Biomarkers to predict and diagnose pulmonary complications in children post haematopoietic stem cell transplant.

OBJECTIVES: Haematopoietic cell transplant (HCT) is a cellular therapy for a group of high-risk children with cancer, immunodeficiency and metabolic disorders. Whilst curative for a child's underlying condition, HCT has significant risks associated, including lung injury. These complications are associated with increased post HCT mortality and require improved methods of risk stratification, diagnosis and treatment. METHODS: Biomarkers measured in bronchoalveolar fluid and peripheral blood have been identified for both acute and chronic lung injury post HCT.This review evaluates the current research available investigating the use of these biomarkers to improve clinical care, with a focus on the paediatric cohort. RESULTS: Elevated levels of cytokines such as IL-6, IL-8, G-CSF and TNF were identified as potential predictive biomarkers for the development of post HCT lung disease. The pulmonary microbiome was found to have strong potential as a biomarker pre and post HCT for the development of pulmonary complications. General limitations of the studies identified were study design, retrospective or single centre and not exclusively performed in the paediatric population. CONCLUSION: To translate biomarker discovery into clinical implementation further research is required, utilising larger cohorts of children in prospective trials to validate these biomarkers and determine how they can be translated into better outcomes for children post HCT.

Pulmonary complications post allogeneic haematopoietic stem cell transplant in children.

Objectives: Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications. Methods: Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio. Results: In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non-infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, P = 0.02), matched unrelated donor (RR1.34, P = 0.03), peripheral blood (RR 1.36, P = 0.028) or cord blood (RR 1.73, P = 0.012) as the stem cell source and pre-existing lung disease (RR1.72, P < 0.0001). Children with a post-HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, P < 0.0001). Conclusion: This study demonstrates pulmonary complications continue to occur frequently in children post-HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre-transplant and enhanced treatments for those who develop lung disease.

Life with pets study: lower income veterinary clients' perception of pets' quality of life.

Perception of quality of life for cats and dogs of low-income Spanish and English-speaking veterinary clients attending problem focused or routine veterinary visits is an important area of focus for community based veterinary service providers. Using a qualitative approach, 50 New York City based American Society for the Prevention of Cruelty to Animals (ASPCA) veterinary clients completed semi-structured interviews as well as a survey about their perception of life with their pets. Veterinary clients shared both human-animal bond (HAB) related and quality of life (QoL) related factors in their daily experience of life with their pets. Results indicated that this demographic perceives QoL similarly to previous QoL research that either does not report sample demographics or reports sample demographics with more affluence. Moreover, 60% of qualitative excerpts included both HAB and QoL themes and 40% were discretely HAB or QoL. An analog single item 10-point scale measuring veterinary client perception of their pets QoL did not differentiate between sample demographics at a statistically significant level. Finally, pet QoL literature has not traditionally reflected diverse demographic identities of veterinary clients or widely included reliable and valid measures of the human-animal bond (HAB). These results support the importance of measuring the HAB when researching pet QoL and provide evidence that lower-income Spanish and English-speaking veterinary clients are similarly bonded and attentive to their pets as other demographics.

Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome.

Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in the ADNP gene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood. Here, we investigated the longitudinal effect of ketamine on the blood transcriptome of 10 individuals with ADNP syndrome. Transcriptomic profiling was performed before and at multiple time points after a single low-dose intravenous ketamine infusion (0.5 mg/kg). We show that ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These acute alterations encompass diverse signaling pathways and co-expression networks, implicating upregulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings enhance our understanding of ketamine's molecular effects and lay the groundwork for further research elucidating its specific cellular and molecular targets. Moreover, they contribute to the development of therapeutic strategies for ADNP syndrome and potentially, ASD more broadly.

Small but mighty: Case report and practical guidance for peripheral blood stem cell collection in small infants.

Modern apheresis devices, with increased procedural precision, automation, and monitoring, have been shown to allow for safe delivery of apheresis therapies in young children. Medical advances are increasing demand for apheresis procedures like mononuclear cell collection in infants <10 kg, including stem-cell supported chemotherapy, cell collection for chimeric antigen receptor T cell development, and now ex vivo gene therapies for rare genetic diseases. Nevertheless, safe delivery in small infants involves a range of unique considerations and challenges, beyond just size, and experience will vary between centers. In this case report we describe our experience performing mononuclear cell collection in our smallest patient to date and outline a practice guideline developed following a literature review and discussion with both international experts and device representatives. This case may help to inform other clinicians aiming to provide apheresis care to very small infants in their own centers.

Posaconazole in paediatric malignancy and haematopoietic stem cell transplant: dosing to achieve therapeutic concentration.

OBJECTIVES: Posaconazole is increasingly used for the treatment and prophylaxis of invasive fungal infections in immunocompromised children. We aimed to review evidence for paediatric posaconazole dosing regimens focusing on attainment of target concentrations and frequency of adverse effects. METHODS: In May 2023, the Cochrane, Embase, MEDLINE and PubMed databases were searched for articles reporting posaconazole dosing in children with malignancy or post-haematopoietic stem cell transplantation. Studies reporting the attainment of target serum concentrations were included. RESULTS: Overall, 24 studies were included. Eighteen studies of the oral suspension consistently reported poor attainment of target concentrations for prophylaxis (≥0.7 µg/mL, 12%-78%) despite high daily doses of 14-23 mg/kg/day (max. 1200 mg/day). Target attainment was significantly affected by gastric pH and food intake. Six studies of the delayed-release tablet (DRT) reported 58%-94% achieved concentrations ≥0.7 µg/mL, with the majority using lower doses of 4-12 mg/kg/day (max. 300 mg/day). Similarly, one study of powder for oral suspension found 67%-100% achieved target concentrations with a dose of 6 mg/kg/day (max. 300 mg/day). As expected, the IV formulation had high attainment of prophylaxis targets (81%-90%) with 6-10 mg/kg/day (max. 400 mg/day). All formulations were well tolerated, and no relationship between adverse effects and posaconazole concentrations was identified. CONCLUSIONS: The required posaconazole dose in immunocompromised children varies depending on the formulation. The IV infusion had the highest attainment of therapeutic concentration followed by the DRT and powder for suspension. By contrast, the oral suspension had low attainment of target concentrations despite higher daily doses.

Metastatic oropharyngeal squamous cell carcinoma to the thyroid: A case report and review of literature.

Oral squamous cell carcinoma (OSCC) with metastasis to the thyroid gland is exceedingly rare, with limited documentation within the literature. Between 1984 and 2023, only 40 cases of head and neck squamous cell carcinoma (SCC) with thyroid gland metastasis were described in published literature. Herein, we present a distinctive case of second primary oropharyngeal SCC with metastasis to the thyroid, detected during surveillance positron emission tomography (PET) scanning subsequent to negative margin resection and radiation therapy for SCC originating from the hard palate. The underlying mechanisms overseeing metastasis remain elusive, with hypotheses ranging from lymphatic drainage routes connecting the thyroid gland and retropharyngeal lymph nodes to hematologic dissemination. The management of metastases to the thyroid gland is multifaceted, encompassing approaches ranging from lobectomy and total thyroidectomy to palliative interventions. We present this atypical case alongside supportive pathological and radiological findings and a comprehensive review of this rare clinical entity to offer insight into its diagnosis and management.

Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease.

Suppurative lung disease and wheezing are common respiratory diseases of childhood, however, due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and chronic suppurative lung disease for identification of endotypes that can inform improved clinical management. We used clinical microbiology data, highly multiplexed flow cytometry and immunoassays to compare pulmonary [bronchoalveolar lavage (BAL)] and systemic immunity in children with lung disease and controls. Unsupervised analytical approaches were applied to BAL immune data to explore biological endotypes. We identified two endotypes that were analogous in both frequency and immune signature across both respiratory diseases. The hyper-inflammatory endotype had a 12-fold increase in neutrophil infiltration and upregulation of 14 soluble signatures associated with type 2 inflammation and cell recruitment to tissue. The non-inflammatory endotype was not significantly different from controls. We showed these endotypes are measurable in a clinical setting and can be defined by measuring only three immune factors in BAL. We identified hyper-inflammatory and non-inflammatory endotypes common across pediatric wheeze and chronic suppurative lung disease that, if validated in future studies, have the potential to inform clinical management.

Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome.

Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD) and is due to mutations in the ADNP gene. Ketamine treatment has emerged as a promising therapeutic option for ADNP syndrome, showing safety and apparent behavioral improvements in a first open label study. However, the molecular perturbations induced by ketamine remain poorly understood. Here, we investigated the longitudinal effect of ketamine on the blood transcriptome of 10 individuals with ADNP syndrome. Transcriptomic profiling was performed before and at multiple time points after a single low-dose intravenous ketamine infusion (0.5mg/kg). We show that ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These acute alterations encompass diverse signaling pathways and co-expression networks, implicating up-regulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings enhance our understanding of ketamine's molecular effects and lay the groundwork for further research elucidating its specific cellular and molecular targets. Moreover, they contribute to the development of therapeutic strategies for ADNP syndrome and potentially, ASD more broadly.

Evaluating real-world emissions from in-use buses and taxis using on-road remote sensing.

Assessing real-world emissions from buses and taxis is vital to comprehend their impact on urban air quality. Such vehicles differ significantly from the majority of the fleet owing to their higher mileage rates. However, few studies have focused on specifically assessing the emissions from this segment of the vehicle fleet. In this context, this study evaluated the real-world emissions of nitrogen oxides (NOx) from in-use buses and taxis in Dublin, Ireland, using crossroad remote sensing technology. The remote sensing system was deployed at strategic locations throughout the city to capture on-road emissions from passing vehicles. The collected data included vehicle related information such as emission standard, make, and mileage, and pollutants including NOx. Based on this data, analysis was aimed to understand the impact of Euro emission standard, ambient temperature, mileage, and make of the vehicle on NOx emissions. The results reveal that the average emissions from taxis reduce by 37% from Euro 5 to Euro 6b, and average emissions from Euro 6 buses are 87% lower compared to Euro 5. The trends in emission factors (EFs) of buses and taxis were similar during summer and winter sampling. Moreover, on comparing the emissions from the top five taxi manufacturers, different trends in the emission factors were observed. Finally, the study found that the effect of vehicle mileage on emissions was unclear for both buses and taxis. In any case, these findings provide valuable insights into the real-world emission performance of the existing fleet of buses and taxis in Dublin and highlight the need for targeted measures to reduce emissions from these vehicles. The results can assist policymakers and urban planners in formulating evidence-based strategies to improve air quality in Dublin and other cities facing similar challenges.

Initiation of Breast Cancer Screening at a Later Age May Disproportionately Impact Minority Groups: Review of Ohio Data (1996-2022).

Among women with breast cancer, delays in diagnosis and earlier presentation have been documented among minority women. Consequently, initiation of breast cancer screening at a later age may disproportionately harm minority groups. This study seeks to determine whether minority women face a higher proportional risk of younger age breast cancer than their White peers. Using publicly available data from the Ohio Department of Public Health Data Warehouse, we constructed a database allowing for retrospective evaluation of all breast cancer patients in the state of Ohio from 1996 to 2020. White women represented the bulk of total breast cancer cases in each age group and overall; however, the proportion of cancers attributable to White women increased in each successively older cohort group: 80.7% of cases under age 40 up to 91.3% of the 80 or older group. By a significant margin, the opposite is true in minority groups with African American women accounting for 15% of cases under the age of 40, trending down to 7.8% of the 80 and older group. Comparison of the proportions of these groups demonstrates statistically significant proportional decreases among minority groups and statistically significant increases among White women. Our findings suggest that women of color in the Ohio population face a disproportionately high risk of being diagnosed with younger age breast cancer and support the findings of other authors who recommend tailoring breast cancer screening by racial cohort. Efforts should be made to promote younger-age screening for minority women to prevent disproportionate harm.

An investigation of the associations between trauma exposure, racial stereotypes, and racist beliefs.

OBJECTIVE: Given the concerning rise in hate crimes in recent years, it is critical to better understand factors associated with racist beliefs. As suggested by terror management theory (TMT), trauma exposure and posttraumatic stress symptoms (PTSS) may activate existential distress and anxiety, which may strengthen worldviews, including prejudiced beliefs (Greenberg & Kosloff, 2008; Weise et al., 2012). Although PTSS include negative alterations in beliefs about other people and the world, the connection between trauma and racist beliefs has not been investigated. There may also be key differences in terms of types of trauma exposure, such as interpersonal and noninterpersonal trauma, and racial beliefs. METHOD: The present study aimed to determine: (a) whether cumulative trauma exposure and PTSS are associated with endorsement of racist perceptions and stereotypes regarding Black people, and (b) if interpersonal trauma is more strongly tied to prejudiced and stereotyped beliefs than noninterpersonal trauma among 277 White undergraduates (Mage = 23.33, SD = 6.11; 76.4% female). RESULTS: Neither cumulative trauma nor PTSS were found to be related to elevated racist beliefs or positive or negative stereotypes. However, noninterpersonal trauma exposure was associated with stronger endorsement of racist beliefs and negative stereotypes (ηp² = .03, .01). Surprisingly, interpersonal trauma exposure corresponded with lower racist beliefs (ηp² = .02). CONCLUSIONS: Noninterpersonal trauma exposure may thus activate TMT and strengthen prejudiced ideology, whereas interpersonal traumatic experiences and PTSS may not. More research is needed to better understand how types of traumatic events may relate to the development of prejudiced beliefs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Participatory Implications of Racialized Policy Feedback.

How do involuntary interactions with authoritarian institutions shape political engagement? The policy feedback literature suggests that interactions with authoritarian policies undercut political participation. However, research in racial and ethnic politics offers reason to believe that these experiences may increase citizens' engagement. Drawing on group attachment and discrimination research, we argue that mobilization is contingent on individuals' political psychological state. Relative to their counterparts, individuals with a politicized group identity will display higher odds of political engagement when exposed to authoritarian institutions. To evaluate our theory, we draw on the 2016 Collaborative Multiracial Post-Election Study to examine the experiences of Blacks, Latinos, and Asian Americans. For all subgroups and different types of institutions, we find that, for those with a politicized group identity, institutional contact is associated with higher odds of participation. Our research modifies the classic policy feedback framework, which neglects group-based narratives in the calculus of collective action.

Gait Abnormalities in Children with Phelan-McDermid Syndrome.

Background: Phelan-McDermid syndrome is a genetic disorder caused by haploinsufficiency of the SHANK3 gene on chromosome 22q13.3 and is characterized by autism spectrum disorder, intellectual disability, speech and language abnormalities, hypotonia, and mild dysmorphic features. Early literature in Phelan-McDermid syndrome did not include gait abnormalities as part of the syndrome although recent prospective studies report that the prevalence of gait abnormalities ranges from 55% to 94%. We compared gait abnormalities in individuals with Phelan-McDermid syndrome, idiopathic autism spectrum disorder, and typically developing controls, and explored associations between gait abnormalities, autism spectrum disorder, and intellectual functioning. Method: The study cohort consists of 67 participants between the ages of 3 and 18 years, divided into 3 groups: Phelan-McDermid syndrome (n = 46), idiopathic autism spectrum disorder (n = 11), and typically developing controls (n = 10). Gait was recorded using a video camera and scored across 26 gait features using a "Gait Clinical Observations scale" designed specifically for this study. Results: Gait abnormalities were significantly higher in the Phelan-McDermid syndrome group as compared to idiopathic autism spectrum disorder or typically developing controls. The number of gait abnormalities across groups was also significantly correlated with Intellectual Quotient/Developmental Quotient (IQ/DQ). In analysis of covariance including IQ/DQ, the effect of group was not significant, but the effect of IQ/DQ was significant. Conclusions: Overall differences in gait abnormalities were determined by the degree of intellectual disability, which was significantly higher in Phelan-McDermid syndrome.

Delayed skin grafting protocol following Integra™ application for non-radiated scalp reconstruction for decreased wound depth and improved contour.

The clinical use of Integra™ has expanded to include scalp reconstruction since its FDA approval in 1996. Integra™, or dermal regeneration template, can be utilized in patients who are elderly with multiple medical comorbidities. Well-established Integra™ techniques utilize skin grafting 1-2 weeks following evidence of template vascularity. Most studies show the time to graft placement as <30 days, with almost all <52 days. No single article proposes a time frame for applying STSG after neodermis regeneration. Therefore, we aimed to describe our protocol to define a time frame for delaying scalp reconstruction with STSG following dermal regeneration. Over the last several years, the senior author has utilized a delayed reconstruction with skin grafting method where-in Integra™ is applied to either debrided bone or exposed pericranium in selected patients, and allowed to mature for ~6 weeks before performing skin grafting. The results have been predictable, reproducible, and have yielded high levels of patient and provider satisfaction due to the improved contour cosmesis. In this pictorial essay, the authors' novel protocol is detailed.

Predation risk drives aposematic signal conformity.

Contrary to expectations regarding efficient predator education mediated by lack of ambiguity and enhanced prey recognition, aposematic signals often show considerable intraspecific variability. For example, some striped skunks (Mephitis mephitis) are almost entirely white, others have black-and-white stripes of equivalent thicknesses, yet others are mostly black. We tested the ecological correlates of this variation in patterning using 749 museum skins collected across North America. Skunks had longer white-black borders and more bilaterally symmetrical stripes in areas with a greater number of potential predator species, and this effect was more marked for mammalian than avian predators, the latter of which may be less deterred by noxious defenses. Skunks from locations with greater predator diversity were less variable in the extent of whiteness on their dorsa and less variable in the length of their white-black borders, suggesting strong selection from predators leads to greater conformity in stripe patterns, even at the same location, but weak selection from predators leads to relaxed selection on pattern conformity. Skunks exhibited greater areas of black pelage in areas of greater humidity conforming to Gloger's rule. Our results indicate that relaxed predation pressure is key to warning signal variation in this iconic species, whereas stronger pressure leads to signal conformity and stronger signals.

Physical Health Outcomes of Trauma Exposure Across the Lifespan.

Trauma exposure and posttraumatic stress symptoms (PTSS) are established risk factors for poorer physical health. Prior work has focused on childhood adversities and PTSS in relation to physical health conditions, but trauma exposure over the lifespan has been overlooked. Further, the associations between trauma and PTSS and other physical health markers, such as diet and exercise, are less clear. Very little is known regarding how different trauma types (i.e., interpersonal, non-interpersonal), may be tied to aspects of physical health. To expand this area of research, this study aimed to: (a) examine the links between cumulative trauma and PTSS, and body mass index (BMI), diet, and exercise; and (b) investigate the relations between interpersonal and non-interpersonal trauma and these three health indices, while controlling for PTSS. Participants were 493 Midwestern University students (Mage = 23.87, standard deviation [SD] = 6.90, range = 18-63; 79.3% female; 57.4% White). Cumulative trauma corresponded with higher BMIs and less exercise use (B = 0.10; B = -0.09), while PTSS were unrelated. Conversely, PTSS were tied to greater consumption of added sugars (B = 0.11), and cumulative trauma was not linked with diet. Interpersonal and non-interpersonal traumas were not tied to BMI or exercise, although interpersonal trauma and PTSS were linked with greater sugar intake and non-interpersonal trauma was associated with fruit and vegetable consumption. Trauma exposure and PTSS may have complicated and distinct associations with physical health indices, such as BMI, diet, and exercise, and additional research is needed to further parse out these relations.