Effect of ribose incubation on physical, chemical, and mechanical properties of human cortical bone.

Raman spectroscopy (RS) is sensitive to the accumulation of advanced glycation end-products (AGEs), and it measures matrix-sensitive properties that correlate with the fracture toughness of human cortical bone. However, it is unclear whether sugar-mediated accumulation of AGEs affects the fracture toughness of human cortical bone in a manner that is consistent with the negative correlations between amide I sub-peak ratios and fracture toughness. Upon machining 64 single-edge notched beam (SENB) specimens from cadaveric femurs (8 male and 7 female donors between 46 years and 61 years of age), pairs of SENB specimens were incubated in 15 mL of phosphate buffered saline with or without 0.1 M ribose for 4 weeks at 37 °C. After acquiring 10 Raman spectra per bone specimen (n = 32 per incubation group), paired SENB specimens were loaded in three-point bending at a quasi-static or a high loading rate approximating 10-4 s-1 or 10-2 s-1, respectively (n = 16 per incubation group per loading rate). While 2 amide I sub-peak ratios, I1670/I1640 and I1670/I1610, decreased by 3-5% with a 100% increase in AGE content, as confirmed by fluorescence measurements, the ribose incubation to accumulate AGEs in bone did not affect linear elastic (KIc) nor non-linear elastic (KJc) measurements of bone's ability to resist crack growth. Moreover, AGE accumulation did not affect the change in these properties when the loading rate changed. Increasing the loading rate increased KIc but decreased KJc. Ribose incubation did not affect mineral-related RS properties such as mineral-to-matrix ratios, Type B carbonate substitutions, and crystallinity. It did however increase the thermal stability of demineralized bone (differential scanning calorimetry), without affecting the network connectivity of the organic matrix (i.e., maximum slope during a hydrothermal isometric tension test of demineralized bone). In conclusion, RS is sensitive to AGE accumulation via the amide I band (plus the hydroxyproline-to-proline ratio), but the increase in AGE content due to ribose incubation was not sufficient to affect the fracture toughness of human cortical bone.

A critical review on biochar-assisted free radicals mediated redox reactions influencing transformation of potentially toxic metals: Occurrence, formation, and environmental applications.

Potentially toxic metals have become a viable threat to the ecosystem due to their carcinogenic nature. Biochar has gained substantial interest due to its redox-mediated processes and redox-active metals. Biochar has the capacity to directly adsorb the pollutants from contaminated environments through several mechanisms such as coprecipitation, complexation, ion exchange, and electrostatic interaction. Biochar's electron-mediating potential may be influenced by the cyclic transition of surface moieties and conjugated carbon structures. Thus, pyrolysis configuration, biomass material, retention time, oxygen flow, and heating time also affect biochar's redox properties. Generally, reactive oxygen species (ROS) exist as free radicals (FRs) in radical and non-radical forms, i.e., hydroxyl radical, superoxide, nitric oxide, hydrogen peroxide, and singlet oxygen. Heavy metals are involved in the production of FRs during redox-mediated reactions, which may contribute to ROS formation. This review aims to critically evaluate the redox-mediated characteristics of biochar produced from various biomass feedstocks under different pyrolysis conditions. In addition, we assessed the impact of biochar-assisted FRs redox-mediated processes on heavy metal immobilization and mobility. We also revealed new insights into the function of FRs in biochar and its potential uses for environment-friendly remediation and reducing the dependency on fossil-based materials, utilizing local residual biomass as a raw material in terms of sustainability.

Identifying Bone Matrix Impairments in a Mouse Model of Neurofibromatosis Type 1 (NF1) by Clinically Translatable Techniques.

Three-to-four percent of children with neurofibromatosis type 1 (NF1) present with unilateral tibia bowing, fracture, and recalcitrant healing. Alkaline phosphatase (ALP) enzyme therapy prevented poor bone mineralization and poor mechanical properties in mouse models of NF1 skeletal dysplasia; but transition to clinical trials is hampered by the lack of a technique that (i) identifies NF1 patients at risk of tibia bowing and fracture making them eligible for trial enrollment and (ii) monitors treatment effects on matrix characteristics related to bone strength. Therefore, we assessed the ability of matrix-sensitive techniques to provide characteristics that differentiate between cortical bone from mice characterized by postnatal loss of Nf1 in Osx-creTet-Off ;Nf1flox/flox osteoprogenitors (cKO) and from wild-type (WT) mice. Following euthanasia at two time points of bone disease progression, femur and tibia were harvested from both genotypes (n ≥ 8/age/sex/genotype). A reduction in the mid-diaphysis ultimate force during three-point bending at 20 weeks confirmed deleterious changes in bone induced by Nf1 deficiency, regardless of sex. Pooling females and males, low bound water (BW), and low cortical volumetric bone mineral density (Ct.vBMD) were the most accurate outcomes in distinguishing cKO from WT femurs with accuracy improving with age. Ct.vBMD and the average unloading slope (Avg-US) from cyclic reference point indentation tests were the most sensitive in differentiating WT from cKO tibias. Mineral-to-matrix ratio and carbonate substitution from Raman spectroscopy were not good classifiers. However, when combined with Ct.vBMD and BW (femur), they helped predict bending strength. Nf1 deficiency in osteoprogenitors negatively affected bone microstructure and matrix quality with deficits in properties becoming more pronounced with duration of Nf1 deficiency. Clinically measurable without ionizing radiation, BW and Avg-US are sensitive to deleterious changes in bone matrix in a preclinical model of NF1 bone dysplasia and require further clinical investigation as potential indicators of an onset of bone weakness in children with NF1. © 2022 American Society for Bone and Mineral Research (ASBMR).

Rapid trace element analysis of microgram soft materials with cryogenic milling and laser ablation spectroscopy.

Trace element analysis of soft materials, to determine the content of low concentration elements, is important in many industries such as food quality control and medical biopsy analysis. Many of these applications would benefit from faster analysis with smaller sample requirements. Further, some natural samples are soft and have high water content, which brings challenges to element analysis. Here, we develop a cryogenic pelletization pretreatment to address those challenges. The soft samples are cryogenically milled, freeze-dried, and pelletized before elemental analysis. Analysis is performed by laser ablation spectroscopy, the combination of laser-induced breakdown spectroscopy (LIBS) and laser ablation inductively coupled plasma mass spectroscopy (LA-ICP-MS), to rapidly analyze light and heavy analytes. For this initial study, aluminum (Al) content in soft samples is determined by LIBS and lead (Pb) content by LA-ICP-MS. The standard addition method is performed to build calibration curves for element quantification. The measurements are compared with a Hong Kong government certified acid digestion and ICP-MS procedure. The experiment is performed on standard reference materials and selected food samples. The relative errors compared with certified measurements are less than 10% for all samples, with Al content ranging from 63-1466 µg/g and Pb content from 0.37-2.35 µg/g (dry mass). Microscopy of pellets shows that laser ablation spectroscopy can be performed with 100 µg of sample (dry mass). Total analysis time from raw sample to final measurement, including preparation, is under 1 h. The results indicate that the laser ablation spectroscopy with cryogenic pelletization is a promising technique for many applications such as screening of small food samples for toxic metals and trace element analysis of millimeter biopsies.

Synchronous Bilateral Tubal Serous Carcinomas in a Patient With Exon 13 Duplication and Loss of Function of BRCA1.

We report the first case of distinct, synchronous serous carcinomas of the adnexa arising in a patient with a family history of breast and ovarian cancer and a germline loss of function mutation in BRCA1. Illustrating an exceedingly rare phenomenon of synchronous high-grade carcinomas with distinct histomorphologic, immunohistochemical and cytogenetic features, the case serves as a point of departure for the discussion of phenotypic patterns of carcinomas arising in BRCA1 mutation carriers. We also review patient management, including the importance of risk-reducing salpingo-oophorectomy in women with deleterious BRCA1 mutations, as well as the potential need for an intraoperative pathologic assessment to find occult, high-grade carcinomas in this setting.

Preclinical Evaluation of 18F-ML-10 to Determine Timing of Apoptotic Response to Chemotherapy in Solid Tumors.

PURPOSE: We investigated 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) positron emission tomography (PET) imaging of apoptosis posttherapy to determine optimal timing for predicting chemotherapy response in a mouse head/neck xenograft cancer model. PROCEDURES: BALB/c nude mice (4-8 weeks old) were implanted with UM-SCC-22B tumors. The treatment group received 2 doses of doxorubicin (10 mg/kg, days 0, 2). Small animal 18F-ML-10 PET/computed tomography was performed before and on days 1, 3, and 7 postchemotherapy. Using regions of interest around tumors, 18F-ML-10 uptake change was measured as %ID/g and uptake relative to liver. Terminal Uridine Nick-End Labeling (TUNEL) immunohistochemistry assay was performed using tumor samples of baseline and on days 1, 3, and 7 posttreatment. RESULTS: Treated mice demonstrated increased 18F-ML-10 uptake compared to baseline and controls, and 10 of 13 mice showed tumor volume decreases. All control mice showed tumor volume increases. Tumor-to-liver (T/L) ratios from the control group mice did not show significant change from baseline ( P > .05); however, T/L ratios of the treatment group showed significant 18F-ML-10 uptake differences from baseline compared to days 3 and 7 posttreatment ( P < .05), but no significant difference at 1 day posttreatment. CONCLUSION: 2-(5-Fluoro-pentyl)-2-methyl-malonic acid PET imaging has the potential for early assessment of treatment-induced apoptosis. Timing and image analysis strategies may require optimization, depending on the type of tumor and cancer treatment.

Framed, Interactive Theory-Driven Texting: Effects of Message Framing on Health Behavior Change for Weight Loss.

More approaches to support weight control are needed, especially among racial minorities who shoulder a disproportionate obesity burden. Using an approach influenced by regulatory fit theory, we conducted a 28-day, 4-arm experimental trial with 89 obese adults recruited from urban, predominantly African American churches to ascertain the efficacy of framed text messages to motivate behaviors conducive to weight loss. Participants were assigned to receive message framing that was matched versus mismatched to their motivational orientation. Results were mixed overall; however, matched texts elicited greater motivation to change eating and exercise behavior, suggesting promise in using motivational approaches to tailor messages.

Variability in myocardial metabolism on serial tumor (18)F-FDG PET/CT scans.

(18)F Fluorodeoxyglucose (FDG) positron emission tomography (PET) scans are performed routinely for oncologic patients. Myocardial uptake can vary among patients and between serial studies in the same patient. Our study aims to evaluate myocardial metabolism on staging FDG PET scans and to analyze factors influencing patterns of cardiac uptake, and their relevance. We analyzed retrospectively 100 PET-CT scans from 20 fasting lymphoma patients. Distribution of myocardial uptake was determined by visual assessment and the maximum standardized uptake value (SUVm) was calculated. Multiple variables were analyzed including: fasting length, cardiovascular risk factors, SUVm, and location of uptake. We found no correlation between fasting hours and cardiac uptake (p-value: 0.4786). There was a trend that showed less uptake in patients scanned in the afternoon versus the morning, although this was not statistically significant. The location of maximum uptake was unexpectedly variable in several patients and could not be ascertained to a specific cause. Interestingly, we found no correlation between cardiac risk factors and the amount of myocardial uptake. Myocardial FDG uptake is spatially and temporally heterogeneous. Differences in myocardial wall pattern and peak uptake exist and may not be explained by the length of fasting, gender, age or cardiac risk factors. This variability may occur in daily cardiac evaluations and affect interpretations of sarcoidosis and viability studies and should be further explored. A larger cohort study is necessary to confirm that our findings do not confer a higher cardiac risk profile to the cancer patient.

Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods.

Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12-15 months for glioblastomas and 2-5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas.

Surgical management of inferior vena cava strut penetration causing hydronephrosis: case report.

We present a case of penetration of inferior vena cava (IVC) by primary struts of Cook Celect filter and impingement on right ureter, causing symptomatic hydronephrosis and hydroureter, which was managed surgically by ureterolysis, mobilization of the ureter by retroperitoneal approach, excision of the filter strut, and omental wrap around the ureter.