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Mechanism study on the effect of androgen antagonism in prostate cancer

Zhonghua Nan Ke Xue. 2023 May;29(5):402-408.

ABSTRACT

OBJECTIVE: To explore the mechanism of tetrahydroxynonene (4-HNE) in the androgen antagonistic effect of prostate cancer through the androgen receptor (AR) – mitogen activated protein kinase (MAPK) signaling pathway.

METHOD: Prostate cancer LNCaP cells were divided into wild-type group (NC, control group) and transfection group. The transfection group was further divided into empty vector transfection group (NC-L7 group) and GSTA4 gene transfection group (A0718, GSTA4-OE group). The GSTA4-OE group received LNCaP cell culture and GSTA4 plasmid transfection to construct LNCaP stable 4-HNE cell lines, while the control group received LNCaP cell culture without GSTA4 plasmid transfection. Stimulating prostate cancer cells with different concentrations of 4-HNE (0, 40, 80, 120μmol/L) to activate the AR signaling pathway, Western blot was used to detect the expression of AR, MAKp, AKT, and PKCα proteins. Sixty cases of prostate cancer tissues and sixty cases of benign prostatic hyperplasia tissues were selected. Immunohistochemical staining was used to determine the positive expression rate of 4-HNE in the aforementioned tissues. The correlation between the positive expression of 4-HNE and tumor Gleason grade, as well as the progression of prostate cancer to CRPC, was analyzed.

RESULT: The level of 4-HNE in the GSTA4-OE group cells was inhibited. Western blot analysis showed that compared with the control group, the GSTA4-OE group had PKC in cells α The protein expression level significantly decreased (P<0.05), while the expression levels of AR and AKT proteins significantly increased (P<0.05). After treating prostate cancer cells with 40, 80, and 120μmol/L 4-HNE, compared with the control group, the expression level of AKT in the treatment group was significantly reduced (P<0.01), while the expression levels of MAKP (P<0.01), PKC (P<0.01), and AR (P<0.01) were significantly increased. The immunohistochemical results showed that the positive rate of 4-HNE was 5.0% in 60 cases of benign prostatic hyperplasia tissue and 63.3% in 60 cases of prostate cancer tissue, with a statistically significant difference (P<0.01). The positive rates of 4-HNE in Gleason grades 1-5 were 41.2%, 50.0%, 63.6%, 81.8%, and 100.0%, respectively. The higher the Gleason grade, the higher the positive rate of 4-HNE, and the difference was statistically significant (P<0.05). During a follow-up period of 10-35 months, 33 patients advanced to CRCP, while 27 patients did not. The positive expression rate of 4-HNE in the two groups showed a statistically significant difference (P<0.01).

CONCLUSION: Under the action of 4-HNE, the expression of AR-MAPK pathway related proteins increase. 4-HNE may promote the progression of prostate cancer through the AR-MAPK pathway, and 4-HNE is expected to become a new therapeutic target for CRPC.

PMID:38602755

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Difference between prostate cancer patients’ Gleason scores from preoperative biopsy and those from postoperative pathology

Zhonghua Nan Ke Xue. 2023 May;29(5):393-401.

ABSTRACT

OBJECTIVE: To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology, identify the possible factors influencing results of scoring, and construct a risk scoring model.

METHODS: We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis. Using paired sample t-test, we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology, analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores, and calculated and visualized the relative risk values of the factors through Poisson regression. From the continuous variables with statistical significance, we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis, established a risk scoring model, generated risk coefficients, and evaluated the predictive ability of the model using the ROC curve. Based on the results of imaging examination with statistically significant differences, we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves, decision curves and ROC curves.

RESULTS: The results of paired sample t-test for 210 PCa patients showed statistically significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology (P < 0.001). There were significant differences in the body weight, BMI and PSA level as well as in all other factors but prostate calcification between the patients with consistent and those with inconsistent Gleason scores (all P < 0.05). An 8-factor prediction model was successfully constructed, which could predict the consistency of Gleason scores, with a better predicting performance than the single indicator within the model. The nomogram exhibited a C-index value of 0.85, with the calibration curve similar to the standard one, the threshold of the decision curve 0.10-0.92, and the area under the ROC curve higher than other predictive indicators.

CONCLUSION: Based on the demographic and clinical data on PCa patients, a risk prediction model and a column chart were successfully constructed, which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

PMID:38602754

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Nevin Manimala Statistics

Nanostructure and dynamics of N-truncated copper amyloid-β peptides from advanced X-ray absorption fine structure

IUCrJ. 2024 May 1. doi: 10.1107/S2052252524001830. Online ahead of print.

ABSTRACT

An X-ray absorption spectroscopy (XAS) electrochemical cell was used to collect high-quality XAS measurements of N-truncated Cu:amyloid-β (Cu:Aβ) samples under near-physiological conditions. N-truncated Cu:Aβ peptide complexes contribute to oxidative stress and neurotoxicity in Alzheimer’s patients’ brains. However, the redox properties of copper in different Aβ peptide sequences are inconsistent. Therefore, the geometry of binding sites for the copper binding in Aβ4-8/12/16 was determined using novel advanced extended X-ray absorption fine structure (EXAFS) analysis. This enables these peptides to perform redox cycles in a manner that might produce toxicity in human brains. Fluorescence XAS measurements were corrected for systematic errors including defective-pixel data, monochromator glitches and dispersion of pixel spectra. Experimental uncertainties at each data point were measured explicitly from the point-wise variance of corrected pixel measurements. The copper-binding environments of Aβ4-8/12/16 were precisely determined by fitting XAS measurements with propagated experimental uncertainties, advanced analysis and hypothesis testing, providing a mechanism to pursue many similarly complex questions in bioscience. The low-temperature XAS measurements here determine that CuII is bound to the first amino acids in the high-affinity amino-terminal copper and nickel (ATCUN) binding motif with an oxygen in a tetragonal pyramid geometry in the Aβ4-8/12/16 peptides. Room-temperature XAS electrochemical-cell measurements observe metal reduction in the Aβ4-16 peptide. Robust investigations of XAS provide structural details of CuII binding with a very different bis-His motif and a water oxygen in a quasi-tetrahedral geometry. Oxidized XAS measurements of Aβ4-12/16 imply that both CuII and CuIII are accommodated in an ATCUN-like binding site. Hypotheses for these CuI, CuII and CuIII geometries were proven and disproven using the novel data and statistical analysis including F tests. Structural parameters were determined with an accuracy some tenfold better than literature claims of past work. A new protocol was also developed using EXAFS data analysis for monitoring radiation damage. This gives a template for advanced analysis of complex biosystems.

PMID:38602752 | DOI:10.1107/S2052252524001830

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Analysis of 10 years’ data of systematic male reproductive system ultrasonography in diagnosis of azoospermia etiology

Zhonghua Nan Ke Xue. 2023 Jun;29(6):498-504.

ABSTRACT

OBJECTIVE: To explore the value of systematic male reproductive system ultrasonography in the diagnosis of azoospermia etiology.

METHODS: Retrospective analysis and classification statistics were conducted on the data of azoospermia cases who underwent systematic male reproductive system ultrasound examination at the First Affiliated Hospital of Ningbo University from January 2013 to January 2023.

RESULTS: A total of 375 cases were included in the group, of which 303 cases could be diagnosed by ultrasound, including 161 cases of obstructive causes, 110 cases of non obstructive causes, and 32 cases of mixed causes. Obstructive causes mainly include bilateral absence or underdevelopment of the seminal vesicles and vas deferens, non obstructive causes mainly include bilateral simple testicular dysplasia, and the most common combined causes are bilateral absence or underdevelopment of the seminal vesicles and vas deferens combined with bilateral testicular dysplasia. The main causes involved a single organ in 174 cases, with 82 cases, 43 cases, and 4 cases involving 2-4 organs, respectively. In addition, there are multiple accompanying ultrasound manifestations of non primary causes.

CONCLUSION: Systematic ultrasound examination can comprehensively evaluate the male reproductive system, effectively diagnose the causes of most azoospermia, and provide valuable imaging evidence for clinical treatment.

PMID:38602721

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Regulatory Standards and Guidance for the Use of Health Apps for Self-Management in Sub-Saharan Africa: Scoping Review

J Med Internet Res. 2024 Apr 11;26:e49163. doi: 10.2196/49163.

ABSTRACT

BACKGROUND: Health apps are increasingly recognized as crucial tools for enhancing health care delivery. Many countries, particularly those in sub-Saharan Africa, can substantially benefit from using health apps to support self-management and thus help to achieve universal health coverage and the third sustainable development goal. However, most health apps published in app stores are of unknown or poor quality, which poses a risk to patient safety. Regulatory standards and guidance can help address this risk and promote patient safety.

OBJECTIVE: This review aims to assess the regulatory standards and guidance for health apps supporting evidence-based best practices in sub-Saharan Africa with a focus on self-management.

METHODS: A methodological framework for scoping reviews was applied. A search strategy was built and applied across the following databases, gray literature sources, and institutional websites: PubMed, Scopus, World Health Organization (WHO) African Index Medicus, OpenGrey, WHO Regional Office for Africa Library, ICTworks, WHO Directory of eHealth policies, HIS Strengthening Resource Center, International Telecommunication Union, Ministry of Health websites, and Google. The search covered the period between January 2005 and January 2024. The findings were analyzed using a deductive descriptive content analysis. The policy analysis framework was adapted and used to organize the findings. The Reporting Items for Stakeholder Analysis tool guided the identification and mapping of key stakeholders based on their roles in regulating health apps for self-management.

RESULTS: The study included 49 documents from 31 sub-Saharan African countries. While all the documents were relevant for stakeholder identification and mapping, only 3 regulatory standards and guidance contained relevant information on regulation of health apps. These standards and guidance primarily aimed to build mutual trust; promote integration, inclusion, and equitable access to services; and address implementation issues and poor coordination. They provided guidance on systems quality, software acquisition and maintenance, security measures, data exchange, interoperability and integration, involvement of relevant stakeholders, and equitable access to services. To enhance implementation, the standards highlight that legal authority, coordination of activities, building capacity, and monitoring and evaluation are required. A number of stakeholders, including governments, regulatory bodies, funders, intergovernmental and nongovernmental organizations, academia, and the health care community, were identified to play key roles in regulating health apps.

CONCLUSIONS: Health apps have huge potential to support self-management in sub-Saharan Africa, but the lack of regulatory standards and guidance constitutes a major barrier. Hence, for these apps to be safely and effectively integrated into health care, more attention should be given to regulation. Learning from countries with effective regulations can help sub-Saharan Africa build a more robust and responsive regulatory system, ensuring the safe and beneficial use of health apps across the region.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-025714.

PMID:38602718 | DOI:10.2196/49163

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Effectiveness of Comprehensive Environmental Support for Community-Dwelling Older Adults: A Single-Blind Randomized Controlled Trial

Am J Occup Ther. 2024 May 1;78(3):7803205070. doi: 10.5014/ajot.2024.050431.

ABSTRACT

IMPORTANCE: The importance of developing age-friendly environments is globally recognized. However, few clinical trials have comprehensively evaluated physical and social components of environments and examined the effects of offering support.

OBJECTIVE: To clarify the effectiveness of occupational therapy-based comprehensive environmental support for community-dwelling older adults.

DESIGN: A single-blind parallel-groups randomized controlled trial with blinded participants.

SETTING: Eight community-based settings under the long-term-care insurance system in regional towns and cities throughout Japan.

PARTICIPANTS: Sixty older adults age ≥65 yr who were new users of adult day care or adult day health care and allocated by stratified block randomization on the basis of age.

INTERVENTION: Comprehensive environmental support was provided to participants for 3 mo according to results on the Comprehensive Environmental Questionnaire for older adults (CEQ) to make improvements in environmental factors participants wanted to change to create a more satisfying life.

OUTCOMES AND MEASURES: The primary outcome measure was the Japanese Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) score at 3 mo postrandomization. Additionally, scores on the Short-Form Six-Dimension utility index were calculated.

RESULTS: The experimental group showed significant improvements in the SF-36’s Role/Social Component Summary (p = .005) and Role-Physical (p = .02), Role-Emotional (p = .01), and Mental Health (p = .05) domains, with moderate effect sizes. The number needed to treat was 3.46, showing statistical significance.

CONCLUSIONS AND RELEVANCE: Occupational therapy-based comprehensive environmental support based on CEQ scores was effective, resulting in moderate improvements in health-related quality of life among community-dwelling older adults. Plain-Language Summary: Older adults experience a decline in physical and mental functions along with changes in social relationships. These problems make it challenging for older adults to perform valuable occupations, thus reducing their quality of life. This study demonstrated that occupational therapy based on the Comprehensive Environmental Questionnaire for older adults can improve health-related quality of life among community-dwelling older adults. Our findings pave the way for the development of an effective compensatory intervention model in occupational therapy practice.

PMID:38602705 | DOI:10.5014/ajot.2024.050431

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Costs associated with adverse events during treatment episodes for adult attention-deficit/hyperactivity disorder

J Med Econ. 2024 Apr 11:1-13. doi: 10.1080/13696998.2024.2342749. Online ahead of print.

ABSTRACT

Aims: Attention-deficit/hyperactivity disorder (ADHD) medication is frequently associated with adverse events (AEs), but limited real-world data exist regarding their costs from a payer’s perspective. Therefore, this study evaluated the healthcare costs associated with common AEs among adult patients treated for ADHD in the US.Materials and methods: Eligible adults treated for ADHD were identified from a large US claims database (10/1/2015─9/30/2021). A retrospective cohort study design was used to assess excess healthcare costs and costs directly related to AE-specific claims per-patient-per-month (PPPM) associated with 10 selected AEs during ADHD treatment. To account for all costs associated with the AE, treatment episodes with a given AE were compared to similar treatment episodes without this AE. Entropy balancing was used to create cohorts with similar characteristics. Studied AEs were selected based on their prevalence in clinical trials for common ADHD medications and were identified from ICD-10-CM diagnosis codes recorded in claims.Results: Among the 461,464 patients included (mean age: 34.2 years; 45.5% male), 49.4% had ≥1 AE during their treatment episode. Treatment episodes with AEs were associated with statistically significant AE-specific medical costs (erectile dysfunction: $57; fatigue: $82; dry mouth: $90; diarrhea: $162; insomnia: $147; anxiety: $281; nausea: $299; constipation: $356; urinary hesitation: $491; feeling jittery: $723) and excess healthcare costs PPPM (erectile dysfunction: $120, fatigue: $248, insomnia: $265, anxiety: $380, diarrhea: $441, dry mouth: $485, nausea: $709, constipation: $802, urinary hesitation: $1,105, feeling jittery: $1,160; p < 0.05).Limitations: AEs were identified based on recorded diagnosis on medical claims and likely represent more severe AEs. Therefore, costs may not be representative of milder AEs.Conclusions: This study found that AEs occurring during ADHD treatment episodes are associated with significant healthcare costs. This highlights the potential of treatments with favorable safety profiles to alleviate the burden experienced by patients and the healthcare system.

PMID:38602691 | DOI:10.1080/13696998.2024.2342749

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User Information Sharing and Hospital Website Privacy Policies

JAMA Netw Open. 2024 Apr 1;7(4):e245861. doi: 10.1001/jamanetworkopen.2024.5861.

ABSTRACT

IMPORTANCE: Hospital websites frequently use tracking technologies that transfer user information to third parties. It is not known whether hospital websites include privacy policies that disclose relevant details regarding tracking.

OBJECTIVE: To determine whether hospital websites have accessible privacy policies and whether those policies contain key information related to third-party tracking.

DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional content analysis of website privacy policies of a nationally representative sample of nonfederal acute care hospitals, hospital websites were first measured to determine whether they included tracking technologies that transferred user information to third parties. Hospital website privacy policies were then identified using standardized searches. Policies were assessed for length and readability. Policy content was analyzed using a data abstraction form. Tracking measurement and privacy policy retrieval and analysis took place from November 2023 to January 2024. The prevalence of privacy policy characteristics was analyzed using standard descriptive statistics.

MAIN OUTCOMES AND MEASURES: The primary study outcome was the availability of a website privacy policy. Secondary outcomes were the length and readability of privacy policies and the inclusion of privacy policy content addressing user information collected by the website, potential uses of user information, third-party recipients of user information, and user rights regarding tracking and information collection.

RESULTS: Of 100 hospital websites, 96 (96.0%; 95% CI, 90.1%-98.9%) transferred user information to third parties. Privacy policies were found on 71 websites (71.0%; 95% CI, 61.6%-79.4%). Policies were a mean length of 2527 words (95% CI, 2058-2997 words) and were written at a mean grade level of 13.7 (95% CI, 13.4-14.1). Among 71 privacy policies, 69 (97.2%; 95% CI, 91.4%-99.5%) addressed types of user information automatically collected by the website, 70 (98.6%; 95% CI, 93.8%-99.9%) addressed how collected information would be used, 66 (93.0%; 95% CI, 85.3%-97.5%) addressed categories of third-party recipients of user information, and 40 (56.3%; 95% CI, 44.5%-67.7%) named specific third-party companies or services receiving user information.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of hospital website privacy policies, a substantial number of hospital websites did not present users with adequate information about the privacy implications of website use, either because they lacked a privacy policy or had a privacy policy that contained limited content about third-party recipients of user information.

PMID:38602678 | DOI:10.1001/jamanetworkopen.2024.5861

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Physician Empathy and Chronic Pain Outcomes

JAMA Netw Open. 2024 Apr 1;7(4):e246026. doi: 10.1001/jamanetworkopen.2024.6026.

ABSTRACT

IMPORTANCE: Empathy is an aspect of the patient-physician relationship that may be particularly important in patients with chronic pain.

OBJECTIVE: To measure the association of physician empathy with pain, function, and health-related quality of life (HRQOL) among patients with chronic low back pain.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included adult enrollees from the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation national pain research registry. Study dates were from April 1, 2016, to July 25, 2023, with up to 12 months of follow-up.

EXPOSURE: Physician empathy was assessed with the Consultation and Relational Empathy measure and dichotomized to yield very empathic physician and slightly empathic physician groups.

MAIN OUTCOMES AND MEASURES: Main outcomes were patient-reported pain, function, and HRQOL measured with a numerical rating scale for low back pain intensity, the Roland-Morris Disability Questionnaire for back-related disability, and the Patient-Reported Outcomes Measurement Information System for HRQOL deficits pertaining to anxiety, depression, fatigue, sleep disturbance, and pain interference. Data were collected at 5 quarterly encounters from registry enrollment through 12 months and analyzed with generalized estimating equations, including multivariable models to measure temporal trends and to adjust for baseline and longitudinal covariates.

RESULTS: Among the 1470 patients, the mean (SD) age was 53.1 (13.2) years, and 1093 (74.4%) were female. Patients completed 5943 encounters in which multivariable analyses demonstrated that greater physician empathy was inversely associated with pain intensity (β = -0.014; 95% CI, -0.022 to -0.006; P < .001), back-related disability (β = -0.062; 95% CI, -0.085 to -0.040; P < .001), and HRQOL deficits on each measure (eg, pain interference: β = -0.080; 95% CI, -0.111 to -0.049; P < .001). Correspondingly, compared with the slightly empathic physician group, the very empathic physician group reported lower mean pain intensity (6.3; 95% CI, 6.1-6.5 vs 6.7; 95% CI, 6.5-6.9; P < .001), less mean back-related disability (14.9; 95% CI, 14.2-15.6 vs 16.8; 95% CI, 16.0-17.6; P < .001), and fewer HRQOL deficits on each measure (eg, fatigue: 57.3; 95% CI, 56.1-58.5 vs 60.4; 95% CI, 59.0-61.7; P < .001). All physician empathy group differences were clinically relevant, with Cohen d statistics ranging from 0.21 for pain intensity to 0.30 for back-related disability, fatigue, and pain interference. Physician empathy was associated with more favorable outcomes than non-pharmacological treatments, opioid therapy, and lumbar spine surgery.

CONCLUSIONS AND RELEVANCE: In this cohort study of adult patients with chronic pain, physician empathy was associated with better outcomes over 12 months. Greater efforts to cultivate and improve physician empathy appear warranted.

PMID:38602675 | DOI:10.1001/jamanetworkopen.2024.6026

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Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis

Transl Stroke Res. 2024 Apr 11. doi: 10.1007/s12975-024-01251-y. Online ahead of print.

ABSTRACT

The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 moderate quality. FD treatment showed a 95% rate of favorable clinical outcomes (95% CI, 89-99%), 81% (95% CI, 74-88%) complete aneurysmal occlusion, 4% (95% CI, 2-7%) ischemic complication incidence, 1% (95% CI, 0-3%) hemorrhagic complication incidence, 95% (95% CI, 87-100%) posterior inferior cerebellar artery (PICA) preservation, and 6% (95% CI, 3-10%) in-stent stenosis or occlusion across clinical and angiographic follow-up periods of 13.62 months (95% CI, 10.72-16.52) and 11.85 months (95% CI, 9.36-14.33), respectively. Subgroup analyses, based on a 12-month angiographic follow-up threshold, indicated no statistically significant differences in rates of complete aneurysm occlusion, PICA preservation, or in-stent stenosis or occlusion incidence (p > 0.05) between subgroups. Moreover, significant differences were observed in clinical and angiographic outcomes between ruptured and unruptured aneurysms, particularly in hemorrhagic complications (p < 0.05), without significant disparity in ischemic complications (p > 0.05). The results’ stability was confirmed via sensitivity analysis. FDs treatment for VA aneurysms is efficacious and safe, offering high rates of positive clinical and angiographic outcomes with minimal complications, underscoring FDs’ viability as a treatment option for VA aneurysms. The study was registered with PROSPERO (registration number: CRD42024499894).

PMID:38602659 | DOI:10.1007/s12975-024-01251-y