Development and preliminary testing of the psychosocial adjustment to hereditary diseases scale

Background: The presence of Lynch syndrome (LS) can bring a lifetime of uncertainty to an entire family as members adjust to living with a high lifetime cancer risk. The research base on how individuals and families adjust to genetic-linked diseases following predictive genetic testing has increased our understanding of short-term impacts but gaps continue to exist in knowledge of important factors that facilitate or impede long-term adjustment. The failure of existing scales to detect psychosocial adjustment challenges in this population has led researchers to question the adequate sensitivity of these instruments. Furthermore, we have limited insight into the role of the family in promoting adjustment. Methods: The purpose of this study was to develop and initially validate the Psychosocial Adjustment to Hereditary Diseases (PAHD) scale. This scale consists of two subscales, the Burden of Knowing (BK) and Family Connectedness (FC). Items for the two subscales were generated from a qualitative data base and tested in a sample of 243 participants from families with LS. Results: The Multitrait/Multi-Item Analysis Program-Revised (MAP-R) was used to evaluate the psychometric properties of the PAHD. The findings support the convergent and discriminant validity of the subscales. Construct validity was confirmed by factor analysis and Cronbach’s alpha supported a strong internal consistency for BK (0.83) and FC (0.84). Conclusion: Preliminary testing suggests that the PAHD is a psychometrically sound scale capable of assessing psychosocial adjustment. We conclude that the PAHD may be a valuable monitoring tool to identify individuals and families who may require therapeutic interventions

A global analysis of IFT-A function reveals specialization for transport of membrane-associated proteins into cilia

Intraflagellar transport (IFT), which is essential for the formation and function of cilia in most organisms, is the trafficking of IFT trains (i.e. assemblies of IFT particles) that carry cargo within the cilium. Defects in IFT cause several human diseases. IFT trains contain the complexes IFT-A and IFT-B. To dissect the functions of these complexes, we studied a Chlamydomonas mutant that is null for the IFT-A protein IFT140. The mutation had no effect on IFT-B but destabilized IFT-A, preventing flagella assembly. Therefore, IFT-A assembly requires IFT140. Truncated IFT140, which lacks the N-terminal WD repeats of the protein, partially rescued IFT and supported formation of half-length flagella that contained normal levels of IFT-B but greatly reduced amounts of IFT-A. The axonemes of these flagella had normal ultrastructure and, as investigated by SDS-PAGE, normal composition. However, composition of the flagellar \u27membrane+matrix\u27 was abnormal. Analysis of the latter fraction by mass spectrometry revealed decreases in small GTPases, lipid-anchored proteins and cell signaling proteins. Thus, IFT-A is specialized for the import of membrane-associated proteins. Abnormal levels of the latter are likely to account for the multiple phenotypes of patients with defects in IFT140. This article has an associated First Person interview with the first author of the paper

Heavy metal and proximate composition associated with the composting of cassava (Manihot esculenta) peels used in the cultivation of mushrooms in Ghana

Changes in the heavy metal content and proximate composition during the 28 day composting of cassava peels used in the cultivation of the oyster mushrooms Pleurotus ostreatus strain EM-1 was studied. Significant dry weight variations of cellulose, hemicellulose and fat contents were observed from day 0 to 12. Decreases from day 12 to 28 had the values of 15.4, 57.6 and 56.12%, respectively, while lignin, protein and crude fibre values showed a gradual increase from day 0 to 28, with maximum values of 23.73, 49 and 73%, respectively. Cyanide content however showed a reduction from the initial 3.89 to 2.01 mg/L by day 12 and a marginal increase of 16 by day 28. This was however not detected in the mushroom harvested. The levels of heavy metal content in composted cassava peels in decreasing order was iron (Fe), manganese (Mn), zinc (Zn), lead (Pb) and copper (Cu) while that for uncomposted cassava was Fe, Zn, Pb, Mn and Cu. Levels of Cu, Mn, Pd and Zn in mushroom samples analysed were in agreement with reported values in literature. Of all the heavy metals examined, iron accumulated excessively, indicating that P. ostreatus strain EM-1 is a good bio-accumulator of Fe.Keywords: Cassava, composting, heavy metals, productionAfrican Journal of Biotechnology, Vol 13(22) 2208-221

Impact of Body Mass Index on Short-Term Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Newfoundland and Labrador, Canada

Background and Aim. Obesity (BMI ≥ 30 kg/m2) is associated with advanced cardiovascular disease requiring procedures such as percutaneous coronary intervention (PCI). Studies report better outcomes in obese patients having these procedures but results are conflicting or inconsistent. Newfoundland and Labrador (NL) has the highest rate of obesity in Canada. The aim of the study was to examine the relationship between BMI and vascular and nonvascular complications in patients undergoing PCI in NL. Methods. We studied 6473 patients identified in the APPROACH-NL database who underwent PCI from May 2006 to December 2013. BMI categories included normal, 18.5 ≤ BMI < 25.0 (n=1073); overweight, 25.0 ≤ BMI < 30 (n=2608); and obese, BMI ≥ 30.0 (n=2792). Results. Patients with obesity were younger and had a higher incidence of diabetes, hypertension, and family history of cardiac disease. Obese patients experienced less vascular complications (normal, overweight, and obese: 8.2%, 7.2%, and 5.3%, p=0.001). No significant differences were observed for in-lab (4.0%, 3.3%, and 3.1%, p=0.386) or postprocedural (1.0%, 0.8%, and 0.9%, p=0.725) nonvascular complications. After adjusting for covariates, BMI was not a significant factor associated with adverse outcomes. Conclusion. Overweight and obesity were not independent correlates of short-term vascular and nonvascular complications among patients undergoing PCI

From “trust” to “trustworthiness”: Retheorizing dynamics of trust, distrust, and water security in North America

Assumptions of trust in water systems are widespread in higher-income countries, often linked to expectations of “modern water.” The current literature on water and trust also tends to reinforce a technoscientific approach, emphasizing the importance of aligning water user perceptions with expert assessments. Although such approaches can be useful to document instances of distrust, they often fail to explain why patterns differ over time, and across contexts and populations. Addressing these shortcomings, we offer a relational approach focused on the trustworthiness of hydro-social systems to contextualize water-trust dynamics in relation to broader practices and contexts. In doing so, we investigate three high-profile water crises in North America where examples of distrust are prevalent: Flint, Michigan; Kashechewan First Nation; and the Navajo Nation. Through our theoretical and empirical examination, we offer insights on these dynamics and find that distrust may at times be a warranted and understandable response to experiences of water insecurity and injustice. We examine the interconnected experiences of marginality and inequity, ontological and epistemological injustice, unequal governance and politics, and histories of water insecurity and harm as potential contributors to untrustworthiness in hydro-social systems. We close with recommendations for future directions to better understand water-trust dynamics and address water insecurity

Sox6 Directly Silences Epsilon Globin Expression in Definitive Erythropoiesis

Sox6 is a member of the Sox transcription factor family that is defined by the conserved high mobility group (HMG) DNA binding domain, first described in the testis determining gene, Sry. Previous studies have suggested that Sox6 plays a role in the development of the central nervous system, cartilage, and muscle. In the Sox6-deficient mouse, p(100H), ɛy globin is persistently expressed, and increased numbers of nucleated red cells are present in the fetal circulation. Transfection assays in GM979 (erythroleukemic) cells define a 36–base pair region of the ɛy proximal promoter that is critical for Sox6 mediated repression. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays demonstrate that Sox6 acts as a repressor by directly binding to the ɛy promoter. The normal expression of Sox6 in wild-type fetal liver and the ectopic expression of ɛy in p(100H) homozygous fetal liver demonstrate that Sox6 functions in definitive erythropoiesis. The present study shows that Sox6 is required for silencing of ɛy globin in definitive erythropoiesis and suggests a role for Sox6 in erythroid cell maturation. Thus, Sox6 regulation of ɛy globin might provide a novel therapeutical target in the treatment of hemoglobinopathies such as sickle cell anemia and thalassemia

Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin A or toxin B in cell-based in vitro neutralization assays. Three anti-toxin A HuMAbs (3H2, CDA1, and 1B11) could all inhibit the enterotoxicity of toxin A in mouse intestinal loops and the in vivo toxicity in a systemic mouse model. Four anti-toxin B HuMAbs (MDX-1388, 103-174, 1G10, and 2A11) could neutralize cytotoxicity in vitro, although systemic toxicity in the mouse could not be neutralized. Anti-toxin A HuMAb CDA1 and anti-toxin B HuMAb MDX-1388 were tested in the well-established hamster model of C. difficile disease. CDA1 alone resulted in a statistically significant reduction of mortality in hamsters; however, the combination treatment offered enhanced protection. Compared to controls, combination therapy reduced mortality from 100% to 45% (P\u3c0.0001) in the primary disease hamster model and from 78% to 32% (P\u3c0.0001) in the less stringent relapse model