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Aims: Congenital athymia is an ultra-rare pediatric condition characterized by the lack of thymus in utero and the naïve T cells critical for infection defense and immune regulation. Patients with congenital athymia receive supportive care to minimize and treat infections, autoimmune phenomena, and autologous graft-versus-host disease (aGVHD) manifestations, but historically, die within the first 3 years of life with supportive care only. We estimated the healthcare resource utilization and economic burden of supportive care over patients' first 3 years of life in the United States. Methods: A medical chart audit by the treating physician was used to collect patient data from birth to age 3 on clinical manifestations associated with congenital athymia (clinical manifestations due to underlying syndromic conditions excluded). Using costs and charges from publicly available sources, the total economic burden of direct medical costs and charges for the first 3 years of life (considered "lifetime" for patients receiving supportive care) and differences in economic burden between patients with higher and lower inpatient hospitalization durations were estimated. Results: All patients (n=10) experienced frequent infections and aGVHD manifestations; 40% experienced -1 episode of sepsis, and 20% had recurrent sepsis episodes annually. The estimated mean 3-year economic burden per patient was US$5,534,121 (2020 US dollars). The annual mean inpatient hospitalization duration was 150.6 days. Inpatient room charges accounted for 79% of the economic burden, reflecting the high costs of specialized care settings required to prevent infection, including isolation. Patients with high inpatient utilization (n=5; annual mean inpatient hospitalization duration, 289.6 days) had an estimated 3-year economic burden of US$9,926,229. Limitations: The total economic burden may not be adequately represented due to underestimation of some direct costs or overestimation of others. Conclusions: Current treatment of patients with congenital athymia (supportive care) presents a high economic burden to the healthcare system. [ABSTRACT FROM AUTHOR]

Purpose: There is a growing number of youth and their parents seeking assistance from care providers related to gender dysphoria and transitional care for transgender and gender‐nonconforming (TGNC) youth. The purpose of this study was to determine pediatric nurse practitioners' (PNP) attitudes/beliefs and knowledge/competence in caring for TGNC youth. Design and Methods: This cross‐sectional descriptive study surveyed PNPs (N = 93) from eight states using two survey instruments to measure attitudes and beliefs and knowledge and perceived competence related to caring for TGNC youth. Results: Eighty‐one percent of PNPs reported caring for TGNC youth in their practice. Despite this, only 15% of the PNPs received education related to transgender patients during their advanced practice education. Results showed that attending continuing education offerings related to caring for TGNC patients increases PNP perceived competence as well as knowledge. Attitudes and behaviors towards the transgender population were also more positive if the PNP had attended continuing nursing education offerings. Three themes emerged from a qualitative portion of the survey, asking the participant to share thoughts related to caring for transgender youth: lack of education for healthcare providers, the need to refer patients to comprehensive gender services, and the need for support for transgender patients and their families. Practice Implications: Education plays an important part in nurses' attitudes, beliefs, and perceived competence in caring for transgender patients. Because the PNP is likely to be exposed to patients with TGNC, it is imperative they seek out opportunities to learn about transgender issues and caring for transgender patients. [ABSTRACT FROM AUTHOR]

In this study, we illustrate, for the first time, that preexisting low-avidity neutralizing measles maternal antibodies do not interfere with the development of high concentrations of high-avidity measles antibodies in children immunized at age 12 months. This suggests that the quality of measles maternal antibodies, rather than the quantity, impacts immunogenicity of primary measles immunization. [ABSTRACT FROM AUTHOR]

Residents of Southwest Virginia (SWVA) face significant barriers in accessing the most advanced forms of cancer care, cancer risk reduction, and clinical trials involvement. A collaboration between the University of Virginia (UVA) Cancer Center and UVA School of Nursing was forged with oncology caregivers in this region to build community capacity to support Cancer Clinical trials (CCT) by strengthening the workforce, and thus improving health outcomes for this underserved region of Appalachia. The UVA School of Nursing designed an educational workshop focusing on the basics of CCT to facilitate the development of a skilled nursing workforce in the SWVA region that could provide care to patients on protocol and/or to encourage residents to participate in trials. The goal of the workshop was to offer a CCT training session for oncology nurses that fostered the knowledge and skills necessary to facilitate and support CCT infrastructure across this high‐risk region. This evaluation reports the learning outcomes of the CCT training on 32 nurse participants from SWVA. Evaluations of the training program showed high rates of satisfaction, increased comfort level with CCTs, and increased knowledge and attitude toward CCTs. These findings provide information about a curriculum that could be useful in educating other oncology nurses and student nurses how to care for patients who may be enrolled in a clinical trial. Nurses can also be advocates for participation in clinical trials once they have the knowledge and are comfortable in their own understanding of a trial's usefulness. Educating the nursing workforce is an essential component of building capacity and infrastructure to support clinical trials research. [ABSTRACT FROM AUTHOR]

The publication of the human genome project has launched a number of discoveries set to change the landscape of healthcare. Unfortunately, nursing faculty across the United States report they are unprepared to teach students who will be practicing in the genomic era. The purpose of this study, utilizing Rogers' (2003) Diffusion of Innovation theory as a framework, was to determine the degree to which nursing school characteristics predict graduating undergraduate nursing students' perceived knowledge and competence of genetic family history risk assessment. School characteristics included school size, proximity to a large city, faculty's perceived barriers to diffusion of genomics into nursing practice, faculty innovativeness, faculty who have attended a genetics program for nursing faculty, and the integration of genomics into the curriculum. Faculty and students from 103 nursing schools across the United States participated in the study by completing online surveys. Hierarchical multiple regression was employed to determine how well the independent variables predicted student perceived knowledge and student perceived competence. No combination of the independent variables in this study predicted student knowledge or competence to the degree expected. This could be attributed to a lack of diffusion of genomics content across nursing curricula, based on Rogers' (2003) theory. Other findings included faculty continue to believe they are not competent to teach genomics, and the curriculum is too dense to include more content. However, contrary to prior research, faculty did believe genomics was valuable. The findings of this study give direction for further research into student outcomes and curriculum evaluation after 2011, when a consensus panel working to diffuse genomics into nursing curriculum and practice will have implemented their strategic plan for this diffusion. [ABSTRACT FROM AUTHOR]

Ubiquitin was first described as a tag allowing cells to degrade and recycle their own proteins. Recent research has shown ubiquitin to be central for immune system recognition of invading bacteria. This review describes a set of complex host–pathogen interactions that are dependent on ubiquitination. From the host perspective, ubiquitin-dependent activation of inflammation and degradation of bacterial effectors is protective. Several pathogens become ubiquitinated in the host cell cytosol, and recent research suggests that this could trigger a form of autophagy, increasingly recognized as an important mechanism for the control of infection by a variety of human pathogens. Meanwhile, bacteria have developed mechanisms to evade or exploit the fundamental processes activated by ubiquitination, producing both ubiquitin ligases and deubiquitinases that modulate host responses. [Copyright &y& Elsevier]

Like several other intracellular pathogens, Mycobacterium marinum (Mm) escapes from phagosomes into the host cytosol where it can polymerize actin, leading to motility that promotes spread to neighboring cells. However, only ∼25% of internalized Mm form actin tails, and the fate of the remaining bacteria has been unknown. Here we show that cytosolic access results in a new and intricate host pathogen interaction: host macrophages ubiquitinate Mm, while Mm shed their ubiquitinated cell walls. Phagosomal escape and ubiquitination of Mm occurred rapidly, prior to 3.5 hours post infection; at the same time, ubiquitinated Mm cell wall material mixed with host-derived dense membrane networks appeared in close proximity to cytosolic bacteria, suggesting cell wall shedding and association with remnants of the lysed phagosome. At 24 hours post-infection, Mm that polymerized actin were not ubiquitinated, whereas ubiquitinated Mm were found within LAMP-1-positive vacuoles resembling lysosomes. Though double membranes were observed which sequestered Mm away from the cytosol, targeting of Mm to the LAMP-1-positive vacuoles was independent of classical autophagy, as demonstrated by absence of LC3 association and by Atg5-independence of their formation. Further, ubiquitination and LAMP-1 association did not occur with mutant avirulent Mm lacking ESX-1 (type VII) secretion, which fail to escape the primary phagosome; apart from its function in phagosome escape, ESX-1 was not directly required for Mm ubiquitination in macrophages or in vitro. These data suggest that virulent Mm follow two distinct paths in the cytosol of infected host cells: bacterial ubiquitination is followed by sequestration into lysosome-like organelles via an autophagy-independent pathway, while cell wall shedding may allow escape from this fate to permit continued residence in the cytosol and formation of actin tails. [ABSTRACT FROM AUTHOR]

OBJECTIVE(S): The purpose of the study was to describe definitions of health in Hispanic and African American elders. METHOD(S): This study employed a qualitative framework conducted through a doctoral-level multicultural nursing course. Quasi-statistics and a semi-structured interview format tabulated a frequency in themes in the sample. Hispanic and African American clients at senior citizen centers comprised the convenience sample. Data collection occurred concurrently and the raw data was then shared throughout the class, which led to the study's major limitation. RESULT(S): Eight reoccurring themes were identified: spirituality, without pain/feeling good, positive attitude with good mentality, high priority, independent/active, health promotion/maintenance, socialization and helping others. CONCLUSION(S): Consistency was found between the existing literature and the results of the study. Differences were discovered between the groups, however more similarities were identified. The study results serve as a reminder to the importance in avoiding stereotypes when caring for individuals from any cultural background. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of the study was to describe definitions of health in Hispanic and African American elders. METHODS: This study employed a qualitative framework conducted through a doctoral level multicultural nursing course. Quasi-statistics and a semi-structured interview format tabulated a frequency in themes in the sample. Hispanic and African American clients at senior citizen centers comprised the convenience sample. Data collection occurred concurrently and the raw data was then shared throughout the class, which led to the stud\;'s major limitation. RESULTS: Eight reoccurring themes were Identified: spirituality, without pain/feeling good, positive attitude with good mentality, high priority, independent/active, health promotion/maintenance, socialization, and helping others. CONCLUSIONS: Consistency was found between the existing literature and the results of the study. Differences were discovered between the groups, however more similarities were identified. The study results serve as a reminder to the importance in avoiding stereotypes when caring for individuals from any cultural background. [ABSTRACT FROM AUTHOR]

SHP-1 is a cytoplasm protein tyrosine phosphatase expressed primarily in hematopoietic cells. In the immune system, SHP-1 plays critical roles in regulation of many receptor-mediated signaling cascades, and SHP-1 deficiency in mice causes spontaneous inflammation and autoimmunity. Here, we report a unique requirement for SHP-1 in interleukin-12/23 p40 (IL-12p40) production in response to Toll-like receptor (TLR) stimulation in macrophages. Bone marrow-derived macrophages (BMDMs) lacking significant SHP-1 activity display a profound defect in IL-12p40 synthesis in response to lipopolysaccharide, peptidoglycan, and synthetic TLR ligands, while producing normal amounts of other proinflammatory cytokines, such as TNFalpha and IL-6. Inhibition of SHP-1 function in wild-type BMDMs decreases IL-12p40, and expression of functional SHP-1 protein in mutant cells restores IL-12p40 production following TLR ligation. SHP-1 regulation of IL-12p40 transcription requires both its catalytic activity and phosphotyrosine binding by its N-terminal SH2 domain and is mediated via repression of, and interaction with, phosphatidylinositol 3-kinase, without affecting c-Rel activation. In contrast to normal NF-kappaB activation, SHP-1-defective me(v)/me(v) macrophages display a defect in nucleosome remodeling at the IL-12p40 promoter, and phosphatidylinositol 3-kinase inhibition significantly restores normal nucleosome remodeling in me(v)/me(v) macrophages. Thus, there is a critical role for the tyrosine phosphatase activity of SHP-1 for induction of IL-12p40 production in macrophages in response to TLR ligands, a novel mechanism for host regulation of a specific proinflammatory cytokine important in both innate and adaptive immunity.