A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia.

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

Optimizing Interprofessional Simulation with Intentional Pre-Briefing and Debriefing.

The use of simulation and interprofessional education (IPE) has been shown to enhance healthcare student and provider confidence, strengthen teamwork, and improve patient outcomes. Although debriefing has been widely practiced and studied, the value of intentional pre-briefing has been recently recognized. At the University of the Incarnate Word (UIW), Doctor of Physical Therapy (DPT) and Bachelor of Science in Nursing (BSN) students engaged in a simulation with multiple acute care scenarios. The goal of this activity was to foster competence and confidence in coordinating care for patients with complex medical conditions while functioning as integral members of a team. Faculty members recognized an opportunity to practice interprofessional care coordination behaviors through this simulation. The activity was intentionally structured with three key components: (1) thorough advanced preparation, (2) a well-organized pre-briefing session encompassing pre-simulation orientation, and (3) a structured debrief that encouraged reflection on patient care prioritization. The simulation addressed the activity goals and provided students with opportunities for growth in the Interprofessional Education Collaborative (IPEC) core competencies.

Unlicensed GS-441524-Like Antiviral Therapy Can Be Effective for at-Home Treatment of Feline Infectious Peritonitis.

The goal of this study was to formally evaluate the administration of unlicensed, crowd-sourced antiviral GS-441524-like therapy for cats suspected to have feline infectious peritonitis (FIP), a previously fatal disease. Members of a large social media support and GS-441524-like drug distribution group were surveyed via the Internet. The survey was targeted toward owners who had treated their cats for at least 12 weeks with unlicensed GS-441524-like drugs. Of the 393 analyzed surveys which met inclusion criteria, 73.7% of owners utilizing this therapy were from the United States. Only 8.7% of owners reported receiving help from their veterinarian in administering the treatment to their cat. The mean cost of treatment was USD 4920. A majority of owners (88.2%) reported noticeable improvement in clinical signs within one week of initiating therapy. At the time of the survey, 96.7% (380 cats) were alive, with 54.0% of them considered cured and another 43.3% being monitored in the 12-week observation period. A total of 12.7% of the cats suffered a relapse of clinical signs of FIP, and 3.3% of the cats died despite GS-441524-like therapy. Reported complications were mostly related to owner administration of subcutaneous injections of the acidic GS-441525-like therapy, such as vocalization, pain, struggling, and injection-site wounds. Limitations of this study include a retrospective design, bias in case selection, reliance on owner-reported data, and inability to confirm the contents of unlicensed pharmaceuticals; however, important lessons can be learned from the experiences of these owners. While unconventional, and certainly not free from medical and legal risks, unlicensed, at-home GS-441524-like therapy, according to owner reports, can apparently offer benefits in the treatment of cats suspected of FIP.

Predicting HESI® Exit Exam Success: A Retrospective Study.

Controversy surrounds the use of standardized exit exams to predict and prepare students for NCLEX success. The purpose of this study was to explore the relationships between Kaplan integrated exam scores and the HESI® exit exam score to determine early indicators of success on the exit exam. A retrospective records review was used to explore relationships between performance on integrated tests and the standardized exit exam. A solid Kaplan comprehensive medical surgical exam score was highly correlated with success on the HESI exit exam. Tracking and follow-up resulted in exit exam success for nearly all students.

Listening and responding to the voices of Latina prenursing students.

AIM: To describe how successful Latina prenursing students experience and respond to academic challenges. BACKGROUND: Nursing schools are challenged to enhance persistence and graduation rates of Hispanic students to meet the health care needs of the Hispanic population in the United States. METHOD: The researcher used private semistructured interviews to explore the lived experiences of six successful Latina students when they encountered academic challenges in prerequisite nursing courses. RESULTS: Seven superordinate themes emerged through interpretative phenomenological analysis: a) facing academic challenges, b) recognizing emotional response, c) seeking help, d) transcending academic challenges, e) owning knowledge, f) persevering, and g) living out values and beliefs. CONCLUSION: Faculty need to recognize and respond to the importance of family, relationships, values, and beliefs to academic success among Latinas. Promoting academic success of Latina prenursing students helps prepare a health care workforce that reflects the population of the United States.

Global stability for an epidemic model with applications to feline infectious peritonitis and tuberculosis.

A general compartmental model of disease transmission is studied. The generality comes from the fact that new infections may enter any of the infectious classes and that there is an ordering of the infectious classes so that individuals can be permitted (or not) to pass from one class to the next. The model includes staged progression, differential infectivity, and combinations of the two as special cases. The exact etiology of feline infectious peritonitis and its connection to coronavirus is unclear, with two competing theories - mutation process vs multiple virus strains. We apply the model to each of these theories, showing that in either case, one should expect traditional threshold dynamics. A further application to tuberculosis with multiple progression routes through latency is also presented.

Developing nurse educator competency in the pedagogy of simulation.

Faculty development is needed for nurse educators to effectively use simulation as a learning tool. A synthesis of research evidence regarding current practices in preparing educators to use simulation provided a foundation for faculty development. Implementation of a two-pronged approach within a regional collaboration of four schools of nursing is described; results of the evaluation of the approaches are presented. Use of the National League for Nursing Core Competencies of Nurse Educators as the organizing framework and Roger's Diffusion of Innovations Model as the theoretical framework is discussed. An overview is provided of the two prongs: (a) a short course for novice educators, and (b) examples of continuing education programming for experienced faculty members new to simulation to enhance effective application of this pedagogy. Recommendations include designing faculty development for simulation within a framework for systems change, maintaining flexibility to meet diverse needs, and using existing online resources.

Vascular endothelial growth factor in the cerebrospinal fluid of infants who died of sudden infant death syndrome: evidence for antecedent hypoxia.

OBJECTIVES: Recurrent hypoxemia has been proposed as an important pathophysiological mechanism underlying sudden infant death syndrome (SIDS). However, conflicting results emerged when xanthines were used as markers for hypoxia. The vascular endothelial growth factor (VEGF) gene is highly sensitive to changes in tissue partial oxygen tension, and changes in genomic and protein expression occur even after changes in oxygenation within the physiologic range. METHODS: For determining whether hypoxia precedes SIDS, VEGF levels were measured using an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) of 51 SIDS infants and in 33 additional control infants who died of an identifiable cause. In addition, 6 rats that had a chronically implanted catheter in the lateral ventricle were exposed to a short hypoxic challenge, and VEGF concentrations were measured in CSF at various time points for 24 hours. Another set of 6 rats were killed with a pentobarbital overdose, and VEGF CSF levels were obtained at different time points after death. RESULTS: Mean VEGF concentrations in CSF were 308.2 +/- 299.1 pg/dL in the SIDS group and 85.1 +/- 82.9 pg/dL in those who died of known causes. Mean postmortem delay averaged 22 hours for both groups. In rat experiments, hypoxic exposures induced time-dependent increases in VEGF, peaking at 12 hours and returning to baseline at 24 hours. Postmortem duration in the animals was associated with gradual increases in VEGF that reached significance only at 36 hours. CONCLUSIONS: We conclude that VEGF CSF concentrations are significantly higher in infants who die of SIDS. We postulate that hypoxia is a frequent event that precedes the sudden and unexpected death of these infants.

A comparison of respiratory symptoms and inflammation in sudden infant death syndrome and in accidental or inflicted infant death.

Upper respiratory infection and pulmonary inflammation are common in sudden infant death syndrome, but their role in the cause of death remains controversial. Controlled studies comparing clinical upper respiratory infection and inflammation in sudden infant death syndrome with sudden infant deaths caused by accidents and inflicted injuries (controls) are unavailable. Our aim was to compare respiratory inflammation and upper respiratory infection within 48 hours of death and postmortem culture results in these two groups. A retrospective analysis of upper respiratory infection and pathologic variables in the trachea and lung of 155 infants dying of sudden infant death syndrome and 33 control infants was undertaken. Upper respiratory infection was present in 39% of sudden infant death syndrome cases and 40% of control cases. Upper respiratory infection was more likely to have occurred in association with more severe lymphocytic interstitial pneumonitis when sudden infant death syndrome cases and control cases were combined ( P=.04). Proximal and distal tracheal lymphocytic infiltration was more severe in control cases than in sudden infant death syndrome cases ( P=.01 and.01, respectively). Lymphocytic infiltrations of the bronchi, bronchioles, and pulmonary interstitium were similar between groups. Bronchial associated lymphoid tissue was more prominent in control cases ( P=.04). Cultures were positive in 80% of sudden infant death syndrome cases, 78% of which were polymicrobial. Among control cases, 89% were positive, with 94% being polymicrobial. This study confirms that microscopic inflammatory infiltrates in sudden infant death syndrome are not lethal.

Infanticide: is its incidence among postneonatal infant deaths increasing?: an 18-year population-based analysis in California.

The decline in the incidence of sudden infant death syndrome (SIDS) and recent recommendations regarding the differentiation of SIDS and child abuse has generated speculation that some cases of infanticide were misdiagnosed as SIDS. The aims of this study were to determine the change in incidences and proportions of postneonatal deaths from all causes, SIDS, and infanticide in California over an 18-year interval encompassing years before and after the Back to Sleep campaign. Selected postneonatal mortality data from 1981 through 1998 obtained from the California Department of Health Services were analyzed and graphically displayed. The total postneonatal mortality and incidence of SIDS deaths per 100,000 live births decreased 45% and 66%, respectively, during the study interval; the incidence of infanticide remained low. The ratio of infanticide to SIDS increased from 4.3 per 100 in 1981 to 10.2 per 100 in 1998. Infanticide deaths, as a percentage of the total number of postneonatal deaths, increased slightly from the first to the second half of the study interval but never rose above 3.2%. It is concluded that this increased percentage is due to a decrease in SIDS deaths and not to an actual increase in infanticide deaths.

Medial smooth muscle thickness in small pulmonary arteries in sudden infant death syndrome revisited.

Increased relative medial thickness (RMT) of smooth muscle in small pulmonary arteries, peripheral extension of smooth muscle into the alveolar wall arteries, and right ventricular hypertrophy (RVH), in response to purported prolonged hypoxia, have been reported in sudden infant death syndrome (SIDS). Prone sleep position, an important risk factor for SIDS, predisposes infants to hypoxia from airway obstruction or rebreathing. Since publication of the earlier pulmonary artery studies, the SIDS definition has been expanded, and sudden infant death investigational protocols have been implemented. Our aims in this study were to (1) compare RMT in preacinar arteries (PA), intra-acinar arteries accompanying small airways (SIA), and alveolar wall arteries (AW) in SIDS infants and controls; (2) correlate RMT with postmortem variables; (3) determine if peripheral extension occurred more often in SIDS infants than in controls; and (4) determine if RVH occurred in SIDS. Movat-stained sections from standardized tissue blocks taken prospectively from the apex of the right upper lobe from 88 SIDS cases and 17 controls were evaluated using a computer-assisted digitizing system with images obtained from a microscope with an attached video camera. When adjusted for age, the RMT values for the SIA arteries were significantly greater in controls, while the PA and AW arteries were not statistically different between the SIDS cases and controls. Peripheral medial smooth muscle extension did not differ between the groups, and RVH was not seen in SIDS cases. Given the recent identification of brain stem abnormalities interfering with protective cardiorespiratory responses against acute life-threatening hypoxia perhaps precipitated by prone sleeping, our data suggest that SIDS is an acute event not preceded by recurrent or prolonged apnea and hypoxia.