Enhanced anticancer efficacy of TRAIL-conjugated and odanacatib-loaded PLGA nanoparticles in TRAIL resistant cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates unique characteristics in anticancer therapies as it selectively induces apoptosis in cancer cells. However, most cancer cells are TRAIL-resistant. Odanacatib (ODN), a cathepsin K inhibitor, is considered a novel sensitizer for cancer treatment. Combination therapy between TRAIL and sensitizers is considered a potent platform that improves TRAIL-based anticancer therapies beyond TRAIL monotherapy. Herein, we developed ODN loaded poly(lactic-co-glycolic) nanoparticles conjugated to GST-TRAIL (TRAIL-ODN-PLGA-NPs) to target and treat TRAIL-resistant cancer. TRAIL-ODN-PLGA-NPs demonstrated a significant increase in cellular uptake via death receptors (DR5 and DR4) on surface of cancer cells. TRAIL-ODN-PLGA-NPs exposure destroyed more TRAIL-resistant cells compared to a single treatment with free drugs. The released ODN decreased the Raptor protein, thereby increasing damage to mitochondria by elevating reactive oxygen species (ROS) generation. Additionally, Bim protein stabilization improved TRAIL-resistant cell sensitization to TRAIL-induced apoptosis. The in vivo biodistribution study revealed that TRAIL-ODN-PLGA-NPs demonstrated high location and retention in tumor sites via the intravenous route. Furthermore, TRAIL-ODN-PLGA-NPs significantly inhibited xenograft tumor models of TRAIL-resistant Caki-1 and TRAIL-sensitive MDA-MB-231 cells.The inhibition was associated with apoptosis activation, Raptor protein stabilizing Bim protein downregulation, Bax accumulation, and mitochondrial ROS generation elevation. Additionally, TRAIL-ODN-PLGA-NPs affected the tumor microenvironment by increasing tumor necrosis factor-α and reducing interleukin-6. In conclusion, we evealed that our formulation demonstrated synergistic effects against TRAIL compared with the combination of free drug in vitro and in vivo models. Therefore, TRAIL-ODN-PLGA-NPs may be a novel candidate for TRAIL-induced apoptosis in cancer treatment.

Acquired Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Resistance of Human Colorectal Cancer Cells Is Linked to Histone Acetylation and Is Synergistically Ameliorated by Combination with HDAC Inhibitors.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for the treatment of various malignancies; however, its therapeutic potential is limited because of the frequent occurrence of tumor cell resistance. In this study, we determined whether TRAIL resistance acquired by repeated administration could be overcome by HDAC inhibition in human colorectal cancer cells. METHODS: TRAIL-resistant HCT116 human colorectal cancer cells (HCT116-TR) were generated by repeated treatment with 10 and 25 ng/mL TRAIL twice weekly for 28 days. RESULTS: The resulting TRAIL-resistant cells were noncross-resistant to other chemotherapeutic agents. The levels of histone acetylation-related proteins, such as ac-histone H4 and HDAC1, were altered in HCT116-TR cells compared with the parental HCT116 cell line. The combined treatment with TRAIL and HDAC inhibitors significantly increased apoptosis in HCT116-TR cells and indicated a synergistic effect. The mechanism by which HDAC inhibition sensitizes HCT116-TR cells to TRAIL is dependent on the intrinsic pathway. In addition, we found that HDAC inhibition enhanced the sensitivity of cells to TRAIL through mitogen-activated protein kinases/CCAAT/enhancer-binding protein homologs of protein-dependent upregulation of death receptor 5. CONCLUSION: These results suggest that histone acetylation is responsible for acquired TRAIL resistance after repeated exposure and acquired resistance to TRAIL may be overcome by combination therapies with HDAC inhibitors.

Osteoprotegerin (OPG) and its ligands RANKL and TRAIL in falciparum, vivax and knowlesi malaria: correlations with disease severity, and B cell production of OPG.

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of NF-ƙB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL), and is increasingly recognised as a marker of poor prognosis in a number of diseases. Here we demonstrate that in Malaysian adults with falciparum and vivax malaria, OPG is increased, and its ligands TRAIL and RANKL decreased, in proportion to disease severity. In volunteers experimentally infected with P. falciparum and P. vivax, RANKL was suppressed, while TRAIL was unexpectedly increased, suggesting binding of OPG to RANKL prior to TRAIL. We also demonstrate that P. falciparum stimulates B cells to produce OPG in vitro, and that B cell OPG production is increased ex vivo in patients with falciparum, vivax and knowlesi malaria. Our findings provide further evidence of the importance of the OPG/RANKL/TRAIL pathway in pathogenesis of diseases involving systemic inflammation, and may have implications for adjunctive therapies. Further evaluation of the role of B cell production of OPG in host responses to malaria and other inflammatory diseases is warranted.

A randomized controlled study of neoadjuvant metformin with chemotherapy in nondiabetic breast cancer women: The METNEO study.

AIMS: Clinical data demonstrate that metformin exhibits antiproliferative, proapoptotic and antimetastatic actions. Here, correlative molecular studies were undertaken to determine the roles of transmembrane tumour necrosis factor-related apoptosis-inducing ligand death receptors (DRs) and CD133, a glycoprotein biomarker of breast cancer (BC) stem cells, in the advantageous action of metformin on pathological and clinical outcomes in BC patients on neoadjuvant chemotherapy. METHODS: We randomly assigned 70 nondiabetic BC patients in a 1:1 ratio to either neoadjuvant AC-T chemotherapy (4 cycles of adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2, followed by 12 cycles of weekly paclitaxel 80 mg/m2) or AC-T with adjunct metformin (850 mg twice/day). The expressions of DR4, DR5 and CD133 were quantified in excised tissue samples with residual tumour cells. RESULTS: The overall clinical response (odds ratio: 22.67 [2.77-185.18], P = .004), breast-conserving surgery (odds ratio: 3.67 [1.303-10.321], P = .014) and pathological complete response (ß = 2.49 ± 1.13 [0.274-4.712], P = .028) rates were significantly improved in the metformin arm. Tissues obtained from the metformin arm had upregulated mRNA expression of DR4 (Mean delta cycle thresholds ± standard error of the mean: 2.68 ± 0.25 vs. 4.87 ± 0.53, P = .0003) and DR5 (0.21 ± 0.25 vs. 4.29 ± 0.95, P = .0004) compared to control arm. The enhanced DR expression negatively correlated with that of CD133 + BC stem cells, which was significantly reduced by metformin at both cytoplasmic/membranous (43.48 vs. 100.00%, P < .0001) and nuclear sites (4.35 vs. 95.00%, P < .0001). CONCLUSION: Metformin improves clinical and pathological responses to neoadjuvant AC-T chemotherapy in BC via prompting directionally opposite changes in DRs (increments) and CD133 + (decrements) expressions. This study was registered in ClinicalTrials.gov (registration number: NCT04170465, https://clinicaltrials.gov/ct2/show/NCT04170465).

Multiple mechanisms contribute to acquired TRAIL resistance in multiple myeloma.

Multiple Myeloma (MM) prognosis has recently improved thanks to the incorporation of new therapies to the clinic. Nonetheless, it is still a non-curable malignancy. Targeting cancer cells with agents inducing cell death has been an appealing alternative investigated over the years, as is the case of TRAIL, an agonist of DR4 and DR5 death receptors. This pathway, involved in apoptosis triggering, has demonstrated efficacy on MM cells. In this research, we have investigated the sensitivity of a panel of MM cells to this agent and generated TRAIL-resistant models by continuous culture of sensitive cells with this peptide. Using genomic and biochemical approaches, the mechanisms underlying resistance were investigated. In TRAIL-resistant cells, a strong reduction in cell-surface receptor levels was detected and impaired the apoptotic machinery to respond to the treatment, enabling cells to efficiently form the Death Inducing Signalling Complex. In addition, an upregulation of the inhibitory protein c-FLIP was detected. Even though the manipulation of these proteins was able to modify cellular responses to TRAIL, it was not complete, pointing to other mechanisms involved in TRAIL resistance.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. METHODS: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. RESULTS: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. DISCUSSION: CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. HIGHLIGHTS: Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

Chinese classical decoction Wuwei Xiaodu Drink alleviates gout arthritis by suppressing NLRP3-Mediated inflammation.

Background: Wuwei Xiaodu Drink (WWXDD), a classical decoction of traditional Chinese medicine, has been clinically used for the treatment of gout in China for many years. This study aimed to demonstrate the efficacy of WWXDD in treating gout flares and elucidate its underlying therapeutic mechanism. Methods: A randomized control trial was conducted to compare the effectiveness of WWXDD with low-dose colchicine in gout arthritis. The primary outcome was the clinical response rate on the 7th day, and joint syndrome score and serological tests were secondary outcome measures and were compared in the two groups on the 1st and 7th day. Then we used a network pharmacology approach to investigate the possible mechanism of WWXDD in treating gout, and the effects of WWXDD on the MSU-induced rat model were observed. Results: In the clinical trial, a total of 78 participants completed the study, and the results demonstrated comparable clinical complete response rates, joint symptom scores, and serological test outcomes between the two groups on the 7th day. Network pharmacology analysis identified 51 core genes that target gout and WWXDD interactions. Notably, strong significant correlations were observed with inflammation cytokine genes and metabolism-related genes. Furthermore, it was found that WWXDD reduced gene expression levels of inflammation cytokines including IL-1ß, TNF, and IL-18 in an MSU-induced rat model while increasing IL-10 expression. Additionally, WWXDD decreased insulin gene expression in this model. Moreover, WWXDD exhibited a reduction in both gene and protein expressions associated with the NLRP3-mediated inflammatory pathway in inflamed joints of rats. Conclusion: The results of the present study suggested the anti-inflammatory effects of WWXDD in the treatment of gouty arthritis, partially through inhibiting NLRP3 inflammasome activation. Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2100047807.

Combining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.

Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) in vitro. We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resistant LN229 cell line. This combination also showed robust tumor suppression and enhanced survival of mice bearing human xenografts of both solid and invasive GBMs. These findings elucidate a novel combination regimen and suggest that the combination of these clinically relevant agents may represent a new therapeutic option with increased efficacy for patients with GBM.

Spatiotemporal parameters and kinematics differ between race stages in trail running-a field study.

Introduction: Trail running is an emerging discipline with relatively few studies performed in ecological conditions. The aim of this work was to investigate if and how spatiotemporal parameters (STP) and kinematics differ between initial and final stage of a field trial. Methods: Twenty trail runners (10 F, 10 M) were recruited and ran a solo 9.1 km trial. During the test, participants wore a GPS watch and an IMU-based motion capture system. Running speed, elapsed time, STP and kinematics were compared between initial and final stage, separately for uphill (UH) and downhill (DH) sections. Results: Running speed decreased in the final stage ( p < 0.05 ). Total test time was more correlated to the time elapsed in UH sections. In the final stage and in both UH and DH sections, contact time and duty factor increased, whilst stride length and flight time decreased ( p < 0.05 ). In the final stage, ankle joint was more dorsiflexed in stance and swing phases in UH sections and stance phase only in DH sections ( p < 0.05 ). In the final stage, knee joint was less extended in swing phase in UH and DH sections, as well as less extended in stance in UH sections ( p < 0.05 ). In the final stage, hip joint was less flexed in the swing phase in UH and DH sections ( p < 0.05 ). In the final stage, forward trunk lean was higher across the entire gait cycle in in UH sections ( p < 0.05 ). Trunk contralateral axial rotation was lower, in DH sections ( p < 0.05 ). Discussion: During the final stage, results indicate a less efficient propulsion phase, in both UH and DH sections. In UH sections, results suggest lower energy generation at the ankle joint. In DH sections, results suggest that the kinematics of swing leg may play a role in sub-optimizing propulsion phase. This study demonstrates how, in UH and DH sections, similar changes in spatiotemporal parameters can be elicited by dissimilar changes in running kinematics. To optimize performance in trail running, coaches and practitioners are advised to work on different (incline-specific) aspects of running technique.

Mitoxantrone Combined with Engineered TRAIL-Nanovesicles for Enhanced Cancer Immunotherapy Via Converting Apoptosis into Pyroptosis.

Pyroptosis, a highly inflammatory form of programmed cell death, has emerged as a promising target for cancer immunotherapy. However, in the context of pyroptosis execution, while both caspase-3 and GSDME are essential, it is noteworthy that GSDME is frequently under-expressed in cold tumors. To overcome this limitation, engineered cellular nanovesicles (NVs) presenting TRAIL on their membranes (NVTRAIL) are developed to trigger the upregulation of cleaved caspase-3. When strategically combined with the chemotherapeutic agent mitoxantrone (MTO), known for its ability to enhance GSDME expression, MTO@NVTRAIL can convert cancer cells from apoptosis into pyroptosis, inhibit the tumor growth and metastasis successfully in primary tumor. The microparticles released by pyroptotic tumor cells also exhibited certain cytotoxicity against other tumor cells. In addition, tumor cells exposed to the combination treatment of MTO@NVTRAIL in vitro have also demonstrated potential utility as a novel form of vaccine for cancer immunotherapy. Flow analysis of the tumor microenvironment and draining lymph nodes reveals an increased proportion of matured dendritic cells and activation of T cells. In summary, the research provided a reference and alternative approach to induce cancer pyroptosis for clinical antitumor therapy based on engineered cellular nanovesicles and chemotherapy.

Cognitive screening test for rehabilitation using spatiotemporal data extracted from a digital trail making test part-A.

We investigated a newly developed digitized Trail Making Test using an iPad (iTMT) as a brief cognitive function screening test. We found that the iTMT part-A (iTMT-A) can estimate generalized cognitive function in rehabilitation inpatients examined using the Mini-Mental State Examination (MMSE). Forty-two hospitalized participants undergoing rehabilitation (rehab participants), 30 of whom had cerebral infarction/hemorrhage (stroke participants), performed the iTMT five times (first three times: iTMT-A; fourth: paper version of TMT-A; fifth: the inverse version of iTMT-A) and the MMSE once. Each iTMT-A trial's completion time was divided into the move and dwell times. A linear mixed model following post-hoc tests revealed that the completion time of the third and fourth iTMT-A was faster compared to that of the first iTMT-A, suggesting the presence of a learning effect. In the partial least squares (PLS) regression analysis, the coefficient of determination for estimating the MMSE score was increased by using the dwell and move times extracted from the repeated iTMT-A and the availability of TMT-B, even for subjects with low MMSE scores. These findings indicate that the dwell time of iTMT-A may be important for estimating cognitive function. The iTMT-A extracts significant factors temporally and spatially, and by incorporating the learning effect of repeated trials, it may be possible to screen cognitive and physical functions for rehabilitation patients.

Continued stepped care model improves early-stage self-report quality of life and knee function after total knee arthroplasty.

BACKGROUND: The Stepped Care Model (SCM) is an evidence-based treatment approach that tailors treatment intensity based on patients' health status, aiming to achieve the most positive treatment outcomes with the least intensive and cost-effective interventions. Currently, the effectiveness of the Stepped Care Model in postoperative rehabilitation for TKA (Total Knee Arthroplasty) patients has not been reported. OBJECTIVE: The present study aimed to investigate whether the stepped care model could improve early-stage self-report quality of life and knee function after total knee arthroplasty via a prospective randomized controlled design. METHODS: It was a mono-center, parallel-group, open-label, prospective randomized controlled study. Patients who aging from 60-75 years old as well as underwent unilateral primary total knee arthroplasty due to end-stage knee osteoarthritis between 2020.06 to 2022.02 were enrolled. Participants were randomized and arranged into two groups in a 1:1 allocation. The control group was given traditional rehabilitation guidance, while the stepped care model group was given continued stepped care. Hospital for special surgery knee score, daily living ability (ADL), knee flexion range, and adverse events at 1, 3, and 6 months after total knee arthroplasty were recorded. RESULTS: 88 patients proceeded to the final analysis. There was no significant difference of age, gender, length of stay, BMI, and educational level between the two groups at the baseline. After specific stepped care model interventions, patients showed significant improvements in HHS in 1 month (85.00 (82.25, 86.00) vs. 80.00 (75.00, 83.00), p< 0.001), 3 months (88.00 (86.00, 92.00) vs. 83.00 (76.75, 85.00), p< 0.001), and 6 months (93.00 (90.25, 98.00) vs. 88.00 (84.25, 91.75), p< 0.001) when compared with the control group. Similar results were also found in both daily living ability and knee flexion angle measurements. No adverse event was observed during the follow-up. CONCLUSION: The present study found that the stepped care model intervention significantly improved early-stage knee function and self-reported life quality after total knee arthroplasty due to knee osteoarthritis. Female patients and those less than 70 years old benefit more from the stepped care model intervention after total knee arthroplasty.

Tumor micro-environment induced TRAIL secretion from engineered macrophages for anti-tumor therapy.

The high plasticity and long-term persistency make macrophages excellent vehicles for delivering anti-tumor cytokines. Macrophage delivery of chemokines and cytokines shows potential in tumor therapy. TRAIL, a promising anti-tumor cytokine, induces apoptosis in tumor cells with low toxicity to normal cells. However, its off-target toxicity and limited stability have limited its clinical progress. Here, we engineered macrophages with Mono-TRAIL and Tri-TRAIL and found that Tri-TRAIL had higher cytotoxic activity against tumor cells than Mono-TRAIL in vitro. To target the tumor microenvironment (TME), we generated macrophages secreting trimeric TRAIL (Tri-TRAIL-iM) induced by the TME-specific promoter Arg1. The Tri-TRAIL-iM cells displayed high specific activatable activity in cell-based co-culture assay and tumor-baring mice models. In addition, we demonstrated that compared to macrophages over-expressing TRAIL under a non-inducible promoter, Tri-TRAIL-iM could more effectively induce apoptosis in cancer cells, inhibit tumor growth, and reduce systemic side effects. This strategy of inducing TRAIL delivery holds great potential for cancer therapy. It is promising to be combined with other engineering methods to maximize the therapeutic effects of solid tumors.

The Shape Trail Test Is Sensitive in Differentiating Older Adults with Mild Cognitive Impairment: A Culture-neutral Five-minute Test.

INTRODUCTION: The Shape Trail Test (STT) was developed based upon the Trail Making Test, as a culture-neutral test for measuring processing speed and mental flexibility. This study aims to evaluate the accuracy and validity of this five-minute test for differentiating individuals with normal cognition (NC), subjective memory impairment (SMI), and mild cognitive impairment (MCI). METHOD: The study included 210 participants aged 50-80 years, with 70 participants in each group matched for age, education, and gender. RESULTS: No significant difference in STT measures was found between the NC and SMI groups. In contrast, both the NC and SMI groups exhibited significantly better performance (shorter completion time in STT-A and STT-B and fewer STT-B errors) than the MCI group. No significant group differences were found in STT-A errors. Stepwise regression analysis identified three significant predictors for classifying the MCI group from the NC and/or SMI groups, including the STT-B completion time, the STT-A errors, and the interaction between STT-B completion time and STT-B errors. The composite score of these three predictors demonstrated good discriminatory power for classifying the MCI group from the other groups, with area under the curves (AUCs) of 0.76 - 0.79 (p < 0.001), sensitivities of 78.6% - 80%, and specificities of 60% - 61.4%. However, none of the STT measures or their interactions were significant predictors for differentiating the SMI group from the NC group. Besides, the STT measures were significantly correlated with age, education, and executive function measures. DISCUSSION: The STT could be a culture- and language-free, reliable test for assessing executive function and a sensitive test for predicting MCI.

Assessment of Cognitive Flexibility in Jordanian Diabetic Patients by Wisconsin Card Sorting and Trail Making Tests: Implications with Demographic, Anthropometric and Therapeutic Variables.

Purpose: Cognitive flexibility is a mental ability that aids in smoothly alternating between them tasks in the brain. Diabetes Mellitus (DM) is a, common disorder that has been associated with impairments in cognitive functions. This research is a retrospective case-control study aimed at establishing a clear relationship between cognitive flexibility and diabetes among Jordanians, considering demographic, anthropometric, and therapeutic variables. Patients and Methods: The Wisconsin Card Sorting Test (WCST)-64 item and the Trail Making Test (TMT) assessed cognitive flexibility in 268 people with diabetes and healthy control. Demographic, therapeutic data were collected. We also measured waist-to-hip ratio (WHR) and body mass index (BMI). As the variables were non-normally distributed, non-parametric statistical tests were used to examine differences (Kruskal-Wallis) and correlation (Spearman) between variables. Results: The patient group did worse on the WCST In contrast to the control group, patients exhibited more significant delays for both Part A and Part B of the TMT (p<0.05). Males had higher WCST conceptual level responses than females. In addition, participants with professional jobs showed less delay in TMT Part A (p<0.05). Age was positively correlated with WCST's total errors and TMT's Parts A and B (p<0.05). BMI was negatively correlated with the WCST's conceptual level of responses and positively correlated with TMT's Part B (p<0.05). In addition, urea and albumin levels were positively correlated with TMT's Part A (p<0.05). Furthermore, creatinine was positively correlated with WCST's total errors and TMT's Part A (p<0.05). Conclusion: Some measures of cognitive flexibility are associated with DM status in the studied sample of Jordanians and other variables (educational levels, occupation, lifestyle, average duration of illness, and age).

[Application of the Trail Making Test in the schizophrenia research]. / A Trail Making Teszt alkalmazása a szkizofrénia-kutatásban.

Even the Kraepelinian concept of dementia praecox suggests a link between schizophrenia and various cognitive deficits. Although cognitive impairment is not a fundamental symptom of schizophrenia, it is considered to be one of the basic features of the disease. The deficit can affect a number of cognitive domains and is most often specific. One of the most pronounced cognitive symptoms of schizophrenia is impairment in attentional and executive functions. The Trail Making Test (TMT) is a screening test commonly used in the clinic that is very sensitive to impairments in attention and executive functions. The aim of the present study is to summarise the research conducted in the last five years in which the Trail Making Test has been used to screen schizophrenics. A search was conducted in the PubMed database using the keywords "schizophrenia" and "Trail Making Test". A total of 43 relevant studies have been published on this topic since 2018. A review of the research on this topic shows that the TMT can be used to identify cognitive deficits in schizophrenics, affecting executive functions and attention. It also shows that schizophrenic patients performed significantly worse on the test than healthy individuals.

The accuracy of trail cameras to aid manual identification and counts of items placed in separate collection bins of recyclables.

Checking each item placed in a separate collection bin of recyclables to examine contamination is often difficult for a researcher relying on such data. This is because of the time and inconvenience involved to manually identify items. We test a proof-of-concept experiment on the ability of trail cameras to identify items placed within separate collection bins. After a pre-test of seven camera models, we selected one with the best image quality. We use this camera for lab and field trials to count the number of identifiable items based on photos compared to manual hand-counts of the items. Three lab trials of this camera resulted in an average of 82% accuracy in item identification. We then conducted a field experiment, testing photo quality to identify items in six separate collection bins across a university campus over a one-month period with a total of over 9,700 photos. Of the 1343 items placed in the separate collection bins, the trail cameras provided photographs of high enough quality such that successful identification occurred for 68.5% of the items, with poor identification for paper items and small items. We conclude that trail cameras can be useful for data collection in separate collection behavior, especially for items with the largest surface size greater than a credit card.

Using blood TNF-related apoptosis-inducing ligand levels to discriminate between viral and bacterial infections: A prospective observational study.

OBJECTIVE: The aim of the investigation was to evaluate variations in blood TNF-related apoptosis-inducing ligand (TRAIL) levels between patients with viral and bacterial infections and the diagnostic performance of TRAIL for identifying viral and bacterial infections. METHODS: The investigation included 169 adult (>18 years) patients presenting with medical signs of acute infections (inclusion criteria included a body temperature over 37.5 °C, an onset of symptoms no more than 12 days). Reference standard was based on a rigorous expert panel and the majority of the panel determined the infectious etiology. Finally, 104 patients with 78 bacterial and 26 viral reference standard outcomes were enrolled in this investigation (24 were eliminated depending on the exclusion criteria; 41 had indeterminate reference standard diagnosis). ELISA was employed to measure TRAIL levels in the group of 78 subjects with bacterial infections and 26 individuals with viral infections, and the diagnostic performance of TRAIL was identified by receiver operating characteristic (ROC) analysis. RESULTS: The TRAIL level in individuals with bacterial infections was significantly lower than that in subjects with viral infections (16.59 (2.61-32.6) pg/mL vs. 97.39 (36.18-127.74) pg/mL, P < 0.05). The area under the ROC curve (AUC) of TRAIL was 0.86 (95 %CI:0.79 to 0.94) for identifying bacterial and viral infections. Combining TRAIL with C-reactive protein (CRP), the AUC was 0.94 (95 %CI:0.89 to 1.00). CONCLUSIONS: TRAIL is diagnostic for discriminating between viral and bacterial infections. Combining TRAIL with CRP increases the AUC.

Effect of comprehensive geriatric assessment on hospitalizations in older adults with frailty initiating curatively intended oncologic treatment: The PROGNOSIS-RCT study.

INTRODUCTION: Frailty constitutes a risk for unplanned hospitalizations in older adults with cancer. This study examines whether comprehensive geriatric assessment (CGA) as an add-on to standard oncologic care can prevent unplanned hospitalizations in older adults with frailty and cancer who initiate curative oncological treatment. MATERIALS AND METHODS: This randomized controlled trial included older adults aged ≥70 with frailty (Geriatric 8 [G8] ≤14), and solid cancers who initiated curative oncological treatment. Participants were randomized 1:1 to either standard oncologic care (control) or standard oncologic care supplemented with CGA-guided interventions (intervention). Baseline characteristics were retrieved prior to randomization. The primary endpoint, the between-group rate ratio of unplanned hospitalizations within six months of treatment initiation, was analyzed using negative binominal regression. Analyses were performed using an intention-to-treat approach, followed by per-protocol analysis, including participants receiving CGA within 30 days of randomization, and preplanned subgroup analyses based on treatment modality and Geriatric 8 screening. Secondary endpoints included acute hospital contacts, treatment adherence, and toxicity. RESULTS: From November 1, 2020 to May 31, 2023, 173 participants were enrolled. Median age was 75 (interquartile range 72-79), 51.5% were female, 58% had a G8 score > 12, and 84% had Eastern Cooperative Oncology Group performance status 0-1. The most common cancer sites were lung (23%), upper gastrointestinal (15%), and breast (13%). The rate (per person-years) of unplanned hospitalization was 1.32 in the intervention group and 1.81 in the control group, with a between-group rate ratio of 0.74 (95% confidence interval [CI] 0.45-1.23, P = 0.25) favoring the intervention. The between-group rate ratio increased in the per-protocol analysis (0.64 [95% CI 0.37-1.10, P = 0.10]). Similarly, no significant between group differences were found in treatment adherence, rate of acute hospital contacts, or toxicity. DISCUSSION: In this study, CGA did not significantly reduce the rate of unplanned hospitalizations. Furthermore, no between-group differences were found in treatment adherence, toxicity lead hospitalizations, or treatment completion in older adults with cancer and frailty. However, per-protocol analysis suggests that increasing adherence to CGA may improve the outcome. Larger studies ensuring higher CGA adherence are warranted to confirm our findings.

Short-term skin reactions and changes in stratum corneum following different ways of facial sheet mask usage.

BACKGROUND: The global facial mask market grows steadily at 8.5 % annually. However, prolonged use may lead to skin inflammation. OBJECTIVE: To investigate how various mask types and wearing durations impact skin physiology and aquaporins3 (AQP3) expression in healthy subjects. METHODS: We used a randomized controlled design to investigate the effects of three types of facial masks (pure water, hyaluronan, and bifida ferment lysate) and four different duration(5, 15, 25, and 40 min) on various skin parameters in volunteers, assessing moisture content, transepidermal water loss (TEWL), sebum, corneocyte size, and AQP3 expression before and after mask application, while also evaluating adverse reactions, discomfort, and noncompliance. RESULT: Hydration and TEWL increased at first, then decreased. Sebum increased with all types of masks, particularly after 40 min. Vasodilation and AQP3 expression were linked to mask duration. Corneocyte sizes remained constant. The main adverse reactions were redness (10.71 %, n = 28) and dryness (57.14 %, n = 28), especially with pure water masks lasting over 25 min. CONCLUSION: Short-term use of facial sheet masks (<25 min) benefits skin with improved hydration, reduced redness, and AQP3 activation, while prolonged use can lead to increased dryness and redness.