The central nucleus of the amygdala (CEA) is a brain region that integrates external and internal sensory information and executes innate and adaptive behaviors through distinct output pathways. ...Despite its complex functions, the diversity of molecularly defined neuronal types in the CEA and their contributions to major axonal projection targets have not been examined systematically. Here, we performed single-cell RNA-sequencing (scRNA-seq) to classify molecularly defined cell types in the CEA and identified marker genes to map the location of these neuronal types using expansion-assisted iterative fluorescence in situ hybridization (EASI-FISH). We developed new methods to integrate EASI-FISH with 5-plex retrograde axonal labeling to determine the spatial, morphological, and connectivity properties of ~30,000 molecularly defined CEA neurons. Our study revealed spatiomolecular organization of the CEA, with medial and lateral CEA associated with distinct molecularly defined cell families. We also found a long-range axon projection network from the CEA, where target regions receive inputs from multiple molecularly defined cell types. Axon collateralization was found primarily among projections to hindbrain targets, which are distinct from forebrain projections. This resource reports marker gene combinations for molecularly defined cell types and axon-projection types, which will be useful for selective interrogation of these neuronal populations to study their contributions to the diverse functions of the CEA.
Acute respiratory failure is a common reason for emergency department visits and hospital admissions. Diverse underlying physiologic abnormalities lead to unique aspects about the most common causes ...of acute respiratory failure: acute decompensated heart failure, acute exacerbation of chronic obstructive pulmonary disease, and acute de novo hypoxemic respiratory failure. Noninvasive respiratory support strategies are increasingly used methods to support work of breathing and improve gas exchange abnormalities to improve outcomes relative to conventional oxygen therapy or invasive mechanical ventilation. Noninvasive respiratory support includes noninvasive positive pressure ventilation and nasal high flow, each with unique physiologic mechanisms. This paper will review the physiology of respiratory failure and noninvasive respiratory support modalities and offer data and guideline‐driven recommendations in the context of key clinical controversies.
ObjectivesAn estimated 1.7 billion children around the world do not have access to safe, affordable and timely surgical care, with the financing through out-of-pocket (OOP) expenses being one of the ...main barriers to care. Our study modelled the impact of reducing OOP costs related to surgical care for children in Somaliland on the risk of catastrophic expenditures and impoverishment.Design and settingThis cross-sectional nationwide economic evaluation modelled several different approaches to reduction of paediatric OOP surgical costs in Somaliland.Participants and outcome measuresA surgical record review of all procedures on children up to 15 years old was conducted at 15 surgically capable hospitals. We modelled two rates of OOP cost reduction (reduction of OOP proportion from 70% to 50% and from 70% to 30% reduction in OOP costs) across five wealth quintiles (poorest, poor, neutral, rich, richest) and two geographical areas (urban and rural). The outcome measures of the study are catastrophic expenditures and risk of impoverishment due to surgery. We followed the Consolidated Health Economic Evaluation Reporting Standards.ResultsWe found that the risk of catastrophic and impoverishing expenditures related to OOP expenditures for paediatric surgery is high across Somaliland, but most notable in the rural areas and among the poorest quintiles. Reducing OOP expenses for surgical care to 30% would protect families in the richest wealth quintiles while minimally affecting the risk of catastrophic expenditure and impoverishment for those in the lowest wealth quintiles, particularly those in rural areas.ConclusionOur models suggest that the poorest communities in Somaliland lack protection against the risk of catastrophic health expenditure and impoverishment, even if OOP payments are reduced to 30% of surgical costs. A comprehensive financial protection in addition to reduction of OOP costs is required to prevent risk of impoverishment in these communities.
Breast terminal duct lobular units (TDLUs), the source of most breast cancer (BC) precursors, are shaped by age-related involution, a gradual process, and postpartum involution (PPI), a dramatic ...inflammatory process that restores baseline microanatomy after weaning. Dysregulated PPI is implicated in the pathogenesis of postpartum BCs. We propose that assessment of TDLUs in the postpartum period may have value in risk estimation, but characteristics of these tissues in relation to epidemiological factors are incompletely described.
Using validated Artificial Intelligence and morphometric methods, we analyzed digitized images of tissue sections of normal breast tissues stained with hematoxylin and eosin from donors ≤ 45 years from the Komen Tissue Bank (180 parous and 545 nulliparous). Metrics assessed by AI, included: TDLU count; adipose tissue fraction; mean acini count/TDLU; mean dilated acini; mean average acini area; mean "capillary" area; mean epithelial area; mean ratio of epithelial area versus intralobular stroma; mean mononuclear cell count (surrogate of immune cells); mean fat area proximate to TDLUs and TDLU area. We compared epidemiologic characteristics collected via questionnaire by parity status and race, using a Wilcoxon rank sum test or Fisher's exact test. Histologic features were compared between nulliparous and parous women (overall and by time between last birth and donation recent birth: ≤ 5 years versus remote birth: > 5 years) using multivariable regression models.
Normal breast tissues of parous women contained significantly higher TDLU counts and acini counts, more frequent dilated acini, higher mononuclear cell counts in TDLUs and smaller acini area per TDLU than nulliparas (all multivariable analyses p < 0.001). Differences in TDLU counts and average acini size persisted for > 5 years postpartum, whereas increases in immune cells were most marked ≤ 5 years of a birth. Relationships were suggestively modified by several other factors, including demographic and reproductive characteristics, ethanol consumption and breastfeeding duration.
Our study identified sustained expansion of TDLU numbers and reduced average acini area among parous versus nulliparous women and notable increases in immune responses within five years following childbirth. Further, we show that quantitative characteristics of normal breast samples vary with demographic features and BC risk factors.
Summary
Background
Non‐alcoholic fatty liver disease (NAFLD) is a highly prevalent condition that requires a comprehensive and coordinated response across sectors and disciplines.
Aims
In the absence ...of a multisectoral framework to tackle this condition, we developed one using the sustainable development goals (SDGs) as the basis for converging thinking about the design and delivery of public health responses.
Methods
A multidisciplinary group identified the SDG targets and indicators for inclusion in the new framework through a two‐stage process. Firstly, a core team of three researchers independently reviewed the 169 targets and 231 indicators of the SDGs to select a shortlist. Over two Delphi rounds, a multidisciplinary group of 12 experts selected which of the shortlisted targets and indicators to include. Respondents also provided written feedback on their selection. Targets and indicators with 75% or greater agreement were included in the final framework.
Results
The final framework comprises 16 targets—representing 9% of all targets and 62% (16/26) of the shortlisted targets—and seven indicators, accounting for 50% (7/14) of the shortlisted indicators and 3% of all indicators. The selected targets and indicators cover a broad range of factors, from health, food and nutrition to education, the economy, and the built environment.
Conclusions
Addressing the challenge of NAFLD will require a re‐envisioning of the liver health landscape, with greater focus on joined‐up systems thinking and action. This new framework can help guide this process, including by outlining the stakeholders with whom the liver health community needs to engage.
A two‐stage Delphi process to create a NAFLD‐SDG framework.
Abstract Purpose The role of helicopter emergency medical services (HEMS) in pediatric trauma remains controversial. We examined its use in pediatric trauma and its effectiveness in children with ...moderate/severe injuries. Methods All blunt/penetrating trauma patients ≤ 18 years old in the National Trauma Data Bank were evaluated for use of HEMS and in-hospital mortality. In a comparative effectiveness study, only patients treated at Level I/II pediatric centers with injury severity score (ISS) ≥ 9 were included. Results Of 127,489 included patients, 18,291 (14%) arrived via HEMS, compared to 56% by ground ambulance and 29% by private vehicle/walk-in. HEMS patients had more severe injuries (ISS ≥ 25; 28% vs. 14%) and altered mental status (GCS ≤ 8; 29% vs. 11%), but also contained many patients with only minor injuries or no major physiologic derangements. In unadjusted analysis, HEMS was associated with increased mortality (OR: 1.6; 95% CI: 1.4–1.7). However, it had decreased mortality by regression (0.5; 0.4–0.6) and propensity analysis (0.7; 0.6–0.8) to adjust for confounders. Conclusion We found multiple indicators for overuse of HEMS, with nearly 40% of children having only minor injuries. In moderate/severe injuries, HEMS is associated with decreased mortality, potentially saving one life for every 47 flights. Research is needed to determine appropriate criteria for helicopter triage. Comparative Study / Level of Evidence III
Micronutrient deficiencies continue to be a major public health concern worldwide with many South Asian countries suffering a significant proportion of the global burden. A lack of nationally ...representative data on micronutrient deficiencies hampers sustained action to address the problem. Using data on the national food supply produced by the Food and Agriculture Organisation of the United Nations, and international food composition tables, the present study estimated the prevalence of inadequacy of seven micronutrients (vitamin A, thiamine, riboflavin, folate, vitamin B-12, zinc and calcium) in seven South Asian countries - Bangladesh, India, Iran, Maldives, Nepal, Pakistan and Sri Lanka. The estimated average requirement cut-point method was employed to determine the likelihood of inadequate micronutrient intakes. We report multiple micronutrient inadequacies in the food supply in the region, especially in the low and lower-middle income countries. Of the seven micronutrients investigated, calcium had the highest risk levels of inadequacy. Folate, riboflavin, vitamin B-12 and zinc were also deemed to be at high risk of inadequacy, although results differed markedly between countries. Various strategies to combat micronutrient deficiencies are currently underway in these countries. In order to facilitate the implementation of these efforts, the collection of nationally representative nutritional assessment survey data are urgently required to ascertain the true burden of micronutrient malnutrition.
A brusque opinion by the U.S. Supreme Court in a patent case has launched a revolution in the law of equitable remedies. The Court's opinion in eBay Inc. v. MercExchange, L.L.C, asserted that it was ...merely upholding "traditional pnnciples" regarding when injunctions should issue. But in circuit after circuit and for subject matter ranging from federal constitutional law to state tort law, lower courts have understood eBay to abrogate longstanding approaches. Focusing on the law for permanent injunctions, this Article examines the eBay opinion and the far-reaching changes that have resulted. For a better perspective on these changes, this Article discusses how courts historically have addressed equity's traditional concerns with risks of irreparable injury and the balance of hardships. Finally, this Article provides a normative account of the structured sets of equitable presumptions and safety valves that current understandings of eBay threaten to sweep aside.
Background
Delayed access to surgical care for congenital conditions in low- and middle-income countries is associated with increased risk of death and life-long disabilities, although the actual ...burden of delayed access to care is unknown. Our goal was to quantify the burden of disease related to delays to surgical care for children with congenital surgical conditions in Somaliland.
Methods
We collected data from medical records on all children (
n
= 280) receiving surgery for a proxy set of congenital conditions over a 12-month time period across all 15 surgically equipped hospitals in Somaliland. We defined delay to surgical care for each condition as the difference between the ideal and the actual ages at the time of surgery. Disability-adjusted life years (DALYs) attributable to these delays were calculated and compared by the type of condition, travel distance to care, and demographic characteristics.
Results
We found long delays in surgical care for these 280 children with congenital conditions, translating to a total of 2970 attributable delayed DALYs, or 8.4 avertable delayed DALYs per child, with the greatest burden among children with neurosurgical and anorectal conditions. Over half of the families seeking surgical care had to travel over 2 h to a surgically equipped hospital in the capital city of Hargeisa.
Conclusions
Children with congenital conditions in Somaliland experience substantial delays to surgical care and travel long distances to obtain care. Estimating the burden of delayed surgical care with avertable delayed DALYs offers a powerful tool for estimating the costs and benefits of interventions to improve the quality of surgical care.
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