Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake.

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p<0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p<0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

The PAX LC Trial: A Decentralized, Phase 2, Randomized, Double-Blind Study of Nirmatrelvir/Ritonavir Compared with Placebo/Ritonavir for Long COVID.

BACKGROUND: Individuals with long COVID lack evidence-based treatments and have difficulty participating in traditional site-based trials. Our digital, decentralized trial investigates the efficacy and safety of nirmatrelvir/ritonavir, targeting viral persistence as a potential cause of long COVID. METHODS: The PAX LC trial (NCT05668091) is a Phase 2, 1:1 randomized, double-blind, superiority, placebo-controlled trial in 100 community-dwelling, highly symptomatic adult participants with long COVID residing in the 48 contiguous US states to determine the efficacy, safety, and tolerability of 15 days of nirmatrelvir/ritonavir compared with placebo/ritonavir. Participants are recruited via patient groups, cultural ambassadors, and social media platforms. Medical records are reviewed through a platform facilitating participant-mediated data acquisition from electronic health records nationwide. During the drug treatment, participants complete daily digital diaries using a web-based application. Blood draws for eligibility and safety assessments are conducted at or near participants' homes. The study drug is shipped directly to participants' homes. The primary endpoint is the PROMIS-29 Physical Health Summary Score difference between baseline and Day 28, evaluated by a mixed model repeated measure analysis. Secondary endpoints include PROMIS-29 (Mental Health Summary Score and all items), Modified GSQ-30 with supplemental symptoms questionnaire, COVID Core Outcome Measures for Recovery, EQ-5D-5L (Utility Score and all items), PGIS 1 and 2, PGIC 1 and 2, and healthcare utilization. The trial incorporates immunophenotyping to identify long COVID biomarkers and treatment responders. CONCLUSION: The PAX LC trial uses a novel decentralized design and a participant-centric approach to test a 15-day regimen of nirmatrelvir/ritonavir for long COVID.

Hohlraum fields with monoenergetic proton radiography at OMEGA.

A more complete understanding of laser-driven hohlraum plasmas is critical for the continued development and improvement of ICF experiments. In these hohlraums, self-generated electric and magnetic fields can play an important role in modifying plasma properties such as heat transport; however, the strength and distribution of electromagnetic fields in such hohlraums remain largely uncertain. To explore this question, we conducted experiments at the OMEGA laser facility, using monoenergetic proton radiography to probe laser-driven vacuum hohlraums. We then utilized reconstructive methods to recover information about proton deflections. To interpret these reconstructions, a new technique for detangling the contributions of electric and magnetic fields to proton deflections was developed. This work was supported in part by the U.S. Department of Energy, the National Laser Users' Facility, and the Laboratory for Laser Energetics.

Development of an All-Marine 3D Printed Bioactive Hydrogel Dressing for Treatment of Hard-to-Heal Wounds.

Current standard wound care involves dressings that provide moisture and protection; however, dressings providing active healing are still scarce and expensive. We aimed to develop an ecologically sustainable 3D printed bioactive hydrogel-based topical wound dressing targeting healing of hard-to-heal wounds, such as chronic or burn wounds, which are low on exudate. To this end, we developed a formulation composed of renewable marine components; purified extract from unfertilized salmon roe (heat-treated X, HTX), alginate from brown seaweed, and nanocellulose from tunicates. HTX is believed to facilitate the wound healing process. The components were successfully formulated into a 3D printable ink that was used to create a hydrogel lattice structure. The 3D printed hydrogel showed a HTX release profile enhancing pro-collagen I alpha 1 production in cell culture with potential of promoting wound closure rates. The dressing has recently been tested on burn wounds in Göttingen minipigs and shows accelerated wound closure and reduced inflammation. This paper describes the dressings development, mechanical properties, bioactivity, and safety.

Biomedical treatment and divine assistance: complementary reproductive itineraries among catholic women users of assisted reproduction technology in Argentina.

This paper explores how Catholic women in Argentina use assisted reproduction technologies (ARTs), and particularly the way in which they resort to biomedicine and religion as complementary sources of knowledge, support and assistance during reproductive treatments. It is concerned about the role of the Catholic religion in local reproductive itineraries, seeing that Catholicism has such significant social, political and cultural influence in the country. Drawing on a qualitative and ethnographic study of Catholic spaces of worship, a maternity hospital and in-depth interviews with former users from three metropolitan areas in Argentina, we examine how reproductive itineraries involve the users' agency in building health resources from religion, with reference to biomedicine. The data reveal that women address religion as an affective, social and therapeutic recourse intertwined with biomedical power. These findings highlight the multiple and complex forms reproduction acquires in specific social, cultural and normative contexts, and contribute to discussing the complementarity between religion and biomedicine in health experiences.

Parenting With a Kind Mind: Exploring Kindness as a Potentiator for Enhanced Brain Health.

A growing body of research has suggested that high levels of family functioning-often measured as positive parent-child communication and low levels of parental stress-are associated with stronger cognitive development, higher levels of school engagement, and more successful peer relations as youth age. The COVID-19 pandemic has brought tremendous disruption to various aspects of daily life, especially for parents of young children, ages 3-5, who face isolation, disconnection, and unprecedented changes to how they engage and socialize. Fortunately, both youth and parent brains are plastic and receptive to change. Resilience research shows that factors such as engaging in acts of kindness, developing trusting relationships, and responding compassionately to the feelings of others can help lay new neural pathways and improve quality of life. Yet, little research has investigated the effects of brain healthy parental practices of kindness with pre-school aged children. The current study examines whether an interactive, parent-child kindness curriculum can serve as a potentiator for brain health as measured by resilience and child empathy levels. During a peak of the pandemic, mother participants between the ages of 26-46 (n = 38, completion rate 75%) completed questionnaires on parental resilience levels and parent-reported child empathic pro-social behaviors before and after engaging in a 4 weeks online, self-paced, kindness curriculum. Half of the group received additional brain health education explaining the principles of neuroplasticity, empathy, perspective taking, and resiliency. Mothers in both groups showed increased resilience ( p < 0.001) and reported higher levels of empathic behavior in their child ( p < 0.001) after completing the curriculum. There was no significant difference between groups. Comparison of mean resilience levels during COVID-19 to pre-pandemic general means indicated that mothers are reporting significantly lower levels of resilience as well as decreased empathetic behaviors in their children. These results support the notion that kindness is a powerful brain health booster that can increase resilience and empathy. This research study was timely and relevant for parents in light of the myriad of stresses brought about by the ongoing COVID-19 pandemic. There are broader public health implications for equipping individuals with tools to take a proactive and preventative approach to their brain health.

Los sentidos sobre los fetos y embriones: imágenes, discursos y tecnología en las experiencias de usuarias de TRHA en Argentina / Os sentidos de fetos e embriões: imagens, discursos e tecnologia nas experiências de usuárias de TRHA na Argentina / The senses about fetuses and embryos: Images, discourses and technology in the ARTs user's experiences in Argentina

Resumen El presente trabajo analiza los sentidos que las usuarias de TRHA construyen sobre los embriones y fetos de forma situada. Desde un método cualitativo y un enfoque biográfico, se exploran las maneras en que las usuarias dan sentido y subjetivan a los embriones en diferentes momentos: durante la gestación, ante la pérdida de un embarazo, como frente a las tecnologías de visualización y de criopreservación, dando cuenta de diferentes interpretaciones y resignificaciones. Situado en la Provincia de Córdoba, estas experiencias permiten dar cuenta de los sentidos locales de lo reproductivo y comprender las controversias que afrontan las usuarias un campo biomédico poco regulado en Argentina.

Resumo Este documento analisa os significados que as usuárias de TRHA constroem sobre embriões e fetos de uma forma situada. Utilizando um método qualitativo e uma abordagem biográfica, exploramos as formas como as usuárias dão sentido e subjetividade aos embriões em diferentes momentos: durante a gestação, face à perda de gravidez, e face às tecnologias de visualização e criopreservação, dando conta de diferentes interpretações e ressignificações. Situadas na província de Córdoba, estas experiências nos permitem dar conta dos significados locais das questões reprodutivas e compreender as controvérsias enfrentadas pelos utilizadores de um campo biomédico mal regulado na Argentina.

Abstract The present work analyzes the construction-meaning process in ART users about embryos and fetuses in a situated way. From a qualitative method and a biographical approach, it explores the ways that ART users construct and subject ART embryos at different times: during gestation, in the face of pregnancy loss, as well as in front of visualization and cryopreservation technologies, accounting for different interpretations and resignifications. Located in the Province of Córdoba, these experiences allow us to account for the local meanings of reproductive issues and to understand the controversies faced by users of a biomedical field that is not very regulated in Argentina.

The Effectiveness of RAADS-R as a Screening Tool for Adult ASD Populations.

Adult referrals to specialist autism spectrum disorder diagnostic services have increased in recent years, placing strain on existing services. It was proposed that the Ritvo Autism Asperger's Diagnostic Scale could be used as a screening tool, in order to identify and prioritise patients most likely to receive an ASD diagnosis. This study evaluates the validity of the RAADS-R as a screening tool for ASD in an adult population. Retrospective case note analysis was used to evaluate the efficacy of the RAADS-R as a screening tool to predict ASD diagnostic outcomes in 50 service users of a NHS specialist autism service. Results indicate no association between RAADS-R scores and clinical diagnostic outcome, suggesting the RAADS-R is not an effective screening tool for identifying service users most likely to receive an ASD diagnosis. In conclusion, used as a self-report measure pre-full diagnostic assessment, the RAADS-R lacks predictive validity and is not a suitable screening tool for adults awaiting autism assessments. Future research should aim to identify reliable screening tools for this purpose.

A new tri-particle backlighter for high-energy-density plasmas (invited).

A new tri-particle mono-energetic backlighter based on laser-driven implosions of DT3He gas-filled capsules has been implemented at the OMEGA laser. This platform, an extension of the original D3He backlighter platform, generates 9.5 MeV deuterons from the T3He reaction in addition to 14.7 and 3.0 MeV protons from the deuterium and helium-3 reactants. The monoenergetic 14.7 and 3.0 MeV protons have been used with success at OMEGA and the NIF for both radiography and stopping-power studies. There are several advantages of having a third particle to diagnose plasma conditions: an extra time-of-flight-separated radiograph and an improved ability to discern between electric and magnetic fields. In cases where the 3.0 MeV protons cannot penetrate an experiment, the benefit of the additional 9.5 MeV deuterons is magnified. This capability is well-suited for NIF experiments, where large fields and plasma densities often preclude useful 3.0 MeV proton data. The advantages are demonstrated with radiographs of OMEGA plasmas with magnetic and electric fields. Tests using backlighter-scale 420 µm diameter thin glass capsules validate the platform's extended backlighting capability. The performance characteristics of this backlighter, such as source size and timing, are discussed.

Adiposity, reproductive and metabolic health, and activity levels in zoo Asian elephant (Elephas maximus).

Many captive Asian elephant populations are not self-sustaining, possibly due in part to obesity-related health and reproductive issues. This study investigated relationships between estimated body composition and metabolic function, inflammatory markers, ovarian activity (females only) and physical activity levels in 44 Asian elephants (n=35 females, n=9 males). Deuterium dilution was used to measure total body water from which fat mass (FM) and fat-free mass (FFM) could be derived to estimate body composition. Serum was analyzed for progestagens and estradiol (females only), deuterium, glucose, insulin and amyloid A. Physical activity was assessed by an accelerometer placed on the elephant's front leg for at least 2 days. Relative fat mass (RFM) - the amount of fat relative to body mass - was calculated to take differences in body size between elephants into consideration. Body fat percentage ranged from 2.01% to 24.59%. Male elephants were heavier (P=0.043), with more FFM (P=0.049), but not FM (P>0.999), than females. For all elephants, estimated RFM (r=0.45, P=0.004) was positively correlated with insulin. Distance walked was negatively correlated with age (r=-0.46, P=0.007). When adjusted for FFM and age (P<0.001), non-cycling females had less fat compared with cycling females, such that for every 100 kg increase in FM, the odds of cycling were 3 times higher (P<0.001). More work is needed to determine what an unhealthy amount of fat is for elephants; however, our results suggest higher adiposity may contribute to metabolic perturbations.

Repair and remodeling of partial-weightbearing, uninstrumented long bone fracture model in mice treated with low intensity vibration therapy.

BACKGROUND: While vibration therapy has shown encouraging results across many fields of medicine in the last decade, its role as originally envisioned for bone health remains uncertain. Especially regarding its efficacy in promoting fracture healing, mixed and incomplete outcomes suggest a need to clarify its potential. In particular, the definitive effect of vibration, when isolated from the confounding mechanical inputs of gait and stabilizing instrumentation, remains largely unknown. METHODS: Four cohorts of C57BL/6 male mice underwent single-leg, open fibula fracture. Vibration was applied at 0.3 g to two groups for 20 min/d. At 3 and 6 weeks, fibulae were harvested for microcomputed tomography and 3-point bending to failure. FINDINGS: In bone volume and tissue volume, the groups at each healing time point were statistically not different. At 3 weeks, however, the ratio of bone-to-tissue volume was lower for the vibrated group than control. Likewise, while bone mineral density did not differ, tissue volume density was lowest with vibration. At 6 weeks, mean differences were nominal. Biomechanically, vibration consistently trended ahead of control in strength and stiffness, but did not achieve statistical significance. INTERPRETATION: At this stage of therapeutic development, vibration therapy in isolation does not demonstrate a clear efficacy for bone healing, although further treatment permutations and translational uses remain open for investigation.

Stage Specific Expression Pattern of Alpha-Hemoglobin-Stabilizing-Protein (AHSP) Portrayed in Erythroblast Chronology.

During erythropoiesis, the molecular chaperone alpha-hemoglobin-stabilizing protein (AHSP) sequesters free alpha-hemoglobin (αHb) and prevents precipitation of excess αHb. While AHSP is linked to hereditary anemia, the pattern of expression during specific erythroblast stages is poorly understood. We investigated gene and protein expressions of AHSP throughout progressive maturation stages of erythroblasts in biphasic cultures of blood and bone marrow samples from healthy donors. Differentiating erythroblasts were periodically subjected to flow cytometry, Amnis imaging and RT-qPCR analyses. We made parallel in vivo validations from naive murine bone marrow cells. Percentages of AHSP+ erythroblasts, protein expressions and AHSP gene expressions are negligible on culture day 6 (CFU-Es) and progressively increases from culture days 8-12 (peaks on day 12) and declines on day 14. Notably, sub-cellular location of AHSP is both in the cytoplasm and nucleus in the early erythroblasts while in the late stages of maturation AHSP is found predominantly in the nucleus, being expelled with it during enucleation. As both human bone marrow and peripheral blood mononuclear cells (PBMC) derived erythroblasts demonstrated similar expression patterns, sampling of erythroblasts from day 11 cultures could portray erythroblast chronology and provide optimum representative stage specific expression patterns. PBMCs may be suitable for comparison studies of AHSP expression in pathologic erythropoiesi.

'That is why we raise children': African American fathers' race-related concerns for their adolescents and parenting strategies.

INTRODUCTION: The current study highlights the voices and perspectives of African American fathers, with specific emphasis on their race-related concerns for their adolescents as well as how these concerns guide their parenting strategies. METHOD: Twenty-four African American fathers participated in 1.5-3 h long focus group interviews. All fathers (M = 42.24 years, SD = 6.93) resided in a mid-sized city in the Southeastern United States. All participants were either biological fathers (n = 20) or non-biological (n = 4) fathers. Fathers were residential (76%) and non-residential (24%), with at least one adolescent child (M = 14.32 years, SD = 5.80; Range: 10-16 years). Fifty-eight percent of fathers (n = 14) had both male and female children, 29% had only female children (n = 7) and 13% had only male children (n = 3). After codebook development and refinement, key themes were explored using a theoretical thematic analysis. RESULTS: In response to race-related and other social risks for African American adolescents, fathers articulated a number of parenting motivations and intentions: 1) fathers' own racial experiences; 2) negative media images of Black youth and families (e.g. media influences, negative stereotypes, and portrayals of Black fathers); 3) preserving families through community support; 4) developing awareness of discrimination and coping strategies; 5) cultivating positive personal and cultural identities; and 6) achievement as necessity. Also, gender emerged as a critical lens for African American fathers' concerns and parenting strategies. CONCLUSION: Overall, our investigation highlights African American fathers' own meaning-making around concerns for their adolescents as well as how they shape parenting processes.

The conceptual design of 1-ps time resolution neutron detector for fusion reaction history measurement at OMEGA and the National Ignition Facility.

The nuclear burn history provides critical information about the dynamics of the hot-spot formation and high-density fuel-shell assembly of an Inertial Confinement Fusion (ICF) implosion, as well as information on the impact of alpha heating, and a multitude of implosion failure mechanisms. Having this information is critical for assessing the energy-confinement time τE and performance of an implosion. As the confinement time of an ICF implosion is a few tens of picoseconds, less than 10-ps time resolution is required for an accurate measurement of the nuclear burn history. In this study, we propose a novel 1-ps time-resolution detection scheme based on the Pockels effect. In particular, a conceptual design for the experiment on the National Ignition Facility and OMEGA are elaborated upon herein. A small organic Pockels crystal "DAST" is designed to be positioned ∼5 mm from the ICF implosion, which is scanned by a chirped pulse generated by a femto-second laser transmitted through a polarization-maintained optical fiber. The originally linearly polarized laser is changed to an elliptically polarized laser by the Pockels crystal when exposed to neutrons, and the modulation of the polarization will be analyzed. Our study using 35-MeV electrons showed that the system impulse response is 0.6 ps. The response time is orders of magnitude shorter than current systems. Through measurements of the nuclear burn history with unprecedented time resolution, this system will help for a better understanding of the dynamics of the hot-spot formation, high-density fuel-shell assembly, and the physics of thermonuclear burn wave propagation.

[Emotions, concerns and reflections regarding the COVID-19 pandemic in Argentina]. / Emociones, preocupaciones y reflexiones frente a la pandemia del COVID-19 en Argentina.

The scope of this work is to explore the feelings and expectations that COVID-19 has generated in Argentina during the first stage of the pandemic. A survey of the World Health Organization adapted to the local context was applied. Open-ended questions were included to study people's feelings about COVID-19, and content analysis was subsequently conducted. In terms of results, it is revealed that the population surveyed feels uncertainty, fear and anguish, albeit a feeling of responsibility and care in the face of COVID-19 also emerges. Moreover, positive feelings regarding society stand out as an achievement of social interdependence. The results obtained show that the impact on mental health differs in accordance with gender, educational level, and perceived comfort in the home. The study concludes that the emotional and bonding dimensions of people are central to confronting the COVID-19 pandemic in Argentina. It is recommended that these dimensions, as well as their subjective and differential social impact among the different population groups, should be considered in the planning of policies to address the COVID-19 pandemic.

El objetivo de este trabajo es explorar los sentimientos y expectativas que genera el COVID-19 en Argentina durante la primera etapa de la pandemia. Se aplicó una encuesta de la Organización Mundial de la Salud adaptada al contexto local. Se incluyeron preguntas abiertas para indagar sentimientos de las personas frente al COVID-19, y se realizó un análisis de contenido. Como resultados se advierte que la población encuestada siente incertidumbre, miedo y angustia, pero también emerge un sentimiento de responsabilidad y cuidado frente al COVID-19. Así mismo se destacan sentimientos positivos para la sociedad como una valoración de la interdependencia social. Los resultados arribados señalan que el impacto en la salud mental es desigual según el género, el nivel educativo alcanzado y el confort percibido en el hogar. El estudio permite concluir que las dimensiones emocionales y vinculares de las personas resultan aspectos centrales ante la pandemia del COVID-19 en Argentina. Es recomendable que estas dimensiones, así como y su impacto subjetivo y social diferencial entre los diversos grupos poblacionales, sean consideradas en la planificación de políticas para afrontar el COVID-19.

Emociones, preocupaciones y reflexiones frente a la pandemia del COVID-19 en Argentina / Emotions, concerns and reflections regarding the COVID-19 pandemic in Argentina

Resumen El objetivo de este trabajo es explorar los sentimientos y expectativas que genera el COVID-19 en Argentina durante la primera etapa de la pandemia. Se aplicó una encuesta de la Organización Mundial de la Salud adaptada al contexto local. Se incluyeron preguntas abiertas para indagar sentimientos de las personas frente al COVID-19, y se realizó un análisis de contenido. Como resultados se advierte que la población encuestada siente incertidumbre, miedo y angustia, pero también emerge un sentimiento de responsabilidad y cuidado frente al COVID-19. Así mismo se destacan sentimientos positivos para la sociedad como una valoración de la interdependencia social. Los resultados arribados señalan que el impacto en la salud mental es desigual según el género, el nivel educativo alcanzado y el confort percibido en el hogar. El estudio permite concluir que las dimensiones emocionales y vinculares de las personas resultan aspectos centrales ante la pandemia del COVID-19 en Argentina. Es recomendable que estas dimensiones, así como y su impacto subjetivo y social diferencial entre los diversos grupos poblacionales, sean consideradas en la planificación de políticas para afrontar el COVID-19.

Abstract The scope of this work is to explore the feelings and expectations that COVID-19 has generated in Argentina during the first stage of the pandemic. A survey of the World Health Organization adapted to the local context was applied. Open-ended questions were included to study people's feelings about COVID-19, and content analysis was subsequently conducted. In terms of results, it is revealed that the population surveyed feels uncertainty, fear and anguish, albeit a feeling of responsibility and care in the face of COVID-19 also emerges. Moreover, positive feelings regarding society stand out as an achievement of social interdependence. The results obtained show that the impact on mental health differs in accordance with gender, educational level, and perceived comfort in the home. The study concludes that the emotional and bonding dimensions of people are central to confronting the COVID-19 pandemic in Argentina. It is recommended that these dimensions, as well as their subjective and differential social impact among the different population groups, should be considered in the planning of policies to address the COVID-19 pandemic.

[The senses on in vitro embryos and the religious dimension: contributions for debate.] / Los sentidos sobre los embriones in vitro y la dimensión religiosa: aportes para el debate.

Based on a biographical investigation of the experiences of assisted reproduction users in Córdoba, this work seeks contribute on the religious dimension as a category that a priori does not determine the users senses about reproduction and embryos in vitro.

A partir de una investigación biográfica sobre experiencias de usuarias de reproducción asistida en Córdoba, este trabajo busca realizar un aporte sobre la dimensión religiosa como una categoría que a priori no determina los sentidos que las personas usuarias tienen sobre la reproducción y los embriones in vitro.

A Shift in Myeloid Cell Phenotype via Down Regulation of Siglec-1 in Island Macrophages of Bone Marrow Is Associated With Decreased Late Erythroblasts Seen in Anemia of Critical Illness.

Burn injury has been shown to significantly dampen erythropoiesis in both burn patients and in murine models. Our previous findings elucidated the erythropoietin independent defects in red cell development stages involving erythroid progenitor production and late stage erythroblast enucleation processes. We hypothesized that macrophages (MØ) in erythroblast islands (EBI) could be yet another roadblock impeding erythropoiesis following burn injury. Here we highlight that the methodology to study EBI can be achieved with single cell suspensions using a simple technique such as flow cytometry, as obtaining the central erythroblast island macrophages (EBIMØs) of interest is a delicate process. We elucidated the requisite of EBIMØ from the erythroblast as well as the MØ perspective. In addition to the primary erythropoiesis organ, the bone marrow (BM), spleens were also examined for extra-medullary erythropoiesis. Femurs and spleens were harvested from adult mice (B6D2F1) subjected to 15% total body surface area (TBSA) scald burn (B) or sham burn (S). Total bone marrow cells (TBM) and splenocytes were probed for total erythrons, early and late erythroblasts and EBIMØ by flow cytometry. There was only a marginal increase in the number of EBIMØ after burn, but, between the signatures of EBIMØ, Siglec-1 expression (MFI) was reduced by 40% in B with and a parallel 44% decrease in TBM erythrons in the BM. There were more (2.5-fold) EEBs and less LEBs (2.4-fold) per million TBM cells in B; with a corresponding decrease in Siglec-1 and Ly6G expressions in EBIMØ associated with EEB. Conversely, extra-medullary erythropoiesis was robust in spleens from B. Not only were the numbers of EBIMØs increased in B (p < 0.002), both EEBs and LEBs associated with EBIMØ were higher by 30 and 75%, respectively. Importantly, an increase in Siglec-1 and Vcam1 expressing F480+ splenic macrophages was observed after burn injury. Therefore, stagnant EEBs in the BM after burn injury could be due to low Siglec1 expressing EBIMØ, which perhaps impede their maturation into LEBs and reticulocytes. Repercussion of myeloid cell phenotype specific to BM after burn injury could plausibly account for a defective late stage RBC maturation resulting in anemia of critical illness. Summary Sentence: Characterization of erythroblast island macrophages (EBIMØ) in the bone marrow and spleen at different stages of erythropoiesis after burn injury.

Fat mass compared to four body condition scoring systems in the Asian elephant (Elephas maximus).

Captive elephant populations are not self-sustaining due to health concerns possibly related to obesity. Categorizing obesity relies on qualitative analyses like body condition scores (BCS). However, elephant indices have not been validated against measured body composition. The objective was to compare BCS systems to body composition determined by deuterium dilution in 28 zoo-kept Asian elephants. Elephants were weighed and given deuterated water orally (0.05 ml/kg). Blood was collected at ~0, 24, 120, 240, 360, and 480 hr after dosing. Photographs were taken to score the elephant based on four BCS systems (BCSWemmer [0 to 11 scoring], BCSMorfeld [1 to 5 scoring], BCSFernando [0 to 10 scoring], BCSWijeyamohan [1 to 10 scoring]). Based on regression analysis, relative fat ranged from -305 kg to 515 kg, where negative values indicate less and positive values indicate more fat than expected for the elephant's mass in this population. BCSFernando was associated with relative fat (p = .020, R2 = 0.194). Relative fat, adjusted for sex and age in the statistical model, was associated with BCSWemmer (p = .027, R2 = 0.389), BCSFernando (p = .002, R2 = 0.502), and BCSWijeyamohan (p = .011, R2 = 0.426). Inclusion of zoo and familial relatedness resulted in all BCS systems associated with relative fat (p ≤ .015). Only BCSFernando predicted relative fat, unadjusted, suggesting it is the most capable system for practical use. Compared to absolute fat, relative fat may be more biologically relevant as greater fat relative to body mass is more likely to lead to health issues.

Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study.

X-Adrenoleukodystrophy (X-ALD) and its adult-onset, most prevalent variant adrenomyeloneuropathy (AMN) are caused by mutations in the peroxisomal transporter of the very long-chain fatty acid ABCD1. AMN patients classically present spastic paraparesis that can progress over decades, and a satisfactory treatment is currently lacking. Oxidative stress is an early culprit in X-ALD pathogenesis. A combination of antioxidants halts the clinical progression and axonal damage in a murine model of AMN, providing a strong rationale for clinical translation. In this phase II pilot, open-label study, 13 subjects with AMN were administered a high dose of α-tocopherol, N-acetylcysteine, and α-lipoic acid in combination. The primary outcome was the validation of a set of biomarkers for monitoring the biological effects of this and future treatments. Functional clinical scales, the 6-minute walk test (6MWT), electrophysiological studies, and cerebral MRI served as secondary outcomes. Most biomarkers of oxidative damage and inflammation were normalized upon treatment, indicating an interlinked redox and inflammatory homeostasis. Two of the inflammatory markers, MCP1 and 15-HETE, were predictive of the response to treatment. We also observed a significant decrease in central motor conduction time, together with an improvement or stabilization of the 6MWT in 8/10 subjects. This study provides a series of biomarkers that are useful to monitor redox and pro-inflammatory target engagement in future trials, together with candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials. Moreover, the clinical results suggest a positive signal for extending these studies to phase III randomized, placebo-controlled, longer-term trials with the actual identified dose. ClinicalTrials.gov Identifier: NCT01495260.