Enhancing traceability of wheat quality through the supply chain.

With the growing global population, the need for food is expected to grow tremendously in the next few decades. One of the key tools to address such growing food demand is minimizing grain losses and optimizing food processing operations. Hence, several research studies are underway to reduce grain losses/degradation at the farm (upon harvest) and later during the milling and baking processes. However, less attention has been paid to changes in grain quality between harvest and milling. This paper aims to address this knowledge gap and discusses possible strategies for preserving grain quality (for Canadian wheat in particular) during unit operations at primary, process, or terminal elevators. To this end, the importance of wheat flour quality metrics is briefly described, followed by a discussion on the effect of grain properties on such quality parameters. This work also explores how drying, storage, blending, and cleaning, as some of the common post-harvest unit operations, could affect grain's end-product quality. Finally, an overview of the available techniques for grain quality monitoring is provided, followed by a discussion on existing gaps and potential solutions for quality traceability throughout the wheat supply chain.

Better Operating Room Ventilation as Determined by a Novel Ventilation Index is Associated With Lower Rates of Surgical Site Infections.

OBJECTIVE: The aim was to assess the impact of operating room (OR) ventilation quality on surgical site infections (SSIs) using a novel ventilation index. BACKGROUND: Previous studies compared laminar air flow with conventional ventilation, thereby ignoring many parameters that influence air flow properties. METHODS: In this cohort study, we surveyed hospitals participating in the Swiss SSI surveillance and calculated a ventilation index for their ORs, with higher values reflecting less turbulent air displacement. For procedures captured between January 2017 and December 2019, we studied the association between ventilation index and SSI rates using linear regression (hospital-level analysis) and with the individual SSI risk using generalized linear mixed-effects models (patient-level analysis). RESULTS: We included 47 hospitals (182 ORs). Among the 163,740 included procedures, 6791 SSIs were identified. In hospital-level analyses, a 5-unit increase in the ventilation index was associated with lower SSI rates for knee and hip arthroplasty (-0.41 infections per 100 procedures, 95% confidence interval: -0.69 to -0.13), cardiac (-0.89, -1.91 to 0.12), and spine surgeries (-1.15, -2.56 to 0.26). Similarly, patient-level analyses showed a lower SSI risk with each 5-unit increase in ventilation index (adjusted odds ratio 0.71, confidence interval: 0.58-0.87 for knee and hip; 0.72, 0.49-1.06 for spine; 0.82, 0.69-0.98 for cardiac surgery). Higher index values were mainly associated with a lower risk for superficial and deep incisional SSIs. CONCLUSIONS: Better ventilation properties, assessed with our ventilation index, are associated with lower rates of superficial and deep incisional SSIs in orthopedic and cardiac procedures. OR ventilation quality appeared to be less relevant for other surgery types.

Intratumoral STING activation causes durable immunogenic tumor eradication in the KP soft tissue sarcoma model.

Introduction: Soft tissue sarcomas (STS) are highly metastatic, connective-tissue lineage solid cancers. Immunologically, sarcomas are frequently characterized by a paucity of tumor infiltrating lymphocytes and an immune suppressive microenvironment. Activation of the STING pathway can induce potent immune-driven anti-tumor responses within immunogenic solid tumors; however, this strategy has not been evaluated in immunologically cold sarcomas. Herein, we assessed the therapeutic response of intratumoral STING activation in an immunologically cold murine model of undifferentiated pleomorphic sarcoma (UPS). Materials and Results: A single intratumoral injection of the murine STING agonist, DMXAA resulted in durable cure in up to 60% of UPS-bearing mice. In mice with synchronous lung metastases, STING activation within hindlimb tumors resulted in 50% cure in both anatomic sites. Surviving mice all rejected UPS re-challenge in the hindlimb and lung. Therapeutic efficacy of STING was inhibited by lymphocyte deficiency but unaffected by macrophage deficiency. Immune phenotyping demonstrated enrichment of lymphocytic responses in tumors at multiple timepoints following treatment. Immune checkpoint blockade enhanced survival following STING activation. Discussion: These data suggest intratumoral activation of the STING pathway elicits local and systemic anti-tumor immune responses in a lymphocyte poor sarcoma model and deserves further evaluation as an adjunctive local and systemic treatment for sarcomas.

The KrasG12D;Trp53fl/fl murine model of undifferentiated pleomorphic sarcoma is macrophage dense, lymphocyte poor, and resistant to immune checkpoint blockade.

Sarcomas are rare, difficult to treat, mesenchymal lineage tumours that affect children and adults. Immunologically-based therapies have improved outcomes for numerous adult cancers, however, these therapeutic strategies have been minimally effective in sarcoma so far. Clinically relevant, immunologically-competent, and transplantable pre-clinical sarcoma models are essential to advance sarcoma immunology research. Herein we show that Cre-mediated activation of KrasG12D, and deletion of Trp53, in the hindlimb muscles of C57Bl/6 mice results in the highly penetrant, rapid onset undifferentiated pleomorphic sarcomas (UPS), one of the most common human sarcoma subtypes. Cell lines derived from spontaneous UPS tumours can be reproducibly transplanted into the hindlimbs or lungs of naïve, immune competent syngeneic mice. Immunological characterization of both spontaneous and transplanted UPS tumours demonstrates an immunologically-'quiescent' microenvironment, characterized by a paucity of lymphocytes, limited spontaneous adaptive immune pathways, and dense macrophage infiltrates. Macrophages are the dominant immune population in both spontaneous and transplanted UPS tumours, although compared to spontaneous tumours, transplanted tumours demonstrate increased spontaneous lymphocytic infiltrates. The growth of transplanted UPS tumours is unaffected by host lymphocyte deficiency, and despite strong expression of PD-1 on tumour infiltrating lymphocytes, tumours are resistant to immunological checkpoint blockade. This spontaneous and transplantable immune competent UPS model will be an important experimental tool in the pre-clinical development and evaluation of novel immunotherapeutic approaches for immunologically cold soft tissue sarcomas.

The Assessment of Skeletal Muscle and Cortical Bone by Second-generation HR-pQCT at the Tibial Midshaft.

BACKGROUND: Peripheral quantitative computed tomography (pQCT) is the current densitometric gold-standard for assessing skeletal muscle at the 66% proximal tibia site. High resolution peripheral quantitative computed tomography (HR-pQCT) is a leading technology for quantifying bone microarchitecture at the distal extremities, and with the second-generation HR-pQCT it is possible to measure proximal limb sites. Therefore, the objectives of this study were to: (1) assess the feasibility of using HR-pQCT to assess skeletal muscle parameters at the 66% proximal tibia site, and (2) test HR-pQCT skeletal muscle measurement reproducibility at this site. METHODS: Adult participants (9 males; 7 females; ages 31-75) received 1 pQCT scan and 2 HR-pQCT scans at the 66% proximal site of the nondominant tibia. Participants were repositioned between HR-pQCT scans to test reproducibility. HR-pQCT and pQCT scans were analyzed to quantify muscle cross-sectional area (CSA) and muscle density. Coefficients of determination and Bland-Altman plots compared muscle parameters between pQCT and HR-pQCT. For short-term reproducibility, root-mean-square of coefficient of variance and least significant change were calculated. RESULTS: HR-pQCT and pQCT measured muscle density and muscle CSA were positively correlated (R2 = 0.66, R2 = 0.95, p < 0.001, respectively). Muscle density was equivalent between HR-pQCT and pQCT; however, there was systematic and directional bias for muscle CSA, such that muscle CSA was 11% lower with HR-pQCT and bias increased with larger muscle CSA. Root-mean-square of coefficient of variance was 0.67% and 0.92% for HR-pQCT measured muscle density and muscle CSA, respectively, while least significant change was 1.4 mg/cm3 and 174.0 mm2 for muscle density and muscle CSA, respectively. CONCLUSION: HR-pQCT is capable of assessing skeletal muscle at the 66% site of the tibia with good precision. Measures of muscle density are comparable between HR-pQCT and pQCT.

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BACKGROUND: The putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent. QUESTIONS/PURPOSES: (1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma. METHODS: In this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H2O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation. RESULTS: Constitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm versus 1316 ± 387.4 mm, mean difference 1009 mm [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm versus 326.1 ± 72.8 mm, mean difference 326.1 mm [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10 ± 8.3x10 photons/s versus 9.3 x 10 ± 1.5 x 10 photons/s, mean difference 8.6 x 10 photons/s [95% CI 5.1 x 10 to 1.2 x 10]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm versus 1335 ± 102.7 mm, mean difference 840.3 mm [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions. CONCLUSIONS: As demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted. CLINICAL RELEVANCE: Our results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.