Children affected by differences/disorders of sex development (DSDs) and their families are vulnerable to significant risks across developmental stages that threaten quality of life and psychosocial ...functioning. Accordingly, both experts in DSD treatment and patient advocacy groups have endorsed the incorporation of psychosocial care into interdisciplinary management of DSD conditions.
This study assessed psychosocial needs and received services reported by parents of children with DSD treated at two large US academic medical centers. Specifically, differences in parents' perceptions of psychosocial service needs were compared between those who received or did not receive interdisciplinary care that included psychology/social work professionals.
In a cross-sectional study, sixty-four parents of children with DSD aged 0–19 years attending two major academic centers with interdisciplinary teams completed a questionnaire about their receipt and perception of 12 individual psychosocial services throughout their child's DSD treatment.
Receipt of individual psychosocial services ranged from 27 to 81%. Most commonly, parents reported having a psychosocial provider explain medical terms and answer questions after talking with a doctor (81%), assist with words and terms to describe the condition and treatment (69%), and help navigate the hospital system (63%). Families positively endorsed psychosocial services, with 91–100% of services received rated as helpful. Parents of children who received care as part of an interdisciplinary team were significantly more likely to receive psychosocial services than those treated by single providers (e.g., urologists). Specific gaps in psychosocial care were noted in regard to access to mental health providers familiar with DSD, fertility counseling, and support with community advocacy (e.g., arranging for accommodations at the school or advocating on patient's behalf with the insurance company). Among families who had not received them, services most desired were assistance with words and terms to describe condition or treatment; explanation of medical terms and answering questions after meeting with a doctor; connection to resources such as books, pamphlets, websites, and support groups; and a central care coordinator for the medical team.
Families value psychosocial services but are far less likely to receive services if they are not seen in an interdisciplinary clinic visit that includes a psychosocial provider. Families desire but often lack mental health, advocacy, and fertility-related support. This study highlights the need for sustained psychosocial follow-up across development, even in the absence of pressing medical concerns, to provide support and anticipatory guidance as needs and issues evolve.Extended Summary TablePsychosocial services received by DSD interdisciplinary clinic visit (yes/no).Extended Summary TablePsychosocial service receivedInterdisciplinary DSD clinic visitp-valueYesNon%n%Emotional support for the family at diagnosis2463.2415.40.0002Strategies for talking with others about diagnosis2257.9623.10.006Ways to help the family talk with the child about diagnosis2668.4623.10.0004Central contact person or care coordinator2155.3726.90.03Emotional support as the child aged2668.4416.0<0.0001Patient and family advocacy to the community (e.g., school, insurance company)1539.527.70.005Connection to resources (e.g., books, support groups)2668.4726.90.001Mental health services with a provider who is knowledgeable about the condition2257.927.7<0.0001Individual to talk with the child about fertility1539.527.70.005DSD, difference or disorder of sex development.
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Laminins are important components of the extracellular matrix, and participate in neuronal development, survival and regeneration. The tissue plasminogen activator/plasmin extracellular protease ...cascade and downstream laminin degradation are implicated in excitotoxin-induced neuronal degeneration. To determine which specific laminin chains are involved, we investigated the expression of laminins in the hippocampus, and the cell types expressing them. Reverse transcription-PCR demonstrated that the messenger RNAs for all laminin chains could be detected in the hippocampus. To determine the localization of laminin chain expression, immunostaining was used. This method showed that α5, β1 and γ1 are most highly expressed in the neuronal cell layers. Immunoblotting confirmed the hippocampal expression of the chains α5, β1 and γ1, and RNA
in situ hybridization showed a neuronal expression pattern of α5, β1 and γ1. At early time points following intrahippocampal injection of kainate, α5, β1 and γ1 chain immunoreactivities were lost. In addition, tissue plasminogen activator-deficient mice, which are resistant to kainate-induced neuronal death, show no significant change in laminins α5, β1 and γ1 after intrahippocampal kainate injection.
Taken together, these results suggest that laminin-10 (α5-β1-γ1) comprises a major neuronal laminin in the mouse hippocampus, and is degraded before neuronal death during excitotoxic injury by the tissue plasminogen activator/plasmin protease cascade. By identifying a neuronal laminin (laminin-10) that participates in neuronal degeneration after excitotoxic injury, this study clarifies the molecular definition of the extracellular matrix in the hippocampus and further defines a pathway for mechanisms of neuronal death.
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The potential of utilizing lunar regolith as the raw material for manufacturing structural members is very appealing for future exploration and settlement of the Moon. Future lunar missions will ...depend on in-situ resource utilization (ISRU) for structural components, among other things. Sintered lunar regolith has been proposed as a structural material. In general, it has been assumed that the regolith would be at least minimally processed before use. We propose the possibility of manufacturing structural components directly using unrefined sintered lunar regolith with the advantage of requiring fewer specialized material processing equipment.
Our purpose in this study was the quantification of the material properties of unrefined sintered lunar regolith simulant. Two batches of sintered lunar regolith simulant JSC-1A samples, with porosities of 1.44% and 11.78%, underwent compression testing using an Instron series 4500 Universal Test System machine. Material properties were evaluated from the acquired load vs. deflection data. Stress vs. strain, modulus of elasticity, toughness, bulk modulus and compressive strength were evaluated as a function of porosity. The average compressive strength of the 1.44% porosity material was 218.8 MPa, and 84.6 MPa for the 11.78% porosity material. Our tests show that even unrefined sintered 11.78% porosity lunar regolith holds the possibility of being a useful structural material for lunar construction. Comparing our experimental results with those of other ISRU derived structural materials, unrefined sintered lunar regolith is expected to be one of the strongest material derived from lunar sources.
•Evaluation of current lunar ISRU structural materials which have been tested.•Evaluation of SLS mechanical material properties by experimental methods.•Comparison of SLS material properties with Lunar derived structural materials.•Comparison of the SLS material properties with terrestrial derived materials.
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Laminins are extracellular matrix proteins that participate in neuronal development, survival, and regeneration. During excitotoxin challenge in the mouse hippocampus, neuron interaction with ...laminin-10 (alpha5,beta1,gamma1) protects against neuronal death. To investigate how laminin is involved in neuronal viability, we infused laminin-1 (alpha1,beta1,gamma1) into the mouse hippocampus. This infusion specifically disrupted the endogenous laminin layer. This disruption was at least partially due to the interaction of the laminin-1 gamma1 chain with endogenous laminin-10, because infusion of anti-laminin gamma1 antibody had the same effect. The disruption of the laminin layer by laminin-1 1) did not require the intact protein because infusion of plasmin-digested laminin-1 gave similar results; 2) was posttranscriptional, because there was no effect on laminin mRNA expression; and 3) occurred in both tPA(-/-) and plasminogen(-/-) mice, indicating that increased plasmin activity was not responsible. Finally, although tPA(-/-) mice are normally resistant to excitotoxin-induced neurodegeneration, disruption of the endogenous laminin layer by laminin-1 or anti-laminin gamma1 antibody renders the tPA(-/-) hippocampal neurons sensitive to kainate. These results demonstrate that neuron interactions with the deposited matrix are not necessarily recapitulated by interactions with soluble components and that the laminin matrix is a dynamic structure amenable to modification by exogenous molecules.
Neuronal damage in the CNS after excitotoxic injury is correlated with blood-brain barrier (BBB) breakdown. We have used a glutamate analog injection model and genetically altered mice to investigate ...the relationship between these two processes in the hippocampus. Our results show that BBB dysfunction occurs too late to initiate neurodegeneration. In addition, plasma infused directly into the hippocampus is not toxic and does not affect excitotoxin-induced neuronal death. To test plasma protein recruitment in neuronal degeneration, we used plasminogen-deficient (plg(-/-)) mice, which are resistant to excitotoxin-induced degeneration. Plasminogen is produced in the hippocampus and is also present at high levels in plasma, allowing us to determine the contribution of each source to cell death. Intrahippocampal delivery of plasminogen to plg(-/-) mice restored degeneration to wild-type levels, but intravenous delivery of plasminogen did not. Finally, although the neurons in plg(-/-) mice do not die after excitotoxin injection, BBB breakdown occurs to a similar extent as in wild-type mice, indicating that neuronal death is not necessary for BBB breakdown. These results indicate that excitotoxin-induced neuronal death and BBB breakdown are separable events in the hippocampus.
We aimed to examine the concurrent associations of gender-affirming hormonal interventions (i.e., puberty blockers, testosterone, estrogen), as well as family and friend social support, on ...transgender and nonbinary (TNB) adolescents' reports of anxiety symptoms, depressive symptoms, nonsuicidal self-injury (NSSI), and suicidality. We hypothesized that gender-affirming hormonal interventions and greater social support would be associated with lower levels of mental health concerns.
Participants (n = 75; aged 11–18; Mage = 16.39 years) were recruited for this cross-sectional study from a gender-affirming multidisciplinary clinic. Fifty-two percent were receiving gender-affirming hormonal interventions. Surveys assessed anxiety and depressive symptoms, NSSI and suicidality in the past year, and social support from family, friends, and significant others. Hierarchical linear regression models examined associations between gender-affirming hormonal interventions and social support (i.e., family, friend) with mental health while accounting for nonbinary gender identity.
Regression models explained 15%–23% of variance in TNB adolescents' mental health outcomes. Gender-affirming hormonal interventions were associated with fewer anxiety symptoms (β = −0.23; p < .05). Family support was associated with fewer depressive symptoms (β = −0.33; p = .003) and less NSSI (β = −0.27; p = .02). Friend support was associated with fewer anxiety symptoms (β = −0.32; p = .007) and less suicidality (β = −0.25; p = .03).
TNB adolescents had better mental health outcomes in the context of receiving gender-affirming hormonal interventions and having greater support from family and friends. Findings highlight the important role of quality family and friend support for TNB mental health. Providers should aim to address both medical and social factors to optimize TNB mental health outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aflatoxin M1 (AFM1) is found in the milk of cows exposed to feed spoiled by Aspergillus fungi species. These fungi may produce the secondary metabolite aflatoxin B1, which is converted in the cow ...liver by hydroxylation to AFM1 and is then expressed in milk. AFM1 is regulated in milk and other dairy products because it can cause serious health issues, such as liver and kidney cancers, in humans and is an immunosuppressant.
To optimize the chromatographic protocol and to extend the matrix scope to include a wider range of dairy products: whey powder, whey protein concentrate, whey protein isolate, liquid milk, skim milk powder, whole milk powder, adult nutritional products, and yogurt.
AFM1 is extracted using 1% acetic acid in acetonitrile incorporating ionic salts. The AFM1 in the resulting extract is concentrated using an automated RIDA®CREST IMMUNOPREP® online cartridge coupled to quantification by HPLC-fluorescence.
The method was shown to be accurate, with acceptable recovery (81.2-97.1%) from spiked samples. Acceptable precision was confirmed, with a relative standard deviation (RSD) for repeatability of 6.6-11.2% and an RSD for intermediate precision of 7.5-16.7%. Method LOD and robustness experiments further demonstrated the suitability of this method for routine compliance testing. Analysis of an international proficiency trial sample generated results that were comparable with the value assigned from alternative independent methods.
A method with improved chromatography for high-throughput, routine testing of AFM1 in an extended range of dairy products is described. The method was subjected to single-laboratory validation and was found to be accurate, precise, and fit for purpose.
Single-laboratory validation of an automated online immunoaffinity cleanup fluorescence HPLC method for AFM1 in whey proteins, milk powders, nutritional products, liquid milk, and yogurt. Allows for high-throughput analysis of AFM1 with enhanced chromatographic performance. Method applicable to the analysis of AFM1 in an extended range of milk and milk-based products.
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Comprehensive school-based programs applying the WHO Health Promoting School Model have the potential to initiate and sustain behavior change and impact health. However, since they often include ...intervention efforts on a school's policies, physical environment, curriculum, health care and involving parents and communities, they significantly 'intrude' on a complex system that is aimed primarily at education, not health promotion. More insights into and concrete strategies are therefore needed regarding their adoption, implementation, and sustainment processes to address the challenge to sustainable implementation of HPS initiatives in a primarily educational setting. This study consequently evaluates adoption, implementation and sustainment processes of Amsterdam's Jump-in healthy nutrition HPS intervention from a multi-stakeholder perspective.
We conducted semi-structured interviews and focus groups with all involved stakeholders (n = 131), i.e., Jump-in health promotion professionals (n = 5), school principals (n = 7), at-school Jump-in coordinators (n = 7), teachers (n = 20), parents (n = 50, 9 groups) and children (n = 42, 7 groups) from 10 primary schools that enrolled in Jump-in in the school year 2016-2017. Included schools had a higher prevalence of overweight and/or obesity than the Dutch average and they were all located in Amsterdam's low-SEP neighborhoods. Data were analyzed using a directed content analysis, in which the Determinants of Innovation Model was used for obtaining theory-based predetermined codes, supplemented with new codes emerging from the data.
During intervention adoption, all stakeholders emphasized the importance of parental support, and accompanying workshops and promotional materials. Additionally, parents and teachers indicated that a shared responsibility for children's health and nuanced framing of health messages were important. During implementation, all stakeholders needed clear guidelines and support structures. Teachers and children highlighted the importance of peer influence, social norms, and uniform application of guidelines. School staff also found further tailoring of the intervention and dealing with financial constraints important. For long-term intervention sustainment, incorporating the intervention policies into the school statutes was crucial according to health promotion professionals.
This qualitative evaluation provides valuable insights into factors influencing the adoption, implementation, and sustainment processes of dietary interventions, such as the importance of transparent and consistent intervention guidelines, clear communication regarding the rationale behind intervention guidelines, and, stakeholders' involvement in decision-making.
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Abstract
Background
Thiamine and pantothenic acid play a critical role in numerous metabolic reactions and are typically supplemented in infant and adult nutritional formulas as thiamine chloride ...hydrochloride and calcium pantothenate salts.
Objective
A rapid compliance method for the analysis of thiamine and pantothenic acid applicable to infant formula and milk-based nutritional products is described.
Method
Proteins are removed by centrifugal ultrafiltration, followed by analysis by reversed-phase liquid chromatography‒tandem mass spectrometry (LC-MS/MS), with quantitation accomplished by internal standard technique.
Results
The method was shown to be accurate, with acceptable recovery (thiamine, 99.3–101.1%; pantothenic acid, 99.2–108.6%). A certified reference material (NIST 1849a), showed no statistical bias (α = 0.05) for thiamine (P = 0.64); although a statistically significant bias (P < 0.01) for pantothenic acid was found, the nominal bias was only 4.7% (mean = 7.1 mg/hg; certified value = 6.8 mg/hg). A comparison of results by LC-MS/MS and current methods showed negligible bias (mean bias: thiamine, 0.01 mg/hg; pantothenic acid, 0.17 mg/hg) and no statistical significance (α = 0.05; thiamine, P = 0.399; pantothenic acid, P = 0.058). Acceptable precision was demonstrated with a repeatability of 7.2% repeatability relative standard deviation (RSDr) (HorRat: 0.6) and an intermediate precision of 7.0% RSD for thiamine, and a repeatability of 5.7% RSDr (HorRat: 0.5) and an intermediate precision of 6.1% RSD for pantothenic acid.
Conclusions
This rapid method is intended for use in high-throughput laboratories as part of routine product compliance release testing of thiamine and pantothenic acid in manufactured infant and milk-based nutritional products.
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Abstract
Background
Choline and l-carnitine are classified as pseudo-vitamins because of their conditionally essential status. As they are involved in multiple physiological metabolic pathways in the ...human body, they are routinely fortified in infant and adult nutritional formulas.
Objective
The performance of an LC-MS/MS method for the analysis of choline and carnitine, compared with enzymatic methods in routine use for the analysis of total carnitine and total choline, is described.
Method
Powder samples were reconstituted, with release of carnitine and choline facilitated by both acid and alkaline hydrolysis and the extract analyzed by LC-MS/MS. Quantitation was by internal standard technique using deuterium-labeled carnitine and deuterium-labeled choline.
Results
Method range, specificity, sensitivity, precision, recovery, accuracy, and ruggedness were assessed for milk powders, infant formulas, and soy- and milk-based nutritional products. Spike recoveries of 94.0–108.4% were obtained for both total carnitine and choline, and no statistical bias (α = 0.05) between measured results and certified values (choline: P = 0.36; free carnitine: P = 0.67) was found for NIST 1849a certified reference material (NIST1849a). Precision, as repeatability relative standard deviation (RSD), was 2.0% RSDr for total carnitine and 1.7% RSDr for total choline. Equivalent results for total choline and total carnitine were obtained by LC-MS/MS and enzymatic methods (n = 30).
Conclusions
The described LC-MS/MS method is fit for purpose for routine product compliance release testing environments. This validation study has confirmed that alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.
Highlights
An LC-MS/MS method was evaluated and found to be fit-for-purpose for routine product compliance release testing of infant formula. The LC-MS/MS method was compared with enzymatic methods for the analysis of total carnitine and total choline. Alternative enzymatic assays can be used with confidence in laboratories in which LC-MS/MS platforms are unavailable.
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