Facilitating an Interprofessional Course on Climate Change and Public Health Preparedness.

In this paper, we share the theories that guided the design of an interprofessional education course on Climate Change and Public Health Preparedness and how the course supported students' professional interest and action competence as they move through their education and into their professional work in the context of our unfolding climate crisis. The course was guided by the public health emergency preparedness domains and was built to allow for students to explore applications of the content for themselves and their own profession. We designed the learning activities to support personal and professional interest development and help students move into perceived and demonstrated action competence. For the evaluation of our course, we asked the following research questions: What kinds of personal and professional commitments to action did students propose by the end of the course? Did these vary in depth and specificity and by the number of credits they enrolled in? In what ways did students develop personal and professional action competence over the course? Finally, how did they show personal, professional, and collective agency related to the course content on adaptation, preparedness, and mitigation of the health impacts from climate change? Using qualitative analysis guided by action competence and interest development theories, we coded student writing from course assignments. We also conducted comparative statistical analysis to assess differential impacts for students who enrolled for one versus three credits. The results show that this course design supported students' progression of knowledge and perceived ability in specific individual and professional collective actions to reduce the health impacts of climate change.

The physiology, assessment, and treatment of neonatal pain.

Studies have clearly shown that development of pain receptors starts as early as 20-weeks' gestation. Despite contrary belief, the human fetus develops a similar number of receptive pain fibers as seen in adults. These receptors' maturation is based on response to sensory stimuli received after birth which makes the NICU a critical place for developing central nervous system's pain perception. In practice, the assessment of pain relies mostly on bedside staff. In this review we will discuss the various developing features of pain pathways in the neonatal brain and the modification of pain perception secondary to various interactions immediately after birth. We also discuss the various tools utilized in the NICU for pain assessment that rely on physiological and behavioral patterns. Finally, we address the management of pain in the NICU by either pharmacological or non-pharmacological intervention while highlighting potential benefits, disadvantages, and situations where one may be preferred over another.

An examination of psychosocial and professional effects of the COVID-19 pandemic on genetic counselors.

For healthcare workers, recognized professional challenges associated with the COVID-19 pandemic include changes to service delivery models, increased burnout, furlough, and loss of income. The main goal of this study was to more clearly define the impact on mental health and quality of life of genetic counselors during the COVID-19 pandemic in the contexts of their personal, professional, and social lives. Eligible genetic counselors (GCs) (n = 283) responded to an online survey that incorporated validated instruments: Patient Health Questionnaire, Generalized Anxiety Disorder, Professional Quality of Life, and the In Charge Financial Distress/Financial Well-Being Scale. Additionally, original questions were developed from previous qualitative research on COVID-19 challenges for healthcare workers. Results showed 62% of respondents felt their mental health was impacted for the worse, 45% found it more difficult to achieve work/life balance, 16.8% scored within moderate-to-severe depression severity, 19.2% scored within moderate-to-severe anxiety, 26.3% reported high burnout, and 7% had high financial distress. GCs reported generally lower levels of anxiety and depression compared to healthcare workers and the general population. Thematic analysis identified feelings of isolation and difficulties balancing professional/personal responsibilities with more remote work. However, some participants reported greater flexibility in their schedule and more time with family. Self-care activities increased, with 93% engaging in more meditation and 54% began exercising. There were similar themes reported in this survey compared to other healthcare workers' experiences. There is also a dichotomy in positive and negative impacts with some GCs appreciating the flexibility of working from home but others reporting this blurs the line between personal and professional responsibilities. These results suggest consequences of the COVID-19 pandemic will continue to impact the field of genetic counseling and understanding these changes will be instrumental in addressing the needs of GCs to practice effectively.

IRF7 and UNC93B1 variants in an infant with recurrent herpes simplex virus infection.

Neonatal herpes simplex virus (HSV) infection is a devastating disease with substantial morbidity and mortality. The genetic basis of susceptibility to HSV in neonates remains undefined. We evaluated a male infant with neonatal skin/eye/mouth (SEM) HSV-1 disease, who had complete recovery after acyclovir but developed HSV-1 encephalitis at 1 year of age. An immune workup showed an anergic PBMC cytokine response to TLR3 stimulation but no other TLRs. Exome sequencing identified rare missense variants in IFN-regulatory factor 7 (IRF7) and UNC-93 homolog B1 (UNC93B1). PBMC single-cell RNA-Seq done during childhood revealed decreased expression of several innate immune genes and a repressed TLR3 pathway signature at baseline in several immune cell populations, including CD14 monocytes. Functional studies in fibroblasts and human leukemia monocytic THP1 cells showed that both variants individually suppressed TLR3-driven IRF3 transcriptional activity and the type I IFN response in vitro. Furthermore, fibroblasts expressing the IRF7 and UNC93B1 variants had higher intracellular viral titers with blunting of the type I IFN response upon HSV-1 challenge. This study reports an infant with recurrent HSV-1 disease complicated by encephalitis associated with deleterious variants in the IRF7 and UNC93B1 genes. Our results suggest that TLR3 pathway mutations may predispose neonates to recurrent, severe HSV.

Preterm sepsis is associated with acute lung injury as measured by pulmonary severity score.

BACKGROUND: Sepsis related acute lung injury (ALI) is established in adults but has not been investigated in premature infants. Herein, we used pulmonary severity score (PSS) trajectories and C-reactive protein (CRP) to examine the relation between sepsis and ALI in premature infants. METHODS: This retrospective study identified 211 sepsis and 123 rule out (RO) events in 443 infants born <31 weeks and <1500 grams. The PSS was calculated prior to, at the time of, and up to 1 week after each event. Initial and peak CRP values were collected for each event. RESULTS: PSS significantly increased at 0 h from baseline (-72h) and remained increased at all subsequent time points (all p < 0.002) in sepsis events. Mean PSS in sepsis episodes were also higher compared to RO events at +24 h, +48 h, +72 h, and +168 h (all p < 0.004). A positive correlation was noted between peak CRP values in sepsis events and PSS at 0 h, +24 h, +48 h, and +72 h. CONCLUSIONS: The temporal PSS trends and correlation with CRP levels observed in sepsis but not in RO events supports the hypothesis that neonatal sepsis is associated with ALI and contributes to the accumulating evidence that neonatal ARDS occurs. IMPACT: To evaluate pulmonary severity scores and c-reactive protein values over time to establish an association between preterm neonatal sepsis and acute lung injury (ALI). Though sepsis is well established as the most common indirect cause of ALI leading to acute respiratory distress syndrome (ARDS) in adults and pediatrics, this phenomenon remains undefined in neonates. This study validates the proposal by the Neonatal ARDS Project that ARDS also occurs in neonates by demonstrating acute and sustained changes in markers of pulmonary injury temporally related to a diagnosis of neonatal sepsis in preterm infants.

Loeys-Dietz syndrome caused by 1q41 deletion including TGFB2 is associated with a neurodevelopmental phenotype.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that commonly results in a dilated aorta, aneurysms, joint laxity, craniosynostosis, and soft skin that bruises easily. Neurodevelopmental abnormalities are uncommon in LDS. Two previous reports present a total of four patients with LDS due to pure 1q41 deletions involving TGFB2 (Gaspar et al., American Journal of Medical Genetics Part A, 2017, 173, 2289-2292; Lindsay et al., Nature Genetics, 2012, 44, 922-927). The current report describes an additional five patients with similar deletions. Seven of the nine patients present with some degree of hypotonia and gross motor delay, and three of the nine present with speech delay and/or intellectual disability (ID). The smallest deletion common to all patients is a 785 kb locus that contains two genes: RRP15 and TGFB2. Previous studies report that TGFB2 knockout mice exhibit severe perinatal anomalies (Sanford et al., Development, 1997, 124, 2659-2670) and TGFB2 is expressed in the embryonic mouse hindbrain floor (Chleilat et al., Frontiers in Cellular Neuroscience, 2019, 13). The deletion of TGFB2 may be associated with a neurodevelopmental phenotype with incomplete penetrance and variable expression.

Improving safe sleep practices in an urban inpatient newborn nursery and neonatal intensive care unit.

OBJECTIVE: To improve safe sleep compliance in a newborn nursery (NN) and neonatal intensive care unit (NICU) to >80% in 1 year. STUDY DESIGN: Prospective quality improvement study of infants admitted to a NN and NICU. Interventions were targeted at parent education, staff education, and system processes. RESULTS: Compliance with safe sleep improved to >80% in both units. Tracking of process measures revealed NICU parents received safe sleep education 98-100% of the time. No change was observed in the balancing measures. Transfers from the NN to the NICU for temperature instability did not increase. Parent satisfaction with discharge preparedness did not change (98.2% prior to and 99.6% after). CONCLUSION: We achieved improved compliance with safe sleep practices in our NN and NICU through education of staff and parents and improved system processes. We believe this will translate to improved safe sleep practices used by parents at home.

Postnatal Sepsis and Bronchopulmonary Dysplasia in Premature Infants: Mechanistic Insights into "New BPD".

Bronchopulmonary dysplasia (BPD) is a debilitating disease in premature infants resulting from lung injury that disrupts alveolar and pulmonary vascular development. Despite the use of lung-protective ventilation and targeted oxygen therapy, BPD rates have not significantly changed over the last decade. Recent evidence suggests that sepsis and conditions initiating the systemic inflammatory response syndrome in preterm infants are key risk factors for BPD. However, the mechanisms by which sepsis-associated systemic inflammation and microbial dissemination program aberrant lung development are not fully understood. Progress has been made within the last 5 years with the inception of animal models allowing mechanistic investigations into neonatal acute lung injury and alveolar remodeling attributable to endotoxemia and necrotizing enterocolitis. These recent studies begin to unravel the pathophysiology of early endothelial immune activation via pattern recognition receptors such as Toll-like receptor 4 and disruption of critical lung developmental processes such as angiogenesis, extracellular matrix deposition, and ultimately alveologenesis. Here we review scientific evidence from preclinical models of neonatal sepsis-induced lung injury to new data emerging from clinical literature.

Outcomes following perinatal palliative care consultation: a retrospective review.

OBJECTIVE: To inform clinical practice by describing a model of perinatal palliative care delivery within a fully staffed fetal health center (FHC) inside a freestanding children's hospital. STUDY DESIGN: The team conducted a retrospective chart review of the palliative care team (PaCT) database from FHC's inception in 2010 to 31 December, 2018, and surveyed the FHC neonatologists. RESULTS: PaCT consults in the FHC increased from 1 in 2010 to 102 in 2018. PaCT met 430 mothers for prenatal consultation. Of the 390 live-born infants, 172 died; 48 received comfort care only from birth; and 19 survived to discharge home with hospice. At the time of review, PaCT still follows 109 children met prenatally. PaCT discharged 96 patients that no longer required PaCT services. CONCLUSIONS: PaCT provides an integral service within the FHC as evidenced by the increasing volume of consultations, variety of care provided and perceived value by FHC neonatologists.

Rare Genetic Variants in Immune Genes and Neonatal Herpes Simplex Viral Infections.

Neonatal herpes simplex virus (HSV) infection is a devastating disease with high mortality, particularly when disseminated. Studies in adults and children suggest that susceptibility to herpes simplex encephalitis (HSE) may represent phenotypes for inborn errors in toll-like receptor 3 (TLR3) signaling. However, the genetic basis of susceptibility to neonatal HSV including disseminated disease remains unknown. To test the hypothesis that variants in known HSE-susceptible genes as well as genes mediating HSV immunity will be identified in neonatal HSV, we performed an unbiased exome sequencing study in 10 newborns with disseminated, HSE, and skin, eyes, and mouth disease. Determination of potential impact on function was determined by following American College of Medical Genetics and Genomics guidelines. We identified deleterious and potentially deleterious, rare variants in known HSE-related genes including a stop IRF3 variant (disseminated), nonsynonymous variants in TLR3 and TRAF3 (HSE), STAT1 (skin, eyes, and mouth), and DBR1 (disseminated) in our cohort. Novel and rare variants in other immunodeficiency genes or HSV-related immune genes GRB2, RAG2, PRF1, C6, C7, and MSR1 were found in 4 infants. The variant in GRB2, essential for T-lymphocyte cell responses to HSV, is a novel stop variant not found in public databases. In this pilot study, we identified deleterious or potentially deleterious variants in TLR3 pathway and genes that regulate anti-HSV immunity in neonates with HSV including disseminated disease. Larger, definitive studies incorporating functional analysis of genetic variants are required to validate these data and determine the role of immune genetic variants in neonatal HSV susceptibility.

Fetal Inflammatory Response Syndrome Associated With Maternal SARS-CoV-2 Infection.

Amid the coronavirus disease 2019 pandemic, uncertainty exists about the potential for vertical transmission from mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the fetus in utero. In this case report, we aim to demonstrate the occurrence of a fetal inflammatory response syndrome associated with maternal SARS-CoV-2 infection resulting in neonatal morbidity. In this report we describe an infant of a SARS-CoV-2-positive mother born prematurely with late-onset fever, thrombocytopenia, and elevated levels of inflammatory markers, all of which are consistent with a systemic inflammatory response. The neonate was tested for SARS-CoV-2 by using 2 nasopharyngeal swabs 24 hours apart, and results of both were negative. The result of a full workup for additional infectious pathogens was also negative. Although initially in critical condition in the perinatal period, the infant recovered completely before discharge. We hypothesize that this systemic inflammation occurred in response to maternal viral infection in the absence of vertical transmission of the virus. During the coronavirus disease 2019 pandemic, it will be important to consider the virus as a nidus for a fetal inflammatory response syndrome and resulting morbidity, even in the setting of a negative SARS-CoV-2 testing result in the infant.

Heme and sensory neuropathy: insights from novel mutations in the heme exporter feline leukemia virus subgroup C receptor 1.

Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system mainly characterized by impaired nociception and autonomic dysfunction. We previously identified heme metabolism as a novel pathway contributing to sensory neurons maintenance and nociception. Indeed, we reported mutations in the feline leukemia virus subgroup C receptor 1 (FLVCR1) gene in individuals affected by HSAN. FLVCR1 gene encodes for 2 heme export proteins, FLVCR1a (plasma membrane) and FLVCR1b (mitochondria), crucially involved in the regulation of cellular heme homeostasis. Here, we report on 2 additional patients carrying novel biallelic mutations in FLVCR1 translation initiation codon (c.2T>C; p.(Met1Thr) and c.3G>T; p.(Met1Ile)). We overexpressed the c.2T>C; p.(Met1Thr) mutant in human cell lines and we describe its impact on protein structure and function in comparison with other HSAN-related mutations. We found that the mutation interferes with translation in 2 different ways: by lowering levels of translation of wild-type protein and by inducing translation initiation from a downstream in-frame ATG, leading to the production of an N-terminal truncated protein that is retained in the endoplasmic reticulum. The impact of different kinds of mutations on FLVCR1a localization and structure was also described. The identification of novel FLVCR1 mutations in HSAN reinforces the crucial role of heme in sensory neuron maintenance and pain perception. Moreover, our in vitro findings demonstrate that heme export is not completely lost in HSAN patients, thus suggesting the possibility to improve FLVCR1 expression/activity for therapeutic purposes.

Movement of Genetic Counselors from Clinical to Non-clinical Positions: Identifying Driving Forces.

A previous study of genetic counselors (GCs) in the state of Indiana identified movement out of clinical positions within the past 2 years. The aims of this study were to determine if this trend is nationwide and identify reasons why GCs are leaving their positions and factors that might help employers attract and retain GCs. An email was sent to members of the American Board of Genetic Counseling with a link to an online confidential survey. There were 939 responses (23.5% response rate). Overall, 52% of GCs report being highly satisfied in their current position, although almost two thirds think about leaving and one third had changed jobs within the past 2 years. Of those who had changed jobs (n = 295), 74.9% had been working in a hospital/clinic setting but only 46.3% currently do, demonstrating a major shift out of the clinic (p < 0.001). The top three reasons cited for leaving a position were work environment/institutional climate, salary/benefits, and a lack of feeling valued/recognized as a professional. These results confirm that GCs are moving out of clinical positions and document elements of job satisfaction. We suggest points for employers to consider when trying to recruit or retain GCs.

Estimating Demand and Cross-Price Elasticity for Very Low Nicotine Content (VLNC) Cigarettes Using a Simulated Demand Task.

Introduction: Very Low Nicotine Content (VLNC) cigarettes might be useful as part of a tobacco control strategy, but relatively little is known about their acceptability as substitutes for regular cigarettes. We compared subjective effects and demand for regular cigarettes and VLNC cigarettes, and estimated cross-price elasticity for VLNC cigarettes, using simulated demand tasks. Method: Forty New Zealand smokers sampled a VLNC cigarette and completed Cigarette Purchase Tasks to indicate their demand for regular cigarettes and VLNC cigarettes at a range of prices, and a cross-price task indicating how many regular cigarettes and VLNC cigarettes they would purchase at 0.5x, 1x, and 2x the current market price for regular cigarettes, assuming the price of VLNC cigarettes remained constant. They also rated the subjective effects of the VLNC cigarette and their usual-brand regular cigarettes. Results: Cross-price elasticity for VLNC cigarettes was estimated as 0.32 and was significantly positive, indicating that VLNC cigarettes are partially substitutable for regular cigarettes. VLNC cigarettes were rated as less satisfying and psychologically rewarding than regular cigarettes, but this was unrelated to demand or substitutability. Conclusion: VLNC cigarettes are potentially substitutable for regular cigarettes. Their availability may reduce tobacco consumption, nicotine intake and addiction; making it easier for smokers to quit. Implications: VLNC cigarettes share the behavioral and sensory components of smoking while delivering negligible levels of nicotine. Although smokers rated VLNCs as less satisfying than regular cigarettes, smokers said they would increase their consumption of VLNCs as the price of regular cigarettes increased, if VLNCs were available at a lower price. This suggests that VLNCs are partially substitutable for regular cigarettes. VLNCs can be part of an effective tobacco control strategy, by reducing nicotine dependence and improving health and financial outcomes for smokers.

Predicting Short-Term Uptake of Electronic Cigarettes: Effects of Nicotine, Subjective Effects, and Simulated Demand.

Introduction: E-cigarettes have potential to support tobacco cessation or reduction, but how nicotine content affects smokers' subjective perceptions and use of e-cigarettes, rather than tobacco, is unclear. Method: Thirty-five adult daily smokers who had not previously tried e-cigarettes were recruited from two cities in New Zealand in 2016-2017. Smokers were given four e-cigarette cartridges (0, 6, 12, and 18 mg nicotine) in a randomized, blinded order over four 2-week periods. Daily cigarette smoking and e-cigarette use was monitored using ecological momentary analysis and participants completed the modified Cigarette Evaluation Questionnaire after each 2-week period. Results: Mean cigarettes per day decreased by 37% (9.69 to 6.09) when e-cigarettes were available relative to baseline (p = .008). Nicotine-containing cartridges (>0 mg) were associated with greater use (p = .023) and craving reduction (p = .026) than 0 mg. Alleviation of withdrawal symptoms (p = .048) and taste and enjoyment factors (p = .039) predicted e-cigarette use. Conclusion: Availability of e-cigarettes reduced cigarette smoking behavior regardless of nicotine content, and e-cigarette use was greater with nicotine-containing cartridges. First-time users' e-cigarette use can be predicted using subjective ratings and more research is required to clarify the effect of nicotine content on subjective perceptions and use. Implications: For low-moderate dependence smokers, availability of e-cigarettes may reduce cigarette smoking behavior regardless of nicotine content, but the availability of nicotine-containing cartridges may promote greater e-cigarette use. First response to trialing e-cigarettes is an important factor in determining subsequent experimental and possibly longer-term use.