Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease.
Recent data has indicated that the traditional view of Parkinson's disease (PD) as an isolated disorder of the nigrostriatal dopaminergic system alone is an oversimplification of its complex symptomatology. Aside from classical motor deficits, various non-motor symptoms including autonomic dysfunction, sensory and cognitive impairments as well as neuropsychiatric alterations and sleep disturbances are common in PD. Some of these non-motor symptoms can even antedate the motor problems. Many of them are associated with extranigral neuropathological changes, such as extensive α-synuclein pathology and also neuroinflammatory responses in specific brain regions, i.e. microglial activation, which has been implicated in several aspects of PD pathogenesis and progression. However, microglia do not represent a uniform population, but comprise a diverse group of cells with brain region-specific phenotypes that can exert beneficial or detrimental effects, depending on the local phenotype and context. Understanding how microglia can be neuroprotective in one brain region, while promoting neurotoxicity in another, will improve our understanding of the role of microglia in neurodegeneration in general, and of their role in PD pathology in particular. Since neuroinflammatory responses are in principle modifiable, such approaches could help to identify new targets or adjunctive therapies for the full spectrum of PD-related symptoms.


[Stabilization of biological membranes with various acetylene amines].
In experiments with mitochondrial membranes and membranes of the endoplasmatic reticulum of the rats' liver the membrane-stabilizing action of a number of unsaturated amines was evaluated. The acetylene compounds studied reduced the extent of the membranes damage following UV-irradiation, treatment with detergents and their incubation in a hypoosmotic medium. Such an action displayed gutimine and sovcaine. Hydrated compounds, analogues of acetylene amines are devoid of the ability to raise the resistance of the cellular organoids membranes to damaging factors


Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel.
Diagnostic laboratories gather phenotypic data through requisition forms, but there is no consensus as to which data are essential for variant interpretation. The ClinGen Cardiomyopathy Variant Curation Expert Panel defined a phenotypic data set for hypertrophic cardiomyopathy (HCM) variant interpretation, with the goal of standardizing requisition forms. Phenotypic data elements listed on requisition forms from nine leading cardiomyopathy testing laboratories were compiled to assess divergence in data collection. A pilot of 50 HCM cases was implemented to determine the feasibility of harmonizing data collection. Laboratory directors were surveyed to gauge potential for adoption of a minimal data set. Wide divergence was observed in the phenotypic data fields in requisition forms. The 50-case pilot showed that although demographics and assertion of a clinical diagnosis of HCM had 86% to 98% completion, specific phenotypic features, such as degree of left ventricular hypertrophy, ejection fraction, and suspected syndromic disease, were completed only 24% to 44% of the time. Nine data elements were deemed essential for variant classification by the expert panel. Participating laboratories unanimously expressed a willingness to adopt these data elements in their requisition forms. This study demonstrates the value of comparing and sharing best practices through an expert group, such as the ClinGen Program, to enhance variant interpretation, providing a foundation for leveraging cumulative case-level data in public databases and ultimately improving patient care.


Improving Outcomes in Patients With Sepsis.
Sepsis mortality may be improved by early recognition and appropriate treatment based on evidence-based guidelines. An intervention was developed that focused on earlier identification of sepsis, early antimicrobial administration, and an educational program that was disseminated throughout all hospital units and services. There were 1331 patients with sepsis during the intervention period and 1401 patients with sepsis during the control period. After controlling for expected mortality, patients in the intervention period had 30% lower odds of dying (odds ratio = 0.70, 95% confidence interval [CI] = 0.57 to 0.84). They also had 1.07 fewer days on average in the intensive care unit (95% CI = -1.98 to -0.16), 2.15 fewer hospital days (95% CI = -3.45 to -0.86), and incurred on average $1949 less in hospital costs, although the effect on costs was not statistically significant. Continued incremental improvement and sustainment is anticipated through organizational oversight, continued education, and initiation of an automated electronic sepsis alert function.


Variations in the recruitment of syntactic knowledge contribute to SES differences in syntactic development.
Average differences in children's language abilities by socioeconomic status (SES) emerge early in development and predict academic achievement. Previous research has focused on coarse-grained outcome measures such as vocabulary size, but less is known about the extent to which SES differences exist in children's strategies for comprehension and learning. We measured children's (N = 98) comprehension of passive sentences to investigate whether SES differences are more pronounced in overall knowledge of the construction or in more specific abilities to process sentences during real-time interpretation. SES differences in comprehension emerged when syntactic revision of passives was necessary, and disappeared when the need to revise was removed. Further, syntactic revision but not knowledge of the passive best explained the association between SES and a standardized measure of syntactic development. These results demonstrate that SES differences in syntactic development may result from how children recruit syntactic information within sentences.


The future of urban water services in Latin America.
In recent decades, problems with the provision of drinking water and sanitation services around the world have increasingly been addressed by attempts at privatisation, recasting clean water as an essentially economic, rather than public, good. This approach gained particular acceptance in Latin America, but with limited success. In order to address the full range of social, economic and environmental values necessary to sustain water resources over time, public and governmental involvement in establishing integrated water management, pursuing 'soft path' approaches, assuring stakeholder input and setting policy will be essential to the process.


Comparison of the effect of aromatherapy with Jasminum officinale and Salvia officinale on pain severity and labor outcome in nulliparous women.
Using non-pharmacological pain relief methods for reducing labor pain has always been one of the major concerns in obstetrics and gynecology. Comparing the effects of aromatherapy with jasmine and salvia on pain severity and labor outcome in nulliparous women. In this randomized clinical trial, 156 nulliparous women in labor were randomly selected and divided into salvia, jasmine, and control groups (52 in each group). The study duration was 6 months (from October 2009 to March 2010). Each group underwent aromatherapy using an incense mask for 15 min (distilled water for the control group). Pain severity was measured before and 30 and 60 min after the incense aromatherapy. Also, duration of the first and second stages of labor, first- and fifth-minute APGAR scores of the baby, and the frequency of labor type were measured and recorded in each group. In comparison to the other groups, pain severity and duration of the first and second stages of labor were significantly lower in the aromatherapy group of salvia 30 min after the intervention (P = 0.001). However, no significant difference was found among the three groups regarding pain severity 60 min after the aromatherapy, first- and fifth-minute APGAR scores of the baby, and the frequency of labor type. The results of the present study indicated that aromatherapy with saliva had beneficial effects on pain relief, shortened the labor stages, and had no negative impact on the baby's APGAR score.


Relapsing Thrombotic Thrombocytopenic Purpura (TTP) in a Patient Treated with Infliximab for Chronic Uveitis.
To report a case of relapsing thrombotic thrombocytopenic purpura (TTP) in a patient treated with infliximab for chronic uveitis. A 57-year-old African American woman with chronic anterior and intermediate uveitis, treated with infliximab for more than 1 year, presented with fatigue, dark colored urine, and ecchymosis on her extremities. She was diagnosed with thrombotic thrombocytopenic purpura (TTP) and recovered after treatment. After a remission period of 8 months, she was treated again with infliximab for recurrent intraocular inflammation. She developed a relapse of TTP 4 weeks after reintroducing infliximab. Relapsing thrombotic thrombocytopenic purpura can be a rare complication associated with infliximab. To our knowledge, it has not been reported in the literature to date.


Hydration: The New FIFA World Cup's Challenge for Referee Decision Making?
Various continental sporting events have exposed team sports referees to different environmental conditions. Several studies have focused on strategies to prevent athlete performance impairment induced by heat or warm (or both) conditions, but few authors have investigated the effect of heat on referees' performance. In a thermoneutral environment, referees' physical activity induced mild 2.0% dehydration, which was responsible for reductions in physical, psychomotor, and cognitive performances. Therefore, the hydration status of referees should be taken into account to reduce referees' errors and misjudgments in the heat.


Effects of early human handling on the pain sensitivity of young lambs.
Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species.


A new approach to practical acute toxicity testing.
A method for the investigation of the acute toxicity of an unknown chemical substance, with an estimation on the LD50, is described. Using this, it is possible to obtain with 13 experimental animals adequate information on the acute toxicity and on the LD50. This method has no limitations and applies to drugs, agricultural and industrial chemicals. It can be used for every route of administration.


Mass spawning in tropical reef corals.
Synchronous multispecific spawning by a total of 32 coral species occurred a few nights after late spring full moons in 1981 and 1982 at three locations on the Great Barrier Reef, Australia. The data invalidate the generalization that most corals have internally fertilized, brooded planula larvae. In every species observed, gametes were released; external fertilization and development then followed. The developmental rates of externally fertilized eggs and longevities of planulae indicate that planulae may be dispersed between reefs.


Tumor-infiltrating B cell immunoglobulin variable region gene usage in invasive ductal breast carcinoma.
A major focus of tumor immunology is to reveal the potential role and capacity of immunocompetent cells found in different solid tumor tissues. The most abundant infiltrating cells (TIL), the T lymphocytes have been investigated in details concerning T-cell receptor usage and specificity. However, B cells have hardly been investigated in this respect, although high cellular B-cell infiltration has been correlated with improved patients' survival in some breast carcinomas. This led to our objectives to study variable region gene usage of the tumor-infiltrating B cells in different breast carcinoma types. By defining the immunoglobulin repertoire of the tumor-infiltrating B lymphocytes in the most common invasive ductal carcinoma (IDC) of the breast we compared it to the rare medullary breast carcinoma (MBC). After phenotyping infiltrating ductal carcinomas, B cells were obtained from tumor tissue by microdissection technique. Numerous rearranged TIL-B immunoglobulin heavy chain V genes (VH) were amplified, cloned, sequenced, and comparatively analyzed. Some characteristics were found for both breast carcinoma types. The immunoglobulins produced by TIL-B in ductal carcinoma are highly matured and oligoclonal. We conclude that Ig variable region gene usage reveals similar and distinguishable characteristics of TIL-B immunoglobulin repertoires, which are representative of the nature of the immune responses in invasive ductal and medullary breast carcinomas.


Hemagglutinating and chemotactic properties of synthetic peptide segments of fimbrial protein from Porphyromonas gingivalis.
Porphyromonas gingivalis 381 fimbriae, their synthetic peptide segments, and lipopolysaccharide (LPS) were examined for hemagglutinating and migration-stimulating activities. P. gingivalis 381 fimbriae clearly caused hemagglutination, and several oligopeptide segments such as FP381(61-80), FP381(171-185), and FP381(302-321), corresponding to the amino acid residue numbers based on the amino acid sequence of fimbrillin proposed by Dickinson et al. (D. P. Dickinson, M. A. Kubiniec, F. Yoshimura, and R. J. Genco, J. Bacteriol. 170:1658-1665, 1988), were also demonstrated to agglutinate erythrocytes although less effectively than the native fimbriae. Furthermore, P. gingivalis 381 LPS but not Escherichia coli O55:B5 LPS definitely exhibited hemagglutination. P. gingivalis fimbriae as well as their synthetic peptides possessing hemagglutinating activity enhanced the chemotaxically induced migration of human peripheral blood monocytes. The results of the analyses using synthetic peptide FP381(61-80), its related compounds, and an analog suggested that the amino acid sequence XLTXXLTXXNXX within fimbrial protein molecules may play an important role structurally in the attachment of the protein to host cells such as erythrocytes and monocytes.


Drug sourcing and motivations among a sample of people involved in the supply of pharmaceutical drugs in Australia.
The non-medical use (NMU) of pharmaceuticals is increasing internationally, along with mortality. Previous research indicates that end-users access pharmaceuticals through social networks, however little is known about supplier sources particularly outside the US. This study examined sourcing and motivations among a sample of people involved in pharmaceutical diversion and supply in Australia. Semi-structured, telephone interviews were conducted with 51 people involved in supplying pharmaceuticals in the previous six months. Multi-stage recruitment involved the distribution of flyers to participants of two Australian drug-monitoring programs: the Ecstasy and related Drugs Reporting System (capturing regular psycho-stimulant users) and the Illicit Drug Reporting System (capturing people who regularly inject drugs), followed by a screening of interested participants. Interviews were audio-recorded, transcribed and analysed using a mixed methods approach. First, correlates of drug sourcing and motivations were examined including demographics, frequency and quantity of supply. Second, thematic analysis of the qualitative data was undertaken on strategies for obtaining the drugs and motivating factors. Drug supplies were sourced from a variety of medical and non-medical sources, primarily legitimately obtained prescriptions (47%), friends or family (18%) and dealers (14%). Suppliers using medical sources were more likely to be unemployed/retired and reported supplying for therapeutic purposes, while suppliers using non-medical sources were more likely to be employed/students, earned higher incomes and reported supplying for recreational purposes. Those who sourced via doctor shopping (IRR = 47.5) and friends and family (IRR = 10.1) distributed higher quantities, while those who sourced legitimately obtained prescriptions (IRR = 0.1) and from illicit drug dealers (IRR = 0.0) distributed lower quantities. Similar proportions supplied for financial (65%) and altruistic (61%) reasons, however the latter supplied lower quantities (IRR = 0.1). This study offers novel insight into the diversion of pharmaceuticals from the supplier perspective. A nuanced policy approach is required to address varied supply practices by source and motive.


Impact of Sahara dust transport on Cape Verde atmospheric element particles.
The objectives of this study were to (1) conduct an elemental characterization of airborne particles sampled in Cape Verde and (2) assess the influence of Sahara desert on local suspended particles. Particulate matter (PM(10)) was collected in Praia city (14°94'N; 23°49'W) with a low-volume sampler in order to characterize its chemical composition by k0-INAA. The filter samples were first weighed and subsequently irradiated at the Portuguese Research Reactor. Results showed that PM(10) concentrations in Cape Verde markedly exceeded the health-based air quality standards defined by the European Union (EU), World Health Organization (WHO), and U.S. Environmental Protection Agency (EPA), in part due to the influence of Sahara dust transport. The PM(10) composition was characterized essentially by high concentrations of elements originating from the soil (K, Sm, Co, Fe, Sc, Rb, Cr, Ce, and Ba) and sea (Na), and low concentrations of anthropogenic elements (As, Zn, and Sb). In addition, the high concentrations of PM measured in Cape Verde suggest that health of the population may be less affected compared with other sites where PM(10) concentrations are lower but more enriched with toxic elements.


Experts offer differing views on the impact of a recession.
What are the risks of a prolonged recession for hospitals? Although health care would probably not be hurt as much as other industries by a lengthy downturn, financial experts are saying a continuation of the current soft economy would add to hospitals' already long list of financial woes. The coming recession "will exacerbate the problems for hospitals already facing fiscal stress," says Glenn Wagner, an investment banking consultant based in New York City.


Fate of frog embryos implanted into forelimbs of adults.
No teratoma formation and very little growth and differentiation followed implantation of late gastrula-stage frog embryos into forelimbs of adults. This is attributed to poor blood supply and rigid walls of muscle and bone surrounding the implants. The fate of embryos in nonamputated limbs is compared with that of regeneration-promoting implants in amputated limbs.


Effective production of glycosyl-steviosides by alpha-1,6 transglucosylation of dextrin dextranase.
Dextrin dextranase (EC 126.96.36.199; DDase), which is produced by Acetobacter capsulatus ATCC 11894, acted on a mixture of stevioside and starch hydrolysate with isoamylase, so that the enzyme was found to convert stevioside to predominantly mono-glucosyl-stevioside (SG1) and di-glucosyl-stevioside (SG2), and little of the stevioside initially added remained. SG1 was separated into two compounds (SG1a and SG1b) by reversed-phase high-pressure liquid chromatography. The structures of SG1a, SG1b, and SG2 were analyzed and concluded to be 13-O-(6-alpha-glucosyl-2-beta-glucosyl-beta-glucosyl)-19-O-beta-glucosyl -steviol, 13-O-[(6-alpha-glucosyl)(2-beta-glucosyl)-beta-glucosyl]-19-O- glucosyl-steviol, and 13-O-[(6-alpha-glucosyl)(6-alpha-glucosyl-2-beta- glucosyl)-beta-glucosyl]-19-O-beta-glucosyl-steviol, respectively. During the reaction for production of glycosyl-steviosides, DDase catalyzes transglucosylations from glucosyl donor compounds to stevioside to be SG1a and SG1b, and to SG1b to be SG2 rapidly forming alpha-1,6 glucosidic linkages. However transglucosylation to SG1a to be SG2 rarely occurred, and the conversions among stevioside and these glycosyl-steviosides were catalyzed by the action of DDase to transfer alpha-1,6 linked glucosyl residues, forming alpha-1,6 linkages.


Sarcoptic manage in wildlife.
Sarcoptic manage caused by Sarcoptes scabiei is responsible for epizootic disease in populations of wild canids in North America, Europe and Australia, wild cats in Europe and Africa, wild ungulates and wild boars in Europe, wombats and koalas in Australia, and great apes and various wild bovids in Africa. Although short-term mortality may appear devastating, in a self-sustaining population, mortality is non-compensatory and a mange epizootic generally does not affect long-term population dynamics. Alternatively, the net effect of a mange epizootic can have serious consequences in remnant or fragmented populations of CITES-listed, threatened, or endangered species where loss of even a few individuals can be critical to the survival or restoration of a species (CITES: Convention on International Trade in Endangered Species of Wild Fauna and Flora). The pathogenesis and concordant clinical symptoms of mange depends on the immune status of the respective host. Naïve, immunocompromised or anergic animals that are unable to evoke hypersensitivity responses develop an extensive epidermal hyperkeratosis usually without marked alopecia, but with an underlying chronic dermal inflammation and an abundance of mites in the skin. Immunocompetent hosts are able to develop strong types I and IV hypersensitivity responses that result in a marked decrease and eventual loss of mites in the skin. However, there are dramatic structural and functional changes in the skin; it becomes extensively thickened, greyish in colour and there is a marked eosinophilia throughout the epidermis and dermis. There is often almost complete alopecia. Isolation and treatment of infected individuals may be warranted, and has met with some success in small remaining populations of certain highly endangered species.


Evaluation of emerging NASH therapies: the impact of treatment efficacy profiles on long-term health outcomes.
Aim: Evaluations of nonalcoholic steatohepatitis (NASH) treatments require predicting lifetime outcomes from short-term clinical trials. Materials & methods: A Markov model with NASH fibrosis stages F0-F3, NASH resolution, compensated cirrhosis (F4/CC), and liver-related complication (LRC) states was developed using literature-based standard of care (SoC) data. Hypothetical efficacy profiles were defined affecting resolution (100%-increase), fibrosis improvement (100% increase), or fibrosis worsening (50% decrease). Results: For the SoC, 10-year LRC rates increased with baseline fibrosis stage (F1: 3.0%; F2: 9.8%; F3: 27.2%; F4/CC: 64.9%). The fibrosis worsening profile reduced predicted 10-year LRC rates (F1: 1.9%; F2: 6.5%; F3: 19.1%; F4/CC: 55.0%) more than the resolution and fibrosis improvement profiles (F1: 2.6%/2.6%; F2: 8.5%/8.3%; F3: 23.3%/23.0%; F4/CC: NA/59.0%). Scenario analyses considered alternative SoC progression, treatment efficacy and treatment-stopping rules. Conclusion: Potential NASH efficacy profiles have differing impacts on predicted long-term outcomes, providing insights for future stakeholders.


Vandetanib Versus placebo in patients with advanced non-small-cell lung cancer after prior therapy with an epidermal growth factor receptor tyrosine kinase inhibitor: a randomized, double-blind phase III trial (ZEPHYR).
Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor (EGFR), and RET signaling. This placebo-controlled trial assessed whether vandetanib conferred an overall survival benefit in patients with advanced non-small-cell lung cancer (NSCLC) after prior treatment with an EGFR tyrosine kinase inhibitor and one or two chemotherapy regimens. Eligible patients were randomly assigned 2:1 to receive vandetanib 300 mg/d or placebo until disease progression or unacceptable toxicity. The primary objective was to compare the outcomes between the two arms with respect to overall survival. Overall, 924 patients received vandetanib (n = 617) or placebo (n = 307). No significant increase in overall survival was detected in the vandetanib cohort compared with placebo (hazard ratio = 0.95; 95.2% CI, 0.81 to 1.11; P = .527); median overall survival was 8.5 months versus 7.8 months for vandetanib and placebo patients, respectively. Statistically significant advantages favoring vandetanib were observed for progression-free survival (hazard ratio = 0.63; P < .001) and objective response rate (2.6% v 0.7%; P = .028). Postprogression therapy was balanced across the cohorts in both number and type. Adverse events were generally consistent with previous NSCLC studies of vandetanib 300 mg; common events occurring with a greater frequency in the vandetanib arm versus placebo included diarrhea (46% v 11%), rash (42% v 11%), and hypertension (26% v 3%). The study did not demonstrate an overall survival benefit for vandetanib versus placebo. There was a higher incidence of some adverse events with vandetanib.


Mammographic abnormalities of the skin and subcutaneous tissues.
Primary attention is often directed toward examination of the breast parenchyma rather than the skin and subcutaneous tissue. Important radiographic changes should not be overlooked in this latter area because they may be the only sign of disease within the breast or draw attention to accompanying pathologic change in the underlying breast tissue. Three categories of abnormality are seen in the skin and subcutaneous tissue: (1) skin thickening, either diffuse or focal; (2) calcifications; and (3) subcutaneous masses. Examples of these are illustrated, and imaging strategies, including ultrasound and CT, are discussed.


Neomyogenesis in 3D Dynamic Responsive Prosthesis for Inguinal Hernia Repair.
Despite undisputed improvements, prosthetics hernia repair continues to be affected by unacceptable rates of complications. Postoperative adverse events such as discomfort and chronic pain represent a subject of increasing concern among the surgical community. Poor quality biologic response, stiff scar plates, and mesh shrinkage, a typical effect of conventional static meshes and plugs, are all indicated as the main reasons for many of the complications related to inguinal hernia repair. Even the conventional concept of treatment based upon a supposed reinforcement of the groin consequent to the fibrotic incorporation of meshes, would appear to be inadequate in the light of the latest scientific evidence concerning the degenerative genesis of inguinal hernia. Following these recent studies, a newly conceived 3D dynamically responsive implant has been developed. It concerns a multilamellar shaped prosthesis, intended to be placed fixation-free to obliterate the hernia defect. This 3D structure has already demonstrated to induce a probiotic biological response with development of viable tissue, instead of the fibrotic plaque typical of conventional meshes. Newly formed elastic fibers, neo-angiogenesis, and neo-nerve genesis in a surrounding of well perfused connective tissue are the typical elements of the biologic response in the newly conceived implant. In addition to these elements, muscle fibers have also been detected in the implant structure. The aim of this research was to determine the ingrowth of muscle fibers in the implant by assessing the quantity and quality of muscle development in the short, medium, and long term post-implantation. Histological examination of biopsy samples excised from patients who underwent dynamic hernia repair with the 3D dynamic implant showed the presence of muscular elements that in the short term could be described as multiple spots of myocytes in the early stage of development. Over the mid- to long-term, muscle fibers increased in number and level of maturation, assuming the typical aspect of standard muscle bundles in the final phase. Effectively, long term, myocytes histologically evidenced the distinctive arrangement of the muscle structure, with nuclei and striated elements being similar to normal muscle elements. The development of this highly specialized connective tissue in the 3D dynamic responsive implant seems to document the finalization of an enhanced biologic response leading to the ingrowth of typical tissue components of the groin. Reverting degenerative pathogenesis into effective regeneration recognized in the newly conceived 3D prosthesis would appear to represent a significant concept change in the repair of inguinal hernias.


Approximate Green's Function Coupled Cluster Method Employing Effective Dimension Reduction.
The Green's function coupled cluster (GFCC) method, originally proposed in the early 1990s, is a powerful many-body tool for computing and analyzing the electronic structure of molecular and periodic systems, especially when electrons of the system are strongly correlated. However, in order for the GFCC to become a method that may be routinely used in the electronic structure calculations, robust numerical techniques and approximations must be employed to reduce its extremely high computational overhead. In our recent studies, it has been demonstrated that the GFCC equations can be solved directly in the frequency domain using iterative linear solvers, which can be easily distributed in a massively parallel environment. In the present work, we demonstrate a successful application of model-order-reduction (MOR) techniques in the GFCC framework. Briefly speaking, for a frequency regime of interest that requires high-resolution descriptions of spectral function, instead of solving the GFCC linear equation of full dimension for every single frequency point of interest, an efficiently solvable linear system model of a reduced dimension may be built upon projecting the original GFCC linear system onto a subspace. From this reduced order model is obtained a reasonable approximation to the full dimensional GFCC linear equations in both interpolative and extrapolative spectral regions. Here, we show that the subspace can be properly constructed in an iterative manner from the auxiliary vectors of the GFCC linear equations at some selected frequencies within the spectral region of interest. During the iterations, the quality of the subspace, as well as the linear system model, can be systematically improved. The method is tested in this work in terms of the efficiency and accuracy of computing spectral functions for some typical molecular systems such as carbon monoxide, 1,3-butadiene, benzene, and adenine. To reach the same level of accuracy as that of the original GFCC method, the application of MOR in the GFCC method is able to significantly lower the original computational cost for the aforementioned molecules in designated frequency regimes. As a byproduct, the reduced order model obtained by this method is found to provide a high-quality initial guess, which improves the convergence rate for the existing iterative linear solver.


Stress and mental health among midlife and older gay-identified men.
We investigated associations between stress and mental health (positive affect, depressive symptoms) among HIV-negative and HIV-positive midlife and older gay-identified men, along with the mediating and moderating effects of mastery and emotional support. We also studied the mental health effects of same-sex marriage. We obtained data from self-administered questionnaires completed in 2009 or 2010 by a subsample (n = 202; average age = 56.91 years; age range = 44-75 years) of participants in the University of California, Los Angeles component of the Multicenter AIDS Cohort Study, one of the largest and longest-running natural-history studies of HIV/AIDS in the United States. Both sexual minority stress (perceived gay-related stigma, excessive HIV bereavements) and aging-related stress (independence and fiscal concerns) appeared to have been detrimental to mental health. Sense of mastery partially mediated these associations. Being legally married was significantly protective net of all covariates, including having a domestic partner but not being married. Education, HIV status, and race/ethnicity had no significant effects. Sexual minority and aging-related stress significantly affected the emotional lives of these men. Personal sense of mastery may help to sustain them as they age. We observed specific mental health benefits of same-sex legal marriage.


Current status of experimental chemical carcinogenesis and its applications to human cancer risk.
The history of chemical carcinogenesis is a record of the observations of physicians and epidemiologists of the relation between the occurrence of uncommon cancers in humans and the exposures of those people to certain chemical agents. In parallel with some of these findings, experimental animal models were developed to imitate the findings in humans. From these experimental studies has been obtained most of the information we have about the mechanisms of chemical carcinogenesis. Many of the biochemical studies have focused on liver cancer which might be an inappropriate general model for chemically induced cancer, liver cancer being comparatively rare in humans. It is not known to what extent exposures to any particular chemical carcinogens are responsible for the major human cancers, and the agents responsible for most of them are not known. It is probable that many noncarcinogenic chemicals act as promotors of carcinogenesis, and among these alcohol can be included as in important contributor.


Psychological trauma and posttraumatic stress disorder: risk factors and associations with birth outcomes in the Drakenstein Child Health Study.
Prenatal and peripartum trauma may be associated with poor maternal-fetal outcomes. However, relatively few data on these associations exist from low-middle income countries, and populations in transition. We investigated the prevalence and risk factors for maternal trauma and posttraumatic stress disorder (PTSD), and their association with adverse birth outcomes in the Drakenstein Child Health Study, a South African birth cohort study. Pregnant women were recruited from two clinics in a peri-urban community outside Cape Town. Trauma exposure and PTSD were assessed using diagnostic interviews; validated self-report questionnaires measured other psychosocial characteristics. Gestational age at delivery was calculated and birth outcomes were assessed by trained staff. Multiple logistic regression explored risk factors for trauma and PTSD; associations with birth outcomes were investigated using linear regression. Potential confounders included study site, socioeconomic status (SES), and depression. A total of 544 mother-infant dyads were included. Lifetime trauma was reported in approximately two-thirds of mothers, with about a third exposed to past-year intimate partner violence (IPV). The prevalence of current/lifetime PTSD was 19%. In multiple logistic regression, recent life stressors were significantly associated with lifetime trauma, when controlling for SES, study site, and recent IPV. Childhood trauma and recent stressors were significantly associated with PTSD, controlling for SES and study site. While no association was observed between maternal PTSD and birth outcomes, maternal trauma was significantly associated with a 0.3 unit reduction (95% CI: 0.1; 0.5) in infant head-circumference-for-age z-scores (HCAZ scores) at birth in crude analysis, which remained significant when adjusted for study site and recent stressors in a multivariate regression model. In this exploratory study, maternal trauma and PTSD were found to be highly prevalent, and preliminary evidence suggested that trauma may adversely affect fetal growth, as measured by birth head circumference. However, these findings are limited by a number of methodological weaknesses, and further studies are required to extend findings and delineate causal links and mechanisms of association.


[Effects of exercise interventions in early psychosis: a qualitative review].
Several studies show positive effects of exercise interventions on physical and mental health in patients with early psychosis. However, the patient's perspective concerning the experienced effects on functioning often remains unmentioned due to the quantitative study designs. To summarize the experiences of patients with early psychosis regarding the psychological, physical and social functioning after participating in a lifestyle intervention to improve physical activity. Systematized literature review in MEDLINE/PubMed, Embase and PsycINFO. The search led to 101 publications, of which six qualitative studies were included describing the experiences of early psychosis patients after participating in an exercise intervention. The results show three main themes of recovery or improvement regarding the psychological, physical and social functioning. Obstacles to participation range from psychotic symptoms, anxiety and negative thoughts to insufficient financial resources. Exercise interventions on early psychotic patients seem to restore or improve: self-image, self-confidence and/or self-esteem; physical activity, energy level, vitality and fitness and to reduce social exclusion. However, conclusions should be interpreted with some caution due to the large heterogeneity and methodological limitations in the six studies.


Modulation of outflow resistance by the pores of the inner wall endothelium.
The juxtacanalicular connective tissue (JCT) is widely believed to generate the bulk of aqueous humor outflow resistance, while the pores of the inner wall endothelium are thought to generate at most 10% of this resistance in humans. However, the hydrodynamic interaction of these two components of the aqueous outflow system, which arises because of their spatial proximity, has only recently been considered. Modelling the JCT as a homogeneously distributed porous material upstream of a low porosity filter (the inner wall endothelium), the pores of the inner wall are found to cause a "funneling effect," in which the aqueous humor flows preferentially through those regions of the JCT nearest the inner wall pores. The bulk of the pressure drop occurs in the immediate proximity of the pores (within three pore radii). This greatly increases the apparent flow resistance of the JCT. For a set of parameters characterizing the normal eye, this enhancement is approximately 30-fold. The conclusion of this study is that changes in inner wall porosity may greatly affect aqueous outflow resistance, despite the low flow resistance of the inner wall pores themselves.


Evaluation of Risk Factors for Second Hip Fractures in Elderly Patients.
Hip fracture is a worldwide public health problem that primarily affects osteoporotic individuals and the elderly. A second hip fracture can occur in elderly patients who have already suffered an initial hip fracture. The aim of this study was to investigate possible risk factors for second hip fractures in elderly patients with hip fractures. Between 2010 and 2014, 230 patients who underwent uncemented bipolar hemiarthroplasty for hip fractures were retrospectively analyzed. The patients were divided into two groups: those with a first hip fracture (group 1) and those with a second hip fracture (group 2). The mean time from the first hip fracture to second hip fracture was 22 months. There were no significant differences in the American Society of Anesthesiologist scores, comorbidities were observed in the two groups. The mean length of hospitalization was not significantly different between the two groups. The mean postoperative functional scores after second hip fractures were significantly lower in group 2 than in group 1. Although there are not certain risk factors for second hip fractures in elderly patients with hip fractures, to prevent second hip fractures, elderly patients should be provided with physical and medical therapy as well as orthotic support and their functional activity should be maintained.


Propensity-Weighted Comparison of Long-Term Risk of Urinary Adverse Events in Elderly Women Treated For Cervical Cancer.
Cervical cancer treatment is associated with a risk of urinary adverse events (UAEs) such as ureteral stricture and vesicovaginal fistula. We sought to measure the long-term UAE risk after surgery and radiation therapy (RT), with confounding controlled through propensity-weighted models. From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women ≥66 years old with nonmetastatic cervical cancer treated with simple surgery (SS), radical hysterectomy (RH), external beam RT plus brachytherapy (EBRT+BT), or RT+surgery. We matched them to noncancer controls 1:3. Differences in demographic and cancer characteristics were balanced by propensity weighting. Grade 3 to 4 UAEs were identified by diagnosis codes plus treatment codes. Cumulative incidence was measured using Kaplan-Meier methods. The hazard associated with different cancer treatments was compared using Cox models. UAEs occurred in 272 of 1808 cases (17%) and 222 of 5424 (4%) controls; most (62%) were ureteral strictures. The raw cumulative incidence of UAEs was highest in advanced cancers. UAEs occurred in 31% of patients after EBRT+BT, 25% of patients after RT+surgery, and 15% of patients after RH; however, after propensity weighting, the incidence was similar. In adjusted Cox models (reference = controls), the UAE risk was highest after RT+surgery (hazard ratio [HR], 5.07; 95% confidence interval [CI], 2.32-11.07), followed by EBRT+BT (HR, 3.33; 95% CI, 1.45-7.65), RH (HR, 3.65; 95% CI, 1.41-9.46) and SS (HR, 0.99; 95% CI, 0.32-3.01). The higher risk after RT+surgery versus EBRT+BT was statistically significant, whereas, EBRT+BT and RH were not significantly different from each other. UAEs are common after cervical cancer treatment, particularly in patients with advanced cancers. UAEs are more common after RT, but these women tend to have the advanced cancers. After propensity weighting, the risk after RT was similar to that after surgery.


Postpartum psychiatric disorders.
This review summarises the psychiatry of the puerperium, in the light of publications during the past 5 years. A wide variety of disorders are seen. Recognition of disorders of the mother-infant relationship is important, because these have pernicious long-term effects but generally respond to treatment. Psychoses complicate about one in 1000 deliveries. The most common is related to manic depression, in which neuroleptic drugs should be used with caution. Post-traumatic stress disorder, obsessions of child harm, and a range of anxiety disorders all require specific psychological treatments. Postpartum depression necessitates thorough exploration. Cessation of breastfeeding is not necessary, because most antidepressant drugs seem not to affect the infant. Controlled trials have shown the benefit of involving the child's father in therapy and of interventions promoting interaction between mother and infant. Owing to its complexity, multidisciplinary specialist teams have an important place in postpartum psychiatry.


Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model.
One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.


Sequential anaerobic-aerobic biodegradation of emerging insensitive munitions compound 3-nitro-1,2,4-triazol-5-one (NTO).
Insensitive munitions, such as 3-nitro-1,2,4-triazol-5-one (NTO), are being considered by the U.S. Army as replacements for conventional explosives. Environmental emissions of NTO are expected to increase as its use becomes widespread; but only a few studies have considered the remediation of NTO-contaminated sites. In this study, sequential anaerobic-aerobic biodegradation of NTO was investigated in bioreactors using soil as inoculum. Batch bioassays confirmed microbial reduction of NTO under anaerobic conditions to 3-amino-1,2,4-triazol-5-one (ATO) using pyruvate as electron-donating cosubstrate. However, ATO biodegradation was only observed after the redox condition was switched to aerobic. This study also demonstrated that the high-rate removal of NTO in contaminated water can be attained in a continuous-flow aerated bioreactor. The reactor was first fed ATO as sole energy and nitrogen source prior to NTO addition. After few days, ATO was removed in a sustained fashion by 100%. When NTO was introduced together with electron-donor (pyruvate), NTO degradation increased progressively, reaching a removal efficiency of 93.5%. Mineralization of NTO was evidenced by the partial release of inorganic nitrogen species in the effluent, and lack of ATO accumulation. A plausible hypothesis for these findings is that NTO reduction occurred in anaerobic zones of the biofilm whereas ATO was mineralized in the bulk aerobic zones of the reactor.


Distribution of virulence markers among Vibrio vulnificus isolates of clinical and environmental origin and regional characteristics in Japan.
Vibrio vulnificus is an opportunistic human pathogen that is widely distributed in estuarine environments and is capable of causing necrotizing fasciitis and sepsis. In Japan, based on epidemiological research, the incidences of V. vulnificus were concentrated in Kyusyu, mainly in coastal areas of the Ariake Sea. To examine the virulence potential, various genotyping methods have recently been developed. This study aimed to investigate the distribution of virulence markers among V. vulnificus isolates of clinical and environmental origin in three coastal areas with different infection incidences and to determine whether these isolates have the siderophore encoding gene viuB. We examined the distribution of genotypes of the 16S ribosomal ribonucleic acid (rRNA) gene, vvhA, vcg, and capsular polysaccharide (CPS), and the presence of viuB in 156 isolates collected from patients and environmental samples in Japan. The environmental samples were collected from three coastal areas: the Ariake Sea, Ise & Mikawa Bay, and Karatsu Bay. The results showed disparity in the ratios of genotypes depending on the sample origins. V. vulnificus isolates obtained from patients were classified into the clinical type for all genotypes. In the environmental isolates, the ratios of the clinical type for genotypes of the 16S rRNA gene, vvhA, and vcg were in the order of the Ariake Sea>Ise & Mikawa Bay>Karatsu Bay. Meanwhile, CPS analysis showed no significant difference. Most isolates possessed viuB. Many V. vulnificus belonging to the clinical type existed in the Ariake Sea. Three coastal areas with different infection incidences showed distinct ratios of genotypes. This may indicate that the distribution of clinical isolates correlates with the incidence of V. vulnificus infection.


Role of beta-catenin and endocannabinoids in the nucleus accumbens in extinction in rats exposed to shock and reminders.
The response to a traumatic experience may be rapid recovery or development of psychopathology such as post-traumatic stress disorder (PTSD). Impaired extinction of fear memories is thought to contribute to the development of the persistent trauma memories and avoidance. The Wnt/β-catenin pathway and the endocannabinoid system appear to play significant roles in anxiety and depressive symptoms. Here we examined the involvement of β-catenin in the nucleus accumbens (NAc) in extinction in rats exposed to the shock and reminders model of PTSD. We found that increased β-catenin levels in the NAc were correlated with facilitated extinction kinetics in rats exposed to shock and reminders, suggesting that increased levels of NAc β-catenin are associated with a resilient response to the stressor. Furthermore, downregulating β-catenin expression in the NAc in shocked rats using sulindac (0.0178, 0.178mg/side) impaired extinction whereas upregulating the Wnt/β-catenin pathway using LiCl (2µg/side) facilitated extinction. Exposure to shock and reminders resulted in attenuated levels of the endocannabinoid N-arachidonylethanolamine (AEA) in the NAc; the cannabinoid CB1/2 receptor agonist WIN55,212-2 (5µg/side) microinjected into the NAc facilitated extinction in shocked rats. Importantly, the facilitating effect of WIN55,212-2 on extinction was blocked by co-administration of sulindac in doses that downregulated β-catenin levels. Taken together, the results suggest that β-catenin in the NAc may serve as a protective buffer against the effects of severe stress, and that inhibiting this system in the NAc may prevent the therapeutic effects of cannabinoids against stress-related disorders.


Phosphorylation of histone H3 at serine 10 has an essential role in arsenite-induced expression of FOS, EGR1 and IL8 mRNA in cultured human cell lines.
Trivalent inorganic arsenite [iAs(III)] is known to alter the expression of a number of genes associated with transcription and cell proliferation, which was thought to be one of the possible mechanisms of arsenical carcinogenesis. However, the detailed mechanisms underlying iAs(III) induction of changes in gene expression are not fully understood. Here we examine the role of histone H3 phosphorylation at serine 10 (Ser(10) ) in gene regulation when the cells were treated with iAs(III). Among the 34 genes tested, iAs(III) induced mRNA expression of JUN, FOS, EGR1, HMOX1, HSPA1A, IL8, GADD45A, GADD45B and GADD153. Phosphorylation of histone H3 Ser(10) was induced by iAs(III) in interphase cells, and was effectively blocked by the ERKs pathway inhibitor (U0126). U0126 treatment significantly reduced constitutive mRNA expression of FOS and EGR1, and dramatically suppressed the induction of FOS, EGR1 and IL8 mRNA in iAs(III)-treated cells. The other genes, which were induced by iAs(III), were not affected by U0126 treatment. When the histone H3 nonphosphorylatable mutant of serine 10 (S10A) was overexpressed in cells, iAs(III) induction of FOS, EGR1and IL8 expression was significantly decreased as compared with wild-type cells. The other genes induced by iAs(III) were not changed in S10A cells nor by U0126 treatment. In addition, S10A cells were more resistant to iAs(III) cytotoxicity. These results indicated that the phosphorylation of histone H3 at Ser(10) through the ERKs pathway in interphase cells is an important regulatory event for iAs(III)-mediated gene expression. Aberrant gene expression seems to be an important cause of cytotoxicity and may have some relation to iAs(III) carcinogenicity.


Perinatal mortality in diabetic pregnancy.
Perinatal mortality rate (PMR) is one of the most important perinatal health indicators. PMR in diabetic pregnancies varies throughout the world and is higher than the background PMR. The prevalence of pregestational diabetes is increasing and is associated with an elevated risk of congenital malformations, macrosomia, preeclampsia, and preterm delivery. The incidence of PMR in preexisting diabetes mellitus ranges considerably, with congenital abnormalities and preterm labor the main factors contributing to the higher PMR. Women with gestational diabetes mellitus or impaired glucose tolerance are a mixed group that may have low to a high PMR, especially if they require insulin in their pregnancy. All the known diabetic women should plan their pregnancies and optimize glycemic control periconceptually and throughout pregnancy, as this reduces the frequency of congenital abnormalities, obstetric complications, and perinatal mortality.


Does vitamin D status influence lumbar disc degeneration and low back pain in postmenopausal women? A retrospective single-center study.
To investigate the relationship between serum vitamin D concentration and lumbar disc degeneration (LDD) in postmenopausal women and the epidemiologic factors affecting low back pain (LBP). Between July 2017 and December 2018, 232 participants were retrospectively enrolled. Serum concentrations of bone turnover markers were measured using electrochemiluminescence assays. Disc degeneration was evaluated using the Pfirrmann grading system. Other variables were assessed using relevant questionnaires. The mean age of the women was 65.6 ± 10.1 and their serum 25(OH)D concentrations were 19.38 ± 9.21 ng/mL. The prevalences of severe vitamin D deficiency (<10 ng/mL) and normal status (>30 ng/mL) were 12.9% and 12.5%, respectively. The severely deficient group had higher visual analog scale (VAS) scores for LBP (P = 0.002) and lower bone mineral density T scores (P = 0.004) than the other groups. Lower 25(OH)D concentration (<10 ng/mL) was significantly associated with more severe LDD in the lumbosacral region (L4-S1, L1-S1, P < 0.05), but less so in the upper lumbar region. There was an inverse relationship between vitamin D concentration and the severity of disc degeneration (L2-L3, L4-S1, L1-S1, P < 0.05). After adjustment for confounding factors, smoking, vitamin D deficiency, lack of vitamin D supplementation, high body mass index, and low bone mineral density T score were associated with higher incidence of moderate-to-severe pain in postmenopausal women (P < 0.05). Vitamin D deficiency is associated with LDD and LBP in postmenopausal women. Specifically, a serum vitamin D concentration < 10 ng/mL is a marker of severe LDD and LBP. Smoking, severe vitamin D deficiency, lack of vitamin D supplementation, high body mass index, and osteoporosis are associated with a higher prevalence of moderate-to-severe pain.


Development of measures of food neophobia in children.
In order to construct a behavioral neophobia measure for children, we had 5-, 8- and 11-year-olds choose from ten novel and ten familiar foods which ones they were willing to taste. Meanwhile, their parents indicated their own willingness to taste each of the foods, predicted the children's willingness, estimated the number of times they and their children had eaten the foods, and completed trait measures of food neophobia for themselves and the children. The children's levels of behavioral neophobia were significantly related to both their levels of trait neophobia and their parents' predictions of their willingness to eat the foods (r = 0.38 and 0.34, respectively; p < 0.001). In addition, children's and parents' behavioral and trait neophobia scores were significantly related (both r = 0.31; p < 0.001). Finally, parents but not children were more neophobic with respect to foods of animal (vs. vegetable) origin.


The magnetosphere of uranus: hot plasma and radiation environment.
The low-energy charged-particle (LECP) instrument on Voyager 2 measured lowenergy electrons and ions near and within the magnetosphere of Uranus. Initial analysis of the LECP measurements has revealed the following. (i) The magnetospheric particle population consists principally of protons and electrons having energies to at least 4 and 1.2 megaelectron volts, respectively, with electron intensities substantially excceding proton intensities at a given energy. (ii) The intensity profile for both particle species shows evidence that the particles were swept by planetry satellites out to at least the orbit of Titania. (iii) The ion and electron spectra may be described by a Maxwellian core at low energies (less than about 200 kiloelectron volts) and a power law at high energies (greater than about 590 kiloelectron volts; exponentmicro, 3 to 10) except inside the orbit of Miranda, where power-law spectra (micro approximately 1.1 and 3.1 for electrons and protons, respectively) are observed. (iv) At ion energies between 0.6 and 1 megaelectron volt per nucleon, the composition is dominated by protons with a minor fraction (about 10(-3)) of molecular hydrogen; the lower limit for the ratio of hydrogen to helium is greater than 10(4). (v) The proton population is sufficiently intense that fluences greater than 10(16) per square centimeter can accumulate in 10(4) to 10(') years; such fluences are sufficient to polymerize carbon monoxide and methane ice surfaces. The overall morphology of Uranus' magnetosphere resembles that of Jupiter, as evidenced by the fact that the spacecraft crossed the plasma sheet through the dawn magnetosheath twice per planetary rotation period (17.3 hours). Uranus' magnetosphere differs from that of Jupiter and of Saturn in that the plasma 1 is at most 0.1 rather than 1. Therefore, little distortion ofthe field is expected from particle loading at distances less than about 15 Uranus radii.


Long-term followup of proximal femoral allografts.
Between 1972 and 1999, the orthopaedic service at the authors' institution treated 137 patients with proximal femoral bone lesions by resection and reconstruction with frozen allografts from cadavers. The data were entered into a computer program allowing a comprehensive analysis. Thirty-eight patients had proximal femoral osteoarticular allografts, 69 had allograft-endoprosthesis composites, 22 had intercalary allografts, and eight had an allograft arthrodesis. There were 74 complications in 54 of the 137 patients with allografts, which included 26 allograft fractures (19%), 15 infections (11%), and 20 nonunions (15%). The overall success rate for the patients with these procedures was 103 of 137 (75%) at a mean followup of 7.9 years +/- 5.6 years. If the eight patients with tumor recurrences (surgical failures rather than allograft failures) are not included, the success rate is 103 of 129 (80%). Eighty-three of these patients (55%) without any allograft complications who have been treated and followed up for at least 2 years had a 92% success rate. It is concluded that although allograft reconstruction after resection of the proximal femur for patients with aggressive or malignant tumors has a high complication rate, approximately 80% of the patients have a successful outcome.


A generalized cortico-muscular-cortical network to evaluate the effects of three-week brain stimulation.
Post-stroke transcranial magnetic stimulation (TMS) has gradually become a brain intervention to assist patients in the recovery of motor function. The long lasting regulatory of TMS may involve the coupling changes between cortex and muscles. However, the effects of multi-day TMS on motor recovery after stroke is unclear. This study proposed to quantify the effects of three-week TMS on brain activity and muscles movement performance based on a generalized cortico-muscular-cortical network (gCMCN). The gCMCN-based features were further extracted and combined with the partial least squares (PLS) method to predict the Fugl-Meyer of upper extremity (FMUE) in stroke patients, thereby establishing an objective rehabilitation method that can evaluate the positive effects of continuous TMS on motor function. We found that the improvement of motor function after three-week TMS was significantly correlated with the complexity trend of information interaction between hemispheres and the intensity of corticomuscular coupling. In addition, the fitting coefficient (R2) for predicted and actual FMUE before and after TMS were 0.856 and 0.963, respectively, suggesting that the gCMCN-based measurement may be a promising method for evaluating the therapeutic effect of TMS. From the perspective of a novel brain-muscles network with dynamic contraction as the entry point, this work quantified TMS-induced connectivity differences while evaluating the potential efficacy of multi-day TMS. It provides a unique insight for the further application of intervention therapy in the field of brain diseases.


A Logical levothyroxine dose Individualization: Optimization Approach at discharge from Radioiodine therapy ward and during follow-up in patients of Differentiated Thyroid Carcinoma: Balancing the Risk based strategy and the practical issues and challenges: Experience and Views of a large volume referral centre in India.
In this communication, the authors discuss the issue of individualization of thyrotropin suppressive therapy in differentiated thyroid carcinoma (DTC) patients and share their views with respect to optimizing the dose of levothyroxine (LT) prescription both during discharge from radioiodine therapy ward and during follow-up. The changing management paradigm at our Institute during post-thyroidectomy period and during the preparation for radioiodine scan is also briefly highlighted. Five factors can be identified as important determinants for the dose individualization approach: (1) Persistence or absence of metastatic disease, (2) the risk characteristics of the patient and the tumor (3) patient's clinical profile, symptomatology, and contraindications (4) the feasibility to ensure a proper thyroid stimulating hormone TSH suppression level (depends on patient's socio-economic and educational background, the connectivity with the local physician and his expertise) (5) time period elapsed since initial diagnosis. While discussing each individual case scenario, the authors, based upon their experience in one of the busiest thyroid cancer referral centers in the country, discuss certain unaddressed points in the current guideline recommendations, deviations made and some challenges toward employing them into practice, which could be situation and center specific. In addition to these, the value of clinical examination, patient profile and detailed enquiry about clinical symptomatology by the attending physician in each follow-up visit cannot be overemphasized. According to the authors, this aspect, quite important for dose determination in an individual, is relatively underrepresented in the present guidelines. It would also be worthwhile to follow a conservative approach (till clear data emerges) in patients who have characteristics of "high-risk" disease, but are clinically and biochemically disease free, if no medical contraindications exist and patient tolerates the suppressive therapy well. This would be particularly applicable in the presence of aggressive histopathological variants, where, in the event of recurrence/metastasis, the disease demonstrates adverse prognosis and higher incidence of radioiodine refractoriness. At the end, certain important and noteworthy concepts pertaining to LT prescription that has definitive practical implications for the suppressive therapy in DTC patients are described.


[Cytophotometric expression of the tumor markers CD-34 and factor VIII in colorectal cancer].
In colorectal cancer, to describe the cytophotometric expression of the CD-34 and Factor VIII; to evaluate the degree of correlation between them; and to compare the CD-34 and Factor VIII expressions in relationship to label index and optical density. Seventeen cases of colorectal adenocarcinoma recovered from paraffin-embedded archival tissue and confirmed by hematoxilin-eosin staining, were submitted to streptavidin-biotin-peroxidase immunohistochemical method. In this process was used the tumor markers CD-34 and Factor VIII. The obtained slides were analysed using the SAMBA 4000 system with Immuno software. The results were evaluated into two parameters: label index and optical density, and expressed by averages, medians, minimum values, maximum values, and standard deviation values. The normality condition of the quantitative variables was investigated by using the Shapiro-Wilks test. In order to evaluate the degree of association between the expressions of the markers, Pearson's Correlation Coefficient or Spearman's Correlation Coefficient were applied. To evaluate the comparison degree of the markers expression, Student's t test or Wilcoxon's no parametric test were used. For the CD-34 there was no data normality for the label index and there was normality in the optical density. For the Factor VIII, there was data normality for the label index and for the optical density. When the expressions of CD-34 and Factor VIII markers were correlated, there was no difference between them in relationship to the average label index and average optical density. When the expressions of the CD-34 and Factor VIII were compared, there was no correlation between the two variables.


[Diet and gastric cancer in Mexico and in the world].
Gastric cancer (GC) is the fourth leading cause of cancer death at global level. Diet, alcohol and tobacco, in addition to Helicobacter pylori infection, account for a large number of cases. Some substances contained in foods may influence GC carcinogenesis process; however, the underlying mechanisms have not been fully elucidated. In Mexico and worldwide, a low intake of fruits, non-starchy and allium vegetables, pulses, and foods containing selenium, as well as high intake of salt, salty, salted and smoked foods, chili pepper, processed and grilled/barbecued meats, have been respectively associated with an increased risk of GC. Based on the available evidence, programs for GC prevention and control could be developed and evaluated.


The effect of colloid formulation on colloid osmotic pressure in horses with naturally occurring gastrointestinal disease.
Naturally occurring gastrointestinal disease is an important cause of acute hypoproteinemia in adult horses and hydroxyethyl starch colloid fluid treatment is a component of supportive care in these cases to improve plasma volume and maintain colloid osmotic pressure (COP). The objectives of the present study were to compare 2 formulations of high molecular weight hydroxyethyl starch and their relative effect on COP, acid-base status, and survival of horses with acute hypoproteinemia secondary to gastrointestinal disease. Twenty adult horses, ≥ 1 year of age, were prospectively enrolled, with informed client consent, if they developed acute hypoproteinemia, defined as a plasma total protein <5.0 g/dL or albumin <2.2 g/dL during hospitalization while undergoing treatment for gastrointestinal disease. Horses were randomly assigned to receive a rapid infusion of either 6% hydroxyethyl starch in 0.9% saline or 6% hydroxyethyl starch in lactated ringers solution at a dose of 10 ml/kg. Venous blood gas analysis, COP, and PCV were evaluated before and after colloid administration. For both groups, average COP prior to treatment was 11.0 mmHg (9.7 - 12.2 mmHg) and post colloid treatment was 13.2 mmHg (12.0 -14.7 mmHg) [Normal range 18 - 22 mmHg]. COP was significantly increased with colloid treatment (p<0.001) but this increase was not significantly different between treatment groups. Venous pH did not change significantly with treatment. Twelve horses survived to hospital discharge and survival did not differ significantly between treatment groups. Post-treatment COP improved approximately 20% regardless of the formulation used, however, values did not reach the normal range of COP observed in healthy horses. Acid-base parameters were not significantly impacted by either treatment. Further study is needed to determine how these two products compare with regards to other outcome measures. Evaluation of the relative effects of colloid formulation in horses with clinical disease is a future area of interest.


Orofacial characteristics of adolescents with diagnosed spinal disorders.
The objective of the current epidemiological study is to show the correlation of various postural abnormalities and spinal deformities and the clinically identifiable dentofacial anomalies by orthodontic examination. Twenty-three children with Scheuermann's disease [mean age: 14 years 8 months; standard deviation (SD): 1 year 8 months] and 28 with scoliosis (mean age: 14 years 7 months; SD: 2 years 3 months) participated in the study. Standardized orthodontic screening protocols were used to map the occlusal relations in the sagittal, vertical, and horizontal dimensions; the space relations of the maxillary and mandibular frontal segment; the temporomandibular joint (TMJ) status; and the facial asymmetries. Statistically significant differences (p<0.05) were found between the values of the examined groups of patients for the following measurements: incisal overjet and overbite, upper and lower midline deviation, mandibular frontal spacing, TMJ pathological symptoms and functional characteristics, and frequency of facial asymmetries. A large percentage of patients with pre-pubertal developments of spinal deformities have various dentofacial anomalies. The majority of these anomalies are present in patients with Scheuermann's disease. Early treatment of the malocclusions closely correlated to postural disorders should minimize the progression of the dentofacial anomalies, making necessary performing orthodontic screening of these patients as early as possible.


Intercellular Communication between Hepatic Cells in Liver Diseases.
Liver diseases are perpetuated by the orchestration of hepatocytes and other hepatic non-parenchymal cells. These cells communicate and regulate with each other by secreting mediators such as peptides, hormones, and cytokines. Extracellular vesicles (EVs), small particles secreted from cells, contain proteins, DNAs, and RNAs as cargos. EVs have attracted recent research interests since they can communicate information from donor cells to recipient cells thereby regulating physiological events via delivering of specific cargo mediators. Previous studies have demonstrated that liver cells secrete elevated numbers of EVs during diseased conditions, and those EVs are internalized into other liver cells inducing disease-related reactions such as inflammation, angiogenesis, and fibrogenesis. Reactions in recipient cells are caused by proteins and RNAs carried in disease-derived EVs. This review summarizes cell-to-cell communication especially via EVs in the pathogenesis of liver diseases and their potential as a novel therapeutic target.


Steatorrhea and weight loss in a 72-year-old man: primary biliary cirrhosis? Celiac disease? Bacterial overgrowth? What else?
Unintentional weight loss is an ominous sign, particularly when it occurs in the elderly; concern for malignancy is especially worrisome. In this report, we describe a 72-yr-old man who presented with weight loss and was found to have massive steatorrhea. An extensive evaluation revealed evidence of primary biliary cirrhosis (PBC), celiac disease, and small intestinal bacterial overgrowth. No malignancy was identified. The weight loss was attributed to severe steatorrhea due, in part, to intraluminal bile salt deficiency, small bowel mucosal disease, and bacterial overgrowth. Several points are discussed regarding gastrointestinal function in elderly patients with chronic liver disease secondary to PBC. The rare association between PBC and celiac disease in adults is also discussed. Finally, we suggest that bacterial overgrowth plays a significant role in the development of steatorrhea in some persons with PBC and that an assessment for bacterial overgrowth should be performed on persons with steatorrhea and PBC.


Samples from subdivided populations yield biased estimates of effective size that overestimate the rate of loss of genetic variation.
Many empirical studies estimating effective population size apply the temporal method that provides an estimate of the variance effective size through the amount of temporal allele frequency change under the assumption that the study population is completely isolated. This assumption is frequently violated, and the magnitude of the resulting bias is generally unknown. We studied how gene flow affects estimates of effective size obtained by the temporal method when sampling from a population system and provide analytical expressions for the expected estimate under an island model of migration. We show that the temporal method tends to systematically underestimate both local and global effective size when populations are connected by gene flow, and the bias is sometimes dramatic. The problem is particularly likely to occur when sampling from a subdivided population where high levels of gene flow obscure identification of subpopulation boundaries. In such situations, sampling in a manner that prevents biased estimates can be difficult. This phenomenon might partially explain the frequently reported unexpectedly low effective population sizes of marine populations that have raised concern regarding the genetic vulnerability of even exceptionally large populations.


Reinforced carbon nanotubes as electrically conducting and flexible films for space applications.
Chemical vapor deposition (CVD)-grown entangled carbon nanotube (CNT) sheets are characterized by high electrical conductivity and durability to bending and folding. However, since freestanding CNT sheets are mechanically weak, they cannot be used as stand-alone flexible films. In this work, polyimide (PI) infiltration into entangled cup-stacked CNT (CSCNT) sheets was studied to form electrically conducting, robust, and flexible films for space applications. The infiltration process preserved CNTs' advantageous properties (i.e., conductivity and flexibility), prevented CNT agglomeration, and enabled CNT patterning. In particular, the CNT-PI films exhibited ohmic electrical conductance in both the lateral and vertical directions, with a sheet resistivity as low as 122 Ω/□, similar to that of as-grown CNT sheets, with minimal effect of the insulating matrix. Moreover, this high conductivity was preserved under mechanical and thermal manipulations. These properties make the reported CNT-PI films excellent candidates for applications where flexibility, thermal stability, and electrical conductivity are required. Particularly, the developed CNT-PI films were found to be durable in space environment hazards such as high vacuum, thermal cycling, and ionizing radiation, and hence they are suggested as an alternative for the electrostatic discharge (ESD) protection layer in spacecraft thermal blankets.


Disturbance alters relationships between soil carbon pools and aboveground vegetation attributes in an anthropogenic peatland in Patagonia.
Anthropogenic-based disturbances may alter peatland soil-plant causal associations and their ability to sequester carbon. Likewise, it is unclear how the vegetation attributes are linked with different soil C decomposition-based pools (i.e., live moss, debris, and poorly- to highly-decomposed peat) under grassing and harvesting conditions. Therefore, we aimed to assess the relationships between aboveground vegetation attributes and belowground C pools in a Northern Patagonian peatland of Sphagnum magellanicum with disturbed and undisturbed areas. We used ordination to depict the main C pool and floristic gradients and structural equation modeling (SEM) to explore the direct and indirect relationships among these variables. In addition, we evaluated whether attributes derived from plant functional types (PFTs) are better suited to predict soil C pools than attributes derived from species gradients. We found that the floristic composition of the peatland can be classified into three categories that follow the C pool gradient. These categories correspond to (1) woody species, such as Baccharis patagonica, (2) water-logged species like Juncus procerus, and (3) grasslands. We depicted that these classes are reliable indicators of soil C decomposition stages. However, the relationships change between management. We found a clear statistical trend showing a decrease of live moss, debris, and poorly-decomposed C pools in the disturbed area. We also depicted that plant diversity, plant height, and PFT composition were reliable indicators of C decomposition only under undisturbed conditions, while the species-based attributes consistently yielded better overall results predicting soil C pools than PFT-based attributes. Our results imply that managed peatlands of Northern Patagonia with active grassing and harvesting activities, even if small-scaled, will significantly alter their future C sequestration capacities by decreasing their live and poorly-decomposed components. Finally, aboveground vegetation attributes cannot be used as proxies of soil C decomposition in disturbed peatlands as they no longer relate to decomposition stages.


Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity.
Seasonal epidemics of influenza virus result in ∼36,000 deaths annually in the United States. Current vaccines against influenza virus elicit an antibody response specific for the envelope glycoproteins. However, high mutation rates result in the emergence of new viral serotypes, which elude neutralization by preexisting antibodies. T lymphocytes have been reported to be capable of mediating heterosubtypic protection through recognition of internal, more conserved, influenza virus proteins. Here, we demonstrate using a recombinant influenza virus expressing the LCMV GP33-41 epitope that influenza virus-specific CD8+ T cells and virus-specific non-neutralizing antibodies each are relatively ineffective at conferring heterosubtypic protective immunity alone. However, when combined virus-specific CD8 T cells and non-neutralizing antibodies cooperatively elicit robust protective immunity. This synergistic improvement in protective immunity is dependent, at least in part, on alveolar macrophages and/or other lung phagocytes. Overall, our studies suggest that an influenza vaccine capable of eliciting both CD8+ T cells and antibodies specific for highly conserved influenza proteins may be able to provide heterosubtypic protection in humans, and act as the basis for a potential "universal" vaccine.


Frequency of cancer genes on the chicken z chromosome and its human homologues: implications for sex chromosome evolution.
It has been suggested that there are special evolutionary forces that act on sex chromosomes. Hemizygosity of the X chromosome in male mammals has led to selection for male-advantage genes, and against genes posing extreme risks of tumor development. A similar bias against cancer genes should also apply to the Z chromosome that is present as a single copy in female birds. Using comparative database analysis, we found that there was no significant underrepresentation of cancer genes on the chicken Z, nor on the Z-orthologous regions of human chromosomes 5 and 9. This result does not support the hypothesis that genes involved in cancer are selected against on the sex chromosomes.


Retention, Antiretroviral Therapy Use and Viral Suppression by History of Injection Drug Use Among HIV-Infected Patients in an Urban HIV Clinical Cohort.
Compared to HIV-infected persons who do not inject drugs (non-IDU), persons who inject drugs (PWID) experience disparities in linking to medical care, initiating antiretroviral therapy (ART) and achieving viral suppression. There has been little attention to changes in these disparities over time. We estimated the proportion of PWID and non-IDU retained in care, on ART, and virally suppressed each year from 2001-2012 in the Johns Hopkins HIV Clinical Cohort (JHHCC). We defined active clinic patients as those who had ≥1 clinical visit, CD4 cell count, or viral load between July 1 of the prior year, and June 30 of the analysis year. Within a calendar year, retention was defined as ≥2 clinical visits or HIV-related laboratory measurements >90 days; ART use was defined as ≥1 ART prescription active ≥30 days; and viral suppression was defined as ≥1 HIV viral load <400 copies/mL. While PWID were less likely to be retained in earlier years, the gaps in retention closed around 2010. After 2003-2004, PWID and non-IDU retained in care had similar probability of receiving a prescription for ART and PWID and non-IDU on ART had similar probability of viral suppression.


Co-morbid anxiety disorders in bipolar disorder and major depression: familial aggregation and clinical characteristics of co-morbid panic disorder, social phobia, specific phobia and obsessive-compulsive disorder.
Co-morbidity of mood and anxiety disorders is common and often associated with greater illness severity. This study investigates clinical correlates and familiality of four anxiety disorders in a large sample of bipolar disorder (BP) and major depressive disorder (MDD) pedigrees. The sample comprised 566 BP families with 1416 affected subjects and 675 MDD families with 1726 affected subjects. Clinical characteristics and familiality of panic disorder, social phobia, specific phobia and obsessive-compulsive disorder (OCD) were examined in BP and MDD pedigrees with multivariate modeling using generalized estimating equations. Co-morbidity between mood and anxiety disorders was associated with several markers of clinical severity, including earlier age of onset, greater number of depressive episodes and higher prevalence of attempted suicide, when compared with mood disorder without co-morbid anxiety. Familial aggregation was found with co-morbid panic and OCD in both BP and MDD pedigrees. Specific phobia showed familial aggregation in both MDD and BP families, although the findings in BP were just short of statistical significance after adjusting for other anxiety co-morbidities. We found no evidence for familiality of social phobia. Our findings suggest that co-morbidity of MDD and BP with specific anxiety disorders (OCD, panic disorder and specific phobia) is at least partly due to familial factors, which may be of relevance to both phenotypic and genetic studies of co-morbidity.


Family Planning and Zika Virus: The Power of Prevention.
The connection between infection with the Zika virus (ZKV) and congenital anomalies such as microcephaly has been generally accepted. Although efforts are underway to develop preventive interventions such as vaccines, these are not yet available. Family planning is an effective preventive approach that has been underemphasized in many lists of research priorities. In addition to acquisition of ZKV from mosquitoes, sexual transmission from males to females has been documented. Women at risk of ZKV need access to effective contraception if they want to avoid or postpone pregnancy, as well as access to safe abortion. There is often overlap between areas where risk of ZKV acquisition is highest, and areas where access to reproductive health services may be more limited. Data on the impact of ZKV on contraceptive use and abortion are sparse, but a few studies have begun to address these questions. ZKV highlights the need to provide at-risk women and couples with effective means to prevent or postpone childbearing. Contraception, prenatal care, and safe abortion should be available to all women.


Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone.
Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized rat myotube model. Compound A (a lactone) and Cerivastatin (an open acid) induced apoptosis, as measured by TUNEL and active caspase 3 staining, in a concentration- and time-dependent manner. In contrast, an epimer of Compound A (Compound B) exhibited a much weaker apoptotic response. Statin-induced apoptosis was completely prevented by mevalonate or geranylgeraniol, but not by farnesol. Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was not a result of cholesterol synthesis inhibition. The geranylgeranyl transferase inhibitors GGTI-2133 and GGTI-2147 caused apoptosis in myotubes; the farnesyl transferase inhibitor FTI-277 exhibited a much weaker effect. In addition, the prenylation of rap1a, a geranylgeranylated protein, was inhibited by Compound A in myotubes at concentrations that induced apoptosis. A similar statin-induced apoptosis profile was seen in human myotube cultures but primary rat hepatocytes were about 200-fold more resistant to statin-induced apoptosis. Although the statin-induced hepatotoxicity could be attenuated with mevalonate, no effect was found with either geranylgeraniol or farnesol. In studies assessing ubiquinone levels after statin treatment in rat and human myotubes, there was no correlation between ubiquinone levels and apoptosis. Taken together, these observations suggest that statins cause apoptosis in myotube cultures in part by inhibiting the geranylgeranylation of proteins, but not by suppressing ubiquinone concentration. Furthermore, the data from primary hepatocytes suggests a cell-type differential sensitivity to statin-induced toxicity.


Oreocharisphuongii (Gesneriaceae), a new species from central Vietnam.
Oreocharisphuongii, a new species of Gesneriaceae from central Vietnam, is described and illustrated here. The new species is most similar to O.longifolia by sharing peduncles up to 22 cm long, bracts 2, zygomorphic, yellow flowers with tubular corolla, stamens 4 with two pairs of coherent anthers and capsules up to 6 cm long. It mainly differs from the latter by the combination of some morphological characters of leaves (shape, base, apex and margin), size of calyx lobes, indumentum of corolla tube and inner surface of three lower corolla lobes. Detailed morphological description together with colour illustration, information on phenology, distribution, ecology, preliminarily conservation status of the new species and comparison with its similar species are also presented.


Stress echocardiography in patients with native valvular heart disease.
Valve stress echocardiography (VSE) can be performed as exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) depending on the patient's clinical status, severity and type of valve disease. ESE combines exercise testing with two-dimensional grey scale and Doppler echocardiography during exercise. Thus, it provides objective assessment of symptomatic status (exercise test), as well as exercise-induced changes of a series of echocardiographic parameters (different depending on the valve disease type), which yield prognostic information in individual patients and help in a better treatment planning. DSE is useful in symptomatic patients with low-gradient aortic stenosis. It clarifies its severity and helps in assessing surgical risk in patients with severe disease and systolic dysfunction. It can be also used to test valve haemodynamics in asymptomatic patients with significant mitral stenosis unable to perform an exercise test or to test the left ventricle response, namely to test viability, in patients with ischaemic secondary mitral regurgitation. VSE has taught us that history taking, clinical examination and resting echocardiography give an 'incomplete picture' of the disease in patients presenting with a severe valve disease. Therefore, its use should be encouraged in such patients.


Human T lymphotropic virus I infection deregulates surface expression of the transferrin receptor.
Human T-lymphotropic virus I (HTLV-I) is an etiologic agent in adult T cell leukemia. In an effort to understand the relationship between HTLV-I infection and malignant transformation, we have examined transferrin receptor expression in HTLV-I-infected cells. Transferrin receptor expression in normal T cells is tightly regulated and essential for cell proliferation. We have used matched T cell sets originating from a normal donor, consisting of tetanus toxoid-specific normal T cell clones (TM3 and TM5) and their in vitro HTLV-I-infected counterparts (TM3H and TM5H). Using these matched sets of virus-infected and normal T cells, we have determined that HTLV-I infection leads to hyperexpression of surface transferrin receptors (five- to six-fold higher than normal counterparts). Although the growth rates of the virus-infected cells did not differ significantly from their normal controls, HTLV-I-infected cells constitutively hyperexpressed surface transferrin receptors, whereas the level of surface receptor expression of normal counterpart cells varied during the cycle of antigenic stimulation. Immunoprecipitation of total (surface plus cytoplasmic) transferrin expression showed that the HTLV-I-infected cells did not possess a greater total number of transferrin receptors than their normal counterparts. This data was supported by Northern blot analysis, which showed equivalent transferrin receptor mRNA expression in HTLV-I-infected and uninfected cells. Functional analysis revealed a marked defect in 59Fe-transferrin internalization in the HTLV-I-infected cells. Furthermore, the HTLV-I-infected cells showed markedly decreased transferrin receptor phosphorylation and internalization in response to active phorbol ester. Thus the data demonstrate that in peripheral blood T cells, HTLV-I infection is accompanied by surface transferrin receptor overexpression secondary to subcellular redistribution and defective internalization.


Testing the waters - A cross-sectional survey of views about waterbirth among Swedish health professionals.
For women with low risk births, waterbirth is an alternative that is requested and provided in approximately a hundred countries. However, in some countries, including Sweden, waterbirth is not generally available. To explore the experiences, knowledge and attitudes regarding waterbirth among midwives, obstetricians/gynaecologists and neonatologists. A cross-sectional study was conducted in Sweden, using a web-based survey distributed via The Swedish Association of Midwives and the Heads of department of all Swedish maternity wards between April and June 2016. The respondents (n = 1609) answered a combination of Likert-scale and open-ended questions. The responses were analysed with descriptive statistics and quantitative content analyses. Both midwives and physicians stated a lack of experience, knowledge and clinical guidelines related to attending and assisting waterbirths. Overall, midwives had more positive attitudes to waterbirth (38.8% vs 4.5%) as well as towards providing and implementing waterbirth, compared to physicians (71.0% vs 14.9%). Midwives stated significantly more benefits and fewer risks for women and babies, compared to physicians who requested more evidence. Opinions regarding waterbirth are to some extent based on attitudes rather than actual experience and knowledge. There are diverse interpretations of the strength of evidence and a lack of updating in the research field of waterbirth. As waterbirth is requested by women, health professionals need to update their knowledge in this topic in order to give coherent and evidence-based information and care to prospective parents.


Highs and downs: A scoping review of public opinion about cannabis, alcohol and tobacco in Canada.
Since the legalisation of cannabis in October 2018, Canada has emerged as a privileged place for research on the properties of this substance, its health effects, but also on its relation with public opinion. However, this scoping review points out the complexity of tracing the evolution of Canadian public opinion on cannabis based on available scientific data. This review follows the guidelines of the Joanna Briggs Institute and summarises more than 60 years of research on Canadians' public opinion, perception and knowledge of cannabis. The study also includes alcohol and tobacco in order to provide a meaningful comparison between substances. One hundred and sixty-one references selected from over 30 000 studies, with the oldest dating back to 1956, show that public opinion on cannabis is under-studied in Canada compared to alcohol and tobacco. Young people and students are among the most studied populations, unlike Aboriginal communities, immigrants and elderly people. The study reveals the absence of experts in public opinion and political communication, and calls for an imperative need for theoretical frameworks rooted in the work of social scientists. These findings do not suggest slowing the rate of publication on alcohol, tobacco, youth or students. Rather, they encourage increasing the rate of publication on other substances used and on other groups also targeted as being particularly at risk of misuse. New studies need to measure and contribute to the understanding of Canadian public opinion on cannabis in comparison with public policies currently in place.


CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model.
Accumulating recent evidence suggests that cannabinoid-1 (CB(1)) receptor activation may promote inflammation and cell death and its pharmacological inhibition is associated with anti-inflammatory and tissue-protective effects in various preclinical disease models, as well as in humans. In this study, using molecular biology and biochemistry methods, we have investigated the effects of genetic deletion or pharmacological inhibition of CB(1) receptors on inflammation, oxidative/nitrosative stress and cell death pathways associated with a clinically relevant model of nephropathy, induced by an important chemotherapeutic drug cisplatin. Cisplatin significantly increased endocannabinoid anandamide content, activation of p38 and JNK mitogen-activated protein kinases (MAPKs), apoptotic and poly (ADP-ribose)polymerase-dependent cell death, enhanced inflammation (leucocyte infiltration, tumour necrosis factor-alpha and interleukin-1beta) and promoted oxidative/nitrosative stress [increased expressions of superoxide-generating enzymes (NOX2(gp91phox), NOX4), inducible nitric oxide synthase and tissue 4-hydroxynonenal and nitrotyrosine levels] in the kidneys of mice, accompanied by marked histopathological damage and impaired renal function (elevated creatinine and serum blood urea nitrogen) 3 days following its administration. Both genetic deletion and pharmacological inhibition of CB(1) receptors with AM281 or SR141716 markedly attenuated the cisplatin-induced renal dysfunction and interrelated oxidative/nitrosative stress, p38 and JNK MAPK activation, cell death and inflammatory response in the kidney. The endocannabinoid system through CB(1) receptors promotes cisplatin-induced tissue injury by amplifying MAPK activation, cell death and interrelated inflammation and oxidative/nitrosative stress. These results also suggest that inhibition of CB(1) receptors may exert beneficial effects in renal (and most likely other) diseases associated with enhanced inflammation, oxidative/nitrosative stress and cell death.