Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

BACKGROUND: Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. MATERIALS AND METHODS: A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. RESULTS: Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. CONCLUSIONS: We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Enzymatic Assessment of the State of Oil-Contaminated Soils in the South of Russia after Bioremediation.

Soil pollution with oil as a result of accidents at oil pipelines and oil refineries is a frequent occurrence in the south of Russia. To restore such polluted lands, it is necessary to carry out soil remediation measures. This work aimed to evaluate the use of ameliorants of various natures (biochar, sodium humate, and microbial preparation Baikal EM-1) to restore the ecological state of oil-contaminated soils with different properties (Haplic Chernozem, Haplic Arenosols, Haplic Cambisols). To assess the ecological state of soils, the following physicochemical and biological indicators were studied: residual oil content, redox potential, and medium reaction (pH). Changes in enzymatic activity were also studied, including catalase, dehydrogenases, invertase, urease, and phosphatase. The greatest decomposition of oil in Haplic Chernozem and Haplic Cambisols was provided by Baikal EM-1 (56 and 26%), and in Haplic Arenosols, this was provided by biochar (94%) and sodium humate (93%). In oil-contaminated Haplic Cambisols, the content of easily soluble salts with the addition of biochar and Baikal EM-1 increased by 83 and 58%, respectively. The introduction of biochar caused an increase in pH from 5.3 (Haplic Cambisols) to 8.2 (Haplic Arenosols). The introduction of oil-contaminated Haplic Arenosols of biochar, humate, and Baikal stimulated the activity of catalase and dehydrogenases by 52-245%. The activity of invertase was stimulated in the Haplic Chernozem after the introduction of ameliorants by 15-50%. The activity of urease was stimulated after the introduction of ameliorants into borax and Arenosol by 15-250%. The most effective ameliorant for restoring the ecological state of Haplic Cambisols after oil pollution was biochar. For Haplic Arenosols, this was sodium humate, and for Haplic Chernozem, the effectiveness of biochar and sodium humate did not differ. The most informative indicator for the remediation of Haplic Chernozem and Haplic Cambisols was the activity of dehydrogenases, and for Haplic Arenosols, this was the activity of phosphatase. The results of the study should be used to biomonitor the ecological state of oil-contaminated soils after bioremediation.

The use of serum alkaline phosphatase as a choledocholithiasis marker to mitigate the cost of magnetic resonance cholangiography

ABSTRACT Objective To assess the predictive value of preoperative serum laboratory test results for identifying choledocholithiasis and reduce the use of cholangioresonance and its inherent costs. Methods Patients aged 21-69 years who underwent preoperative cholangioresonance examination at our institute were included. Patients with a history of fluctuating jaundice or biliary pancreatitis, bile duct dilatation on ultrasonography, and elevated levels of canalicular enzymes (alkaline phosphatase >100U/L and gamma-glutamyl transferase >50U/L) underwent cholangioresonance-guided surgery. Cases of choledocholithiasis confirmed by cholangioresonance were compared with those without choledocholithiasis. Serum laboratory data were evaluated and the diagnostic capabilities of these examinations were analyzed. Results A total of 104 patients were included. For detecting choledocholithiasis using alkaline phosphatase, the cut-off point was 78U/L, sensitivity was 97.6% (95%CI: 87.4-99.9), and specificity was 72.6% (95%CI: 59.8-83.1). In the binary logistic regression analysis, age (OR= 0.92; 95%CI: 0.86-0.98) and alkaline phosphatase level (OR= 1.02; 95%CI: 1.01-1.05) were selected for the final model. Conclusion Serum alkaline phosphatase levels may aid preoperative diagnosis of asymptomatic choledocholithiasis. After a global clinical assessment of the patient, serum laboratory findings may contribute to a reduction in cholangioresonance-related heathcare costs.

Single and repeated dose (28 days) intravenous toxicity assessment of bartogenic acid (an active pentacyclic triterpenoid) isolated from Barringtonia racemosa (L.) fruits in mice.

Bartogenic acid (BA), an active pentacyclic triterpenoid, has been reported for anti-diabetic, anti-inflammatory, anti-arthritic, anti-cancer, and anti-tumor activity. However, toxicity profiling of BA has not been reported till date. Hence, this study is designed to evaluate the single dose (12.5, 25, 50 and 100 mg/kg) and repeated dose (1.5, 6, and 24 mg/kg) intravenous toxicity of BA in BALB/c mice. Control group received vehicle. In single dose toxicity study, two mortalities were observed at 100 mg/kg of BA whereas lower doses were well tolerated. In repeated dose toxicity study, no mortality was observed. 1.5 mg/kg of BA was well tolerated in mice of both sexes. At 6 mg/kg of BA, female mice showed significant reduction in the body weight as compared to the control group however no significant change was observed in male mice. 24 mg/kg of BA showed significant reduction in the body weight in mice of both sexes. Further, these mice showed significant change in the relative organ weight. However, no toxicologically relevant changes were observed in hematology, biochemistry, and histopathology. Based on the findings, No-Observed-Adverse-Effect-Level (NOAEL) for BA were found to be<24 mg/kg for male mice and<6 mg/kg for female mice.

In vitro genotoxicity assessment and 28-day repeated dose oral toxicity study of steady-calcium formula in rats.

Steady-calcium formula (SCF), a functional food mixture with potential of joint care, contains five major ingredients. However, the uncertain cross-reactivity among these included ingredients cannot be excluded. Hence, it is important to ensure the safety of this mixture. In this study, the safety of SCF was evaluated through in vitro genotoxicity assessment and 28-day oral toxicity study in rats. The bacterial reverse mutation test and mammalian chromosome aberration test displayed that SCF did not induce mutagenicity and clastogenicity. The 28-day repeated dose assessment of SCF in rats revealed no mortality and adverse effects in clinical signs, body weight, urinalysis, hematology, organ weight, and histopathology at all treated groups. Although some significant changes were observed in food intake and parameters of serum biochemistry at the highest dose in males, they were not dose-related and considered to be within normal range. These findings indicate that SCF does not possess genotoxic potential and no obvious evidence of subacute toxicity. These results demonstrate for the first time that the genotoxicity and subacute toxicity for SCF are negative under our experimental conditions and the no observed adverse effect level (NOAEL) of SCF may be defined as at least 5470 mg/kg/day.

Acute and subchronic oral toxicity assessment of extract from Etlingera pavieana rhizomes.

In Southeast Asia, the rhizome of Etlingera pavieana is commonly consumed and parts of the rhizomes have been used as a medicine for the treatment of several disorders. Its pharmacological effects have previously been reported. However, its potential toxicity has not been described. This study aimed to evaluate in vivo toxicity of E. pavieana rhizome extract (EPE) in Sprague Dawley rats. Acute toxicity testing of EPE at a single dose of 2,000 mg/kg produced no toxic effects in female rats after 14 days of treatment. Subchronic toxicity testing showed that all doses of EPE (500, 1,000, and 2,000 mg/kg/day) produced no sign of toxicity during 90 days of treatment. All biochemical and hematological values were within normal ranges. There were no significant histopathological differences in the internal organs among the tested groups. Therefore, the no-observed-adverse-effect level of EPE was 2,000 mg/kg/day in both male and female rats, thereby confirming the safety of EPE for use in traditional medicines.

Association of Liver Function Tests with Mortality in an Insurance Applicant Population.

OBJECTIVES: -Determine the relationship between liver function test (LFT) results (GGT, alkaline phosphatase, AST, ALT and albumin) and all-cause mortality in life insurance applicants. METHOD: -By use of the Social Security Master Death File, mortality was examined in 15,272,955 insurance applicants for whom blood samples were submitted to the Clinical Reference Laboratory. There were 268,593 deaths observed in this study population, after an average follow-up time of 10.9 years. Results were stratified by sex and by age less/greater than 60, creating 4 groups. Liver function test values were grouped using percentiles of their distribution within these age/ sex groups - so as to update the results generated in prior publications. Additional models were fit using different exclusions and percentile groups within single year age groups. Also, LFTs were treated as continuous variables and included in Cox models with age and smoking status. RESULTS: -Using the risk of the middle 50% of the population by distribution as a reference, relative mortality observed for GGT and alkaline phosphatase was linear with a steep slope from very low to high values. AST showed a J-shaped association with mortality. ALT showed a low-magnitude inverse correlation with mortality. Albumin demonstrated a higher-magnitude inverse correlation with mortality, especially at values below the median. The overall risk associated with LFTs was durable over at least 10 years of follow-up. CONCLUSION: -Liver function tests show a strong and durable correlation to mortality in a large group of insurance applicants. The durability over time suggests that even older values of LFTs found in medical records could be of use in mortality risk prediction.

Assessment of Biochemical Parameters of the Oral Fluid before and after Using Office Teeth Whitening Systems.

One of the most important functions of the oral fluid is to maintain oral homeostasis. In-office teeth whitening systems are able to change the mineral metabolism and the activity of a number of enzymes in the oral fluid, but there are conflicting data in publications about this. The aim of this study was to compare the effect of Opalescense Boost, ZOOM Advance POWER, and ZOOM Phillips White Speed, which contain different percentages of hydrogen peroxide, on the performance of oral fluid. After the procedure of whitening teeth with the studied in-office systems, the concentration of calcium in the oral fluid increased, and the activity of alkaline phosphatase decreased. Calcium levels returned to baseline values after 30 days, and alkaline phosphatase activity returned after 14 days. There was no significant difference in the changes in calcium concentration and alkaline phosphatase activity between different tooth whitening systems. Chemical teeth whitening with the Opalescense Boost system caused the largest change in the activity of superoxide dismutase in the oral fluid compared to the ZOOM Advance POWER and ZOOM Phillips White Speed photocatalytic teeth whitening systems. An increase in the activity of superoxide dismutase by +75.5% was shown immediately after the procedure of teeth whitening with the Opalescense Boost system, which indicated an increase in the power of antioxidant defense mechanisms. To assess the effectiveness and safety of using various whitening systems, it is possible to study the dynamics of the activity of superoxide dismutase, which reflects the processes of antioxidant protection of the oral cavity.

Colimitation assessment of phytoplankton growth using a resource use efficiency approach in the Bay of Seine (French-English Channel).

Eutrophication and dystrophy are two of the main problems affecting coastal ecosystems. In the Bay of Seine, phosphorus (P) inputs from the Seine estuary have been largely reduced in the last decade, in contrast to nitrogen (N), which leads to high N/P ratio inputs. To study the effect of dystrophy, an enrichment bioassay using water sampled from the Bay of Seine was repeated 19 times over a period of 18 months with six different enrichments. After a few days, chlorophyll a (chl a), alkaline phosphatase activity (APA), transparent exopolymeric particles (TEPs), cytometric size structure, and maximum quantum yield of photosystem II were measured. The data provide strong evidence for an N & P colimitation system in the vast majority of the incubations, as only the N + P and N + P + Si enrichments supported phytoplankton growth, and Si only appeared to play a secondary role in our incubations. A N/P ratio of 16 equal to the Redfield ratio was identified as the optimum for balanced growth, as chl a was the highest and TEP and APA production was the lowest at this ratio. To fit the requirements of the colimited system, a new resource use efficiency (RUENP) calculation was developed to account for N and P colimitation instead of only one nutrient, as is usually the case. This calculation allows better representation of RUE in dystrophic conditions, as found in many highly anthropized ecosystems. The relationships between RUENP and the size structure of the phytoplankton community were explored, and a significant positive correlation between RUENP and larger cells (>2 µm) and a negative correlation with smaller cells (<2 µm) were noted, showing a better use of nutrients by larger cells. This study highlights an increase of RUENP with the phytoplankton cell size in a colimited system.

An effective in-gel assay protocol for the assessment of acid phosphatase (ACPase) isoform expression in the fungus Serendipita indica.

The induction of acid phosphatase (ACPase) in the mycorrhizal fungi is an adaptive survival mechanism to cope in a low-phosphate environment. A mycorrhizal fungi Serendipita indica can induce the ACPase enzyme and enhance the phosphate (Pi) level to the host plant through Pi-solubilization mechanism, both intracellular and extracellular (media) levels. The spectrophotometer technique has been widely and commonly used to measure the ACPase enzyme activity in all microorganisms and plants using pNPP as a substrate. However, this technique cannot be useful when studying the involvement of ACPase isoforms in Pi-solubilization. In this article, we developed a single method to identify and express the ACPase isoforms of S. indica that contribute to the Pi-nutrition in the plant. This is native-PAGE electrophoresis with the in-gel assay and staining to detect the isoforms of the ACPase enzyme. The dark red-brown color developed after staining indicates the non-denatured (native) ACPase enzyme. This method utilized a modified minimal media for the de-repression of P-responsive genes such as ACPases with minimum salt contamination in the samples. This method will be helpful for the characterization of secretory and intracellular ACPases in fungi.

Root phosphatase activity aligns with the collaboration gradient of the root economics space.

The adoption of diverse resource acquisition strategies is critical for plant growth and species coexistence. Root phosphatase is of particular importance in the acquisition of soil phosphorus (P), yet it is often overlooked in studies of root trait syndromes. Here, we evaluated the role of root phosphatase activity (RPA) within the root economics space and the order-based variation of RPA, as well as the correlations between RPA and a suite of leaf traits and soil properties over a range of evergreen tree species in a subtropical forest. Root phosphatase activity exhibited a high degree of inter-specific variation. We found that there were two leading dimensions of the multidimensional root economics space, the root diameter-specific root length axis (collaboration trait gradient) and the root tissue density-root nitrogen concentration axis (classical trait gradient), and RPA aligned with the former. Root phosphatase activity is used as a 'do it yourself' strategy of soil P acquisition, and was found to be inversely correlated with mycorrhizal colonization, which suggests a trade-off in plant P acquisition strategies. Compared with soil and foliar nutrient status, root traits mattered most for the large inter-specific changes in RPA. Furthermore, RPA generally decreased from first- to third-order roots. Taken together, such diverse P-acquisition strategies are conducive to plant coexistence within local forest communities. The use of easily measurable root traits and their tight correlations with RPA could be a feasible and promising approach to estimating species-specific RPA values, which would be helpful for better understanding plant P acquisition and soil P cycling.

Evaluation of vitamin D protocol in the neonatal intensive care unit at Rush University Medical Center.

BACKGROUND: In 2017, the neonatal intensive care unit (NICU) at Rush University Medical Center (RUMC) implemented a protocol to provide individualized vitamin D supplementation dosing for very low-birth-weight (VLBW) and very preterm infants. This study evaluated the association of demographic and socioeconomic factors, vitamin D dose, and health indicators, including bone mineral status, measured by alkaline phosphatase and phosphorus levels; linear growth velocity; and occurrence of fractures. METHOD: This retrospective cross-sectional study included 227 VLBW or very preterm infants (34 VLBW, 12 very preterm, and 181 VLBW and very preterm) born in and discharged from the RUMC NICU between February 1, 2017, and October 31, 2019. Vitamin D dose was classified as adjusted (supplemental dose of 800 IU/day, n = 169) or standard (recommended dose of 400 IU/day, n = 58), per the protocol. Binary logistic and linear regression models were constructed to test the associations between infant and maternal characteristics and vitamin D dose group and between vitamin D dose group and health indicators. RESULTS: The analysis found a statistically significant association between maternal age, gestational age, infant birth weight, and race/ethnicity and receipt of an adjusted vitamin D dose. No significant associations were found between health indicators and vitamin D dose. CONCLUSION: Sociodemographic factors may influence vitamin D deficiency in VLBW and very preterm infants in the NICU. At this time, there is insufficient evidence to support a tailored approach, but further research in this area is warranted.

Highly sensitive fluorescent quantification of acid phosphatase activity and its inhibitor pesticide Dufulin by a functional metal-organic framework nanosensor for environment assessment and food safety.

Developing a rapid and accurate strategy of sensing Dufulin is a vital challenge for risk assessment and food crops along with its spreading usage. Herein a dye-encapsulated azoterephthalate metal-organic framework (MOF)-based fluorescent sensing system was designed for Dufulin analysis by acid phosphatase (ACP) enzyme-controlled collapse of MOF framework and subsequent release of the encapsulated dye. The fluorescence intensity of the DMOF/AAP/ACP system was negatively related to the dosage of Dufulin (0-5 µg mL-1) with detection limit of 2.96 ng mL-1. The sensing system able to rapidly and sensitively sense the activity of ACP and Dufulin, and was also applicable for assessment of the real samples including paddy water and soil, polished rice and cucumber. Accordingly, this study illustrated the feasibility and the potential of MOF-derived nanosensors for improving pesticide analysis and opening up the design of the enzyme-based probes for pesticide sensing in environmental assessment and food safety.

Prevalence of low alkaline phosphatase activity in laboratory assessment: Is hypophosphatasia an underdiagnosed disease?

BACKGROUND: Tissue-nonspecific alkaline phosphatase (TNSALP) encoded by the ALPL gene is of particular importance for bone mineralization. Mutation in the ALPL gene can lead to persistent low ALP activity resulting in the rare disease Hypophosphatasia (HPP) that is characterized by disturbed bone and dental mineralization. While severe forms are extremely rare with an estimated prevalence of 1/100.000, recent studies suggest that moderate form caused by heterozygous mutations are much more frequent with an estimated prevalence of 1/508. The purpose of this study was to estimate the prevalence of low AP levels in the population based on laboratory measurements. METHODS: In this study, the prevalence of low AP activity and elevated pyridoxal-5-phosphate (PLP) levels was analyzed in 6.918.126 measurements from 2011 to 2016 at a single laboratory in northern Germany. Only laboratory values of subjects older than 18 years of age were included. Only the first measurement was included, all repeated values were excluded. RESULTS: In total, 8.46% of the measurements of a total of 6.918.126 values showed a value < 30 U/L. 0.59% of the subjects with an ALP activity below 30 U/L had an additional PLP measurement. Here, 6.09% showed elevated pyridoxal-5-phosphate (PLP) levels. This suggest that 0.52% (1:194) of subjects show laboratory signs of HPP. CONCLUSION: These data support the genetic estimation that the prevalence of moderate forms of HPP may be significantly higher than expected. Based on these data, we recommend automatically measurement of PLP in the case of low ALP activity and a notification to the ordering physician that HPP should be included in the differential diagnosis and further exploration is recommended.

Formulation development and in vitro-in vivo assessment of protransfersomal gel of anti-resorptive drug in osteoporosis treatment.

Osteoporosis is a major cause of morbidity, mortality, and economic burden worldwide. Despite being an effective in combating the bone-deteriorating disorders, bisphosphonates have several shortcomings including poor and variable bioavailability, low permeability, high toxicity, etc. In this study, we developed and optimized protransfersome formulation for the drug risedronate sodium (RIS-Na) with the goal of enhancing its bioavailability and hence patient compliance. Phase separation coacervation technique was utilized for development of optimized formulation. Optimization was achieved by using three-factor, three-level Box-Behnken design combined with Response Surface Methodology (RSM). This enabled us to decipher the effect of 3 independent variables (Phospholipid, Tween-80 and Sodium Deoxycholate) on three dependent parameters (entrapment efficiency, vesicle size and transdermal flux). Optimized formulation was further evaluated for pharmacokinetic and pharmacodynamic parameters. Smooth, spherical protransfersomes with a size of 260 ± 18 nm, having entrapment efficiency and flux of 80.4 ± 4.90% and 8.41 ± 0.148 µg/cm2/h, respectively were prepared. Ex vivo studies revealed a shorter lag time of 1.21 ± 0.18 h and higher flux associated with transdermal formulation. CLSM analysis further revealed better drug penetration (220 µm) through the skin in case of protransfersomes as compared to drug solution (72 µm). Additionally, biomechanical, biochemical, and histo-pathological studies further validated the results. Thus, it was concluded that protransfersome formulation has a great potential in providing better therapeutic efficacy of risedronate than its conventional counterpart.

Assessment of Osteoporosis and Fracture Risk in Mastocytosis within a North American Cohort.

BACKGROUND: Systemic mastocytosis (SM), a clonal expansion of mast cells affecting multiple organs including the skeletal system, puts patients at risk for osteoporosis and fractures. Various aspects of skeletal disease in SM have been reported among European cohorts. OBJECTIVE: To determine fracture prevalence and risk predictors in SM in a North American (NA) cohort and compare findings with studies of other populations. METHODS: Fifty patients, aged 25-74 years, were grouped based on fracture type and history. Data collected included laboratory findings and radiographic markers such as serum tryptase, bone turnover markers, dual-energy x-ray absorptiometry images, and trabecular bone scores. We performed univariate and multivariate analyses of these findings. RESULTS: Fracture history was found in 74% of patients. Significantly different median age, body mass index, dual-energy x-ray absorptiometry scores, and alkaline phosphatase levels were observed between fracture groups, consistent with French and Dutch studies. Significant findings included the difference in trabecular bone scores among fracture groups, the association between alkaline phosphatase and fracture type and occurrence, and the model for predicting fracture risk based on DXA spine T-scores, alkaline phosphatase, and age (81.3% accuracy and 77.1% sensitivity). CONCLUSIONS: Our findings in an NA cohort are in overall agreement with those reported in European studies of skeletal disease and fracture risk for individuals with SM. We include an interactive calculator designed from a predictive model based on the NA cohort, which may be used for improved screening for fracture risk.

Assessment of Antidiabetic Activity of the Shikonin by Allosteric Inhibition of Protein-Tyrosine Phosphatase 1B (PTP1B) Using State of Art: An In Silico and In Vitro Tactics.

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin's in silico interaction with protein tyrosine phosphate 1B, as well as it's in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule's module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.

Refinement of decision tree to assess the consequences of increased serum ALP in dogs: Additional analysis on toxicity studies of pesticides evaluated recently in Japan.

Recently we provided a new interpretation that increased serum ALP in dogs is not adverse if no hepatotoxic finding coexists in the analysis of toxicity studies of over 200 pesticides evaluated in Japan (Yokoyama et al., 2019). We also proposed a decision tree to evaluate the adversity of the increased ALP. The present analysis was conducted to validate the reliability of this interpretation with 129 pesticides more recently evaluated. Before applying, the decision tree was revised to be consistent in all steps. The pesticides showed similar characterization of increased ALP to the previous analysis in that the increase was more frequent than in rats and that liver hypertrophy and hepatotoxicity commonly coexisted with an increase in ALP in dogs. When short- and long-term studies of 58 pesticides inducing ALP activity in dogs were applied to the revised tree, the increased ALP in 8 pesticides was judged not adverse in either study. The revision of the tree did not affect the NOAEL judgment of these pesticides; however, the revised routes contributed to the judgment more robustly. This study showed the reliability of our interpretation and applicability of the decision tree to evaluate the adversity of increased ALP in dogs.