Lack of SPNS1 results in accumulation of lysolipids and lysosomal storage disease in mouse models.

Accumulation of sphingolipids, especially sphingosines, in the lysosomes is a key driver of several lysosomal storage diseases. The transport mechanism for sphingolipids from the lysosome remains unclear. Here, we identified SPNS1, which shares the highest homology to SPNS2, a sphingosine-1-phosphate (S1P) transporter, functions as a transporter for lysolipids from the lysosome. We generated Spns1-KO cells and mice and employed lipidomic and metabolomic approaches to reveal SPNS1 ligand identity. Global KO of Spns1 caused embryonic lethality between E12.5 and E13.5 and an accumulation of sphingosine, lysophosphatidylcholines (LPC), and lysophosphatidylethanolamines (LPE) in the fetal livers. Similarly, metabolomic analysis of livers from postnatal Spns1-KO mice presented an accumulation of sphingosines and lysoglycerophospholipids including LPC and LPE. Subsequently, biochemical assays showed that SPNS1 is required for LPC and sphingosine release from lysosomes. The accumulation of these lysolipids in the lysosomes of Spns1-KO mice affected liver functions and altered the PI3K/AKT signaling pathway. Furthermore, we identified 3 human siblings with a homozygous variant in the SPNS1 gene. These patients suffer from developmental delay, neurological impairment, intellectual disability, and cerebellar hypoplasia. These results reveal a critical role of SPNS1 as a promiscuous lysolipid transporter in the lysosomes and link its physiological functions with lysosomal storage diseases.

Stakeholders' preferences for the design and delivery of virtual care services: A systematic review of discrete choice experiments.

This systematic review aimed to synthesise evidence from discrete choice experiments (DCEs) eliciting preferences for virtual models of care, as well as to assess the quality of those DCEs and compare the relative preferences for different stakeholder groups. Articles were included if published between January 2010 and December 2022. Data were synthesised narratively, and attributes were assessed for frequency, significance, and relative importance using a semi-quantitative approach. Overall, 21 studies were included encompassing a wide range of virtual care modalities, with the most common setting being virtual consultations for outpatient management of chronic conditions. A total of 135 attributes were identified and thematically classified into six categories: service delivery, service quality, technical aspects, monetary aspects, health provider characteristics and health consumer characteristics. Attributes related to service delivery were most frequently reported but less highly ranked. Service costs were consistently significant across all studies where they appeared, indicating their importance to the respondents. All studies examining health providers' preferences reported either system performance or professional endorsement attributes to be the most important. Substantial heterogeneity in attribute selection and preference outcomes were observed across studies reporting on health consumers' preferences, suggesting that the consideration of local context is important in the design and delivery of person-centred virtual care services. In general, the experimental design and analysis methods of included studies were clearly reported and justified. An improvement was observed in the quality of DCE design and analysis in recent years, particularly in the attribute development process. Given the continued growth in the use of DCEs within healthcare settings, further research is needed to develop a standardised approach for quantitatively synthesising DCE findings. There is also a need for further research on preferences for virtual care in post-pandemic contexts, where emerging evidence suggests that preferences may differ to those observed in pre-pandemic times.

Preferences in the Design and Delivery of Neurodevelopmental Follow-Up Care for Children: A Systematic Review of Discrete Choice Experiments.

Neurodevelopmental disorders are a significant cause of morbidity. Early detection of neurodevelopmental delay is essential for timely diagnosis and intervention, and it is therefore important to understand the preferences of parents and clinicians for engaging with neurodevelopmental surveillance and follow-up care. Discrete choice experiment (DCE) may be an appropriate method for quantifying these preferences. This review systematically examined how DCEs have been designed and delivered in studies examining neurodevelopmental care of children and identified the preferred attributes that have been reported. PubMed, Embase, CINAHL, and Scopus databases were systematically searched. Studies were included if they used DCE to elicit preferences for a neurodevelopmental follow-up program for children. Two independent reviewers conducted the title and abstract and full-text screening. Risk of bias was assessed using a DCE-specific checklist. Findings were presented using a narrative synthesis. A total of 6618 records were identified and 16 papers were included. Orthogonal (n=5) and efficient (n=5) experimental designs were common. There was inconsistent reporting of design-related features. Analysis was primarily completed using mixed logit (n=6) or multinomial logit (n=3) models. Several key attributes for neurodevelopmental follow-up care were identified including social, behavioral and emotional support, therapy, waiting time, and out-of-pocket costs. DCE has been successfully used as a preference elicitation method for neurodevelopmental-related care. There is scope for improvement in the design and analysis of DCE in this field. Nonetheless, attributes identified in these studies are likely to be important considerations in the design and implementation of programs for neurodevelopmental care.

Are stunted child - overweight mother pairs a real defined entity or a statistical artifact?

In a methodological contribution, Dieffenbach & Stein (DS) (The Journal of Nutrition, 142(4), 771-773.) concluded that the double burden of malnutrition (DBM), represented by stunted child - overweight mother pairs (SCOM), is a statistical artifact, meaning that SCOM does not describe a unique phenomenon because the observed rates of SCOM across a number of countries were not strongly different from the product of observed rates of maternal overweight (OM) and child stunting (SC), which DS referred to as the expected rate of SCOM. However, a growing literature continues to use SCOM as an indicator of the DBM. This study shows that the analysis by DS is not sufficient to conclude that SCOM can be explained by the co-occurrence of OM and SC due to chance alone because the analysis by DS was conducted at the country level, but applied to SCOM, which is a household-level variable. Using Demographic and Health Surveys data from 202 country-year data sets, we do not confirm important implicit assumptions that are required for the claim by DS to be supported. We also outline that comparing the expected to the observed rate of SCOM is primarily informative when putting it in relation to factors that influence the supply and demand of food consumed by households. When considering these factors, we find further evidence that it is misleading to consider SCOM as a statistical artifact, as the difference between the observed and the expected rate of SCOM significantly differs by household wealth. Recognizing that SCOM is a distinct phenomenon is important for policymakers who develop double-duty strategies that address malnutrition, and for researchers who need useful indicators to study the determinants of malnutrition at the household level.

Exploring the macroeconomic and socioeconomic determinants of simultaneous over and undernutrition in Asia: An analysis of stunted child - overweight mother households.

MANY LOW: Many low and middle-income countries in Asia experience greater food availability as their economies grow, potentially solving previous problems of undernutrition. However, economic growth may not sufficiently reduce undernutrition and instead increase over nutrition, creating a double burden of malnutrition. In this paper we investigate one of the most prevalent and seemingly paradoxical manifestations of the double burden, a stunted child and an overweight mother (SCOM) living in the same household. We use household-level data from 11 Asian countries from 2005 to 2018, as well as macroeconomic data on the Gross Domestic Product (GDP) and the GDP growth of these countries to estimate which household-level and macroeconomic factors predict SCOM. We also determine the relative predictive power of our variables for SCOM and investigate if predictors of SCOM also predict other forms of malnutrition. We find that the predictive power of household-level factors for SCOM is comparatively more important than that of macroeconomic variables. Additionally, we explore the effect of including population subgroup-level trends in maternal overweight and child stunting on the predictive power of our macro-level and household-level variables. The increasing prevalence of SCOM is driven by a rise in maternal overweight, coupled with stagnant rates of child stunting, but remains a unique phenomenon that differs from other indicators of malnutrition. This supports explanations that suggest increasing consumption of high-energy but low-nutrient foods is the underlying cause of SCOM, leading to weight gain in adults and stunting in under-five children.