TLR signaling is required for Salmonella typhimurium virulence.

Toll-like receptors (TLRs) contribute to host resistance to microbial pathogens and can drive the evolution of virulence mechanisms. We have examined the relationship between host resistance and pathogen virulence using mice with a functional allele of the nramp-1 gene and lacking combinations of TLRs. Mice deficient in both TLR2 and TLR4 were highly susceptible to the intracellular bacterial pathogen Salmonella typhimurium, consistent with reduced innate immune function. However, mice lacking additional TLRs involved in S. typhimurium recognition were less susceptible to infection. In these TLR-deficient cells, bacteria failed to upregulate Salmonella pathogenicity island 2 (SPI-2) genes and did not form a replicative compartment. We demonstrate that TLR signaling enhances the rate of acidification of the Salmonella-containing phagosome, and inhibition of this acidification prevents SPI-2 induction. Our results indicate that S. typhimurium requires cues from the innate immune system to regulate virulence genes necessary for intracellular survival, growth, and systemic infection.

The Wallet Biopsy: Medical Crowdfunding for Heart Transplantation.

Financial considerations continue to impact access to heart transplantation. Transplant recipients face various costs, including, but not limited to, the index hospitalization, immunosuppressive medications, and lodging and travel to appointments. In this study, we sought to describe the state of crowdfunding for individuals being evaluated for heart transplantation. Using the search term heart transplant, 1000 GoFundMe campaigns were reviewed. After exclusions, 634 (63.4%) campaigns were included. Most campaigns were in support of white individuals (57.8%), males (63.1%) and adults (76.7%). Approximately 15% of campaigns had not raised any funds. The remaining campaigns fundraised a median of $53.24 dollars per day. Of the patients, 44% were admitted at the time of the fundraising. Within the campaigns in the United States, the greatest proportions were in the Southeast United States in non-Medicaid expansion states. These findings highlight the significant financial toxicities associated with heart transplantation and the need for advocacy at the governmental and payer levels to improve equitable access and coverage for all.

An attention-based deep learning method for right ventricular quantification using 2D echocardiography: Feasibility and accuracy.

AIM: To test the feasibility and accuracy of a new attention-based deep learning (DL) method for right ventricular (RV) quantification using 2D echocardiography (2DE) with cardiac magnetic resonance imaging (CMR) as reference. METHODS AND RESULTS: We retrospectively analyzed images from 50 adult patients (median age 51, interquartile range 32-62 42% women) who had undergone CMR within 1 month of 2DE. RV planimetry of the myocardial border was performed in end-diastole (ED) and end-systole (ES) for eight standardized 2DE RV views with calculation of areas. The DL model comprised a Feature Tokenizer module and a stack of Transformer layers. Age, gender and calculated areas were used as inputs, and the output was RV volume in ED/ES. The dataset was randomly split into training, validation and testing subsets (35, 5 and 10 patients respectively). Mean RVEDV, RVESV and RV ejection fraction (EF) were 163 ± 70 mL, 82 ± 42 mL and 51% ± 8% respectively without differences among the subsets. The proposed method achieved good prediction of RV volumes (R2  = .953, absolute percentage error [APE] = 9.75% ± 6.23%) and RVEF (APE = 7.24% ± 4.55%). Per CMR, there was one patient with RV dilatation and three with RV dysfunction in the testing dataset. The DL model detected RV dilatation in 1/1 case and RV dysfunction in 4/3 cases. CONCLUSIONS: An attention-based DL method for 2DE RV quantification showed feasibility and promising accuracy. The method requires validation in larger cohorts with wider range of RV size and function. Further research will focus on the reduction of the number of required 2DE to make the method clinically applicable.

Treatment Complications Associated With Hospital Admission in Oropharyngeal Cancer Patients.

BACKGROUND: Oropharyngeal cancer survivorship is a nursing priority because patients are living longer while significant short-term and long-term treatment complications that require nursing care are increasing. Hospital readmission is costly and reflects the quality of care patients receive. OBJECTIVES: This secondary analysis aimed to determine the prevalence of treatment complications resulting in hospital admissions among persons with OPC and examine the relationship between treatment complications resulting in hospital admission among persons with oropharyngeal cancer and all other persons with head and neck cancer. METHODS: Using the National Inpatient Survey 2008-2019 database, we identified persons with relevant head and neck cancer diagnoses using specific International Classification of Disease (ICD) ICD-9 and ICD-10 codes. Complications were operationalized by diagnosis-related codes; persons with codes for major elective surgery were excluded as our focus was post-treatment symptoms requiring hospitalization. Descriptive statistics were used to characterize persons with OPC hospitalized between 2008 and 2019. Binary logistic regression was used to assess complications using crude comparisons. The Elixhauser Comorbidity Index was used for controlling for comorbidities. RESULTS: The final analysis samples included 751,533: 164,770 persons with oropharyngeal cancer and 586,763 with other head and cancers. The most prevalent diagnoses observed in those with oropharyngeal cancer were esophagitis, nutrition disorder, hematological disorder, and renal failure; the least common diagnoses were sepsis, respiratory tract infection, and pneumonia. Binary regression revealed that persons with oropharyngeal cancer experienced significantly more esophagitis, nutrition disorders, hematological disorders, and renal failure compared to persons with other head and neck cancers. DISCUSSION: Treatment of survivors of oropharyngeal cancer requires more intensive monitoring for early symptoms associated with treatment, including esophagitis, nutrition disorders, bleeding disorders, and renal failure, than persons with other head and neck cancers. Monitoring laboratory values and clinical manifestations of these conditions is imperative. Nurses may encounter persons with oropharyngeal cancer in emergency departments, outpatient radiology, or inpatient general medicine floors to manage swallowing difficulties, dehydration, malnutrition, and bleeding. Delayed or ineffective treatment of these conditions contributes to readmission, financial burden, and impairment of patient's quality of life. Future research should investigate the relationship between targeted treatment for expected complications and readmission rates in persons with oropharyngeal cancer.

Can allogeneic haematopoietic cell transplantation be curative in classical Crohn's disease?

The article by Moser et al. details the outcomes of 11 patients with inflammatory bowel disease (IBD) as the main manifestation of their immune deficiency syndrome who are treated with allogeneic transplantation. The authors report low rates of complications (including graft-versus-host disease) and resolution of symptoms. Here we outline whether allogeneic transplantation should be considered more broadly for IBD. Commentary on: Moser et al. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol 2023;200:595-607.

Paediatric cardiologist adherence to American Heart Association neurodevelopmental recommendations for CHD patients.

A 2012 American Heart Association statement concluded that children with CHD are at an increased risk for neurodevelopmental delays. Routine surveillance and evaluation throughout childhood are recommended. To assess paediatric cardiologist compliance with American Heart Association guidelines and developmental referral practices, a survey was distributed to paediatric cardiologists nationwide (n = 129). The majority of participants (69%) stated they were somewhat familiar or not familiar with the American Heart Association statement and were concerned about patients not being properly referred to specialists for developmental evaluation. Forty paediatric cardiologists (31%) indicated that their institution did not have a neurodevelopmental cardiology programme. Of these, 25% indicated they generally did not refer CHD patients for neurodevelopmental evaluation, 45% performed surveillance and referred if warranted, and 30% generally referred all patients for surveillance. Lastly, 43% of paediatric cardiologists did not feel responsible for developmental surveillance, and 11% did not feel responsible for referrals. To ensure all children with CHD are appropriately screened and referred, paediatricians and cardiologists must work together to address differing impressions of accountability for surveillance and screening of children with CHD.

The phenotype of HLA-binding B cells from sensitized kidney transplant recipients correlates with clinically prognostic patterns of interferon-γ production against purified HLA proteins.

B cells play crucial roles in cell-mediated alloimmune responses. In vitro, B cells can support or regulate indirect T-cell alloreactivity in response to donor antigens on ELISpot and these patterns associate with clinical outcome. Previous reports of associations between B-cell phenotype and function have examined global phenotypes and responses to polyclonal stimuli. We hypothesized that studying antigen-specific B cells, using samples from sensitized patients, would inform further study to identify novel targets for intervention. Using biotinylated HLA proteins, which bind HLA-specific B cells via the B-cell receptor in a dose-dependent fashion, we report the specific phenotype of HLA-binding B cells and define how they associated with patterns of anti-HLA response in interferon-γ ELISpot. HLA-binding class-switched and IgM+CD27+ memory cells associated strongly with B-dependent interferon-γ production and appeared not suppressible by endogenous Tregs. When the predominant HLA-binding phenotype was naïve B cells, the associated functional ELISpot phenotype was determined by other cells present. High numbers of non-HLA-binding transitional cells associated with B-suppressed interferon-γ production, especially if Tregs were present. However, high frequencies of HLA-binding marginal-zone precursors associated with B-dependent interferon-γ production that appeared suppressible by Tregs. Finally, non-HLA-binding marginal zone precursors may also suppress interferon-γ production, though this association only emerged when Tregs were absent from the ELISpot. Thus, our novel data provide a foundation on which to further define the complexities of interactions between HLA-specific T and B cells and identify new targets for intervention in new therapies for chronic rejection.

Rapid Development of a Telehealth Patient Satisfaction Survey Using a Multi-Stakeholder Approach.

Introduction: The COVID-19 pandemic has hastened the adoption of telehealth and the drastic shift to an unfamiliar process may impose significant impact to the quality-of-care delivery. Many providers are interested in understanding the quality of their telehealth services from the patients' experience. Materials and Methods: A telehealth patient satisfaction survey (TPSS) was developed by using an iterative stakeholder-centered design approach, incorporating elements from validated telemedicine and customer service survey instruments, and meeting the operational needs and constraints. A cross-sectional study design was employed to collect survey responses from patients and families of a large pediatric hospital. Finally, we performed exploratory factor analysis (EFA) to extract latent constructs and factor loadings of the survey items to further explain relationships. Results: A 22-item TPSS closely matched the existing in-person patient satisfaction survey and mapped to a revised SERVPERF conceptual model that was proposed by the interdisciplinary committee. Survey was implemented in the HIPAA-compliant online platform REDCap® with survey link embedded in an automated Epic MyChart (Verona, WI) visit follow-up message. In total, 2,394 survey responses were collected between July 7, 2020, and September 2, 2020. EFA revealed three constructs (with factor loadings >0.30): admission process, perceived quality of services, and telehealth satisfaction. Conclusions: We reported the development of TPSS that met the operational needs of compatibility with existing data and possible comparison to in-person survey. The survey is short and yet covers both the clinical experience and telehealth usability, with acceptable survey validity.

The indirect effect of positive affect in the relationship between trait mindfulness and emotion dysregulation.

Mindfulness is correlated with better emotion regulation and mindfulness training improves emotion regulation; however, mechanisms of these effects have not been widely studied. Therefore, the aim of the current study was to examine the indirect effect of greater mindfulness on fewer emotion regulation difficulties through positive affect. Participants were 219 undergraduate students (M age =19.20; 70.5% female; 91.5% Caucasian) who completed self-report measures for course credit. Results indicated a significant direct effect of mindfulness on emotion dysregulation (b = -1.71, t = -6.94, p < .001) and significant indirect effect of greater mindfulness on fewer emotion regulation problems through higher levels of positive affect (indirect effect =-0.50; SE = 0.13; 95% CI = -0.80 to -0.28). These results help to generate testable hypotheses for future mechanistic research in this area by suggesting that one way trait mindfulness may protect against emotion dysregulation could be by cultivating positive affect. Future research using longitudinal designs is needed to explore positive affect as a causal mechanism.

Graft dysfunction in chronic antibody-mediated rejection correlates with B-cell-dependent indirect antidonor alloresponses and autocrine regulation of interferon-γ production by Th1 cells.

Chronic antibody-mediated rejection, a common cause of renal transplant failure, has a variable clinical phenotype. Understanding why some with chronic antibody-mediated rejection progress slowly may help develop more effective therapies. B lymphocytes act as antigen-presenting cells for in vitro indirect antidonor interferon-γ production in chronic antibody-mediated rejection, but many patients retain the ability to regulate these responses. Here we test whether particular patterns of T and B cell antidonor response associate with the variability of graft dysfunction in chronic antibody-mediated rejection. Our results confirm that dynamic changes in indirect antidonor CD4+ T-cell responses correlate with changes in estimated glomerular filtration rates, independent of other factors. Graft dysfunction progressed rapidly in patients who developed unregulated B-cell-driven interferon-γ production. However, conversion to a regulated or nonreactive pattern, which could be achieved by optimization of immunosuppression, associated with stabilization of graft function. Functional regulation by B cells appeared to activate an interleukin-10 autocrine pathway in CD4+ T cells that, in turn, impacted on antigen-specific responses. Thus, our data significantly enhance the understanding of graft dysfunction associated with chronic antibody-mediated rejection and provide the foundation for strategies to prolong renal allograft survival, based on regulation of interferon-γ production.

Health implications of new-age technologies: a systematic review.

INTRODUCTION: New-age technologies are ubiquitous in the lives of adolescents. Recent trends in media use suggest that adolescents are spending more time than ever engaging with technologies, and are able to do so in virtually all settings at any time. Given that new-age technologies are so heavily integrated within the daily life of adolescents, the health risks and benefits they offer must be closely examined. EVIDENCE ACQUISITION: In this systematic review, we present recent literature related to the implications of new-age technologies on adolescent health. A total of 94 articles published since 2006 were collected using PubMed and Google Scholar on the most popular new-age technologies among adolescents: the internet, television, cell phones, and video games. EVIDENCE SYNTHESIS: The current body of research highlights several health risks related to these technologies. Nearly all have the potential for addiction, which can result in other symptoms and impair one's daily life. Excessive use can affect several components of health, such as quality of sleep, body composition, and mental well-being, and certain practices (viewing pornography, sexting) can lead to risky sexual behaviors. However, the technologies discussed in the present review also have tremendous potential to promote adolescent health. CONCLUSIONS: Pediatricians must educate parents and patients on how to safely use technology to minimize the potentially harmful outcomes.

Pokémon Go and augmented virtual reality games: a cautionary commentary for parents and pediatricians.

PURPOSE OF REVIEW: The recent release of Pokémon Go has ushered in a new set of challenges for parents and pediatricians, highlighting the importance of parents setting guidelines for video game use with their children. Within 1 week of its launch, the game attracted over 65 million users, many of whom are young children. Despite the potential benefits of the game described in our article, this location-based game format poses specific threats to the safety and physical wellbeing of children. RECENT FINDINGS: Reports have discussed both the benefits and adverse effects of this extremely popular video game. Benefits include increased exercise, socialization, and outdoor activity. Negative effects include increased risk of injury, abduction, trespassing, violence, and cost. SUMMARY: Pediatricians play a key role in counseling parents and children about safety precautions and setting appropriate limits for impressionable youth. Parents and pediatricians should be aware of this new and remarkably popular game that appeals to a wide variety of individuals. To protect children from injury, predators, and inappropriate situations, parents and pediatricians must regulate children's participation in this game and maintain vigilance for potentially dangerous circumstances.

Laser cellulite treatment and laser-assisted lipoplasty of the thighs and buttocks: Combined modalities for single stage contouring of the lower body.

BACKGROUND AND OBJECTIVES: Cellulite and lipodystrophy are often found together, especially in areas of the buttocks and thighs, causing skin surface irregularities. Each of these conditions is currently treated independently as two separate surgical procedures. In our practice, we developed a novel combined approach for the simultaneous treatment of cellulite and lipodystrophy, as a single stage procedure in the same anatomic area. For the treatment of cellulite, we used the Nd:YAG laser at a wavelength of 1,440-nm, along with an innovative 1,000-micron directional side-firing fiber optic laser system. For the treatment of lipodystrophy, the Nd:YAG laser with a 1,440 nm wavelength, along with a fiber optic laser system was used. The objective of this study is to determine the efficacy and safety of a combined approach for the simultaneous treatment of cellulite and lipodystrophy. STUDY DESIGN, PATIENTS AND METHODS: In 2012, 16 subjects with noticeable cellulite, Grade II and Grade III, accompanied by mild-to-moderate lipodystrophy of the lower body received single treatments of the Nd:YAG laser at a wavelength of 1,440-nm along with the 1,000-micron side-firing fiber optic laser system for simultaneous treatments of both cellulite and lipodystrophy. Patients were assessed at baseline and 3-6 months post-treatment by a modified Nurnberger-Muller scale utilized to quantify the cellulite severity. Additionally, patient satisfaction and a global aesthetic improvement scale were used to measure the improvement in lipodystrophy. RESULTS: Blinded reviewers identified the correct baseline photographs 97% of the time when presented with a set of photographs. The median modified Nurnberger-Muller scale score at baseline was 4.75 ± 1.2 and the average improvement was 2.0 ± 1.2. Global aesthetic improvement scores ranged from 1 to 3 with an average of 1.58 indicating a much-improved overall appearance. Satisfaction was high for both physicians and patients with scores corresponding to extremely satisfied/satisfied. CONCLUSION: Precise, effective delivery of laser energy to the dermal-adipose tissue, as well as the deep adipose lipodystrophy is feasible as a safe modality for the simultaneous treatment of cellulite and lipodystrophy in the buttocks and thighs, as a single stage procedure.

B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection.

We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on 'for cause'. Using enzyme-linked immunosorbent spot assays, we found interferon-γ production by indirect allorecognition in 45 of 119 total samples from the 65 patients. B-cells preferentially processed and presented donor alloantigens in samples from AMR patients. In a further 25 samples, B-cell-dependent allo-specific reactivity was shown by depletion of CD25(+) cells and these individuals had higher percentages of CD4CD25hi cells. In 21 samples, reactivity was shown by depletion of CD19(+) cells, associated with polarized cytokine production toward IL-10 after polyclonal activation by IgG/IgM. Overall, this shows a significant contribution by B-cells to indirect donor-specific T-cell reactivity in vitro in patients with AMR. Active suppression by distinct phenotypes of T- or B-cells in approximately half of the patients indicates that chronic AMR is not characterized by a universal loss of immune regulation. Thus, stratified approaches that accommodate the heterogeneity of cell-mediated immunity might be beneficial to treat graft dysfunction.

Taste dysfunction and eating behaviors in survivors of head and neck cancer treatment.

Radiation, chemotherapy, and surgery result in eating problems for patients with head and neck cancer. Eating is essential to physical and social functioning. Strategies for head and neck cancer survivors to cope with eating and taste impairments are reported in this study.

The Prevalence of Type II Workplace Violence in US Nurses 2000 to 2022: A Meta-Analysis.

BACKGROUND: Physical violence against nurses is a concern in the United States; however, its prevalence is not well quantified. OBJECTIVE: We sought to describe the prevalence of workplace violence against nurses in the United States over a 22-year period. METHODS: A meta-analysis was performed following a literature search of English texts through Scopus, CINAHL Plus, and Ovid MEDLINE. Inclusion criteria included the following: (1) primary reports of workplace violence incidents in the United States against nurses, (2) perpetrator was a patient, family member, or visitor, and (3) publications between January 1, 2000, and June 21, 2022. Reports where prevalence rates for nurses could not be calculated were excluded. Study quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. RESULTS: Thirty-seven studies met the inclusion criteria; 27 030 nurses were included. The pooled prevalence of workplace violence was 0.35 (95% confidence interval [CI]: 0.29-0.42; Q = 3189.40; I2 = 98.87). Pooled rates of workplace violence increased from 30% in 2000 to 2004 to 43% in 2020 to 2022; however, the overlapping CIs indicate that the increase may not be statistically significant. The mean prevalence of reported workplace violence among nurses who work in the emergency department, in corrections, and psychiatric mental health settings (pooled prevalence = 0.59, 95% CI: 0.46-0.71) was higher than that of nurses who worked in all other settings (pooled prevalence = 0.24, 95% CI: 0.18-0.30). CONCLUSIONS: Workplace violence is a significant and potentially increasing problem for nurses in the United States. This critical problem requires an effective response from nurse policymakers.

A survey of stakeholder knowledge, experience, and opinions of advance directives for mental health in Virginia.

An innovative Virginia health care law enables competent adults with serious mental illness to plan for treatment during incapacitating crises using an integrated advance directive with no legal distinction between psychiatric or other causes of decisional incapacity. This article reports results of a survey of 460 individuals in five stakeholder groups during the initial period of the law's implementation. All respondents held favorable views of advance directives for mental health care. Identified barriers to completing and using advance directives varied by group. We conclude that relevant stakeholders support implementation of advance directives for mental health, but level of baseline knowledge and perception of barriers vary. A multi-pronged approach will be needed to achieve successful implementation of advance directives for mental health.

Response to "Patients With Limited English Proficiency: A Challenge for Oncology Nursing Providers".

Limited English proficiency (LEP) is challenging for oncology nursing because language barriers affect access to health services and patient outcomes. Strategies to mitigate this problem may differ based on the region of the.

Family environment of youth with first episode Mania.

BACKGROUND: The purpose is to compare youth- and caregiver-reported characteristics of family environment, within and between families with a child experiencing a first manic episode of bipolar disorder (BPD), and families without a child with BPD or familial history of psychiatric disorders (HF). METHODS: Family environment of 61 families with a child with BPD and 44 HF were assessed with Family Environment Scale (FES). We compared FES subscale scores between families with BPD and HF, and caregiver- and youth-rated scores. RESULTS: Families with BPD differed significantly from HF on 8/10 FES subscales scores. Youth differed significantly from their caregivers on 7/10 subscales. An interaction effect was observed such that youth with BPD reported lower cohesion and organization, and higher conflict than their caregivers; however, HF did not differ significantly on these domains. CONCLUSIONS: Our results suggest that families with BPD have higher conflict and lower cohesion and organization compared to HF. Results also indicate differences between youth and caregiver perspectives in both groups, which may contribute to family discord. Interventions targeting areas of cohesion, organization, and conflict may be beneficial for youth with BPD and their families, specifically those that identify and bridge perceptual divides.