A Prospective Cohort Study of Acute Pain and In-Hospital Opioid Consumption After Cardiac Surgery: Associations With Psychological and Medical Factors and Chronic Postsurgical Pain.

BACKGROUND: Understanding the association of acute pain intensity and opioid consumption after cardiac surgery with chronic postsurgical pain (CPSP) can facilitate implementation of personalized prevention measures to improve outcomes. The objectives were to (1) examine acute pain intensity and daily mg morphine equivalent dose (MME/day) trajectories after cardiac surgery, (2) identify factors associated with pain intensity and opioid consumption trajectories, and (3) assess whether pain intensity and opioid consumption trajectories are risk factors for CPSP. METHODS: Prospective observational cohort study design conducted between August 2012 and June 2020 with 1-year follow-up. A total of 1115 adults undergoing cardiac surgery were recruited from the preoperative clinic. Of the 959 participants included in the analyses, 573 completed the 1-year follow-up. Main outcomes were pain intensity scores and MME/day consumption over the first 6 postoperative days (PODs) analyzed using latent growth mixture modeling (GMM). Secondary outcome was 12-month CPSP status. RESULTS: Participants were mostly male (76%), with a mean age of 61 ± 13 years. Three distinct linear acute postoperative pain intensity trajectories were identified: "initially moderate pain intensity remaining moderate" (n = 62), "initially mild pain intensity remaining mild" (n = 221), and "initially moderate pain intensity decreasing to mild" (n = 251). Age, sex, emotional distress in response to bodily sensations, and sensitivity to pain traumatization were significantly associated with pain intensity trajectories. Three distinct opioid consumption trajectories were identified on the log MME/day: "initially high level of MME/day gradually decreasing" (n = 89), "initially low level of MME/day remaining low" (n = 108), and "initially moderate level of MME/day decreasing to low" (n = 329). Age and emotional distress in response to bodily sensations were associated with trajectory membership. Individuals in the "initially mild pain intensity remaining mild" trajectory were less likely than those in the "initially moderate pain intensity remaining moderate" trajectory to report CPSP (odds ratio [95% confidence interval, CI], 0.23 [0.06-0.88]). No significant associations were observed between opioid consumption trajectory membership and CPSP status (odds ratio [95% CI], 0.84 [0.28-2.54] and 0.95 [0.22-4.13]). CONCLUSIONS: Those with moderate pain intensity right after surgery are more likely to develop CPSP suggesting that those patients should be flagged early on in their postoperative recovery to attempt to alter their trajectory and prevent CPSP. Emotional distress in response to bodily sensations is the only consistent modifiable factor associated with both pain and opioid trajectories.

Prevalence and Risk Factors for Chronic Postsurgical Pain After Thoracic Surgery: A Prospective Cohort Study.

OBJECTIVE: Thoracic surgery is associated with one of the highest rates of chronic postsurgical pain (CPSP) among all surgical subtypes. Chronic postsurgical pain carries significant medical, psychological, and economic consequences, and further interventions are needed to prevent its development. This study aimed to determine the prevalence, characteristics, and risk factors associated with CPSP after thoracic surgery. DESIGN: A prospective cohort study. SETTING: Single-center tertiary care hospital. PARTICIPANTS: This study included 285 adult patients who underwent thoracic surgery at Toronto General Hospital in Toronto, Canada, between 2012 and 2020. MEASUREMENTS AND MAIN RESULTS: Demographic, psychological, and clinical data were collected perioperatively, and follow-up evaluations were administered at 3, 6, and 12 months after surgery to assess CPSP. Chronic postsurgical pain was reported in 32.4%, 25.4%, and 18.2% of patients at 3, 6, and 12 months postoperatively, respectively. Average CPSP pain intensity was rated to be 3.37 (SD 1.82) at 3 months. Features of neuropathic pain were present in 48.7% of patients with CPSP at 3 months and 71% at 1 year. Multivariate logistic regression models indicated that independent predictors for CPSP at 3 months were scores on the Hospital Anxiety and Depression Scale (adjusted odds ratio [aOR] of 1.07, 95% CI of 1.02 to 1.14, p = 0.012) and acute postoperative pain (aOR of 2.75, 95% CI of 1.19 to 6.36, p = 0.018). INTERVENTIONS: None. CONCLUSIONS: Approximately 1 in 3 patients will continue to have pain at 3 months after surgery, with a large proportion reporting neuropathic features. Risk factors for pain at 3 months may include preoperative anxiety and depression and acute postoperative pain.

Prevalence and Risk Factors for Chronic Postsurgical Pain after Cardiac Surgery: A Single-center Prospective Cohort Study.

BACKGROUND: Chronic postsurgical pain is a common complication of surgery. The role of psychologic risk factors like depression and anxiety is substantially understudied in cardiac surgery. This study sought to identify perioperative factors associated with chronic pain at 3, 6, and 12 months after cardiac surgery. The authors hypothesize that baseline psychologic vulnerabilities have a negative influence on chronic postsurgical pain. METHODS: The authors prospectively collected demographic, psychologic, and perioperative factors in a cohort of 1,059 patients undergoing cardiac surgery at the Toronto General Hospital between 2012 and 2020. Patients were followed and completed chronic pain questionnaires at 3, 6, and 12 months after surgery. RESULTS: The study included 767 patients who completed at least one follow-up questionnaire. The incidence of postsurgical pain (more than 0 out of 10) at 3, 6, and 12 months after surgery was 191 of 663 (29%), 118 of 625 (19%), and 89 of 605 (15%), respectively. Notably, among patients reporting any pain, the incidence of pain compatible with a neuropathic phenotype increased from 56 of 166 (34%) at 3 months to 38 of 97 (39%) at 6 months and 43 of 67 (64%) at 12 months. Factors associated with postsurgical pain scores at 3 months include female sex, pre-existing chronic pain, previous cardiac surgery, preoperative depression, baseline pain catastrophizing scores, and moderate-to-severe acute pain (4 or more out of 10) within 5 postoperative days. CONCLUSIONS: Nearly one in three patients undergoing cardiac surgery reported pain at 3 months of follow-up, with approximately 15% reporting persistent pain at 1 yr. Female sex, pre-existing chronic pain, and baseline depression were associated with postsurgical pain scores across all three time periods.

Predictors of one year chronic post-surgical pain trajectories following thoracic surgery.

PURPOSE: Chronic post-surgical pain (CPSP) is a highly prevalent complication following thoracic surgery. This is a prospective cohort study that aims to describe the pain trajectories of patients undergoing thoracic surgery beginning preoperatively and up to 1 year after surgery METHODS: Two hundred and seventy nine patients undergoing elective thoracic surgery were enrolled. Participants filled out a preoperative questionnaire containing questions about their sociodemographic information, comorbidities as well as several psychological and pain-related statuses. They were then followed-up during their immediate postoperative period and at the three, six and 12 month time-points to track their postoperative pain, complications and pain-related outcomes. Growth mixture modeling was used to construct pain trajectories. RESULTS: The first trajectory is characterized by 185 patients (78.1%) with mild pain intensity across the 12 month period. The second is characterized by 32 patients (7.5%) with moderate pain intensity immediately after surgery which decreases markedly by 3 months and remains low at the 12 month follow-up. The final trajectory is characterized by 20 patients (8.4%) with moderate pain intensity immediately after surgery which persists at 12 months. Patients with moderate to severe postoperative pain intensity were much more likely to develop CPSP compared to patients with mild pain intensity. Initial pain intensity levels immediately following surgery as well as levels of pain catastrophizing at baseline were predicting pain trajectory membership. None of the surgical or anesthetic-related variables were significantly associated with pain trajectory membership. CONCLUSION: Patients who undergo thoracic surgery can have postoperative pain that follows one of the three different types of trajectories. Higher levels of immediate postoperative pain and preoperative pain catastrophizing were associated with moderately severe CPSP.

Genetically Compromising Phospholipid Metabolism Limits Candida albicans' Virulence.

Perturbing ergosterol synthesis has been previously shown to reduce the virulence of Candida albicans. We tested the hypothesis that further altering cell membrane composition by limiting phospholipid synthesis or remodeling will have the same effect. To model partial inhibition, C. albicans strains independently harboring heterozygous deletion of four genes that encode for enzymes that mediate phospholipid synthesis or modification were generated. Quantitative PCR determined that heterozygous deletion routinely caused a nearly 50% reduction in the respective gene's transcript abundance. Compensatory increased transcript abundance was only found with the deletion of LRO1, a homolog of phospholipid diacylglycerol acyltransferases. Virulence of the mutants was assayed in a Caenorhabditis elegans host model. Even modestly reduced expression of LRO1, phosphatidylserine synthase (CHO1), and lysophospholipid acyltransferase (LPT1) significantly reduced virulence by 23-38%. Reintroducing a second functional allele, respectively, to all three mutants restored virulence. Heterozygous deletion of SLC1, a homolog of 1-acylglycerol-3-phosphate O-acyltransferases, did not significantly reduce virulence. Electrospray ionization tandem mass spectrometry analysis of phospholipid composition followed by principal component analysis identified comprehensive changes in the LRO1 and CHO1 deletion heterozygotes. Strikingly (p < 0.001), univariate comparisons found that both deletion heterozygotes had 20% more phosphatidylinositol, 75% less lysophosphatidylcholine, and 35% less lysophosphatidylethanolamine compared to wild type. Heterozygous deletion of LPT1 also significantly increased phosphatidylinositol abundance. No growth phenotype, including filamentation, was affected by any mutation. Together, these data predict that even partial pharmacological inhibition of Lro1p, Cho1p, and Lpt1p will limit C. albicans virulence through altering phospholipid composition.

Exploring the use of tablet computer-based electronic data capture system to assess patient reported measures among patients with chronic kidney disease: a pilot study.

BACKGROUND: Collecting patient reported outcome measures (PROMs) via computer-based electronic data capture system may improve feasibility and facilitate implementation in clinical care. We report our initial experience about the acceptability of touch-screen tablet computer-based, self-administered questionnaires among patients with chronic kidney disease (CKD), including stage 5 CKD treated with renal replacement therapies (RRT) (either dialysis or transplant). METHODS: We enrolled a convenience sample of patients with stage 4 and 5 CKD (including patients on dialysis or after kidney transplant) in a single-centre, cross-sectional pilot study. Participants completed validated questionnaires programmed on an electronic data capture system (DADOS, Techna Inc., Toronto) on tablet computers. The primary objective was to evaluate the acceptability and feasibility of using tablet-based electronic data capture in patients with CKD. Descriptive statistics, Fischer's exact test and multivariable logistic regression models were used for data analysis. RESULTS: One hundred and twenty one patients (55% male, mean age (± SD) of 58 (±14) years, 49% Caucasian) participated in the study. Ninety-two percent of the respondents indicated that the computer tablet was acceptable and 79% of the participants required no or minimal help for completing the questionnaires. Acceptance of tablets was lower among patients 70 years or older (75% vs. 95%; p = 0.011) and with little previous computer experience (81% vs. 96%; p = 0.05). Furthermore, a greater level of assistance was more frequently required by patients who were older (45% vs. 15%; p = 0.009), had lower level of education (33% vs. 14%; p = 0.027), low health literacy (79% vs. 12%; p = 0.027), and little previous experience with computers (52% vs. 10%; p = 0.027). CONCLUSIONS: Tablet computer-based electronic data capture to administer PROMs was acceptable and feasible for most respondents and could therefore be used to systematically assess PROMs among patients with CKD. Special consideration should focus on elderly patients with little previous computer experience, since they may require more assistance with completion.

Impact of a Transitional Pain Service on postoperative opioid trajectories: a retrospective cohort study.

INTRODUCTION: It has been well described that a small but significant proportion of patients continue to use opioids months after surgical discharge. We sought to evaluate postdischarge opioid use of patients who were seen by a Transitional Pain Service compared with controls. METHODS: We conducted a retrospective cohort study using administrative data of individuals who underwent surgery in Ontario, Canada from 2014 to 2018. Matched cohort pairs were created by matching Transitional Pain Service patients to patients of other academic hospitals in Ontario who were not enrolled in a Transitional Pain Service. Segmented regression was performed to assess changes in monthly mean daily opioid dosage. RESULTS: A total of 209 Transitional Pain Service patients were matched to 209 patients who underwent surgery at other academic centers. Over the 12 months after surgery, the mean daily dose decreased by an estimated 3.53 morphine milligram equivalents (95% CI 2.67 to 4.39, p<0.001) per month for the Transitional Pain Service group, compared with a decline of only 1.05 morphine milligram equivalents (95% CI 0.43 to 1.66, p<0.001) for the controls. The difference-in-difference change in opioid use for the Transitional Pain Service group versus the control group was -2.48 morphine milligram equivalents per month (95% CI -3.54 to -1.43, p=0.003). DISCUSSION: Patients enrolled in the Transitional Pain Service were able to achieve opioid dose reduction faster than in the control cohorts. The difficulty in finding an appropriate control group for this retrospective study highlights the need for future randomized controlled trials to determine efficacy.

Barriers to Accessing Kidney Transplantation Among Populations Marginalized by Race and Ethnicity in Canada: A Scoping Review Part 2-East Asian, South Asian, and African, Caribbean, and Black Canadians.

BACKGROUND: Kidney transplantation (KT), a treatment option for end-stage kidney disease (ESKD), is associated with longer survival and improved quality of life compared with dialysis. Inequities in access to KT, and specifically, living donor kidney transplantation (LDKT), have been documented in Canada, along various demographic dimensions. In this article, we review existing evidence about inequitable access to KT and LDKT for patients from communities marginalized by race and ethnicity in Canada. OBJECTIVE: To characterize the currently published data on rates of KT and LDKT among East Asian, South Asian, and African, Caribbean, and Black (ACB) Canadian communities and to answer the research question, "what factors may influence inequitable access to KT among East Asian, South Asian, and ACB Canadian communities?." ELIGIBILITY CRITERIA: Databases and gray literature were searched in June and November 2020 for full-text original research articles or gray literature resources addressing KT access or barriers in East Asian, South Asian, and ACB Canadian communities. A total of 25 articles were analyzed thematically. SOURCES OF EVIDENCE: Gray literature and CINAHL, OVID Medline, OVID Embase, and Cochrane databases. CHARTING METHODS: Literature characteristics were recorded and findings which described rates of and factors that influence access to KT were summarized in a narrative account. Key themes were subsequently identified and synthesized thematically in the review. RESULTS: East Asian, South Asian, and ACB communities in Canada face barriers in accessing culturally appropriate medical knowledge and care and experience inequitable access to KT. Potential barriers include gaps in knowledge about ESKD and KT, religious and spiritual concerns, stigma of ESKD and KT, health beliefs, social determinants of health, and experiences of systemic racism in health care. LIMITATIONS: This review included literature that used various methodologies and did not assess study quality. Data on ethnicity and race were not reported or defined in a standardized manner. The communities examined in this review are not homogeneous and views on organ donation and KT vary by individual. CONCLUSIONS: Our review has identified potential barriers for communities marginalized by race and ethnicity in accessing KT and LDKT. Further research is urgently needed to better understand the barriers and support needs of these communities, and to develop strategies to improve equitable access to LDKT for the growingly diverse population in Canada.

CONTEXTE: La transplantation rénale (TR), une des options de traitement de l'insuffisance rénale terminale (IRT), est associée à une meilleure qualité de vie et à une prolongation de la survie comparativement à la dialyse. Au Canada, les inégalités dans l'accès à la transplantation et plus particulièrement à la transplantation d'un rein provenant d'un donneur vivant (TRDV) ont été documentées selon diverses dimensions démographiques. Cet article fait état des données existantes sur les inégalités d'accès à la TR et à la TRDV des Canadiens issus de communautés marginalisées en raison de la race et de l'ethnicité. OBJECTIFS: L'objectif est bipartite: 1) caractériser les données publiées sur les taux de TR et de TRDV parmi les Canadiens des communautés noires originaires d'Afrique et des Caraïbes (NAC) et les Canadiens originaires de l'Asie de l'Est et de l'Asie du Sud; 2) répondre à la question de recherche « Quels facteurs pourraient mener à un accès inéquitable à la TR pour les Canadiens des communautés NAC et des communautés est-asiatiques et sud-asiatiques? ¼. CRITÈRES D'ADMISSIBILITÉ: Les bases de données et la littérature grise ont été passées en revue en juin et novembre 2020 à la recherche d'articles de recherche originaux (texte intégral) ou de ressources de la littérature grise traitant de l'accès à la TR ou des obstacles rencontrés par les Canadiens des communautés NAC et des communautés est-asiatiques et sud-asiatiques. En tout, 25 articles ont été analysés de façon thématique. SOURCES: La littérature grise et les bases de données CINAHL, OVID Medline, OVID Embase et Cochrane. MÉTHODOLOGIE: Les caractéristiques tirées de la littérature ont été consignées et les conclusions décrivant les taux de TR et les facteurs influençant l'accès ont été résumées sous forme de compte rendu. Les principaux thèmes ont été dégagés puis synthétisés thématiquement. RÉSULTATS: Les Canadiens des communautés NAC, est-asiatiques et sud-asiatiques se heurtent à divers obstacles dans l'accès à des informations et des soins médicaux adaptés à leur culture, ce qui entraîne un accès inéquitable à la TR. Le manque de connaissances concernant l'IRT et la TR, les préoccupations religieuses et spirituelles, la stigmatisation de l'IRT et de la TR, les croyances en matière de santé, les déterminants sociaux de la santé et les expériences de racisme systémique dans les soins de santé figurent parmi les possibles obstacles rencontrés. LIMITES: Cette revue inclut de la documentation dont la méthodologie varie, et la qualité des études retenues n'a pas été évaluée. Les données sur la race et l'ethnicité n'étaient pas consignées ou définies de façon normalisée. Les communautés examinées ne sont pas homogènes, les avis individuels sur le don d'organes et la TR pourraient varier. CONCLUSION: Cet examen de la portée a permis de cerner les obstacles dans l'accès à la TR et à la TRDV rencontrés par les patients des communautés marginalisées en raison de la race et de l'ethnicité. Il est urgent de poursuivre la recherche afin de mieux comprendre les obstacles et les besoins de soutien de ces communautés et pour élaborer des stratégies qui permettront un accès plus équitable à la TRDV à la population de plus en plus diversifiée du Canada.

Barriers to Accessing Kidney Transplantation Among Populations Marginalized by Race and Ethnicity in Canada: A Scoping Review Part 1-Indigenous Communities in Canada.

BACKGROUND: Kidney transplantation (KT), a treatment option for end-stage kidney disease (ESKD), is associated with longer survival and improved quality of life compared with dialysis. Inequities in access to KT, and specifically, living donor kidney transplantation (LDKT), have been documented in Canada along various demographic dimensions. In this article, we review existing evidence about inequitable access and barriers to KT and LDKT for patients from Indigenous communities in Canada. OBJECTIVE: To characterize the current state of literature on access to KT and LDKT among Indigenous communities in Canada and to answer the research question, "what factors may influence inequitable access to KT among Indigenous communities in Canada." ELIGIBILITY CRITERIA: Databases and gray literature were searched in June and November 2020 for full-text original research articles or gray literature resources addressing KT access or barriers in Indigenous communities in Canada. A total of 26 articles were analyzed thematically. SOURCES OF EVIDENCE: Gray literature and CINAHL, OVID Medline, OVID Embase, and Cochrane databases. CHARTING METHODS: Literature characteristics were recorded and findings which described rates of and factors that influence access to KT were summarized in a narrative account. Key themes were subsequently identified and synthesized thematically in the review. RESULTS: Indigenous communities in Canada experience various barriers in accessing culturally safe medical information and care, resulting in inequitable access to KT. Barriers include insufficient incorporation of Indigenous ways of knowing and being in information dissemination and care for ESKD and KT, spiritual concerns, health beliefs, logistical hurdles to accessing care, and systemic mistrust resulting from colonialism and systemic racism. LIMITATIONS: This review included studies that used various methodologies and did not assess study quality. Data on Indigenous status were not reported or defined in a standardized manner. Indigenous communities are not homogeneous and views on organ donation and KT vary by individual. CONCLUSIONS: Our scoping review has identified potential barriers that Indigenous communities may face in accessing KT and LDKT. Further research is urgently needed to better understand barriers and support needs and to develop strategies to improve equitable access to KT and LDKT for Indigenous populations in Canada.

CONTEXTE: La transplantation rénale (TR), une des options de traitement de l'insuffisance rénale terminale (IRT), est associée à une meilleure qualité de vie et à une prolongation de la survie comparativement à la dialyse. Au Canada, les inégalités dans l'accès à la transplantation et plus particulièrement à la transplantation d'un rein provenant d'un donneur vivant (TRDV) ont été documentées selon diverses dimensions démographiques. Cet article fait état des données existantes sur les inégalités d'accès à la TR et à la TRDV des patients canadiens d'origine autochtone. OBJECTIFS: Caractériser les données publiées sur les taux de TR et de TRDV chez les Canadiens d'origine autochtone et répondre à la question de recherche « Quels facteurs pourraient mener à un accès inéquitable à la TR pour les autochtones du Canada? ¼. CRITÈRES D'ADMISSIBILITÉ: Les bases de données et la littérature grise ont été passées en revue en juin et novembre 2020 à la recherche d'articles de recherche originaux (texte intégral) ou de ressources de la littérature grise traitant de l'accès à la TR ou des obstacles rencontrés par les autochtones au Canada. En tout, 26 articles ont été analysés de façon thématique. SOURCES: La littérature grise et les bases de données CINAHL, OVID Medline, OVID Embase et Cochrane. MÉTHODOLOGIE: Les caractéristiques tirées de la littérature ont été consignées et les conclusions décrivant les taux de TR et les facteurs influençant l'accès ont été résumées sous forme de compte rendu. Les principaux thèmes ont été dégagés puis synthétisés thématiquement. RÉSULTATS: Les communautés autochtones du Canada rencontrent divers obstacles dans l'accès à des informations et des soins médicaux adaptés à leur culture, ce qui entraîne un accès inéquitable à la TR. Parmi ces obstacles, on note l'intégration insuffisante des façons d'être et de faire autochtones dans la prestation de soins et dans la diffusion d'informations sur l'IRT et la TR, des préoccupations d'ordre spirituel, des croyances en matière de santé, des obstacles logistiques dans l'accès aux soins, et une méfiance bien intégrée résultant du colonialisme et du racisme systémique. LIMITATIONS: Cette revue inclut de la documentation dont la méthodologie varie, et la qualité des études retenues n'a pas été évaluée. Les données sur le statut d'Autochtone n'étaient pas consignées ou définies de façon normalisée. Les communautés autochtones ne sont pas homogènes, les avis individuels sur le don d'organes et la TR pourraient varier. CONCLUSIONS: Cet examen de la portée a permis de cerner les obstacles dans l'accès à la TR et à la TRDV rencontrés par les patients autochtones du Canada. Il est urgent de poursuivre la recherche afin de mieux comprendre les obstacles et les besoins de soutien, et pour élaborer des stratégies visant un meilleur accès à la TRDV pour les autochtones du Canada.

Desire to Belong Affects Instagram Behavior and Perceived Social Support.

Social networking site (SNS) use has been shown to predict both positive and negative well-being. These discrepant findings may be explained by people's motivations for and frequency of using SNSs. This study aimed to explore how frequency of online interactions can be affected by users' motives, specifically, being motivated by a sense of belonging, and possible perceived social support derived from the popular image-based SNS, Instagram. A total of 313 Instagram users (84.4% female, median age = 22 years) completed an online survey between March and September 2017 asking about their motives for using Instagram, perceived social support, and frequency of Instagram use. Multiple regression mediation analyses examined the relationship between being motivated by a desire to belong, mediator variables (frequency of posting, liking, and viewing posts), and perceived social support. A greater desire to belong significantly positively predicted frequency of Instagram use, total perceived social support, and perceived social support from friends and significant others. However, frequency of Instagram use did not predict perceived social support. As such, frequency of Instagram use did not mediate the relationship between motivation and social support. Future research could explore how other user motives and peer feedback affect Instagram use and other well-being outcomes.

A multi-stage approach to clustering and imputation of gene expression profiles.

MOTIVATION: Microarray experiments have revolutionized the study of gene expression with their ability to generate large amounts of data. This article describes an alternative to existing approaches to clustering of gene expression profiles; the key idea is to cluster in stages using a hierarchy of distance measures. This method is motivated by the way in which the human mind sorts and so groups many items. The distance measures arise from the orthogonal breakup of Euclidean distance, giving us a set of independent measures of different attributes of the gene expression profile. Interpretation of these distances is closely related to the statistical design of the microarray experiment. This clustering method not only accommodates missing data but also leads to an associated imputation method. RESULTS: The performance of the clustering and imputation methods was tested on a simulated dataset, a yeast cell cycle dataset and a central nervous system development dataset. Based on the Rand and adjusted Rand indices, the clustering method is more consistent with the biological classification of the data than commonly used clustering methods. The imputation method, at varying levels of missingness, outperforms most imputation methods, based on root mean squared error (RMSE). AVAILABILITY: Code in R is available on request from the authors.

Dual phosphorylation of Ric-8A enhances its ability to mediate G protein α subunit folding and to stimulate guanine nucleotide exchange.

Resistance to inhibitors of cholinesterase-8A (Ric-8A) and Ric-8B are essential biosynthetic chaperones for heterotrimeric G protein α subunits. We provide evidence for the direct regulation of Ric-8A cellular activity by dual phosphorylation. Using proteomics, Western blotting, and mutational analyses, we determined that Ric-8A was constitutively phosphorylated at five serines and threonines by the protein kinase CK2. Phosphorylation of Ser435 and Thr440 in rat Ric-8A (corresponding to Ser436 and Thr441 in human Ric-8A) was required for high-affinity binding to Gα subunits, efficient stimulation of Gα subunit guanine nucleotide exchange, and mediation of Gα subunit folding. The CK2 consensus sites that contain Ser435 and Thr440 are conserved in Ric-8 homologs from worms to mammals. We found that the homologous residues in mouse Ric-8B, Ser468 and Ser473, were also phosphorylated. Mutation of the genomic copy of ric-8 in Caenorhabditis elegans to encode alanine in the homologous sites resulted in characteristic ric-8 reduction-of-function phenotypes that are associated with defective Gq and Gs signaling, including reduced locomotion and defective egg laying. The C. elegans ric-8 phosphorylation site mutant phenotypes were partially rescued by chemical stimulation of Gq signaling. These results indicate that dual phosphorylation represents a critical form of conserved Ric-8 regulation and demonstrate that Ric-8 proteins are needed for effective Gα signaling. The position of the CK2-phosphorylated sites within a structural model of Ric-8A reveals that these sites contribute to a key acidic and negatively charged surface that may be important for its interactions with Gα subunits.

House dust mite allergen (Derp1 and Blot5) levels in asthmatics' home in Hongkong.

OBJECTIVE: To measure Derp1 and Blot5 allergen levels in asthmatics' homes in Hongkong. METHODS: Seventy houses were enrolled for a mite indoor environment study. Dust samples were obtained from two sites of each patients' house: bed and floor. Derp1 and Blot5 levels were quantified by a two-site monoclonal antibody-based ELISA technique. RESULTS: The levels of Derp1 allergens found in bed (geometric mean (GM) 3.43 microg/g of dust; 95%CI, 1.89-4.96 microg/g) and on the floor (GM 1.12 microg/g of dust; 95%CI, 0.71-1.53 microg/g) indicated significant differences (P=0.005). However, the levels of Blot5 allergens found in bed (GM 19.00 microg/g of dust; 95%CI, 0.89-38.90 microg/g) and on the floor (GM 6.14 microg/g of dust; 95%CI, 0.40-11.90 microg/g) showed no statistically significant difference. In addition, in regards to the exposure index for Derp1 and Blot5 allergens found in bed and on the floor, 17.6% in bed and 8.6% on the floor had levels of Blot5 > or = 10 microg/g of dust, higher than those obtained for Derp1 (7.2% and 0% in bed and on the floor respectively, P<0.05); higher percentages in bed and on the floor (25.0% and 35.7%) were observed for levels of Blot5 = 0 microg/g of dust as compared with Derp1 in bed and on the floor (4.3% and 14.5% respectively, P<0.05). CONCLUSIONS: Derp1 and Blot5 are the major allergens found in this regional study, Blot5 is a more potent allergen in Hongkong, probably reflecting the high level of exposure to Blomia tropicalis (Bt). Bt and Dermatophagoides pteronyssinus (Dp) allergens should be included for precise diagnosis and effective immuno-therapeutic treatment of mite allergy in Hongkong.

The clinical significance of "squamous intraepithelial lesion of indeterminate grade" as a distinct cytologic category.

The histologic and/or cytologic follow-up of 127 cases of cervical lesions termed "squamous intraepithelial lesion of indeterminate grade" (SIL) on Papanicolaou (Pap) smears by the 2001 Bethesda System was compared with 150 control cases of low-grade SIL (LSIL), high-grade SIL (HSIL), and atypical squamous cells, cannot exclude HSIL (ASC-H). A follow-up diagnosis of cervical intraepithelial neoplasia (CIN) 2 or higher was identified in 22.8% of SIL cases, which was 2.6 times higher than LSIL, 3 times lower than HSIL, and 1.5 times lower than ASC-H. A follow-up diagnosis of CIN 1 was identified in 31.5% of SIL cases, which was 2 times lower than the LSIL group, 1.5 times higher than the ASC-H cases, and 1.8 times higher than the HSIL group. We found that 22.0% of cases diagnosed as SIL were followed up by Pap smears rather than colposcopy and biopsy, compared with about 1% of LSIL and HSIL cases. Because SIL cases have a significant risk of harboring CIN 2 or greater, we recommend follow-up by colposcopy and biopsy.

Left ventricular rupture due to HIV-associated T-cell lymphoma.

Patients with lymphoma can develop cardiac involvement that includes malignant pericardial effusions and myocardial infiltration, but extensive myocardial invasion by tumor with resultant rupture has been reported only rarely. We report a case of a patient with human immunodeficiency virus and T-cell lymphoma who presented with signs and symptoms that were suggestive of a non-ST-elevation myocardial infarction. Plans were made for cardiac catheterization, but the patient developed thrombocytopenia after the initiation of heparin and eptifibatide. Cardiac catheterization was deferred, and shortly afterwards he had a witnessed cardiac arrest in the hospital and could not be resuscitated. Autopsy revealed transmural infiltration of the myocardium with lymphoma and resultant rupture of the left ventricular free wall. To our knowledge, this is the 1st reported case of left ventricular free-wall rupture due to transmural infiltration by human-immunodeficiency-virus-associated peripheral T-cell lymphoma.We conclude that noncoronary causes of chest pain, including direct myocardial infiltration, should be considered in immunocompromised patients with lymphoma.