Nevin Manimala

Ecotoxicology. 2024 Jul 12. doi: 10.1007/s10646-024-02784-6. Online ahead of print.

ABSTRACT

Electronic waste (e-waste) has been identified as an emerging pollutant and is the fastest growing waste stream at the present time. Significant technological development and modernization within the last decade has led to the rapid accumulation of outdated, broken and unwanted electrical and electronic equipment (EEE). Electronic products mainly consist of a range of metal containing components that, when disposed of improperly, could result in metal constituents leached into the environment and posing a health risk to humans and animals alike. Metal exposure can induce oxidative stress in organisms, which could lead to synergistic, antagonistic and additive effects. The metals found highest in abundance in the simulated e-waste leachate, were nickel (Ni), barium (Ba), zinc (Zn), lithium (Li), iron (Fe), aluminium (Al) and copper (Cu). An acute exposure study was conducted over a 96 h period to determine the potential toxicity of e-waste on the test organism Danio rerio. Biomarker analysis results to assess the biochemical and physiological effects induced by e-waste leachate, showed a statistically significant effect induced on acetylcholinesterase activity, superoxide dismutase, catalase activity, reduced glutathione content, glutathione s-transferase, malondialdehyde and glucose energy available. The Integrated Biomarker Response (IBRv2) analysis revealed a greater biomarker response induced as the exposure concentration of e-waste leachate increased.

PMID:38995499 | DOI:10.1007/s10646-024-02784-6

J Patient Rep Outcomes. 2024 Jul 12;8(1):71. doi: 10.1186/s41687-024-00750-8.

ABSTRACT

BACKGROUND: Cancer-associated malnutrition is associated with worse symptom severity, functional status, quality of life, and overall survival. Malnutrition in cancer patients is often under-recognized and undertreated, emphasizing the need for standardized pathways for nutritional management in this population. The objectives of this study were to (1) investigate the relationship between malnutrition risk and self-reported symptom severity scores in an adult oncology outpatient population and (2) to identify whether a secondary screening tool for malnutrition risk (abPG-SGA) should be recommended for patients with a specific ESAS-r cut-off score or group of ESAS-r cut-off scores.

METHODS: A single-institution retrospective cross-sectional study was conducted. Malnutrition risk was measured using the Abridged Patient-Generated Subjective Global Assessment (abPG-SGA). Cancer symptom severity was measured using the Revised Edmonton Symptom Assessment System (ESAS-r). In accordance with standard institutional practice, patients completed both tools at first consult at the cancer centre. Adult patients who completed the ESAS-r and abPG-SGA on the same day between February 2017 and January 2020 were included. Spearman’s correlation, Mann Whitney U tests, receiver operating characteristic curves, and binary logistic regression models were used for statistical analyses.

RESULTS: 2071 oncology outpatients met inclusion criteria (mean age 65.7), of which 33.6% were identified to be at risk for malnutrition. For all ESAS-r parameters (pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, and wellbeing), patients at risk for malnutrition had significantly higher scores (P < 0.001). All ESAS-r parameters were positively correlated with abPG-SGA score (P < 0.01). The ESAS-r parameters that best predicted malnutrition risk status were total ESAS-r score, lack of appetite, tiredness, and wellbeing (area under the curve = 0.824, 0.812, 0.764, 0.761 respectively). Lack of appetite score ≥ 1 demonstrated a sensitivity of 77.4% and specificity of 77.0%. Combining lack of appetite score ≥ 1 with total ESAS score > 14 yielded a sensitivity of 87.9% and specificity of 62.8%.

CONCLUSION: Malnutrition risk as measured by the abPG-SGA and symptom severity scores as measured by the ESAS-r are positively and significantly correlated. Given the widespread use of the ESAS-r in cancer care, utilizing specific ESAS-r cut-offs to trigger malnutrition screening could be a viable way to identify cancer patients at risk for malnutrition.

PMID:38995461 | DOI:10.1186/s41687-024-00750-8

AIDS Behav. 2024 Jul 12. doi: 10.1007/s10461-024-04419-7. Online ahead of print.

ABSTRACT

Loss to follow-up (LTFU) in high-resolution anoscopy (HRA) programs jeopardizes the procedure’s potential to help prevent anal cancer. We explored quality improvement factors to understand how to address this LTFU. Using the transtheoretical COM-B Model (Capability, Opportunity, Motivation, and Behavior) and a sequential explanatory mixed-methods design, we surveyed and interviewed 13 patients who remained engaged in HIV care but who delayed their HRA monitoring or treatment visits in the same community clinic, and 6 HRA clinicians and medical assistants. Analyses involved descriptive statistics and rapid qualitative analysis. Patients were racially, ethnically, and economically representative of the LTFU population, and were generally experienced with HRA (Mean HRA visits = 4.6, SD = 2.8, mdn = 3). Providers were experienced clinicians and medical assistants (Mean years providing HRA = 6.0, SD = 2.2). Analyses revealed two primary, related barriers: (A) motivational barriers such as physical pain, discomfort, embarrassment, and anxiety; which were largely borne from (B) opportunity barriers such as difficulties with scheduling, inconsistent after-care (particularly for pain and discomfort), anxiety-inducing exam rooms and equipment, and internalized and anticipated stigma. Capability barriers, such as limited health literacy about HRA, were less common and, like motivational barriers, linked to opportunity barriers. Participants recommended potential facilitators, including easier scheduling, standardization of pain management and after-care services, and examination room modifications to reduce anxiety. To retain HRA patients in community settings, interventions should address social and physical opportunity barriers that strongly determine motivational and capability barriers. Improving convenience, standardizing pain management, and introducing stigma interventions specific to HRA, could alleviate both motivational and capability barriers.

PMID:38995441 | DOI:10.1007/s10461-024-04419-7

Pediatr Surg Int. 2024 Jul 12;40(1):184. doi: 10.1007/s00383-024-05780-3.

ABSTRACT

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection.

METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance.

RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010).

CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.

PMID:38995440 | DOI:10.1007/s00383-024-05780-3

Bull Math Biol. 2024 Jul 12;86(9):105. doi: 10.1007/s11538-024-01335-8.

ABSTRACT

The growing complexity of biological data has spurred the development of innovative computational techniques to extract meaningful information and uncover hidden patterns within vast datasets. Biological networks, such as gene regulatory networks and protein-protein interaction networks, hold critical insights into biological features’ connections and functions. Integrating and analyzing high-dimensional data, particularly in gene expression studies, stands prominent among the challenges in deciphering these networks. Clustering methods play a crucial role in addressing these challenges, with spectral clustering emerging as a potent unsupervised technique considering intrinsic geometric structures. However, spectral clustering’s user-defined cluster number can lead to inconsistent and sometimes orthogonal clustering regimes. We propose the Multi-layer Bundling (MLB) method to address this limitation, combining multiple prominent clustering regimes to offer a comprehensive data view. We call the outcome clusters “bundles”. This approach refines clustering outcomes, unravels hierarchical organization, and identifies bridge elements mediating communication between network components. By layering clustering results, MLB provides a global-to-local view of biological feature clusters enabling insights into intricate biological systems. Furthermore, the method enhances bundle network predictions by integrating the bundle co-cluster matrix with the affinity matrix. The versatility of MLB extends beyond biological networks, making it applicable to various domains where understanding complex relationships and patterns is needed.

PMID:38995438 | DOI:10.1007/s11538-024-01335-8

Eur J Clin Pharmacol. 2024 Jul 12. doi: 10.1007/s00228-024-03729-y. Online ahead of print.

ABSTRACT

This study aimed to investigate the current knowledge and experiences of consumers in Australia on adverse drug reaction (ADR) reporting and their reasons for reporting or not reporting ADRs, with a focus on the use of digital tools for ADR reporting.

METHODS: A cross-sectional online survey was conducted among adults who had taken medicine in Australia. A structured questionnaire with multiple choice or Likert scale responses with an option for participants to provide free-text responses and pretested for face validity was used. Consumer characteristics, knowledge, and ADR reporting practices were analyzed using descriptive statistics and the chi-square test or Fisher’s exact test.

RESULTS: A total of 544 survey responses were included in the analysis. The majority of respondents were women (68%), and 22% were aged between 65 and 74 years. Fifty-eight percent (n = 317) of respondents knew that they could report ADRs to either the Therapeutic Goods Administration (TGA), state or territory government health department, or healthcare professionals. Three-quarters (n = 405) of respondents stated that they had experienced an ADR; of these, 36% reported an ADR to either the TGA, state or territory government health department, or healthcare professionals. Among those who reported ADRs, 58% were unaware that they could use digital tools to report ADRs. The main reason for not reporting was that they did not think the ADR was serious enough to report (39%).

CONCLUSION: Over half of consumers knew that they could report ADR; however, improved consumer awareness about using digital tools for ADR reporting and increased ADR reporting is needed.

PMID:38995427 | DOI:10.1007/s00228-024-03729-y

J Med Virol. 2024 Jul;96(7):e29790. doi: 10.1002/jmv.29790.

ABSTRACT

The effect of COVID-19 booster vaccination on SARS-CoV-2 T-cell mediated immune responses in elderly nursing home residents has not been explored in depth. Thirty-nine elderly nursing home residents (median age, 91 years) were included, all fully vaccinated with mRNA vaccines. The frequency of and the integrated mean fluorescence (iMFI) for peripheral blood SARS-CoV-2-Spike reactive IFN-γ-producing CD4⁺ or CD8⁺ T cells before and after the first (Pre-3D and Post-3D) and second (Pre-4D and Post-4D) vaccine booster doses was determined using flow cytometry for an intracellular staining method. 3D increased significantly (p = 0.01) the percentage of participants displaying detectable SARS-CoV-2-T-cell responses compared with pre-3D (97% vs. 74%). The magnitude of the increase was statistically significant for CD8⁺ T cells (p = 0.007) but not for CD4⁺ T cells (p = 0.77). A trend towards higher frequencies of peripheral blood SARS-CoV-2-CD8⁺ T cells was observed post-3D compared with pre-3D (p = 0.06). The percentage of participants with detectable SARS-S-CoV-2 CD4⁺ T-cell responses decreased post-4D (p = 0.035). Following 4D, a nonsignificant decrease in the frequencies of both T cell subsets was noticed (p = 0.94 for CD8⁺ T cells and p = 0.06 for CD4⁺ T cells). iMFI data mirrored that of T-cell frequencies. The kinetics of SARS-CoV-2 CD8⁺ and CD4⁺ T cells following receipt of 3D and 4D were comparable across SARS-CoV-2-experienced and -naïve participants and between individuals receiving a homologous or heterologous vaccine booster. 3D increased the percentage of elderly nursing home residents displaying detectable SARS-CoV-2 T-cell responses but had a marginal effect on T-cell frequencies. The impact of 4D on SARS-CoV-2 T-cell responses was negligible; whether this was due to suboptimal priming or rapid waning could not be ascertained.

PMID:38994662 | DOI:10.1002/jmv.29790

Biometrics. 2024 Jul 1;80(3):ujae062. doi: 10.1093/biomtc/ujae062.

ABSTRACT

We estimate relative hazards and absolute risks (or cumulative incidence or crude risk) under cause-specific proportional hazards models for competing risks from double nested case-control (DNCC) data. In the DNCC design, controls are time-matched not only to cases from the cause of primary interest, but also to cases from competing risks (the phase-two sample). Complete covariate data are available in the phase-two sample, but other cohort members only have information on survival outcomes and some covariates. Design-weighted estimators use inverse sampling probabilities computed from Samuelsen-type calculations for DNCC. To take advantage of additional information available on all cohort members, we augment the estimating equations with a term that is unbiased for zero but improves the efficiency of estimates from the cause-specific proportional hazards model. We establish the asymptotic properties of the proposed estimators, including the estimator of absolute risk, and derive consistent variance estimators. We show that augmented design-weighted estimators are more efficient than design-weighted estimators. Through simulations, we show that the proposed asymptotic methods yield nominal operating characteristics in practical sample sizes. We illustrate the methods using prostate cancer mortality data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Study of the National Cancer Institute.

PMID:38994640 | DOI:10.1093/biomtc/ujae062

Biometrics. 2024 Jul 1;80(3):ujae061. doi: 10.1093/biomtc/ujae061.

ABSTRACT

What is the best way to split one stratum into two to maximally reduce the within-stratum imbalance in many covariates? We formulate this as an integer program and approximate the solution by randomized rounding of a linear program. A linear program may assign a fraction of a person to each refined stratum. Randomized rounding views fractional people as probabilities, assigning intact people to strata using biased coins. Randomized rounding is a well-studied theoretical technique for approximating the optimal solution of certain insoluble integer programs. When the number of people in a stratum is large relative to the number of covariates, we prove the following new results: (i) randomized rounding to split a stratum does very little randomizing, so it closely resembles the linear programming relaxation without splitting intact people; (ii) the linear relaxation and the randomly rounded solution place lower and upper bounds on the unattainable integer programming solution; and because of (i), these bounds are often close, thereby ratifying the usable randomly rounded solution. We illustrate using an observational study that balanced many covariates by forming matched pairs composed of 2016 patients selected from 5735 using a propensity score. Instead, we form 5 propensity score strata and refine them into 10 strata, obtaining excellent covariate balance while retaining all patients. An R package optrefine at CRAN implements the method. Supplementary materials are available online.

PMID:38994639 | DOI:10.1093/biomtc/ujae061

Comb Chem High Throughput Screen. 2024 Jul 11. doi: 10.2174/0113862073324077240624094140. Online ahead of print.

ABSTRACT

BACKGROUND: According to current worldwide cancer data, Prostate Cancer (PC) ranks as the second most common type of cancer and is the fifth leading cause of cancer-related mortality among men worldwide. PC in China has the 10th highest number of new cases and the 13th highest fatality rate, both of which show an ongoing annual increase. One of the significant challenges with prostate cancer is the difficulty in early detection, often resulting in diagnosis at intermediate or late stages, complicating treatment. Although hormonal therapy is initially successful in controlling the progression of prostate cancer, almost all tumors that respond to hormones eventually transform into Castration-resistant Prostate Cancer (CRPC) within 18-24 months of hormonal therapy. This poses clinical difficulties due to an absence of successful therapeutic approaches. Therefore, understanding the fundamental mechanisms of prostate cancer development, identifying effective therapeutic targets, and discovering reliable molecular biomarkers are crucial objectives.

METHODS: CircRNA expression in plasma was assessed in 4 samples obtained from patients with Benign Prostatic Hyperplasia (BPH), and PC was detected through microarray probes. Statistical analysis of the expression of circDUSP22 and clinicopathological features was conducted. The investigation of target genes was conducted using luciferase reporter assays and bioinformatics analysis. The expression levels of circDUSP22, miR-18a-5p, and Solute Carrier Family 7 member 11 (SLC7A11) were assessed using a quantitative Real-time Polymerase Chain Reaction (qRT-PCR) assay. Cell invasion, migration, colony formation, and proliferation were evaluated using Transwell, wound healing, colony formation, and CCK-8 assays, respectively. RNA Immunoprecipitation (RIP) and dual-luciferase reporter assays were used to examine the connections among circDUSP22, miR-18a-5p, and SLC7A11. The impact of circDUSP22 on the expression of ferroptosis-related proteins, specifically SLC7A11, as well as its effects on Fe2+ and ROS were also examined.

RESULTS: In both plasma samples and PCa cell lines, there was a substantial elevation of circDUSP22 and SLC7A11 expression and a decline in miR-18a-5p expression. Suppression of circDUSP22 significantly impeded the migration, invasion, and proliferation of PC cells in vitro. The target gene of miR-18a-5p, SLC7A11, was found to be upregulated as an effect of circDUSP22’s competitive binding to miR-18a-5p. Cellular experiments demonstrated that interference with circDUSP22 expression in DU145 and PC-3 cells led to increased ferroptosis and decreased SLC7A11 expression. The modulation of prostate cancer cell proliferation was reversed by either overexpressing SLC7A11 or inhibiting miR-18a-5p in response to the silencing of circDUSP22.

CONCLUSION: The circDUSP22 has been found to have a substantial effect on the development of ferroptosis in PC. It has been observed to influence the formation and evolution of this disorder by affecting the miR-18a-5p/SLC7A11 signaling pathway.

PMID:38994627 | DOI:10.2174/0113862073324077240624094140