Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD

Converting Endangered Species Categories to Probabilities of Extinction for Phylogenetic Conservation Prioritization

Categories of imperilment like the global IUCN Red List have been transformed to probabilities of extinction and used to rank species by the amount of imperiled evolutionary history they represent (e.g. by the Edge of Existence programme). We investigate the stability of such lists when ranks are converted to probabilities of extinction under different scenarios.Using a simple example and computer simulation, we show that preserving the categories when converting such list designations to probabilities of extinction does not guarantee the stability of the resulting lists.Care must be taken when choosing a suitable transformation, especially if conservation dollars are allocated to species in a ranked fashion. We advocate routine sensitivity analyses

A Systematic Analysis of Temporal Trends in the Handgrip Strength of 2,216,320 Children and Adolescents Between 1967 and 2017

Objective: To estimate national and international temporal trends in handgrip strength for children and adolescents, and to examine relationships between trends in handgrip strength and trends in health-related and sociodemographic indicators. Methods: Data were obtained through a systematic search of studies reporting temporal trends in the handgrip strength for apparently healthy 9–17 year-olds, and by examining large national fitness datasets. Temporal trends at the country-sex-age level were estimated by sample-weighted regression models relating the year of testing to mean handgrip strength. International and national trends were estimated by a post-stratified population-weighting procedure. Pearson’s correlations quantified relationships between trends in handgrip strength and trends in health-related/sociodemographic indicators. Results: 2,216,320 children and adolescents from 13 high-, 5 upper-middle-, and 1 low-income countries/special administrative regions between 1967 and 2017 collectively showed a moderate improvement of 19.4% (95%CI: 18.4 to 20.4) or 3.8% per decade (95%CI: 3.6 to 4.0). The international rate of improvement progressively increased over time, with more recent values (post-2000) close to two times larger than those from the 1960s/1970s. Improvements were larger for children (9–12 years) compared to adolescents (13–17 years), and similar for boys and girls. Trends differed between countries, with relationships between trends in handgrip strength and trends in health-related/sociodemographic indicators negligible-to-weak and not statistically significant. Conclusions: There has been a substantial improvement in absolute handgrip strength for children and adolescents since 1967. There is a need for improved international surveillance of handgrip strength, especially in low- and middle-income countries, to more confidently determine true international trends. PROSPERO registration number: CRD42013003657

Is youth unemployment really the major worry? (AOM)

Youth unemployment is neither the only nor the basic problem of the European labour market. The comparative analysis of unemployment data demonstrates that the unemployment of older people is even more serious. The article proves that the weight of young people in total unemployment has as a tendency been declining in the “inner periphery” of the EU, among them in Central and Eastern European member states (CEECs). The trend is just the opposite in the developed or “core” countries of the Union where youngsters took a higher share in total unemployment in 2012 than 10-12 years ago. In Europe there are millions of young people beyond the active unemployed who do not want to work or think they cannot find a job that fulfils their expectations and refuse to take part in any kind of education or training (NEETs-“Not in Employment, Education or Training”). By estimating the rate of NEETs in the adult population the article claims that the NEETs-phenomenon is not the differentia specifica of the youth. At the end the article details two suggestions for the mitigation of the problem. It concludes that the joblessness in Europe is an old and tendencially worsening problem that cannot be solved by particular policies

Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls.

The role of the human microbiome in schizophrenia remains largely unexplored. The microbiome has been shown to alter brain development and modulate behavior and cognition in animals through gut-brain connections, and research in humans suggests that it may be a modulating factor in many disorders. This study reports findings from a shotgun metagenomic analysis of the oropharyngeal microbiome in 16 individuals with schizophrenia and 16 controls. High-level differences were evident at both the phylum and genus levels, with Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria dominating both schizophrenia patients and controls, and Ascomycota being more abundant in schizophrenia patients than controls. Controls were richer in species but less even in their distributions, i.e., dominated by fewer species, as opposed to schizophrenia patients. Lactic acid bacteria were relatively more abundant in schizophrenia, including species of Lactobacilli and Bifidobacterium, which have been shown to modulate chronic inflammation. We also found Eubacterium halii, a lactate-utilizing species. Functionally, the microbiome of schizophrenia patients was characterized by an increased number of metabolic pathways related to metabolite transport systems including siderophores, glutamate, and vitamin B12. In contrast, carbohydrate and lipid pathways and energy metabolism were abundant in controls. These findings suggest that the oropharyngeal microbiome in individuals with schizophrenia is significantly different compared to controls, and that particular microbial species and metabolic pathways differentiate both groups. Confirmation of these findings in larger and more diverse samples, e.g., gut microbiome, will contribute to elucidating potential links between schizophrenia and the human microbiota

Data incongruence and the problem of avian louse phylogeny

Recent studies based on different types of data (i.e. morphological and molecular) have supported conflicting phylogenies for the genera of avian feather lice (Ischnocera: Phthiraptera). We analyse new and published data from morphology and from mitochondrial (12S rRNA and COI) and nuclear (EF1-) genes to explore the sources of this incongruence and explain these conflicts. Character convergence, multiple substitutions at high divergences, and ancient radiation over a short period of time have contributed to the problem of resolving louse phylogeny with the data currently available. We show that apparent incongruence between the molecular datasets is largely attributable to rate variation and nonstationarity of base composition. In contrast, highly significant character incongruence leads to topological incongruence between the molecular and morphological data. We consider ways in which biases in the sequence data could be misleading, using several maximum likelihood models and LogDet corrections. The hierarchical structure of the data is explored using likelihood mapping and SplitsTree methods. Ultimately, we concede there is strong discordance between the molecular and morphological data and apply the conditional combination approach in this case. We conclude that higher level phylogenetic relationships within avian Ischnocera remain extremely problematic. However, consensus between datasets is beginning to converge on a stable phylogeny for avian lice, at and below the familial rank

Incidence and Factors Associated with Postpartum Anemia at Mbarara Regional Referral Hospital

Background: The World Health organization defines postpartum anemia as hemoglobin <11g/dl at 1 week postpartum and <12g/dl at 8 weeks postpartum. Postpartum anemia can also be defined as less than 11.8 g/dl for women aged 12–15 years and less than 12g/dl for women at least age 15 years. In Uganda, 23% of women age 15-49 are anemic, with 18 percent having mild anemia, 5 percent having moderate anemia, and less than 1 percent having severe anemia. Objective: To determine the incidence and factors associated with the new cases of post natal anemia in Mbarara Regional Referral Hospital. Methods:  A prospective cohort study of 271 postpartum mothers without anemia enrolled on discharge after delivery. Participants were followed up to determine development of anemia at 10 weeks postpartum and associated factors on the subsequent postnatal visits. Incidence of postpartum anemia in MRRH was 29.9%, 95% CI (24 - 35). Helminthes infestations AOR95%CI; 12.88(5.25- 31.64, P<0.000), malaria infections AOR95%CI 4.74(1.50-14.94, P=0.008), poor hematinic adherence AOR95%CI, 6.81(3.17-14.62, P<0.000), high parity AOR95%CI, 2.48(1.11- 5.54, P=0.026), and husband unemployment AOR 3.92(1.14 – 13.39, P=0.030) were found to be statistically associated with post-partum anemia. Conclusion: The incidence of postpartum anemia in Mbarara Regional Referral Hospital is very high. Hematinics non adherence, husband unemployment, increased parity; malaria infection and helminthes infestation were found to be associated with post-partum anemia at MRRH

The institutional shaping of management: in the tracks of English individualism

Globalisation raises important questions about the shaping of economic action by cultural factors. This article explores the formation of what is seen by some as a prime influence on the formation of British management: individualism. Drawing on a range of historical sources, it argues for a comparative approach. In this case, the primary comparison drawn is between England and Scotland. The contention is that there is a systemic approach to authority in Scotland that can be contrasted to a personal approach in England. An examination of the careers of a number of Scottish pioneers of management suggests the roots of this systemic approach in practices of church governance. Ultimately this systemic approach was to take a secondary role to the personal approach engendered by institutions like the universities of Oxford and Cambridge, but it found more success in the different institutional context of the USA. The complexities of dealing with historical evidence are stressed, as is the value of taking a comparative approach. In this case this indicates a need to take religious practice as seriously as religious belief as a source of transferable practice. The article suggests that management should not be seen as a simple response to economic imperatives, but as shaped by the social and cultural context from which it emerges