Bodily relations and reciprocity in the art of Sonia Khurana

This article explores the significance of the ‘somatic’ and ‘ontological turn’ in locating the radical politics articulated in the contemporary performance, installation, video and digital art practices of New Delhi-based artist, Sonia Khurana (b. 1968). Since the late 1990s Khurana has fashioned a range of artworks that require new sorts of reciprocal and embodied relations with their viewers. While this line of art practice suggests the need for a primarily philosophical mode of inquiry into an art of the body, such affective relations need to be historicised also in relation to a discursive field of ‘difference’ and public expectations about the artist’s ethnic, gendered and national identity. Thus, this intimate, visceral and emotional field of inter- and intra-action is a novel contribution to recent transdisciplinary perspectives on the gendered, social and sentient body, that in turn prompts a wider debate on the ethics of cultural commentary and art historiography

The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification

PURPOSE: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. METHODS: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. RESULTS: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. CONCLUSION: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Leprosy among Patient Contacts: A Multilevel Study of Risk Factors

Leprosy is an infectious disease that can lead to physical disabilities, social stigma, and great hardship. Transmitted from person to person, it is still endemic in developing countries, like Brazil and India. Effective treatment has been available since 1960, but early diagnosis of the disease remains the most effective way to stop the transmission chain and avoid late diagnoses and subsequent disabilities. Knowledge of the risk factors for leprosy can facilitate early detection; therefore, our study aimed to investigate the factors presented by leprosy patients and their contacts, who are considered at highest risk of contracting the disease. We studied 6,158 contacts of 1,201 patients under surveillance from 1987 to 2007 in a Public Health Care Center in the City of Rio de Janeiro, Brazil. We evaluated the ways patient and contact demographics and epidemiological characteristics were associated with the detection of leprosy. Statistical analyses took into account both individual and group characteristics and their interrelationships. The main characteristics facilitating the contraction of leprosy among contacts were shown to be consanguinity and household association. Conversely, the bacillary load index of leprosy patients was the principle factor leading to disease among their contacts

Multiple splice defects in ABCA1 cause low HDL-C in a family with Hypoalphalipoproteinemia and premature coronary disease

<p>Abstract</p> <p>Background</p> <p>Mutations at splice junctions causing exon skipping are uncommon compared to exonic mutations, and two intronic mutations causing an aberrant phenotype have rarely been reported. Despite the high number of functional <it>ABCA1 </it>mutations reported to date, splice variants have been reported infrequently. We screened DNA from a 41 year-old male with low HDL-C (12 mg/dL [0.31 mmol/L]) and a family history of premature coronary heart disease (CHD) using polymerase chain reaction single-strand conformation polymorphism (SSCP) analysis.</p> <p>Methods</p> <p>Family members with low levels of HDL-C (n = 6) were screened by SSCP for mutations in <it>ABCA1</it>. Samples with altered SSCP patterns were sequenced directly using either an ABI 3700 or ABI3730Xl DNA Analyzer. To screen for splicing defects, cDNA was isolated from the proband's RNA and was sequenced as above. A series of minigenes were constructed to determine the contribution of normal and defective alleles.</p> <p>Results</p> <p>Two novel splice variants in <it>ABCA1 </it>were identified. The first mutation was a single base pair change (T->C) in IVS 7, 6 bps downstream from the exon7/intron7 junction. Amplification of cDNA and allelic subcloning identified skipping of Exon 7 that results in the elimination of 59 amino acids from the first extracellular loop of the ABCA1 protein. The second mutation was a single base pair change (G->C) at IVS 31 -1, at the intron/exon junction of exon 32. This mutation causes skipping of exon 32, resulting in 8 novel amino acids followed by a stop codon and a predicted protein size of 1496 AA, compared to normal (2261 AA). Bioinformatic studies predicted an impact on splicing as confirmed by <it>in vitro </it>assays of constitutive splicing.</p> <p>Conclusion</p> <p>In addition to carnitine-acylcarnitine translocase (CACT) deficiency and Hermansky-Pudlak syndrome type 3, this represents only the third reported case in which 2 different splice mutations has resulted in an aberrant clinical phenotype.</p

Genetic characterisation of farmed rainbow trout in Norway: intra- and inter-strain variation reveals potential for identification of escapees

<p>Abstract</p> <p>Background</p> <p>The rainbow trout (<it>Oncorhynchus mykiss</it>) is one of the most important aquaculture species in the world, and Norway is one of the largest producers. The present study was initiated in response to a request from the Norwegian police authority to identify the farm of origin for 35 escaped rainbow trout captured in a fjord. Eleven samples, each consisting of approximately 47 fish, were collected from the three farms operating in the fjord where the escapees were captured. In order to gain a better general understanding of the genetic structure of rainbow trout strains used in Norwegian aquaculture, seven samples (47 fish per sample) were collected from six farms located outside the region where the escapees were captured. All samples, including the escapees, were genotyped with 12 microsatellite loci.</p> <p>Results</p> <p>All samples displayed considerable genetic variability at all loci (mean number of alleles per locus per sample ranged from 5.4–8.6). Variable degrees of genetic differentiation were observed among the samples, with pair-wise <it>F</it>_STvalues ranging from 0–0.127. Self-assignment tests conducted among the samples collected from farms outside the fjord where the escapees were observed gave an overall correct assignment of 82.5%, demonstrating potential for genetic identification of escapees. In the "real life" assignment of the 35 captured escapees, all were excluded from two of the samples included as controls in the analysis, and 26 were excluded from the third control sample. In contrast, only 1 of the escapees was excluded from the 11 pooled samples collected on the 3 farms operating in the fjord.</p> <p>Conclusion</p> <p>Considerable genetic variation exists within and among rainbow trout strains farmed in Norway. Together with modern statistical methods, this will provide commercial operators with a tool to monitor breeding and fish movements, and management authorities with the ability to identify the source of escapees. The data generated in this study were used by the Norwegian police to initiate an investigation of the company operating the three farms in the fjord where escapees were observed.</p

Beneficial and Detrimental Effects of Plasmin(ogen) during Infection and Sepsis in Mice

Plasmin has been proposed to be an important mediator during inflammation/infection. In this study, by using mice lacking genes for plasminogen, tissue-type plasminogen activator (tPA), and urokinase-type PA (uPA), we have investigated the functional roles of active plasmin in infection and sepsis. Two models were used: an infection model by intravenous injection of 1×107 CFU of S. aureus, and a sepsis model by intravenous injection of 1.6×108 CFU of S. aureus. We found that in the infection model, wild-type (WT) mice showed significantly higher survival rates than plasminogen-deficient (plg-/-) mice. However, in the sepsis model, plg-/- or tPA-/-/uPA-/- mice showed the highest survival rate whereas WT and tPA+/-/uPA+/- mice showed the lowest survival rate, and plg+/-, tPA-/-, and uPA-/- mice had an intermediate survival rate. These results indicate that the levels of active plasmin are critical in determining the survival rate in the sepsis, partly through high levels of inflammatory cytokines and enhanced STAT3 activation. We conclude that plasmin is beneficial in infection but promotes the production of inflammatory cytokines in sepsis that may cause tissue destruction, diminished neutrophil function, and an impaired capacity to kill bacteria which eventually causes death of these mice

Factors Influencing Engagement, Perceived Usefulness and Behavioral Mechanisms Associated with a Text Message Support Program

Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours. We aimed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement, perceived usefulness, behavior change and program delivery preferences. Methods Mixed methods qualitative design combining four data sources; (i) analytic data extracted directly from the software system, (ii) participant survey, (iii) focus groups to identify barriers and enablers to implementation and mechanisms of effect and (iv) recruitment screening logs and text message responses to examine engagement. This evaluation was conducted within the TEXT ME trial—a parallel design, single-blind randomized controlled trial (RCT) of 710 patients with coronary heart disease (CHD). Qualitative data were interpreted using inductive thematic analysis. Results 307/352 (87% response rate) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group. Factors increasing engagement included (i) ability to save and share messages, (ii) having the support of providers and family, (iii) a feeling of support through participation in the program, (iv) the program being initiated close to the time of a cardiovascular event, (v) personalization of the messages, (vi) opportunity for initial face-to-face contact with a provider and (vii) that program and content was perceived to be from a credible source. Clear themes relating to program delivery were that diet and physical activity messages were most valued, four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer. Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aimed at improving health-related behavior. The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling