Feline aortic thromboembolism with and without congestive heart failure did not exhibit hypercoagulability using a novel viscoelastic coagulation monitor.

OBJECTIVE: To demonstrate hypercoagulability with a benchtop viscoelastic monitor in cats with congestive heart failure (CHF) and/or aortic thromboembolism (ATE) compared to controls. METHODS: 97 cats were enrolled throughout this prospective observational cohort study from September 2022 through October 2023. Cats were grouped by diagnosis of CHF, ATE, ATE plus CHF, or controls. Enrollment required diagnosis of heart disease and no previous antithrombotic therapy. The results of viscoelastic testing with the benchtop viscoelastic coagulation monitor (VCM Vet [VCM]; Entegrion) were compared between groups using factorial analysis of variance. RESULTS: Cats with heart disease had significantly higher clot times when compared to controls (control: mean, 285.3 [SD, 172.6]; CHF: mean, 391.7 [SD, 106.8]; ATE: mean, 415.9 [SD, 109.2]; and ATE plus CHF: mean, 368.6 [SD, 232.6]). Heart disease cats were noted to have significantly lower 45-minute lysis index values (control: median, 100 [range, 93 to 100]; CHF: median, 99 [range, 89 to 100]; ATE: median, 98 [range, 88 to 100]; and ATE plus CHF: range, 98 [91 to 100]). Age was a covariate to this variable, and when applied to analysis, statistical significance was lost. No significant difference in any other variables were noted. CLINICAL RELEVANCE: The hypercoagulability of ATE and CHF cats was not detected by the VCM. Further research with other coagulation monitors is required in this population.

Transvection between nonallelic genomic positions in Drosophila.

In Drosophila, pairing of maternal and paternal homologous chromosomes can permit trans-interactions between enhancers on one homolog and promoters on another, an example of transvection. Although trans-interactions have been observed at many loci in the Drosophila genome and in other organisms, the parameters that govern enhancer action in trans remain poorly understood. Using a transgenic reporter system, we asked whether enhancers and promoters at nonallelic, but nearby, genomic positions can communication in trans. Using one transgenic insertion carrying the synthetic enhancer GMR and another nearby insertion carrying the hsp70 promoter driving a fluorescent reporter, we show that transgenes separated by 2.6 kb of linear distance can support enhancer action in trans at the 53F8 locus. Furthermore, transvection between the nonallelic insertions can be augmented by a small deletion flanking one insert, likely via changes to the paired configuration of the homologs. Subsequent analyses of other insertions in 53F8 that carry different transgenic sequences demonstrate that the capacity to support transvection between nonallelic sites varies greatly, suggesting that factors beyond the linear distance between insertion sites play an important role. Finally, analysis of transvection between nearby nonallelic sites at other genomic locations shows evidence of position effects, where one locus supported GMR action in trans over a linear distance of over 10 kb, whereas another locus showed no evidence of transvection over a span <200 bp. Overall, our data demonstrate that transvection between nonallelic sites represents a complex interplay between genomic context, interallelic distance, and promoter identity.

Ropinirole has similar efficacy to apomorphine for induction of emesis and removal of foreign and toxic gastric material in dogs.

OBJECTIVE: Assess efficacy of ropinirole versus apomorphine in inducing vomiting in dogs. ANIMALS: 279 client-owned dogs with known or suspected ingestion of a foreign material (n = 129) or toxin (150) between August 2021 and February 2022. PROCEDURES: In this non-randomized non-controlled clinical trial, ropinirole topical ophthalmic solution was applied to dogs' eyes, with a target dose of 3.75 mg/m2. A second dose was administered after 15 minutes based on clinician discretion. Reversal with metoclopramide was provided based on clinician discretion. Results of ropinirole's efficacy were compared to previous literature assessing the efficacy of apomorphine. RESULTS: Of 279 dogs, 255 (91.4%) vomited after ropinirole administration, including 116 of the 129 dogs (89.9%) dogs that ingested foreign material and 139 of the 150 dogs (92.7%) that ingested toxins. Success of emesis did not differ between groups. With a single dose of ropinirole, 78.9% produced vomit. Fifty-nine dogs received 2 doses of ropinirole, resulting in 79.7% that produced vomit. Overall, 74.2% of the dogs vomited all the expected ingested material. Average time to emesis was 11.0 minutes with 50% of dogs vomiting within 7 to 18 minutes. Adverse effects were observed for 17.0% of dog and were self-limiting. Ropinirole was less effective than apomorphine in inducing vomiting (91.4% ropinirole, 95.6% apomorphine [P < .0001]) and equally effective at evacuating all ingested material (74.2% ropinirole, 75.6% apomorphine [P = .245]). CLINICAL RELEVANCE: Ropinirole ophthalmic solution is a safe and effective emetic for use in dogs. It has a small but statistically significant decrease in efficacy compared to IV apomorphine.

Altering enhancer-promoter linear distance impacts promoter competition in cis and in trans.

In Drosophila, pairing of maternal and paternal homologs can permit trans-interactions between enhancers on one homolog and promoters on another, an example of a phenomenon called transvection. When chromosomes are paired, promoters in cis and in trans to an enhancer can compete for the enhancer's activity, but the parameters that govern this competition are as yet poorly understood. To assess how the linear spacing between an enhancer and promoter can influence promoter competition in Drosophila, we employed transgenic constructs wherein the eye-specific enhancer GMR is placed at varying distances from a heterologous hsp70 promoter driving a fluorescent reporter. While GMR activates the reporter to a high degree when the enhancer and promoter are spaced by a few hundred base pairs, activation is strongly attenuated when the enhancer is moved 3 kb away. By examining transcription of endogenous genes near the point of transgene insertion, we show that linear spacing of 3 kb between GMR and the hsp70 promoter results in elevated transcription of neighboring promoters, suggesting a loss of specificity between the enhancer and its intended transgenic target promoter. Furthermore, increasing spacing between GMR and hsp70 by just 100 bp can enhance transvection, resulting in increased activation of a promoter on a paired homolog at the expense of a promoter in cis to the enhancer. Finally, cis-/trans-promoter competition assays in which one promoter carries mutations to key core promoter elements show that GMR will skew its activity toward a wild-type promoter, suggesting that an enhancer is in a balanced competition between its potential target promoters in cis and in trans.

Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in Drosophila.

Three-dimensional eukaryotic genome organization provides the structural basis for gene regulation. In Drosophila melanogaster, genome folding is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, how homologs identify one another and pair has remained mysterious. Recently, this process has been proposed to be driven by specifically interacting 'buttons' encoded along chromosomes. Here, we turned this hypothesis into a quantitative biophysical model to demonstrate that a button-based mechanism can lead to chromosome-wide pairing. We tested our model using live-imaging measurements of chromosomal loci tagged with the MS2 and PP7 nascent RNA labeling systems. We show solid agreement between model predictions and experiments in the pairing dynamics of individual homologous loci. Our results strongly support a button-based mechanism of somatic homolog pairing in Drosophila and provide a theoretical framework for revealing the molecular identity and regulation of buttons.

Voices on diversity: recruiting underrepresented scientists.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. In this piece, they discuss strategies to recruit underrepresented minority students to universities and careers in science. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on diversity: confronting racial bias.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. Here, they discuss the impact of racial bias and share strategies for addressing it. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on Diversity: Creating a Sense of Belonging.

As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. Here they tell us about behaviors that can lead underrepresented scientists to feel that they do not belong and what the scientific community can do to provide better support. These are the personal opinions of the authors and may not reflect the views of their institutions.

Voices on Diversity: Multiple Paths to Becoming a Scientist.

As part of our commitment to amplifying the voices of underrepresented scientists, we will be publishing the insights and experiences of a panel of underrepresented scientists. To kick off this series, they introduce themselves, tell us what sparked their interest in science, and describe their scientific journeys. These are the personal opinions of the authors and may not reflect the views of their institutions.

Diagnosis of pulmonary contusions with point-of-care lung ultrasonography and thoracic radiography compared to thoracic computed tomography in dogs with motor vehicle trauma: 29 cases (2017-2018).

OBJECTIVE: To determine the accuracy of lung ultrasound (LUS) using the Veterinary Bedside Lung Ultrasound Examination (VetBLUE) protocol and 3-view thoracic radiographs (TXR) compared to thoracic computed tomography (TCT) for diagnosing the presence and quantification of pulmonary contusions (PC). DESIGN: Prospective cohort study conducted from February 2017 to June 2018. SETTING: Private emergency and referral center. ANIMALS: Thirty-two dogs having sustained motor vehicle trauma were consecutively enrolled. Three dogs were excluded from statistical analysis. All dogs survived to hospital discharge. INTERVENTIONS: Within 24 hours of sustaining trauma, dogs had LUS, TXR, and TCT performed. Using the VetBLUE protocol, LUS PC were scored according to the presence and number of B-lines and C-lines, indicating extravascular lung water. Thoracic radiographs and TCT were scored for PC in a similar topographical pattern to the VetBLUE protocol. Lung ultrasound and TXR were compared to "gold standard" TCT for the presence and quantification of PC. MEASUREMENTS AND MAIN RESULTS: On TCT, 21 of 29 (72.4%) dogs were positive and 8 of 29 (27.6%) dogs were negative for PC. When LUS was compared to TCT, 19 of 21 dogs were positive for PC (90.5% sensitivity) and 7 of 8 dogs were negative (87.5% specificity) for PC. LUS PC score correlated strongly with TCT PC score (R = 0.8, P < 0.001). When TXR was compared to TCT, 14 of 21 dogs were positive for PC (66.7% sensitivity) and 7 of 8 dogs were negative (87.5% specificity) for PC. TXR PC score correlated strongly with TCT PC score (R = 0.74, P < 0.001). CONCLUSIONS: In this population of dogs with motor vehicle trauma, LUS had high sensitivity for diagnosis of PC when compared to "gold standard" TCT. LUS provides reliable diagnosis of PC after trauma. More patients with PC were identified with LUS than with TXR, and additional studies are warranted to determine whether this increased sensitivity is statistically significant.

Comparing unfamiliar voice and face identity perception using identity sorting tasks.

Identity sorting tasks, in which participants sort multiple naturally varying stimuli of usually two identities into perceived identities, have recently gained popularity in voice and face processing research. In both modalities, participants who are unfamiliar with the identities tend to perceive multiple stimuli of the same identity as different people and thus fail to "tell people together." These similarities across modalities suggest that modality-general mechanisms may underpin sorting behaviour. In this study, participants completed a voice sorting and a face sorting task. Taking an individual differences approach, we asked whether participants' performance on voice and face sorting of unfamiliar identities is correlated. Participants additionally completed a voice discrimination (Bangor Voice Matching Test) and a face discrimination task (Glasgow Face Matching Test). Using these tasks, we tested whether performance on sorting related to explicit identity discrimination. Performance on voice sorting and face sorting tasks was correlated, suggesting that common modality-general processes underpin these tasks. However, no significant correlations were found between sorting and discrimination performance, with the exception of significant relationships for performance on "same identity" trials with "telling people together" for voices and faces. Overall, any reported relationships were however relatively weak, suggesting the presence of additional modality-specific and task-specific processes.

Overactive Bladder Symptoms After Pelvic Organ Prolapse Repair.

OBJECTIVES: This study aimed to identify the characteristics associated with overactive bladder (OAB) symptoms perioperatively in patients undergoing pelvic organ prolapse (POP) surgery with and without slings and to determine the rate of OAB symptom resolution postoperatively. METHODS: This retrospective, single-institution study involved women undergoing prolapse surgery with and without concomitant midurethral sling from 2011 to 2016. A validated questionnaire was used to determine OAB symptoms preoperatively and postoperatively. The primary outcome was rate of resolution in OAB symptoms after POP surgery with and without midurethral sling. Baseline characteristics and surgery type were presented, and univariate and multivariate logistic regression models were applied to evaluate characteristics associated with OAB symptoms at the first postoperative visit. RESULTS: The analysis included 203 patients. Among those with baseline OAB symptoms, 103 (61%) had symptom resolution, whereas 66 (39.1%) reported persistent symptoms. Among 34 patients without baseline OAB symptoms, 6% developed de novo symptoms. Older age was found to be a significant risk factor for persistence of symptoms postoperatively both on univariate (odds ratio, 0.97; 95% confidence interval, 0.94-1; P = 0.038) and multivariate logistic regression (odds ratio, 0.96, 95% confidence interval, 0.92-1; P = 0.049). The rate of medication discontinuation postoperatively was 25%. CONCLUSIONS: Approximately 61% of patients undergoing POP surgery had resolution of OAB symptoms postoperatively whether or not an incontinence procedure was performed. Older age was significantly related to persistent OAB symptoms in both univariate (P = 0.038) and multivariate (P = 0.049) models. The rate of de novo OAB symptoms was 6%.

Essay On Being a Doctor: Oh, This Place!

Through the generosity of Charles R. Millikan, DMin, vice president for Spiritual Care and Values Integration, an annual award competition was established at Houston Methodist Hospital among the resident staff. To enter the writing competition, residents must submit a poem or essay of 1,000 words or less on the topic, "On Being a Doctor." A committee of seven was selected from Houston Methodist Hospital Education Institute to establish the judging criteria and select the winning entries. The following is the second-place winning entry for 2019; the third-place entry will be published in the next issue of this journal.

Position Effects Influence Transvection in Drosophila melanogaster.

Transvection is an epigenetic phenomenon wherein regulatory elements communicate between different chromosomes in trans, and is thereby dependent upon the three-dimensional organization of the genome. Transvection is best understood in Drosophila, where homologous chromosomes are closely paired in most somatic nuclei, although similar phenomena have been observed in other species. Previous data have supported that the Drosophila genome is generally permissive to enhancer action in trans, a form of transvection where an enhancer on one homolog activates gene expression from a promoter on a paired homolog. However, the capacity of different genomic positions to influence the quantitative output of transvection has yet to be addressed. To investigate this question, we employed a transgenic system that assesses and compares enhancer action in cis and in trans at defined chromosomal locations. Using the strong synthetic eye-specific enhancer GMR, we show that loci supporting strong cis-expression tend to support robust enhancer action in trans, whereas locations with weaker cis-expression show reduced transvection in a fluorescent reporter assay. Our subsequent analysis is consistent with a model wherein the chromatin state of the transgenic insertion site is a primary determinant of the degree to which enhancer action in trans will be supported, whereas other factors such as locus-specific variation in somatic homolog pairing are of less importance in influencing position effects on transvection.

Efficacy of intravenous administration of apomorphine for removal of gastric foreign material in dogs: 495 cases (2010-2015).

OBJECTIVE: To evaluate the efficacy of IV administration of apomorphine for removal of gastric foreign bodies in dogs. ANIMALS: 495 dogs with gastric foreign bodies. PROCEDURES: Records of a veterinary hospital were searched to identify dogs that received an injectable formulation of apomorphine between January 1, 2010, and July 30, 2015. Dogs with a gastric foreign body that received an IV injection of apomorphine were included in the study. Information extracted from the record of each dog included signalment, type of foreign material ingested, duration between foreign material ingestion and emesis, dose and number of doses of apomorphine administered, and whether emesis occurred and did or did not result in successful removal of the foreign body. Descriptive data were compared between dogs with and without successful foreign body removal. RESULTS: Emesis with successful foreign body removal was achieved in 363 and 11 dogs after administration of 1 and 2 doses of apomorphine, respectively. Successful removal was more likely for young dogs and dogs that had ingested fabric, leather, or bathroom waste. Successful removal was less likely as the duration between foreign body ingestion and emesis increased and for dogs that received opioids, sedatives, or antiemetics before apomorphine administration. Minor adverse effects were recorded for only 4 dogs. CONCLUSIONS AND CLINICAL RELEVLANCE: IV administration of apomorphine was a viable alternative for induction of emesis and removal of gastric foreign bodies in dogs. Dogs should be examined as soon as possible after foreign body ingestion and should not receive any medications that might affect apomorphine efficacy.

Two modes of transvection at the eyes absent gene of Drosophila demonstrate plasticity in transcriptional regulatory interactions in cis and in trans.

For many genes, proper gene expression requires coordinated and dynamic interactions between multiple regulatory elements, each of which can either promote or silence transcription. In Drosophila, the complexity of the regulatory landscape is further complicated by the tight physical pairing of homologous chromosomes, which can permit regulatory elements to interact in trans, a phenomenon known as transvection. To better understand how gene expression can be programmed through cis- and trans-regulatory interactions, we analyzed transvection effects for a collection of alleles of the eyes absent (eya) gene. We find that trans-activation of a promoter by the eya eye-specific enhancers is broadly supported in many allelic backgrounds, and that the availability of an enhancer to act in trans can be predicted based on the molecular lesion of an eya allele. Furthermore, by manipulating promoter availability in cis and in trans, we demonstrate that the eye-specific enhancers of eya show plasticity in their promoter preference between two different transcriptional start sites, which depends on promoter competition between the two potential targets. Finally, we show that certain alleles of eya demonstrate pairing-sensitive silencing resulting from trans-interactions between Polycomb Response Elements (PREs), and genetic and genomic data support a general role for PcG proteins in mediating transcriptional silencing at eya. Overall, our data highlight how eya gene regulation relies upon a complex but plastic interplay between multiple enhancers, promoters, and PREs.

Chronic kidney disease in patients infected with human immunodeficiency virus (HIV) in an urban cohort.

BACKGROUND AND OBJECTIVES: HIV-infected patients are at risk for developing chronic kidney disease (CKD), defined by estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2. Our purpose was to understand the genesis of CKD in HIV patients from a large urban clinic in Houston, Texas, USA, and to characterize progression of CKD in the cohort. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A retrospective cohort study (2012-2016) was conducted in all HIV-infected patients seen in a federally qualified community health center in Houston, Texas. CKD prevalence and its association with HIV viral load and CD4 count were determined. The association of the change in eGFR over time and comorbidities was assessed using linear mixed models. RESULTS: Of 3714 HIV-infected patients analyzed, 153 (4.1%) had CKD. The prevalence of CKD in the different racial groups was 5.4% White, 4.0% African American, 2.8% Hispanic/Latino and 3.2% Asian. There was no difference in the rate of decline in kidney function in White vs. African American HIV infected patients with CKD. Compared with non-CKD patients, CKD patients were older, had lived longer with HIV infection, had lower CD4 cell counts, higher proportions of hypertension, hyperlipidemia, and cerebrovascular disease, and had significantly higher rates of eGFR deterioration represented by a median decrease of 26.5% from first to last follow-up eGFR (versus 0% change). Linear mixed modeling identified older age, male gender, White race, longer time with HIV infection, hypertension, history of kidney stones, cerebrovascular disease, autoimmune disease, increased potassium and total cholesterol levels, and being treated with combination ART as associated with a worsening eGFR over time. CONCLUSION: This study demonstrates a prevalence of CKD in HIV-infected patients of 4.1% and points to an important role for HIV medications and other common comorbidities in the genesis and progression of kidney disease. Importantly, CKD was not more prevalent in African Americans than in Whites, perhaps due to a low prevalence of IV drug abuse as inferred from the lower prevalence of HCV infection in this cohort.

Essay on Being a Doctor: Dr. Edwards.

Through the generosity of Charles R. Millikan, D. Min., vice president for Spiritual Care and Values Integration, an annual award competition was established at Houston Methodist Hospital among the resident staff. To enter the writing competition, residents must submit a poem or essay of 1,000 words or less on the topic, "On Being a Doctor." A committee of seven was selected from Houston Methodist Hospital Education Institute to establish the judging criteria and select the winning entries. The following is the first-place winning entry for 2018; the second- and third-place entries will be published in the next two issues of this journal.

A Review of Posttraumatic Stress Disorder and Obesity: Exploring the Link.

OBJECTIVE: The incidence of posttraumatic stress disorder (PTSD) and obesity are on the rise, and evidence continues to support the observation that individuals who have symptoms of PTSD are more likely to develop obesity in their lifetime. The incidence of obesity in individuals with PTSD, including war veterans, women, and children exposed to trauma, is not solely attributable to psychotropic medications, but actual pathophysiologic mechanisms have not been fully delineated. Additionally, there are no studies to date demonstrating that obese individuals are predisposed to developing PTSD compared to the general population. This review explores the pathogenic pathways common to both PTSD and obesity, which include inflammation, the renin-angiotensin-aldosterone system, cellular structures, and neuroendocrine activation. DATA SOURCES AND SYNTHESIS: A PubMed search for the years 2000-2015 with the keywords PTSD and obesity was performed. There were no language restrictions. RESULTS: More research is needed in human subjects to understand the pathogenic pathways common to both PTSD and obesity and to further clarify the direction of identified associations. Ideally, in the future, clinical interventions targeting these pathways may be able to modify the course of PTSD and obesity. The outcome of studies investigating the utility of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the treatment of PTSD symptoms will be relevant to control both PTSD and obesity. Importantly, outcomes assessing inflammation, obesity, and cardiac function in the same subjects also should be determined. CONCLUSION: Research is needed to reveal the multidimensional and intricate relationship between PTSD and obesity. The implications of this research would be essential for treatment, prevention, and potential public health reforms.

The Capacity to Act in Trans Varies Among Drosophila Enhancers.

The interphase nucleus is organized such that genomic segments interact in cis, on the same chromosome, and in trans, between different chromosomes. In Drosophila and other Dipterans, extensive interactions are observed between homologous chromosomes, which can permit enhancers and promoters to communicate in trans Enhancer action in trans has been observed for a handful of genes in Drosophila, but it is as yet unclear whether this is a general property of all enhancers or specific to a few. Here, we test a collection of well-characterized enhancers for the capacity to act in trans Specifically, we tested 18 enhancers that are active in either the eye or wing disc of third instar Drosophila larvae and, using two different assays, found evidence that each enhancer can act in trans However, the degree to which trans-action was supported varied greatly between enhancers. Quantitative analysis of enhancer activity supports a model wherein an enhancer's strength of transcriptional activation is a major determinant of its ability to act in trans, but that additional factors may also contribute to an enhancer's trans-activity. In sum, our data suggest that a capacity to activate a promoter on a paired chromosome is common among Drosophila enhancers.