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The climate crisis encompasses a constellation of risks that threaten human livelihoods, well-being, and survival globally. In this article, we present a new framework based on bioecological and dynamic systems perspectives, and on evidence for conceptualizing how the distinctive dual time frame of both acute (e.g., extreme weather events) and chronic (e.g., ecological degradation) climate change-related risks experienced prenatally and early in life across multiple ecological contexts can threaten human development. We conclude with a call to developmental researchers, practitioners, and policymakers to invest more efforts in understanding and addressing the climate crisis and its developmental consequences to ensure a sustainable future for all.

Research has shown the importance of responsive caregiving for fostering positive development early in life; however, tools measuring these interactions are often impractical for larger scale intervention trials and in settings with resource constraints. The present study provides reliability and validity evidence from Sindh, Pakistan for a tool developed to quantify responsive caregiving. Data were collected from 200 randomly selected households on responsive caregiving, sociodemographic characteristics, early learning, and early child development. The results indicated that the responsive care tool can be feasibly administered in less than 5 min in a low-resource setting. An exploratory factor analysis found that the tool's indicators reliably loaded onto two distinct factors, responsive interactions and caregiver-initiated interactions, accounting for 96.01% of the underlying variation in scores. A confirmatory factor analysis reflecting input from modification indices showed satisfactory fit statistics and adequate factor loadings (all above 0.70). Internal consistencies of the two factors were also high, with alphas of 0.93 and 0.83, respectively. Convergent validity of the responsive interactions factor was demonstrated by a strong and positive correlation with measures of psychosocial stimulation, early learning, maternal education, and household wealth. Predictive validity of the responsive interactions factor was demonstrated by a strong and positive association with child development. The caregiver-initiated interactions factor was significantly and negatively associated with psychosocial stimulation and child development. The resulting evidence provides programs with an open access, observational, reliable, and valid measure to quantify responsive caregiving at the program level in low-resource settings.

Background: People with cystic fibrosis carrying two nonsense alleles lack CFTR-specific treatment. Growing evidence supports the hypothesis that nonsense mutation identity affects therapeutic response, calling for mutation-specific CF models. We describe a novel W1282X mouse model and compare it to an existing G542X mouse., Methods: The W1282X mouse was created using CRISPR/Cas9 to edit mouse Cftr. In this model, Cftr transcription was assessed using qRT-PCR and CFTR function was measured in the airway by nasal potential difference and in the intestine by short circuit current. Growth, survival, and intestinal motility were examined as well. Correction of W1282X CFTR was assessed pharmacologically and by gene-editing using a forskolin-induced swelling (FIS) assay in small intestine-derived organoids., Results: Homozygous W1282X mice demonstrate decreased Cftr mRNA, little to no CFTR function, and reduced survival, growth, and intestinal motility. W1282X organoids treated with various combinations of pharmacologic correctors display a significantly different amount of CFTR function than that of organoids from G542X mice. Successful gene editing of W1282X to wildtype sequence in intestinal organoids was achieved leading to restoration of CFTR function., Conclusions: The W1282X mouse model recapitulates common human manifestations of CF similar to other CFTR null mice. Despite the similarities between the congenic W1282X and G542X models, they differ meaningfully in their response to identical pharmacological treatments. This heterogeneity highlights the importance of studying therapeutics across genotypes., Competing Interests: Declaration of competing interest Authors report no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Programmable shunt valves (PSVs) used to treat hydrocephalus require specialized valve-specific devices that determine their setting. However, these devices are typically only accessible in major medical centers. This study explores the feasibility of using smartphone magnetometers to assess PSV settings., Methods: We investigated 2 PSVs, the Codman Certas Plus and Medtronic Strata II, using 3 different smartphones. Free open-source software was used to measure magnetic flux densities of the shunts, and PSV-specific algorithms were developed to interpret these measurements. All measurements were performed ex vivo., Results: We demonstrated that this method could accurately determine PSV settings with 100% accuracy in ex vivo blinded trials. The technique was effective even with a scalp analog simulating different skin thicknesses., Conclusion: This proof-of-concept study suggests that smartphones can be used for PSV assessment. However, further development and validation are needed to refine this method for clinical use. This technology could enhance PSV management accessibility, allowing for remote or at-home evaluations by trained individuals or caregivers, thus improving patient care in underserved areas., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Disruption of inhibitory interneurons is common in the epileptic brain and is hypothesized to play a pivotal role in epileptogenesis. Abrupt disruption and loss of interneurons is well-characterized in status epilepticus models of epilepsy, however, status epilepticus is a relatively rare cause of epilepsy in humans. How interneuron disruption evolves in other forms of epilepsy is less clear. Here, we explored how somatostatin (SST) interneuron disruption evolves in quadruple transgenic Gli1-CreER T2 , Pten fl/fl , SST-FlpO, and frt-eGFP mice. In these animals, epilepsy develops following deletion of the mammalian target of rapamycin (mTOR) negative regulator phosphatase and tensin homolog (Pten) from a subset of dentate granule cells, while downstream Pten-expressing SST neurons are fate-mapped with green fluorescent protein (GFP). The model captures the genetic complexity of human mTORopathies, in which mutations can be restricted to excitatory neuron lineages, implying that interneuron involvement is later developing and secondary. In dentate granule cell (DGC)-Pten knockouts (KOs), the density of fate-mapped SST neurons was reduced in the hippocampus, but their molecular phenotype was unchanged, with similar percentages of GFP+ cells immunoreactive for SST and parvalbumin (PV). Surviving SST neurons in the dentate gyrus had larger somas, and the density of GFP+ processes in the dentate molecular layer was unchanged despite SST cell loss and expansion of the molecular layer, implying compensatory sprouting of surviving cells. The density of Znt3-immunolabeled puncta, a marker of granule cell presynaptic terminals, apposed to GFP+ processes in the hilus was increased, suggesting enhanced granule cell input to SST neurons. Finally, the percentage of GFP+ cells that were FosB positive was significantly increased, implying that surviving SST neurons are more active. Together, findings suggest that somatostatin-expressing interneurons exhibit a combination of pathological (cell loss) and adaptive (growth) responses to hyperexcitability and seizures driven by upstream Pten KO excitatory granule cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Drake, Jerow, Ruksenas, McCoy and Danzer.)

Interneuron loss is a prominent feature of temporal lobe epilepsy in both animals and humans and is hypothesized to be critical for epileptogenesis. As loss occurs concurrently with numerous other potentially proepileptogenic changes, however, the impact of interneuron loss in isolation remains unclear. For the present study, we developed an intersectional genetic approach to induce bilateral diphtheria toxin-mediated deletion of Vgat-expressing interneurons from dorsal and ventral hippocampus. In a separate group of mice, the same population was targeted for transient neuronal silencing with DREADDs. Interneuron ablation produced dramatic seizure clusters and persistent epileptiform activity. Surprisingly, after 1 week seizure activity declined precipitously and persistent epileptiform activity disappeared. Occasional seizures (≈1/day) persisted to the end of the experiment at 4 weeks. In contrast to the dramatic impact of interneuron ablation, transient silencing produced large numbers of interictal spikes, a significant but modest increase in seizure occurrence and changes in EEG frequency band power. Taken together, findings suggest that the hippocampus regains relative homeostasis-with occasional breakthrough seizures-in the face of an extensive and abrupt loss of interneurons., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Dusing et al.)

Context: Lack of access to food is a significant concern for child well-being, and it creates many health disparities and adverse social outcomes. Food insecurity and its many associated risk factors increase parental stress, which are strongly correlated with an increased risk of child abuse and maltreatment. Research now identifies being witness to domestic abuse as a form of child maltreatment, and exposure to violence in the community has been shown to result in similar long-term impacts., Objectives: Given the potential for lifelong adverse effects from experiencing adverse childhood events involving violence and food insecurity, our primary objective was to assess the relationship between the two and disparities among demographic factors., Methods: We conducted an observational study utilizing data from the National Survey of Children's Health (NSCH) 2016-2021. The NSCH is a United States nationally representative survey completed by primary caregivers of one child per home aged 0-17 years. We determined population estimates (n=216,799; n=83,424,126) and rates of children experiencing food insecurity and parent-reported exposure to violence. We then constructed logistic regression models to assess associations, through odds ratios (ORs), between food security and exposure to violence including demographic factors., Results: Among the sample, 5.42 % of children experienced low food security and 7.4 % were exposed to violence. The odds of exposure to violence are 5.19 times greater for children with low food security compared to food-secure children (95 % confidence interval [CI]: 4.48-6.02). Indigenous and Black children were 7.8 and 6.81 times more likely to experience or witness violence when food insecure compared to food secure White children, respectively (95 % CI: 3.18-19.13, 5.24-8.86 respectively)., Conclusions: Food insecurity was associated with increased odds of children experiencing and/or witnessing violence compared to those who were food secure. The interaction between exposure to violence and food insecurity also disproportionately impacts children with specific demographic factors, notably race/ethnicity including multiracial, Indigenous, and Black children. By developing and adapting strategies to improve food security, it is possible to indirectly reduce the rates of childhood exposure to violence and the long-term impacts that result., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

The mortality due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) approaches 40% in recipients of chimeric antigen receptor (CAR) T cell therapy (CAR-T). The efficacy of repeated vaccine doses, including bivalent boosters, remains unknown. We examined the efficacy of repeated vaccine doses among CAR-T recipients who received at least 2 or more vaccine doses after T cell infusion. This single-center retrospective study included adults age >18 years receiving CAR-T for relapsed/refractory (R/R) B cell hematologic malignancies targeting CD19, BCMA, or CD19 and CD20 between September 2018 through March 2022 and were alive beyond 2021 to receive incremental SARS-CoV-2 vaccine doses with available seroconversion data. Multivariable analyses were performed using the design-adjusted Cox regression and logistic regression approaches with stratification. In multivariable analysis, seroconversion rates were significantly greater with a total of 4 or more vaccine doses (odds ratio [OR], 8.22; P = .008). CAR-T recipients with other B cell hematologic malignancies had significantly lower seroconversion rates and diminished Ab titers compared to those with R/R multiple myeloma (OR, .07; P = .003). One patient died due to COVID-19 in this vaccinated study cohort, accounting for a COVID-19-attributable mortality rate of 1.7%. The results provide baseline vaccine response data in a contemporary cohort including patients with diverse group of SARS-COV2 variants and support the latest Centers for Disease Control and Prevention guidelines for repeated vaccinations directed against the prevalent variant of concern., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Introduction: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices. Winning facilities/regions receive external facilitation to aid in replication/implementation over the course of a year. DoE staff then support diffusion of successful practices across the nationwide VHA., Methods: Organized around the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, we summarize results of an ongoing long-term mixed-methods implementation evaluation of DoE. Data sources include: Shark Tank application and bid details, tracking practice adoptions through a Diffusion Marketplace, characteristics of VHA facilities, focus groups with Shark Tank bidders, structured observations of DoE events, surveys of DoE program participants, and semi-structured interviews of national VHA program office leaders, VHA healthcare system/facility executives, practice developers, implementation teams and facilitators., Results: In the first eight Shark Tanks (2016-2022), 3,280 Shark Tank applications were submitted; 88 were designated DoE Promising Practices (i.e., practices receive facilitated replication). DoE has effectively spread practices across the VHA, with 1,440 documented instances of adoption/replication of practices across the VHA. This includes 180 adoptions/replications in facilities located in rural areas. Leadership decisions to adopt innovations are often based on big picture considerations such as constituency support and linkage to organizational goals. DoE Promising Practices that have the greatest national spread have been successfully replicated at new sites during the facilitated replication process, have close partnerships with VHA national program offices, and tend to be less expensive to implement. Two indicators of sustainment indicate that 56 of the 88 Promising Practices are still being diffused across the VHA; 56% of facilities originally replicating the practices have sustained them, even up to 6 years after the first Shark Tank., Conclusion: DoE has developed a sustainable process for the identification, replication, and spread of promising practices as part of a learning health system committed to providing equitable access to high quality care., Competing Interests: AS was employed by Agile Six Applications, Inc. All authors have been employees or contractors of the United States Department of Veterans Affairs., (© 2024 Jackson, Fix, White, Cutrona, Reardon, Damschroder, Burns, DeLaughter, Opra Widerquist, Arasim, Lindquist, Gifford, King, Kaitz, Jasuja, Hogan, Lopez, Henderson, Fitzgerald, Goetschius, Hagan, McCoy, Seelig and Nevedal.)