Effect of intermittent bladder flushing on recurrence rate in feline urethral obstruction: 72 cases.

Objective: To evaluate the effect of intermittent bladder flushing on recurrent urethral obstruction (rUO) at 7 d and 30 d after discharge and the risk of bacteriuria as a result of indwelling urethral catheterization. Animals: There were 72 cats with suspected obstructive feline idiopathic cystitis admitted to the hospital. Procedures: Cats were randomly assigned to either intermittent bladder flushing (n = 34) or no-flush (control) groups (n = 38). Bladder flushing was performed with 5 mL/kg of sterile 0.9% saline, q8h during indwelling urinary catheterization. Urine was tested for bacteriuria by a point-of-care test at the time of urinary catheterization and via cystocentesis following catheter removal before discharge. Risk of rUO by groups and its association with other variables were evaluated. Results: The age (median: 3.0 years) in the flush group was younger (P = 0.01), and the length of hospitalization (> 24 hours) was longer (P < 0.01) than that of the control group. Overall rUO was 6.6% on Day 7 and 21.8% on Day 30 after discharge, but there was no significant difference between groups. A shorter duration of catheterization (< 24 hours) was associated with higher risk of rUO (odds ratio: 6.0). The incidence of catheter-related bacteriuria was 14.5% and was not significantly different between groups (13.8% and 15.2% in the flush and control, respectively). Conclusion and clinical relevance: Intermittent bladder flushing during hospitalization appears safe but did not decrease the incidence of rUO. The incidence of bacteriuria following catheterization was not affected by intermittent bladder flushing.

Effet des rinçages intermittents de la vessie sur le taux de récidive de l'obstruction urétrale féline: 72 cas. Objectif: Évaluer l'effet du rinçage intermittent de la vessie sur l'obstruction urétrale récurrente (rUO) à 7 jours et 30 jours après le congé et le risque de bactériurie résultant d'un cathétérisme urétral à demeure. Animaux: Il y avait 72 chats suspects de cystite idiopathique féline obstructive admis à l'hôpital. Procédures: Les chats ont été assignés au hasard à des groupes avec rinçage intermittent de la vessie (n = 34) ou sans rinçage (témoin) (n = 38). Le rinçage de la vessie a été effectué avec 5 mL/kg de solution saline stérile à 0,9 %, toutes les 8 heures pendant le cathétérisme urinaire à demeure. L'urine a été testée pour la bactériurie par un test au point de service au moment du cathétérisme urinaire et par cystocentèse après le retrait du cathéter avant le congé. Le risque de rUO par groupes et son association avec d'autres variables ont été évalués. Résultats: L'âge (médiane: 3,0 ans) dans le groupe rinçage était plus jeune (P = 0,01) et la durée d'hospitalisation (> 24 heures) était plus longue (P < 0,01) que celle du groupe témoin. La rUO globale était de 6,6 % au jour 7 et de 21,8 % au jour 30 après le congé, mais il n'y avait pas de différence significative entre les groupes. Une durée de cathétérisme plus courte (< 24 heures) était associée à un risque plus élevé de rUO (rapport de cotes: 6,0). L'incidence de la bactériurie liée au cathéter était de 14,5 % et n'était pas significativement différente entre les groupes (13,8 % et 15,2 % dans le rinçage et le témoin, respectivement). Conclusion et pertinence clinique: Le rinçage intermittent de la vessie pendant l'hospitalisation semble sans danger mais n'a pas diminué l'incidence de rUO. L'incidence de la bactériurie après cathétérisme n'a pas été affectée par le rinçage intermittent de la vessie.(Traduit par Dr Serge Messier).

Sexual and Physical Assault Before Age 18 and Young Adults' Perception of Unfair Treatment.

Research indicates that sexual and physical assault generate negative emotions of shame and anger, undermine self-esteem, and increase interpersonal sensitivity. This in turn may bring about behavioral changes and cognitive bias, which may adversely affect victims' social interactions. The purpose of this study was to examine whether sexual or physical assault before age 18 is associated with a heightened sense of being treated unfairly in early adulthood. A nationally representative sample of young adults age 18-21 (N = 2,770; 49% female) self-reported on whether they had ever been sexually or physically assaulted, whether it first occurred in childhood or adolescence, and how frequently they are treated unfairly in their everyday interactions with other people, as measured by the Everyday Discrimination Scale (EDS). Multivariate regression results indicated that child (≤age 12) physical assault and adolescent-onset (age 13-17) physical assault were associated with higher scores on the EDS for both men and women. Child sexual assault was associated with the EDS for men; adolescent-onset sexual assault was associated with the EDS for women. Violence as a minor was associated with each item of the EDS (e.g., treated with less respect, less courtesy, other people act of afraid of you, etc.). Violence victims attributed their elevated levels of perceived unfair treatment to their gender, race, age, and aspects of their physical appearance. Overall, the results suggest a mechanism through which a history of sexual and physical assault can affect social interactions.

Fluctuating asymmetry of finger lengths, digit ratio (2D:4D), and tattoos: A pre-registered replication and extension of Koziel et al. (2010).

BACKGROUND: Tattoos bring risks yet no obvious evolutionary benefit. Koziel et al. (2010) reported increased fluctuating symmetry (a proxy for low developmental instability) in tattooed men, suggesting they could serve as fitness indicators. AIMS: We replicate and extend the findings of Koziel et al. by examining fluctuating asymmetry of finger lengths and digit ratio (2D:4D) (a putative indicator of prenatal testosterone exposure) as predictors of adult tattoo prevalence. STUDY DESIGN: We used an online survey with a correlational design. SUBJECTS: Participants were recruited from the UK and Poland via university participant pools and social media. Data were available for presence/absence of tattoos and at least one predictor variable (composite Fluctuating Asymmetry [cFA], right-hand digit ratio [R2D:4D] and left-hand digit ratio [L2D:4D]) for n = 186 males and n = 997 females. OUTCOME MEASURES: We firstly assessed presence/absence of tattoos; when at least one tattoo was present, we also examined overall number and highest visibility. RESULTS: Greater cFA was associated with lower likelihood of having tattoos in males, though in females greater cFA was associated with higher numbers of tattoos. R2D:4D and L2D:4D correlated negatively with number of tattoos in males, and a positive correlation between L2D:4D and number of tattoos was observed in females. However, these latter findings did not remain significant after controlling for covariates. CONCLUSIONS: Tattoos may act as fitness indicators in males, though this explanation appears not to extend to females. Prenatal testosterone may also play a role, though doubt is cast on this premise because 2D:4D effects did not remain statistically significant after controlling for covariates.

Outcome and treatments of dogs with aortic thrombosis: 100 cases (1997-2014).

BACKGROUND: Aortic thrombosis (ATh) is an uncommon condition in dogs, with limited understanding of risks factors, outcomes, and treatments. OBJECTIVES/HYPOTHESIS: To describe potential risk factors, outcome, and treatments in dogs with ATh. ANIMALS: Client-owned dogs with a diagnosis of ATh based on ultrasonographic or gross necropsy examination. METHOD: Multicentric retrospective study from 2 academic institutions. RESULTS: One hundred dogs were identified. Anti-thrombin diagnosis, 35/100 dogs were nonambulatory. The dogs were classified as acute (n = 27), chronic (n = 72), or unknown (n = 1). Fifty-four dogs had at least one comorbidity thought to predispose to ATh, and 23 others had multiple comorbidities. The remaining 23 dogs with no obvious comorbidities were classified as cryptogenic. Concurrent illnesses potentially related to the development of ATh included protein-losing nephropathy (PLN) (n = 32), neoplasia (n = 22), exogenous corticosteroid administration (n = 16), endocrine disease (n = 13), and infection (n = 9). Dogs with PLN had lower antithrombin activity than those without PLN (64% and 82%, respectively) (P = .04). Sixty-five dogs were hospitalized with 41 subsequently discharged. Sixteen were treated as outpatient and 19 euthanized at admission. In-hospital treatments varied, but included thrombolytics (n = 12), alone or in combination with thrombectomy (n = 9). Fifty-seven dogs survived to discharge. Sixteen were alive at 180 days. Using regression analysis, ambulation status at the time of presentation was significantly correlated with survival-to-discharge (P < .001). CONCLUSIONS/CLINICAL IMPORTANCE: Dogs with ATh have a poor prognosis, with nonambulatory dogs at the time of presentation having worse outcome. Although the presence of comorbid conditions associated with hypercoagulability is common, an underlying cause for ATh was not always identified.

Association of abdominal effusion with a single decompressive cystocentesis prior to catheterization in male cats with urethral obstruction.

OBJECTIVE: To evaluate the occurrence of abdominal effusion and its association with decompressive cystocentesis in male cats with urethral obstruction. DESIGN: Prospective observational clinical study. ANIMALS: Forty-five male neutered, client-owned cats with naturally occurring urethral obstruction. PROCEDURES: Laboratory testing and point-of-care ultrasonography were performed. Presence of abdominal effusion was evaluated using the Focused Assessment with Sonography for Trauma (FAST) technique at presentation. Decompressive cystocentesis was then performed prior to catheterization by a standardized technique. Repeat FAST examination was performed 15 minutes after cystocentesis and the following day to further assess for the presence of abdominal effusion. RESULTS: A mean volume of 92.3 ± 35.2 mL of urine was removed from each cat via cystocentesis prior to catheterization. At presentation, 15 of 45 (33%) had abdominal effusion (13/15 with scant effusion, 2/15 with mild), with an additional 7 cats developing scant effusion 15 minutes post-cystocentesis. By the following day, 4 cats still had scant effusion present. No significant complications secondary to cystocentesis were reported. No association was found between severity of azotemia, or volume removed by cystocentesis, and the presence of effusion at presentation or after decompressive cystocentesis was performed. CONCLUSIONS AND CLINICAL RELEVANCE: A single decompressive cystocentesis prior to catheterization did not lead to development of clinically significant abdominal effusion or other discernable complications and appears to be a safe procedure in this population of patients. Abdominal effusion may be found at presentation in cats with urethral obstruction. The significance of this effusion remains to be determined.

The influence of quotations uttered in emergency service triage traffic and hospitalization (Quiet).

This study aims to determine whether the use of the word, Quiet increases veterinary emergency service triage traffic or hospital admissions. Days were randomized to be a control or test phrase day. On control days, the phrase, Have a nice day! was announced to the entire hospital staff. On test days, the phrase, Have a quiet day! was announced. No statistical difference in mean number of the patients presenting to the emergency service for triage (test phrase 30.1 ± 10.4 cases vs control phrase 30.3 cases ± 10.5, p = 0.91) or hospital admissions (test phrase 3.5 ± 1.9 cases vs control phrase 4.3 ± 2.4 cases, p = 0.13) was found for 24-h following phrase utterance. No statistical difference in mean number of patients presenting to the emergency service for triage (test phrase 2.7 ± 1.4 cases vs control phrase 2.6 ± 1.9 cases, p = 0.84) or hospital admissions (test phrase 0.3 ± 0.5 cases vs control phrase 0.5 ± 0.8 cases, p = 0.08) was found in the 2-h window immediately following phrase announcement. Despite popular myth, using the word, Quiet does not increase veterinary emergency service triage traffic or hospital admissions.

Home Healthcare Visits Following Hospital Discharge: Does the Timing of Visits Affect 30-Day Hospital Readmission Rates for Heart Failure Patients?

The purpose of this study was to determine if the timing of home care visits post hospitalization for heart failure influenced hospital readmission rates. Using a randomized control study design, hospital readmission data were collected from 67 recently discharged patients with heart failure. The control group (n = 32) received the usual care, whereas the intervention group (n = 35) received an altered scheduling of home care visits. Seven study participants were readmitted during the study time frame (control group n = 3; intervention group n = 4). Emergency room visits occurred three times (control group n = 1; intervention group n = 2). The timing of the home healthcare visit did not affect hospital readmission. Adherence to weight monitoring, fluid restriction, and medication administration improved with the home care visits. Greater attention to these activities should be the focus of home healthcare visits as they may decrease hospital readmissions.

Influence of hang time and location on bacterial contamination of intravenous bags in a veterinary emergency and critical care setting.

OBJECTIVE: To assess the rate of bacterial contamination of fluid and ports in intravenous bags in a veterinary emergency room (ER) and intensive care unit (ICU). DESIGN: Experimental model. SETTING: Ninety intravenous fluid bags of lactated balanced-electrolytes solution (1 L) hung in a university hospital. INTERVENTIONS: Bags were hung in 2 different locations in the ER (sink and bins) and one location in the ICU (sink) for 11 days. Bags were punctured 3 times daily with a sterile needle to simulate clinical use. Injection ports were swabbed and 50 mL of fluid were collected in duplicates on days 0, 2, 4, 7, and 10. Aerobic bacterial cultures were performed on the fluid and injection port. Contamination was defined as bacterial growth of a similar phenotype across 2 consecutive times. Increase in the fluid contamination rate from day 0 was tested using an exact binomial test. Port contamination rate between locations was tested using Fisher's exact test. MAIN RESULTS: Combined bacterial growth on injection ports reached a mean (95% confidence interval) of 8.1 (0.005-16.2) cfu/port on day 10. The combined port contamination was 3.3%, 11.1%, 17.8%, and 31.1% on days 0, 2, 4, and 7, respectively. Port contamination was similar between ER and ICU. However, port contamination was higher in the sink versus the bins area (38.3% vs 16.7%, P = 0.032). No fluid bag was contaminated at days 0 and 2. The contamination rate of fluid bag was 1.1% and 4.4% on days 4 and 7, respectively. All bags with contaminated fluid were in the ER (6.7%, 95% exact binomial confidence interval 1.9-16.2%). CONCLUSIONS: Injection port contamination reached 31.1% on day 7. Contamination was more likely when the bags were hung next to a sink. In our model of bag puncture, fluid contamination occurred between days 2 and 4.

Amelioration of X-Linked Related Autophagy Failure in Danon Disease With DNA Methylation Inhibitor.

BACKGROUND: Danon disease is an X-linked disorder that leads to fatal cardiomyopathy caused by a deficiency in lysosome-associated membrane protein-2 (LAMP2). In female patients, a later onset and less severe clinical phenotype have been attributed to the random inactivation of the X chromosome carrying the mutant diseased allele. We generated a patient-specific induced pluripotent stem cell (iPSCs)-based model of Danon disease to evaluate the therapeutic potential of Xi-chromosome reactivation using a DNA methylation inhibitor. METHODS: Using whole-exome sequencing, we identified a nonsense mutation (c.520C>T, exon 4) of the LAMP2 gene in a family with Danon disease. We generated iPSC lines from somatic cells derived from the affected mother and her 2 sons, and we then differentiated them into cardiomyocytes (iPSC-CMs) for modeling the histological and functional signatures, including autophagy failure of Danon disease. RESULTS: Our iPSC-CM platform provides evidence that random inactivation of the wild-type and mutant LAMP2 alleles on the X chromosome is responsible for the unusual phenotype in female patients with Danon disease. In vitro, iPSC-CMs from these patients reproduced the histological features and autophagy failure of Danon disease. Administration of the DNA demethylating agent 5-aza-2'-deoxycytidine reactivated the silent LAMP2 allele in iPSCs and iPSC-CMs in female patients with Danon disease and ameliorated their autophagy failure, supporting the application of a patient-specific iPSC platform for disease modeling and drug screening. CONCLUSIONS: Our iPSC-CM platform provides novel mechanistic and therapeutic insights into the contribution of random X chromosome inactivation to disease phenotype in X-linked Danon disease.

Assessment of microcirculatory perfusion in healthy anesthetized cats undergoing ovariohysterectomy using sidestream dark field microscopy.

OBJECTIVE: To: (1) determine the feasibility of using sidestream dark field microscopy (SDM) to measure microcirculatory parameters in healthy, anesthetized cats and (2) determine if surgical tissue manipulation and anesthesia time alter these parameters during ovariohysterectomy. DESIGN: Prospective observational study. SETTING: University teaching hospital. ANIMALS: Eighteen healthy female cats. INTERVENTIONS: Sublingual mucosa microcirculatory videos were obtained under general anesthesia preoperatively, intraoperatively, and postoperatively using an SDM device in healthy cats presenting for ovariohysterectomy. At each video acquisition point, macrovascular parameters (heart rate, blood pressure, pulse oximetry, end-tidal CO2) were recorded. Vascular analysis software was used to calculate standard microcirculatory parameters. Multivariate analysis was performed to compare microvascular and macrovascular parameters, as well as correlation with the effect of surgical manipulation and time under anesthesia. MEASUREMENTS AND MAIN RESULTS: Twelve of 18 cats were included in final video analysis; 6 were removed for poor video quality. Values for total vessel density (TVD, 47.7 ± 8.39 mm/mm(2)), proportion of perfused vessels (PPV, 88.2 ± 5.95%), perfused vessel density (PVD, 43.0 ± 9.00 mm/mm(2)), microcirculatory flow index (MFI, 2.33 ± 0.33) were determined preoperatively. There were no significant changes in TVD, PPV, and PVD across intervention points. The MFI increased significantly from preoperative to intra- and postoperative data collection points. No correlation between microcirculatory parameters and length of anesthesia or macrocirculatory values was found. CONCLUSIONS AND CLINICAL RELEVANCE: This study demonstrated that SDM can be utilized to obtain sublingual microvascular parameters in healthy, anesthetized cats. Limitations include difficulty in obtaining high quality images, presumed need for general anesthesia, and need for off-line video analysis. This technology has potential as a tool in experimental and clinical monitoring of microcirculatory changes in felines.

Promoting inquiry-based teaching in laboratory courses: are we meeting the grade?

Over the past decade, repeated calls have been made to incorporate more active teaching and learning in undergraduate biology courses. The emphasis on inquiry-based teaching is especially important in laboratory courses, as these are the courses in which students are applying the process of science. To determine the current state of research on inquiry-based teaching in undergraduate biology laboratory courses, we reviewed the recent published literature on inquiry-based exercises. The majority of studies in our data set were in the subdisciplines of biochemistry, cell biology, developmental biology, genetics, and molecular biology. In addition, most exercises were guided inquiry, rather than open ended or research based. Almost 75% of the studies included assessment data, with two-thirds of these studies including multiple types of assessment data. However, few exercises were assessed in multiple courses or at multiple institutions. Furthermore, assessments were rarely based on published instruments. Although the results of the studies in our data set show a positive effect of inquiry-based teaching in biology laboratory courses on student learning gains, research that uses the same instrument across a range of courses and institutions is needed to determine whether these results can be generalized.

Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study.

Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis.

Poverty and adolescent depressive symptoms.

Longitudinal data on non-Hispanic White children from the Panel Study of Income Dynamics (N = 1,056) were used to examine whether the relationship between poverty (early childhood poverty, poverty persistence, and current poverty) and adolescent depressive symptoms (measured by the Children's Depression Inventory and the Internalizing Index) can be explained by the mother's own childhood depression and family characteristics measured during the child's first year of life. Associations between poverty and depressive symptoms among adolescents were explained by mother's childhood depression and whether the adolescent had lived with both parents during the first year of life. The findings highlight the need for appropriate treatment of childhood depression so as to reduce the adverse consequences in adulthood and for the next generation.

The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research.

Schizophrenia is a devastating mental disorder. The level of risk in the general population is sustained by the persistence of social, environmental and biological factors, as well as their interactions. Socio-environmental risk factors for schizophrenia are well established and robust. The same can belatedly be said of genetic risk factors for the disorder. Recent progress in schizophrenia genetics is primarily fuelled by genome-wide association, which is able to leverage substantial proportions of additional explained variance previously classified as 'missing'. Here, we provide an outline of the emerging genetic landscape of schizophrenia and demonstrate how this knowledge can be turned into a simple empirical measure of genetic risk, known as a polygenic risk score. We highlight the statistical framework used to assess the clinical potential of the new score and finally, draw relevance to and discuss the clinical implications for the study of gene-environment interaction.

Spirituality and health: the development of a field.

Spirituality has played a role in health care for centuries, but by the early 20th century, technological advances in diagnosis and treatment overshadowed the more human element of medicine. In response, a core group of medical academics and practitioners launched a movement to reclaim medicine's spiritual roots, defining spirituality broadly as a search for meaning, purpose, and connectedness. This commentary describes the history of the field of spirituality and health-its origins, its furtherance through the Medical School Objectives Project, and its ultimate incorporation into the curricula of over 75% of U.S. medical schools. The diverse efforts in developing this field within medical education and in national and international organizations created a need for a cohesive framework. The National Competencies in Spirituality and Health-created at a consensus conference of faculty from seven medical schools and reported here for the first time-answered that need.Also reported are some of the first applications of these competencies-competency-linked curricular projects. This issue of Academic Medicine features articles from three of the participating medical schools as well as one from an additional medical school. This commentary also describes another competency application: the George Washington Institute of Spirituality and Health-Templeton Reflection Rounds initiative, known as G-TRR, which has provided clerkship students with the opportunity, through reflection on their patient encounters, to develop their own inner resources to address the suffering of others. This commentary concludes with the authors' proposals for future directions for the field.

Common variants on Xq28 conferring risk of schizophrenia in Han Chinese.

Schizophrenia is a highly heritable, severe psychiatric disorder affecting approximately 1% of the world population. A substantial portion of heritability is still unexplained and the pathophysiology of schizophrenia remains to be elucidated. To identify more schizophrenia susceptibility loci, we performed a genome-wide association study (GWAS) on 498 patients with schizophrenia and 2025 controls from the Han Chinese population, and a follow-up study on 1027 cases and 1005 controls. In the follow-up study, we included 384 single nucleotide polymorphisms (SNPs) which were selected from the top hits in our GWAS (130 SNPs) and from previously implicated loci for schizophrenia based on the SZGene database, NHGRI GWAS Catalog, copy number variation studies, GWAS meta-analysis results from the international Psychiatric Genomics Consortium (PGC) and candidate genes from plausible biological pathways (254 SNPs). Within the chromosomal region Xq28, SNP rs2269372 in RENBP achieved genome-wide significance with a combined P value of 3.98 × 10(-8) (OR of allele A = 1.31). SNPs with suggestive P values were identified within 2 genes that have been previously implicated in schizophrenia, MECP2 (rs2734647, P combined = 8.78 × 10(-7), OR = 1.28; rs2239464, P combined = 6.71 × 10(-6), OR = 1.26) and ARHGAP4 (rs2269368, P combined = 4.74 × 10(-7), OR = 1.25). In addition, the patient sample in our follow-up study showed a significantly greater burden for pre-defined risk alleles based on the SNPs selected than the controls. This indicates the existence of schizophrenia susceptibility loci among the SNPs we selected. This also further supports multigenic inheritance in schizophrenia. Our findings identified a new schizophrenia susceptibility locus on Xq28, which harbor the genes RENBP, MECP2, and ARHGAP4.

Investigating the genetic variation underlying episodicity in major depressive disorder: suggestive evidence for a bipolar contribution.

BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias. CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.

Microcirculatory effects of a hyperviscous hemoglobin-based solution administered intravenously in dogs with experimentally induced hemorrhagic shock.

OBJECTIVE: To determine whether increasing the viscosity of a standard hemoglobin-based oxygen-carrying solution (HBOC) would offset its associated vasoconstrictive effects and result in improved microvascular perfusion in healthy splenectomized dogs with experimentally induced hemorrhagic shock. ANIMALS: 12 male American Foxhounds. PROCEDURES: Each dog underwent anesthesia and splenectomy. Shock was induced by controlled hemorrhage until a mean arterial blood pressure of 40 mm Hg was achieved and maintained for 60 minutes. Dogs were then randomly assigned to receive either a standard or hyperviscous HBOC (6 dogs/group). Sidestream dark-field microscopy was used to assess the effects of shock and HBOC administration on the microcirculation of the buccal mucosa and the jejunal serosa. Video recordings of the microcirculation were collected before shock was induced (baseline) and at intervals up to 180 minutes following HBOC administration. Vascular analysis software was used to compute microcirculatory variables. RESULTS: Compared with baseline findings, hemorrhagic shock resulted in decreases in all microvascular variables in the buccal mucosa and the jejunal serosa. At all time points following HBOC administration, microvascular variables were similar to initial values and no significant differences between treatment groups were detected. At all time points following HBOC administration, blood and plasma viscosities in dogs treated with the hyperviscous solution were significantly higher than values in dogs receiving the standard solution. CONCLUSIONS AND CLINICAL RELEVANCE: In splenectomized dogs with experimentally induced hemorrhagic shock, administration of a hyperviscous HBOC did not significantly affect microvascular variables, compared with effects of a standard HBOC. Microcirculatory flow returned to baseline values in both treatment groups, suggesting that marked HBOC-associated vasoconstriction did not occur.