Systemic Osteoporosis and Osteopenia Among Periprosthetic Fractures After Total Hip Arthroplasty.

BACKGROUND: Most periprosthetic fractures following total hip arthroplasty (THA) are fragility fractures that qualify patients for osteoporosis diagnoses. However, it remains unknown how many patients were diagnosed who had osteoporosis before injury or received the proper evaluation, diagnosis, and treatment after injury. METHODS: We identified 171 Vancouver B2 (109) and B3 (62) periprosthetic femur fractures treated with a modular fluted tapered stem from 2000 to 2018 at one institution. The mean patient age was 75 years (range, 35 to 94), 50% were women, and the mean BMI was 29 (range, 17 to 60). We identified patients who had osteoporosis or osteopenia diagnoses, a fracture risk assessment tool (FRAX), bone mineral density (BMD) testing, an endocrinology consult, and osteoporosis medications. Age-appropriate BMD testing was defined as no later than one year after the recommended ages of 65 (women) or 70 years (men). The mean follow-up was 11 years (range, 4 to 21). RESULTS: Falls from standing height caused 94% of fractures and thus, by definition, qualified as osteoporosis-defining events. The prevalence of osteoporosis diagnosis increased from 20% before periprosthetic fracture to 39% after (P < 0.001). The prevalence of osteopenia diagnosis increased from 13% before the fracture to 24% after (P < 0.001). The prevalence of either diagnosis increased from 24% before fracture to 44% after (P < 0.001). No patients had documented FRAX scores before fracture, and only 2% had scores after. The prevalence of BMD testing was 21% before fracture and 22% after (P = 0.88). By the end of the final follow-up, only 16% had received age-appropriate BMD testing. The proportion of patients who had endocrinology consults increased from 6% before the fracture to 25% after (P < 0.001). The proportion on bisphosphonate therapy was 19% before fracture and 25% after (P = 0.08). CONCLUSIONS: Although most periprosthetic fractures following THA are fragility fractures that qualify patients for osteoporosis diagnoses, there remain major gaps in diagnosis, screening, endocrinology follow-up, and treatment. Like non-arthroplasty fragility fractures, a systematic approach is needed after periprosthetic fractures.

Periprosthetic fractures are osteoporotic fractures: missed opportunities for osteoporosis diagnosis.

Joint replacement surgery is common in older adults, leading to increasing periprosthetic fracture (PPFx) occurrence. We reviewed all PPFx seen over a 4-year period at an academic hospital. Clinical osteoporosis could be diagnosed based on existing data in 104 (67%) at the time of PPFx. Periprosthetic fractures are generally osteoporosis-related. PURPOSE: Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. METHODS: The electronic medical record (EMR) of PPFx patients seen over 4 years in a university orthopedic practice were reviewed. Demographic data and osteoporosis relevant parameters were collected. Prior DXA studies were reviewed, and L1 Hounsfield unit (HU) measurements were performed on CT scans obtained within 2 years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. RESULTS: Records of 156 PPFx patients (115 F/41 M), mean (SD) age 75.4 (11.9), were reviewed. Almost all 153/156 (98%) of these fractures were femoral. Falls caused 139 (89%); 12 (8%) were spontaneous. Mean time post-arthroplasty was 7.9 (6.3) years. Prior fragility fracture(s) occurred in 72 (46%); 14 were PPFx. Osteoporosis was previously diagnosed in 45 (29%) and medications prescribed in 41 (26%). Prior to PPFx, DXA data were available in 62, mean (SD) lowest T-score was - 1.9 (0.9) and was ≤ - 2.5 in 19. CT data were available in 46; mean (SD) L1 HU was 79.0 (29.4) and was ≤ 100 in 35. Based on existing data, clinical osteoporosis could have been diagnosed in 104 (67%) at the time of PPFx. CONCLUSION: Periprosthetic fractures are osteoporosis-related. They occur in older adults, often female, and result from falls; BMD, when assessed, is low. Data available at the time of PPFx often allows osteoporosis diagnosis; this should prompt evaluation and pharmacologic treatment consideration.

Molecular Mechanisms Associated with the Development of the Metritis Complex in Dairy Cattle.

The metritis complex (MC), a group of post-partum uterine diseases, is associated with increased treatment costs and reduced milk yield and fertility. The goal of this study was to identify genetic variants, genes, or genomic regions that modulate MC disease. A genome-wide association study was performed using a single-locus mixed linear model of 1967 genotypes (624,460 SNPs) and metritis complex records. Then, in-silico functional analyses were performed to detect biological mechanisms and pathways associated with the development of MC. The ATP8A2, COX16, AMN, and TRAF3 genes, located on chromosomes 12, 10, and 21, were associated with MC at p ≤ 0.0001. These genes are involved in the regulation of cholesterol metabolism in the stromal tissue of the uterus, which can be directly associated with the mode of transmission for pathogens causing the metritis complex. The modulation of cholesterol abundance alters the efficiency of virulence factors and may affect the susceptibility of the host to infection. The SIPA1L1, DEPDC5, and RNF122 genes were also significantly associated with MC at p ≤ 0.0001 and are involved in the PI3k-Akt pathway, responsible for activating the autophagic processes. Thus, the dysregulation of these genes allows for unhindered bacterial invasion, replication, and survival within the endometrium.

The impact of sociodemographic determinants and diabetes type-2 on oral health outcomes: An analytical cross-sectional study.

OBJECTIVES: This study compared adults with type 2 diabetes (T2DM) and those without diabetes (ND) from East London in terms of sociodemographic characteristics, oral health behaviors, dietary practices, and alcohol and tobacco-related habits. MATERIALS AND METHODS: A total of 182 participants (n = 91 for each group) were recruited and requested to complete the validated questionnaire with 33 items. RESULTS: Results showed that the mean ± SD age was 61 ± 11.7 in the T2DM, while 51 ± 11.2 in the ND group. The mean ± SD age at T2DM diagnosis was 43 ± 10. There was a significant gender difference, with more males in the T2DM group (67.7%) and more females in the ND group (64.8%). Asian-British (38.4%) were significantly high in the T2DM group when compared to other ethnicities. 92.3% of T2DM participants were significantly more likely to use medications in comparison to the ND group (29.7%). The T2DM participants' personal statements on general health were fair (34%) and good (46.2%) when compared with the ND group (15.4% and 59.3%, respectively). The majority of T2DM and ND participants (98%) lacked dental insurance. In the T2DM group, 31.8% were receiving benefits, and 39.5% were retired, while 46% of the ND group were full-time employees. Tooth brushing twice a day was slightly less common in T2DM (68%) when compared to the ND group (78%). Nearly half of the participants in both groups failed to carry out interdental cleaning (T2DM = 52%; ND = 47%), and 38.5% of the T2DM group used mouthwash occasionally, while 30% of the ND group had it twice daily. There was a weak association between chewing paan and annual income in ND participants (r = .90, p = .49). There were significant differences in the presence of removable prostheses, juice, and sweetened juice consumptions between the two groups (p < .05). CONCLUSION: Within the confines of this study, being male, Asian British, retired due to disability, polypharmacy, and the presence of removable prostheses were all significant factors for T2DM.

An orthotopic syngeneic mouse model of bortezomib-resistant multiple myeloma.

While bortezomib has significant benefits in multiple myeloma (MM) therapy, the disease remains incurable due to the invariable development of bortezomib resistance. This emphasises the need for advanced models for preclinical evaluation of new therapeutic approaches for bortezomib-resistant MM. Here, we describe the development of an orthotopic syngeneic bortezomib-resistant MM mouse model based on the most well-characterised syngeneic MM mouse model derived from spontaneous MM-forming C57BL/KaLwRij mice. Using bortezomib-resistant 5TGM1 cells, we report and characterise a robust syngeneic mouse model of bortezomib-resistant MM that is well suited to the evaluation of new therapeutic approaches for proteasome inhibitor-resistant MM.

Influence of gender and combined estrogen-progestin oral contraceptive on parotid saliva flow rate, pH, and electrolytes concentration.

OBJECTIVES: Endocrinal variations within an individual impact the electrolyte composition, pH, and flow-rate (FR) of saliva. The aim of this study was to evaluate the gender-specific differences and the effect of combined estrogen-progestin oral contraceptives (COCs) on FR, pH, and electrolyte concentrations in the parotid saliva (PS) of a group of healthy adults. MATERIAL AND METHODS: Stimulated PS was collected from 20 healthy adults using a Lashley cup; 11 males, 8 females, and 1 female undertaking combined contraceptive therapy (levonorgestrel/ethinyloestradiol 0.1 mg + 0.02 mg). FR and pH were recorded for each saliva sample. Electrolytes concentrations (Na+ , Ca2+ , K+ , Mg2+ ) were measured using inductively coupled plasma optical emission spectrometer (ICP-OES). Statistical analysis was performed, and the significance level was set at p < .05. RESULTS: PS FR varied from 0.13 to 0.42 mL/min in females not taking any medication and from 0.08 to 0.5 mL/min in males not taking any medication. PS pH of females and males not taking any medication ranged from 6.23 to 7.50 and from 6.15 to 7.55. PS pH and FR of the female taking COCs were 6.5 and 0.1 mL/min. PS pH, FR, and electrolytes concentrations (Ca2+ , Na+ , K+ , Mg2+ ) were not statistically significantly different between females and males not taking any medication. PS concentrations of Ca2+  and Na+ were significantly higher in the females taking COCs than in the females not taking any medication. Whereas, concentrations of K+ and Mg2+ did not differ significantly between the females taking COCs and the females not taking any medication. CONCLUSIONS: There are no significant gender-specific differences in PS flow rate, pH, and electrolyte concentrations of Na+ , Ca2+ , Mg2+ , and K+ . Combined hormonal oral contraceptive has a significant effect on PS flow rate, pH, Ca2+ , and Na+ concentrations. Whereas the PS concentration of K+ and Mg2+ are not influenced by COCs. These results warrant further investigation.

An exploration of knowledge-organizing technologies to advance transdisciplinary back pain research.

Chronic low back pain (LBP) is influenced by a broad spectrum of patient-specific factors as codified in domains of the biopsychosocial model (BSM). Operationalizing the BSM into research and clinical care is challenging because most investigators work in silos that concentrate on only one or two BSM domains. Furthermore, the expanding, multidisciplinary nature of BSM research creates practical limitations as to how individual investigators integrate current data into their processes of generating impactful hypotheses. The rapidly advancing field of artificial intelligence (AI) is providing new tools for organizing knowledge, but the practical aspects for how AI may advance LBP research and clinical are beginning to be explored. The goals of the work presented here are to: (1) explore the current capabilities of knowledge integration technologies (large language models (LLM), similarity graphs (SGs), and knowledge graphs (KGs)) to synthesize biomedical literature and depict multimodal relationships reflected in the BSM, and; (2) highlight limitations, implementation details, and future areas of research to improve performance. We demonstrate preliminary evidence that LLMs, like GPT-3, may be useful in helping scientists analyze and distinguish cLBP publications across multiple BSM domains and determine the degree to which the literature supports or contradicts emergent hypotheses. We show that SG representations and KGs enable exploring LBP's literature in novel ways, possibly providing, trans-disciplinary perspectives or insights that are currently difficult, if not infeasible to achieve. The SG approach is automated, simple, and inexpensive to execute, and thereby may be useful for early-phase literature and narrative explorations beyond one's areas of expertise. Likewise, we show that KGs can be constructed using automated pipelines, queried to provide semantic information, and analyzed to explore trans-domain linkages. The examples presented support the feasibility for LBP-tailored AI protocols to organize knowledge and support developing and refining trans-domain hypotheses.

Reversible Cross-linked Thermoresponsive Polycaprolactone Micelles for Enhanced Stability and Controlled Release.

Thermoresponsive amphiphilic poly(ε-caprolactone)s (PCL)s are excellent candidates for drug delivery due to their biodegradability, biocompatibility, and controlled release. However, the thermoresponsivity of modified PCL can often lead to premature drug release because their lower critical solution temperature (LCST) is close to physiological temperature conditions. To address this issue, we developed a novel approach that involves functionalizing redox-responsive lipoic acid to the hydrophobic block of PCL. Lipoic acid has disulfide bonds that undergo reversible cross-linking after encapsulating the drug. Herein, we synthesized an ether-linked propargyl-substituted PCL as the hydrophobic block of an amphiphilic copolymer along with unsubstituted PCL. The propargyl group was used to attach lipoic acid through a postpolymerization modification reaction. The hydrophilic block is composed of an ether-linked, thermoresponsive tri(ethylene glycol)-substituted PCL. Anticancer drug doxorubicin (DOX) was encapsulated within the core of the micelles and induced cross-linking in the presence of a reducing agent, dithiothreitol. The developed micelles are thermodynamically stable and demonstrated thermoresponsivity with an LCST value of 37.5 °C but shifted to 40.5 °C after cross-linking. The stability and release of both uncross-linked (LA-PCL) and cross-linked (CLA-PCL) micelles were studied at physiological temperatures. The results indicated that CLA-PCL was stable, and only 35% release was observed after 46 h at 37 °C while LA-PCL released more than 70% drug at the same condition. Furthermore, CLA-PCL was able to release a higher amount of DOX in the presence of glutathione and above the LCST condition (42 °C). Cytotoxicity experiments revealed that CLA-PCL micelles are more toxic toward MDA-MB-231 breast cancer cells at 42 °C than at 37 °C, which supported the thermoresponsive release of the drug. These results indicate that the use of reversible cross-linking is a great approach toward synthesizing stable thermoresponsive micelles with reduced premature drug leakage.

Unbiased gene expression analysis of the delayed fracture healing observed in Zucker diabetic fatty rats.

Aims: Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods: Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results: Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion: These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients.

Opportunistic CT-Based Hounsfield Units Strongly Correlate with Biomechanical CT Measurements in the Thoracolumbar Spine.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Hounsfield units (HUs) are known to correlate with clinical outcomes, no study has evaluated how they correlate with BCT and DXA measurements. SUMMARY OF BACKGROUND: Low bone mineral density (BMD) represents a major risk factor for fracture and poor outcomes following spine surgery. Dual-energy x-ray absorptiometry (DXA) can provide regional BMD measurements but has limitations. Opportunistic HUs provide targeted BMD estimates; however, they are not formally accepted for diagnosing osteoporosis in current guidelines. More recently, biomechanical computed tomography (BCT) analysis has emerged as a new modality endorsed by the International Society for Clinical Densitometry (ISCD) for assessing bone strength. METHODS: Consecutive cases from 2017-2022 at a single institution were reviewed for patients who underwent BCT in the thoracolumbar spine. BCT-measured vertebral strength, trabecular BMD, and the corresponding American College of Radiology (ACR) Classification were recorded. DXA studies within three months of the BCT were reviewed. Pearson Correlation Coefficients were calculated, and receiver-operating characteristic curves were constructed to assess the predictive capacity of HUs. Threshold analysis was performed to identify optimal HU values for identifying osteoporosis and low BMD. RESULTS: Correlation analysis of 114 cases revealed a strong relationship between HUs and BCT vertebral strength (r=0.69; P<0.0001; R2=0.47) and trabecular BMD (r=0.76; P<0.0001; R2=0.58). However, DXA poorly correlated with opportunistic HUs and BCT measurements. HUs accurately predicted osteoporosis and low BMD (Osteoporosis: C=0.95, 95% CI 0.89-1.00; Low BMD: C=0.87, 95% CI 0.79-0.96). Threshold analysis revealed that 106 and 122 HUs represent optimal thresholds for detecting osteoporosis and low BMD. CONCLUSION: Opportunistic HUs strongly correlated with BCT-based measures, while neither correlated strongly with DXA-based BMD measures in the thoracolumbar spine. HUs are easy to perform at no additional cost and provide accurate BMD estimates at non-instrumented vertebral levels across all ACR-designated BMD categories.

MRI-based vertebral bone quality score: relationship with age and reproducibility.

Vertebral bone quality (VBQ) score is an opportunistic measure of bone mineral density using routine preoperative MRI in spine surgery. VBQ score positively correlates with age and is reproducible across serial scans. However, extrinsic factors, including MRI machine and protocol, affect the VBQ score and must be standardized. PURPOSE: The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3 months. METHODS: This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3 months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. RESULTS: One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5 years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). CONCLUSION: Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.

De novo genome assembly and comparative genomics for the colonial ascidian Botrylloides violaceus.

Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian, Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc. short and Oxford Nanopore Technologies long-read sequencing technologies. The resulting assembly is comprised of 831 contigs, has a total length of 121 Mbp, N50 of 1 Mbp, and a BUSCO score of 96.1%. Genome annotation identified 13 K protein-coding genes. Comparative genomic analysis with other tunicates reveals patterns of conservation and divergence within orthologous gene families even among closely related species. Characterization of the Wnt gene family, encoding signaling ligands involved in development and regeneration, reveals conserved patterns of subfamily presence and gene copy number among botryllids. This supports the use of genomic data from nonmodel organisms in the investigation of biological phenomena.

High-Resolution N-Glycan MALDI Mass Spectrometry Imaging of Subchondral Bone Tissue Microarrays in Patients with Knee Osteoarthritis.

N-glycan alterations contribute to the progression of several joint diseases, including knee osteoarthritis (KOA). However, molecular changes in KOA subchondral trabecular bone, when exposed to different joint loading forces, are still unknown. The aim of this study was, therefore, to demonstrate the feasibility to differentiate N-glycan changes in subchondral trabecular bone from four different joint loading forces of the tibial plateau regions (i.e., Lateral Anterior (L-A), Lateral Posterior (L-P), Medial Anterior (M-A), and Medial Posterior (M-P)) in KOA patients (n = 10) using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) at 20 µm spatial resolution. The degree of cartilage degeneration was evaluated histologically, and the subchondral bone tissue microarrays (TMAs) were subsequently manually constructed from formalin-fixed paraffin-embedded (FFPE) KOA osteochondral (i.e., cartilage-subchondral bone) tissues. Overall, the Osteoarthritis Research Society International (OARSI) histological grade was significantly higher and the size of chondrocytes in the superficial zone was much larger for both M-A and M-P compared to L-A and L-P of cartilage (p = 0.006, p = 0.030, p = 0.028, and p = 0.010; respectively). Among the 65 putative N-glycans observed by MALDI-MSI, 2 core fucosylated bi-antennary N-glycans, m/z 1809.64; (Hex)5(HexNAc)4(Fuc)1 and 2100.73; (NeuAc)1(Hex)5(HexNAc)4(Fuc)1, were significantly higher in intensity in M-A compared to L-A of the trabecular bone (p = 0.027, and p = 0.038, respectively). These N-glycans were then further structurally characterized by in situ MS/MS fragmentation post-MALDI-MSI. Our results demonstrate, for the first time, N-glycan alterations can occur at different joint loading forces in the KOA tibial plateau and the feasibility of subchondral bone TMA construction for N-glycan MALDI-MSI.

Complex-Type N-Glycans Are Associated with Cartilage Degeneration within Different Loading Sites of the Tibial Plateau for Knee Osteoarthritis Patients.

Abnormal N-glycosylation has been shown to play an important role in the pathogenesis of multiple diseases. However, little is known about the relationship between N-glycosylation and knee osteoarthritis (KOA) progression at the tissue level. Thus, the aim of this study was to quantify the cartilage histomorphometric changes in formalin-fixed paraffin-embedded (FFPE) tissue collected from the lateral and medial compartments of the tibial plateau KOA patients (n = 8). Subsequently, N-glycans were analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) followed by in situ MS/MS fragmentation. Overall, the Osteoarthritis Research Society International (OARSI) histological grade and cartilage surface fibrillation index were significantly higher, and chondrocyte size in the superficial zone was much larger, for the medial high-loaded cartilage compared to the lateral less-loaded cartilage. Among 92 putative N-glycans observed by MALDI-MSI, 3 complex-type N-glycans, (Hex)4(HexNAc)3, (Hex)4(HexNAc)4, and (Hex)5(HexNAc)4, and 1 oligomannose-type N-glycan, (Hex)9(HexNAc)2, were significantly higher in intensity in the medial cartilage compared to the lateral cartilage, whereas 2 tetra-antennary fucosylated-type N-glycans, (Hex)3(HexNAc)6(Fuc)2 and (Hex)3(HexNAc)6(Fuc)3, were significantly higher in intensity in the lateral cartilage than the medial cartilage. Our findings indicate that complex-type N-glycans are associated with higher severity of cartilage degeneration and may influence the cellular processes of KOA.

Vitamin D is a potential treatment for the management of gastrointestinal mucositis.

PURPOSE OF THE REVIEW: Gastrointestinal mucositis (GM) is a severe side effect of cancer treatments, negatively impacting the patient's quality of life, and has limited treatment. GM consists of complex biological processes involving apoptosis and inflammation, leading to damage and ulceration of the gastrointestinal system. Recently, vitamin D has been shown to have multiple roles in the gut, including immunomodulation, epithelial barrier regulation and microbiome regulation. Hence, this review aims to put forth vitamin D as a potential therapeutic due to its protective role in the intestine. RECENT FINDINGS: Recent studies have shown that vitamin D can reduce intestinal inflammation by reducing NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. Vitamin D also targets and maintains the intestinal epithelial barrier via the tight junction protein expression and the inhibition of microbiome translocation. Significant evidence also suggests that vitamin D exerts multiple therapeutic effects through binding to vitamin D receptors (VDRs), and the downregulation of VDR has been associated with the severity of the disease. Additionally, vitamin D deficiency is reported in cancer patients. SUMMARY: There is a dire need for effective treatment for GM, and recent animal and human studies show that vitamin D may be a potential therapy to prevent or treat GM.

Advances in Osteoporosis Therapy: Focus on Osteoanabolic Agents, Secondary Fracture Prevention, and Perioperative Bone Health.

PURPOSE OF REVIEW: This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including those undergoing bone-related surgery. RECENT FINDINGS: Two osteoanabolic agents, abaloparatide and romosozumab, were recently approved for treatment of patients with osteoporosis at high fracture risk. These agents, along with teriparatide, are valuable for primary and secondary fracture prevention. Orthopedic surgeons are well positioned to facilitate secondary fracture prevention via referrals to fracture liaison services or other bone health specialist colleagues. This review aims to help surgeons understand how to identify patients with sufficiently high fracture risk to warrant consideration of osteoanabolic therapy. Recent evidence around the perioperative use and potential benefits of osteoanabolic agents in fracture healing and other orthopedic settings (e.g., spinal fusion and arthroplasty) in individuals with osteoporosis is also discussed. Osteoanabolic agents should be considered for patients with osteoporosis at very high fracture risk, including those with prior osteoporotic fractures and those with poor bone health who are undergoing bone-related surgery.

Caprin-1 binding to the critical stress granule protein G3BP1 is influenced by pH.

G3BP is the central node within stress-induced protein-RNA interaction networks known as stress granules (SGs). The SG-associated proteins Caprin-1 and USP10 bind mutually exclusively to the NTF2 domain of G3BP1, promoting and inhibiting SG formation, respectively. Herein, we present the crystal structure of G3BP1-NTF2 in complex with a Caprin-1-derived short linear motif (SLiM). Caprin-1 interacts with His-31 and His-62 within a third NTF2-binding site outside those covered by USP10, as confirmed using biochemical and biophysical-binding assays. Nano-differential scanning fluorimetry revealed reduced thermal stability of G3BP1-NTF2 at acidic pH. This destabilization was counterbalanced significantly better by bound USP10 than Caprin-1. The G3BP1/USP10 complex immunoprecipated from human U2OS cells was more resistant to acidic buffer washes than G3BP1/Caprin-1. Acidification of cellular condensates by approximately 0.5 units relative to the cytosol was detected by ratiometric fluorescence analysis of pHluorin2 fused to G3BP1. Cells expressing a Caprin-1/FGDF chimera with higher G3BP1-binding affinity had reduced Caprin-1 levels and slightly reduced condensate sizes. This unexpected finding may suggest that binding of the USP10-derived SLiM to NTF2 reduces the propensity of G3BP1 to enter condensates.

Inorganic Arsenic Concentration in Fish Governed by Trophic Level and Size, not Water Concentration: Implications for Human Health Water Quality Criteria.

In 2019, the Idaho Department of Environmental Quality implemented a paired surface water and fish tissue data collection program to derive a state-specific bioaccumulation factor (BAF) for inorganic arsenic (iAs) as part of the development of new human health water quality criteria (HHWQC). No statistically significant relationship was found between total arsenic (tAs) or iAs in surface water and fish tissue. Fish body weight was the only parameter with a statistically significant effect on iAs concentration in fish tissue. The ratio of iAs to tAs in fish tissue declined significantly with both increasing trophic level and increasing body weight. The decrease in iAs concentration in fish tissue with increasing size and trophic level as well as the decrease in the proportion of tAs that is iAs with increasing trophic level are likely the result of metabolic transformation of iAs to organic As by organisms in each level of the aquatic food web. Although the linear regression-based BAF using the Idaho paired fish and water data best predicted observed iAs fish tissue concentrations compared to several alternative BAFs, it was not statistically significant (p < 0.05) and was a poor predictor (R2 = 0.01) of iAs concentrations in fish tissue. These results illustrate that iAs, and possibly other metals, in the natural environment do not conform with commonly used bioaccumulation models and the paradigm used by the US Environmental Protection Agency for determining HHWQC. These results indicate that modifications to the paradigm are necessary, such as a fish tissue criterion as Idaho has proposed, to assure that public health is protected. Environ Toxicol Chem 2023;42:1542-1552. © 2023 SETAC.

Intraoperative physician assessment of bone: correlation to bone mineral density.

This study evaluated the intraoperative physician assessment (IPA) of bone status at time of total knee arthroplasty. IPA was highly correlated with distal femur and overall bone mineral density. When IPA identifies poor bone status, formal bone health assessment is indicated. PURPOSE: Intuitively, intraoperative physician assessment (IPA) would be an excellent measure of bone status gained through haptic feedback during bone preparation. However, no studies have evaluated the orthopedic surgeon's ability to do so. This study's purpose, in patients undergoing total knee arthroplasty (TKA), was to relate IPA with (1) the lowest bone mineral density (BMD) T-score at routine clinical sites; and (2) with distal femur BMD. METHODS: Seventy patients undergoing TKA by 3 surgeons received pre-operative DXA. Intraoperatively, bone quality was assessed on a 5-point scale (1 excellent to 5 poor) based on tactile feedback to preparation. Demographic data, DXA results, and IPA score between surgeons were compared by factorial ANOVA. Lowest T-score and distal femur BMD were associated with IPA using Spearman's correlation. RESULTS: The mean (SD) age and BMI were 65.8 (7.6) years and 31.4 (5.1) kg/m2, respectively. Patient demographic data, BMD, and IPA (mean [SD] = 2.74 [1.2]) did not differ between surgeons. IPA correlated with the lowest T-score (R = 0.511) and distal femur BMD (R = 0.603-0.661). Based on the lowest T-score, no osteoporotic patients had an IPA above average, and none with normal BMD was classified as having poor bone. CONCLUSIONS: IPA is highly correlated with local (distal femur) and overall BMD. This study supports the International Society for Clinical Densitometry position that surgeon concern regarding bone quality should lead to bone health assessment. As IPA is comparable between surgeons, it is logical this can be widely applied by experienced orthopedic surgeons. Future studies evaluating IPA at other anatomic sites are indicated.