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The biological properties of human mesenchymal stromal cells (hMSCs) have been explored in over a thousand clinical trials in the last decade. Although hMSCs can be isolated from multiple sources, the degree of biological similarity between cell populations from these sources remains to be determined. A comparative study was performed investigating the growth kinetics and functionality of hMSCs isolated from adipose tissue (AT), bone marrow (BM) and umbilical cord tissue (UCT) expanded in monolayer over five passages. Adult hMSCs (AT, BM) had a slower proliferation ability than the UCT-hMSCs, with no apparent differences in their glucose consumption profile. BM-hMSCs produced higher concentrations of endogenous vascular endothelial growth factor (VEGF) compared to AT- and UCT-hMSCs. This study also revealed that UCT-hMSCs were more efficiently transduced by a lentiviral vector carrying a VEGF gene than their adult counterparts. Following cellular immunophenotypic characterization, no differences across the sources were found in the expression levels of the typical markers used to identify hMSCs. This work established a systematic approach for cell source selection depending on the hMSC's intended clinical application. [ABSTRACT FROM AUTHOR]

We devised and clinically validated a schema of rapid personalized predictive dosimetry for 177Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. It supersedes traditional empiric prescription by providing clinically meaningful predicted absorbed doses for first-strike optimization. Methods: Prostate-specific membrane antigen PET was conceptualized as a simulation study that captures the complex dosimetric interplay between tumor, marrow, and kidneys at a single time point. Radiation principles of fractionation, heterogeneity, normal-organ constraints (marrow, kidney), absorbed dose, and dose rate were introduced. We created a predictive calculator in the form of a free, open-source, and user-friendly spreadsheet that can be completed within minutes. Our schema achieves speed and accuracy by sampling tissue radioconcentrations (kBq/cm3) to be analyzed in conjunction with clinical input from the user that reflect dosimetric preconditions. The marrow-absorbed dose constraint was 0.217 Gy (dose rate, ≤0.0147 Gy/h) per fraction with an interfraction interval of at least 6 wk. Results: Our first 10 patients were analyzed. The first-strike mean tumor-absorbed dose threshold for any prostate-specific antigen (PSA) response was more than 10 Gy (dose rate, >0.1 Gy/h). The metastasis with the lowest first-strike tumor-absorbed dose correlated the best with the percentage decrease of PSA; its threshold to achieve hypothetical zero PSA was 20 Gy or more. Each patient's PSA doubling time can be used to personalize their unique absorbed dose–response threshold. The predicted mean first-strike prescription constrained by marrow-absorbed dose rate per fraction was 11.0 ± 4.0 GBq. Highly favorable conditions (tumor sink effect) were dosimetrically expressed as the combination of tumor–to–normal-organ ratios of more than 150 for marrow and more than 4 for kidney. Our schema obviates the traditional role of the SUV as a predictive parameter. Conclusion: Our rapid schema is feasible to implement in any busy real-world theranostics unit and exceeds today's best practice standards. Our dosimetric thresholds and predictive parameters can radiobiologically rationalize each patient's first-strike prescription down to a single becquerel. Favorable tumor–to–normal-organ ratios can be prospectively exploited by predictive dosimetry to optimize the first-strike prescription. The scientific framework of our schema may be applied to other systemic radionuclide therapies. [ABSTRACT FROM AUTHOR]

Adipocyte is a unique and versatile component of bone marrow microenvironment (BMM). However, the dynamic evolution of Bone Marrow (BM) adipocytes from the diagnosis of B cell Acute Lymphoblastic Leukemia (B-ALL) to the post-treatment state, and how they affect the progression of leukemia, remains inadequately explicated. Primary patient-derived xenograft models (PDXs) and stromal cell co-culture system are employed in this study. We show that the dynamic evolution of BM adipocytes from initial diagnosis of B-ALL to the post-chemotherapy phase, transitioning from cellular depletion in the initial leukemia niche to a fully restored state upon remission. Increased BM adipocytes retards engraftment of B-ALL cells in PDX models and inhibits cells growth of B-ALL in vitro. Mechanistically, the proliferation arrest of B-ALL cells in the context of adipocytes-enrichment niche, might attribute to the presence of adiponectin secreted by adipocytes themselves and the absence of cytokines secreted by mesenchymal stem cell (MSCs). In summary, our findings offer a novel perspective for further in-depth understanding of the dynamic balance between BMM and B-ALL.

Objective In-phase and opposed-phase chemical shift imaging (CSI) is a useful technique for assessing skeletal lesions. This study determined the frequency of significant differences in measurements obtained from longitudinal (coronal or sagittal) sequences to those obtained from axial sequences. Methods Chemical shift imaging was undertaken in 96 consecutive patients referred from the Musculoskeletal Sarcoma and Spinal Oncology services for assessment of possible bone tumours as part of a standard tumour protocol, which included turbo spin echo and inversion recovery sequences. For spinal lesions, CSI was obtained in the sagittal and axial planes, while for all other sites, it was obtained in the coronal and axial planes. Results The study included 49 (51.0%) males and 47 (49.0%) females with mean age 42.4 years (range 2-91 years). In 4 cases, 2 individual lesions were assessed, making a total of 100 lesions. Based on typical imaging features (n  = 57) or histology (n  = 43), 22 lesions (22%) were classified as non-neoplastic, 44 (44%) as benign neoplasms, 6 (6%) as intermediate-grade neoplasms, and 28 (28%) as malignant neoplasms. A significant discrepancy, wherein a lesion was classified as fat-containing (% SI drop >20%-25%) in the longitudinal plane, while in the axial plane it was classified as fat-replacing (% SI drop <20%-25%), or vice versa , occurred in 9%-14% of cases. However, this discrepancy had no appreciable effect on overall diagnostic accuracy, which was calculated at 79% for the longitudinal plane and 75%-80% for the axial plane. Conclusions Significant differences in CSI measurements occur in 9%-14% of cases based on imaging plane, but with no significant effect on diagnostic accuracy. Advances in knowledge Radiologists should be aware that CSI measurements in different planes appear to have significant differences in up to 14% of lesions. However, diagnostic accuracy does not seem to be significantly affected. [ABSTRACT FROM AUTHOR]

There is no formally defined terminology for the related entities transient osteoporosis of the hip (TOH), localized or regional migratory osteoporosis (RMO) and bone marrow edema syndrome (BMES). This study aimed to map the diversity and frequency of diagnostic terms and vocabulary utilized in the literature. A comprehensive search of electronic databases and reference lists was conducted. Publications that reported on patients with TOH, RMO, BMES, or related variants were eligible for inclusion. The terminologies were categorized based on the wording of the titles, abstracts, or texts. We included 561 publications, of which 423 were case reports, involving 2921 patients. Overall, TOH was the most commonly used term, occurring in 257 (45.8%). RMO was used in 34 (6.1%) and BMES in 57 (10.2%). The remaining used various combinations of transient, migratory, and regional in conjunction with either osteoporosis or bone marrow edema. Localized osteoporosis was not used. We identified three different terms related to pregnancy. In 76.3% of the publications, the terminology was related to osteoporosis and in 18.2% to bone marrow edema, although terminology did not correspond to actual findings. Bone marrow edema occurred as often as osteoporosis, and osteoporosis was generally ascertained by visual inspection of radiographs, seldom by bone densitometry. Many publications used osteoporosis-related terms without evidence that osteoporosis had been detected. The terminology of these closely related entities is confusing and unstandardized. The lack of formal definitions impedes accurate diagnosis, research on disease mechanisms, and effective treatment. [ABSTRACT FROM AUTHOR]

Adipocyte is a unique and versatile component of bone marrow microenvironment (BMM). However, the dynamic evolution of Bone Marrow (BM) adipocytes from the diagnosis of B cell Acute Lymphoblastic Leukemia (B-ALL) to the post-treatment state, and how they affect the progression of leukemia, remains inadequately explicated. Primary patient-derived xenograft models (PDXs) and stromal cell co-culture system are employed in this study. We show that the dynamic evolution of BM adipocytes from initial diagnosis of B-ALL to the post-chemotherapy phase, transitioning from cellular depletion in the initial leukemia niche to a fully restored state upon remission. Increased BM adipocytes retards engraftment of B-ALL cells in PDX models and inhibits cells growth of B-ALL in vitro. Mechanistically, the proliferation arrest of B-ALL cells in the context of adipocytes-enrichment niche, might attribute to the presence of adiponectin secreted by adipocytes themselves and the absence of cytokines secreted by mesenchymal stem cell (MSCs). In summary, our findings offer a novel perspective for further in-depth understanding of the dynamic balance between BMM and B-ALL. [ABSTRACT FROM AUTHOR]

Joint pain and dysfunction are common presenting symptoms of both younger and older patients, resulting in significant cost and burden to the healthcare system. In both the acute and chronic setting, the advanced imaging evaluation for assessing joint dysfunction most commonly utilizes magnetic resonance imaging that allows for detailed evaluation of all components of a joint, including the cartilage, bone, fibrocartilage, and ligamentous components. Signal alterations of the subchondral bone and marrow have been recently recognized as an important component in both trauma and arthritis and modern treatment strategies focus on addressing both the cartilage and bone in an attempt to optimize joint preservation and restore function. The presence of bone marrow signal abnormalities is often associated with patient symptoms, cartilage loss, and risk of disease progression. A thorough understanding of the unique anatomy and biomechanics of the chondro-osseous junction can help to explain the many marrow signal abnormalities and clinical implications that are commonly encountered by imagers. In this review article, we will describe the anatomy and basic physiology of the subchondral bone, and discuss multiple pathologic appearances of the bone with an emphasis on edema-like signal changes seen in the setting of osteoarthritis and trauma.

Objective(s): The traditional practice of empiric radioiodine (I-131) prescription is scientifically obsolete and inappropriate for inoperable metastatic differentiated thyroid cancer. However, theranostically guided prescription is still years away for many institutions. A personalized predictive method of radioiodine prescription that bridges the gap between empiric and theranostic methods is presented. It is an adaptation of the “maximum tolerated activity” method, where serial blood sampling is replaced by population kinetics carefully chosen by the user. It aims to maximize crossfire benefits within safety constraints to overcome tumour absorbed dose heterogeneity for a safe and effective first radioiodine fraction i.e., the First Strike.Methods: The EANM method of blood dosimetry was incorporated with population kinetics, marrow and lung safety constraints, body habitus and clinical assessment of metastatic extent. Population data of whole body and blood kinetics in patients with and without metastases, prepared by recombinant human thyroid stimulating hormone or thyroid hormone withdrawal, and the maximum safe marrow dose rate were deduced from published data. For diffuse lung metastases, the lung safety limit was linearly scaled by height and separated into lung and remainder-of-body components.Results: The slowest whole body Time Integrated Activity Coefficient (TIAC) amongst patients with any metastases was 33.5±17.0 h and the highest percentage of whole body TIAC attributed to blood was 16.6±7.9%, prepared by thyroid hormone withdrawal. A variety of other average radioiodine kinetics is tabulated. Maximum safe marrow dose rate was deduced to be 0.265 Gy/h per fraction, where blood TIAC is normalised to administered activity. An easy-to-use calculator was developed which only requires height, weight and gender to populate recommendations for personalized First Strike prescription. The user decides by clinical gestalt whether the prescription is to be constrained by marrow or lung, then selects an activity depending on how extensive the metastases are likely to be. A Standard Female with oligometastasis and good urine output without diffuse lung metastasis is expected to safely tolerate 8.03 GBq of radioiodine as the First Strike.Conclusion: This predictive method will help institutions rationalise the First Strike prescription based on radiobiologically sound principles, personalised to individual circumstances.

The state of the peripheral blood reflects on bone marrow activity. Therefore, we need to know the normal red bone marrow, and it can be a reference for those interested in hematology. Calves of apparently healthy local breeds were used to examine the state of the bone marrow, take a sample of peripheral blood before slaughter, and then a bone marrow biopsy that was immediately after slaughter. The calves that showed typical values for the parameters of red blood cells and total and differential white blood cells were included in the study. The result of bone marrow smears for nine normal calves appeared to have a faint coloration of granulated myelocytic than erythroid cells. As well as the myeloid was less than the erythroid, and that M: E ratio was 0.91±0.03. The erythroid series, Rubriblast, and Rubricyte were present as the most common progenitor red cell, including basophilic, polychromic, and normochromic cytoplasm, metarubricyte as a reduced nucleus. The myeloid series: Myeloblast, myelocyte was the most common progenitor white cells with granulation as basophilic, eosinophilic and neutrophilic within their cytoplasm, metamyelocyte with shrunken nuclei and band cell with horseshoe nucleus. They rarely found the megakaryocyte, enormous multinucleate cell.

Background and Objectives: Bone marrow (BM) harvesting is one of the essential sources of stem cells for haematopoietic stem cell transplantation. In 2019, commercial BM collection kits became unavailable in Europe. Consequently, we created an in‐house BM collection kit as an alternative. Materials and Methods: We compared two groups of BM collections. The first collections were taken using an in‐house kit from June 2022 through February 2023 and the second with a commercial kit from February 2021 through May 2022. These all took place at seven collection centres (CC). We analysed the harvest quality (cell blood count, CD34+ cells, viability, potency and sterility), the incidents occurring with each kit and the time to neutrophil and platelet engraftment in recipients. Results: A total of 23 donors underwent BM harvesting with the in‐house kit and 23 with the commercial one. Both cohorts were comparable regarding donor characteristics, CC and time to procedure. No statistical differences were found in harvest quality between the in‐house and commercial kits. A new transfusion set was required in three BM harvests (13%) with the in‐house kit because of filter clogging. The median time to neutrophil and platelet engraftment was 21 days for both cohorts and 29 days (in‐house) and 33 days (commercial), p = 0.284, respectively. Conclusion: The in‐house BM collection kit offers a real approach to solve the diminished supply of commercial kits. A higher risk of filter clogging was observed compared with commercial kits due to the lack of 850 and 500 μm filters. [ABSTRACT FROM AUTHOR]

Common pediatric malignancies often surprise clinicians with unusual presentations. In this narrative, we report two patients with common childhood cancer having unique neuroophthalmic characteristics. In the first case, we have a child with a common childhood solid tumor presenting with blindness without proptosis, while the second case is of a child with a common hematological malignancy presenting with unilateral proptosis without visual impairment. The report highlights that common childhood cancers may present with neuroophthalmic symptoms on rare occasions, creating a diagnostic conundrum. [ABSTRACT FROM AUTHOR]

Background: Bone marrow edema (BME) and erosion of the sacroiliac joint are both key lesions for diagnosing axial spondyloarthritis (axSpA) on magnetic resonance imaging (MRI). Purpose: To qualitatively and quantitatively compare intermediate-weighted MRI with fat suppression (IW-FS) with T2-weighted short tau inversion recovery (T2-STIR) in assessment of sacroiliac BME and erosion in axSpA. Material and Methods: Patients aged 18–60 years with axSpA were prospectively enrolled. All patients underwent a 3.0-T MRI examination of the sacroiliac joints. Para-coronal IW-FS, T2-STIR, and T1-weighted (T1W) images were acquired. BME and erosion were scored by two readers in consensus on IW-FS and STIR using a modified Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. Consensus scores on T1WI were used as the reference for erosion. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured for BME. Results: In total, 49 patients (mean age=33.4 ± 7.6 years) were included. More patients were scored as having BME on T2-STIR (36 vs. 29, P = 0.016). SPARCC-BME score on IW-FS was lower than that acquired on T2-STIR (mean, 11.5 vs. 14.7, P = 0.002). SNR and CNR of BME were both lower on IW-FS than on T2-STIR (mean SNR, 118 vs. 218, P < 0.001; mean CNR, 44 vs. 137, P < 0.001). The sensitivity of erosion detection was higher on IW-FS (83%) than on T2-STIR (54%, P = 0.006). Conclusion: IW-FS is not sufficient for BME detection using T2-STIR as the reference standard in patients with axSpA. IW-FS has a much higher sensitivity than T2-STIR for erosion detection in the sacroiliac joint. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to explore the effect of periodontitis on Th‐cell subsets in local and systemic environments. Methods: A total of 32 male Sprague‒Dawley rats were randomly divided into periodontitis and control groups. Silk ligatures were applied to the mandibular first (M1) molars in the periodontitis group. Inflammation and alveolar bone loss around the M1 molars were analyzed by histological staining and microcomputed tomography. The mRNA expression of interferon‐γ (IFN‐γ), interleukin 4 (IL‐4), IL‐17, and IL‐10 in the gingiva was measured by qRT‐PCR. The proportions of Th1, Th2, Th17, and Treg cells in the submandibular lymph nodes, peripheral blood, and jaw bone marrow were tested using flow cytometry. Results: More inflammatory cells and alveolar bone resorption were found in the periodontitis group, with upregulated mRNA expression of IFN‐γ, IL‐17, and IL‐10. The proportion of Th1 and Th17 cells was significantly elevated in submandibular lymph nodes, and the proportion of Th1, Th2, and Th17 cells was significantly elevated in peripheral blood, while the proportion of Th1, Th17, and Treg cells was significantly elevated in jaw bone marrow in the periodontitis group. Conclusion: This study suggests that periodontitis affects the differentiation of Th‐cell subsets in both local and systemic environments, resulting in an increased proportion of proinflammatory cells. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people. Design: Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.0, 30.0). Methods: Detailed assessment of bone microarchitecture (constructive interference in the steady state (CISS) sequence, voxel size 0.2 × 0.2 × 0.4 mm3), bone geometry (T1-weighted turbo spin echo (TSE) sequence, voxel size 0.4 × 0.4 × 2 mm3) and bone marrow (1H-MRS, point resolved spectroscopy sequence (PRESS) (single voxel size 20 × 20 × 20 mm3) size and muscle adiposity (Dixon, voxel size 1.1 × 1.1 × 2 mm3). Results: There was an inverse association of apparent bone volume/total volume (appBV/TV) with age (r = −0.5, P < 0.0005). Cortical area, endosteal and periosteal circumferences and muscle cross-sectional area showed a positive association to age (r > 0.49, P < 0.0001). In those over 17 years of age, these parameters were also higher in males than females (P < 0.05). This sex difference was also evident for appBV/TV and bone marrow adiposity (BMA) in the older participants (P < 0.05). AppBV/TV showed a negative correlation with BMA (r = −0.22, P = 0.01) which also showed an association with muscle adiposity (r = 0.24, P = 0.04). Cortical geometric parameters were highly correlated with muscle area (r > 0.57, P < 0.01). Conclusions: In addition to providing deep insight into the normal relationships between bone, fat and muscle in young people, these novel data emphasize the role of MRI as a non-invasive method for performing a comprehensive and integrated assessment of musculoskeletal health in the growing skeleton.

Objective The evaluation of bone marrow (BM) status is an integral part of the initial workup of patients diagnosed with lymphoma as it plays an important role in staging and predicting prognosis in these patients. This article determines the incidence and pattern of BM involvement in lymphoma cases and distinguishes benign from malignant lymphoid aggregates in BM biopsies. Materials and Methods The study group included 121 cases of Hodgkin and non-Hodgkin lymphomas for which BM biopsies were performed, fixed in acetic acid-zinc formalin solution, decalcified using 10% formic acid, and subjected to hematoxylin and eosin and immunohistochemistry. Results The overall incidence of BM biopsy involvement in our study was 31.4% (37/118), including 34.7% (35/101) in cases of B cell lymphomas, 25% (2/8) in cases of T cell lymphomas, and no involvement in Hodgkin lymphoma. The predominant histological pattern of BM involvement was diffused (14/37; 37.8%), followed by interstitial (10/37; 27.1%). Five cases revealed benign nonparatrabecular lymphoid aggregates which could be confused with lymphomatous involvement, especially in low grade lymphomas. Conclusion A careful examination of the BM biopsies along with clinical history, peripheral blood examination, flow cytometry, and immunohistochemistry will help in arriving at the correct diagnosis. [ABSTRACT FROM AUTHOR]

Postradiotherapy bone fragility fractures are a frequent late‐onset complication in cancer survivors. There is a critical need to develop preventative interventions, and the use of Food and Drug Administration‐approved drugs remains an attractive option. Prior data from our lab and others have shown that parathyroid hormone [1–34] mitigates radiotherapy‐induced bone loss, but only for the duration of drug delivery. Utilizing a murine hindlimb radiotherapy model, we investigated whether orchestrated delivery of single‐dose zoledronic acid could extend these anabolic benefits after cessation of parathyroid hormone delivery. We then explored the potential use of parathyroid hormone as a bone marrow radioprotectant. While the addition of zoledronic acid to parathyroid hormone increased irradiated bone mass, there was no increase in femur bending strength. In this model, the parathyroid hormone was not effective as a marrow radioprotectant, although this could be due to the short course of parathyroid hormone treatment. Marrow repopulation kinetics differed from those in total body irradiation, with hematopoietic stem cell repopulation occurring relatively early at four weeks postirradiation. Furthermore, we found radiation induced a loss of marrow stromal cells and an increase in inflammatory monocytes. Statement of Clinical Significance: Staged delivery of parathyroid hormone and zoledronic acid shows promise as an off‐the‐shelf intervention to mitigate post‐radiotherapy bone damage in cancer patients, but parathyroid hormone is unlikely to function as a broad‐spectrum marrow radioprotectant. [ABSTRACT FROM AUTHOR]

• Priming with karrikinolide (KAR 1) enhanced seed germination in aged marrow, cabbage and pepper seeds. • Repair mechanism of seed aging by the treatments operated through repairing cell structure reducing solute leakage lower electrical conductivity and less K leakage in treated seeds. • Treatments with smoke extract affected ROS enzyme activity i.e. catalase, ascorbate peroxidase and superoxide dismutase activity of aged seeds. • Smoke extract treatments can be an efficient tool for enhancing seedling quality in marrow, cabbage and pepper seeds. The aging process induces the deterioration of seed vigor and viability. Priming methods have been shown to regenerate and rejuvenate aged crop seeds. Several studies have established that plant-derived smoke from burning plant material enhances germination and post-germination. Karrikinolide (KAR 1), which has been identified as a molecule derived from smoke, can improve the germination of seeds of a range of plant species. However, the effect of KAR 1 on aged seeds is not well known. Therefore, this study was carried out to determine the impact of KAR 1 and hydropriming on germination and repair mechanism in unaged and artificially aged pepper, marrow, and cabbage seeds. Aged seeds were artificially produced at 40 ± 1 °C and 100% relative humidity for 48 h in cabbage and 72 h in marrow and pepper. KAR 1 (10−7 M) was applied by dipping seeds in solution at a weight ratio of 1:5 seed: solution for 16 h at 20 °C. Hydropriming was applied under the same conditions using distilled water. Following the treatments, germination, seedling emergence, electrical conductivity, potassium leaching, and enzyme analysis were determined. Results showed that KAR 1- treated seeds had the lowest electrical conductivity and potassium leakage in unaged and artificially aged seeds in all three species. The influence of KAR 1 was more prominent on catalase activity in both artificially aged and unaged seeds. Additionally, KAR 1 treatment improved germination and fresh and dry weights of seedlings in all three species. The results of the present study show that the application of KAR 1 can help improve the performance of marrow, cabbage and pepper seeds in artificially aged (low-quality) seed germination. [ABSTRACT FROM AUTHOR]

The common cellular origin between bone marrow adipocytes (BMAds) and osteoblasts contributes to the intimate link between bone marrow adipose tissue (BMAT) and skeletal health. An imbalance between the differentiation ability of BMSCs towards one of the two lineages occurs in conditions like aging or osteoporosis, where bone mass is decreased. Recently, we showed that the sodium-phosphate co-transporter PiT2/SLC20A2 is an important determinant for bone mineralization, strength and quality. Since bone mass is reduced in homozygous mutant mice, we investigated in this study whether the BMAT was also affected in PiT2-/- mice by assessing the effect of the absence of PiT2 on BMAT volume between 3 and 16 weeks, as well as in an ovariectomy-induced bone loss model. Here we show that the absence of PiT2 in juveniles leads to an increase in the BMAT that does not originate from an increased adipogenic differentiation of bone marrow stromal cells. We show that although PiT2-/- mice have higher BMAT volume than control PiT2+/+ mice at 3 weeks of age, BMAT volume do not increase from 3 to 16 weeks of age, leading to a lower BMAT volume in 16-week-old PiT2-/- compared to PiT2+/+ mice. In contrast, the absence of PiT2 does not prevent the increase in BMAT volume in a model of ovariectomy-induced bone loss. Our data identify SLC20a2/PiT2 as a novel gene essential for the maintenance of the BMAd pool in adult mice, involving mechanisms of action that remain to be elucidated, but which appear to be independent of the balance between osteoblastic and adipogenic differentiation of BMSCs. [ABSTRACT FROM AUTHOR]

Bone marrow is one of the most important organs in the human body. The evaluation of bone marrow microstructure and gender-related cellular and capillary networks in healthy young adults can help to better understand the process of bone metabolism. Intravoxel incoherent motion (IVIM) provides both diffusion and perfusion quantifications without requiring intravenous contrast agent injection. In this prospective study, 60 healthy young agematched volunteers (30 men and 30 women) underwent MRI scans at 1.5 T using multi-b-value diffusion-weighted imaging on sagittal planes covering the lumbar bone marrow. The apparent diffusion coefficient (ADC), true ADC (D), pseudo-ADC (D*), and perfusion fraction (f) were calculated from the diffusion-weighted images using the mono- and bi-exponential models. Lumbar cancellous bone (L2-L4) was selected as the region of interest. An independent t-test was used to detect significant differences in ADC values and IVIM parameters between men and women. The differences in IVIM parameters among the L2, L3, and L4 groups were compared with analysis of variance. The D and f values in women were significantly higher than that in men (p = 0.001, 0.026). However, D* was significantly lower in women than that in men (p = 0.001). Furthermore, there was no significant gender difference for the conventional ADC value (p = 0.186). Moreover, there were no significant differences in the D, f, and D* values among the L2, L3, and L4 vertebras of women or men. IVIM parameters can show differences in bone marrow between young women and men. As a non-invasive method, it can assess bone marrow microstructure, such as cellularity and perfusion. [ABSTRACT FROM AUTHOR]

The common cellular origin between bone marrow adipocytes (BMAds) and osteoblasts contributes to the intimate link between bone marrow adipose tissue (BMAT) and skeletal health. An imbalance between the differentiation ability of BMSCs towards one of the two lineages occurs in conditions like aging or osteoporosis, where bone mass is decreased. Recently, we showed that the sodium-phosphate co-transporter PiT2/SLC20A2 is an important determinant for bone mineralization, strength and quality. Since bone mass is reduced in homozygous mutant mice, we investigated in this study whether the BMAT was also affected in PiT2-/- mice by assessing the effect of the absence of PiT2 on BMAT volume between 3 and 16 weeks, as well as in an ovariectomy-induced bone loss model. Here we show that the absence of PiT2 in juveniles leads to an increase in the BMAT that does not originate from an increased adipogenic differentiation of bone marrow stromal cells. We show that although PiT2-/- mice have higher BMAT volume than control PiT2+/+ mice at 3 weeks of age, BMAT volume do not increase from 3 to 16 weeks of age, leading to a lower BMAT volume in 16-week-old PiT2-/- compared to PiT2+/+ mice. In contrast, the absence of PiT2 does not prevent the increase in BMAT volume in a model of ovariectomy-induced bone loss. Our data identify SLC20a2/PiT2 as a novel gene essential for the maintenance of the BMAd pool in adult mice, involving mechanisms of action that remain to be elucidated, but which appear to be independent of the balance between osteoblastic and adipogenic differentiation of BMSCs.

Implant subsidence into the underlying trabecular bone is a common problem in orthopaedic surgeries; however, the ability to pre-operatively predict implant subsidence remains limited. Current state-of-the-art computational models for predicting subsidence have issues addressing this clinical problem, often resulting from the size and complexity of existing subject-specific, image-based finite element (FE) models. The current study aimed to develop a simplified approach to FE modeling of subject-specific trabecular bone indentation resulting from implant penetration. Confined indentation experiments of human trabecular bone with flat- and sharp-tip indenters were simulated using FE analysis. A generalized continuum-level approach using a meshless smoothed particle hydrodynamics (SPH) approach and an isotropic crushable foam (CF) material model was developed for the trabecular bone specimens. Five FE models were generated with CF material parameters calibrated to cadaveric specimens spanning a range of bone mineral densities (BMD). Additionally, an alternative model configuration was developed that included consideration of bone marrow, with bone and marrow material parameters assigned to elements randomly according to bone volume (BV%) measurements of experimental specimens, owing to the non-uniform nature of trabecular bone tissue microstructure. Statistical analysis found significant correlation between the shapes of the numerical and experimental force-displacement curves. FE models accurately captured the bone densification patterns observed experimentally. Inclusion of marrow elements offered improved response prediction of the flat-tip indenter tests. Ultimately, the developed approach demonstrates the ability of a generalizable continuum-level SPH approach to capture bone variability using clinical bone imaging metrics without needing detailed image-based geometries, a significant step towards simplified subject-specific modeling of implant subsidence. [Display omitted] • Developed a continuum-based approach for modeling trabecular bone indentation. • Examined trabecular bone with marrow using smoothed particle hydrodynamics. • Crushable foam material accurately represented post-yield bone densification. • Model was adaptable to pre-clinical imaging metrics like bone mineral density. [ABSTRACT FROM AUTHOR]

Early B cell factor 1 (EBF1) is a transcription factor expressed by multiple lineages of stromal cells within the bone marrow. While cultures of Ebf1 -deficient cells have been demonstrated to have impaired differentiation into either the osteoblast or adipogenic lineage in vitro by several groups, in vivo there has been a nominal consequence of the loss of EBF1 on skeletal development. In this study we used Prx -cre driven deletion of Ebf1 to eliminate EBF1 from the entire mesenchymal lineage of the skeleton and resolve this discrepancy. We report here that EBF1 is expressed primarily in the Mesenchymal Stem and Progenitor Cell (MSPC)-Adipo, MSPC-Osteo, and the Early Mesenchymal Progenitors, and that loss of EBF1 has a plethora of consequences to maintenance of the skeleton throughout adulthood. S troma from the Prx -cre; Ebf1 fl/fl bones had impaired osteogenic differentiation, an age-dependent loss of CFU-F, and elevated senescence accompanying Ebf1 -deletion. New bone formation was reduced after 3 months, and resulted in a quiescent bone environment with fewer osteoblasts and an accompanied reduction in osteoclast-mediated remodeling. Consequently, bones were less ductile at a younger age, and deletion of EBF1 dramatically impaired fracture repair. Disruption of EBF1 in perivascular populations also rearranged the vascular network within these bones and disrupted cytokine signaling from key hematopoietic niches resulting in anemia, reductions in B cells, and myeloid skewing of marrow hematopoietic lineages. Mechanistically we observed disrupted BMP signaling within Ebf1 -deficient progenitors with reduced SMAD1-phosphorylation, and elevated secretion of the soluble BMP-inhibitor Gremlin from the MSPC-Adipo cells. Ebf1 -deficient progenitors also exhibited posttranslational suppression of glucocorticoid receptor expression. Together, these results suggest that EBF1 signaling is required for mesenchymal progenitor mobilization to maintain the adult skeleton, and that the primary action of EBF1 in the early mesenchymal lineage is to promote proliferation, and differentiation of these perivascular cells to sustain a healthy tissue. [Display omitted] • Removing EBF1 from bone marrow MSPC precipitates a premature marrow aging phenotype • EBF1 is needed to properly mobilize perivascular CAR cells • EBF1 controls the expression of Glucocorticoid Receptor post-translationally • SMAD signaling is disrupted by and abundance of Gremlin production without EBF1 [ABSTRACT FROM AUTHOR]

Objectives: Glucose transporter 1 (GLUT1), a glucose transporter, is an abundant protein in erythrocytes with expression beginning early in erythropoiesis. We sought to evaluate the utility of GLUT1 immunohistochemistry (IHC) as a diagnostic marker for identifying erythroid differentiation in hematopoietic tissues, including neoplastic erythroid proliferations.Methods: A variety of benign and neoplastic bone marrow biopsy specimens containing variable proportions of erythroid precursors were selected (n = 46, including 36 cases of leukemia). GLUT1 IHC was performed using a commercially available polyclonal antibody. Each case was evaluated for staining of erythroid precursors, nonerythroid hematopoietic cells, and blasts. A GATA1/GLUT1 double stain was performed on one case to confirm coexpression of GLUT1 on early erythroid precursors. Staining was compared with other erythroid markers, including glycophorin C.Results: GLUT1 demonstrated strong membranous staining in erythroid precursors of all cases, which was restricted largely to the erythroid lineage. Of the 36 leukemia cases, all 6 cases of pure erythroid leukemia and both cases of therapy-related acute myeloid leukemia with erythroid differentiation showed positive GLUT1 staining in blasts. Otherwise, only lymphoblasts in B-lymphoblastic leukemia showed weak to moderate granular cytoplasmic staining (four of five cases).Conclusions: GLUT1 IHC is a highly sensitive and relatively specific marker for erythroid lineage in benign and neoplastic bone marrow biopsy specimens. [ABSTRACT FROM AUTHOR]

It is an important cognition of the theory of traditional Chinese medicine that the kidney dominates bone and produces marrow. It is believed that the dysfunction of the kidney viscera is the fundamental cause of the occurrence and development of bone disease in TCM. Based on clinical experience and this theory, combined with ancient literature and modern research, Zhejiang scholars of orthopedics and traumatologists have creatively put forward the impact of the marrow of extraordinary Fu-organ on orthopedic diseases as an independent research topic, systematically constructed a theoretical system of myeloid bone disease, and established the marrow regulating therapy. Hemophilia-induced osteoporosis is one of such diseases. Its main pathogenesis is the abnormality of congenital essence, which causes blood flow outside the pulse, triggering the imbalance of storage and diarrhea of the marrow, and then the imbalance of bone homeostasis, resulting in osteoporosis. The treatment principle should both treat the symptoms and the root causes, regulate the marrow internally and externally, and restore bone homeostasis. Based on the relationship among the essence, bone, marrow, and blood, this paper expounds the cognition of TCM and modern medicine of hemophilic osteoporosis, and probes into the treatment of hemophilia-induced osteoporosis with marrow regulating method. [ABSTRACT FROM AUTHOR]

Abstract In this study, we investigated the influence of the loss of cathepsin K (Ctsk) gene on the hematopoietic system in vitro and in vivo. We found that cultures with lineage− SCA1+ KIT+ (LSK) cells on Ctsk deficient stromal cells display reduced colony formation and proliferation, with increased differentiation, giving rise to repopulating cells with reduced ability to repopulate the donor LSKs and T cell compartments in the bone marrow (BM). Subsequent in vivo experiments showed impairment of lymphocyte numbers, but, gross effects on early hematopoiesis or myelopoiesis were not found. Most consistently in in vivo experimental settings, we found a significant reduction of (donor) T cell numbers in the BM. Lymphocyte deregulation is also found in transplantation experiments, which revealed that Ctsk is required for optimal regeneration of small populations of T cells, particularly in the BM, but also of thymic B cells. Interestingly, cell nonautonomous Ctsk regulates both B and T cell numbers, but T cell numbers in the BM require an additional autonomous Ctsk‐dependent process. Thus, we show that Ctsk is required for the maintenance of hematopoietic stem cells in vitro, but in vivo, Ctsk deficiency most strongly affects lymphocyte homeostasis, particularly of T cells in the BM.

Abstract Background Joints withstand huge forces, but little is known about subchondral pressures and perfusion during loading. We developed an in vitro calf foot model to explore intraosseous pressure (IOP) and subchondral perfusion during weight bearing. Methods Freshly culled calf forefeet were perfused with serum. IOP was measured at three sites in the foot using intraosseous needles, pressure transducers, and digital recorders. IOP was measured during perfusion, with and without a tourniquet and with differing weights, including static loading and dynamic loading to resemble walking. Results IOP varied with perfusion pressure. Static loading increased subchondral IOP whether the bone was non-perfused, perfused, or perfused with a proximal venous tourniquet (p < 0.0001). Under all perfusion states, IOP was proportional to the load (R 2 = 0.984). Subchondral IOP often exceeded perfusion pressure. On removal of a load, IOP fell to below the pre-load value. Repetitive loading led to a falling IOP whether the foot was perfused or not. Conclusion Superimposed on a variable background IOP, increased perfusion and physiological loading caused a significant increase in subchondral IOP. Force was thereby transmitted through subchondral bone partly by hydraulic pressure. A falling IOP with repeat loading suggests that there is an intraosseous one-way valve. This offers a new understanding of subchondral perfusion physiology.

Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (CY) after ablative HLA-matched bone marrow (BM) transplantation has been reported to have comparable rates of acute GVHD with an apparent reduction in chronic GVHD and infections when compared to historical prophylaxis with a calcineurin-inhibitor (CNI) and methotrexate (MTX). We conducted a phase II trial of post-transplantation CY (post-CY) after reduced-intensity conditioning (RIC) using intravenous busulfan (area under the curve of 4000 micromolar minute), fludarabine (40 mg/m(2)) for 4 days, and CY 50 mg/kg on days +3 and +4 after BM or peripheral blood (PB) transplantations from matched related (MRD) or unrelated donors (MUD). MUD recipients received antithymocyte globulin (ATG); however, a later amendment removed ATG. Forty-nine patients were treated (acute myeloid leukemia/myelodysplastic syndrome, 82%). Median age was 62 years (range, 39 to 72). Fifteen patients received an MRD (9 PB/6 BM); 34 had a MUD (2 PB/32 BM). The cumulative incidence of grade II to IV acute GVHD, III to IV acute GVHD, and chronic GVHD was 58%, 22%, and 18%, respectively. A matched cohort analysis compared outcomes to tacrolimus/methotrexate GVHD prophylaxis and indicated higher rates of acute GVHD grade II to IV (46% versus 19%; hazard ratio [HR], 2.8; P = .02) and treatment-related mortality (HR, 3.3; P = .035) and worse overall survival (HR, 1.9; P = .04) with post-CY. The incidence of chronic GVHD and CMV reactivation did not differ. This study suggests that post-CY should not be used as sole GVHD prophylaxis after a RIC transplantation from HLA-matched donors.

Background. Detection of the pathogenicity factors is one of the actual directions in studying of the anthrax causative agent. First of all, it includes the presence of tripartite toxin, capsule and the related structural and regulatory genes. Their presence or absence is defined by structural changes in cellular structure of blood and immunocomplex organs of a macroorganism.Objective: To conduct a comparative analysis of subpopulational structure of marrow and peripheral blood cells at anthrax infection in experimental animals and to trace dynamics of the infectious process caused by Bacillus anthracis of different genotypes.Methods. Comparative examination of subpopulational structure of red marrow and peripheral blood cells of white mice in dynamics of the infectious process caused by B. anthracis of different genotypes was conducted. Also, neutrophil maturing index and leucoerythrocytic correlation were calculated in red marrow. Degree of manifestation of neutrophil pathological granularity was revealed in peripheral blood smears stained by the Freifeld’s method. Statistical processing of the received data was conducted using the computer program “Statistics”, version 6 (Novosibirsk). Authentic results were considered if the error probability was less than 0.05 (р < 0.05) in relation to the control.Results. It is revealed that alterations in white mice infected by B. anthracis strains with the same set of plasmids are significantly various.Conclusion. The resulted data permit to assume that the distinction of pathological alterations in peripheral blood and red marrow is probably connected with the other factors of the pathogen invasiveness like enzymatic activity, ability to adhesion and many others.

Abstract Background Bone marrow mononuclear cells have been successfully utilized for numerous regenerative purposes. In the current study, patients suffering from erectile dysfunction (ED) unresponsive to phosphodiesterase 5 inhibitors were administered autologous bone marrow concentrate delivered intracavernously utilizing a point of care FDA cleared medical device. Methods A total of 40 patients were treated in the primary trial and 100 in the clinical registry, with the longest follow up of 12 months. Results Minimal treatment associated adverse effects where observed related to short term bruising at the site of harvest or injection. No long-term adverse events were noted related to the intervention. Mean improvements in IIEF-5 score were 2 in the Caverstem 1.0 low dose group, 3 in the high dose Caverstem 1.0 group and 9 in the Caverstem 2.0 group. Furthermore, improvements peaked by 3 months and maintained at 6 months follow-up. Conclusion These data support the safety and efficacy of point of care, minimally to non-manipulated, non-expanded bone marrow concentrate for the treatment of ED. Trial registration Funded by Creative Medical Health, Inc.; Clinicaltrials.gov number: NCT03699943; https://clinicaltrials.gov/ct2/show/NCT03699943?term=caverstem&rank=1 ; initially registered December 12, 2015.

Abstract Background Numerous predatory insects were recorded on different plants; some were fed on the floral nectar and others as visitors. Other insects used any plant as a shelter or associated with their prey. Pollinators and beneficial arthropods suffering from a wide range of chemical pesticides are used. So, seeking for safer alternatives is mandatory to conserve such beneficial arthropods. Sorell-98% is a sulphur formulation which was examined against some insect predators with minimal adverse impacts. Method Agricultural Sorell-98% (commercial Sulphur formulation) was applied to protect many crops against some plant diseases and sucking insect pests (aphis, whiteflies, thrips) and mite pests as well. This formulation was applied at a rate of 30 kg/Feddan after 30 days of plantation. Two rectangular areas (ca. 700 m2 each) were chosen to execute experiments. The first area was in a field which was sown with marrow plant, while the second was in an okra field. Each area was partitioned into four equal plots (ca. 75 m2). Similar plots (third area) were done but received no treatments (second control area). Examination of the mean numbers of the natural enemies was recorded at several intervals and was achieved at 7 am. Samples of 50 plants were inspected—on spot—per plot/time interval in the three experimental zones. The mean number of each predator/time interval and percentage of increase and/or decrease was calculated. Results Results reveal that the abundance of the target predators was affected indirectly in different cultivated plants after sulphur application, as a result of different plant nature and consequently the population of pests invaded. At all inspection periods, it was observed that the mean numbers and abundance of adult predators on marrow plants was more than that reported in an okra field. Under all inspection times, there was a significant difference between the mean numbers of recorded predators, where Coccinella adults recorded the highest mean numbers, followed by Chrysoperla adults. Stethorus adults recorded the least mean number, either before or after sulphur application. Conclusion The abundance of any arthropod predators is closely related with their favourable insect prey and did not relate to a certain plant by itself. The three tested adult predators were—to some extent—affliction from the sulphur application.

In this study, we investigated the influence of the loss of cathepsin K (Ctsk) gene on the hematopoietic system in vitro and in vivo. We found that cultures with lineage− SCA1+ KIT+ (LSK) cells on Ctsk deficient stromal cells display reduced colony formation and proliferation, with increased differentiation, giving rise to repopulating cells with reduced ability to repopulate the donor LSKs and T cell compartments in the bone marrow (BM). Subsequent in vivo experiments showed impairment of lymphocyte numbers, but, gross effects on early hematopoiesis or myelopoiesis were not found. Most consistently in in vivo experimental settings, we found a significant reduction of (donor) T cell numbers in the BM. Lymphocyte deregulation is also found in transplantation experiments, which revealed that Ctsk is required for optimal regeneration of small populations of T cells, particularly in the BM, but also of thymic B cells. Interestingly, cell nonautonomous Ctsk regulates both B and T cell numbers, but T cell numbers in the BM require an additional autonomous Ctsk‐dependent process. Thus, we show that Ctsk is required for the maintenance of hematopoietic stem cells in vitro, but in vivo, Ctsk deficiency most strongly affects lymphocyte homeostasis, particularly of T cells in the BM. [ABSTRACT FROM AUTHOR]

We devised and clinically validated a schema of rapid personalized predictive dosimetry for 177 Lu-PSMA-I&T in metastatic castration-resistant prostate cancer. It supersedes traditional empiric prescription by providing clinically meaningful predicted absorbed doses for first-strike optimization. Methods: Prostate-specific membrane antigen PET was conceptualized as a simulation study that captures the complex dosimetric interplay between tumor, marrow, and kidneys at a single time point. Radiation principles of fractionation, heterogeneity, normal-organ constraints (marrow, kidney), absorbed dose, and dose rate were introduced. We created a predictive calculator in the form of a free, open-source, and user-friendly spreadsheet that can be completed within minutes. Our schema achieves speed and accuracy by sampling tissue radioconcentrations (kBq/cm 3 ) to be analyzed in conjunction with clinical input from the user that reflect dosimetric preconditions. The marrow-absorbed dose constraint was 0.217 Gy (dose rate, ≤0.0147 Gy/h) per fraction with an interfraction interval of at least 6 wk. Results: Our first 10 patients were analyzed. The first-strike mean tumor-absorbed dose threshold for any prostate-specific antigen (PSA) response was more than 10 Gy (dose rate, >0.1 Gy/h). The metastasis with the lowest first-strike tumor-absorbed dose correlated the best with the percentage decrease of PSA; its threshold to achieve hypothetical zero PSA was 20 Gy or more. Each patient's PSA doubling time can be used to personalize their unique absorbed dose-response threshold. The predicted mean first-strike prescription constrained by marrow-absorbed dose rate per fraction was 11.0 ± 4.0 GBq. Highly favorable conditions (tumor sink effect) were dosimetrically expressed as the combination of tumor-to-normal-organ ratios of more than 150 for marrow and more than 4 for kidney. Our schema obviates the traditional role of the SUV as a predictive parameter. Conclusion: Our rapid schema is feasible to implement in any busy real-world theranostics unit and exceeds today's best practice standards. Our dosimetric thresholds and predictive parameters can radiobiologically rationalize each patient's first-strike prescription down to a single becquerel. Favorable tumor-to-normal-organ ratios can be prospectively exploited by predictive dosimetry to optimize the first-strike prescription. The scientific framework of our schema may be applied to other systemic radionuclide therapies., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Increased risk of fracture identified in obese children has led to a focus on the relationship between fat, bone, and the impact of obesity during skeletal development. Early studies have suggested that despite increased fracture risk, obese children have a higher bone mass. However, body size corrections applied to account for wide variations in size between children led to the finding that obese children have a lower total body and regional bone mass relative to their body size. Advances in skeletal imaging have shifted the focus from quantity of bone in obese children to evaluating the changes in bone microarchitecture that result in a change in bone quality and strength. The findings suggest that bone strength in the appendicular skeleton does not appropriately adapt to an increase in body size which results in a mismatch between bone strength and force from falls. Recent evidence points to differing influences of fat compartments on skeletal development—visceral fat may have a negative impact on bone which may be related to the associated adverse metabolic environment, while marrow adipose tissue may have an independent effect on trabecular bone development in obese children. The role of brown fat has received recent attention, demonstrating differences in the influence on bone mass between white and brown adipose tissues. Obesity results in a shift in growth and pubertal hormones as well as influences bone development through the altered release of adipokines. The change in the hormonal milieu provides an important insight into the skeletal changes observed in childhood obesity.

Abstract Background For the sake of environmental safety, many sulfur formulations were recommended in many Integrated Pest Management (IPM) programs to protect, particularly, edible vegetables and fruit trees from insect and mite pests as well as plant pathogenic diseases. Such formulations, at the recommended application rates, proved to be safer to mammals. Regarding their safety to beneficial arthropods, diversified results were reported. This study was designed to investigate and evaluate the impact of sulfur formulation against some natural enemies naturally prevailing in some vegetable crops. Method Sulfur formulation (Agricultural Sorell-98%) was recommended by the Ministry of Agriculture, Egypt, as a protectant for vegetable crops against some plant diseases and piercing-sucking pests (aphis, whiteflies, thrips, and mites) at the rate of 30 kg/Feddan 30 days post plantation. The experiment was undertaken in two similar rectangle areas during the season (2016/2017). Each area about 700 m2 was sown with marrow plant. The first area was divided longwise into two halves, each half comprises six rows and divided horizontally into four plots each about 75 m2. Similar plots were done in the second area but no treatments were made (check area). Monitoring the density fluctuations of the natural enemies in the target areas was undertaken at certain intervals (just before dusting, 2, 12, 24, 48, and 72 h and 7 days after application) and achieved early in the morning (7 am). Fifty plants were inspected per plot per time interval in treated and untreated areas. The average number of each natural enemy/time interval and percent increase or decrease in the population density in the treated half and the untreated one were calculated. Results The obtained data revealed that the least number of the prevailing adults was recorded at the treated plot after 2 h post treatment for Coccinella and after 12 h for Stethorus adults. In addition, it could be observed that the mean number of the recorded adults occurred in the untreated plot of the first area was increased significantly than that of the untreated second area at 12 and 48 h and after 1 week post treatment, this could be referred to the following: when the treated plot was sprayed with sulfur compound, most of the prevailing adults escaped from the dust and migrate to the untreated plot or other clean plants (untreated plot or other surrounding plants), then they returned back gradually to the treated plot. Conclusion The obtained results clarify that the intelligent handling of sulfur formulations in order to control some pests and plant diseases with minimal or harmless effects towards the adult predators under investigation must be taken in consideration; thus, this could be more favorable to keep the environment clean and non-polluted. In addition, results throw light on that Stethorus punctillum was more susceptible than Coccinella undecimpunctata especially for the sulfur residues on treated plants.

Data on the efficiency of low-molecular peptide preparations, selected from cultivated stem cells of marrow, in the treatment of acute kidney insufficiency in experimental animals are resulted. It is demonstrated that the use of peptide preparations reliably promotes survivability of experimental animals suffering from acute kidney insufficiency.

The development of safe and reliable haematopoietic cell transplantation (HCT) protocols to treat human patients with malignant and non‐malignant blood disorders was highly influenced by preclinical studies obtained in random‐bred canines. The surmounted barriers included recognizing the crucial importance of histocompatibility matching, establishing long‐term donor haematopoietic cell engraftment, preventing graft‐vs‐host disease and advancing effective conditioning and post‐grafting immunosuppression protocols, all of which were evaluated in canines. Recent studies have applied the tolerance inducing potential of HCT to solid organ and vascularized composite tissue transplantation. Several advances in HCT and tolerance induction that were first developed in the canine preclinical model and subsequently applied to human patients are now being recruited into veterinary practice for the treatment of malignant and non‐malignant disorders in companion dogs. Here, we review recent HCT advancements attained in the canine model during the past 15 years. [ABSTRACT FROM AUTHOR]

Bone grease rendering is a low-return activity well described in the ethnohistorical and ethnographic literature. However, identifying this activity in archaeological contexts is complex because diagnostic criteria are few. The goals of this article are twofold: (1) to provide new experimental data on bone grease manufacture for assemblages associated with severe fragmentation, and (2) to assess how these data can be used to make stronger inferences about skeletal fat processing in the archaeological record. The results presented here show that, despite some variation, several forms of damage appear to be diagnostic of bone grease manufacture, regardless of the degree of fragmentation. The results indicate that extensive pounding produces many fragments that can be identified as deriving from articular ends, which conflicts with the oft-cited notion that articular ends are destroyed "beyond recognition" during this activity. Consequently, assemblages with few epiphyseal remains are not consistent with bone grease rendering, assuming that the comminuted fragments were not burned or discarded off-site after boiling. Because bone grease manufacture produces many small fragments, a close analysis of the indeterminate remains is strongly recommended, as is the use of fine mesh screens (2 mm or smaller) in excavations. [ABSTRACT FROM AUTHOR]

Background: Joints withstand huge forces, but little is known about subchondral pressures and perfusion during loading. We developed an in vitro calf foot model to explore intraosseous pressure (IOP) and subchondral perfusion during weight bearing. Methods: Freshly culled calf forefeet were perfused with serum. IOP was measured at three sites in the foot using intraosseous needles, pressure transducers, and digital recorders. IOP was measured during perfusion, with and without a tourniquet and with differing weights, including static loading and dynamic loading to resemble walking. Results: IOP varied with perfusion pressure. Static loading increased subchondral IOP whether the bone was non-perfused, perfused, or perfused with a proximal venous tourniquet (p < 0.0001). Under all perfusion states, IOP was proportional to the load (R2 = 0.984). Subchondral IOP often exceeded perfusion pressure. On removal of a load, IOP fell to below the pre-load value. Repetitive loading led to a falling IOP whether the foot was perfused or not. Conclusion: Superimposed on a variable background IOP, increased perfusion and physiological loading caused a significant increase in subchondral IOP. Force was thereby transmitted through subchondral bone partly by hydraulic pressure. A falling IOP with repeat loading suggests that there is an intraosseous one-way valve. This offers a new understanding of subchondral perfusion physiology. [ABSTRACT FROM AUTHOR]

There is a lack of randomized research measuring how music therapy might influence fatigue in oncology patients. The purpose of this randomized pilot study was to evaluate the effects of music therapy in the form of patient-preferred live music (PPLM) on fatigue, energy and pain in adults hospitalized on a blood and marrow transplant (BMT) unit. Participants (n = 35) were randomly assigned to an experimental or wait-list control group and completed the Lee Fatigue Scale and a 10-point Likert-type pain scale at pre- and posttest. Between-group posttest results were statistically significant for fatigue and pain, with the experimental group having less fatigue and pain than the control group. PPLM can be a preferred and effective intervention to immediately lessen fatigue and pain without pharmacological intervention. Implications for clinical practice, limitations and suggestions for future research are provided. [ABSTRACT FROM AUTHOR]