Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis.

Nocardioform placentitis (NP) continues to result in episodic outbreaks of abortion and preterm birth in mares and remains a poorly understood disease. The objective of this study was to characterize the transcriptome of the chorioallantois (CA) of mares with NP. The CA were collected from mares with confirmed NP based upon histopathology, microbiological culture and PCR for Amycolatopsis spp. Samples were collected from the margin of the NP lesion (NPL, n = 4) and grossly normal region (NPN, n = 4). Additionally, CA samples were collected from normal postpartum mares (Control; CRL, n = 4). Transcriptome analysis identified 2892 differentially expressed genes (DEGs) in NPL vs. CRL and 2450 DEGs in NPL vs. NPN. Functional genomics analysis elucidated that inflammatory signaling, toll-like receptor signaling, inflammasome activation, chemotaxis, and apoptosis pathways are involved in NP. The increased leukocytic infiltration in NPL was associated with the upregulation of matrix metalloproteinase (MMP1, MMP3, and MMP8) and apoptosis-related genes, such as caspases (CASP3 and CASP7), which could explain placental separation associated with NP. Also, NP was associated with downregulation of several placenta-regulatory genes (ABCG2, GCM1, EPAS1, and NR3C1), angiogenesis-related genes (VEGFA, FLT1, KDR, and ANGPT2), and glucose transporter coding genes (GLUT1, GLUT10, and GLUT12), as well as upregulation of hypoxia-related genes (HIF1A and EGLN3), which could elucidate placental insufficiency accompanying NP. In conclusion, our findings revealed for the first time, the key regulators and mechanisms underlying placental inflammation, separation, and insufficiency during NP, which might lead to the development of efficacious therapies or diagnostic aids by targeting the key molecular pathways.

Challenging Corporate Power: Human Rights Globalization from Above and Below.

To address the most pressing issues of our day, the United Nations must be redesigned to transform global social relations in ways that reduce corporate power and empower civil society and local authorities as global actors. People's movements have made deliberate efforts to advance what I have called human rights globalization, building foundations for an alternative global order from the ground up. These emerging transformative projects can end corporate impunity and foster global norms and identities that contest corporate governance and the monopoly authority of states.

Phase I study of DFP-11207, a novel oral fluoropyrimidine with reasonable AUC and low Cmax and improved tolerability, in patients with solid tumors.

5-fluorouracil (5-FU) and 5-FU derivatives, such as capecitabine, UFT, and S-1, are the mainstay of chemotherapy treatment for gastrointestinal cancers, and other solid tumors. Compared with other cytotoxic chemotherapies, these drugs generally have a favorable safety profile, but hematologic and gastrointestinal toxicities remain common. DFP-11207 is a novel oral cytotoxic agent that combines a 5-FU pro-drug with a reversible DPD inhibitor and a potent inhibitor of OPRT, resulting in enhanced pharmacological activity of 5-FU with decreased gastrointestinal and myelosuppressive toxicities. In this Phase I study (NCT02171221), DFP-11207 was administered orally daily, in doses escalating from 40 mg/m2/day to 400 mg/m2/day in patients with esophageal, colorectal, gastric, pancreatic or gallbladder cancer (n = 23). It was determined that DFP-11207 at the dose of 330 mg/m2/day administered every 12 hours was well-tolerated with mild myelosuppressive and gastrointestinal toxicities. The pharmacokinetic analysis determined that the 5-FU levels were in the therapeutic range at this dose. In addition, fasted or fed states had no influence on the 5-FU levels (patients serving as their own controls). Among 21 efficacy evaluable patients, 7 patients had stable disease (33.3%), of which two had prolonged stable disease of >6 months duration. DFP-11207 can be explored as monotherapy or easily substitute 5-FU, capecitabine, or S-1 in combination regimens.

An epidemiologic study of antimicrobial resistance of Staphylococcus species isolated from equine samples submitted to a diagnostic laboratory.

BACKGROUND: Antimicrobial resistance limits traditional treatment options and increases costs. It is therefore important to estimate the magnitude of the problem so as to provide empirical data to guide control efforts. The aim of this study was to investigate the burden and patterns of antimicrobial resistance (AMR) among equine Staphylococcus samples submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) from 1993 to 2009. Retrospective data of 1711 equine Staphylococcus samples submitted to the UKVDL during the time period 1993 to 2009 were included in the study. Antimicrobial susceptibility testing, that included 16 drugs, were performed using cultures followed by the Kirby-Bauer disk diffusion susceptibility test. The proportion of resistant isolates by animal breed, species of organism, sample source, and time period were computed. Chi-square and Cochran-Armitage trend tests were used to identify significant associations and temporal trends, respectively. Logistic regression models were used to investigate predictors of AMR and multidrug resistance (MDR). RESULTS: A total of 66.3% of the isolates were resistant to at least one antimicrobial, most of which were Staphylococcus aureus (77.1%), while 25.0% were MDR. The highest level of resistance was to penicillins (52.9%). Among drug classes, isolates had the highest rate of AMR to at least one type of ß-lactams (49.2%), followed by aminoglycosides (30.2%). Significant (p < 0.05) associations were observed between odds of AMR and horse breed, species of organism and year. Similarly, significant (p < 0.05) associations were identified between odds of MDR and breed and age. While some isolates had resistance to up to 12 antimicrobials, AMR profiles featuring single antimicrobials such as penicillin were more common than those with multiple antimicrobials. CONCLUSION: Demographic factors were significant predictors of AMR and MDR. The fact that some isolates had resistance to up to 12 of the 16 antimicrobials assessed is quite concerning. To address the high levels of AMR and MDR observed in this study, future studies will need to focus on antimicrobial prescription practices and education of both practitioners and animal owners on judicious use of antimicrobials to slow down the development of resistance.

Intracellular antibody receptor TRIM21 prevents fatal viral infection.

Host species have evolved mechanisms that can inhibit pathogen replication even after a cell has been successfully invaded. Here we show that tripartite-motif protein 21 (TRIM21), a ubiquitously expressed E3 ubiquitin ligase that targets viruses inside the cytosol, protects mice against fatal viral infection. Upon infection with mouse adenovirus-1, naive mice lacking TRIM21 succumb to encephalomyelitis within 7 d. In contrast, wild-type mice rapidly up-regulate TRIM21 and control viremia. Trim21 heterozygous mice have a haploinsufficiency phenotype in which reduced TRIM21 expression leads to a viral load that is higher than wild types but lower than knockouts. TRIM21 is a high-affinity antibody receptor that allows antibodies to operate inside an infected cell. In passive transfer experiments at high viral dose, antisera that fully protects wild-type mice fails to protect most Trim21 knockout animals. These results demonstrate that TRIM21 provides potent antiviral protection and forms an important part of the humoral immune response.

Letter to the Editor.

The editorial in BJN 24(15) written by BJN Editor in Chief, Ian Peate, challenged the Nursing and Midwifery Council's (NMC) Chief Executive and Registrar's assertion that the progress her organisation has achieved over the past 12 months is something to be 'delighted' about. The NMC responded and their letter is below. If you would like to comment on the issue email us: bjn@markallengroup.com.

Families parenting adolescents with substance abuse--recovering the mother's voice: a narrative literature review.

Alcohol and substance dependency are complex, problematic phenomena, which are growing worldwide. In particular, drug use and abuse among young people is a significant concern. Although addiction presents as a problem of dependent individuals, families are also profoundly affected by the family member's addiction. In this narrative literature review, we review published research from 1937 to 2014 to capture a narrative and historical perspective of addiction and family. We condense and analyze the experiences of parents with alcohol- and drug-dependent children, to emphasize the need for a more specific, in-depth exploration of mothers' experiences. Such exploration may advance nurses' understandings of individual, familial, and social complexities of parenting an addicted child.

A synthesis of research examining timely removal of cervical collars in the obtunded trauma patient with negative computed tomography: an evidence-based review.

OBJECTIVE: Currently, the standard to clear the cervical spine in obtunded blunt trauma patients is computed tomography in combination with plain films, dynamic fluoroscopy, or magnetic resonance imaging. The objective of this study was to answer the question "Can computed tomography alone provide adequate clinical information to clear the cervical spine in the obtunded patient?" METHODS: The author performed a search of the literature for studies that compared computed tomography (CT) with other radiologic modalities utilized to clear the cervical spine in obtunded patients. PubMed, TRIPdatabase, SUMsearch, Cochrane library, and Google Scholar were the databases applied. Additional sources included bibliographies of selected articles. Studies that integrated CT scan with at least 1 other diagnostic examination were included. RESULTS: A review of 11 studies and 1 meta-analysis encompassing 2458 and 14327 patients, respectively, met inclusion criteria. The meta-analysis generated a negative predictor value for CT scan of 100% without evidence of acute injury with an overall sensitivity and specificity of 99.9% each. CONCLUSION: The results suggest that CT alone is a reliable clinical indicator to clear the cervical spine in obtunded patients.

Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study.

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24-31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.

Correlates of adverse childhood experiences and secondary traumatic stress in school personnel.

While previous research has noted the large numbers of school personnel with exposure to potentially traumatic experiences and its relation to secondary traumatic stress, it is unclear how different patterns of adverse childhood experiences influence secondary traumatic stress. As such, the present study employed latent profile analysis to examine natural groups of adverse childhood experience (ACE) history in 218 school mental health professionals (65% female; 55% White, 17.9% Black; 39% early career, 34% midcareer, and 28% late career; Mage = 32.91) and 348 teachers (80% female; 80.5% White, 6.3% Black; 16% early career, 14% midcareer, and 70% late career; Mage = 41.03) to examine the magnitude of secondary traumatic stress. The present study also examined the moderating effect of trauma-informed practice efficacy on the relationship between ACE history latent profiles and secondary traumatic stress. Four latent profiles were revealed among school personnel: (a) low ACEs, (b) average ACEs (c) neglected, and (d) high ACEs. Additionally, trauma-informed practice efficacy did not moderate the relationship between ACEs history profiles and secondary traumatic stress. Implications include targeted approaches for helping school personnel decrease secondary traumatic stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Randomized Clinical Trial of a Self-care and Communication Intervention for Parents of Adolescent/Young Adults Undergoing High-Risk Cancer Treatment: A Report From the Children's Oncology Group.

BACKGROUND: Parents of adolescents and young adults (AYAs) with cancer offer primary support to their children and often experience their own high levels of distress, affecting parent-AYA communication and quality of life. OBJECTIVE: To reduce parent distress and improve communication during high-risk cancer treatment, we examined efficacy of a self-care and communication intervention for parents and indirect benefit for AYAs receiving a therapeutic music video (TMV) intervention. METHODS: In this study, we conducted a multisite, randomized controlled trial with AYAs and parents enrolled as dyads (n = 110). Parents were randomized to intervention or low-dose control; all AYAs received TMV. Data collection occurred at baseline, 2 weeks post intervention (T2), and 90 days post intervention (T3). RESULTS: There were no significant between-group differences on primary outcomes for parents or AYAs. We did find significant differences favoring the parent intervention group on parenting confidence at T2 and marginally better outcomes for family adaptability/cohesion at T3. Both groups exhibited significant within-group improvement for parent distress (state anxiety, T3; perceived stress, T2 and T3; mood, T3), state anxiety (T2) intervention only, and family strengths control group only. Qualitative data demonstrate the parent intervention raised self-awareness and parent confidence in the short term. CONCLUSION: Parents found their intervention helpful. Absence of significant results may be due to short intervention duration, need for tailored content, underpowered sample, and potential indirect parent benefit from AYA participation in TMV. The parent intervention did not provide an indirect benefit for AYAs. IMPLICATIONS FOR NURSING: Parents identified their own need for communication and support from nurses. Nurses can optimize AYA care by attending to parent needs through supportive listening and encouraging self-care.

Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease.

Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating hormone, causing the characteristic clinical phenotype. Although early studies investigating the TSHR and GD proved inconclusive, more recently we provided convincing evidence for association of the TSHR region with disease. In the current study, we investigated a combined panel of 98 SNPs, including 70 tag SNPs, across an extended 800 kb region of the TSHR to refine association in a cohort of 768 GD subjects and 768 matched controls. In total, 28 SNPs revealed association with GD (P < 0.05), with strongest SNP associations at rs179247 (chi(2) = 32.45, P = 8.90 x 10(-8), OR = 1.53, 95% CI = 1.32-1.78) and rs12101255 (chi(2) = 30.91, P = 1.95 x 10(-7), OR = 1.55, 95% CI = 1.33-1.81), both located in intron 1 of the TSHR. Association of the most associated SNP, rs179247, was replicated in 303 GD families (P = 7.8 x 10(-4)). In addition, we provide preliminary evidence that the disease-associated genotypes of rs179247 (AA) and rs12101255 (TT) show reduced mRNA expression ratios of flTSHR relative to two alternate TSHR mRNA splice variants.

Antibiotic prescription practices and opinions regarding antimicrobial resistance among veterinarians in Kentucky, USA.

BACKGROUND: Inappropriate antimicrobial use (AMU) is a global concern. Opinions of veterinarians regarding AMU and its role in the development of antimicrobial resistance (AMR) may influence their prescription practices. It is important to understand these opinions, prescription practices and their potential impact on the development of AMR in order to guide efforts to curb the problem. Therefore, the objective of this study was to investigate the antimicrobial prescription practices and opinions of veterinarians in Kentucky regarding AMU and AMR. METHODS: This cross-sectional study used a 30-question survey questionnaire administered to veterinarians who were members of the Kentucky Veterinary Medical Association. Survey responses from 101 participants were included in the study. Descriptive statistics were computed and associations between categorical variables assessed using Chi-square or Fisher's exact tests. Firth logistic models were used to investigate predictors of "Compliance with prescription policies" and "Cost of antimicrobial affects prescription decisions". RESULTS: Almost all (93%) respondents indicated that improper AMU contributed to selection for AMR. A total of 52% of the respondents believed that antimicrobials were appropriately prescribed, while the remaining 48% believed that antimicrobials were inappropriately prescribed. Significant predictors of compliance with prescription policies were availability of prescription policy at the veterinary facility (Odds Ratio (OR) = 4.2; p<0.001) and over-prescription (OR = 0.35; p = 0.025). Similarly, significant predictors of cost of antimicrobials affecting prescription decisions were lack of post-graduate training (OR = 8.3; p = 0.008) and practice type, with large animal practices having significantly lower odds of the outcome (OR = 0.09; p = 0.004) than small animal practices. CONCLUSION: Most veterinarians indicated that improper AMU contributed to selection for AMR. Since the odds of compliance with prescription policies were 4-times higher among veterinarians working at facilities that had prescription policies compared to those at facilities that didn't, more veterinary facilities should be encouraged to adopt prescription policies to help improve compliance and reduce AMR. Veterinarians would also benefit from continued professional education to help improve prescription practices, antimicrobial stewardship and curb AMR.

Graduate student seminars as a faculty development activity.

Because most new nurse academicians are prepared as expert clinicians, rather than as educators, they lack the skills and knowledge of effective teachers when they accept a position in an educational institution. In this article, the authors discuss a program in which graduate students being prepared as entry-level nurse educators have the opportunity to practice the art and science of teaching in a supervised environment in which seminar participants are their peers, novice faculty, and seasoned faculty. Teaching seminars conducted by graduate students are a successful component of faculty development in teaching. Graduate students, known as faculty interns, are able to share their newly acquired skills and lived experiences with novice faculty not prepared as nurse educators and seasoned faculty who need updates on current educational practices and strategies.

Reducing inappropriate urine cultures through a culture standardization program.

BACKGROUND: The objective of this study was to evaluate the impact of a urine culture standardization program that included order indications and urinalysis (U/A) with reflexive culture. The program applied to all adult and pediatric inpatients at an academic medical center; emergency department and ambulatory clinic patients were excluded. METHODS: The analysis compared outcomes in the pre-implementation (January 2015-May 2016) and post-implementation (July 2016-September 2017) periods. The primary outcomes were urine culture and U/A orders per 1,000 patient days, catheter-associated urinary tract infection (CAUTI) rate per 1,000 catheter days, and urine culture contamination rate per 1,000 patient days. Catheter standardized utilization ratios (SURs) were also examined. RESULTS: The intervention was associated with a significant decrease in urine culture rates by 6.9 cultures per 1,000 patient days (95% CI -4.44, -9.44; P < .0001). The U/A testing rate per 1,000 patient days significantly increased pre-intervention, was not affected acutely by the intervention institution, and significantly decreased post-implementation. The CAUTI rate was not significantly changed by the intervention but did significantly increase post-implementation by 0.2 per 1,000 catheter days (95% CI 0.01, 0.47; P = .04); SURs significantly decreased (0.03; 95% CI -0.003, -0.05; P = .03); and the urine culture contamination rate per month showed no significant change. Sixty-four percent of urine cultures ordered using the reflexive test did not reflex to culture by U/A criteria. CONCLUSIONS: A urine culture standardization program led to a significant reduction in urine cultures and did not lead to an increase in U/A testing rates. CAUTI rates increased post-implementation, which may have been confounded by reduced catheter utilization.

Application of an automated surveillance-data-analysis system in a laboratory-based early-warning system for detection of an abortion outbreak in mares.

OBJECTIVE: To develop an early-warning automated surveillance-data-analysis system for early outbreak detection and reporting and to assess its performance on an abortion outbreak in mares in Kentucky. SAMPLE POPULATION: 426 data sets of abortions in mares in Kentucky during December 2000 to July 2001. PROCEDURES: A custom software system was developed to automatically extract and analyze data from a Laboratory Information Management System database. The software system was tested on data on abortions in mares in Kentucky reported between December 1, 2000, and July 31, 2001. The prospective space-time permutations scan statistic, proposed by Kulldorff, was used to detect and identify abortion outbreak signals. RESULTS: Results indicated that use of the system would have detected the abortion outbreak approximately 1 week earlier than traditional surveillance systems. However, the geographic scale of analysis was critical for highest sensitivity in outbreak detection. Use of the lower geographic scale of analysis (ie, postal [zip code]) enhanced earlier detection of significant clusters, compared with use of the higher geographic scale (ie, county). CONCLUSIONS AND CLINICAL RELEVANCE: The automated surveillance-data-analysis system would be useful in early detection of endemic, emerging, and foreign animal disease outbreaks and might help in detection of a bioterrorist attack. Manual analyses of such a large number of data sets (ie, 426) with a computationally intensive algorithm would be impractical toward the goal of achieving near real-time surveillance. Use of this early-warning system would facilitate early interventions that should result in more positive health outcomes.

An examination of adherence strategies and challenges in poison control communication.

INTRODUCTION: The principal objective of this study was to characterize how nurses and pharmacists at a poison control center (PCC) determine the likelihood of caller adherence to a health care facility referral. METHODS: A focus group was conducted with 6 nurses and 4 pharmacists from a regional PCC. Content analysis was used to determine themes within the discussion. All participants were certified as specialists in poison information (SPIs). RESULTS: Four themes were identified: (1) SPIs' generation of informal "likelihood-of-adherence" assessments as to whether a caller will follow the recommendation to go to a health care facility, (2) SPI communication strategies used to promote adherence, (3) behavior of SPIs during periods of high call volume, and (4) communication training for PCC staff members. DISCUSSION: This pilot study provides insights in SPIs' current assessment and communication, particularly those related to promoting caller adherence to recommendations.