMA), Wolf Motor Function Test (WMFT), motor activity log (MAL), and the severity of spasticity was measured with modified Ashworth scale (MAS) at BoNTA injection, discharge and four weeks post-discharge. All patients completed the protocol without any adverse effects. The FMA score and MAL scores, but not WMFT performance time, improved significantly at discharge. The MAS score of all examined muscles decreased significantly between BoNTA and discharge. The beneficial effect of the protocol on motor function and spasticity was almost maintained until four weeks after discharge. The protocol is safe and feasible, although further larger studies are needed to confirm its efficacy. The protocol is a potentially useful neurorehabilitative approach for this patient population.


Depletion of neutrophil extracellular traps in vivo results in hypersusceptibility to polymicrobial sepsis in mice.
Although the formation of neutrophil (PMN) extracellular traps (NETs) has been detected during infection and sepsis, their role in vivo is still unclear. This study was performed in order to evaluate the influence of NETs depletion by administration of recombinant human (rh)DNase on bacterial spreading, PMN tissue infiltration and inflammatory response in a mouse model of polymicrobial sepsis. In a prospective controlled double-armed animal trial, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). After CLP, mice were treated with rhDNase or phosphate buffered saline, respectively. Survival, colony forming unit (CFU) counts in the peritoneal cavity, lung, liver and blood were determined. PMN and platelet counts, IL-6 and circulating free (cf)-DNA/NETs levels were monitored. PMN infiltration, as well as organ damage, was analyzed histologically in the lungs and liver. Capability and capacity of PMN to form NETs were determined over time. cf-DNA/NETs were found to be significantly increased 6, 24, and 48 hours after CLP when compared to the levels determined in sham and naïve mice. Peak levels after 24 hours were correlated to enhanced capacity of bone marrow-derived PMN to form NETs after ex vivo stimulation with phorbol-12-myristate-13-acetate at the same time. rhDNase treatment of mice resulted in a significant reduction of cf-DNA/NETs levels 24 hours after CLP (P < 0.001). Although overall survival was not affected by rhDNase treatment, median survival after 24 hours was significantly lower when compared with the CLP group (P < 0.01). In mice receiving rhDNase treatment, CFU counts in the lung (P < 0.001) and peritoneal cavity (P < 0.05), as well as serum IL-6 levels (P < 0.001), were found to be already increased six hours after CLP. Additionally, enhanced PMN infiltration and tissue damage in the lungs and liver were found after 24 hours. In contrast, CFU counts in mice without rhDNase treatment increased later but more strongly 24 hours after CLP (P < 0.001). Similarly, serum IL-6 levels peaked after 24 hours (P < 0.01). This study shows, for the first time, that depletion of NETs by rhDNase administration impedes the early immune response and aggravates the pathology that follows polymicrobial sepsis in vivo.


A review of the first five years of the University of Arizona telepsychiatry programme.
We performed a retrospective review of the first five years of activity in the University of Arizona Telepsychiatry Programme. The programme began in 1998 as part of a telemedicine service for underserved rural areas. Over the first five years, 1086 teleconsultations were carried out for a total of 206 patients. There were 159 adult (77%) and 47 paediatric patients (23%). During the study period, the racial/ethnic diversity of the paediatric patients increased, as did the number of follow-up visits for adult patients (average 5.3/patient). These trends suggested that telepsychiatry became an integral part of the mental health service system at the six referring sites. Adult patients completed 81 satisfaction surveys (51%) and psychiatrists completed 47 (23%). The responses showed that providers and patients found telepsychiatry services satisfactory, although in a minority of teleconsultations (18% for providers and 17% for patients) equipment problems were distracting. The continued use of the services suggests that the telepsychiatry programme fills a service gap in rural areas of the state.


A case of disseminated Cryptococcosis with skin eruption in a patient with acute leukemia.
Disseminated cryptococcosis is a life-threatening infection caused by Cryptococcus neoformans and cutaneous dissemination occurs in 10-15% of patients. We report a case of a 49-y-old leukemic patient with disseminated cryptococcosis who presented with fever, headache, normal cerebrospinal fluid profile and multiple skin lesions mimicking molluscum contagiosum.


Insurance status, not race, is associated with mortality after an acute cardiovascular event in Maryland.
It is unclear how lack of health insurance or otherwise being underinsured contributes to observed racial disparities in health outcomes related to cardiovascular disease. To determine the relative risk of death associated with insurance and race after hospital admission for an acute cardiovascular event. Prospective cohort study in three hospitals in Maryland representing different demographics between 1993 and 2007. Patients with an incident admission who were either white or black, and had either private insurance, state-based insurance or were uninsured. 4,908 patients were diagnosed with acute myocardial infarction, 6,759 with coronary atherosclerosis, and 1,293 with stroke. Demographic and clinical patient-level data were collected from an administrative billing database and neighborhood household income was collected from the 2000 US Census. The outcome of all-cause mortality was collected from the Social Security Death Master File. In an analysis adjusted for race, disease severity, location, neighborhood household income among other confounders, being underinsured was associated with an increased risk of death after myocardial infarction (relative hazard, 1.31 [95 % CI: 1.09, 1.59]), coronary atherosclerosis (relative hazard, 1.50 [95 % CI: 1.26, 1.80]) or stroke (relative hazard, 1.25 [95 % CI: 0.91, 1.72]). Black race was not associated with an increased risk of death after myocardial infarction (relative hazard, 1.03 [95 % CI: 0.85, 1.24]), or after stroke (relative hazard, 1.18 [95 % CI: 0.86, 1.61]) and was associated with a decreased risk of death after coronary atherosclerosis (relative hazard, 0.82 [95 % CI: 0.69, 0.98]). Race was not associated with an increased risk of death, before or after adjustment. Being underinsured was strongly associated with death among those admitted with myocardial infarction, or a coronary atherosclerosis event. Our results support growing evidence implicating insurance status and socioeconomic factors as important drivers of health disparities, and potentially racial disparities.


A two-part phase I trial of high-dose interleukin 2 in combination with soluble (Chinese hamster ovary) interleukin 1 receptor.
Our purpose was to determine the maximum tolerated dose and toxicity associated with soluble Chinese hamster ovary [s(CHO)] recombinant human interleukin (IL) 1 receptor (IL-1R; Immunex, Seattle, WA) administration in humans and to determine the effective biological dose and/or maximum tolerated dose of the s(CHO) IL-1R in combination with high-dose IL-2 as determined by reduction in IL-2 toxicity and modulation of its biological effects. Twenty-seven patients with metastatic cancer were treated with escalating doses of s(CHO) IL-1R at 1, 1, 5, 10, 20, 40, and 55 mg/m2 i.v. on days -6 (except cohort 2), 1, and 15 and IL-2 at doses of 300,000 IU/kg (cohort 1) and 600,000 IU/kg (cohorts 2-7) i.v. every 8 h on days 1-5 and 15-19. No toxicity directly attributable to s(CHO) IL-1R was observed. The median number of IL-2 doses was 23. Hypotension and neurotoxicity were the major dose-limiting toxicities for the IL-2/s(CHO) IL-1R combination. Of the 24 patients treated with full-dose IL-2, there were six responses, three complete and three partial (response rate, 25%). Three patients developed thyroid dysfunction, and all 3 responding melanoma patients exhibited vitiligo. The t1/2 of s(CHO) IL-1R alone was 24-30 h and was not significantly altered by coadministration with IL-2. Whole-blood functional assays indicated that sufficient s(CHO) IL-1R was present in the circulation at top dose levels to inhibit the in vitro effects of IL-1beta on IL-8 induction; however, no effect on IL-2-induced IL-8 induction, or on the IL-1beta- or IL-2-induced tumor necrosis factor production, was observed. Suppression of IL-2-mediated tumor necrosis factor alpha and IL-6 induction in vivo during the first 24 h after IL-2 administration was observed, and the neutrophil chemotactic defect normally seen with IL-2 was not observed. IL-1R antagonist induction far exceeded that seen previously with IL-2 alone. No inhibition of either serum C-reactive protein induction or enhanced urinary nitrate excretion and no consistent effect on IL-2-related changes in peripheral blood mononuclear cell phenotype or endothelial adhesion molecule expression were seen. The coadministration of s(CHO) IL-1R produced no apparent reduction in IL-2 clinical toxicity manifested by either the ability to administer more IL-2 than anticipated or a reduction in the toxicity associated with a given amount of IL-2. Therefore, no effective biological dose could be identified for the s(CHO) IL-1R.


Pleuropulmonary blastoma with intrabronchial extension.
A 3-year-old male presented with an episode of respiratory distress that was superimposed on a 2 1/2 years history of recurrent chest infections. The chest radiograph and a contrast enhanced CT scan revealed a cystic cavity in the left upper lobe with an endobronchial soft tissue mass in left bronchus. Left bronchotomy and removal of the endobronchial soft tissue mass and left upper lobectomy were performed. The histology of the specimen revealed a pleuropulmonary blastoma (PPB) type II. The presentation, diagnosis, and management of this uncommon case of PPB with intrabronchial extension are described.


Guttate psoriasis triggered by perianal streptococcal dermatitis in a four-year-old boy.
Perianal streptococcal dermatitis (PSD) is a superficial bacterial infection usually with group A beta-hemolytic streptococci. PSD is often misdiagnosed for long periods and patients are subjected to treatments for a variety of differential diagnoses without success. We report a 4-year-old boy with PSD who presented to our clinic with guttate psoriasis for 2 reasons: first, to make dermatologists aware of PSD and second, to emphasize the necessity to examine patients, particularly pediatric patients, with guttate psoriasis very thoroughly and swab both the pharynx and perianal and/or perigenital areas even when they are, or seem to be, asymptomatic for bacterial infections. Once PSD has been diagnosed, systemic antibiotic therapy with penicillin, erythromycin, roxithromycin, or azithromycin (probably augmented by topical mupirocin ointment) should be the treatment of choice. Therapy should be monitored by posttreatment perianal and throat swabs as well as a urine analysis to monitor for poststreptococcal glomerulonephritis.


Analysis of Outcomes After TKA: Do All Databases Produce Similar Findings?
Use of large clinical and administrative databases for orthopaedic research has increased exponentially. Each database represents unique patient populations and varies in their methodology of data acquisition, which makes it possible that similar research questions posed to different databases might result in answers that differ in important ways. (1) What are the differences in reported demographics, comorbidities, and complications for patients undergoing primary TKA among four databases commonly used in orthopaedic research? (2) How does the difference in reported complication rates vary depending on whether only inpatient data or 30-day postoperative data are analyzed? Patients who underwent primary TKA during 2010 to 2012 were identified within the National Surgical Quality Improvement Programs (NSQIP), the Nationwide Inpatient Sample (NIS), the Medicare Standard Analytic Files (MED), and the Humana Administrative Claims database (HAC). NSQIP is a clinical registry that captures both inpatient and outpatient events up to 30 days after surgery using clinical reviewers and strict definitions for each variable. The other databases are administrative claims databases with their comorbidity and adverse event data defined by diagnosis and procedure codes used for reimbursement. NIS is limited to inpatient data only, whereas HAC and MED also have outpatient data. The number of patients undergoing primary TKA from each database was 48,248 in HAC, 783,546 in MED, 393,050 in NIS, and 43,220 in NSQIP. NSQIP definitions for comorbidities and surgical complications were matched to corresponding International Classification of Diseases, 9 Revision/Current Procedural Terminology codes and these coding algorithms were used to query NIS, MED, and HAC. Age, sex, comorbidities, and inpatient versus 30-day postoperative complications were compared across the four databases. Given the large sample sizes, statistical significance was often detected for small, clinically unimportant differences; thus, the focus of comparisons was whether the difference reached an absolute difference of twofold to signify an important clinical difference. Although there was a higher proportion of males in NIS and NSQIP and patients in NIS were younger, the difference was slight and well below our predefined threshold for a clinically important difference. There was variation in the prevalence of comorbidities and rates of postoperative complications among databases. The prevalence of chronic obstructive pulmonary disease (COPD) and coagulopathy in HAC and MED was more than twice that in NIS and NSQIP (relative risk [RR] for COPD: MED versus NIS 3.1, MED versus NSQIP 4.5, HAC versus NIS 3.6, HAC versus NSQIP 5.3; RR for coagulopathy: MED versus NIS 3.9, MED versus NSQIP 3.1, HAC versus NIS 3.3, HAC versus NSQIP 2.7; p < 0.001 for all comparisons). NSQIP had more than twice the obesity as NIS (RR 0.35). Rates of stroke within 30 days of TKA had more than a twofold difference among all databases (p < 0.001). HAC had more than twice the rates of 30-day complications at all endpoints compared with NSQIP and more than twice the 30-day infections as MED. A comparison of inpatient and 30-day complications rates demonstrated more than twice the amount of wound infections and deep vein thromboses is captured when data are analyzed out to 30 days after TKA (p < 0.001 for all comparisons). When evaluating research utilizing large databases, one must pay particular attention to the type of database used (administrative claims, clinical registry, or other kinds of databases), time period included, definitions utilized for specific variables, and the population captured to ensure it is best suited for the specific research question. Furthermore, with the advent of bundled payments, policymakers must meticulously consider the data sources used to ensure the data analytics match historical sources. Level III, therapeutic study.