The core minimum dataset for measuring pain outcomes in pain services across Scotland. Developing and testing a brief multi-dimensional questionnaire

BACKGROUND: There is currently no agreed minimum dataset to inform specialist chronic pain service provision. We aimed to develop a Core Minimum Dataset (CMD) for pain services in Scotland and perform preliminary analysis to evaluate its psychometric properties in adults with chronic pain. METHODS: The questionnaire was developed following a review of existing relevant data collection instruments and national consultation. The CMD questionnaire was completed alongside a routine pre-clinic questionnaire by patients attending two pain services over 3 months. Concurrent validity was tested by comparing scores between the CMD and pre-existing questionnaires. Reliability was assessed by test-retest and discriminative validity via receiver operating characteristic (ROC) curves. RESULTS: The final CMD questionnaire consisted of five questions on four domains: pain severity (Chronic Pain Grade [CPG] Q1); pain interference (CPG Q5); emotional impact (Patient Health Questionnaire-2 [PHQ-2], two questions); and quality of life (Short Form Health Survey-36 [SF-36] Q1). 530 patients completed the questionnaire. Strong correlation was found with the Hospital Anxiety and Depression Scale (r(s) = 0.753, p < 0.001). Moderate correlations were found with the Brief Pain Inventory for pain interference (r(s) = 0.585, p < 0.001) and pain severity (r(s) = 0.644, p < 0.001). Moderate to good reliability was demonstrated (Intra-class Correlation Coefficient = 0.572–0.845). All items indicated good discrimination for relevant health states. CONCLUSIONS: The findings represent initial steps towards developing an accurate questionnaire that is feasible for assessing chronic pain in adults attending specialist pain clinics and measuring service improvements in Scotland. Further validation testing, in clinical settings, is now required

A conserved arginine residue is critical for stabilizing the N2 FeS cluster in mitochondrial complex I.

Respiratory complex I (NADH:ubiquinone oxidoreductase), the first enzyme of the electron-transport chain, captures the free energy released by NADH oxidation and ubiquinone reduction to translocate protons across an energy-transducing membrane and drive ATP synthesis during oxidative phosphorylation. The cofactor that transfers the electrons directly to ubiquinone is an iron-sulfur cluster (N2) located in the NDUFS2/NUCM subunit. A nearby arginine residue (R121), which forms part of the second coordination sphere of the N2 cluster, is known to be posttranslationally dimethylated but its functional and structural significance are not known. Here, we show that mutations of this arginine residue (R121M/K) abolish the quinone-reductase activity, concomitant with disappearance of the N2 signature from the electron paramagnetic resonance (EPR) spectrum. Analysis of the cryo-EM structure of NDUFS2-R121M complex I at 3.7 Å resolution identified the absence of the cubane N2 cluster as the cause of the dysfunction, within an otherwise intact enzyme. The mutation further induced localized disorder in nearby elements of the quinone-binding site, consistent with the close connections between the cluster and substrate-binding regions. Our results demonstrate that R121 is required for the formation and/or stability of the N2 cluster and highlight the importance of structural analyses for mechanistic interpretation of biochemical and spectroscopic data on complex I variants

Mutations in Nonessential eIF3k and eIF3l Genes Confer Lifespan Extension and Enhanced Resistance to ER Stress in Caenorhabditis elegans

The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans. In contrast to previously described mutations in genes encoding translation initiation components that confer lifespan extension in C. elegans, loss-of-function mutations in eif-3.K or eif-3.L are viable, and mutants show normal rates of growth and development, and have wild-type levels of bulk protein synthesis. Lifespan extension resulting from EIF-3.K or EIF-3.L deficiency is suppressed by a mutation in the Forkhead family transcription factor DAF-16. Mutations in eif-3.K or eif-3.L also confer enhanced resistance to ER stress, independent of IRE-1-XBP-1, ATF-6, and PEK-1, and independent of DAF-16. Our data suggest a pivotal functional role for conserved eIF3k and eIF3l accessory subunits of eIF3 in the regulation of cellular and organismal responses to ER stress and agingNational Institutes of Health (U.S.) (Grant R01-GM084477)National Institutes of Health (U.S.) (Pre-Doctoral Training Grant T32GM007287

Primate epididymis-specific proteins: characterization of ESC42, a novel protein containing a trefoil-like motif in monkey and human

Epididymal secreted proteins promote sperm maturation and fertilizing capacity by interacting with sperm during passage through the epididymis. Here we investigate the molecular basis of sperm maturation by isolating cDNA clones for novel epididymis-specific expressed sequences. Thirty-six novel cDNAs were isolated and sequenced from a subtracted Macaca mulatta epididymis library. The clones encode proteins with a range of motifs characteristic of protein-modifying enzymes, protease inhibitors, hydrophobic ligand-binding and transport proteins, extracellular matrix-interacting proteins, and transcription regulatory factors. The full length coding sequences were obtained for 11 clones representing a range of abundance levels. Expression of each is regionally localized and androgen regulated. The most abundant, ESC42, contains a cysteine-rich region similar to the signature binding domain of the trefoil family of motogenic wound repair proteins. The monkey and human proteins are nearly 90% identical. Immunohistochemical staining revealed that the protein is most abundant in the epithelium of the caput and is also present in the lumen and bound to sperm. The ESC42 gene, located on chromosome 20q11, contains two exons encoding two nearly identical predicted signal peptides and a third exon encoding the rest of the protein

The Iowa Homemaker vol.4, no.2

Table of Contents To the High School Girls of Iowa by Anna E. Richardson, page 3 For the College Room by Barbara Mills Dewell, page 4 The Junior-Senior Banquet by Viola Jammer and Pauline Peacock, page 4 Picnic Preparations by Louise Evans Doole, page 5 Finding Yourself by H. M. Hamlin, page 6 Stories of the Sand by Katherine Holden, page 7 Appropriate Pictures for the Home by Amanda Jacobson, page 8 The Individual Scarf by Rhea Fern Schultz, page 9 Using Your Kodak by H. P. Doole, page 10 Something Plus by Laura E. Bublitz, page 11 The Ideal Homemaker by Rosalie Larson, page 12 University Life in France by Mercie Carley, page 12 Homemaker as Citizen by Jeanette Beyer, page 13 Who’s There and Where by Dryden Quist, page 14 Editorial, page 15 The Eternal Question, page 1

LCN6, a novel human epididymal lipocalin

BACKGROUND: The lipocalin (LCN) family of structurally conserved hydrophobic ligand binding proteins is represented in all major taxonomic groups from prokaryotes to primates. The importance of lipocalins in reproduction and the similarity to known epididymal lipocalins prompted us to characterize the novel human epididymal LCN6. METHODS AND RESULTS: LCN6 cDNA was identified by database analysis in a comprehensive human library sequencing program. Macaca mulatta (rhesus monkey) cDNA was obtained from an epididymis cDNA library and is 93% homologous to the human. The gene is located on chromosome 9q34 adjacent LCN8 and LCN5. LCN6 amino acid sequence is most closely related to LCN5, but the LCN6 beta-barrel structure is best modeled on mouse major urinary protein 1, a pheromone binding protein. Northern blot analysis of RNAs isolated from 25 human tissues revealed predominant expression of a 1.0 kb mRNA in the epididymis. No other transcript was detected except for weak expression of a larger hybridizing mRNA in urinary bladder. Northern hybridization analysis of LCN6 mRNA expression in sham-operated, castrated and testosterone replaced rhesus monkeys suggests mRNA levels are little affected 6 days after castration. Immunohistochemical staining revealed that LCN6 protein is abundant in the caput epithelium and lumen. Immunofluorescent staining of human spermatozoa shows LCN6 located on the head and tail of spermatozoa with the highest concentration of LCN6 on the post-acrosomal region of the head, where it appeared aggregated into large patches. CONCLUSIONS: LCN6 is a novel lipocalin closely related to Lcn5 and Lcn8 and these three genes are likely products of gene duplication events that predate rodent-primate divergence. Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility

Argumentation in school science : Breaking the tradition of authoritative exposition through a pedagogy that promotes discussion and reasoning

The value of argumentation in science education has become internationally recognised and has been the subject of many research studies in recent years. Successful introduction of argumentation activities in learning contexts involves extending teaching goals beyond the understanding of facts and concepts, to include an emphasis on cognitive and metacognitive processes, epistemic criteria and reasoning. The authors focus on the difficulties inherent in shifting a tradition of teaching from one dominated by authoritative exposition to one that is more dialogic, involving small-group discussion based on tasks that stimulate argumentation. The paper builds on previous research on enhancing the quality of argument in school science, to focus on how argumentation activities have been designed, with appropriate strategies, resources and modelling, for pedagogical purposes. The paper analyses design frameworks, their contexts and lesson plans, to evaluate their potential for enhancing reasoning through foregrounding the processes of argumentation. Examples of classroom dialogue where teachers adopt the frameworks/plans are analysed to show how argumentation processes are scaffolded. The analysis shows that several layers of interpretation are needed and these layers need to be aligned for successful implementation. The analysis serves to highlight the potential and limitations of the design frameworks

Recurrent structural variation, clustered sites of selection, and disease risk for the complement factor H (CFH) gene family

Data deposition: The data reported in this paper have been deposited as a National Center for Biotechnology Information BioProject (accession no. PRJNA401648). Author contributions: S.C. and E.E.E. designed research; S.C., C.B., L.H., K.P., K.M.M., M.S., A.E.W., V.D., T.A.G.-L., and R.K.W. performed research; S.C., J.H., C.B., L.H., K.P., K.M.M., M.S., A.E.W., V.D., F.G., A.J.R., R.H.G., T.A.G.-L., R.K.W., B.H.F.W., P.N.B., R.A., and E.E.E. contributed new reagents/analytic tools; S.C., B.J.N., J.H., and E.E.E. analyzed data; and S.C., B.J.N., and E.E.E. wrote the paper.Peer reviewedPublisher PD

Rethinking the patient: using Burden of Treatment Theory to understand the changing dynamics of illness

&lt;b&gt;Background&lt;/b&gt; In this article we outline Burden of Treatment Theory, a new model of the relationship between sick people, their social networks, and healthcare services. Health services face the challenge of growing populations with long-term and life-limiting conditions, they have responded to this by delegating to sick people and their networks routine work aimed at managing symptoms, and at retarding - and sometimes preventing - disease progression. This is the new proactive work of patient-hood for which patients are increasingly accountable: founded on ideas about self-care, self-empowerment, and self-actualization, and on new technologies and treatment modalities which can be shifted from the clinic into the community. These place new demands on sick people, which they may experience as burdens of treatment.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Discussion&lt;/b&gt; As the burdens accumulate some patients are overwhelmed, and the consequences are likely to be poor healthcare outcomes for individual patients, increasing strain on caregivers, and rising demand and costs of healthcare services. In the face of these challenges we need to better understand the resources that patients draw upon as they respond to the demands of both burdens of illness and burdens of treatment, and the ways that resources interact with healthcare utilization.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Summary&lt;/b&gt; Burden of Treatment Theory is oriented to understanding how capacity for action interacts with the work that stems from healthcare. Burden of Treatment Theory is a structural model that focuses on the work that patients and their networks do. It thus helps us understand variations in healthcare utilization and adherence in different healthcare settings and clinical contexts