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Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association. Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL. Results: Higher HL scores B = 0.13 (95% CI = 0.06-0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31-0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = -6.12 (95% CI = -7.66 to - 4.58, p = 0.001) and FCoV-19 B = -0.91 (95% CI = -1.03 to - 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary. Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic.
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This study partially replaced the clay with sewer sludge (SS) and rice husk (RH-SS) to make fired bricks. The brick samples were examed in terms of shrinkage, water absorption, and compressive strength. Besides, they were analyzed via XRD and metal extraction to determine the heavy metal residuals in the products. The results showed that it was possible to fabricate fired bricks using sewer sludge or rice husk-blended sludge with up to 30% by weight. These brick samples complied with the technical standard for clay brick production, in which the compressive strength was more than 7.5 MPa, water absorption was from 11-16%, and the linear shrinkage was all less than 5%. The rice husk addition helped mitigate the heavy metal residuals in the bricks and leaching liquid, in which all the values were lower than the US-EPA maximum concentration of contaminants for toxicity characteristics.Implications: Previous studies have proved the possibility of mixing sewage sludge from different origins (sewage sludge, river sediment, canal sediment, sewer sediment, etc.) with clay and some wastes to make bricks. In which, mostof the studies used sewage sludge from wastewater treatment plants, very fewdealt with lake/river or sewer sediment. This study shall be the first to study the possibility of employing sewer sediments with the addition of rice husk powder to achieve two targets, including (1) the reuse of biowaste and sludge for brick fabrication and (2) the reduction of heavy metals in final calcined bricks. Different ratios of the rice-husk blended sewer sludge (RH-SS) - clay mixture shall be tested to find the optimized compositions. The results showed that it was possible to fabricate fired bricks using sewer sludge or rice husk-blended sludge with up to 30% by weight, which meant reduce 30% of clay in the brick production. The final products were proved to meet the quality standard in terms of compressive strength (more than 10 MPa), water absorption(from 11-16%), and the linear shrinkage (less than 5%). Larger scale of this study can be an evident to recommend for policy change in the waste reuse in construction field.
Subject(s)
Construction Materials , Sewage , Sewage/analysis , Sewage/chemistry , Construction Materials/analysis , Metals, Heavy/analysis , Recycling/methods , OryzaABSTRACT
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which multiple organs are damaged by the immune system. Although standard treatment options such as hydroxychloroquine (HCQ), glucocorticoids (GCs), and other immunosuppressive or immune-modulating agents can help to manage symptoms, they do not offer a cure. Hence, there is an urgent need for the development of novel drugs and therapies. In recent decades, cell therapies have been used for the treatment of SLE with encouraging results. Hematopoietic stem cell transplantation, mesenchymal stem cells, regulatory T (Treg) cell, natural killer cells, and chimeric antigen receptor T (CAR T) cells are advanced cell therapies which have been developed and evaluated in clinical trials in humans. In clinical application, each of these approaches has shown advantages and disadvantages. In addition, further studies are necessary to conclusively establish the safety and efficacy of these therapies. This review provides a summary of recent clinical trials investigating cell therapies for SLE treatment, along with a discussion on the potential of other cell-based therapies. The factors influencing the selection of common cell therapies for individual patients are also highlighted.
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Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.
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Objectives: Vertebral fracture is both common and serious among adults, yet it often goes undiagnosed. This study aimed to develop a shape-based algorithm (SBA) for the automatic identification of vertebral fractures. Methods: The study included 144 participants (50 individuals with a fracture and 94 without a fracture) whose plain thoracolumbar spine X-rays were taken. Clinical diagnosis of vertebral fracture (grade 0 to 3) was made by rheumatologists using Genant's semiquantitative method. The SBA algorithm was developed to determine the ratio of vertebral body height loss. Based on the ratio, SBA classifies a vertebra into 4 classes: 0 = normal, 1 = mild fracture, 2 = moderate fracture, 3 = severe fracture). The concordance between clinical diagnosis and SBA-based classification was assessed at both person and vertebra levels. Results: At the person level, the SBA achieved a sensitivity of 100% and specificity of 62% (95% CI, 51%-72%). At the vertebra level, the SBA achieved a sensitivity of 84% (95% CI, 72%-93%), and a specificity of 88% (95% CI, 85%-90%). On average, the SBA took 0.3 s to assess each X-ray. Conclusions: The SBA developed here is a fast and efficient tool that can be used to systematically screen for asymptomatic vertebral fractures and reduce the workload of healthcare professionals.
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OBJECTIVE: To investigate the protective effect of arbutin against CCl4-induced hepatic fibrosis in mice and explore the underlying mechanisms. METHODS: Twenty-four C57BL/6 mice were randomly divided into control group, model group, and low- and high-dose arbutin treatment (25 and 50 mg/kg, respectively) groups. Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4, and arbutin was administered daily via gavage for 6 weeks. After the treatments, serum biochemical parameters of the mice were tested, and liver tissues were taken for HE staining, Sirius Red staining and immunohistochemical staining. RT-qPCR was used to detect the mRNA levels of α-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a, and Western blotting was performed to detect α-SMA protein expression in the liver tissues. In the cell experiment, the effect of arbutin treatment for 24 h on THP-1 and RAW264.7 cell migration and recruitment was examined using Transwell migration assay and DAPI staining; The changes in protein levels of Akt, p65, Smad3, p-Akt, p-p65, p-Smad3 and α-SMA in arbutintreated LX-2 cells were detected with Western blotting. RESULTS: Arbutin treatment significantly lowered serum alanine aminotransferase and aspartate aminotransferase levels, alleviated liver tissue damage and collagen deposition, and reduced macrophage infiltration and α-SMA protein expression in the liver of the mouse models (P < 0.05 or 0.001). Arbutin treatment also significantly reduced CCl4-induced elevation of a-SMA, Pdgfb, Col1α1, Timp-1, Ccl2 and Tnf-a mRNA levels in mice (P < 0.05). In the cell experiment, arbutin treatment obviously inhibited migration and recruitment of THP-1 and RAW264.7 cells and lowered the phosphorylation levels of Akt, p65 and Smad3 and the protein expression level of α-SMA in LX-2 cells. CONCLUSION: Arbutin ameliorates liver inflammation and fibrosis in mice by inhibiting hepatic stellate cell activation via reducing macrophage recruitment and infiltration and suppressing activation of the Akt/NF-κB and Smad signaling pathways.
Subject(s)
Arbutin , Liver Cirrhosis , Macrophages , Proto-Oncogene Proteins c-akt , Signal Transduction , Animals , Male , Mice , Arbutin/pharmacology , Arbutin/therapeutic use , Carbon Tetrachloride , Cell Movement/drug effects , Disease Models, Animal , Hepatic Stellate Cells/metabolism , Hepatic Stellate Cells/drug effects , Liver/metabolism , Liver/pathology , Liver/drug effects , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Macrophages/metabolism , Macrophages/drug effects , Mice, Inbred C57BL , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , RAW 264.7 Cells , Signal Transduction/drug effects , Smad Proteins/metabolismABSTRACT
Diabetic kidney disease (DKD), the most common cause of kidney failure, is a frequent complication of diabetes and obesity, and yet to date, treatments to halt its progression are lacking. We analyze kidney single-cell transcriptomic profiles from DKD patients and two DKD mouse models at multiple time points along disease progression-high-fat diet (HFD)-fed mice aged to 90-100 weeks and BTBR ob/ob mice (a genetic model)-and report an expanding population of macrophages with high expression of triggering receptor expressed on myeloid cells 2 (TREM2) in HFD-fed mice. TREM2high macrophages are enriched in obese and diabetic patients, in contrast to hypertensive patients or healthy controls in an independent validation cohort. Trem2 knockout mice on an HFD have worsening kidney filter damage and increased tubular epithelial cell injury, all signs of worsening DKD. Together, our studies suggest that strategies to enhance kidney TREM2high macrophages may provide therapeutic benefits for DKD.
Subject(s)
Diabetic Nephropathies , Diet, High-Fat , Kidney , Macrophages , Membrane Glycoproteins , Mice, Knockout , Obesity , Receptors, Immunologic , Animals , Receptors, Immunologic/metabolism , Receptors, Immunologic/genetics , Membrane Glycoproteins/metabolism , Membrane Glycoproteins/genetics , Macrophages/metabolism , Obesity/metabolism , Obesity/pathology , Obesity/complications , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Mice , Kidney/pathology , Kidney/metabolism , Humans , Male , Mice, Inbred C57BL , FemaleABSTRACT
BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.
Subject(s)
COVID-19 , Sex Characteristics , Adult , Female , Male , Humans , Latent Class Analysis , Cross-Sectional Studies , Pandemics , COVID-19/epidemiology , Cluster Analysis , Life StyleABSTRACT
Background: A fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP. Methods: This randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity. Inclusion criteria included participants willing to wear ABPM device for 24 h. Exclusion criteria included screening blood pressure >140/90 mmHg and antihypertensive medications not stable for 3 months prior to randomization. Participants received placebo (n = 184), phentermine 30 mg; (n = 191), or PHEN 15 mg/TPM 92 mg; (n = 190). 24-hour ABPM was performed at baseline and at week 8. The primary endpoint was mean 24-h systolic BP (SBP) as measured by ABPM, in the per protocol population. Results: Participants were mostly female (73.5 â%) and White (81.6 â%), with a mean age of 53.4 years; 32.4 â% had no hypertension diagnosis or treatment, 62.5 â% had hypertension using 0 to 2 antihypertensive medications, and 5.1 â% had hypertension using ≥ 3 antihypertensive medications. Baseline mean SBP/diastolic BP (DBP) was 123.9/77.6 âmmHg. At week 8, mean SBP change was -0.1 âmmHg (placebo), +1.4 âmmHg (phentermine 30 âmg), and -3.3 âmmHg (PHEN/TPM). Between-group difference for PHEN/TPM versus placebo was -3.2 âmmHg (95 â% CI: -5.48, -0.93 âmmHg; p â= â0.0059). The between-group difference for PHEN/TPM versus phentermine 30 âmg was -4.7 âmmHg (95 â% CI: -6.96, -2.45 âmmHg; p â< â0.0001). Common (>2 â% in any treatment group) adverse events (i.e., dry mouth, constipation, nausea, dizziness, paresthesia, dysgeusia, headache, COVID-19, urinary tract infection, insomnia, and anxiety) were mostly mild or moderate. Conclusions: In this randomized, multicenter, double-blind ABPM study, PHEN/ TPM reduced SBP compared to either placebo or phentermine 30 mg (Funding: Vivus LLC; ClinicalTrials.gov: NCT05215418).
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OBJECTIVES: The current study investigated the gap between actual and expected work responsibilities of psychiatry vice chairs of education (VCEs), their work satisfaction, and perceived work barriers. METHODS: Psychiatry VCEs were identified through professional memberships and school websites within the USA. In 2021, identified VCEs were emailed an anonymous survey that was based on past research on roles and responsibilities of VCEs. Through qualitative and quantitative questions, the survey assessed demographic characteristics, actual and expected work responsibilities, work satisfaction, and work barriers during time spent in the VCE role. RESULTS: Of 57 identified psychiatry VCEs, 32 (56.1%) completed the survey. Most respondents (59.4%) said their department/institution did not have a written VCE job description. There were gaps between actual and expected VCE responsibilities, especially with the performance review of education leaders (Δ - 11; actual n = 20 vs. expected n = 31). The greatest satisfaction came from mentoring trainees/faculty (respectively 4.88 ± 0.33 and 4.85 ± 0.37 on a 5-point scale) and overseeing/supporting educational programs (4.66 ± 0.48). Comments on work barriers included limited protected time (n = 11), education budget constraints (n = 6), and having multiple leadership roles (n = 5). The actual full-time equivalent in the VCE role was significantly lower than expected (p < .001). CONCLUSION: Considering the role of psychiatry VCEs remains relatively new and is evolving, adequate allocation of resources and improved job descriptions may help close the gap between expected and actual responsibilities. The current findings can assist in developing such job descriptions to attract and define the work of a VCE based on specific responsibilities and associated work satisfaction.
Subject(s)
Faculty , Psychiatry , Humans , Leadership , Surveys and Questionnaires , Psychiatry/education , Job Satisfaction , Faculty, MedicalABSTRACT
The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.
Subject(s)
Osteoporosis , Spinal Fractures , Adult , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Spinal Fractures/diagnostic imaging , Spinal Fractures/epidemiology , Spinal Fractures/etiology , Cohort Studies , Prevalence , Incidence , Vietnam , Osteoporosis/diagnostic imaging , Osteoporosis/epidemiology , Osteoporosis/complications , Bone Density , Absorptiometry, Photon/methods , Risk Factors , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/injuriesABSTRACT
We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.
Subject(s)
Neoplasms , Humans , Reproducibility of Results , Neoplasms/diagnosis , Neoplasms/genetics , Short Interspersed Nucleotide Elements , Machine Learning , AneuploidyABSTRACT
BACKGROUND: Sarcopenia is a geriatric disease characterized by the progressive and generalized loss of skeletal lean mass and strength with age. The prevalence of sarcopenia in the Vietnamese population is unknown. This study sought to estimate the prevalence of and risk factors for sarcopenia among community-dwelling individuals in Vietnam. METHODS: This cross-sectional study is part of the ongoing Vietnam Osteoporosis Study project. The study involved 1308 women and 591 men aged 50 years and older as at 2015 (study entry). Whole-body dual-energy X-ray absorptiometry was used to measure the appendicular skeletal lean mass. Anthropometric and clinical data were collected using a structured questionnaire. Sarcopenia was defined according to the criteria proposed by the Asian Working Group for Sarcopenia in 2019. Logistic regression analysis was used to determine the association between potential risk factors and sarcopenia. RESULTS: The prevalence of sarcopenia in women and men was 14% (n = 183) and 16% (n = 83), respectively. Age (odds ratio [OR] per 10 years = 1.37; 95% confidence interval [CI] 1.26-1.48) and being underweight (OR = 1.61; 95% CI 1.00-2.58) were independently associated with increased risk of sarcopenia. The combination of low physical activity, being underweight and advancing age accounted for ~27% of sarcopenic patients. However, most of the attributable fraction was due to ageing. CONCLUSIONS: Sarcopenia is common in community-dwelling Vietnamese adults, particularly those with advancing age, who are underweight and with low physical activity.
Subject(s)
Osteoporosis , Sarcopenia , Male , Adult , Humans , Female , Middle Aged , Aged , Child , Sarcopenia/etiology , Vietnam/epidemiology , Prevalence , Independent Living , Thinness/complications , Cross-Sectional Studies , Osteoporosis/epidemiology , Osteoporosis/etiology , Risk FactorsABSTRACT
Objectives@#Vertebral fracture is both common and serious among adults, yet it often goes undiagnosed. This study aimed to develop a shape-based algorithm (SBA) for the automatic identification of vertebral fractures. @*Methods@#The study included 144 participants (50 individuals with a fracture and 94 without a fracture) whose plain thoracolumbar spine X-rays were taken. Clinical diagnosis of vertebral fracture (grade 0 to 3) was made by rheumatologists using Genant’s semiquantitative method. The SBA algorithm was developed to determine the ratio of vertebral body height loss. Based on the ratio, SBA classifies a vertebra into 4 classes: 0 = normal, 1 = mild fracture, 2 = moderate fracture, 3 = severe fracture). The concordance between clinical diagnosis and SBAbased classification was assessed at both person and vertebra levels. @*Results@#At the person level, the SBA achieved a sensitivity of 100% and specificity of 62% (95% CI, 51%–72%). At the vertebra level, the SBA achieved a sensitivity of 84% (95% CI, 72%–93%), and a specificity of 88% (95% CI, 85%–90%). On average, the SBA took 0.3 s to assess each X-ray. @*Conclusions@#The SBA developed here is a fast and efficient tool that can be used to systematically screen for asymptomatic vertebral fractures and reduce the workload of healthcare professionals.
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Objectives@#This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. @*Methods@#A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. @*Results@#The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. @*Conclusions@#This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.
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Objective: To investigate the relationship between the expression of CD103+CD8+T cells in locally advanced oral squamous cell carcinoma (LA-OSCC), and the response to neoadjuvant chemoimmunotherapy (NACI). Methods: Thirty LA-OSCC patients from the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, who underwent NACI from June 2020 to December 2022 were analyzed, including 16 responders and 14 non-responders. Using multiple immunofluorescence technique to stain sections of patients to verify the correlation between the expression of CD103+CD8+T cells and the efficacy of NACI. CD103+CD8+T cell density was counted using Inform and HALO software. The Spearman correlation coefficient in rank correlation is used to describe the correlation between CD103+CD8+T cell and neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-lymphocyte ratio (PLR), systemic immune inflammation index (SII) It's effectiveness as a predictive marker to NACI was analyzed by receiver operator characteristic (ROC) curve analysis and decision curve analysis (DCA). Two-tailed t-test or Mann-Whitney U-test was used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. SPSS 22.0 and GraphPad prism 9.0 software were used for statistical analysis and plotting of relevant statistical graphs such as histograms. P<0.05 was considered a statistically significant difference. Results: The density of CD103+CD8+T cells has expanded in advanced OSCC patients who are responsive to NACI. The CD103+CD8+T cell densities in the responsive and nonresponsive groups were 118.30(41.92, 197.80) pcs/mm2 and 21.63(4.91, 71.92) pcs/mm2 respectively, with statistically significant differences(U=52.00, P=0.012). CD103+CD8+T cell abundance was negatively correlated with NLR, dNLR, PLR, and SII (P<0.05). ROC curve analysis showed that the AUC for predicting efficacy of NLR, dNLR, PLR, and SII were 0.781 (P=0.009, 95%CI: 0.5715-0.9910), 0.671 (P=0.105, 95%CI: 0.467-0.881), 0.679 (P=0.020 95%CI: 0.549-0.951), 0.750 (P=0.096, 95%CI: 0.461-0.896), respectively. The AUC for CD103+CD8+T cells alone was 0.861 (P=0.013, 95%CI: 0.585-0.950), and the AUC of combining CD103+CD8+T cells with NLR was 0.896 (P=0.025, 95%CI: 0.454-0.938). Conclusions: The density of CD103+CD8+T cells is expanded in advanced OSCC patients who are responsive to NACI. CD103+CD8+T cells positively predict favorable responses as a strong indicator to NACI in advanced OSCC patients. Co-interpretation of CD103+CD8+T cells and NLR value enhances the predictive accuracy of NACI in advanced OSCC patients.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/pathology , Neutrophils/pathology , Squamous Cell Carcinoma of Head and Neck/therapy , Squamous Cell Carcinoma of Head and Neck/pathology , Neoadjuvant Therapy , Mouth Neoplasms/therapy , Mouth Neoplasms/pathology , Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Inflammation/pathology , Head and Neck Neoplasms/pathology , Retrospective Studies , PrognosisABSTRACT
The human airway contains specialized rare epithelial cells whose roles in respiratory disease are not well understood. Ionocytes express the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), while chemosensory tuft cells express asthma-associated alarmins. However, surprisingly, exceedingly few mature tuft cells have been identified in human lung cell atlases despite the ready identification of rare ionocytes and neuroendocrine cells. To identify human rare cell progenitors and define their lineage relationship to mature tuft cells, we generated a deep lung cell atlas containing 311,748 single cell RNA-Seq (scRNA-seq) profiles from discrete anatomic sites along the large and small airways and lung lobes of explanted donor lungs that could not be used for organ transplantation. Of 154,222 airway epithelial cells, we identified 687 ionocytes (0.45%) that are present in similar proportions in both large and small airways, suggesting that they may contribute to both large and small airways pathologies in CF. In stark contrast, we recovered only 3 mature tuft cells (0.002%). Instead, we identified rare bipotent progenitor cells that can give rise to both ionocytes and tuft cells, which we termed tuft-ionocyte progenitor cells (TIP cells). Remarkably, the cycling fraction of these TIP cells was comparable to that of basal stem cells. We used scRNA-seq and scATAC-seq to predict transcription factors that mark this novel rare cell progenitor population and define intermediate states during TIP cell lineage transitions en route to the differentiation of mature ionocytes and tuft cells. The default lineage of TIP cell descendants is skewed towards ionocytes, explaining the paucity of mature tuft cells in the human airway. However, Type 2 and Type 17 cytokines, associated with asthma and CF, diverted the lineage of TIP cell descendants in vitro , resulting in the differentiation of mature tuft cells at the expense of ionocytes. Consistent with this model of mature tuft cell differentiation, we identify mature tuft cells in a patient who died from an asthma flare. Overall, our findings suggest that the immune signaling pathways active in asthma and CF may skew the composition of disease-relevant rare cells and illustrate how deep atlases are required for identifying physiologically-relevant scarce cell populations.
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Methylene blue (MB) is hazardous in natural water because this dye causes serious diseases that endangers public health and ecosystems. Photocatalytic degradation is a prominent technique for achieving the effective elimination of dye pollutants from wastewater and contribute vitally to ecology and environmental safety. Herein, Cu2+-substituted ZnFe2O4 nanomaterials (CuxZn1-xFe2O4; x = 0, 0.1, 0.2, 0.3, 0.4, 0.6) were synthesized, characterized, and applied for the photocatalytic degradation of MB dye beneath visible light with the assistance of hydrogen peroxide (H2O2). The feature of the photo-catalysts was determined by XRD, EDX, FTIR, DRS, BET, SEM, and TEM techniques. Incorporation of Cu2+ ions changed the crystalline phase, particle size, morphology, and surface area. The photocatalysis condition was optimized with the following major factors, the amout of doping Cu2+ ions, H2O2 concentration, adsorbent dosage, and MB concentration. As a result, the photocatalytic MB degradation efficiency by Cu0.6Zn0.4Fe2O4 catalyst was 99.83% within 90 min under LED light (λ ≥ 420 nm), which was around 4 folds higher than that of pure ZnFe2O4. The photo-Fenton kinetics were in accordance with the pseudo-first-order kinetic model (R2 = 0.981), giving the highes rate constant of 0.034 min-1. It can be, therefore, concluded that Cu2+ substitution considerably boosted the photocatalytic activity of CuxZn1-xFe2O4 ZnFe2O4, suggesting a bright prospect of Cu0.6Zn0.4Fe2O4 as a photo-catalyst in the dyes wastewater treatment.
ABSTRACT
Background: Erlotinib and gefitinib are epidermal growth factor receptor-tyrosine kinase inhibitors approved for non-small cell lung cancer treatment by the US Food and Drug Administration. Drug-drug interactions (DDIs) with these agents are vague and poorly understood. Because DDIs can have an effect on clinical outcomes, we aimed to identify drugs that interact with erlotinib or gefitinib and describe their clinical manifestations. Methods: A retrospective analysis was performed on the health records of patients in the US Department of Defense Cancer Registry (retrieved September 2021), Comprehensive Ambulatory/Professional Encounter Records, and Pharmacy Data Transaction Service database (both retrieved May 2022). Patients' medical history, diagnoses, and demographics were extracted and analyzed for differences in adverse effects when these agents were used alone vs concomitantly with other prescription drugs. Patients' diagnoses and prescription drug use were extracted to compare completed vs discontinued treatment groups, identify medications commonly co-administered with erlotinib or gefitinib, and evaluate DDIs with antidepressants. Results: Of 387 patients using erlotinib, 264 completed treatments; 28 of 33 patients using gefitinib completed treatment. The P value for erlotinib discontinuation when used alone vs concomitantly was < .001, and the P value for gefitinib discontinuation was .06. Patients who took erlotinib or gefitinib concomitantly with a greater number of prescription drugs had a higher rate of treatment discontinuation than those who received fewer medications. Patients in the completed group received 1 to 75 prescription drugs, and those in the completed group were prescribed 3 to 103. Those who discontinued treatment had more diagnosed medical issues than those who completed treatment. Conclusions: This review cannot conclude that concomitant use with prescription drug(s) resulted in erlotinib or gefitinib discontinuation. There were no significant DDIs determined between erlotinib or gefitinib and antidepressants.