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Staphylococcus pseudintermedius is an important pathogen in dogs that occasionally causes infections in humans as an opportunistic pathogen of elderly and immunocompromised people. This study compared the genomic relatedness and antimicrobial resistance genes using genome-wide association study (GWAS) to examine host association of canine and human S. pseudintermedius isolates. Canine (n = 25) and human (n = 32) methicillin-susceptible S. pseudintermedius (MSSP) isolates showed a high level of genetic diversity with an overrepresentation of clonal complex CC241 in human isolates. This clonal complex was associated with carriage of a plasmid containing a bacteriocin with cytotoxic properties, a CRISPR-cas domain and a pRE25-like mobile element containing five antimicrobial resistance genes. Multi-drug resistance (MDR) was predicted in 13 (41%) of human isolates and 14 (56%) of canine isolates. CC241 represented 54% of predicted MDR isolates from humans and 21% of predicted MDR canine isolates. While it had previously been suggested that certain host-specific genes were present the current GWAS analysis did not identify any genes that were significantly associated with human or canine isolates. In conclusion, this is the first genomic study showing that MSSP is genetically diverse in both hosts and that multidrug resistance is important in dog and human-associated S. pseudintermedius isolates.

Background. Radon is a known carcinogen and contaminant in drinking water wells, but is not monitored in drinking water quality programs in Jamaica. Objective. The present study was conducted to obtain radon data in local drinking water and evaluate potential health risks. The data will contribute to determining the level of compliance to public health criteria for radon and to develop a monitoring program based on the identified risks. Methods. This study assesses the concentration of radon in 22 drinking water wells in the parish of St. Catherine, Jamaica. Samples were collected for radon, with 12 other measurements gathered including pH, conductivity, TDS, alkalinity, hardness, phosphates, nitrates, chloride, sulfates, turbidity, well depth and geological features. The data were analyzed for compliance to international limits and association with geological and other parameters. Results. The average radon level was 18 Bq/L ± 2 Bq/L and varied from a low of 11 Bq/L ± 1 Bq/L to a high of 41 Bq/L ± 1 Bq/L. There was a positive correlation between radon levels and both alkalinity and turbidity. No relationship of any significance, however, was identified with the other physicochemical parameters. All the study results fell within the European Union (EU) limit of 100 Bq/L, and well within the United States Environmental Protection Agency (USEPA) limit of 147 Bq/L. Most of the wells in this parish have radon levels exceeding the proposed USEPA limit of 11 Bq/L. The proposed limits are intended to support radon mitigation programs to manage radon in air. No limits are provided in the newest edition of the World Health Organization's (WHO) Guidelines for Safe Drinking Water Quality. Conclusions. Most wells in the study area met existing international limits. Almost all, however, did not meet the proposed USEPA limit for locations without radon mitigation programs. This indicates the need to establish national screening levels for radon, consistent with WHO and USEPA recommendations. Competing Interests. The authors declare no competing financial interests.

Background & objectives Many low- and middle- income countries (LMICs) have attempted to implement trauma registries with varying degrees of success. This study aimed to understand the registry implementation mechanism in LMICs better. Study objectives include assessment of the current use of trauma registries in LMICs, identification of barriers to the process and potential areas for intervention, and investigation of the registry implementation experience of key stakeholders in LMICs. Methods An initial narrative review of articles on trauma registry use in LMICs published in English between January 2017 and September 2023 was conducted. Key findings identified in this review were used to establish a theoretical framework from which an interview guide was subsequently developed. Expert consultation with key stakeholders in trauma registry implementation in two LMICs was conducted to assess the experience of registry implementation further. Results The presence of trauma registries in LMICs is limited. Key implementation barriers include funding concerns, uncoordinated administrative efforts, lack of human and physical resources (i.e., technology, equipment), and challenges in data management, analysis, and quality. Stakeholder interviews highlighted the importance of trauma registry development but echoed some obstacles, notably funding and data collection barriers. Interpretation & conclusions Barriers to registry implementation are ubiquitous and may contribute to the low uptake of registries in LMICs. One potential solution to these challenges is the application of the WHO International Registry for Trauma and Emergency Care. Future studies examining context-specific challenges to registry implementation and sustained utilization are required.

Fast, accurate, and reliable estimates of backfat depth, loin depth, and intramuscular fat percentage in swine breeding stock are used to increase genetic improvement and farm profitability. The objective of this study was to develop an equation-based model for the estimation of swine backfat depth, loin depth, and intramuscular fat percentage estimates obtained from longitudinal ultrasound images. Images were collected from purebred Duroc (n = 230), purebred Large White (n = 154), and commercial (n = 190) pigs born in January 2021 at three farms located in North Carolina. An Exapad ultrasound machine captured longitudinal images across the 10th to 13th ribs at 182 (±12.8 SD) days of pig age. The total number of images processed for Duroc, Large White, and commercial pigs was 1 385, 928, and 1 168 images, respectively. To establish a standard measurement for model comparison, trained personnel following standard company procedures using the BioSoft Toolbox (v4.0.1.2; Biotronics Inc., Ames, IA) obtained backfat and loin depth measurements from the images. Longissimus muscle intramuscular fat percentage was predicted using near-infrared spectroscopy at approximately 22 h postmortem. Backfat and loin depth estimation were conducted only for commercial pigs (n = 190) while intramuscular fat estimation was conducted on all pigs (n = 574). Average backfat depth, loin depth, and intramuscular fat percentage were 14.6 (±2.6 SD) mm, 63.7 (±5.5 SD) mm, and 2.21 (±0.82 SD) %. Image analysis and estimation model development were conducted in MATLAB R2021a. Edge detection via the image gradient was applied to segment ultrasound images into backfat, loin, and rib regions. Segmented images were used to estimate backfat depth, loin depth, and loin intramuscular fat percentage. After image quality control and filtering, the image inclusion rate for each breed-trait combination ranged from 76 to 97%. All Duroc and commercial pigs and 97% of Large White pigs were represented by at least one image for trait estimation. Coefficient of determination of models for the estimation of backfat depth, loin depth, and intramuscular fat percentage were 0.58, 0.57, and 0.56, respectively. Root mean square error of backfat depth, loin depth, and intramuscular fat estimation were 1.65 mm, 3.58 mm, and 0.54%, respectively. Results demonstrate the feasibility of using ultrasound image gradient and an equation-based approach to estimate swine backfat and loin depth, and intramuscular fat percentage. This equation-based approach to estimate carcass traits in live swine can enhance genetic improvement., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction : Health educators have had difficulty introducing health policy and public health training into an already intensive medical school curriculum. Although the COVID-19 pandemic may have changed perspectives on the importance of public health, it may not change educational approaches. Assessment of medical student opinions and perceptions of health policy and public health might influence the weight given to these topics in medical education., Methods: We used a 39-item instrument to cross-sectionally survey medical students, to assess their perceptions of the value of public health and health policy within their professional education., Results: One hundred two students completed the survey (13% response rate). Most students reported an interest in public health (94.1%) and health policy (92.2%). Although interested, most students lacked confidence in their knowledge of public health and health policy on both state (health policy 34.3% confident; public health 43.1%) and national (health policy 41.0%; public health 44.1%) levels. Most students perceived that their institution has not sufficiently prepared them to understand health policy (34% felt prepared) and most reported insufficient information to participate in policy discussions (30.3% sufficiently informed)., Conclusions: Medical students reported an interest in public health and health policy while also reporting a lack of confidence in their level of preparedness to understand and participate in these fields, thus demonstrating a need for increased public health and health policy education within medical school curricula., (© 2023 by the Society of Teachers of Family Medicine.)

Background: On December 13, 2016, the US Congress enacted the 21st Century Cures Act (hereafter the Cures Act), which contained the Final Rule mandate that took effect on April 5, 2021. Since then, health systems have been required to provide patients digital access to their eHealth information "without delay" and without charge., Objective: This study aimed to assess clinicians' initial experiences with, and attitudes toward, sharing visit notes with patients after being mandated to do so by the Cures Act and to determine clinician preferences regarding instant record release., Methods: This cross-sectional survey study was conducted between June 10, 2021, and August 15, 2021, at the University of Kansas Health System, a large academic medical center in Kansas City, Kansas, United States. Participants included clinicians currently employed by the health system, including resident and attending physicians, physician assistants, nurse practitioners, and critical care and emergency medicine registered nurses., Results: A total of 1574 attending physicians, physician assistants, and nurse practitioners, as well as 506 critical care and emergency medicine nurses, were sent invitations; 538 (34.18%) and 72 (14.2%), respectively, responded. Of 609 resident physicians, 4 (response rate not applicable because it was unknown how many residents viewed the website while the link was available) responded. The majority of respondents were attending physicians (402/614, 65.5%) and within the department of internal medicine (160/614, 26.1%). Most agreed that sharing visit notes was a good idea (355/613, 57.9%) and that it is important to speak with the patients before they accessed their records (431/613, 70.3%). Those who agreed that sharing visit notes is a good idea tended to view the practice as a useful tool for engaging patients ("Agree": 139/355, 39.2%; "Somewhat agree": 161/355, 45.4%; P<.001) and experience no change in the clinical value of their notes for other clinicians (326/355, 91.8%; P<.001). Those who disagreed (or were neutral) tended not to encourage patients to read their notes (235/258, 91.1%; P<.001) and were more likely to experience a change in their charting practice (168/257, 65.4%; P<.001) and increased time charting (99/258, 38.4%; P<.001)., Conclusions: The findings of this study may be generalizable to institutions similar to the University of Kansas Health System, and the clinician testimonies gathered in this study may provide valuable insight into the initial opinions and experiences of clinicians at these institutions. In addition, these clinician experiences collected early in the transition period may be used to guide future health policy implementation and to understand how best to prepare clinicians for these changes in practice., (©Sophia M Leonard, Rosalee Zackula, Jonathan Wilcher. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.02.2023.)

The complex environment surrounding young pigs reared in intensive housing systems directly influences their productivity and livelihood. Much of the seminal literature utilized housing and husbandry practices that have since drastically evolved through advances in genetic potential, nutrition, health, and technology. This review focuses on the environmental interaction and responses of pigs during the first 8 wk of life, separated into pre-weaning (creep areas) and post-weaning (nursery or wean-finish) phases. Further, a perspective on instrumentation and precision technologies for animal-based (physiological and behavioral) and environmental measures documents current approaches and future possibilities. A warm microclimate for piglets during the early days of life, especially the first 12 h, is critical. While caretaker interventions can mitigate the extent of hypothermia, low birth weight remains a dominant risk factor for mortality. Post-weaning, the thermoregulation capabilities have improved, but subsequent transportation, nutritional, and social stressors enhance the requisite need for a warm, low draft environment with the proper flooring. A better understanding of the individual environmental factors that affect young pigs as well as the creation of comprehensive environment indices or improved, non-contact sensing technology is needed to better evaluate and manage piglet environments. Such enhanced understanding and evaluation of pig-environment interaction could lead to innovative environmental control and husbandry interventions to foster healthy and productive pigs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Background: Weight bias against persons with obesity impairs health care delivery and utilization and contributes to poorer health outcomes. Despite rising rates of pet obesity (including among dogs), the potential for weight bias in veterinary settings has not been examined., Subjects/methods: In two online, 2 × 2 experimental studies, the effects of dog and owner body weight on perceptions and treatment recommendations were investigated in 205 practicing veterinarians (Study 1) and 103 veterinary students (Study 2). In both studies, participants were randomly assigned to view one of four vignettes of a dog and owners with varying weight statuses (lean vs. obesity). Dependent measures included emotion/liking ratings toward the dog and owners; perceived causes of the dog's weight; and treatment recommendations and compliance expectations. Other clinical practices, such as terms to describe excess weight in dogs, were also assessed., Results: Veterinarians and students both reported feeling more blame, frustration, and disgust toward dogs with obesity and their owners than toward lean dogs and their owners (p values < 0.001). Interactions between dog and owner body weight emerged for perceived causes of obesity, such that owners with obesity were perceived as causing the dog with obesity's weight, while lean owners were perceived as causing the lean dog's weight. Participants were pessimistic about treatment compliance from owners of the dog with obesity, and weight loss treatment was recommended for the dog with obesity when presenting with a medical condition ambiguous in its relationship to weight. Veterinarians and students also reported use of stigmatizing terms to describe excess weight in dogs., Conclusions: Findings from this investigation, with replication, have implications for training and practice guidelines in veterinary medicine.

Most farrowing facilities in the United States use stalls and heat lamps to improve sow and piglet productivity. This study investigated these factors by comparing production outcomes for three different farrowing stall layouts (traditional, expanded creep area, expanded sow area) and use of one or two heat lamps. Data were collected on 427 sows and their litters over one year. Results showed no statistical differences due to experimental treatment for any of the production metrics recorded, excluding percent stillborn. Parity one sows had fewer piglets born alive ( p < 0.001), lower percent mortality ( p = 0.001) and over-lay ( p = 0.003), and a greater number of piglets weaned ( p < 0.001) with lower average daily weight gain (ADG) ( p < 0.001) and more uniform litters ( p = 0.001) as compared to higher parity sows. Farrowing turn, associated with group/seasonal changes, had a significant impact on most of the production metrics measured. Number of piglets born influenced the percent stillborn ( p < 0.001). Adjusted litter size had a significant impact on percent mortality ( p < 0.001), percent over-lay ( p < 0.001), and number of piglets weaned ( p < 0.001). As the number of piglets weaned per litter increased, both piglet ADG and litter uniformity decreased ( p < 0.001). This information can be used to guide producers in farrowing facility design.

Background: Acceptance and commitment therapy (ACT) is a psychological treatment that has been found to increase weight loss in adults when combined with lifestyle modification, compared with the latter treatment alone. However, an ACT-based treatment for weight loss has never been tested in adolescents., Methods: The present pilot study assessed the feasibility and acceptability of a 16-week, group ACT-based lifestyle modification treatment for adolescents and their parents/guardians. The co-primary outcomes were: (1) mean acceptability scores from up to 8 biweekly ratings; and (2) the percentage reduction in body mass index (BMI) from baseline to week 16. The effect size for changes in cardiometabolic and psychosocial outcomes from baseline to week 16 also was examined., Results: Seven families enrolled and six completed treatment (14.3% attrition). The mean acceptability score was 8.8 for adolescents and 9.0 for parents (on a 1-10 scale), indicating high acceptability. The six adolescents who completed treatment experienced a 1.3% reduction in BMI (SD = 2.3, d = 0.54). They reported a medium increase in cognitive restraint, a small reduction in hunger, and a small increase in physical activity. They experienced small improvements in most quality of life domains and a large reduction in depression., Conclusions: These preliminary findings indicate that ACT plus lifestyle modification was a highly acceptable treatment that improved weight, cognitive restraint, hunger, physical activity, and psychosocial outcomes in adolescents with obesity.

To examine the relationship between food cravings and food addiction as defined by the Yale Food Addiction Scale (YFAS) and to assess the effects of these variables on weight loss during a 14-week group lifestyle modification program. Data were from 178 participants who were prescribed a 1000-1200 kcal/day portion-controlled diet and provided with weekly group lifestyle modification sessions. Participants completed the Food Craving Inventory and YFAS pre- and post-treatment. Weight was measured weekly. Participants with YFAS-defined food addiction (6.7%) reported more frequent overall food cravings relative to those without food addiction. More frequent food cravings at baseline were associated with less weight loss over the 14 weeks. Analyzed categorically, participants in the highest tertile of baseline food cravings lost 7.6 ± 0.5% of initial weight, which was significantly less compared to those in the lowest tertile who lost 9.1 ± 0.5%. Percent weight loss did not differ significantly between participants with YFAS-defined food addiction (6.5 ± 1.2%) and those who did not meet criteria (8.6 ± 0.3%). Addictive-like eating behaviors significantly declined from pre- to post-treatment. Participants with frequent food cravings lost less weight than their peers. Targeted interventions for food cravings could improve weight loss in these individuals. Few participants met YFAS-defined criteria for food addiction. Addictive-like eating behaviors tended to decline during behavioral weight loss, but neither baseline nor change in YFAS scores predicted weight loss.

Background: Higher protein (HP) intake and physical activity (PA) have been associated with improved lean soft tissue (LST) and reduced fat mass (FM). Puerto Ricans have among the highest age-adjusted prevalence (42.5%) of obesity, which may be associated with inadequate protein consumption and PA. We examined the relationship between protein intake and PA with body composition and biomarkers of cardiometabolic health in Puerto Rican adults., Methods: Participants included 959 Puerto Rican adults (71.4% women, 28.6% men) from the Boston Puerto Rican Health Study (BPRHS), aged 46-79 y (Women: age, 60.4 ± 7.6 y, BMI, 32.9 ± 6.8 kg/m 2 ; Men: age, 59.8 ± 7.9 y, BMI, 30.1 ± 5.2 kg/m 2 ). Protein intake was assessed using a food frequency questionnaire and expressed as g/kg body weight/day in energy intake-adjusted equal cut point tertile categories (lower, moderate, higher: LP < 0.91 g/kg/d, MP ≥ 0.91 ≤ 1.11 g/kg/d, and HP > 1.11 g/kg/d). PA was assessed by questionnaire and expressed in tertile categories (low, moderate and high; PA1: <0.8 km/d, PA2: ≥0.8  ≤ 3.2 km/d, PA3: >3.2 km/d)., Results: Participants with energy-adjusted HP had lower appendicular LST (ALST: 16.2 ± 3.8 kg), LST (39.7 ± 8.0 kg) and FM (25.6 ± 8.1 kg) when compared to LP (ALST: 20.1 ± 4.5 kg; LST: 49.5 ± 10.0 kg; FM: 40.8 ± 12.3 kg; P < 0.001) and MP (ALST: 18.2 ± 4.3 kg; LST: 44.1 ± 8.8 kg; FM: 32.2 ± 9.8 kg; P < 0.001). However, when adjusted for total body weight (kg), relative LST was significantly greater in HP (58 ± 9%) when compared to LP (53 ± 9%; P < 0.001) and MP (56 ± 9%; P < 0.001). Participants in PA3 had greater ALST (19.5 ± 5.4 kg), and LST (58 ± 10%), compared to PA1 (ALST: 17.2 ± 4.3 kg; LST: 53 ± 9%; P < 0.001) or PA2 (ALST: 17.7 ± 4.7 kg; LST: 56 ± 9%; P < 0.05). Those in HP + PA3 or MP + PA2 had lower c-reactive protein (CRP; HP + PA3: 5.1 ± 6.8 mg/L; MP + PA2: 6.4 ± 10.0 mg/L), when compared to LP + PA1 (8.7 ± 8.8 mg/L; P < 0.05). Insulin concentration was lower for those in both the HP and PA3 (HP + PA3; 11.4 ± 7.9 IU/mL) compared to those in both the LP and PA1 (LP + PA1; 20.7 ± 16.3 UI/mL) (P < 0.001)., Conclusions: The highest tertiles of energy-adjusted protein intake (≥1.11 g/kg/d) and PA (>3.2 km/d) were associated with more desirable indicators of overall body composition and cardiometabolic health, when adjusted for body weight, than those in the lower protein intake and PA in Puerto Rican adults., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Anti-obesity medication may help people maintain diet-induced reductions in appetite. The present exploratory analysis assessed the effects of lorcaserin on changes at 24 weeks post-randomization in emotion- and stress-related eating, food cravings and other measures of appetite (i.e. binge eating, cognitive restraint, disinhibition, hunger, preoccupation with eating and fullness). The parent study investigated the efficacy of combined lorcaserin and behavioural treatment in facilitating weight loss maintenance (WLM) in 137 adults (mean age = 46.1 years, 86.1% female, 68.6% black) who had lost ≥5% of initial weight during a 14-week, low-calorie diet (LCD) run-in. Participants were randomly assigned to lorcaserin or placebo and were provided with group WLM counselling sessions. Emotion- and stress-related eating, food cravings and appetite were measured at the start of the LCD (week -14), randomization (0) and week 24. From randomization, lorcaserin-treated participants had significantly greater improvements in emotion- and stress-related eating compared to placebo-treated participants (P = 0.04). However, groups did not differ significantly after randomization in changes in the frequency of food cravings, binge eating or other measures of appetite (Ps > 0.05). Compared to placebo, lorcaserin may improve emotion- and stress-related eating., (© 2018 World Obesity Federation.)

Objective: The objective of this study was to determine the effects of weight loss and weight loss maintenance (WLM) on weight-specific health-related quality of life in a 66-week trial., Methods: Adults with obesity (N = 137, 86.1% female, 68.6% black, mean age = 46.1 years) who had lost ≥ 5% of initial weight in a 14-week intensive lifestyle intervention/low-calorie diet (LCD) program were randomly assigned to lorcaserin or placebo for an additional 52-week WLM program. The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scale (including five subscales), Patient Health Questionnaire-9 (depression), and Perceived Stress Scale were administered at the start of the 14-week LCD program, randomization, and week 52 of the randomized controlled trial (i.e., 66 weeks total)., Results: Significant improvements in all outcomes, except weight-related public distress, were found following the 14-week LCD program (P values < 0.05). Improvements were largely maintained during the 52-week randomized controlled trial, despite weight regain of 2.0 to 2.5 kg across treatment groups. Participants who lost ≥ 10% of initial weight achieved greater improvements in physical function, self-esteem, sexual life, and the IWQOL-Lite total score than those who lost < 5% and did not differ from those who lost 5% to 9.9%., Conclusions: Improvements in weight-specific health-related quality of life were achieved with moderate weight loss and were sustained during WLM., (© 2018 The Obesity Society.)

To assess the relationship of E2 gene disruption with viral gene expression and clinical outcome in human papillomavirus (HPV) positive head and neck squamous cell carcinoma, we evaluated 31 oropharyngeal and 17 non-oropharyngeal HPV16 positive carcinomas using two PCR-based methods to test for disruption of E2, followed by Sanger sequencing. Expression of HPV16 E6, E7 and E2 transcripts, along with cellular ARF and INK4A, were also assessed by RT-qPCR. Associations between E2 disruption, E2/E6/E7 expression, and clinical outcome were evaluated by Kaplan-Meier analysis for loco-regional recurrence and disease-specific survival. The majority (n = 21, 68%) of HPV16 positive oropharyngeal carcinomas had an intact E2 gene, whereas the majority of HPV16 positive non-oropharyngeal carcinomas (n = 10, 59%) had a disrupted E2 gene. Three of the oropharyngeal tumors and two of the non-oropharyngeal tumors had deletions within E2. Detection of an intact E2 gene was associated with a higher DNA viral load and increased E2/E6/E7, ARF and INK4A expression in oropharyngeal tumors. Oropharyngeal carcinomas with an intact E2 had a lower risk of loco-regional recurrence (log-rank p = 0.04) and improved disease-specific survival (p = 0.03) compared to tumors with disrupted E2. In addition, high E7 expression was associated with lower risk of loco-regional recurrence (p = 0.004) as was high E6 expression (p = 0.006). In summary, an intact E2 gene is more common in HPV16 positive oropharyngeal than non-oropharyngeal carcinomas; the presence of an intact E2 gene is associated with higher HPV viral load, higher viral oncogene expression, and improved clinical outcome compared to patients with a disrupted E2 gene in oropharyngeal cancer.

Objective: Improving the maintenance of lost weight remains a critical challenge, which can be addressed by long-term behavioral and/or pharmacological interventions., Methods: This study investigated the efficacy of combined behavioral and pharmacological treatment in facilitating weight loss maintenance (WLM) in 137 adults (86.1% female; 68.6% black; BMI = 37.0 ± 5.6 kg/m 2 ) who had lost ≥ 5% of initial weight during a 14-week low-calorie diet (LCD) program (mean = 9.3 ± 2.9%). Participants were randomly assigned to lorcaserin (10 mg twice a day) or placebo and were provided 16 group WLM counseling sessions over 52 weeks., Results: At 24 weeks post randomization, more lorcaserin-treated than placebo-treated participants maintained a ≥ 5% loss (73.9% vs. 57.4%; P = 0.033), and the lorcaserin-treated participants lost an additional 2.4 ± 0.8 kg versus a 0.6 ± 0.8 kg gain for placebo (P = 0.010). However, at week 52, groups did not differ on either co-primary outcome; 55.1% and 42.6%, respectively, maintained ≥ 5% loss (P = 0.110), with gains from randomization of 2.0 ± 0.8 kg and 2.5 ± 0.8 kg (P = 0.630), respectively. From the start of the LCD, groups maintained reductions of 7.8% and 6.6%, respectively (P = 0.318)., Conclusions: Combined behavioral and pharmacological treatment produced clinically meaningful long-term weight loss in this group of predominantly black participants. Lorcaserin initially improved upon weight loss achieved with WLM counseling, but this advantage was not maintained at 1 year., (© 2017 The Obesity Society.)

The ability to develop a comprehensive panel of treatment predicting factors would significantly improve our ability to stratify patients for cytotoxic or targeted therapies, and prevent patients receiving ineffective treatments. We have investigated if a recently developed genome-wide haploid genetic screen can be used to reveal the critical mediators of response to anticancer therapy. Pancreatic cancer is known to be highly resistant to systemic therapy. Recently epigenetic changes have been shown to be a key determinant in the maintenance of subpopulations of cancer cells with high-level resistance to cytotoxic therapy. We show that in human pancreatic cancer cell lines, treatment with the potent class I histone deacetylase inhibitor, entinostat, synergistically enhances gemcitabine-induced inhibition of cell proliferation and apoptosis. Using a genome-wide haploid genetic screen, we identified deoxycytidine kinase (DCK) as one of the genes with the highest degree of insertional enrichment following treatment with gemcitabine and entinostat; DCK is already known to be the rate-limiting activating enzyme for gemcitabine. Immunoblotting confirmed loss of DCK protein expression in the resistant KBM7 cells. CRISPR/Cas-9 inactivation of DCK in pancreatic cancer cell lines resulted in resistance to gemcitabine alone and in combination with entinostat. We have identified gemcitabine and entinostat as a potential new combination therapy in pancreatic cancer, and in this proof-of-principle study we have demonstrated that a recently developed haploid genetic screen can be used as a novel approach to identify the critical genes that determine treatment response., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflict of interest.

High-risk human papillomavirus (HR-HPV) causes nearly 100% of cervical carcinoma. However, it remains unclear whether HPV can establish a latent infection, one which may be responsible for the second peak in incidence of cervical carcinoma seen in older women. Therefore, using Ventana in situ hybridisation (ISH), quantitative PCR assays and biomarkers of productive and transforming viral infection, we set out to provide the first robust estimate of the prevalence and characteristics of HPV genomes in FFPE tissue from the cervices of 99 women undergoing hysterectomy for reasons unrelated to epithelial abnormality. Our ISH assay detected HR-HPV in 42% of our study population. The majority of ISH positive samples also tested HPV16 positive using sensitive PCR based assays and were more likely to have a history of preceding cytological abnormality. Analysis of subsets of this population revealed HR-HPV to be transcriptionally inactive as there was no evidence of a productive or transforming infection. Critically, the E2 gene was always disrupted in those HPV16 positive cases which were assessed. These findings point to a reservoir of transcriptionally silent, disrupted HPV16 DNA in morphologically normal cervices, re-expression of which could explain the increase in incidence of cervical cancer observed in later life.

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

The current interest in epigenetic priming is underpinned by the belief that remodelling of the epigenetic landscape will sensitise tumours to subsequent therapy. In this pre-clinical study, paediatric AML cells expanded in culture and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a frontline cytotoxic agent used in the treatment of AML, either alone or in combination. Sequential treatment with decitabine and cytarabine was found to be more effective in reducing tumour burden than treatment with cytarabine alone suggesting that the sequential delivery of these agents may a have real clinical advantage in the treatment of paediatric AML. However we found no evidence to suggest that this outcome was dependent on priming with a hypomethylating agent, as the benefits observed were independent of the order in which these drugs were administered.

The contribution of early virus-induced epigenetic changes to human papillomavirus (HPV)-associated carcinogenesis is poorly understood. Using genome-wide methylation array profiling and a cell-based model, which supports replication of HPV episomes, we found that transfection of primary human foreskin keratinocytes with episomal forms of high-risk HPV types was followed by upregulation of the DNA methyltransferases, DNMT1 and DNMT3B, and changes in the methylation status of cellular genes many of which are reported to be differentially methylated in cervical neoplasia. HPV16- and HPV18-associated changes were not randomly distributed across the genome, but clustered at specific chromosomal locations which mapped on to known HPV integration sites and to chromosomal regions lost and gained in high-grade cervical neoplasia. Methylation changes were directed in part by the same cis-acting factors that appear to direct methylation changes in cancer, the presence of a bivalent chromatin mark in human embryonic stem cells and promoter CpG content; these associations explain much of the ontological profile of genes found to have increased methylation following HPV16 transfection. We were also able to show, using sequential samples from a cohort of young women with incident HPV16 infections, that the detection in cervical samples of methylated forms of the tumour suppressor gene, RARB, often parallels the natural history of cervical HPV infection. Our findings suggest that further investigation of the distribution and determinants of early virus-induced epigenetic reprogramming will provide important insights into the pathogenesis of virus-associated malignancy.

We sought to determine the differential prognosis of patients with a normal single-photon emission computed tomographic (SPECT) perfusion study by type of stress modality. Even with a normal SPECT perfusion study, patients selected for adenosine stress have a worse survival than those selected for exercise stress. In patients who are able, low-level treadmill exercise is commonly performed during adenosine infusion ("walking" adenosine). The adjusted differential prognosis of patients performing walking adenosine is unknown. Our historical cohort underwent adenosine or treadmill stress with SPECT imaging during 2003 and 2004. Adenosine studies were classified as walking or adenosine only (no low-level exercise). Patients with an abnormal single-photon emission computed tomogram or missing demographic information were excluded. All-cause mortality was determined through July 2008. In total 3,479 patients were included, of which 1,451 (41.7%) were stressed with adenosine only, 201 (5.8%) with walking adenosine, and 1,827 (52.5%) with treadmill exercise. Over an average of 4.3 ± 1.0 years of follow-up, 307 (8.8%) died. Mortality was greatest for adenosine only, intermediate for walking adenosine, and least for exercise (p <0.001 by log-rank test), even after accounting for covariates (adjusted hazard ratio for walking adenosine 0.57, p = 0.044). In conclusion, patients with a normal SPECT perfusion scan who are able to undergo an adenosine protocol in conjunction with exercise have an intermediate prognosis between those who cannot perform low-level exercise and patients able to undergo full treadmill exercise. This differential survival remains significant after adjustment, perhaps because of differences in baseline functional capacity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To better stratify risk and to verify previous prevalence reports, we conducted a retrospective cohort study comparing the lifetime incidence of nephrolithiasis in patients with spondyloarthropathies (SpA) and rheumatoid arthritis (RA)., Patients and Methods: Patients with SpA or rheumatoid factor-positive RA were identified from the rheumatology clinics of two Veterans Affairs hospitals and the University of Minnesota. Among them, 168 were confirmed to meet the American College of Rheumatology criteria and gave informed consent to participation. They were sent a survey regarding their rheumatologic diagnosis, coexistent conditions, medications, and history of kidney stones. Of the total, 143 patients responded and met the criteria for analysis. Rheumatoid arthritis patients were age and sex matched with SpA patients as controls., Results: Populations were similar in all categories except that RA patients were more likely to have used prednisone (P < 0.001), bisphosphonates (P < 0.001), and calcium supplementation (P = 0.03). Kidney stones were reported by 23 (29.11%) of the 79 SpA patients compared with 8 (12.5%) of the 64 RA patients (chi (2) = 5.75; P = 0.025). Subgroup analysis of self-reporting stone history in 85 patients was found to be reliable on imaging review (sensitivity 82%; specificity 100%)., Conclusions: Self-reporting of kidney stones by patients is a reliable measure. Despite adjusting for medication use and matching two similar arthritic populations, patients with SpA had a higher incidence of kidney stones than those with RA. This finding suggests that SpA is an independent risk factor for nephrolithiasis. Future studies will evaluate urinary risk factors and polymorphisms in the ANKH gene that may predispose to stone formation in this high-risk group.

Background: Limited data are available about the effects of adjunctive treadmill exercise on adverse effects and the image quality of adenosine perfusion imaging. This study compared the incidence of adverse effects and image quality between standard 6-minute adenosine perfusion imaging and a stress test incorporating a 4-minute adenosine infusion with low-level treadmill exercise., Methods and Results: Nineteen patients underwent both a 6-minute adenosine technetium-99m sestamibi single photon emission computed tomography (SPECT) imaging study and a 4-minute adenosine Tc-99m sestamibi SPECT study with 6 minutes of simultaneous low-level treadmill exercise. Symptoms were recorded at 1-minute intervals during the stress and recovery periods. Heart-to-liver and heart-to-lung count ratios were determined from anterior planar images. More adverse effects were experienced during the standard adenosine study than during the adenosine study with low-level exercise (2.7+/-1.4 vs. 1.4+/-1.1, P = .0003). The duration adverse effects were experienced was longer during the standard 6-minute adenosine protocol (6.6+/-2.1 minutes vs 3.2+/-2.8 minutes, P<.0001). Additionally, the symptom-severity scores were higher with the standard adenosine study (15.5+/-9.8 vs 4.5+/-5.1, P<.0001). The heart-to-liver ratios were noted to be higher in the 4-minute adenosine protocol with low-level exercise (1.0+/-0.3 vs. 0.6+/-0.2, P = .0003)., Conclusions: In comparison with standard 6-minute adenosine perfusion imaging, a protocol incorporating a 4-minute adenosine infusion with low-level treadmill exercise results in a marked reduction in the quantity and severity of adverse effects and an improvement in image quality.

Changes in the neutral lipid (NL), phospholipid (PL) and their fatty acid (FA) profiles in lean samples of cooked and cooked, vacuum-packaged, frozen (28 days) Hereford and Bison L. dorsi muscle were analyzed. Samples from Herefords contained more saturated fatty acids (SFA) in the neutral lipid fraction than Bison. Storage decreased the C(18:2), C(18:3), C(20:1) and C(20:4) content of the NL. Bison samples contained more total PL and phosphatidylethanolamine (PE) than Hereford. Storage decreased the content of the least polar of the PL which were eluted in the solvent front (fraction 1), phosphatidylinositol (PI), phosphatidylserine (PS), PE and sphingomyelin (SPH). In the combined PL fraction, there were no differences in the FA profile of Bison and Hereford. Storage resulted in a decrease in the content of C(18:2), C(20:4), unsaturated fatty acid (UFA) and polyunsaturated fatty acid (PUFA) in the combined PL fraction. In the PE fraction, Bison samples contained more C(20:4) and PUFA than Hereford. Storage had no effect on the FA profile of PE. The LPC fraction of Bison samples contained more saturated SFA, UFA and PUFA than Hereford, and with storage these FA decreased. Cooked frozen storage also decreased SFA, UFA and PUFA in PC/LPE., (Copyright © 1990. Published by Elsevier Ltd.)

Immunohistochemically defined astrocytes from the 10-day chick embryo were stimulated to incorporate increased levels of [3H]thymidine when a low-molecular weight peptide growth factor, chick brain-derived growth factor (CBGF), was added to the cultures. Treatment of these GFAP-positive astrocytes with 10 ng/ml CBGF in medium supplemented with 1% fetal bovine serum resulted in a 3.5-4-fold increase in [3H]thymidine incorporation when compared to astrocytes cultured in defined medium supplemented with 1% serum alone. CBGF had no effect on the survival, proliferation or differentiation of a number of other cell types from the 10-day chick embryo brain, including neurons and meningeal fibroblasts. CBGF was also ineffective as a mitogen for chick embryo skeletal muscle myoblasts, primary mouse embryo fibroblasts and one murine teratocarcinoma-derived cell line (STO). We suggest that CBGF might act as a mitogenic signal for astroglia during central nervous system development and repair.