Growth Deficits Research Articles

Assessing the Synergistic Effects of Deficit Irrigation and Growth Retardants on Insitu Sprouting and Quality Parameters of Groundnut VRI 8

Background: Groundnut is a crucial oilseed crop cultivated year-round, with seed dormancy controlled by genetic and environmental factors. Preventing pre-harvest sprouting is essential, as it is a common issue. To study the effect of deficit irrigation management and foliar application of growth retardant chemicals on pre-harvest sprouting control efficiency to achieve higher yield of groundnut. Methodology: In a field experiment conducted during early summer 2024 at the Agricultural College and Research Institute, Madurai, the effectiveness of different growth retardant chemicals and deficit irrigation management on reducing in-situ sprouting of groundnut kernels was investigated. The experiment included three irrigation management strategies: conventional irrigation and two deficit irrigation treatments where irrigation was withheld from 90 to 105 DAS (Days After Sowing) and 85 to 100 DAS. Additionally, foliar sprays of growth retardant chemicals were applied at 75 and 90 DAS. The chemicals tested were maleic hydrazide (MH) @ 1250 ppm, cycocel (CCC) @ 1000 ppm, abscisic acid (ABA) @ 750 ppm, and salicylic acid (SA) @ 750 ppm. Proper agronomic practices were followed throughout the crop growth cycle. Results: Among the growth retardant chemicals tested, MH @ 1250 ppm proved effective in inducing dormancy. Withdrawal of irrigation from 90 to 105 DAS also significantly contributed to dormancy induction, extending dormancy by more than 5 days post-harvest as well as reduced the pod loss which significantly increased pod yield. It was because of the reduction in soil moisture content during harvest stage and alteration in the hormonal activities. Specifically, the combined treatment of foliar application of MH @ 1250 ppm and no irrigation from 90 to 105 DAS reduced germination percentage by 12.6%, 36.8% and 60.5% immediately 5, 10 and 15 days after harvest respectively. Conclusion: The reduction in soil moisture content during the harvest stage, coupled with changes in hormonal activities, significantly impacts seed sprouting. These factors can lead to stress conditions that hinder germination, ultimately affecting crop yields. Addressing these issues is crucial for ensuring optimal seed development and enhancing agricultural productivity.

8620 Prevalence of Osteopenia of Prematurity and Risk Factors in Neonatal of Maternity Hospital

Abstract Disclosure: D.M. Bastos: None. J.G. Bastos: None. A.C. Bastos: None. Introduction: The osteometabolic disease of prematurity (ODP), formerly known as osteopenia of prematurity, corresponds to a disorder of bone mineralization in the neonatal period in very low birth weight premature newborns. The estimated prevalence is about 30% when the birth weight is less than 1,500 grams and around 60% when it is less than 1,000 grams. There is no specific clinical picture, and it can present with mild manifestations, growth deficit, or even evolve with severe rickets and fractures. To qualify the care of premature newborns (NB) in our Service, we question what is the local prevalence of ODP and what are the clinical, biochemical, or imaging risk factors that are potentially related to a greater predisposition to this condition. Objective: Evaluate the prevalence of ODP and recognize potential risk factors in NBs in a neonatal ICU of a reference maternity hospital in Curitiba/ PR. Method: Retrospective longitudinal study, with analysis of medical records of patients born with a gestational age less than 34 weeks and birth weight less than 1,500 grams, born between January/2013 to August/2016. Discussion: Prematurity is the significant factor, followed by low birth weight, for osteopenia. Newborns (NB) with a birth weight below 1500g should receive 40mg/Kg of calcium and 50 mg/Kg of phosphorus. Supplementation of human milk should be started from 15 days of life or when oral intake reaches 100ml/Kg per day (1g/20 ml of milk). In this study, the classification of the growth curve and prevalence by sex were divergent with the literature. The most vulnerable are those with parenteral nutrition or prolonged fasting, as the adequate diet is the basis of prevention and treatment, similar data being found, as well as association with prolonged use of diuretic, presence of sepsis diagnosis and bronchopulmonary dysplasia. However, there is still a lack of specific and sensitive markers for early diagnosis and treatment. Conclusion: The prevalence of Osteopenia of Prematurity was lower than that found in the literature. The risk factors bronchopulmonary dysplasia and use of diuretics were statistically significant when evaluated in patients with osteopenia. However, no relationship was found between ODP and sepsis, as well as a relationship between ODP and Necrotizing Enterocolitis. Regarding the days kept fasting, use of TPN and Use of antibiotics, a longer duration of use was obtained when compared with the group that did not develop the disease. Presentation: 6/3/2024

Impact of Foreign Direct Investment on Renewable Energy Consumption: Findings from Bootstrap ARDL with a Fourier Function

Renewable energy consumption (REC) is viewed to be a core component for delivering sustainable economic growth. It is broadly acknowledged that REC can significantly contribute to lessening the burden of carbon emissions on the environment and fostering economic progress. Although foreign direct investments (FDI) are perceived as a key catalyst of REC growth, in some cases they can cause negative effects on REC. While there are many studies in the literature exploring the effects of FDI on variables such as economic growth, employment and foreign exchange deficits, the amount of studies examining the effect of the said variable on REC is very limited. The existing study attempts to fill this knowledge gap concerning the relationship between FDI and REC in Türkiye. This research investigates the long-run impact of FDI on RECs in Türkiye for the period 1973-2022 using the bootstrap Fourier ARDL technique. Empirical analysis reveals that FDI affects REC negatively, while GDP has no effect. The study's conclusions confirm the Pollution Haven Hypothesis (PHVH) in Türkiye, suggesting that the country has emerged as a desirable destination for businesses seeking to relocate their operations and evade the strict environmental regulations in their home countries.

Selenium Treatment Ameliorates the Adverse Effects Caused by Dynamin Gene Knockdown in Bombyx mori.

Our previous research reported the influence of 50 μM selenium (Se) on the cytosolization (endocytosis) pathway, which in turn stimulates the growth and development of Bombyx mori. Lately, dynamin is recognized as one of the key proteins in endocytosis. To explore the underlying mechanisms of Se impact, the dynamin gene was knocked down by injecting siRNAs (Dynamin-1, Dynamin-2, and Dynamin-3). This was followed by an analysis of the target gene and levels of silk protein genes, as well as growth and developmental indices, Se-enrichment capacity, degree of oxidative damage, and antioxidant capacity of B. mori. Our findings showed a considerable decrease in the relative expression of the dynamin gene in all tissues 24 h after the interference and a dramatic decrease in the silkworm body after 48 h. RNAi dynamin gene decreased the silkworm body weight, cocoon shell weight, and the ratio of cocoon. In the meantime, malondialdehyde level increased and glutathione level and superoxide dismutase/catalase activities decreased. 50 μM Se markedly ameliorated these growth and physiological deficits as well as decreases in dynamin gene expression. On the other hand, there were no significant effects on fertility (including produced eggs and laid eggs) between the interference and Se treatments. Additionally, the Se content in the B. mori increased after the dynamin gene interference. The dynamin gene was highly expressed in the silk gland and declined significantly after interference. Among the three siRNAs (Dynamin-1, Dynamin-2, and Dynamin-3), the dynamin-2 displayed the highest interference effects to target gene expression. Our results demonstrated that 50 μM Se was effective to prevent any adverse effects caused by dynamin knockdown in silkworms. This provides practical implications for B. mori breeding industry.

Significant Demographic Factors Fuelling Housing Deficit in Ado-Ekiti, Nigeria

This article assesses the significant demographic factors fuelling housing deficit in Ado-Ekiti, Nigeria. Using a mixed method approach as survey design coupled with a combination of purposive and stratified sampling technique, 1254 households were selected for administration of questionnaires during data collection process. Questionnaires, interviews were the major instruments of data collection from seven residential development corridors (RDCs) in Ado-Ekiti. Ministries, Agencies and Departments (MDAs) supported secondary data. Findings revealed that high population growth, rapid urbanisation and migration increased housing deficit in the study area. Hence, this study observed an increase in live births (162, 901) than deaths (45, 046) in Ado-Ekiti. Also, findings revealed an increase in building concentration (57.7%) from 2000-date. Similarly, this study observed an increase in challenges such as urban sprawl and infrastructure deficiency (L-INFRA) encountered as a result of rapid urbanisation. The study noted an increase in quantitative housing deficit (223,086) in 2023. Thus, a quantitative housing deficit of 334,554 housing units would arise in 2034.Furthermore, sharing of dwellings with other households (SHAD), a resultant effect of high migration trends constituted 43.4 percent across the RDCs in Ado-Ekiti. Also, improved infrastructural facilities (33.8%) was the modal reason for staying (RESTAY) in the study area. Using Paired T-test, this study further validated that a perfect positive relationship (1.000) exists between population growth and housing deficit in Ado-Ekiti. Therefore, this study recommends adoption of effective Family Planning Methods (FPMs), regional distribution of infrastructural facilities and conversion of under-utilised lands for an efficient housing delivery in Ado-Ekiti.

Improving growth in infants with CF.

Cystic fibrosis (CF) results in chronic pulmonary infections, inflammation, pancreatic insufficiency, and multiple gastrointestinal manifestations. Malnutrition and poor growth are hallmarks of CF, and strongly associated with poor outcomes. Through newborn screening, many infants can be diagnosed within a few days of life, which allows for early initiation of nutritional counseling and close clinical follow-up. Obstacles to growth for infants with CF start in utero, as newborns with CF can have a lower birth weight than the general population. Improving infant growth has been linked to improved clinical outcomes and survival. It remains a top priority and challenge for caregivers and healthcare teams. An interdisciplinary approach, including registered dietitian and social work support, is essential to optimize health for infants with CF. Remaining barriers to normalcy include deficits in linear growth, lack of accurate nutrition biomarkers, persistence of inequities related to social determinant of health, particularly in the global CF community.

Optimistic growth of marginal region plantations under climate warming: Assessing divergent drought resilience.

Given the context of significant global warming and the intensification of extreme climate events in the last century, large-scale reforestation and afforestation have been recognized as effective strategies to mitigate the climate crisis. Since the 1970s, China has launched several afforestation programs aimed at regional ecological protection, playing an important role in reaching carbon neutrality by 2060. This study provided a detailed analysis of the growth suitability of the main planted conifers (Pinus sylvestris var. mongolica and Pinus tabulaeformis) and broadleaves (Populus spp., Robinia pseudoacacia) in the semi-arid northern China. We compared the radial growth trends of plantations and their responses to extreme droughts from 1980 to 2018. Growth of most plantations has significantly increased over time, but broadleaves showed recent growth reductions in the past decade, which may be related to tree age and reduced soil moisture. Nevertheless, under warmer climate scenarios, the growth of plantations is forecasted to continue increasing. Broadleaves showed a better post-drought recovery, probably linked to their anisohydric behavior, than conifers, which presented a better resistance to drought. Growth of conifers depended more on warmer temperature and better precipitation conditions during the growing season, whereas broadleaves mainly reacted to warm temperature. Additionally, pre-drought growth levels weakened resilience components, while post-drought precipitation compensated for drought-induced growth deficit. Growth and resilience were negatively related to tree age, while higher stand density reduced growth. This assessment and projections of growth and drought resilience indicate the sustainability of most plantations in semi-arid regions, but future warmer and drier conditions may lead to an uncertain future regarding forest health and reduce their carbon sink potential.

Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of cancer chemotherapy that can often limit treatment options for cancer patients or have life-long neurodegenerative consequences that reduce the patient’s quality of life. CIPN is caused by the detrimental actions of various chemotherapeutic agents on peripheral axons. Currently, there are no approved preventative measures or treatment options for CIPN, highlighting the need for the discovery of novel therapeutics and improving our understanding of disease mechanisms. In this study, we utilized human-induced pluripotent stem cell (hiPSC)-derived motor neurons as a platform to mimic axonal damage after treatment with vincristine, a chemotherapeutic used for the treatment of breast cancers, osteosarcomas, and leukemia. We screened a total of 1902 small molecules for neuroprotective properties in rescuing vincristine-induced axon growth deficits. From our primary screen, we identified 38 hit compounds that were subjected to secondary dose response screens. Six compounds showed favorable pharmacological profiles – AZD7762, A-674563, Blebbistatin, Glesatinib, KW-2449, and Pelitinib, all novel neuroprotectants against vincristine toxicity to neurons. In addition, four of these six compounds also showed efficacy against vincristine-induced growth arrest in human iPSC-derived sensory neurons. In this study, we utilized high-throughput screening of a large library of compounds in a therapeutically relevant assay. We identified several novel compounds that are efficacious in protecting different neuronal subtypes from the toxicity induced by a common chemotherapeutic agent, vincristine which could have therapeutic potential in the clinic.

Mll4 regulates postnatal palate growth and midpalatal suture development.

MLL4, also known as KMT2D, is a histone methyltransferase that acts as an important epigenetic regulator during various organogenesis programs. Mutations in the MLL4 gene are the major cause for Kabuki syndrome, a human developmental disorder that involves craniofacial birth defects, including anomalies in the palate. The purpose of this study was to investigate the role of Mll4 and the underlying mechanisms in the development and growth of the palate. We generated a novel conditional knockout (cKO) mouse model with tissue-specific deletion of Mll4 in the palatal mesenchyme. By using micro-computed tomography (CT), histology, cell mechanism assays, and gene expression analysis approaches, we examined the development and growth of the palate in the Mll4 -cKO mice. Gross intra-oral examination at adult stages showed that Mll4 -cKO mice had defects along the midline of the palate, which included disrupted rugae pattern and widened midpalatal suture. Micro-CT-based skeletal analysis in the adult mice revealed that the overall palate width was decreased in the Mll4 -cKO mice. By using whole-mount and histological staining approaches at perinatal stages, we identified that the midline defects started to appear as early as 1 day prior to birth, manifesting initially as a widened midpalatal suture, accompanied by increased cell apoptosis in the suture mesenchyme cells. Genome-wide analysis of mRNA expression in the midpalatal suture tissue showed that Mll4 is essential for timely expression of major genes for cartilage development, such as Col2a1 and Acan , at birth. These results were validated through immunofluorescence staining, confirming that the expression of chondrogenic markers Sox9 and Col2a1 were markedly decreased, whereas that of the osteogenic marker Runx2 remained unchanged, in the midpalatal suture of the Mll4 -cKO mice. Indeed, time-course histological analysis during postnatal palate growth revealed retardation in the development of the suture cartilage in the Mll4 -cKO mice. In parallel, time-course micro-CT analysis during postnatal palatogenesis confirmed a transverse growth deficit in the palate of the Mll4 -cKO mice. Taken together, our results show that Mll4 is essential for timely occurrence of key cellular and molecular events that lead to proper midpalatal suture development and palate growth.

Improving infant Neurocognitive Development and Growth Outcomes with micronutrients (INDiGO): A protocol for an efficacy trial in rural Gambia.

Undernutrition during the early years of life has a harmful and irreversible impact on child growth and cognitive development. Many of the interventions tested to improve outcomes across infancy have had disappointing or inconsistent impact, a common feature being the absence of any attempt to provide nutritional supplements to infants during the first six months. With increasing evidence of micronutrient deficiencies in this age group, alongside strong evidence that growth and developmental deficits begin before six months, a renewed focus on the micronutrient status of infants is required. This study is a five-arm, double-blind, placebo-controlled, randomised efficacy trial of micronutrient supplementation to mothers (during pregnancy or pregnancy and lactation) and infants (Day 8 to six months of age) in rural Gambia, where rates of micronutrient deficiencies are high. 600 pregnant women (<20 weeks gestation) will be enrolled into one of five trial arms and followed to 12 months post-partum. The primary outcome will be infant brain development at six months, with micronutrient status, growth and neurocognitive development to 12 months as secondary outcomes. This novel research will identify the most efficacious way of improving micronutrient status in infancy, and assess impact on infant developmental outcomes, providing an evidence base for future effectiveness trials and policy recommendations. ISRCTN registry ( ISRCTN15063705, 09/07/2021); Pan African Clinical Trials Registry ( PACTR202201552774601, 21/01/2022).

Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of cancer chemotherapy that can often limit treatment options for cancer patients or have life-long neurodegenerative consequences that reduce the patient's quality of life. CIPN is caused by the detrimental actions of various chemotherapeutic agents on peripheral axons. Currently, there are no approved preventative measures or treatment options for CIPN, highlighting the need for the discovery of novel therapeutics and improving our understanding of disease mechanisms. In this study, we utilized human-induced pluripotent stem cell (hiPSC)-derived motor neurons as a platform to mimic axonal damage after treatment with vincristine, a chemotherapeutic used for the treatment of breast cancers, osteosarcomas, and leukemia. We screened a total of 1902 small molecules for neuroprotective properties in rescuing vincristine-induced axon growth deficits. From our primary screen, we identified 38 hit compounds that were subjected to secondary dose response screens. Six compounds showed favorable pharmacological profiles - AZD7762, A-674563, Blebbistatin, Glesatinib, KW-2449, and Pelitinib, all novel neuroprotectants against vincristine toxicity to neurons. In addition, four of these six compounds also showed efficacy against vincristine-induced growth arrest in human iPSC-derived sensory neurons. In this study, we utilized high-throughput screening of a large library of compounds in a therapeutically relevant assay. We identified several novel compounds that are efficacious in protecting different neuronal subtypes from the toxicity induced by a common chemotherapeutic agent, vincristine which could have therapeutic potential in the clinic.

Human organoid model of pontocerebellar hypoplasia 2a recapitulates brain region-specific size differences.

Pontocerebellar hypoplasia type 2a (PCH2a) is an ultra-rare, autosomal recessive pediatric disorder with limited treatment options. Its anatomical hallmark is hypoplasia of the cerebellum and pons accompanied by progressive microcephaly. A homozygous founder variant in TSEN54, which encodes a tRNA splicing endonuclease (TSEN) complex subunit, is causal. The pathological mechanism of PCH2a remains unknown due to the lack of a model system. Therefore, we developed human models of PCH2a using regionalized neural organoids. We generated induced pluripotent stem cell (iPSC) lines from three males with genetically confirmed PCH2a and subsequently differentiated cerebellar and neocortical organoids. Mirroring clinical neuroimaging findings, PCH2a cerebellar organoids were reduced in size compared to controls starting early in differentiation. Neocortical PCH2a organoids demonstrated milder growth deficits. Although PCH2a cerebellar organoids did not upregulate apoptosis, their stem cell zones showed altered proliferation kinetics, with increased proliferation at day 30 and reduced proliferation at day 50 compared to controls. In summary, we generated a human model of PCH2a, providing the foundation for deciphering brain region-specific disease mechanisms. Our first analyses suggest a neurodevelopmental aspect of PCH2a.

Investigating femoral growth disruption in subadults from the 10th-13th century St. Étienne cemetery of Toulouse, France.

The skeleton embodies an individual's environment and lived experiences. Studying childhood growth disruption can, therefore, aid in understanding the experiences of children in the past. This study evaluates growth disruption in a medieval Toulousian subadult sample to explore factors that may have influenced childhood growth and mortality at this site and to assess the utility of Harris line (HL) interpretations in bioarchaeology. Femoral growth disruption was assessed in n = 71 subadults (0.125-12.42 years) from the 10th-13th century St. Étienne cemetery of Toulouse, France, using femoral length, total area, cortical area, and relative cortical area. Femoral radiographs were assessed for HLs. To determine the prevalence of growth disruption, z-scores were calculated using data from the Denver growth study. The majority of subadults in this sample suffered from femoral growth disruption. Young children (1.0-3.99 years) were the most affected, with >65% experiencing reduced appositional growth and linear growth stunting at time-of-death. Additionally, while many individuals presented with observable HLs, linear and appositional growth did not significantly differ between individuals with and without HLs. Maternal malnutrition and inadequate complementary feeding practices likely contributed to the high prevalence of growth disruption among the youngest individuals in the study. The older children and adolescents buried at St. Étienne experienced an amelioration in growth deficits, indicating an improvement in nutrition and/or disease load. The results of this study suggest that more consideration is required when interpreting the presence/absence of HLs, and that studies assessing HLs may benefit from using a more individualistic approach.

Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADRβ2 Content, and Improved Myoblast Function and Muscle Growth.

Intrauterine growth-restricted (IUGR) fetuses exhibit systemic inflammation that contributes to programmed deficits in myoblast function and muscle growth. Thus, we sought to determine if targeting fetal inflammation improves muscle growth outcomes. Heat stress-induced IUGR fetal lambs were infused with eicosapentaenoic acid (IUGR+EPA; n = 9) or saline (IUGR; n = 8) for 5 days during late gestation and compared to saline-infused controls (n = 11). Circulating eicosapentaenoic acid was 42% less (p < 0.05) for IUGR fetuses but was recovered in IUGR+EPA fetuses. The infusion did not improve placental function or fetal O2 but resolved the 67% greater (p < 0.05) circulating TNFα observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p < 0.05) in the ex vivo differentiation of IUGR myoblasts was resolved in IUGR+EPA myoblasts. Semitendinosus, longissimus dorsi, and flexor digitorum superficialis muscles were 24-39% lighter (p < 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p < 0.05) IL6R and reduced (p < 0.05) β2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished β2 adrenergic sensitivity. Although IL6R remained elevated, β2 adrenoceptor deficits were resolved in IUGR+EPA muscle, demonstrating a unique underlying mechanism for muscle dysregulation. These findings show that fetal inflammation contributes to IUGR muscle growth deficits and thus may be an effective target for intervention.

Early ophthalmic growth deficits in preterm-born children are not compensated for during later development.

The renewed focus on eye growth in preterm-born children was primarily triggered by Danish cohort studies, including the Copenhagen Project, which focused on children born from 1959-1961. The retinotoxic effects of excessive oxygen on premature neonates had long been clarified and therapeutically adjusted for. Later, ultrasound oculometry and keratometry established that ocular size deficits, linked to development, also occurred in normally developing children, not just frail outliers. This indicated that general catch-up had not been achieved. This paper discusses whether one early segment of eye development does not occur in preterm, and here even in more robust neonates, without later compensation.

Integration of Sustainability in Risk Management and Operational Excellence through the VIKOR Method Considering Comparisons between Multi-Criteria Decision-Making Methods

In the current context, organizations face an important challenge in managing risks related to environmental, social and governance (ESG) issues. This research presents a general method for prioritizing organizational risks with a focus on sustainability based on the characterization of five typologies of organizational risks and their respective sub-risks, based on an analysis of global reports. Subsequently, paired surveys are administered to a group of experts from various sectors, who assign importance to the organizational sub-risks. Their responses serve as the basis for the prioritization of these risks, using the VIšekriterijumsko KOmpromisno Rangiranje (VIKOR) method, which highlights the following most relevant organizational sub-risks for each type of risk: (1) Lack of ethics in the conduct of business (geopolitical risk); (2) Deficit in economic growth (economic risk); (3) Chemical safety (social risk); (4) Massive data fraud or theft incidents (technological risk); and (5) Water depletion (environmental risk). Additionally, a sensitivity analysis is performed to determine the robustness of the results of the VIKOR method and then compare the correlation coefficients with respect to the results obtained in previous studies for the AHP and ANP methods. Finally, we propose the implementation of a model to manage organizational risks, which are addressed proactively through an integral vision, allowing for continuous improvement and alignment with corporate strategy by means of an operational excellence management system (OEMS).

Research on Financial Crisis Warning Based on Vulnerability Index

After the global financial crisis in 2008, the early warning of financial crisis has become a necessary and urgent issue. It is of great significance to analyze the factors affecting financial crisis and clarify the relationship between credit growth, housing price fluctuation, current account deficit and financial risk in order to objectively and accurately predict the degree of influence of financial risk. This paper takes 41 global economies, including developed economies and emerging economies, from 1980 to 2019 as research objects, and analyzes the early warning ability of financial vulnerability indicators such as credit growth, housing price and current account deficit in a unified framework through panel Logit model. It is found that credit is not the only important indicator to predict crisis: when housing price, current account deficit and credit are under the same research framework, housing price and current account deficit have a lot of leading information, which can predict the occurrence of financial crisis; However, as house prices and current account deficits are added to the model, the early-warning power of credit is significantly lower than that of house prices. Paying attention to house price fluctuations and current account deficits has some implications for future policy making. In view of this, we should do a good job of cross-cycle policy adjustment, persist in curbing real estate financialization and bubbles, pay close attention to the direction and extent of current account adjustment, and prudently manage related financial risks.

In Vivo Administration of Phosphatidic Acid, a Direct Alcohol Target Rescues Fetal Growth Restriction and Maternal Uterine Artery Dysfunction in Rat FASD Model.

Fetal growth restriction is a hallmark of Fetal Alcohol Syndrome (FAS) and is accompanied by maternal uterine circulatory maladaptation. FAS is the most severe form of Fetal Alcohol Spectrum Disorder (FASD), a term for the range of conditions that can develop in a fetus when their pregnant mother consumes alcohol. Alcohol exerts specific direct effects on lipids that control fundamental developmental processes. We previously demonstrated that direct in vitro application of phosphatidic acid (PA, the simplest phospholipid and a direct target of alcohol exposure) to excised uterine arteries from alcohol-exposed rats improved vascular function, but it is unknown if PA can rescue end organ phenotypes in our FASD animal model. Pregnant Sprague-Dawley rats (n = 40 total dams) were gavaged daily from gestational day (GD) 5 to GD 19 with alcohol or maltose dextrin, with and without PA supplementation, for a total of four unique groups. To translate and assess the beneficial effects of PA, we hypothesized that in vivo administration of PA concomitant with chronic binge alcohol would reverse uterine artery dysfunction and fetal growth deficits in our FASD model. Mean fetal weights and placental efficiency were significantly lower in the binge alcohol group compared with those in the control (p < 0.05). However, these differences between the alcohol and the control groups were completely abolished by auxiliary in vivo PA administration with alcohol, indicating a reversal of the classic FAS growth restriction phenotype. Acetylcholine (ACh)-induced uterine artery relaxation was significantly impaired in the uterine arteries of chronic in vivo binge alcohol-administered rats compared to the controls (p < 0.05). Supplementation of PA in vivo throughout pregnancy reversed the alcohol-induced vasodilatory deficit; no differences were detected following in vivo PA administration between the pair-fed control and PA alcohol groups. Maximal ACh-induced vasodilation was significantly lower in the alcohol group compared to all the other treatments, including control, control PA, and alcohol PA groups (p < 0.05). When analyzing excitatory vasodilatory p1177-eNOS, alcohol-induced downregulation of p1177-eNOS was completely reversed following in vivo PA supplementation. In summary, these novel data utilize a specific alcohol target pathway (PA) to demonstrate a lipid-based preventive strategy and provide critical insights important for the development of translatable interventions.

Growth Patterns Between Ages 0 and 36 Months Among US Children With Orofacial Cleft: A Retrospective Cohort Study

BackgroundLittle is known about how young children with orofacial cleft grow over time. ObjectiveTo characterize longitudinal growth patterns from ages 0 to 36 months in US children with an orofacial cleft. DesignA retrospective cohort study. Participants/settingChildren with cleft lip, cleft lip and palate, or cleft palate who were younger than age 36 months at a hospital encounter between 2010 and 2019 (N = 1334) were included. The setting was a US tertiary care children’s hospital with a cleft center that serves a 5-state region. Main outcome measureWeight-for-age z scores (WAZ) and length-for-age z scores (LAZ). Statistical analyses performedLongitudinal growth patterns were characterized using generalized linear mixed models to estimate mean WAZ and LAZ from age 0 to 36 months. ResultsGrowth in infants with cleft slowed dramatically during the first 3 to 4 months of life, rebounded with catch-up growth until age 12 months for cleft lip and cleft palate and until age 36 months for cleft lip and palate. When comparing populations, children with any type of cleft demonstrated subpar growth compared with World Health Organization standards. Growth deficits were more common in those with cleft lip and palate and cleft palate compared with those with cleft lip. The intraclass coefficient showed that most of the variability in the WAZ (65%) was between individuals, whereas 35% was within an individual. The intraclass coefficient for LAZ showed that most of the variability in the LAZ (74%) was between individuals, whereas 26% was within an individual. The proportion of variance attributable to cleft type and/or comorbidities accounted for <5% of the variance for WAZ and LAZ. WAZ and LAZ were lower in children with comorbidities than those without comorbidities with cleft and World Health Organization standards. ConclusionsInfants with cleft lip and palate, cleft palate, and a cleft with comorbidities have higher rates of poor growth than peers with cleft lip and a cleft with no comorbidities, respectively.

Skeletal myoblast proliferation and differentiation are reduced in growth restricted fetal sheep

Fetal growth restriction (FGR) increases the risk of type 2 diabetes due in part to deficits in fetal skeletal muscle growth that are not fully compensated after birth. During prenatal development, muscle progenitor cells proliferate, differentiate, and fuse with existing fibers to support myofiber hypertrophy. The total number of myofibers is set in utero, and reductions in myofiber number, size, and myonuclear accretion suggest that myogenesis is impaired in FGR. Previous studies identify similar rates of proliferation and differentiation in FGR and control (CON) myoblasts exposed to enriched growth media in vitro, despite deficits in myoblast proliferation/differentiation in whole muscle of FGR fetuses. Whether muscle progenitor cells of FGR fetuses exhibit impaired myogenic capacity in vivo remains unknown. Using a novel flow cytometry approach to quantify stages of myogenesis in vivo, we aimed to identify the cellular origins of dysregulated skeletal muscle development in FGR due to placental insuffciency. Pregnant sheep were exposed to elevated temperatures (n=15) from early to mid-gestation to induce placental insuffciency and subsequent FGR, defined as birth weight 2 SD below the mean for gestational age. At 90% gestation, fetuses were weighed, and muscle progenitor cells were isolated from biceps femoris of FGR (n=8) and CON (n=5) fetuses for flow cytometry. Muscle cells were identified by anti-CD56, anti-Pax7, and live/dead dye. DAPI was used to quantify resting (G0/1) versus replicating (S/G2) myoblasts. Myogenic regulatory factors, anti-MyoD and anti-myogenin (MyoG), distinguished non-committed (MyoD-/MyoG-) and activated (MyoD+/MyoG-) myoblasts from those beginning (MyoD+/MyoG+) and completing (MyoD-/MyoG+) differentiation. Statistical significance was determined by Student’s t-tests with α=0.05. Percentages are relative to total myoblasts (live, singlets expressing Pax7/CD56). Total myoblasts per live singlets were not different between FGR and CON muscle. FGR fetuses had more muscle progenitors in G0/1 (97% vs 95%, p&lt;0.0001) and fewer replicating myoblasts in S/G2 compared to CON (3% vs 5%, p&lt;0.0001). Myofactor analysis found decreased activated myoblasts (MyoD+/MyoG-) in FGR versus CON (2.5% vs 5%, p&lt;0.005), though the fraction of non-committed progenitors (MyoD-/MyoG-) was similar between groups (14% vs 15%). Despite reduced myogenic induction in FGR, there were no differences between FGR and CON myoblasts expressing MyoG in early (MyoD+, 38% vs 47%) or terminal differentiation (MyoD-, 47% vs 34%). Correlation analyses of all fetuses (n=15) revealed positive relationships between fetal weight and MyoD+/MyoG- (r=0.57) as well as MyoD+/MyoG+ myoblasts (r=0.56), while MyoD-/MyoG+ cells correlated negatively with fetal weight (r=-0.60). FGR fetuses have decreased myoblast proliferation in vivo. Myogenic lineage commitment is reduced in FGR progenitor cells, and positive correlations between fetal weight and myogenic induction suggest that deficits in muscle size and body mass may result from impaired initiation of myogenesis in utero. The elevated percentage of terminally differentiated myocytes in low birthweight fetuses may be a consequence of impaired fusion, which likely contributes to reductions in myonuclei within FGR myofibers. Since the capacity for growth is conserved in FGR skeletal muscle, indicated by retention of myoblast number and proliferation/differentiation capacity in vitro, therapies that stimulate myogenic induction and/or myoblast fusion during fetal development may be necessary/suffcient to restore muscle growth in FGR. NIH R01HD079404; Evonuk Graduate Fellowship; UO VPRI funds. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.