Selective degradation of endogenous organic metabolites in acidified fresh human urine using sulphate radical-based advanced oxidation.

The human urine metabolome is complex, containing a wide range of organic metabolites that affect treatment of urine collected in resource-oriented sanitation systems. In this study, an advanced oxidation process involving heat-activated peroxydisulphate was used to selectively oxidise organic metabolites in urine over urea and chloride. Initial experiments evaluated optimal conditions (peroxydisulphate dose, temperature, time, pH) for activation of peroxydisulphate in unconcentrated, non-hydrolysed synthetic urine and real urine acidified to pH 3.0. Subsequent experiments determined the fate of 268 endogenous organic metabolites (OMs) and removal of COD from unconcentrated and concentrated real urine (80-90% mass reduced by evaporation). The results revealed >90% activation of 60 mM peroxydisulphate in real unconcentrated urine heated to 90 °C for 1 h, resulting in 43% ΣOMs degradation, 22% COD removal and 56% total organic carbon removal, while >94% of total nitrogen and >97% of urea in real unconcentrated urine were recovered. The mechanism of urea degradation was identified to be chemical hydrolysis to ammonia, with the rate constant for this reaction determined to be 1.9 × 10-6 s-1 at pH 3.0 and 90 °C. Treating concentrated real urine resulted in similar removal of COD, ΣOMs degradation and total nitrogen loss as observed for unconcentrated urine, but with significantly higher chloride oxidation and chemical hydrolysis of urea. Targeted metabolomic analysis revealed that peroxydisulphate treatment degraded 157 organic metabolites in urine, of which 67 metabolites were degraded by >80%. The rate constant for the reaction of sulphate radicals with oxidisable endogenous organic metabolites in urine was estimated to exceed 108 M-1 s-1. These metabolites were preferentially oxidised over chloride and urea in acidified, non-hydrolysed urine treated with peroxydisulphate. Overall, the findings support the development of emerging urine recycling technologies, including alkaline/acid dehydration and reverse osmosis, where the presence of endogenous organic urine metabolites significantly influences treatment parameters such as energy demand and product purity.

The Impact of Social Determinants of Health on Outcomes and Complications After Total Knee Arthroplasty: An Analysis of Neighborhood Deprivation Indices.

BACKGROUND: Social determinants of health (SDOH) are important factors in the delivery of orthopaedic care. The purpose of this study was to investigate the relationship between outcomes following total knee arthroplasty (TKA) and both the Social Vulnerability Index (SVI) and the Area Deprivation Index (ADI). METHODS: The Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI) database was utilized to identify TKA cases for inclusion. Demographic characteristics and medical history were documented. The SVI, its subthemes, and the ADI were analyzed. Outcome data included length of stay, discharge disposition, postoperative change in the Knee Injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR), 90-day incidences of emergency department (ED) visits, readmission, death, deep venous thrombosis (DVT) and/or pulmonary embolism (PE), periprosthetic fracture, implant failure, periprosthetic joint infection (PJI), and all-cause reoperation. Database cross-referencing was completed to document aseptic and septic revisions beyond 90 days postoperatively. Bivariate quartile-stratified and multivariable analyses were used to associate deprivation metrics with outcomes. RESULTS: A total of 19,321 TKA cases met inclusion criteria. Baseline patient characteristics varied among the SVI and/or ADI quartiles, with patients of non-White race and with a greater number of comorbidities noted in higher deprivation quartiles. Higher SVI and/or ADI quartiles were correlated with an increased rate of discharge to a skilled nursing facility (p < 0.05). A higher SVI and/or ADI quartile was associated with increased incidences of ED visits and readmissions postoperatively (p < 0.05). DVT and/or PE and long-term aseptic revision were the complications most strongly associated with higher deprivation metrics. Upon multivariable analysis, greater length of stay and greater incidences of ED visits, readmissions, DVT and/or PE, and aseptic revision remained significantly associated with greater deprivation based on multiple metrics. CONCLUSIONS: Greater deprivation based on multiple SVI subthemes, the composite SVI, and the ADI was significantly associated with increased length of stay, non-home discharge ED visits, and readmissions. The SVI and the ADI may be important considerations in the perioperative assessment of patients who undergo TKA. LEVEL OF EVIDENCE: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Marital Status, Race, Insurance Type, and Socioeconomic Status-Assessment of Social Predictors for Outcomes After Total Knee Arthroplasty.

BACKGROUND: The purpose of this study was to investigate the effect of various social determinants of health on outcomes and dispositions after total knee arthroplasty (TKA). METHODS: A retrospective review was conducted on 14,462 consecutive TKA procedures between 2013 and 2021 at a multicenter hospital system. Data abstraction was done by inquiry to the Michigan Arthroplasty Registry Collaborative Quality Initiative. Data points requested included basic demographics, marital status, race, insurance status, socioeconomic status measured by the Area of Deprivation Index, perioperative course, and incidence of emergency department (ED) visits and readmissions within 3 months of surgery. Subsequent multivariate analyses were conducted. RESULTS: Unmarried patients required markedly greater lengths of hospital stay and had an increased rate of discharge to skilled nursing facilities and a higher likelihood of any purpose ED visit within 90 days of surgery compared with married patients, who had a significantly greater rate of same-day discharge ( P < 0.001). Race did not markedly correlate with outcomes. Medicare patients showed a greater rate of same-day discharge, nonhome discharge, and 90-day ED visits compared with privately insured patients ( P < 0.001). Medicaid patients were more likely than privately insured patients to have a 90-day ED visit ( P < 0.001). Socioeconomic status had a minimal clinical effect on all studied outcomes. CONCLUSION: Social factors are important considerations in understanding outcomes after TKA. Additional investigations are indicated in identifying at-risk patients and subsequent optimization of these patients.

Evaluation of Blood Loss in Conventional vs MAKOplasty Total Knee Arthroplasty.

Background: Primary total knee arthroplasty (TKA) has been historically associated with considerable blood loss. Allogenic transfusions, the standard of care for blood loss following TKA, carry inherent risks. With the expanding use of robotic technology in TKA, one theoretical advantage is decreased blood loss and postoperative blood transfusions requirements. The purpose of this study was to compare postoperative hemoglobin levels and the percentage of patients requiring a transfusion of allogenic packed red blood cells after conventional TKA (CTKA) vs robot-assisted TKA (RATKA). Methods: This is a retrospective review of 486 consecutive patients undergoing either CTKA or RATKA between October 30, 2018, and June 25, 2020, by a single fellowship-trained arthroplasty surgeon. Mako SmartRobotics (Stryker, Kalamazoo, MI) was used for RATKA cases. Primary outcomes included preoperative vs postoperative hemoglobin values and postoperative blood transfusion rates between the 2 groups. Results: The mean hemoglobin on postoperative day 1 was 10.7 gm/dl (±1.3) in the CTKA group and 10.9 gm/dl (±1.3) in the RATKA group, P = .24. The largest decline in hemoglobin from preoperative to within 2 days postoperatively was 3.1 gm/dl (±1.1) in the CTKA group and 3.1 gm/dl (±1.1) in the RATKA group, P = .92. The percentage of patients requiring a blood transfusion was 1.1% in the CTKA group and 1.3% in the RATKA group, P = .79. Conclusions: RATKA and CTKA groups did not have significant differences in postoperative hemoglobin changes or the need for postoperative blood transfusions.

Assessing knee anatomy using Makoplasty software a case series of 99 knees.

BACKGROUND: Role of MAKOplasty software in determining femoral neck version, distal-femoral resection angle, tibial axis difference, distal-femoral rotation, medial/lateral tibial slope, and tibial tubercle alignment has yet to be fully explored. METHODS: Preoperative CT scans and plain films of 99 patients were obtained for each patient according to predetermined MAKO-protocol by four observers. Reliability analyses (Cronbach's Alpha-test) was performed to determine agreement between raters for angle measures. RESULTS: Anatomic measurements were similar to previously published literature, and cronbachs'alpha analysis demonstrated agreement amidst all observers. CONCLUSION: MAKOplasty software produces similar results to anatomic measurements in planning for TKA with good reproducibility.

Lemongrass Extract Possesses Potent Anticancer Activity Against Human Colon Cancers, Inhibits Tumorigenesis, Enhances Efficacy of FOLFOX, and Reduces Its Adverse Effects.

Current chemotherapeutics for metastatic colorectal cancers have limited success and are extremely toxic due to nonselective targeting. Some natural extracts have been traditionally taken and have shown anticancer activity. These extracts have multiple phytochemicals that can target different pathways selectively in cancer cells. We have shown previously that lemongrass (Cymbopogon citratus) extract is effective at inducing cell death in human lymphomas. However, the efficacy of lemongrass extract on human colorectal cancer has not been investigated. Furthermore, its interactions with current chemotherapies for colon cancer is unknown. In this article, we report the anticancer effects of ethanolic lemongrass extract in colorectal cancer models, and importantly, its interactions with FOLFOX and Taxol. Lemongrass extract induced apoptosis in colon cancer cells in a time and dose-dependent manner without harming healthy cells in vitro. Oral administration of lemongrass extract was well tolerated and effective at inhibiting colon cancer xenograft growth in mice. It enhanced the anticancer efficacy of FOLFOX and, interestingly, inhibited FOLFOX-related weight loss in animals given the combination treatment. Furthermore, feeding lemongrass extract to APCmin/+ transgenic mice led to the reduction of intestinal tumors, indicating its preventative potential. Therefore, this natural extract has potential to be developed as a supplemental treatment for colorectal cancer.

Dandelion Root and Lemongrass Extracts Induce Apoptosis, Enhance Chemotherapeutic Efficacy, and Reduce Tumour Xenograft Growth In Vivo in Prostate Cancer.

Many conventional chemotherapies have indicated side effects due to a lack of treatment specificity and are thus not suitable for long-term usage. Natural health products are well-tolerated and safe for consumption, and some have pharmaceutical uses particularly for their anticancer effects. We have previously reported the anticancer efficacy of dandelion (Taraxacum officinale) root and lemongrass (Cymbopogon citratus) extracts. However, their efficacy on prostate cancer and their interactions with standard chemotherapeutics have not been studied to determine if they will be suitable for adjuvant therapies. If successful, these extracts could potentially be used in conjunction with chemotherapeutics to minimize the risk of drug-related toxicity and enhance the efficacy of the treatment. We have demonstrated that both dandelion root extract (DRE) and lemongrass extract (LGE) exhibit selective anticancer activity. Importantly, DRE and LGE addition to the chemotherapeutics taxol and mitoxantrone was determined to enhance the induction of apoptosis when compared to individual chemotherapy treatment alone. Further, DRE and LGE were able to significantly reduce the tumour burden in prostate cancer xenograft models when administered orally, while also being well-tolerated. Thus, the implementation of these well-tolerated extracts in adjuvant therapies could be a selective and efficacious approach to prostate cancer treatment.

Evaluating the Anti-cancer Efficacy of a Synthetic Curcumin Analog on Human Melanoma Cells and Its Interaction with Standard Chemotherapeutics.

Melanoma is the leading cause of skin-cancer related deaths in North America. Metastatic melanoma is difficult to treat and chemotherapies have limited success. Furthermore, chemotherapies lead to toxic side effects due to nonselective targeting of normal cells. Curcumin is a natural product of Curcuma longa (turmeric) and has been shown to possess anti-cancer activity. However, due to its poor bioavailability and stability, natural curcumin is not an effective cancer treatment. We tested synthetic analogs of curcumin that are more stable. One of these derivatives, Compound A, has shown significant anti-cancer efficacy in colon, leukemia, and triple-negative inflammatory breast cancer cells. However, the effects of Compound A against melanoma cells have not been studied before. In this study, for the first time, we demonstrated the efficacy of Compound A for the selective induction of apoptosis in melanoma cells and its interaction with tamoxifen, taxol, and cisplatin. We found that Compound A induced apoptosis selectively in human melanoma cells by increasing oxidative stress. The anti-cancer activity of Compound A was enhanced when combined with tamoxifen and the combination treatment did not result in significant toxicity to noncancerous cells. Additionally, Compound A did not interact negatively with the anti-cancer activity of taxol and cisplatin. These results indicate that Compound A could be developed as a selective and effective melanoma treatment either alone or in combination with other non-toxic agents like tamoxifen.

Hibiscus flower extract selectively induces apoptosis in breast cancer cells and positively interacts with common chemotherapeutics.

BACKGROUND: Current therapeutic approaches to treat metastatic breast cancer, although effective, have shown many inadvertent side effects such as genotoxicity due to a lack of selectivity. Thus, these treatment plans are not suitable for long-term usage. Natural health product extracts are safe for long-term consumption and some have shown to be medicinally active containing multiple bioactive compounds able target multiple vulnerabilities in cancer. One of which, Hibiscus rosa-sinesis (hibiscus) extract, has been reported to have many medicinal and anticancer properties due to its antioxidant and hypolipidemic effects. However, its efficacy against breast cancer has not been fully investigated and characterized. If effective against cancer, hibiscus extract could potentially be combined with chemotherapeutic treatments in adjuvant therapy to reduce chemotherapy-inducing side effects. METHOD: We have investigated aqueous hibiscus flower extract anticancer efficacy, selectivity, and interactions with chemotherapeutics taxol, cisplatin, and tamoxifen in estrogen-receptor positive breast cancer cells, triple-negative human breast cancer cells, and normal non-cancerous cells. Apoptotic morphology and biochemical marker expression were assessed to determine the extent anticancer efficacy of hibiscus. Mitochondrial membrane potential reduction and reactive oxygen species generation were quantified using fluorogenic dyes to determine the mechanism of hibiscus extract action. RESULTS: Hibiscus extract was able to selectively induce apoptosis in both triple-negative and estrogen-receptor positive breast cancer cells in a dosage-dependent manner. Most importantly, addition of hibiscus extract was found to enhance the induction of apoptosis of chemotherapy treatments (taxol and cisplatin) in triple-negative breast cancer cells when compared to treatment alone. Moreover, hibiscus extract addition to chemotherapy treatment was able to increase oxidative stress and decrease mitochondrial membrane potential compared to individual treatments. CONCLUSION: Hibiscus extract is effective on breast cancer, most notably on generally resistant triple-negative breast cancer, while being selective for normal healthy cells. Hibiscus extract could supplement chemotherapeutic regimens as an adjuvant and lead to a more efficacious treatment approach to reduce chemotherapy dosages and related toxicity.