Downregulation of GDF15 suppresses ferroptosis and predicts unfavorable prognosis in clear cell renal cell carcinoma.

BACKGROUND: Growth differentiation factor 15 (GDF15), a member of the transforming growth factor beta (TGF-ß) superfamily, is involved in various pathophysiological processes such as anorexia, obesity, inflammation, and tumorigenesis. However, the role of GDF15 in clear cell renal cell carcinoma (ccRCC) remains poorly understood. METHODS: Clinical significance of GDF15 in ccRCC as well as other types of human cancers was analyzed using the TCGA PANCAN dataset. Gene Set Enrichment Analysis (GSEA) was used to study the significantly enriched pathways associated with GDF15 expression. qRT-PCR was used to quantitatively assess relative mRNA expression level. Flow cytometry was used to detect cell cycle. CCK-8 assay, colony formation assay, wound healing assay, Transwell migration/invasion assay, and EdU assay were used to comprehensively examine tumor viability and aggressiveness. MDA and iron assays were used to determine ferroptosis-related intracellular changes. RESULTS: We found that GDF15 expression is decreased in renal carcinoma tissue. In 769-p and Caki-1 cells, GDF15 knockdown significantly promoted tumor viability, proliferation, and migration. Conversely, overexpression of GDF15 suppressed cell proliferation and invasion. Results from GSEA suggested that GDF15 might play a crucial role in ferroptosis. We further demonstrated that GDF15 is correlated with intracellular iron and lipid peroxidation MDA in 769-p and Caki-1 cells. In summary, we conclude that GDF15 inhibits migration and invasion of ccRCC cells by regulating ferroptosis. CONCLUSION: Our study demonstrates that GDF15 downexpression promotes viability and aggressiveness of ccRCC cells by abolishing ferroptosis, which confers unfavorable patient survival outcomes.

Release of millions of micro(nano)plastic fragments from photooxidation of disposable plastic boxes.

The widespread use of disposable plastic boxes is exacerbating the dangers of microplastics (MPs); however, little is known about the fragmentation behavior of MPs during aging. In this study, the dynamic evolution on the release of micro(nano)plastics and photoaging properties of two disposable plastic boxes (polypropylene (PP) and polystyrene (PS)) were investigated under light irradiation and mechanical abrasion. Results showed that the weight of PP and PS was decreased by 53 % and 100 %, respectively after 60 d of ultraviolet irradiation (UV60). Moreover, a large number of fragmented particles were produced from the combined light irradiation and abrasion, with 0.142 ± 0.006 and 0.141 ± 0.013 million micro(nano)plastics/mL particles from PP and PS boxes, respectively, and the nanometer range (<100 nm) accounted for 70.8 % and 46.8 %. The correlation model of the average size or alteration time versus carbonyl index (CI) was developed, which indicated that the fragmentation behavior was mainly related to the photooxidation, though mechanical abrasion also played a certain enhancing role. Additionally, PS was susceptible to the fragmentation and photooxidation compared to PP possibly since the phenyl ring of PS was more vulnerable to UV attack than the methyl of PP. The findings of this study clarify the dynamic fragmentation process of micro(nano)plastics of disposable plastic boxes and provide useful information to access environmental fate of MPs more holistically.

[Effect of modified holmium laser enucleation of the prostate on postoperative urinary control and sexual function in elderly patients with benign prostatic hyperplasia].

OBJECTIVE: To investigate the impact of retaining part of the urethral mucosa on postoperative urinary control, erectile function, and ejaculatory function in patients undergoing holmium laser enucleation of the prostate (HoLEP) surgery. METHODS: A retrospective analysis was conducted on 176 benign prostatic hyperplasia (BPH) patients who underwent surgical treatment at our hospital from January 2019 to January 2022, including 80 cases of modified HoLEP surgery and 96 cases of standard HoLEP surgery. Preoperative and postoperative clinical data were collected and analyzed. RESULTS: At 3 months postoperatively, both groups showed significant improvement in maximum flow rate (Qmax), International Prostate Symptom Score (IPSS) , residual urine volume (RUV) , and quality of life (QOL) compared to pre-treatment values, with statistically significant differences (P<0.05) . There was a significant difference in QOL scores between the experimental and control groups (P<0.05) . At 3 months postoperatively, the incidence of urinary incontinence was significantly lower in the experimental group compared to the control group (P<0.05) . At 6 months postoperatively, both groups showed a significant increase in International Index of Erectile Function-5 (IIEF-5) scores compared to preoperative values (P<0.05) , with no significant difference between the two groups. The incidence of retrograde ejaculation in the experimental group was significantly lower than that in the control group (P<0.05) . CONCLUSIONS: Retaining part of the urethral mucosa in HoLEP surgery can effectively treat BPH, providing significant advantages in terms of urinary control and playing a positive role in overall postoperative sexual function recovery.

Increasing Access to Care for the Underserved: Voices of Riders, Drivers, & Staff of a Rural Transportation Program.

The qualitative data presented in this paper was part of a larger concurrent mixed methods study evaluating the effectiveness of a transportation program (Project TRIP) for low-income residents in rural eastern North Carolina. Twenty stakeholders involved in TRIP were interviewed, including riders (n = 12) of which 83% were over 50 years old, program staff including the program coordinator and 5 case managers (n = 6), and transportation providers (n = 2). Due to the COVID-19 pandemic, interviews were completed by phone with each participant. Themes from the qualitative data included the: (1) Emotional, health, & financial impacts of TRIP, (2) Changes that should be implemented into TRIP when replicating the program, and (3) Unique aspects of how TRIP operates that could inform other rural transportation programs. Thematic analysis was used to analyze the transcript data. The findings are couched in the context of how TRIP potentially defrays the impacts of cumulative disadvantage that residents experience over the life course by increasing access to healthcare.

Financial Burdens of Out-of-Pocket Spending Among Medicare Fee-for-Service Beneficiaries: Role of the "Big Four" Chronic Health Conditions.

While Medicare is the universal source of health care coverage for Americans aged 65 years or older, the program requires significant cost sharing in terms of out-of-pocket (OOP) spending. We conducted a retrospective study using data from 2016 to 2018 Medicare Current Beneficiary Surveys of elderly community-dwelling beneficiaries (n = 10,431) linked with administrative data to estimate OOP spending associated with the "big four" chronic diseases (cardiovascular disease, cancer, diabetes, and chronic lung disease). We estimated a generalized linear model adjusting for predisposing, enabling, and need factors to estimate annual OOP spending. We found that beneficiaries with any of the "big four" chronic conditions spent 15% (p < .001) higher OOP costs and were 56% more likely to spend ≥20% of annual income on OOP expenditure (adjusted odds ratio = 1.56; p < .001) compared with those without any of those conditions. OOP spending appears to be heterogeneous across disease types and changing by conditions over time.

Desorption of pharmaceuticals from pristine and aged polystyrene microplastics under simulated gastrointestinal conditions.

Microplastics (MPs) in the environment usually undergo extensive weathering and can transport pollutants to organisms once being ingested. However, the transportation mechanism and effect of aging process are poorly understood. This study systematically investigated the desorption mechanisms of pharmaceuticals from pristine and aged polystyrene (PS) MPs under simulated gastric and intestinal conditions of marine organisms. Results showed that the increased desorption in stomach mainly depended on the solubilization of pepsin to pharmaceuticals and the competition for sorption sites on MPs via π-π and hydrophobic interactions. However, high desorption in gut relied on the solubilization of intestinal components (i.e. bovine serum albumin (BSA) and bile salts (NaT)) and the competitive sorption of NaT since the enhanced solubility increased the partition of pharmaceuticals in aqueous phase. Aging process suppressed the desorption of pharmaceuticals because aging decreased hydrophobic and π-π interactions but increased electrostatic interaction between aged MPs and pharmaceuticals, which became less affected by gastrointestinal components. Risk assessment indicated that the MP-associated pharmaceuticals posed low risks to organisms, and warm-blooded organisms suffered relatively higher risks than cold-blooded ones. This study reveals important information to understand the ecological risks of co-existed MPs and pollutants in the environment.

Transurethral holmium laser resection and transurethral electrocision combined with intravesical epirubicin within 24 hours postoperatively for treatment of bladder cancer.

OBJECTIVE: To investigate the efficacy and safety of transurethral holmium laser resection (THOLR) and transurethral electrocision (TUR) combined with intravesical epirubicin within 24 hours postoperatively for treatment of non-muscular invasive bladder cancer. METHODS: A total of 218 consecutive patients who were newly diagnosed with bladder cancer were enrolled in this prospective study from July 2014 to December 2017. The patients were randomly divided into THOLR and TUR groups. All patients received intravesical epirubicin (30 mg dissolved in 5% glucose solution) within 24 hours postoperatively. The operation time, blood loss, rate of obturator reflex, hospitalization time, catheterization time, complications, and recurrence were analyzed. RESULTS: Operation, hospitalization, and catheterization times were significantly greater in the TUR group than in the THOLR group. The rates of blood loss and intraoperative obturator reflex were also significantly greater in the TUR group. There were no significant differences in complications, recurrence rate survival, or recurrence-free survival between the two groups, with the exception of bladder perforation rate. CONCLUSIONS: THOLR and TUR combined with intravesical epirubicin within 24 hours postoperatively were both safe and effective for treatment of bladder tumor; however, patients who undergo THOLR might experience more rapid recovery.

[Clinical effects of the circumcision stapler, foreskin cerclage, and traditional circumcision: A comparative study].

OBJECTIVE: To compare the clinical effects of the circumcision stapler, circumcision cerclage, and traditional circumcision in the treatment of phimosis and redundant prepuce. METHODS: Using the circumcision stapler (group A), foreskin cerclage (group B), and traditional circumcision (group C), we treated 276 patients with phimosis or redundant prepuce. We made comparisons among the three groups in the operation time, intraoperative blood loss, intraoperative and 24-hour postoperative pain scores, and incidence of postoperative complications. Results: The operation time, intraoperative blood loss, and intraoperative pain score were (6.52 ± 2.45) min, (1.93 ± 0.82) ml, and 1.37 ± 0.68 in group A and (7.24 ± 1.86) min, (1.51 ± 0.72) ml, and 1.20 ± 0.79 in group B, all significantly lower than (28. 36 ± 4.22) min, (9.52 ± 3.29) ml, and 3.06 ± 0.75 in group C (P <0.05). The 24-hour postoperative pain score was remarkably higher in group B than in A and C (3. 18 ± 0. 82 vs 1. 85 ± 0. 63 and 1. 82 ± 0. 75, P <0. 05). The incidence rate of postoperative complications was markedly lower in group A than in B (5. 43% vs 14. 13%, P < 0.05), but with no significant differences between either A and C or B and C (P >0.05). CONCLUSION: The circumcision stapler, with its advantages of simple operation, minimal invasiveness, fewer complications, and better cosmetic result, deserves a wider clinical application.

[Relationship between serum ß2-microglobulin and lower extremity atherosclerotic occlusive disease].

OBJECTIVE: To explore the relationship between fasting serum level of ß2-microglobulin (ß2-M) and the development of lower extremity atherosclerotic occlusive disease (LEAOD). METHODS: A total of 59 LEAOD patients at our hospital from March 2011 to August 2012 were recruited into the LEAOD group while another 32 non-LEAOD patients into the control group. Their clinical profiles and the parameters of ankle brachial index (ABI),ß2-M and high-sensitivity C-reactive protein (hsCRP) were recorded and analyzed. RESULTS: The patients had higher serum levels of ß2-M (5.3 ± 3.2 vs 2.6 ± 1.3) and hsCRP (15.1 ± 14.8 vs 8.0 ± 6.7) according to the severity in the LEAOD group than those in the control group (P < 0.05).ß2-M was correlated with smoking (ß 1.248, odds ratio[OR] 0.020, 95% confidence interval [CI] 1.221-9.942), diabetes (ß 1.524,OR 4.591, 95%CI 1.493-14.118) and ABI (ß-4.091,OR 0.017, 95%CI 0.002-0.136) . The receiver operating characteristic (ROC) curve showed that ß2-M level had some value of predicting the occurrence of LEAOD (ROCAUC 0.821, 95%CI 0.731-0.912, P < 0.01). CONCLUSION: Serum level of ß2-M may play a role in pathologic process of LEAOD. And further studies are needed to validate its value as a biomarker for LEAOD.

Association between travel times and food procurement practices among female supplemental nutrition assistance program participants in eastern North Carolina.

OBJECTIVE: To examine associations between self-reported vehicular travel behaviors, perceived stress, food procurement practices, and body mass index among female Supplemental Nutrition Assistance Program (SNAP) participants. ANALYSIS: The authors used correlation and regression analyses to examine cross-sectional associations between travel time and distance, perceived stress, food procurement practices (grocery shopping frequency, fast-food consumption, home meal consumption), and body mass index among female SNAP participants aged 20-65 years (n = 215) in eastern North Carolina. RESULTS: There were positive associations (P < .05) between travel patterns and stress (r = 0.18 for average miles traveled), grocery shopping frequency (r = 0.16 for average miles traveled), and fast-food consumption (r = 0.19 for average miles traveled, r = 0.29 for average minutes traveled). CONCLUSIONS AND IMPLICATIONS: SNAP education materials should focus on healthful interactions with the food environment, even when participants must travel long distances.

Food stamp participation is associated with fewer meals away from home, yet higher body mass index and waist circumference in a nationally representative sample.

OBJECTIVE: To examine associations between Food Stamp (FS) participation, meals away from home (MAFH), body mass index (BMI), and waist circumference (WC). DESIGN: Cross-sectional study. SETTING: Nationally representative. PARTICIPANTS: Data from low-income, FS-eligible individuals (N = 945) ages 20-65 years, responding to the 2005-2006 National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURE(S): MAFH per week, BMI, and WC. ANALYSIS: Multiple linear regression models were used to examine associations between FS participation and MAFH, BMI, and WC, adjusting for age, sex, race, and education level. RESULTS: Food Stamp authorization was associated with fewer MAFH (P = .004). Among females, FS authorization was associated with higher BMI (P = .04) and WC (P = .04). Among females reporting amount of benefits in the prior month, more FS benefits received were associated with lower BMI (P = .03) and WC (P < .001). CONCLUSIONS AND IMPLICATIONS: Seemingly contradictory results regarding associations between FS authorization and FS benefits received in the previous month and BMI and WC should be explored further. Effective nutrition education and environmental change strategies are needed, particularly among female FS recipients.

Commute times, food retail gaps, and body mass index in North Carolina counties.

INTRODUCTION: The prevalence of obesity is higher in rural than in urban areas of the United States, for reasons that are not well understood. We examined correlations between percentage of rural residents, commute times, food retail gap per capita, and body mass index (BMI) among North Carolina residents. METHODS: We used 2000 census data to determine each county's percentage of rural residents and 1990 and 2000 census data to obtain mean county-level commute times. We obtained county-level food retail gap per capita, defined as the difference between county-level food demand and county-level food sales in 2008, from the North Carolina Department of Commerce, and BMI data from the 2007 North Carolina Behavioral Risk Factor Surveillance System. To examine county-level associations between BMI and percentage of rural residents, commute times, and food retail gap per capita, we used Pearson correlation coefficients. To examine cross-sectional associations between individual-level BMI (n = 9,375) and county-level commute times and food retail gap per capita, we used multilevel regression models. RESULTS: The percentage of rural residents was positively correlated with commute times, food retail gaps, and county-level BMI. Individual-level BMI was positively associated with county-level commute times and food retail gaps. CONCLUSION: Longer commute times and greater retail gaps may contribute to the rural obesity disparity. Future research should examine these relationships longitudinally and should test community-level obesity prevention strategies.

Maternal Employment, Migration, and Child Development.

We analyze the roles of and interrelationships among school inputs and parental inputs in affecting child development through the specification and estimation of a behavioral model of household migration and maternal employment decisions. We integrate information on these decisions with observations on child outcomes over a 13-year period from the NLSY. We find that the impact of our school quality measures diminish by factors of 2 to 4 after accounting for the fact that families may choose where to live in part based on school characteristics and labor market opportunities. The positive statistical relationship between child outcomes and maternal employment reverses sign and remains statistically significant after controlling for its possible endogeneity. Our estimates imply that when parental responses are taken into account, policy changes in school quality end up having only minor impacts on child test scores.

Parental Compensatory Behaviors and Early Child Health Outcomes in Cebu, Philippines().

A dynamic optimization model of parents choosing investments in their children's health motivates an empirical model of parents' choices of health inputs for their children and the impacts of these decisions on their children's subsequent health. Estimates of the child health input demand functions and the child health production functions from the Cebu Longitudinal Health and Nutrition Survey accord with the prediction that optimizing behavior results in higher levels of aggregate child health. Observable parental behaviors respond to the physical developmental status of their children. These parental responses appear to yield large and statistically significant improvements in children's early physiological outcomes. However, because some health inputs choices are not observable, it is impossible to ascertain whether these measured effects are due solely to variations in the observed input choices.