Pulmonary surfactant protein B carried by HDL predicts incident CVD in patients with type 1 diabetes.

Atherosclerotic CVD is the major cause of death in patients with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome have been shown to associate with prevalent CVD in T1DM. We therefore sought to determine which proteins carried by HDL might predict incident CVD in patients with T1DM. Using targeted MS/MS, we quantified 50 proteins in HDL from 181 T1DM subjects enrolled in the prospective Coronary Artery Calcification in Type 1 Diabetes study. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). We found that only one HDL protein-SFTPB (pulmonary surfactant protein B)-predicted incident CVD in all the models tested. In a fully adjusted model that controlled for lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P = 0.022). In addition, plasma fractionation demonstrated that SFTPB is nearly entirely bound to HDL. Although previous studies have shown that high plasma levels of SFTPB associate with prevalent atherosclerosis only in smokers, we found that SFTPB predicted incident CVD in T1DM independently of smoking status and a wide range of confounding factors, including HDL-C, LDL-C, and triglyceride levels. Because SFTPB is almost entirely bound to plasma HDL, our observations support the proposal that SFTPB carried by HDL is a marker-and perhaps mediator-of CVD risk in patients with T1DM.

The Atlantic salmon genome provides insights into rediploidization.

The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

Subcellular localization and characterization of estrogenic pathway regulators and mediators in Atlantic salmon spermatozoal cells.

Much progress has been made regarding our understanding of aromatase regulation, estrogen synthesis partitioning and communication between the germinal and somatic compartments of the differentiating gonad. We now know that most of the enzymatic and signaling apparatus required for steroidogenesis is endogenously expressed within germ cells. However, less is known about the expression and localization of steroidogenic components within mature spermatozoa. We have assembled a sperm library presenting 197,015 putative transcripts. Co-expression clustering analysis revealed that 6687 genes were present at higher levels in sperm in comparison to fifteen other salmon tissue libraries. The sperm transcriptome is highly complex containing the highest proportion of unannotated genes (45%) of the tissues analyzed. Our analysis of highly expressed genes in late-stage sperm revealed dedication to tasks involving chromatin remodeling, flagellogenesis and proteolysis. In addition, using various different embedding and microscopic techniques, we examined the morphology of salmon spermatozoa and characterized expression and localization of several estrogenic regulatory and signaling proteins by immunohistochemistry. We provide evidence for the endogenous synthesis and localization of aromatase (CYP19A and CYP19B1) and potential mediators of estrogen [i.e., ER-alpha and soluble adenylyl cyclase (sAC)] or phosphate (i.e., CREB and FOXL2A) signaling. Partitioning of select transcripts that encode AR-beta, FSH and the LH receptor, but not AR-alpha, LH or the FSH receptor, further points to localized specificity of function in the steroidogenic circuitry of the sperm cell. These results open new avenues of investigation to further our understanding of the intra- and intercellular regulatory processes that guide sperm development and biology.

Functional Annotation of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture.

We describe an emerging initiative - the 'Functional Annotation of All Salmonid Genomes' (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.

Implementing shared decision making in federally qualified health centers, a quasi-experimental design study: the Office-Guidelines Applied to Practice (Office-GAP) program.

BACKGROUND: Use of Shared Decision-Making (SDM) and Decision Aids (DAs) has been encouraged but is not regularly implemented in primary care. The Office-Guidelines Applied to Practice (Office-GAP) intervention is an application of a previous model revised to address guidelines based care for low-income populations with diabetes and coronary heart disease (CHD). OBJECTIVE: To evaluate Office-GAP Program feasibility and preliminary efficacy on medication use, patient satisfaction with physician communication and confidence in decision in low-income population with diabetes and coronary heart disease (CHD) in a Federally Qualified Healthcare Center (FQHC). METHOD: Ninety-five patients participated in an Office-GAP program. A quasi-experimental design study, over 6 months with 12-month follow-up. Office-GAP program integrates health literacy, communication skills education for patients and physicians, patient/physician decision support tools and SDM into routine care. MAIN MEASURES: 1) Implementation rates of planned program elements 2) Patient satisfaction with communication and confidence in decision, and 3) Medication prescription rates. We used the GEE method for hierarchical logistic models, controlling for confounding. RESULTS: Feasibility of the Office-GAP program in the FQHC setting was established. We found significant increase in use of Aspirin/Plavix, statin and beta-blocker during follow-up compared to baseline: Aspirin OR 1.5 (95 % CI: 1.1, 2.2) at 3-months, 1.9 (1.3, 2.9) at 6-months, and 1.8 (1.2, 2.8) at 12-months. Statin OR 1.1 (1.0, 1.3) at 3-months and 1.5 (1.1, 2.2) at 12-months; beta-blocker 1.8 (1.1, 2.9) at 6-months and 12-months. Program elements were consistently used (≥ 98 % clinic attendance at training and tool used). Patient satisfaction with communication and confidence in decision increased. CONCLUSIONS: The use of Office-GAP program to teach SDM and use of DAs in real time was demonstrated to be feasible in FQHCs. It has the potential to improve satisfaction with physician communication and confidence in decisions and to improve medication use. The Office-GAP program is a brief, efficient platform for delivering patient and provider education in SDM and could serve as a model for implementing guideline based care for all chronic diseases in outpatient clinical settings. Further evaluation is needed to establish feasibility outside clinical study, reach, effectiveness and cost-effectiveness of this approach.

Expression analysis of sex-determining pathway genes during development in male and female Atlantic salmon (Salmo salar).

We studied the expression of 28 genes that are involved in vertebrate sex-determination or sex-differentiation pathways, in male and female Atlantic salmon (Salmo salar) in 11 stages of development from fertilization to after first feeding. Gene expression was measured in half-sibs that shared the same dam. The sire of family 1 was a sex-reversed female (i.e., genetically female but phenotypically male), and so the progeny of this family are all female. The sire of family 2 was a true male, and so the offspring were 50% male and 50% female. Gene expression levels were compared among three groups: 20 female offspring of the cross between a regular female and the sex-reversed female (family 1, first group), ∼ 10 females from the cross between a regular female and a regular male (family 2, second group) and ∼ 10 males from this same family (family 2, third group). Statistically significant differences in expression levels between males and the two groups of females were observed for two genes, gsdf and amh/mis, in the last four developmental stages examined. SdY, the sex-determining gene in rainbow trout, appeared to be expressed in males from 58 days postfertilization (dpf). Starting at 83 dpf, ovarian aromatase, cyp19a, expression appeared to be greater in both groups of females compared with males, but this difference was not statistically significant. The time course of expression suggests that sdY may be involved in the upregulation of gsdf and amh/mis and the subsequent repression of cyp19a in males via the effect of amh/mis.

Genome-wide association analysis reveals loci associated with resistance against Piscirickettsia salmonis in two Atlantic salmon (Salmo salar L.) chromosomes.

BACKGROUND: Pisciricketssia salmonis is the causal agent of Salmon Rickettsial Syndrome (SRS), which affects salmon species and causes severe economic losses. Selective breeding for disease resistance represents one approach for controlling SRS in farmed Atlantic salmon. Knowledge concerning the architecture of the resistance trait is needed before deciding on the most appropriate approach to enhance artificial selection for P. salmonis resistance in Atlantic salmon. The purpose of the study was to dissect the genetic variation in the resistance to this pathogen in Atlantic salmon. METHODS: 2,601 Atlantic salmon smolts were experimentally challenged against P. salmonis by means of intra-peritoneal injection. These smolts were the progeny of 40 sires and 118 dams from a Chilean breeding population. Mortalities were recorded daily and the experiment ended at day 40 post-inoculation. Fish were genotyped using a 50K Affymetrix® Axiom® myDesignTM Single Nucleotide Polymorphism (SNP) Genotyping Array. A Genome Wide Association Analysis was performed on data from the challenged fish. Linear regression and logistic regression models were tested. RESULTS: Genome Wide Association Analysis indicated that resistance to P. salmonis is a moderately polygenic trait. There were five SNPs in chromosomes Ssa01 and Ssa17 significantly associated with the traits analysed. The proportion of the phenotypic variance explained by each marker is small, ranging from 0.007 to 0.045. Candidate genes including interleukin receptors and fucosyltransferase have been found to be physically linked with these genetic markers and may play an important role in the differential immune response against this pathogen. CONCLUSIONS: Due to the small amount of variance explained by each significant marker we conclude that genetic resistance to this pathogen can be more efficiently improved with the implementation of genetic evaluations incorporating genotype information from a dense SNP array.

Screening Offenders: The Exploration of a Youth Level of Service/Case Management Inventory: (YLS/CMI) Brief Screener.

Although structured assessments have helped standardize juvenile court processes by systematically measuring risk for recidivism, it has been argued that some assessments lack the ability to perform as a brief screener. This study explored the potential for the original 42-item Youth Level of Service/Case Management Inventory (YLS/CMI) risk assessment to perform as a brief screener for a sample of first-time juvenile offenders in a mid-western, industrialized county. Results indicated that the original and shortened version of the YLS/CMI significantly predicted two-year recidivism for male and female offenders. Implications for situationally targeted forms of risk assessment are discussed.

Lymphopenia in the Adult Population With Fontan Physiology: A Potential New Marker for Disease Assessment.

Background: Patients with complex congenital heart disease and Fontan palliation frequently develop extracardiac disease, including hematologic abnormalities, such as lymphopenia. However, the clinical implications of this finding are poorly understood and are therefore the topic of this investigation. Methods: Patients with Fontan physiology in our centre (1999-2018) were evaluated for the presence and impact of lymphopenia. The cohort was divided into a group with lymphopenia (L) (2 consecutive absolute lymphocyte counts ≤ 1∗103 K/ µL) and a group who had never had lymphopenia (NL). Clinical characteristics and hospital admissions (762 patient-years) were evaluated. Results: In 62 adult patients with Fontan physiology (aged 34 ± 9 years; 32 women [52%]), the patients who developed lymphopenia earliest did so 8 years after Fontan completion, with up to 60% of patients developing lymphopenia by 30 years. Lymphopenia was found to be associated with portal hypertension (varices, ascites, splenomegaly, and thrombocytopenia [VAST] score)-NL: 0 (0-2) vs L: 2 (0-4), P < 0.0001). A total of 76 heart failure and 81 arrhythmia-associated admissions occurred per 1000 patient-years. At 40 years post-Fontan, the probability of a heart failure admission was higher in the L group (L: 51 [86%] vs NL: 8 [14%], P < 0.01). Conclusions: Adult patients with Fontan physiology and lymphopenia demonstrated portal hypertension and lymphatic dysfunction more commonly, perhaps suggesting that this may be a marker of Fontan congestion and early Fontan failure. Further investigation into the relationship between lymphopenia, clinical outcomes, and Fontan function is needed.

Contexte: Chez les patients atteints d'une cardiopathie congénitale complexe ayant subi une intervention de Fontan, il est fréquent de voir apparaître des maladies extracardiaques, dont des anomalies hématologiques, comme la lymphopénie. Cependant, les implications cliniques de cette observation sont mal comprises et font donc l'objet de cette étude. Méthodologie: La présence et l'impact d'une lymphopénie ont été évalués chez des patients présentant une physiologie de Fontan dans notre centre (1999-2018). La cohorte a été divisée en un groupe composé de sujets atteints de lymphopénie (L) (2 mesures consécutives du nombre absolu de lymphocytes ≤ 1 x 103 K/µL) et un groupe de sujets n'ayant jamais présenté de lymphopénie (NL). Les caractéristiques initiales et les hospitalisations (762 années-patients) ont été évaluées. Résultats: Chez 62 adultes présentant une physiologie de Fontan (âgés de 34 ± 9 ans; 32 femmes [52 %]), la lymphopénie est apparue au plus tôt 8 ans après l'intervention de Fontan, avant 30 ans chez jusqu'à 60 % des patients. La lymphopénie a été associée à l'hypertension portale (score varices, ascite, splénomégalie et thrombocytopénie [VAST]) ­ NL : 0 (0-2) vs L : 2 (0-4), p < 0,0001. Au total, il y a eu 76 hospitalisations pour insuffisance cardiaque et 81 pour arythmie pour 1000 années-patients. Quarante ans après l'intervention de Fontan, la probabilité d'une hospitalisation pour insuffisance cardiaque était plus élevée dans le groupe L que dans le groupe NL (L : 51 [86 %] vs NL : 8 [14 %], p < 0,01). Conclusions: L'hypertension portale et la dysfonction lymphatique étaient plus fréquentes chez les adultes présentant une physiologie de Fontan et une lymphopénie, ce qui laisse peut-être entendre que ce pourrait être un marqueur d'une congestion et d'une défaillance précoce du système Fontan. D'autres recherches sur le lien entre la lymphopénie, les issues cliniques et la fonction du système Fontan sont nécessaires.

The perception of the scope of oral and maxillofacial surgery and differentiation from similar specialities among dental students, medical students, trainee interns and pre-vocational junior doctors.

PURPOSE: To explore the ability of Dental Students (DS), Medical Students (MS), Trainee Interns (TI) and Pre-vocational Junior Doctors (JD) in identifying procedures performed by Oral and Maxillofacial Surgery (OMS), the scope of practice (SOP) of OMS and ability to differentiate OMS from similar specialities. METHODS: The study included 282 complete responses to a survey consisting of: 9 demographic questions, 11 OMS awareness, professional ambition, teaching and exposure, confidence in identifying and referring questions and 70 procedural/scenario questions across four domains. Collected data was qualitatively and statistically analysed using SPSS V29. RESULTS: OMS awareness was limited. 92.2% reported None to Small amount of OMS teaching and exposure during university, with 66.0% preferring to have had a Fair to Significant amount. DS experienced more than medical respondents (2.1 vs. 1.5, p < 0.001). Most respondents reported No to Low confidence in identifying the SOP and procedures performed by OMS (67.7%) and referring to OMS (62.4%) compared to similar specialities (32.4% and 33.2%, respectively). 52.9% of procedures performed by OMS were correctly identified as being performed by OMS. The ability to identify the OMS SOP (8.7%) and differentiate OMS from similar specialities (5.0%) was low, however better among DS than medical respondents (14.9% vs. 6.3%, p = 0.002 and 12.2% vs. 2.2%, p < 0.001). CONCLUSION: The study has highlighted a deficit in the understanding of OMS with potential implications in the public and private healthcare sector. Identification of procedures, OMS SOP and ability to differentiate OMS from similar specialities is limited however slightly better among DS.

Adult teleost heart expresses two distinct troponin C paralogs: cardiac TnC and a novel and teleost-specific ssTnC in a chamber- and temperature-dependent manner.

The teleost-specific whole genome duplication created multiple copies of genes allowing for subfunctionalization of isoforms. In this study, we show that the teleost cardiac Ca2+-binding troponin C (TnC) is the product of two distinct genes: cardiac TnC (cTnC, TnnC1a) and a fish-specific slow skeletal TnC (ssTnC, TnnC1b). The ssTnC gene is novel to teleosts as mammals have a single gene commonly referred as cTnC but which is also expressed in slow skeletal muscle. In teleosts, the data strongly indicate that these are two TnC genes are different paralogs. Because we determined that ssTnC exists across many teleosts but not in basal ray-finned fish (e.g., bichir), we propose that these paralogs are the result of an ancestral tandem gene duplication persisting only in teleosts. Quantification of mRNA levels was used to demonstrate distinct expression localization patterns of the paralogs within the chambers of the heart. In the adult zebrafish acclimated at 28°C, ssTnC mRNA levels are twofold greater than cTnC mRNA levels in the atrium, whereas cTnC mRNA was almost exclusively expressed in the ventricle. Meanwhile, rainbow trout acclimated at 5°C showed cTnC mRNA levels in both chambers significantly greater than ssTnC. Distinct responses to temperature acclimation were also quantified in both adult zebrafish and rainbow trout, with mRNA in both chambers shifting to express higher levels of cTnC in 18°C acclimated zebrafish and 5°C acclimated trout. Possible subfunctionalization of TnC isoforms may provide insight into how teleosts achieve physiological versatility in chamber-specific contractile properties.

Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome.

RAB, ADP-ribosylation factors (ARFs) and ARF-like (ARL) proteins belong to the Ras superfamily of small GTP-binding proteins and are essential for various membrane-associated intracellular trafficking processes. None of the approximately 50 known members of this family are linked to human disease. Using a bioinformatic screen for ciliary genes in combination with mutational analyses, we identified ARL6 as the gene underlying Bardet-Biedl syndrome type 3, a multisystemic disorder characterized by obesity, blindness, polydactyly, renal abnormalities and cognitive impairment. We uncovered four different homozygous substitutions in ARL6 in four unrelated families affected with Bardet-Biedl syndrome, two of which disrupt a threonine residue important for GTP binding and function of several related small GTP-binding proteins. Analysis of the Caenorhabditis elegans ARL6 homolog indicates that it is specifically expressed in ciliated cells, and that, in addition to the postulated cytoplasmic functions of ARL proteins, it undergoes intraflagellar transport. These findings implicate a small GTP-binding protein in ciliary transport and the pathogenesis of a pleiotropic disorder.

Apolipoprotein A4 Elevates Sympathetic Activity and Thermogenesis in Male Mice.

Long-chain fatty acids induce apolipoprotein A4 (APOA4) production in the small intestine and activate brown adipose tissue (BAT) thermogenesis. The increase in BAT thermogenesis enhances triglyceride clearance and insulin sensitivity. Acute administration of recombinant APOA4 protein elevates BAT thermogenesis in chow-fed mice. However, the physiological role of continuous infusion of recombinant APOA4 protein in regulating sympathetic activity, thermogenesis, and lipid and glucose metabolism in low-fat-diet (LFD)-fed mice remained elusive. The hypothesis of this study was that continuous infusion of mouse APOA4 protein would increase sympathetic activity and thermogenesis in BAT and subcutaneous inguinal white adipose tissue (IWAT), attenuate plasma lipid levels, and improve glucose tolerance. To test this hypothesis, sympathetic activity, BAT temperature, energy expenditure, body weight, fat mass, caloric intake, glucose tolerance, and levels of BAT and IWAT thermogenic and lipolytic proteins, plasma lipids, and markers of fatty acid oxidation in the liver in mice with APOA4 or saline treatment were measured. Plasma APOA4 levels were elevated, BAT temperature and thermogenesis were upregulated, and plasma triglyceride (TG) levels were reduced, while body weight, fat mass, caloric intake, energy expenditure, and plasma cholesterol and leptin levels were comparable between APOA4- and saline-treated mice. Additionally, APOA4 infusion stimulated sympathetic activity in BAT and liver but not in IWAT. APOA4-treated mice had greater fatty acid oxidation but less TG content in the liver than saline-treated mice had. Plasma insulin in APOA4-treated mice was lower than that in saline-treated mice after a glucose challenge. In conclusion, continuous infusion of mouse APOA4 protein stimulated sympathetic activity in BAT and the liver, elevated BAT thermogenesis and hepatic fatty acid oxidation, and consequently attenuated levels of plasma and hepatic TG and plasma insulin without altering caloric intake, body weight gain and fat mass.

Population-size history inferences from the coho salmon (Oncorhynchus kisutch) genome.

Coho salmon (Oncorhynchus kisutch) are a culturally and economically important species that return from multiyear ocean migrations to spawn in rivers that flow to the Northern Pacific Ocean. Southern stocks of coho salmon in Canada and the United States have significantly declined over the past quarter century, and unfortunately, conservation efforts have not reversed this trend. To assist in stock management and conservation efforts, we generated a chromosome-level genome assembly. We also resequenced the genomes of 83 coho salmon across the North American range to identify nucleotide variants and understand the demographic histories of these salmon by modeling effective population size from genome-wide data. From demographic history modeling, we observed reductions in effective population sizes between 3,750 and 8,000 years ago for several northern sampling sites, which may correspond to bottleneck events during recolonization after glacial retreat.

Smelt was the likely beneficiary of an antifreeze gene laterally transferred between fishes.

BACKGROUND: Type II antifreeze protein (AFP) from the rainbow smelt, Osmerus mordax, is a calcium-dependent C-type lectin homolog, similar to the AFPs from herring and sea raven. While C-type lectins are ubiquitous, type II AFPs are only found in a few species in three widely separated branches of teleost fishes. Furthermore, several other non-homologous AFPs are found in intervening species. We have previously postulated that this sporadic distribution has resulted from lateral gene transfer. The alternative hypothesis, that the AFP evolved from a lectin present in a shared ancestor and that this gene was lost in most species, is not favored because both the exon and intron sequences are highly conserved. RESULTS: Here we have sequenced and annotated a 160 kb smelt BAC clone containing a centrally-located AFP gene along with 14 other genes. Quantitative PCR indicates that there is but a single copy of this gene within the smelt genome, which is atypical for fish AFP genes. The corresponding syntenic region has been identified and searched in a number of other species and found to be devoid of lectin or AFP sequences. Unlike the introns of the AFP gene, the intronic sequences of the flanking genes are not conserved between species. As well, the rate and pattern of mutation in the AFP gene are radically different from those seen in other smelt and herring genes. CONCLUSIONS: These results provide stand-alone support for an example of lateral gene transfer between vertebrate species. They should further inform the debate about genetically modified organisms by showing that gene transfer between 'higher' eukaryotes can occur naturally. Analysis of the syntenic regions from several fishes strongly suggests that the smelt acquired the AFP gene from the herring.

Chromosomal differences between European and North American Atlantic salmon discovered by linkage mapping and supported by fluorescence in situ hybridization analysis.

BACKGROUND: Geographical isolation has generated a distinct difference between Atlantic salmon of European and North American Atlantic origin. The European Atlantic salmon generally has 29 pairs of chromosomes and 74 chromosome arms whereas it has been reported that the North American Atlantic salmon has 27 chromosome pairs and an NF of 72. In order to predict the major chromosomal rearrangements causing these differences, we constructed a dense linkage map for Atlantic salmon of North American origin and compared it with the well-developed map for European Atlantic salmon. RESULTS: The presented male and female genetic maps for the North American subspecies of Atlantic salmon, contains 3,662 SNPs located on 27 linkage groups. The total lengths of the female and male linkage maps were 2,153 cM and 968 cM respectively, with males characteristically showing recombination only at the telomeres. We compared these maps with recently published SNP maps from European Atlantic salmon, and predicted three chromosomal reorganization events that we then tested using fluorescence in situ hybridization (FISH) analysis. The proposed rearrangements, which define the differences in the karyotypes of the North American Atlantic salmon relative to the European Atlantic salmon, include the translocation of the p arm of ssa01 to ssa23 and polymorphic fusions: ssa26 with ssa28, and ssa08 with ssa29. CONCLUSIONS: This study identified major chromosomal differences between European and North American Atlantic salmon. However, while gross structural differences were significant, the order of genetic markers at the fine-resolution scale was remarkably conserved. This is a good indication that information from the International Cooperation to Sequence the Atlantic salmon Genome, which is sequencing a European Atlantic salmon, can be transferred to Atlantic salmon from North America.

Type 2 diabetes patient activation and mHealth interventions decreased cardiovascular disease risk.

OBJECTIVES: Cardiovascular disease (CVD) deaths in patients with type 2 diabetes (T2D) are 2 to 4 times higher than among those without T2D. Our objective was to determine whether a patient activation program (Office-Guidelines Applied to Practice [Office-GAP]) plus a mobile health (mHealth) intervention compared with mHealth alone improved medication use and decreased 10-year atherosclerotic CVD (ASCVD) risk score in patients with T2D. STUDY DESIGN: Quasi-experimental design; Office-GAP plus mHealth vs mHealth only. METHODS: The Office-GAP intervention included (1) a patient activation group visit, (2) provider training, and (3) a decision support checklist used in real time during the encounter. The mHealth intervention included daily text messages for 15 weeks. Patients with T2D (hemoglobin A1c ≥ 8%) attending internal medicine residency clinics were randomly assigned to either the combined Office-GAP + mHealth group (Green) or mHealth-only group (White). After group visits, patients followed up with providers at 2 and 4 months. A generalized estimating equation regression model was used to compare change in medication use and ASCVD risk scores between the 2 arms at 0, 2, and 4 months. RESULTS: Fifty-one patients with diabetes (26 in Green team and 25 in White team) completed the study. The 10-year ASCVD risk score decreased in both groups (Green: -3.23; P = .06; White: -3.98; P = .01). Medication use increased from baseline to 4-month follow-up (statin: odds ratio [OR], 2.20; 95% CI, 1.32-3.67; aspirin: OR, 3.21, 95% CI, 1.44-7.17; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker: OR, 2.67, 95% CI, 1.09-6.56). There was no significant difference in impact of the combined intervention (Office-GAP + mHealth) compared with mHealth alone. CONCLUSIONS: Both Office-GAP + mHealth and mHealth alone increased the use of evidence-based medications and decreased 10-year ASCVD risk scores for patients with T2D in 4 months.

Improving diabetic patients' adherence to treatment and prevention of cardiovascular disease (Office Guidelines Applied to Practice-IMPACT Study)-a cluster randomized controlled effectiveness trial.

BACKGROUND: Despite nationwide improvements in cardiovascular disease (CVD) mortality and morbidity, CVD deaths in adults with type 2 diabetes (T2DM) are 2-4 times higher than among those without T2DM. A key contributor to these poor health outcomes is medication non-adherence. Twenty-one to 42% of T2DM patients do not take blood sugar, blood pressure (BP), or statin medications as prescribed. Interventions that foster and reinforce patient-centered communication show promise in improving health outcomes. However, they have not been widely implemented, in part due to a lack of compelling evidence for their effectiveness in real-life primary care settings. METHODS: This pragmatic cluster-randomized trial randomizes 17 teams in 12 Federally Qualified Healthcare Centers (FQHCs) to two experimental groups: intervention (group 1): Office-Gap + Texting vs. control (group 2): Texting only. Office-GAP (Office-Guidelines Applied to Practice) is a patient activation intervention to improve communication and patient-provider partnerships through brief patient and provider training in shared decision-making (SDM) and use of a guideline-based checklist. The texting intervention (Way2Health) is a cell phone messaging service that informs and encourages patients to adhere to goals, adhere to medication use and improve communication. After recruitment, patients in groups 1 and 2 will both attend (1) one scheduled group visit, (90-120 min) conducted by trained research assistants, and (2) follow-up visits with their providers after group visit at 0-1, 3, 6, 9, and 12 months. Data will be collected over 12-month intervention period. Our primary outcome is medication adherence measured using eCAP electronic monitoring and self-report. Secondary outcomes are (a) diabetes-specific 5-year CVD risk as measured with the UK Prospective Diabetes Study (UKPDS) Engine score, (b) provider engagement as measured by the CollaboRATE Shared-Decision Making measure, and (c) patient activation measures (PAM). DISCUSSION: This study will provide a rigorous pragmatic evaluation of the effectiveness of combined mHealth, and patient activation interventions compared to mHealth alone, targeting patients and healthcare providers in safety net health centers, in improving medication adherence and decreasing CVD risk. Given that 20-50% of adults with chronic illness demonstrate medication non-adherence, increasing adherence is essential to improve CVD outcomes as well as healthcare cost savings. TRIAL REGISTRATION: The ClinicalTrials.gov registration number is NCT04874116.

Ribosomal genes and heat shock proteins as putative markers for chronic, sublethal heat stress in Arctic charr: applications for aquaculture and wild fish.

Arctic charr thrive at high densities and can live in freshwater year round, making this species especially suitable for inland, closed containment aquaculture. However, it is a cold-water salmonid, which both limits where the species can be farmed and places wild populations at particular risk to climate change. Previously, we identified genes associated with tolerance and intolerance to acute, lethal temperature stress in Arctic charr. However, there remained a need to examine the genes involved in the stress response to more realistic temperatures that could be experienced during a summer heat wave in grow-out tanks that are not artificially cooled, or under natural conditions. Here, we exposed Arctic charr to sublethal heat stress of 15-18°C for 72 h, and gill tissues extracted before, during (i.e., at 72 h), immediately after cooling and after 72 h of recovery at ambient temperature (6°C) were used for gene expression profiling by microarray and qPCR analyses. The results revealed an expected pattern for heat shock protein expression, which was highest during heat exposure, with significantly reduced expression (approaching control levels) quickly thereafter. We also found that the expression of numerous ribosomal proteins was significantly elevated immediately and 72 h after cooling, suggesting that the gill tissues were undergoing ribosome biogenesis while recovering from damage caused by heat stress. We suggest that these are candidate gene targets for the future development of genetic markers for broodstock development or for monitoring temperature stress and recovery in wild or cultured conditions.

Identification of genes associated with heat tolerance in Arctic charr exposed to acute thermal stress.

Arctic charr is an especially attractive aquaculture species given that it features the desirable tissue traits of other salmonids and is bred and grown at inland freshwater tank farms year round. It is of interest to develop upper temperature tolerant (UTT) strains of Arctic charr to increase the robustness of the species in the face of climate change and to enable production in more southern regions. We used a genomics approach that takes advantage of the well-studied Atlantic salmon genome to identify genes that are associated with UTT in Arctic charr. Specifically, we conducted an acute temperature trial to identify temperature tolerant and intolerant Arctic charr individuals, which were subject to microarray and qPCR analysis to identify candidate UTT genes. These were compared with genes annotated in a quantitative trait locus (QTL) region that was previously identified as associated with UTT in rainbow trout and Arctic charr and that we sequenced in Atlantic salmon. Our results suggest that small heat shock proteins as well as HSP-90 genes are associated with UTT. Furthermore, hemoglobin expression was significantly downregulated in tolerant compared with intolerant fish. Finally, QTL analysis and expression profiling identified COUP-TFII as a candidate UTT gene, although its specific role is unclear given the identification of two transcripts, which appear to have different expression patterns. Our results highlight the importance of using more than one approach to identify candidate genes, particularly when examining a complicated trait such as UTT in a highly complex genome for which there is no reference genome.