Treatment of hypertension in rural Cambodia: results of a 6-year programme

This study was aimed to describe the outcomes of a hypertension treatment programme in two outpatient clinics in Cambodia. We determined proportions of patients who met the optimal targets for blood pressure (BP) control and assessed the evolution of mean systolic and diastolic BP (SBP/DBP) over time. Multivariate analyses were used to identify predictors of BP decrease and risk factors for LTFU. A total of 2858 patients were enrolled between March 2002 and June 2008 of whom 69.2% were female, 30.5% were aged >/=64years and 32.6% were diabetic. The median follow-up time was 600 days. By the end of 2008, 1642 (57.4%) were alive-in-care, 8 (0.3%) had died and 1208 (42.3%) were lost to follow-up. On admission, mean SBP and DBP were 162 and 94 mm Hg, respectively. Among the patients treated, a significant SBP reduction of 26.8 mm Hg (95% CI: 28.4-25.3) was observed at 6 months. Overall, 36.5% of patients reached the BP targets at 24 months. The number of young adults, non-overweight patients and non-diabetics reaching the BP targets was more. Older age (>64 years), uncontrolled DBP (>/=90 mm Hg) on last consultation and coming late for the last consultation were associated with LTFU, whereas non-diabetic patients were 1.5 times more likely to default than diabetics (95% CI: 1.3-1.7). Although the definite magnitude of the BP decrease due to antihypertension medication over time cannot be assessed definitely without a control group, our results suggest that BP reduction can be obtained with essential hypertension treatment in a large-scale programme in a resource-limited setting

A comparison of scavenging and deposition processes in global models: results from the WCRP Cambridge Workshop of 1995

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75543/1/j.1600-0889.2000.00980.x.pd

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction

MLKL is the essential effector of necroptosis, a form of programmed lytic cell death. We have isolated a mouse strain with a single missense mutation, Mlkl(D139V), that alters the two-helix 'brace' that connects the killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation of the salivary glands and mediastinum. The normal embryonic development of Mlkl(D139V) homozygotes until birth, and the absence of any overt phenotype in heterozygotes provides important in vivo precedent for the capacity of cells to clear activated MLKL. These observations offer an important insight into the potential disease-modulating roles of three common human MLKL polymorphisms that encode amino acid substitutions within or adjacent to the brace region. Compound heterozygosity of these variants is found at up to 12-fold the expected frequency in patients that suffer from a pediatric autoinflammatory disease, chronic recurrent multifocal osteomyelitis (CRMO). Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region

Tropological space : the imaginary space of figuration

The paper is devoted to the concept of tropological space, introduced by Michel Foucault in 1966 and alluded to in Hayden White’s tropics of discourse (1973, 1978, 2000), but never described in any detail in literary semantics or linguistic stylistics. The author presents her theory of a triple functional subdivision of stylistic figures and, consequently, of tropes (micro-, macro- and mega (meta)-level of description) and relates it to a gradually expanding tropological space of particular figures, their chains and groupings within a text. The author postulates that tropological space, the imaginary space created through figuration, is a sub-space of the Wittgensteinian logical space as well as a sub-space of textual / discursive space. Although the discussion refers mostly to literary texts, tropology – a branch of stylistics / poetics / rhetoric makes generalizations valid for the study of all kinds of texts / discourses. Figuration is assumed here to be an inherent feature of conceptual and linguistic expression. Finally, the author raises a methodological query as to the ontological status of tropological space, opting for the approach which treats it as a peculiar kind of semantic space rather than a mere metaphoric term. The discussion is based mostly on the Anglo-American studies on figuration (K. Burke, H. White, P. de Man, J. Hillis Miller, G. Hartman) that are rooted in the neo-classical rhetoric and writings of G. Vico. This line of thinking draws its philosophical inspiration from the European hermeneutics of P. Ricoeur, the Foucaultian theory of discourses and the Derridean deconstructionist ideas on the operation of language. The author brings additionally into consideration the conception of artistic space propagated by the Russian semiotic tradition and V. N. Toporov (1983/2003) in particular

Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis

The reaction patterns of chondrocytes in osteoarthritis can be summarized in five categories: (1) proliferation and cell death (apoptosis); changes in (2) synthetic activity and (3) degradation; (4) phenotypic modulation of the articular chondrocytes; and (5) formation of osteophytes. In osteoarthritis, the primary responses are reinitiation of synthesis of cartilage macromolecules, the initiation of synthesis of types IIA and III procollagens as markers of a more primitive phenotype, and synthesis of active proteolytic enzymes. Reversion to a fibroblast-like phenotype, known as 'dedifferentiation', does not appear to be an important component. Proliferation plays a role in forming characteristic chondrocyte clusters near the surface, while apoptosis probably occurs primarily in the calcified cartilage

Identification of Potential Therapeutic Drugs for Huntington's Disease using Caenorhabditis elegans

The prolonged time course of Huntington's disease (HD) neurodegeneration increases both the time and cost of testing potential therapeutic compounds in mammalian models. An alternative is to initially assess the efficacy of compounds in invertebrate models, reducing time of testing from months to days.We screened candidate therapeutic compounds that were identified previously in cell culture/animal studies in a C. elegans HD model and found that two FDA approved drugs, lithium chloride and mithramycin, independently and in combination suppressed HD neurotoxicity. Aging is a critical contributor to late onset neurodegenerative diseases. Using a genetic strategy and a novel assay, we demonstrate that lithium chloride and mithramycin remain neuroprotective independent of activity of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signaling pathway on aging.These results suggest that pathways involved in polyglutamine-induced degeneration are distinct from specific aging pathways. The assays presented here will be useful for rapid and inexpensive testing of other potential HD drugs and elucidating pathways of drug action. Additionally, the neuroprotection conferred by lithium chloride and mithramycin suggests that these drugs may be useful for polyglutamine disease therapy

A global agenda for advancing freshwater biodiversity research

This manuscript is a contribution of the Alliance for Freshwater Life (www.allianceforfreshwaterlife.org). We thank Nick Bond, Lisa Bossenbroek, Lekima Copeland, Dean Jacobsen, Maria Cecilia Londo?o, David Lopez, Jaime Ricardo Garcia Marquez, Ketlhatlogile Mosepele, Nunia Thomas-Moko, Qiwei Wei and the authors of Living Waters: A Research Agenda for the Biodiversity of Inland and Coastal Waters for their contributions. We also thank Peter Thrall, Ian Harrison and two anonymous referees for their valuable comments that helped improve the manuscript. Open access funding enabled and organised by Projekt DEAL