Effect of Roflumilast, a Selective PDE4 Inhibitor, on Bone Phenotypes in ADO2 Mice.

Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption that usually results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene. We previously created mouse models of ADO2 (p.G213R) with one of the most common mutations (G215R) as found in humans and demonstrated that this mutation in mice phenocopies the human disease of ADO2. Previous studies have shown that roflumilast (RF), a selective phosphodiesterase 4 (PDE4) inhibitor that regulates the cAMP pathway, can increase osteoclast activity. We also observed that RF increased bone resorption in both wild-type and ADO2 heterozygous osteoclasts in vitro, suggesting it might rescue bone phenotypes in ADO2 mice. To test this hypothesis, we administered RF-treated diets (0, 20 and 100 mg/kg) to 8-week-old ADO2 mice for 6 months. We evaluated bone mineral density and bone micro-architecture using longitudinal in-vivo DXA and micro-CT at baseline, and 6-, 12-, 18-, and 24-week post-baseline time points. Additionally, we analyzed serum bone biomarkers (CTX, TRAP, and P1NP) at baseline, 12-, and 24-week post-baseline. Our findings revealed that RF treatment did not improve aBMD (whole body, femur, and spine) and trabecular BV/TV (distal femur) in ADO2 mice compared to the control group treated with a normal diet. Furthermore, we did not observe any significant changes in serum levels of bone biomarkers due to RF treatment in these mice. Overall, our results indicate that RF does not rescue the osteopetrotic bone phenotypes in ADO2 heterozygous mice.

Using AI to Write a Review Article Examining the Role of the Nervous System on Skeletal Homeostasis and Fracture Healing.

PURPOSE OF REVIEW: Three review articles have been written that discuss the roles of the central and peripheral nervous systems in fracture healing. While content among the articles is overlapping, there is a key difference between them: the use of artificial intelligence (AI). In one paper, the first draft was written solely by humans. In the second paper, the first draft was written solely by AI using ChatGPT 4.0 (AI-only or AIO). In the third paper, the first draft was written using ChatGPT 4.0 but the literature references were supplied from the human-written paper (AI-assisted or AIA). This project was done to evaluate the capacity of AI to conduct scientific writing. Importantly, all manuscripts were fact checked and extensively edited by all co-authors rendering the final manuscript drafts significantly different from the first drafts. RECENT FINDINGS: Unsurprisingly, the use of AI decreased the time spent to write a review. The two AI-written reviews took less time to write than the human-written paper; however, the changes and editing required in all three manuscripts were extensive. The human-written paper was edited the most. On the other hand, the AI-only paper was the most inaccurate with inappropriate reference usage and the AI-assisted paper had the greatest incidence of plagiarism. These findings show that each style of writing presents its own unique set of challenges and advantages. While AI can theoretically write scientific reviews, from these findings, the extent of editing done subsequently, the inaccuracy of the claims it makes, and the plagiarism by AI are all factors to be considered and a primary reason why it may be several years into the future before AI can present itself as a viable alternative for traditional scientific writing.

Role of the Neurologic System in Fracture Healing: An Extensive Review.

PURPOSE OF REVIEW: Despite advances in orthopedics, there remains a need for therapeutics to hasten fracture healing. However, little focus is given to the role the nervous system plays in regulating fracture healing. This paucity of information has led to an incomplete understanding of fracture healing and has limited the development of fracture therapies that integrate the importance of the nervous system. This review seeks to illuminate the integral roles that the nervous system plays in fracture healing. RECENT FINDINGS: Preclinical studies explored several methodologies for ablating peripheral nerves to demonstrate ablation-induced deficits in fracture healing. Conversely, activation of peripheral nerves via the use of dorsal root ganglion electrical stimulation enhanced fracture healing via calcitonin gene related peptide (CGRP). Investigations into TLR-4, TrkB agonists, and nerve growth factor (NGF) expression provide valuable insights into molecular pathways influencing bone mesenchymal stem cells and fracture repair. Finally, there is continued research into the connections between pain and fracture healing with findings suggesting that anti-NGF may be able to block pain without affecting healing. This review underscores the critical roles of the central nervous system (CNS), peripheral nervous system (PNS), and autonomic nervous system (ANS) in fracture healing, emphasizing their influence on bone cells, neuropeptide release, and endochondral ossification. The use of TBI models contributes to understanding neural regulation, though the complex influence of TBI on fracture healing requires further exploration. The review concludes by addressing the neural connection to fracture pain. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.

PURPOSE OF REVIEW: The traditionally understated role of neural regulation in fracture healing is gaining prominence, as recent findings underscore the peripheral nervous system's critical contribution to bone repair. Indeed, it is becoming more evident that the nervous system modulates every stage of fracture healing, from the onset of inflammation to repair and eventual remodeling. RECENT FINDINGS: Essential to this process are neurotrophins and neuropeptides, such as substance P, calcitonin gene-related peptide, and neuropeptide Y. These molecules fulfill key roles in promoting osteogenesis, influencing inflammation, and mediating pain. The sympathetic nervous system also plays an important role in the healing process: while local sympathectomies may improve fracture healing, systemic sympathetic denervation impairs fracture healing. Furthermore, chronic activation of the sympathetic nervous system, often triggered by stress, is a potential impediment to effective fracture healing, marking an important area for further investigation. The potential to manipulate aspects of the nervous system offers promising therapeutic possibilities for improving outcomes in fracture healing. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Do Not Lose Your Nerve, Be Callus: Insights Into Neural Regulation of Fracture Healing.

PURPOSE OF REVIEW: Fractures are a prominent form of traumatic injury and shall continue to be for the foreseeable future. While the inflammatory response and the cells of the bone marrow microenvironment play significant roles in fracture healing, the nervous system is also an important player in regulating bone healing. RECENT FINDINGS: Considerable evidence demonstrates a role for nervous system regulation of fracture healing in a setting of traumatic injury to the brain. Although many of the impacts of the nervous system on fracture healing are positive, pain mediated by the nervous system can have detrimental effects on mobilization and quality of life. Understanding the role the nervous system plays in fracture healing is vital to understanding fracture healing as a whole and improving quality of life post-injury. This review article is part of a series of multiple manuscripts designed to determine the utility of using artificial intelligence for writing scientific reviews.

Mixed-Species Cover Crop Biomass Estimation Using Planet Imagery.

Cover crop biomass is helpful for weed and pest control, soil erosion control, nutrient recycling, and overall soil health and crop productivity improvement. These benefits may vary based on cover crop species and their biomass. There is growing interest in the agricultural sector of using remotely sensed imagery to estimate cover crop biomass. Four small plot study sites located at the United States Department of Agriculture Agricultural Research Service, Crop Production Systems Research Unit farm, Stoneville, MS with different cereals, legumes, and their mixture as fall-seeded cover crops were selected for this analysis. A randomized complete block design with four replications was used at all four study sites. Cover crop biomass and canopy-level hyperspectral data were collected at the end of April, just before cover crop termination. High-resolution (3 m) PlanetScope imagery (Dove satellite constellation with PS2.SD and PSB.SD sensors) was collected throughout the cover crop season from November to April in the 2021 and 2022 study cycles. Results showed that mixed cover crop increased biomass production up to 24% higher compared to single species rye. Reflectance bands (blue, green, red and near infrared) and vegetation indices derived from imagery collected during March were more strongly correlated with biomass (r = 0-0.74) compared to imagery from November (r = 0.01-0.41) and April (r = 0.03-0.57), suggesting that the timing of imagery acquisition is important for biomass estimation. The highest correlation was observed with the near-infrared band (r = 0.74) during March. The R2 for biomass prediction with the random forest model improved from 0.25 to 0.61 when cover crop species/mix information was added along with Planet imagery bands and vegetation indices as biomass predictors. More study with multiple timepoint biomass, hyperspectral, and imagery collection is needed to choose appropriate bands and estimate the biomass of mix cover crop species.

Is it home delivery or health facility? Community perceptions on place of childbirth in rural Northwest Tanzania using a qualitative approach.

BACKGROUND: In low and middle-income countries, pregnancy and delivery complications may deprive women and their newborns of life or the realization of their full potential. Provision of quality obstetric emergency and childbirth care can reduce maternal and newborn deaths. Underutilization of maternal and childbirth services remains a public health concern in Tanzania. The aim of this study was to explore elements of the local social, cultural, economic, and health systems that influenced the use of health facilities for delivery in a rural setting in Northwest Tanzania. METHODS: A qualitative approach was used to explore community perceptions of issues related to low utilization of health facilities for childbirth. Between September and December 2017, 11 focus group discussions were conducted with women (n = 33), men (n = 5) and community health workers (CHWs; n = 28); key informant interviews were conducted with traditional birth attendants (TBAs; n = 2). Coding, identification, indexing, charting, and mapping of these interviews was done using NVIVO 12 after manual familiarization of the data. Data saturation was used to determine when no further interviews or discussions were required. RESULTS: Four themes emerge; self-perceived obstetric risk, socio-cultural issues, economic concerns and health facility related factors. Health facility delivery was perceived to be crucial for complicated labor. However, the idea that childbirth was a "normal" process and lack of social and cultural acceptability of facility services, made home delivery appealing to many women and their families. In addition, out of pocket payments for suboptimal quality of health care was reported to hinder facility delivery. CONCLUSION: Home delivery persists in rural settings due to economic and social issues, and the cultural meanings attached to childbirth. Accessibility to and affordability of respectful and culturally acceptable childbirth services remain challenging in this setting. Addressing barriers on both the demand and supply side could result in improved maternal and child outcomes during labor and delivery.

The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic.

PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.

Hypophosphatemia is Prevalent among Preterm Infants Less than 1,500 Grams.

OBJECTIVE: This article identifies the prevalence and associated factors of hypophosphatemia (HP) in very low birth weight (VLBW) infants in the first week of life. STUDY DESIGN: Prospective exploratory cohort study of 106 consecutive VLBW infants admitted to neonatal intensive care at Foothills Hospital, Calgary, Canada. HP was defined as at least one measurement of serum phosphate < 1.5 mmol/L (4.5 mg/dL). RESULTS: Seventy-seven percent (82/106) of the VLBW infants had HP, with significantly higher prevalence in infants < 1,000 g (94%) compared to infants ≥ 1,000 g (61%) (p < 0.001). Hypophosphatemic infants had lower birth weight (p < 0.001), gestational age (p < 0.001), and their increase in phosphate intake was slower (p = 0.003). Respiratory distress syndrome (RDS) (p = 0.002), intraventricular hemorrhage (IVH) ≥ grade III (p = 0.020), and hyperglycemia (p = 0.013) were more frequent among hypophosphatemic infants, especially among those < 1,000 g. Mortality, seizures, arrhythmias, and need for transfusion were not different between groups. Birth weight modified the association between RDS, IVH, hyperglycemia, and HP. CONCLUSION: HP was ubiquitous among infants < 1,000 g and highly prevalent among those weighing 1,000 to 1,500 g. While the direction of effect was not clear, RDS, IVH, and hyperglycemia were associated with HP. Prevention of HP in these physiologically immature neonates might improve neonatal outcomes.

Missed opportunities in antenatal care for improving the health of pregnant women and newborns in Geita district, Northwest Tanzania.

BACKGROUND: Despite the significant benefits of early detection and management of pregnancy related complications during antenatal care (ANC) visits, not all pregnant women in Tanzania initiate ANC in a timely manner. The primary objectives of this research study in rural communities of Geita district, Northwest Tanzania were: 1) to conduct a population-based study that examined the utilization and availability of ANC services; and 2) to explore the challenges faced by women who visited ANC clinics and barriers to utilization of ANC among pregnant women. METHODS: A sequential explanatory mixed method design was utilized. Household surveys that examined antenatal service utilization and availability were conducted in 11 randomly selected wards in Geita district. One thousand, seven hundred and nineteen pregnant women in their 3rd trimester participated in household surveys. It was followed by focus group discussions with community health workers and pregnant women that examined challenges and barriers to ANC. RESULTS: Of the pregnant women who participated, 86.74% attended an ANC clinic at least once; 3.62% initiated ANC in the first trimester; 13.26% had not initiated ANC when they were interviewed in their 3rd trimester. Of the women who had attended ANC at least once, the majority (82.96%) had been checked for HIV status, less than a half (48.36%) were checked for hemoglobin level, and only a minority had been screened for syphilis (6.51%). Among women offered laboratory testing, the prevalence of HIV was 3.88%, syphilis, 18.57%, and anemia, 54.09%. In terms of other preventive measures, 91.01% received a tetanus toxoid vaccination, 76.32%, antimalarial drugs, 65.13%, antihelminthic drugs, and 76.12%, iron supplements at least once. Significant challenges identified by women who visited ANC clinics included lack of male partner involvement, informal regulations imposed by health care providers, perceived poor quality of care, and health care system related factors. Socio-cultural beliefs, fear of HIV testing, poverty and distance from health clinics were reported as barriers to early ANC utilization. CONCLUSION: Access to effective ANC remains a challenge among women in Geita district. Notably, most women initiated ANC late and early initiation did not guarantee care that could contribute to better pregnancy outcomes.

Prediction of Late Death or Disability at Age 5 Years Using a Count of 3 Neonatal Morbidities in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate bronchopulmonary dysplasia (BPD), serious brain injury, and severe retinopathy of prematurity (ROP) as predictors of poor long-term outcome in very low birth weight infants. STUDY DESIGN: We examined the associations between counts of the 3 morbidities and long-term outcomes in 1514 of 1791 (85%) infants with birth weights of 500-1250 g who were enrolled in the Caffeine for Apnea of Prematurity trial from October 1999, to October 2004, had complete morbidity data, and were alive at 36 weeks postmenstrual age (PMA). BPD was defined as use of supplemental oxygen at 36 weeks PMA. Serious brain injury on cranial ultrasound included grade 3 and 4 hemorrhage, cystic periventricular leucomalacia, porencephalic cysts, or ventriculomegaly of any cause. Poor long-term outcome was death after 36 weeks PMA or survival to 5 years with 1 or more of the following disabilities: motor impairment, cognitive impairment, behavior problems, poor general health, deafness, and blindness. RESULTS: BPD, serious brain injury, and severe ROP occurred in 43%, 13%, and 6% of the infants, respectively. Each of the 3 morbidities was similarly and independently correlated with poor 5-year outcome. Rates of death or disability (95% CI) in children with none, any 1, any 2, and all 3 morbidities were 11.2% (9.0%-13.7%), 22.9% (19.6%-26.5%), 43.9% (35.5%-52.6%), and 61.5% (40.6%-79.8%), respectively. CONCLUSIONS: In very low birth weight infants who survive to 36 weeks PMA, a count of BPD, serious brain injury, and severe ROP predicts the risk of a late death or survival with disability at 5 years.

How Do Propensity Score Methods Measure Up in the Presence of Measurement Error? A Monte Carlo Study.

Considering that the absence of measurement error in research is a rare phenomenon and its effects can be dramatic, we examine the impact of measurement error on propensity score (PS) analysis used to minimize selection bias in behavioral and social observational studies. A Monte Carlo study was conducted to explore the effects of measurement error on the treatment effect and balance estimates in PS analysis across seven different PS conditioning methods. In general, the results indicate that even low levels of measurement error in the covariates lead to substantial bias in estimates of treatment effects and concomitant reduction in confidence interval coverage across all methods of conditioning on the PS.

Biogeochemical study of termite mounds: a case study from Tummalapalle area of Andhra Pradesh, India.

Termite mounds are abundant components of Tummalapalle area of uranium mineralization of Cuddapah District of Andhra Pradesh, India. The systematic research has been carried out on the application of termite mound sampling to mineral exploration in this region. The distribution of chemical elements Cu, Pb, Zn, Ni, Co, Cr, Li, Rb, Sr, Ba, and U were studied both in termite soils and adjacent surface soils. Uranium accumulations were noticed in seven termite mounds ranging from 10 to 36 ppm. A biogeochemical parameter called "Biological Absorption Coefficient" of the termite mounds indicated the termite affected soils contained huge amounts of chemical elements than the adjacent soils.

The 'picky eater': The toddler or preschooler who does not eat.

The majority of children between one and five years of age who are brought in by their parents for refusing to eat are healthy and have an appetite that is appropriate for their age and growth rate. Unrealistic parental expectations may result in unnecessary concern, and inappropriate threats or punishments may aggravate a child's refusal to eat. A detailed history and general physical examination are necessary to rule out acute and chronic illnesses. A food diary and assessment of parental expectations about eating behaviour should be completed. Where the child's 'refusal' to eat is found to be related to unrealistic expectations, parents should be reassured and counselled about the normal growth and development of children at this age.

La majorité des enfants de un à cinq ans pour qui les parents consultent parce qu'ils refusent de manger sont en bonne santé et ont un appétit qui convient à leur âge et à leur rythme de croissance. Les attentes irréalistes des parents peuvent donner lieu à des inquiétudes inutiles, et les menaces et punitions déplacées peuvent aggraver le refus de manger de l'enfant. Les médecins doivent procéder à une anamnèse détaillée et à un examen physique général pour écarter une maladie aiguë ou chronique. Ils doivent demander un journal alimentaire et évaluer les attentes des parents à l'égard du comportement alimentaire. Lorsque le « refus de manger ¼ de l'enfant semble lié à des attentes irréalistes, il faut rassurer les parents et leur donner des conseils sur la croissance et le développement normaux des enfants de cet âge.

A history of bracing for idiopathic scoliosis in North America.

The care of the patient with scoliosis has a history extending back over two millennia with cast and brace treatment being a relatively recent endeavor, the modern era comprising just over half a century. Much of the previous literature provides a modest overview with emphasis on the history of the operative management. To better understand the current concepts of brace treatment of scoliosis, an appreciation of the history of bracing would be helpful. As such, we review the history of the treatment of scoliosis with an emphasis on modern brace treatment, primarily from a North American perspective. Our review utilizes consideration of historical texts as well as current treatises on the history of scoliosis and includes discussion of brace development with their proponents' rationale for why they work along with an appraisal of their clinical outcomes. We provide an overview of the current standards of care and the braces typically employed toward that standard including: the Milwaukee brace, the Wilmington brace, the Boston brace, the Charleston brace, the Providence brace and the SpineCor brace. Finally, we discuss future trends including improvements in methods of determining the critical period of peak growth velocity in children with scoliosis, the exciting promise of gene markers for progressive scoliosis and "internal bracing" options.

A single gestational weight gain recommendation is possible for all classes of pregnant women with obesity.

OBJECTIVES: Obesity is a known risk factor for adverse pregnancy outcomes; however, appropriate gestational weight gain (GWG) may mitigate these risks. We investigated whether the singular 2009 Institute of Medicine (IOM) GWG guidelines were appropriate for all women with obesity, or whether separate recommendations were needed by class. METHODS: This cross-sectional study of pregnant women with obesity used 2014 U.S. birth certificate data (N=646,642) and included only term pregnancies. Adjusted log-binomial regression models examined the relative risk of adverse maternal, obstetric, and neonatal outcomes for pregnant women with class I-III obesity who: lost weight during pregnancy, gained below IOM guidelines, or gained above IOM guidelines, compared to women who gained within IOM guidelines. RESULTS: Most women (55.1; 95% CI: 55.0-55.3) gained above IOM guidelines. As BMI severity increased, significantly fewer women had excessive GWG (Class I: 61.6%, 95% CI: 61.4-61.7; II: 50.7%, 95% CI: 50.4-50.9; III: 41.1%, 95% CI: 40.8-41.4). All classes of women with obesity who lost weight during pregnancy or gained below had a significantly decreased risk for caesarean delivery (RR (95% CI) class I: 0.92 (0.90-0.94); II: 0.91 (0.89-0.93); III: 0.92 (0.90-0.93)) and large-for-gestational age (LGA) births (class I: 0.80 (0.77-0.83); II: 0.76 (0.73-0.78); III: 0.73 (0.70-0.75)), but significantly increased risk of small-for-gestational age (SGA) births (class I: 1.34 (1.26-1.43); II: 1.38 (1.28-1.49); III: 1.35 (1.24-1.46)). CONCLUSION: The observed pattern of association was the same for all obese classes, hence evidence supports a possible singular GWG recommendation for all women with obesity, regardless of class.

Foxl1 promotes liver repair following cholestatic injury in mice.

Cholangiocyte proliferation is one of the hallmarks of the response to cholestatic injury. We previously reported that the winged helix transcription factor Foxl1 is dramatically induced in cholangiocytes following bile duct ligation. In this study, we investigated the function of Foxl1 in the bile duct ligation model of cholestatic liver injury in Foxl1(-/-) and control mice. We found that Foxl1(-/-) livers exhibit an increase in parenchymal necrosis, significantly impaired cholangiocyte and hepatocyte proliferation, and failure to expand bile ductular mass. Wnt3a and Wnt7b expression was decreased in the livers of Foxl1(-/-) mice along with reduced expression of the beta-catenin target gene Cyclin D1 in Foxl1(-/-) cholangiocytes. These results show that Foxl1 promotes liver repair after bile-duct-ligation-induced liver injury through activation of the canonical wnt/beta-catenin pathway.

Rescue of a Drosophila NF1 mutant phenotype by protein kinase A.

The neurofibromatosis type 1 (NF1) tumor suppressor protein is thought to restrict cell proliferation by functioning as a Ras-specific guanosine triphosphatase-activating protein. However, Drosophila homozygous for null mutations of an NF1 homolog showed no obvious signs of perturbed Ras1-mediated signaling. Loss of NF1 resulted in a reduction in size of larvae, pupae, and adults. This size defect was not modified by manipulating Ras1 signaling but was restored by expression of activated adenosine 3', 5'-monophosphate-dependent protein kinase (PKA). Thus, NF1 and PKA appear to interact in a pathway that controls the overall growth of Drosophila.

Ecological determinants of respiratory health: Examining associations between asthma emergency department visits, diesel particulate matter, and public parks and open space in Los Angeles, California.

Los Angeles County (LAC) low-income communities of color experience uneven asthma rates, evidenced by asthma emergency department visits (AEDV). This has partly been attributed to inequitable exposure to diesel particulate matter (DPM). Promisingly, public parks and open space (PPOS) contribute to DPM mitigation. However, low-income communities of color with limited access to PPOS may be deprived of associated public health benefits. Therefore, this novel study investigates the AEDV, DPM, PPOS nexus to address this public health dilemma and inform public policy in at-risk communities. Optimized Hotspot Analysis was used to examine geographic clustering of AEDVs, DPM, and PPOS at the census tract unit of analysis in LAC. Ordinary Least Squares (OLS) regression analysis was used to examine the extent to which DPM and PPOS predict AEDVs. Finally, Geographic Weighted Regression (GWR) was employed to account for spatial dependence in the global OLS model. Optimized Hotspot Analysis confirmed significant clustering of elevated AEDVs and DPM in census tracts with reduced PPOS. After controlling for pertinent demographic characteristics (poverty, children, race/ethnicity), regression analysis confirmed that DPM was significantly positively associated with AEDVs, whereas PPOS was significantly negatively associated with AEDVs. Furthermore, GWR revealed that 71.5% of LACs census tracts would benefit from DPM reductions and 79.4% would benefit from PPOS increases toward redressing AEDVs. This is the first study to identify AEDV reductions in census tracts with higher concentrations of PPOS. Thus, reducing DPM and increasing PPOS may serve to improve asthma outcomes, particularly in low-income communities of color.

The Use of Antifibrotic Recombinant nAG Protein in a Rat Liver Fibrosis Model.

OBJECTIVES: The "nAG" protein is the key protein mediating the regeneration of amputated limbs in salamanders. The senior author (MMA) developed the original hypothesis that since "nAG" is a "regenerative" protein, it must be also an "antifibrotic' protein. The antifibrotic properties were later confirmed in a rabbit skin hypertrophic scar model as well as in a rat spinal cord injury model. The aim of this study is to evaluate the potential therapeutic properties of the nAG protein in a rat liver fibrosis model. METHODOLOGY: Liver fibrosis was induced using intraperitoneal injections of carbon tetrachloride (CCL4). A total of 45 rats were divided equally into 3 groups: Group I (the control group) received normal saline injections for 8 weeks, Group II received CCL4 for 8 weeks, and Group III received CCL4 and nAG for 8 weeks. At the end of the experiment, the serum levels of 6 proteins (hyaluronic acid, PDGF-AB, TIMP-1, laminin, procollagen III N-terminal peptide, and collagen IV-alpha 1 chain) were measured. Liver biopsies were also taken and the stages of live fibrosis were assessed histologically. RESULTS: The CCL4 treatment resulted in a significant increase in the serum levels of all 6 measured proteins. The nAG treatment significantly reduced these high levels. The degree of liver fibrosis was also significantly reduced in the CCL4/nAG group compared to the CCL4 group. CONCLUSIONS: nAG treatment was able to significantly reduce the serum levels of several protein markers of liver fibrosis and also significantly reduced the histological degree of liver fibrosis.