Low Fragility Research Articles

Height prediction of individuals with osteogenesis imperfecta by machine learning

BackgroundOsteogenesis imperfecta (OI) is a genetic disorder characterized by low bone mass, bone fragility and short stature. There is a significant gap in knowledge regarding the growth patterns across different types of OI, and the prediction of height in individuals with OI was not adequately addressed. In this study, we described the growth patterns and predicted the height of individuals with OI employing multiple machine learning (ML) models. Accurate height prediction enables effective monitoring and facilitates the development of personalized intervention plans for managing OI.MethodThis study included cross-sectional data for 323 participants with OI, and the median height Z-score for OI types I, III and IV were − 0.62 (-5.93 ~ 3.24), -3.97 (-10.44 ~ -0.02) and − 1.64 (-6.67 ~ 2.44), respectively. Based on the cross-sectional data of participants, the height curves across different gender and OI types were plotted and compared. Subsequently, feature selection techniques, specifically the filter and wrapper methods, were employed to identify predictive factors for the height of participants. Finally, multiple machine learning (ML) models were constructed for height prediction, and the performance of each model was systematically evaluated.ResultsThe analysis of height curves revealed that male with OI are significantly taller than female with OI from the age of 14 (p = 0.045), individuals with OI type III are statistically shorter than those with OI types I and IV starting from 3 years old (p = 0.006), and those with OI type IV are statistically shorter than those with OI type I from the age of 10 (p = 0.028). The application of filter and wrapper methods identified gender (p = 0.001), age (p < 0.001), Sillence types (p = 0.007), weight Z-score (p < 0.001) and aBMD Z-score (p = 0.021) as significant predictive factors for height. The optimal performance of predictive models was registered by gradient boosting classifier (GB) (bias = 5.783, accuracy = 92.59%, R2 = 0.828), random forest (RF) (bias = 6.155, accuracy = 90.12%, R2 = 0.788), ensemble machine learning (EML) (bias = 6.250, accuracy = 91.36%, R2 = 0.825) and deep neuron networks (DNNs) (bias = 6.223, accuracy = 90.12%, R2 = 0.821).ConclusionThis study analyzed a large cohort of individuals with OI and provided detailed height patterns across different gender and OI types that are crucial for assessing overall growth. Gender, age, Sillence types, weight Z-score and aBMD Z-score were identified as predictive factors for height. The predictive models of GB, RF, EML and DNNs had higher accuracy to evaluate the height of individuals with OI. This study allows guardians and physicians to timely monitor the height parameters, and facilitate the creation of personalized intervention schedules tailored to the needs of individuals with OI.

Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia.

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically-determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and four BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an AUC of 0.962 with a cut-off of 32μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32U/L (i.e., the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment.

Evaluation of the robustness of randomized controlled trials for the treatment modalities of esophageal cancer using the fragility index - a systematic review.

Esophageal cancer remains a significant global health challenge. Several treatment modalities were explored in randomized controlled trials (RCTs) in recent decades. This study evaluates the robustness of RCTs focusing on esophageal cancer treatment using the fragility index (FI) and reverse fragility index (RFI). A systematic review of RCTs studying different treatment modalities for esophageal cancer from 2000 to 2023 was conducted. The FI and RFI were utilized to gauge the robustness of statistically significant and non-significant outcomes, respectively. The FI represents the minimal number of patient outcomes that would need to alter to overturn a trial's statistical significance, while RFI indicates the minimal changes required to achieve significance in non-significant results. Out of 4028 studies retrieved, 21 RCTs were included for final analysis. The studies spanned 2001 to 2023 with a mean followup of 66 months (range, 29-108 months) and median number of patients of 194 (range, 45-802). The most common treatment modalities examined in these studies were neoadjuvant chemoradiotherapy (n = 7, 33.3%), neoadjuvant chemotherapy (n = 4, 19.0%), and neoadjuvant immunotherapy (n = 2, 9.5%). Only 5 studies (23.8%) had a statistically significant primary outcome result with a median FI of 6 (IQR, 2.5-8.5). Non-significant primary outcomes were seen in 16 studies (76.2%) with a median RFI of 4 (IQR 1-11) and lost to followup of 0 (IQR 0-4). In the study with the highest FI (10), the FI was lower than the number of patients lost to followup (13). Our findings demonstrate that most RCTs on esophageal cancer treatments did not report significant primary outcomes. The few studies that reported significant results had a low fragility index, suggesting a vulnerability in their findings.

Low bone mineral density and its influencing factors in spinal muscular atrophy without disease-modifying treatment: a single-centre cross-sectional study

BackgroundChildren with spinal muscular atrophy (SMA) are at risk of low bone mineral density (BMD) and bone fragility. This study aims to assess lumbar spine BMD measured by quantitative computed tomography (QCT) and investigate influencing factors of low BMD in children with SMA without disease-modifying treatment.MethodsDemographic data, laboratory parameters, QCT data, and data on spinal radiographs were collected. A linear regression model was carried out to explore the correlations between BMD and its related factors.ResultsSixty-six patients with SMA who had complete records between July 2017 and July 2023 were analyzed, with SMA with a mean age of 5.4 years (range, 2.4–9.7 years), including type 1 in 14, type 2 in 37, and type 3 in 15. 28.8% of patients (19/66) were diagnosed with low BMD (Z-scores ≤ − 2), and the mean BMD Z-scores on QCT was − 1.5 ± 1.0. In our model, BMD Z-scores was associated with age (β=-0.153, p = 0.001). SMA phenotype and serum bone metabolism markers, such as serum phosphorus (P), alkaline phosphatase (ALP) and 25-Hydroxyvitamin D (25-OH-D) levels did not independently predict low BMD. ROC analysis showed that the age ≥ 6.3 years predicts a Z-scores ≤ -2.0 with a sensitivity of 68.4% and a specificity of 68.1%.ConclusionsLow BMD were highly prevalent in children with SMA without disease-modifying treatment in our centre. Regular monitoring of BMD is necessary for all types of SMA children, especially those aged ≥ 6.3 years.

DXA In People Living With HIV

Abstract Background As people with HIV now live a near normal life-span, prevention of fractures is increasingly important. Alongside conventional risk factors for fractures, antiretrovirals and chronic inflammation are believed to contribute to their increased fracture risk compared to the general population. Methods We audited a 1-year series of consecutive DXA scans conducted on people living with HIV vs the European AIDS Clinical Society guidelines on bone health. These guidelines specify indications for DXA, for repeat DXA and for osteoporosis treatment. We recorded DXA results, any prior DXA, fracture history, fracture risks and drug treatment history. We assessed frequency of scanning and pharmacological management of low bone mass vs. guidelines. Results N=90 referred for DXA, of whom 18% did not attend, leaving n=74; 58% female, 42% male, median age 52 years [36-64] and 56 years [49-69] respectively. Of the 18% (n=14) who were aged under 50, 43% had no clear indication (fracture risk factor) for DXA. Of those aged &amp;gt;50 years (n=60), all scans were indicated as the guidelines advises this in those aged &amp;gt;50 years. Bone density was normal in n=32 (43%), osteopenic in 36 (49%) and osteoporotic in 7 (9%). Fifteen percent overall had a fragility fracture history, none of whom were taking osteoporosis treatment though it was indicated in at least 4 based on their DXA result. N=12 (16%) had a DXA in preceding years, and just 2 of the repeat scans were indicated according to guidelines. For the 12 with serial scans, there was no significant change in T score after a median three-year period. Conclusion Through an audit of consecutive DXA referrals, rather than consecutive individuals, low bone mass and fragility fractures are prevalent in people living with HIV. With advancing age, fracture incidence may rise sizeable in this group therefore due attention to bone health guidelines in required.

A comparison between IBEX bone health applied to digital radiographs and dual-energy X-ray absorptiometry at the distal-third and ultra-distal regions of the radius

BackgroundIn an ageing population, low impact fragility fractures are becoming increasingly common. However, fracture risk can be reduced where low bone density can be identified at an early stage. In this study we aim to demonstrate that IBEX Bone Health (IBEX BH) can provide a clinically useful prediction from wrist radiographs of aBMD and T-score at the ultra-distal (UD) and distal-third (DT) regions of the radius.MethodsA 261-participant single-centre, non-randomised, prospective, study was carried out to compare a) IBEX BH, a quantitative digital radiography software device, to b) Dual-energy X-ray Absorptiometry (DXA). A total of 257 participants with wrist digital radiograph (DR), forearm DXA pairs were included in the analysis after exclusions.ResultsThe adjusted R2 value for IBEX BH outputs to the radial areal bone mineral density (aBMD) produced by a GE Lunar DXA system for the UD region is 0.87 (99% Confidence Interval (CI) [0.84, 0.89]). The adjusted R2 value for IBEX BH outputs to aBMD for the DT region is 0.88 (99% CI [0.85, 0.90]). The Area Under the Receiver Operating Characteristic curve (AUC) for the forearm T-score ≤ − 2.5 risk prediction model at the UD region is 0.95 (99% CI [0.93, 0.98]). The AUC for the forearm T-score ≤ − 2.5 risk prediction model at the DT region is 0.98 (99% CI [0.97, 0.99]).ConclusionFrom a DR of the wrist, IBEX BH provides a clinically useful i) estimate of aBMD at the two regions of interest on the radius and ii) risk prediction model of forearm T-score ≤ − 2.5 at the UD and DT regions.

Current situation of osteogenesis imperfecta in Spain: results from a Delphi study

BackgroundOsteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and extra-skeletal symptoms that results in an impairment of health-related quality of life of OI patients. Since published studies on OI in Spain are limited, this study aimed to determine the epidemiology, assessed the disease burden, management and unmet needs of OI patients in Spain. Thirty-four experts in the management of patients with osteogenesis imperfecta completed two rounds of online consultation and reported real-life experience and data from Spanish hospitals. Delphi study questionnaires were based on literature review. A working group of nationally recognized clinical experts supported the development of the study questionnaires and the final validation of results.ResultsThe estimated prevalence of patients diagnosed with OI in Spain is 0.56:10,000 inhabitants (95%CI: 0.54–0.59), which represents that, approximately, 2,669 OI patients are currently managed in Spanish hospitals. It is estimated that approximately 269 new patients would be diagnosed with OI each year in Spain, representing an estimated incidence of 0.06 (95%CI: 0.05–0.06) per 10,000 inhabitants per year. Clinical management of OI in Spain is performed by a range of medical specialists; however, multidisciplinary care is not fully implemented. The absence of an approved curative treatment or a treatment to reduce the clinical features of the disease remains the main unmet need.ConclusionsThis study provides a snapshot of the current situation of patients with OI in Spain reported by clinical experts. The results provide an estimation of the epidemiology of the disease, and complement the available evidence on disease burden, clinical management, and unmet needs of these patients in Spain.

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

OA19 Self-reported prevalence and impact of clinical signs, symptoms and events in adults with osteogenesis imperfecta

Assessment of Bone Mineral Density in a cohort of Juvenile Idiopathic Arthritis patients

Introduction: Low bone mass is encountered in patients with Juvenile idiopathic arthritis (JIA) as a serious long-term complication of this pediatric condition and may be associated with fractures and its complications.&#x0D; The present study aimed to evaluate the frequency of low bone mineral density (BMD) and fragility fractures in patients with JIA in its polyarticular or oligo articular forms. Secondary, our aim was to identify factors associated with low bone mass.&#x0D; Patients and methods: This is a retrospective study conducted on 26 patients with JIA meeting the ILAR criteria for poly or oligoarticular form. Patients were divided into two groups according to their age : group1 including patients aged over 16 years-old and group 2 including patients aged under 16 years-old. Sociodemographic, clinical, biological and functional data were collected by consulting patient’s medical records. Bone mineral density was measured at three different sites: whole body, lumbar spine and hip using the dual-energy X-ray absorptiometry (DXA) equipment. Data were entered and analyzed using SPSS version 11.5 software.&#x0D; Results: Twenty-six JIA patients including 20 females (74.1%) and six males (22.2%) were enrolled with a mean disease duration of 20.23 years [2-54 years]. The mean age was 28.2 years [7-58 years]. The distribution of JIA subtypes among patients was as follows: 6 with oligo articular JIA and 20 with polyarticular JIA. Sixteen patients (59%) practiced regular physical activity. In our series, the frequency of low bone mineral density was 41% in children with JIA and 68 % in adults with JIA. Only two patients presented a fragility fracture in adulthood represented by a hip fracture following low-energy trauma and treated surgically in both cases. No patient received an anti-osteoporotic treatment. In-group 1, there was a significant correlation between low bone mass and weight (p=0.020), BMI (p=0.028), disease duration (p=0.045), positivity of AAN (p=0.050), disease activity (p=0.019), oral corticosteroid (p=0.034) and biologic treatment (p=0.043). In-group 2, a statistically significant correlation was found between low bone mass and age at the time of JIA diagnosis (p=0.041), weight (p=0.03), physical activity (p=0.05), disease duration (p=0.021), functional impact of the disease assessed by the HAQ score (p=0.018), oral corticosteroid therapy (p=0.014) and biological therapy (p=0.012).&#x0D; Conclusion: our study showed that a combination of factors contributed to compromise bone health in patients with JIA. Fragility fractures were rare and occurring mainly in adulthood. An adequate control of disease activity, proper management of treatment, adequate calcium and vitamin D intake, as well as regular physical activity, may contribute to preserve bone health in those patients.

Study of bone mineral density in medical faculties and students of Tezpur medical college and hospital

To examine the prevalence of low bone mineral density among the faculties and students of Tezpur medical college and hospital Hospital based cross-sectional study. Study will be conducted in the department of orthopaedics, Tezpur medical college and hospital for a period of 1 year. All faculties and students above 18 years attending outpatient department of orthopaedics were included in the study. Mean T-score among health staffs is -1.4. Maximum people in health staff groups are osteopenic with T-score of -1 to -2.5 comprising of 42%. Mean T-score among students is -1.2 with majority students is normal with T-score comprising of 52%. 45 patients had severe established osteoporosis. It was found that most individual in osteoporotic group had age group above 45 years.Ultrasonography can predict hip fractures and vertebral fractures. People with low bone mass and fragility fractures have osteoporosis and should be treated.

New Perspectives of Therapies in Osteogenesis Imperfecta-A Literature Review.

(1) Background: Osteogenesis imperfecta (OI) is a rare skeletal dysplasia characterized as a heterogeneous disorder group with well-defined phenotypic and genetic features that share uncommon bone fragility. The current treatment options, medical and orthopedic, are limited and not efficient enough to improve the low bone density, bone fragility, growth, and mobility of the affected individuals, creating the need for alternative therapeutic agents. (2) Methods: We searched the medical database to find papers regarding treatments for OI other than conventional ones. We included 45 publications. (3) Results: In reviewing the literature, eight new potential therapies for OI were identified, proving promising results in cells and animal models or in human practice, but further research is still needed. Bone marrow transplantation is a promising therapy in mice, adults, and children, decreasing the fracture rate with a beneficial effect on structural bone proprieties. Anti-RANKL antibodies generated controversial results related to the therapy schedule, from no change in the fracture rate to improvement in the bone mineral density resorption markers and bone formation, but with adverse effects related to hypercalcemia. Sclerostin inhibitors in murine models demonstrated an increase in the bone formation rate and trabecular cortical bone mass, and a few human studies showed an increase in biomarkers and BMD and the downregulation of resorption markers. Recombinant human parathormone and TGF-β generated good results in human studies by increasing BMD, depending on the type of OI. Gene therapy, 4-phenylbutiric acid, and inhibition of eIF2α phosphatase enzymes have only been studied in cell cultures and animal models, with promising results. (4) Conclusions: This paper focuses on eight potential therapies for OI, but there is not yet enough data for a new, generally accepted treatment. Most of them showed promising results, but further research is needed, especially in the pediatric field.

Genetic influence on osteoporosis and fracture risk: Outcome of genome-wide association studies – A systematic review

This systematic review aimed to identify genome-wide association studies (GWASs) highlighting the genes and single-nucleotide polymorphisms linked to osteoporosis and fragility fracture risk. We searched the search engines EMBASE, MEDLINE, Scopus, Web of Science, Science Citation Index, and Cochrane database of systematic reviews between 2005 and May 2022. The articles were reviewed individually for risk of bias and found no variances in the papers designated for analysis. We analyzed 63 studies with 1,326,798 patients, which included postmenopausal and premenopausal women. Thirty-one studies used dual-energy x-ray absorptiometry (DXA) for the diagnosis. Three studies used ultrasonography, and one used peripheral quantitative computed tomography (pQCT) to diagnose osteoporosis. For the risk of fragility fractures, 15 studies with 744,123 were analyzed, which used DXA in 12, two studies of ultrasonography, and one of radiography. Three studies were reported in premenopausal women and three in children with 18,203 subjects. Our analysis showed that 150 genes, 515 loci that target bone mineral density and 15 loci that increase fracture risk in osteoporosis have been identified. Osteoporosis and fragility fractures are common in the Saudi Arabian population. The GWAS gives an understanding of the genetic basis of low bone density, osteoporosis, and fragility fractures. The GWAS data can provide new pathways to understanding the etiology of osteoporosis and a route to prevention and optimum treatment. Hence, we believe that we should conduct GWASs on osteoporosis sooner rather than later so that we can advise at-risk individuals to change their lifestyle so that they can limit complications of osteoporosis and related complications.

Correlation between fragility and surface glass transition temperature of polymers

The fragility of glass describes how rapidly its molecules slow down as it is cooled near its glass transition temperature. In nanoscale films, polymer glasses with higher fragility experience larger reductions in their Tg compared to those with lower fragility. We investigated whether this is due to the free surface of the polymers, which can cause the surface Tg (Tgsurf) to decrease relative to the bulk Tg. By measuring Tgsurf of various polymers, we found that the shift in Tgsurf relative to the bulk Tg increased with fragility. This suggests that more fragile polymers are more susceptible to the free surface effect. We explain this using the concept of energy landscape, as it is used to explain the different slowdown rates between strong and fragile glass formers at Tg.

Seismic assessment and parametric analysis on a multi-level aseismic simply-supported bridge with cable-restraining composite rubber bearings and dissipative controlled rocking piers

Recent earthquakes uncovered the potential risk of widely-used simply-supported bridges (SSBs) to suffer severe bearing and pier damage, which may not be mitigated efficiently by only enhancing one of these components. Hence, this study proposes a novel multi-level aseismic bridge system (MLABS) comprising cable-restraining composite rubber bearings (CRCRBs) and dissipative controlled rocking (DCR) piers to make improvements at the system level. Deterministic and fragility analyses are conducted to compare the seismic performance of the novel system with that of the other three reference ones. Then, an economy analysis is carried out to evaluate economic efficiency. Finally, the effects of four main influential factors are investigated. The results reveal that the novel MLABS is capable of controlling the response of each vulnerable component within an acceptable range so that it can possess a large seismic capacity and a low system fragility. The economy superiority is also proved by the lowest expected losses under the concerned events and the minimum life-cycle cost. The internal sliding area ratio of the bearings is positively related to the performance and the economy, while the optimal design free displacement of the cables is about 140 mm. The pier capacity can be weakened by increasing the initial prestressing force or the energy-dissipating bar area in this case, which reduces the effectiveness and economy in improving the structural performance.

Optimization of the Degradation Processes for Polylactic Acid using Microbial Enzymes: A Brief Summary

Polylactic acid (PLA) has emerged as a desirable bioplastic due to its production from renewable materials and biodegradability. However, its low toughness and fragility limit its applications, prompting the blending of PLA with other biopolymers to enhance its properties. As the global demand for bioplastics increases, efficient processes for PLA degradation are needed to match the high rate of plastic production. Chemical, microbial, and enzymatic processing are the major methods of PLA degradation, with enzymatic processing being environmentally friendly and sustainable. recyclable products like lactic acid can also be recovered. This creates a need to determine suitable enzymes that can hydrolyze polylactic acid. PLA exhibits high resistance to direct microbial degradation, making microbial enzymatic processing a more attractive alternative. Microbial enzymes, including proteases, lipases, esterases, and cutinases, have shown potential for PLA degradation. Nevertheless, current research on the enzymatic degradation of PLA needs comprehensive studies on optimal processes, conditions, and influencing factors. This review aims to address this gap by examining microbial enzymes and their processes for the enzymatic degradation of PLA. Findings indicate that microbial enzymes like proteinase K, Savinase, and Alcalase show promise for efficient PLA degradation under optimized conditions. Further research should, therefore, focus on exploring these enzymes further, refining enzymatic degradation processes, exploring genetic modifications of these enzymes, and developing sustainable recycling methods to advance bioplastics like PLA and address plastic pollution challenges effectively.&#x0D; &#x0D; Keywords: Polylactic acid; enzymatic degradation; microbial enzymes; optimization; bioplastic; biodegradability; plastic pollution; bioremediation.&#x0D;

Novel role for alpha-2-macroglobulin (A2M) as a disease modifying protein in senile osteoporosis.

Introduction: In the rapidly aging U.S. population, age-induced bone loss (senile osteoporosis) represents a major public health concern that is associated with a significant increased risk for low trauma fragility fractures, which are debilitating to patients, cause significant morbidity and mortality, and are costly to treat and manage. While various treatments exist to slow bone loss in osteoporosis patients, these suffer from poor tolerability and label restrictions that limit their overall effectiveness. Over the past decade, skeletal stem/progenitor cells (SSPCs), which are the main precursor of osteoblasts and adipocytes in adult bone marrow (BM), have emerged as important players in osteoporosis. Methods: Age-induced skeletal pathology was quantified in elderly (24-month-old) vs. mature (3-month-old) mice by micro-CT and changes in SSPC abundance in the BM of these mice was quantified by fluorescence-activated cell sorting (FACS). SSPCs from elderly vs. mature mice were also analyzed by RNA-Seq to identify differentially expressed genes (DEGs), and gain and loss-of-function studies were performed in human BM-derived mesenchymal stromal cells (BM-MSCs) to assess A2M function. Results: Elderly mice were shown to exhibit significant age-induced skeletal pathology, which correlated with a significant increase in SSPC abundance in BM. RNA-seq analysis identified alpha-2-macroglobulin (A2M), a pan-protease inhibitor that also binds inflammatory cytokines, as one of the most downregulated transcripts in SSPCs isolated from the BM of elderly vs. mature mice, and silencing of A2M expression in human BM-MSCs induced their proliferation and skewed their lineage bifurcation toward adipogenesis at the expense of osteogenesis thereby recapitulating critical aspects of age-induced stem cell dysfunction. Conclusion: These findings identify A2M as a novel disease modifying protein in osteoporosis, downregulation of which in bone marrow promotes SSPC dysfunction and imbalances in skeletal homeostasis.

Nanosheet architecture of MnO2/carbon with improved reaction kinetics toward advanced zinc energy storage

Aqueous zinc ion batteries (AZIBs) hold substantial promise for large-scale energy storage system by virtue of their good safety and cost-effectiveness. However, the typical cathode material of MnO2 is practically hampered by poor rate/cycling performance owing to its low electrical conductivity and structural fragility. Herein, a nanosheet architecture of MnO2/carbon is constructed via in situ rooting MnO2 nanoarrays on carbon substrate to achieve high-rate and long-durable zinc energy storage. The unique nano-architecture significantly promotes the reaction kinetics by supplying plentiful active sites, short diffusion pathways, and improved charge transfer conductivity. The advantageous features endow the MnO2/carbon with remarkable rate capability (175 mAh/g at 3.0 A/g) and excellent cycling lifespan (87.8 % capacity retention after 1000 cycles at 1.0 A/g). In addition, the kinetic enhancement and fundamental reaction mechanism are systematically investigated. The encouraging results will shed new insight on designing MnO2-based materials to advance the development of AZIBs.

FRI672 Bone Mineral Density In Neurofibromatosis Type 1: A Systematic Review And Meta-analysis

Abstract Disclosure: N. Charoenngam: None. P. Wattanachayakul: None. A. Jaroenlapnopparat: None. P. Ungprasert: None. J. Chenbhanich: None. Neurofibromatosis type 1 (NF1) is known to be associated with low bone mineral density (BMD) and fragility fractures. However, evidence supporting specific age of early BMD measurement is limited as data on the degree of bone loss in NF1 are lacking. Using systematic review and meta-analysis technique, we aimed to identify all available data to assess BMD in patients with NF1. Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2023 using search strategy that comprised of terms for “Bone mineral density” and "Neurofibromatosis type 1”. Eligible study must include adult or pediatric patients with NF1. The study must report mean Z-score with variance of total body, lumbar spine, femoral neck or total hip BMD of the studied patients. Point estimates with standard errors were retrieved from each study and were combined using the generic inverse variance method. A total of 1,165 articles were identified. After systematic review, 19 studies were included. The majority of participants in the included studies were children and younger adults with the mean age of participants lower than 50 years old in all but one study. The meta-analysis revealed that patients with NF1 had negative mean Z-scores for total body BMD (pooled mean Z-score -0.808; 95%CI, -1.025 - -0.591) and BMD at lumbar spine (pooled mean Z-score -1.104; 95%CI, -1.376 - -0.833), femoral neck (pooled mean Z-score -0.726; 95%CI, -0.893 - -0.560) and total hip (pooled mean Z-score -1.126; 95%CI, -2.078 - -0.173). The subgroup meta-analysis in pediatric patients aged &amp;lt;18 years revealed that patients with NF1 had negative mean Z-scores for lumbar spine BMD (pooled mean Z-score -0.938; 95%CI, -1.299 - -0.577) and femoral neck BMD (pooled mean Z-score -0.585; 95%CI, -0.872 - -0.298). Based on the results from the meta-analysis, patients with NF1 had low Z-scores. However, the lower limits of the 95% CIs for the pooled mean Z-score for total body and specific site BMD were all higher than the Z-score cut-off of -2 for “low BMD for chronological age” in children and adults aged &amp;lt;50 years old. Therefore, the degree of low BMD may not be of clinical significance. Our results do not support the role of early BMD screening in children and young adults with NF1. Presentation: Friday, June 16, 2023

The bone-protective benefits of amino-conjugated calcium in an ovariectomized (OVX) rat model

Low bone density, fragility, and microarchitectural disintegration are the symptoms of osteoporosis. An imbalance between bone growth and resorption can lead to osteoporosis. This study evaluated the effects of amino-calcium (AC) on bone protection in ovariectomized control group (NC) rats. Amino-calcium (AC) was characterized using Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), and nuclear magnetic resonance spectroscopy analyses (NMR). After determining the biocompatibility of amino-calcium (AC) with MC3T3-E1 cells, alkaline phosphatase staining revealed significant changes on day 7. Three of the four groups underwent ovariectomy, whereas one group received a placebo. On micro-computed tomography, in vivo, data showed increased bone volume fraction in the femoral head and shaft areas in the amino-calcium (AC) group. Hematoxylin and eosin staining showed a bone mass and architectural protection in the amino-calcium (AC) group compared with the calcium carbonate and OVX control group. RNA sequencing analysis revealed high expression of osteogenesis-related genes in MC3T3-E1 cells. RNA sequencing revealed a significant fold change in the expression of integrin-binding sialoprotein (IBSP), bone gamma-carboxyglutamate proteins 1 and 2(BGLAP1 and BGLAP2), and periostin (POSTN). The study concluded that supplementing the OVX rats with calcium enhanced bone protection.

A Brief Review of Immobilized Oxidoreductase Enzymes for the Removal of Endocrine-Disrupting Chemicals from Wastewater

Modern technological of human activities in industries or housing areas have created an unhealthy environment, particularly through unmanageable wastewater. For the time being, this kind of pollution is getting serious as it caused the emerging pollutant actively to spread to humans and living organisms. These non-biodegradable pollutants, to be specifically known as endocrine-disrupting chemicals (EDCs) are synthetic or natural chemicals that have high toxicity and persistency which can interfere with the endocrine system in humans and animals. The removal of EDCs has received high attraction among researchers using physical-chemical treatments, however, conventional techniques do not effectively remove EDCs from wastewater. This review aims to discuss research related to biological approaches that have been carried out to efficiently remove EDCs from wastewater using oxidoreductase enzymes, especially via an immobilization strategy. In general, free enzymes have limitations to be applied in industrial scales such as low stability and fragility, and unable to separate from the bulk solution. On the other hand, immobilized enzymes offer better operational stability and reusability in harsh environments. This review also discussed the bioremediation of EDCs using several immobilized oxidoreductase enzymes like lignin peroxidase (LiP), manganese peroxidases (MnP), horseradish peroxidases (HRP), laccases and tyrosinases. The application of immobilized enzymes and factors affecting the bioremediation using oxidoreductase enzymes were also explored to highlight their potential for the removal of EDCs from wastewater.