Suggestive Evidence for an Antidepressant Effect of Metreleptin Treatment in Patients with Lipodystrophy

Introduction: Lipodystrophy (LD) syndromes are rare heterogeneous disorders characterized by reduction or absence of subcutaneous fat, low or nondetectable leptin concentrations in blood and impaired hunger/satiety regulation. Metreleptin treatment reverses metabolic complications and improves eating behavior in LD. Because depression in anorexia nervosa (AN), which is also characterized by hypoleptinemia, improves substantially upon treatment with metreleptin, we hypothesized that metreleptin substitution may be associated with an antidepressant effect in patients with LD, too. Methods: In this ancillary study, 10 adult patients with LD were treated with metreleptin. To assess depressive symptoms, the self-rating questionnaire Beck's Depression Inventory (BDI) was filled in at preestablished time points prior (T1) and after initiation of metreleptin (T2: 1 week; T3: 4 weeks; T4: 12 weeks) dosing. The differences between time points were tested with nonparametric Friedman's analysis of variance. Sensitivity analyses were performed upon exclusion of the BDI items addressing appetite and weight changes. Results: According to their BDI scores, 4 patients had mild depression and 2 had moderate depression at baseline. Friedman's test revealed significant differences in BDI scores between the four time points. Post hoc analyses revealed that the difference between T1 and T3 was significant upon Bonferroni correction (p = 0.034, effect size r = 0.88). The sensitivity analyses upon exclusion of the appetite and weight change items again revealed a significant Friedman's test and significant Bonferroni corrected differences in the revised BDI scores between T1 versus T2 (p = 0.002, r = 0.99) and T1 versus T3 (p = 0.007, r = 0.79). Discussion/conclusion: Our study for the first time revealed suggestive evidence for an antidepressant effect of metreleptin in patients with LD. Metreleptin caused a rapid drop in depression scores within 1 week of treatment. A reduction of the depression score was also observed in 2 of the 3 LD patients whose BDI scores were in the normal range before start of the treatment. The reduction in total scores of BDI was still apparent after 3 months (T4) of dosing. This observation matches findings obtained in clinical case studies of AN patients, in whom depression scores also dropped during the first week of metreleptin treatment. It needs to be noted that by the nature of this observational study without a placebo group, nonspecific treatment expectation affecting mood cannot fully be ruled out.info:eu-repo/semantics/publishedVersio

An empirical investigation of the influence of collaboration in Finance on article impact

We investigate the impact of collaborative research in academic Finance literature to find out whether and to what extent collaboration leads to higher impact articles (6,667 articles across 2001-2007 extracted from the Web of Science). Using the top 5 % as ranked by the 4-year citation counts following publication, we also follow related secondary research questions such as the relationships between article impact and author impact; collaboration and average author impact of an article; and, the nature of geographic collaboration. Key findings indicate: collaboration does lead to articles of higher impact but there is no significant marginal value for collaboration beyond three authors; high impact articles are not monopolized by high impact authors; collaboration and the average author impact of high-impact articles are positively associated, where collaborative articles have a higher mean author impact in comparison to single-author articles; and collaboration among the authors of high impact articles is mostly cross-institutional

Chronic paroxysmal hemicrania in paediatric age: report of two cases

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with hemicrania continua and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) as trigeminal autonomic cephalalgia (TACs). CPH is characterised by short-lasting (2–30 min), severe and multiple (more than 5/day) pain attacks. Headache is unilateral, and fronto-orbital-temporal pain is combined with cranial autonomic symptoms. According to the International Classification of Headache Disorders, 2nd edition, the attacks are absolutely responsive to indomethacin. CPH has been only rarely and incompletely described in the developmental age. Here, we describe two cases concerning a 7-year-old boy and a 11-year-old boy with short-lasting, recurrent headache combined with cranial autonomic features. Pain was described as excruciating, and was non-responsive to most traditional analgesic drugs. The clinical features of our children’s headache and the positive response to indomethacin led us to propose the diagnosis of CPH. Therefore, our children can be included amongst the very few cases of this trigeminal autonomic cephalgia described in the paediatric age

Relationship of perfluorooctanoic acid exposure to pregnancy outcome based on birth records in the mid-Ohio Valley.

BACKGROUND: Perfluorooctanoic acid (PFOA) is a potential cause of adverse pregnancy outcomes, but previous studies have been limited by low exposures and small study size. OBJECTIVES: Using birth certificate information, we examined the relation between estimated PFOA exposure and birth outcomes in an area of West Virginia and Ohio whose drinking water was contaminated by a chemical plant. METHODS: Births in the study area from 1990 through 2004 were examined to generate case groups of stillbirth (n = 106), pregnancy-induced hypertension (n = 224), preterm birth (n = 3,613), term low birth weight (n = 918), term small-for-gestational-age (SGA) (n = 353), and a continuous measure of birth weight among a sample of term births (n = 4,534). A 10% sample of term births ≥ 2,500 g were selected as a source of controls (n = 3,616). Historical estimates of serum PFOA were derived from a previously developed fate and transport model. In a second study, we examined 4,547 area births linked to a survey with residential history data. RESULTS: In the analysis based only on birth records, we found no consistent evidence of an association between estimated PFOA exposure and stillbirth, pregnancy-induced hypertension, preterm birth, or indices of fetal growth. In the analysis of birth records linked to the survey, PFOA was unrelated to pregnancy-induced hypertension or preterm birth but showed some suggestion of an association with early preterm birth. Measures of growth restriction showed weak and inconsistent associations with PFOA. CONCLUSIONS: Based on the analysis using the health survey, these results provide little support for an effect of PFOA exposure on most pregnancy outcomes, except for early preterm birth and possibly fetal growth restriction

Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?

Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care.Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition.In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

High connectivity of the Crocodile Shark between the Atlantic and Southwest Indian Oceans: highlights for conservation

Among the various shark species that are captured as bycatch in commercial fishing operations, the group of pelagic sharks is still one of the least studied and known. Within those, the crocodile shark, Pseudocarcharias kamoharai, a small-sized lamnid shark, is occasionally caught by longline vessels in certain regions of the tropical oceans worldwide. However, the population dynamics of this species, as well as the impact of fishing mortality on its stocks, are still unknown, with the crocodile shark currently one of the least studied of all pelagic sharks. Given this, the present study aimed to assess the population structure of P. kamoharai in several regions of the Atlantic and Indian Oceans using genetic molecular markers. The nucleotide composition of the mitochondrial DNA control region of 255 individuals was analyzed, and 31 haplotypes were found, with an estimated diversity Hd = 0.627, and a nucleotide diversity pi = 0.00167. An analysis of molecular variance (AMOVA) revealed a fixation index phi(ST) = -0.01118, representing an absence of population structure among the sampled regions of the Atlantic Ocean, and between the Atlantic and Indian Oceans. These results show a high degree of gene flow between the studied areas, with a single genetic stock and reduced population variability. In panmictic populations, conservation efforts can be concentrated in more restricted areas, being these representative of the total biodiversity of the species. When necessary, this strategy could be applied to the genetic maintenance of P. kamoharai.Foundation for Research Support of the Sao Paulo State - FAPESP [2011/23787-0, 2010/51903-2]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BPD/93936/2013]; Foundation for Research Support of the Sao Paulo State - FAPESP [2011/23787-0, 2010/51903-2]; Portuguese Foundation for Science and Technology (FCT) [SFRH/BPD/93936/2013]info:eu-repo/semantics/publishedVersio

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio