Search

Introduction: As pharmacological strategies remain limited for relieving fatigue and associated cognitive symptoms, integrative modalities such as traditional Chinese medicine (TCM) could be explored as therapeutic strategies in cancer survivors. Here, we evaluate and report the efficacy and safety of a TCM concoction, modified Xiang Bei Yang Rong Tang (XBYRT), on quality of life (QOL), cancer-related fatigue (CRF), and cognitive symptoms, compared to placebo., Methods: In a single-centered, randomized, double-blinded, placebo-controlled pilot trial conducted from 2019 to 2022, fatigued cancer survivors ≥21 years old were recruited to receive the XBYRT intervention or placebo (5% diluted) once daily for the duration of 8 weeks. Patient-reported outcomes for QOL, CRF, cognition, blood samples for biomarker testing, and adverse events were collected at baseline (T0), 4 weeks (T1), 8 weeks (T2), and 10 weeks (T3) after baseline. Linear regression was performed to evaluate differences between groups at T2 and T3., Results: A total of 1502 patients were screened, with 672 patients considered eligible. Of the eligible, 15 XBYRT and 13 placebo subjects with similar mean ages (58.5 vs 58.4) were recruited. Both groups were predominantly Chinese (93% vs 62%), breast cancer patients (87% vs 62%), and diagnosed with stage 2 cancer (60% vs 46%). Although no significant difference was found in QOL between groups, the XBYRT group exhibited improved emotional fatigue at T3 ( P  = .045) and higher BDNF levels at T2 ( P  = .047) and T3 ( P  = .029). After baseline adjustment, XBYRT was associated with better perceived cognitive impairment at T2 ( P  = .011) and T3 ( P  = .017), as well as overall perceived cognitive function at T3 ( P  = .028). XBYRT is well tolerated, with grade 3 adverse events reported in three XBYRT (20%) and two placebo (15%) subjects., Conclusion: In this pilot study, XBYRT as an integrative therapy is safe and generates encouraging improvements in cognitive and fatigue symptoms. Difficulties with recruitment limited the generalizability of trial findings, thus findings should be verified through a larger, multi-centered trial., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Dynamin-1 (DNM1) is crucial for synaptic activity, neurotransmission, and associative memory, positioning it as a potential biomarker of cancer-related cognitive impairment (CRCI), a neurological consequence of cancer treatment characterized by memory loss, poor concentration, and impaired executive function. Through a stepwise approach, this study investigated the role of DNM1 in CRCI pathogenesis, incorporating both human data and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Following that, a syngeneic young-adult WT (C57BL/6) female mouse model of breast cancer chemobrain was developed to study DNM1 expression in the hippocampus. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were 32 ​% lower (P ​= ​0.041) among cancer participants compared to non-cancer prior to treatment. After receiving cytotoxic treatment, cognitively impaired cancer patients were found to have 46 ​% lower DNM1 levels than those without impairment (P ​= ​0.049). In murine breast cancer-bearing mice receiving chemotherapy, we found a greater than 40 ​% decline (P ​< ​0.0001) in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions concurrent with a deterioration in spatial recognition memory (P ​< ​0.02), compared to control mice without exposure to cancer and chemotherapy. Consistently observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. DNM1 might be a biomarker and therapeutic target for CRCI., Competing Interests: Declaration of Competing Interest We do not have any known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors. Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline. RZ is an FDA-approved medication for ALS known to increase BDNF in vivo. In an effort to mitigate the detrimental effects of RT-induced BDNF decline in RICD, we tested the efficacy of RZ in a cranially irradiated (9 Gy) adult mouse model. Notably, RT-exposed mice exhibited significantly reduced hippocampal BDNF, accompanied by increased neuroinflammation, loss of neuronal plasticity-related immediate early gene product, cFos, and synaptic density. Spatial transcriptomic profiling comparing the RT + Vehicle with the RT + RZ group showed gene expression signatures of neuroprotection of hippocampal excitatory neurons post-RZ. RT-exposed mice performed poorly on learning and memory, and memory consolidation tasks. However, irradiated mice receiving RZ (13 mg/kg, drinking water) for 6-7 weeks showed a significant improvement in cognitive function compared to RT-exposed mice receiving vehicle. Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and mature neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the UCI Institutional Animal Care and Use Committee (IACUC) Consent to participate: Not applicable Consent for publication: Not applicable Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: There is a lack of systematic solutions to manage supportive care issues in racial/ethnic minorities (REM) receiving treatment for cancer. We developed and implemented an electronic patient-reported outcome (ePRO)-driven symptom management tool led by oncology pharmacists in a majority-minority cancer center located in Southern California. This study was designed to evaluate the implementation outcomes of our multilevel intervention., Methods: This was a prospective, pragmatic, implementation study conducted between July 2021 and June 2023. Newly diagnosed adult patients with cancer receiving intravenous anticancer therapies completed symptom screening using ePRO that consists of the Patient-Reported Outcomes Measurement Information System measures at each infusion visit during the study. ePRO results were presented to an oncologist pharmacist for personalized symptom management and treatment counseling. The RE-AIM framework was used to guide implementation outcomes. Differences in symptom trajectories and clinical outcomes between groups were tested using generalized estimating equations., Results: We screened 388 patients of whom 250 were enrolled (acceptance rate: 64.4%), with 564 assessments being completed. The sample consisted of non-Hispanic White (NHW, 42.4%), Hispanic/Latinx (H/L, 30.8%), and non-Hispanic Asian (20.4%), with one (21.6%) of five participants preferring speaking Spanish. Compared with NHW, H/L participants had greater odds of reporting mild to severe pain interference (odds ratio [OR], 1.91 [95% CI, 1.18 to 3.08]; P = .008) and nausea and vomiting (OR, 2.08 [95% CI, 1.21 to 3.58]; P = .008), and higher rates of urgent care utilization (OR, 1.92 [95% CI, 1.04 to 3.61]; P = .04) within 30 days. Nausea and vomiting (n = 131, 23.2%), pain (n = 91, 16.1%), and fatigue (n = 72, 12.8%) were most likely to be intervened, with 90% of the participants expressing satisfaction across all visits., Conclusion: Our multilevel ePRO-driven intervention led by oncology pharmacists helps facilitate symptom assessments and management and potentially reduce health disparities among REM.

Purpose: Electronic patient-reported outcome (ePRO) tools are increasingly used to provide first-hand information on patient's symptoms and quality of life. This study explored how patients and health care providers (HCPs) perceive the use of a digital real-time ePRO tool, coupled with digital analytics at a cancer center located in a majority-minority county. Furthermore, we described the implementation barriers and facilitators identified from the participants' perspectives., Methods: We conducted a qualitative substudy as part of a larger implementation study conducted at University of California Irvine Chao Family Comprehensive Cancer Center. Patients and HCPs completed semistructured interviews and a focus group discussion. Thematic analysis was used to identify key themes regarding perceived impact of the intervention on patient's care and implementation factors., Results: A total of 31 participants, comprising 15 patients (67% English-speaking, 33% Spanish-speaking) and 16 HCPs (43.8% pharmacists, 37.5% physicians, 18.8% nurses), were interviewed. The utilization of real-time ePRO was perceived to beneficially affect patient care, improve patient-provider communication, and increase symptom awareness. Implementation facilitators included ease of comprehension and completion within the infusion center. Barriers included the need to incorporate results in electronic medical records and create real-time referral pathways to address patient's needs., Conclusion: The use of real-time ePRO in a majority-minority population was perceived to enhance patient-centered oncology care, yet implementation barriers must be addressed for successful integration in clinical settings. The findings from this study may inform implementation strategies to reduce health disparities.

Objectives: This systematic review (PROSPERO CRD42021275421) synthesized evidence on the efficacy of cognitive rehabilitation on cognitive and functional outcomes in adult cancer survivors., Methods: Articles were identified though PubMed/MEDLINE, EMBASE, PsycINFO, and Web of Science from inception through June 30, 2023. Studies included participants ≥18 years old, diagnosed with cancer. Primary outcomes were validated measures of subjective and objective cognition. Articles were dual reviewed for eligibility and data extraction. Risk of bias was assessed with the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields., Results: The search yielded 3,811 articles; 65 full-text articles were reviewed; 53 articles (15 cognitive training, 14 strategy-based, 21 combinations, three inpatient rehabilitation), representing 52 unique studies, were included. Positive effects were observed in at least one objective cognitive measure in 93% of strategy training, 81% of cognitive training, 79% of combination rehabilitation interventions. Positive effects were observed in subjective cognition in 100% of strategy training, 55% of cognitive training, and 92% of combination interventions. Among studies with comparator groups, processing speed improved in 60% of cognitive training studies, while strategy training did not improve processing speed; otherwise, cognitive domain effects were similar between intervention types. Impact on functional outcomes was inconclusive., Conclusions: Cognitive rehabilitation appear beneficial for cancer-related cognitive impairment (CRCI). Differential effects on specific cognitive domains (eg, processing speed) and subjective cognition may exist between intervention types., Implications for Nursing Practice: Nurses should increase patient and provider awareness of the benefits of cognitive rehabilitation for CRCI., Competing Interests: Declaration of competing interest Diane Von Ah reports financial support was provided by National Cancer Institute R01CA276222. Diane Von Ah reports a relationship with Midwest Nursing Research Society that includes: board membership and travel reimbursement. Diane Von Ah reports a relationship with National Cancer Institute -PDQ Palliative & Supportive Care Editorial Board that includes: board membership and travel reimbursement. Diane Von Ah reports a relationship with Oncology Nursing Society that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cranial radiation therapy (RT) for brain cancers is often associated with the development of radiation-induced cognitive dysfunction (RICD). RICD significantly impacts the quality of life for cancer survivors, highlighting an unmet medical need. Previous human studies revealed a marked reduction in plasma brain-derived neurotrophic factor (BDNF) post-chronic chemotherapy, linking this decline to a substantial cognitive dysfunction among cancer survivors. Moreover, riluzole (RZ)-mediated increased BDNF in vivo in the chemotherapy-exposed mice reversed cognitive decline. RZ is an FDA-approved medication for ALS known to increase BDNF in vivo . In an effort to mitigate the detrimental effects of RT-induced BDNF decline in RICD, we tested the efficacy of RZ in a cranially irradiated (9 Gy) adult mouse model. Notably, RT-exposed mice exhibited significantly reduced hippocampal BDNF, accompanied by increased neuroinflammation, loss of neuronal plasticity-related immediate early gene product, cFos, and synaptic density. Spatial transcriptomic profiling comparing the RT+Veh with the RT+RZ group showed gene expression signatures of neuroprotection of hippocampal excitatory neurons post-RZ. RT-exposed mice performed poorly on learning and memory, and memory consolidation tasks. However, irradiated mice receiving RZ (13 mg/kg, drinking water) for 6-7 weeks showed a significant improvement in cognitive function compared to RT-exposed mice receiving vehicle. Dual-immunofluorescence staining, spatial transcriptomics, and biochemical assessment of RZ-treated irradiated brains demonstrated preservation of synaptic integrity and neuronal plasticity but not neurogenesis and reduced neuroinflammation concurrent with elevated BDNF levels and transcripts compared to vehicle-treated irradiated brains. In summary, oral administration of RZ represents a viable and translationally feasible neuroprotective approach against RICD.

Background: This study evaluated the real-world impact of acupuncture on analgesics and healthcare resource utilization among breast cancer survivors., Methods: From a United States (US) commercial claims database (25% random sample of IQVIA PharMetrics® Plus for Academics), we selected 18-63 years old malignant breast cancer survivors experiencing pain and ≥ 1 year removed from cancer diagnosis. Using the difference-in-difference technique, annualized changes in analgesics [prevalence, rates of short-term (< 30-day supply) and long-term (≥ 30-day supply) prescription fills] and healthcare resource utilization (healthcare costs, hospitalizations, and emergency department visits) were compared between acupuncture-treated and non-treated patients., Results: Among 495 (3%) acupuncture-treated patients (median age: 55 years, stage 4: 12%, average 2.5 years post cancer diagnosis), most had commercial health insurance (92%) and experiencing musculoskeletal pain (98%). Twenty-seven percent were receiving antidepressants and 3% completed ≥ 2 long-term prescription fills of opioids. Prevalence of opioid usage reduced from 29 to 19% (P < 0.001) and NSAID usage reduced from 21 to 14% (P = 0.001) post-acupuncture. The relative prevalence of opioid and NSAID use decreased by 20% (P < 0.05) and 19% (P = 0.07), respectively, in the acupuncture-treated group compared to non-treated patients (n = 16,129). However, the reductions were not statistically significant after adjustment for confounding. Patients receiving acupuncture for pain (n = 264, 53%) were found with a relative decrease by 47% and 49% (both P < 0.05) in short-term opioid and NSAID fills compared to those treated for other conditions. High-utilization patients (≥ 10 acupuncture sessions, n = 178, 36%) were observed with a significant reduction in total healthcare costs (P < 0.001) unlike low-utilization patients., Conclusions: Although adjusted results did not show that patients receiving acupuncture had better outcomes than non-treated patients, exploratory analyses revealed that patients treated specifically for pain used fewer analgesics and those with high acupuncture utilization incurred lower healthcare costs. Further studies are required to examine acupuncture effectiveness in real-world settings., (© 2024. The Author(s).)

Purpose of Review: Symptom burden of cancer diagnosis and treatment has led adolescents and young adult cancer patients (AYAC) and survivors to seek different self-management strategies including integrative oncology (IO) modalities. IO holds great promise to improve survivorship issues in adolescents and young adult (AYA) cancer survivors. This review aims to encompass the current evidence of IO modalities and to analyze the efficacy of IO for managing survivorship issues among AYA cancer patients and survivors., Recent Findings: Nineteen randomized controlled trials included in this review evaluated mind and body modalities including both physical and psychological (74%) and psychological only (26%) modalities. Most assessed IO modalities were physical activity (PA) (37%) and structured exercise (10%). Most effective IO modalities found were PA, massage, mindfulness-based stress reduction (MBSR) and light therapy for treating AYA symptom burden. The Cochrane risk of bias (RoB-2) concluded 21% studies had high risk, 58% possessed some concerns and 21% had low risk., Summary: Although evidence has shown that a number of IO modalities may improve survivorship among AYA cancer survivors, more rigorous study designs are needed in order for these modalities to be routinely recommended for use in clinical practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Corrosion of brass plumbing materials may lead to metal release and deteriorate the drinking water quality. In this study, the initial corrosion of brass coupon cut from commercially available water meter was investigated. High rates of Pb, Cu and Zn release from the brass coupon were found during the early stage of corrosion (0-5 d) due to general corrosion and galvanic corrosion. The corrosion current density (I corr ) increased and resistance (R F ) decreased during this period indicating that severe corrosion had occurred. In a later stage (5-30 d), a decreased I corr and an increased R F were observed due to the development of a denser layer of Pb and Cu corrosion products which regulated the release of soluble Pb and Cu. The release of Zn continued and no significant Zn precipitation was found. Overall, particulate Pb, particulate Cu and soluble Zn dominated in the metal release during the initial corrosion of brass. The release of Pb, Cu and Zn was enhanced by a lower pH. Free chlorine was found to slightly reduce the release of Pb but promote the release of Cu and Zn. The presence of Pb on the brass surfaces was found to alleviate the dezincification process. A conceptual model based on metal release profile and electrochemical characterization was proposed to describe the initial corrosion of brass in typical drinking water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Identifying reliable biomarkers that reflect cancer survivorship symptoms remains a challenge for researchers. DNA methylation (DNAm) measurements reflecting epigenetic changes caused by anti-cancer therapy may provide needed insights. Given lack of consensus describing utilization of DNAm data to predict survivorship issues, a review evaluating the current landscape is warranted., Objective: Provide an overview of current studies examining associations of DNAm with survivorship burdens in cancer survivors., Methods: A literature review was conducted including studies if they focused on cohorts of cancer survivors, utilized peripheral blood cell DNAm data, and evaluated the associations of DNAm and survivorship issues., Results: A total of 22 studies were identified, with majority focused on breast (n = 7) or childhood cancer (n = 9) survivors, and half studies included less than 100 patients (n = 11). Survivorship issues evaluated included those related to neurocognition (n = 5), psychiatric health (n = 3), general wellness (n = 9), chronic conditions (n = 5), and treatment specific toxicities (n = 4). Studies evaluated epigenetic age metrics (n = 10) and DNAm levels at individual CpG sites or regions (n = 12) for their associations with survivorship issues in cancer survivors along with relevant confounding factors. Significant associations of measured DNAm in the peripheral blood samples of cancer survivors and survivorship issues were identified., Discussion/conclusion: Studies utilizing epigenetic age metrics and differential methylation analysis demonstrated significant associations of DNAm measurements with survivorship burdens. Associations were observed encompassing diverse survivorship outcomes and timeframes relative to anti-cancer therapy initiation. These findings underscore the potential of these measurements as useful biomarkers in survivorship care and research., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Dynamin-1 (DNM1) consolidates memory through synaptic transmission and modulation and has been explored as a therapeutic target in Alzheimer's disease. Through a two-prong approach, this study examined its role in cancer-related cognitive impairment (CRCI) pathogenesis using human and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Concurrently, a syngeneic young-adult WT (C57BL/6 female) mouse model of breast cancer was developed to study DNM1 expression in the brain. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were significantly lower among cancer participants compared to non-cancer prior to treatment. While receiving cancer treatment, cognitively impaired patients were found with a significant downregulation of DNM1, but not among those without impairment. In murine breast cancer-bearing mice receiving chemotherapy, we consistently found a significant decline in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions. Observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. Future research should explore the potential of DNM1 in CRCI pathogenesis and therapeutics development.

Purpose: Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy., Methods: In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest., Results: The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting., Conclusion: Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients., (© 2024. The Author(s).)

Background: About 4.5% of new cancer cases affect adolescent and young adult aged between 15 and 39 years in the United States (US). However, the effect of neuropsychiatric conditions on long-term adolescent and young adult cancer (AYAC) survivors has not been formally investigated. Thus, the impact and management of late neuropsychiatric complications in AYAC survivors compared to non-cancer-matched controls (NCMC) in the US were evaluated using the All of Us (AoU) Research Program., Methods: Participants in the AoU Controlled Tier Dataset (v6) diagnosed with cancer between ages 15 and 39 were identified from electronic health records and surveys. AYAC survivors were matched with NCMC using the optimal pair-matching algorithm at a 1:4 ratio. Data on past diagnoses, current follow-up care, and treatment patterns of neuropsychiatric complications were collected., Results: Analysis was performed on 788 AYAC survivors and 3152 NCMC. AYAC survivors, with an average of 8.8 years since their first cancer diagnosis, were more likely than NCMC to receive a diagnosis of neuropathy, memory loss and epilepsy (p  < 0.001). Survivors also had a higher rate of follow-up care and treatment utilization for these neurological conditions compared to NCMC (p  < 0.05). Treatment utilization was highest among survivors receiving care for epilepsy (88%), and lower for neuropathy (70%), memory loss (61%), and chronic fatigue (59%)., Conclusions: This large study reveals that AYAC survivors, on average 9 years after their cancer diagnosis, require more frequent follow-up care for neurological complications compared to non-cancer individuals. However, the management of neuropathy, memory loss, and chronic fatigue is hindered by a lack of mechanism-based effective therapies., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: An adolescent and young adult cancer (AYAC) patient is an individual who has received a cancer diagnosis between 15 and 39 years of age. They require significant survivorship care due to a combination of practical, physical, and mental health problems, but research in these areas is sparse. This study aimed to identify the unmet needs, barriers, and facilitators for conducting AYAC survivorship research in Southern California (SoCal) from the providers' and researchers' perspectives. Methods: A two-round, electronically administered Delphi survey study was conducted, involving a panel of 12 health care professionals and/or researchers with substantial work experience in AYAC. A 10-point Likert scale was used to evaluate 24 areas of unmet needs in AYAC survivors, 39 barriers, and 25 facilitators. Results: The top unmet needs in AYAC survivorship requiring research were in mental health issues, improving school/occupational performance, neurocognitive disorders, subsequent malignant neoplasms, and reproductive health. The top barriers identified were as follows: (1) institutions are too short-staffed to administer survivorship studies; (2) oncologists do not have the time/resources; and (3) lack of available funding. The top facilitators identified were as follows: (1) development of a mechanism/program to fund AYAC survivorship research studies; (2) in-person or virtual investigator engagement between children's hospitals and adult cancer centers to discuss research studies; and (3) developing personalized survivorship goals with AYAC patients and survivors to facilitate enrollment into survivorship studies. Conclusion: Experts identified the lack of time, manpower, funding, and resources as major barriers in AYAC survivorship research. Enhancing communication and collaboration with different stakeholders may facilitate AYAC survivorship research efforts within the SoCal region.

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15-39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p < 0.001) and 6-months post-baseline (median: 8.2 vs 15.3, p = 0.001) compared to non-cancer controls. Through linear mixed modelling adjusted for sociodemographic variables, baseline cognition, fatigue, psychological distress, and time, we observed that among cancer participants, lower baseline BDNF levels were associated with worse attention (p = 0.029), memory (p = 0.018) and self-perceived cognitive abilities (p = 0.020) during cancer treatment. Met/Met was associated with enhanced executive function compared to Val/Val (p = 0.012). Plasma BDNF may serve as a predictive biomarker of cancer-related cognitive impairment., (© 2023. The Author(s).)

Drinking water contaminated with lead has adverse health consequences, particularly in young children. Water dispensed from point-of-use dispensers is generally regarded as drinking water instead of conventional tap water in Taiwan, and such dispensers are installed in all public facilities, including elementary schools. However, studies on drinking water quality are mainly focused on tap water, while dispenser water quality is less known. Hence, this study investigated lead concentrations in drinking water from point-of-use dispensers in elementary schools of Taichung, Taiwan. Water samples were collected between September 2019 and February 2021 from 86 schools across 24 districts utilizing a modified first draw sampling protocol to collect ten 100-mL sequential samples. Approximately 26% of the schools had at least one sample exceeding 10 μg/L (Taiwan EPA standard), with the highest level reaching 99.2 μg/L. Exceedance tendency varied with water use, seasons, and age of the schools. Samples collected over the weekends and during summer showed higher levels and frequencies of contamination. Lead levels surpassing the standard were observed in 14% of weekend and 17% of summer samples, compared to only 4% of weekday and 4% of winter samples. Similarly, while older schools (age > 40 years) exhibited higher contamination, young schools (age < 20 years) were also not entirely safe. This study reveals that point-of-use dispensers do not always provide safe drinking water. Findings also indicate the susceptibility of children in elementary schools to lead exposure through their drinking water. Therefore, a routine monitoring program for heavy metals, including lead, in drinking water is urgently needed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: We examined the research attitudes and willingness to participate in clinical research among cancer survivors with varying degrees of cognitive function., Methods: This is a secondary analysis of data collected through the University of California Irvine Consent-to-Contact registry. Cancer survivors completed the Cognitive Function Instrument (CFI), the Research Attitudes Questionnaire (RAQ), and willingness to participate (WTP) in certain research procedures. Perceived cognitive impairment (CI) was defined as the worst 20% CFI scores., Results: Here, 265 CI and 909 cognitively non-impaired (CNI) participants' data were analyzed. Mean age and sex distribution were similar, with fewer non-Hispanic Whites and education years among CI participants. More CI participants self-reported past diagnoses of Alzheimer's disease, mild cognitive impairment, stroke, depression, post-traumatic stress disorder, and alcohol abuse (all p < 0.05). CI participants were significantly more interested in studies investigating approved medications (92% vs. 87%, p = 0.030), lumbar puncture (47% vs. 38%, p = 0.027), and autopsy (78% vs. 69%, p = 0.022). After removing survivors with co-existing neuropsychiatric conditions, interest in autopsy studies remained statistically higher among CI (79% vs. 69%, p = 0.022)., Conclusions: Participants with cancer and CI are open to research procedures and interventions that are traditionally less utilized, which may facilitate the discovery of the pathogenesis and interventions for cancer-related cognitive impairment (CRCI).

Introduction: Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding., Methods: The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians' input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models., Results: There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632-0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs., Conclusions: We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction., (© 2023. The Author(s).)

Objective: Observational studies can impact patient care but must be robust and reproducible. Nonreproducibility is primarily caused by unclear reporting of design choices and analytic procedures. This study aimed to: (1) assess how the study logic described in an observational study could be interpreted by independent researchers and (2) quantify the impact of interpretations' variability on patient characteristics., Materials and Methods: Nine teams of highly qualified researchers reproduced a cohort from a study by Albogami et al. The teams were provided the clinical codes and access to the tools to create cohort definitions such that the only variable part was their logic choices. We executed teams' cohort definitions against the database and compared the number of subjects, patient overlap, and patient characteristics., Results: On average, the teams' interpretations fully aligned with the master implementation in 4 out of 10 inclusion criteria with at least 4 deviations per team. Cohorts' size varied from one-third of the master cohort size to 10 times the cohort size (2159-63 619 subjects compared to 6196 subjects). Median agreement was 9.4% (interquartile range 15.3-16.2%). The teams' cohorts significantly differed from the master implementation by at least 2 baseline characteristics, and most of the teams differed by at least 5., Conclusions: Independent research teams attempting to reproduce the study based on its free-text description alone produce different implementations that vary in the population size and composition. Sharing analytical code supported by a common data model and open-source tools allows reproducing a study unambiguously thereby preserving initial design choices., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cancer-related cognitive impairment (CRCI) considerably affects the quality of life of millions of cancer survivors. Brain-derived neurotrophic factor (BDNF) has been shown to promote survival, differentiation, and maintenance of in vivo dentate neurogenesis, and chemotherapy induces a plethora of physiological and cellular alterations, including a decline in neurogenesis and increased neuroinflammation linked with cognitive impairments. In our clinical studies, breast cancer patients treated with doxorubicin (Adriamycin ® , ADR) experienced a significant reduction in the blood levels of BDNF that was associated with a higher risk of CRCI. Our past rodent studies in CRCI have also shown a significant reduction in dentate neurogenesis accompanied by cognitive impairment. In this study, using a female mouse model of ADR-induced cognitive decline, we tested the impact of riluzole (RZ), an orally active BDNF-enhancing medication that is FDA-approved for amyotrophic lateral sclerosis. ADR-treated mice receiving RZ in the drinking water for 1 month showed significant improvements in hippocampal-dependent learning and memory function (spatial recognition), fear extinction memory consolidation, and reduced anxiety-like behavior. RZ prevented chemotherapy-induced reductions of BDNF levels in the hippocampus. Importantly, RZ mitigated chemotherapy-induced loss of newly born, immature neurons, dentate neurogenesis, and neuroinflammation. In conclusion, this data provides pre-clinical evidence for a translationally feasible approach to enhance the neuroprotective effects of RZ treatment to prevent CRCI., (© 2023. The Author(s).)

Background: Neuropsychiatric symptoms, comprising cognitive impairment, fatigue, insomnia, depression, and anxiety, are prevalent and may co-occur during and after chemotherapy treatment for cancer. Electroacupuncture (EA), which involves mild electrical stimulation with acupuncture, holds great potential in addressing the management of individual symptoms. However, there is a lack of studies evaluating if EA can manage concurrent neuropsychiatric symptoms in cancer (i.e., symptom cluster). Hence, we designed a trial to evaluate the efficacy, safety, and feasibility of administering EA as an intervention to mitigate neuropsychiatric symptom clusters amongst cancer patients and survivors., Methods: The EAST study is a randomized, sham-controlled, patient- and assessor-blinded clinical trial. Sixty-four cancer patients and survivors with complaints of one or more neuropsychiatric symptom(s) in the seven days prior to enrollment are recruited from the University of California Irvine (UCI) and Children's Hospital of Orange County (CHOC). Individuals with needle phobia, metastases, bleeding disorders, electronic implants, epilepsy, exposure to acupuncture in the three months prior to enrollment, and who are breastfeeding, pregnant, or planning to get pregnant during the duration of the study will be excluded. Screening for metal fragments and claustrophobia are performed prior to the optional neuroimaging procedures. Recruited patients will be randomized (1:1) in random blocks of four or six to receive either ten weekly verum EA (treatment arm, vEA) or weekly sham EA (control arm, sEA) treatment visits with a follow-up appointment four to twelve weeks after their last treatment visit. The treatment arm will receive EA at 13 acupuncture points (acupoints) chosen for their therapeutic effects, while the control arm receives minimal EA at 7 non-disease-related acupoints. Questionnaires and cognitive assessments are administered, and blood drawn to assess changes in symptom clusters and biomarkers, respectively., Conclusion: The EAST study can provide insight into the efficacy of EA, an integrative medicine modality, in the management of cancer symptom clusters in routine clinical practice., Trial Registration: This trial is registered with clinicaltrials.gov NCT05283577., (© 2023. The Author(s).)

Purpose: Young adult childhood cancer survivors (YACCSs) are often impacted by cancer-related cognitive impairment (CRCI) and psychological distress. Using the Project Forward Cohort, we evaluated the relationship between CRCI and substance use behaviors., Methods: YACCSs were surveyed between 2015 and 2018 (N = 1,106, female = 50.8%, Hispanic = 51.5%, median age = 25.5 years). Associations between CRCI and substance use (tobacco, binge drinking, marijuana, prescription drug misuse, and e-cigarette/vaporizer) were examined in multivariate logistic or log-binomial regressions, adjusting for child at diagnosis (0-14 years), years since diagnosis, sex, race/ethnicity, cancer type, and treatment intensity. Mediation analysis was performed to determine opportunities for interventions., Results: CRCI was reported by 144 (13.0%) survivors. The highest prevalence was observed in CNS cancers (25.4%) and leukemia (13.3%) survivors. After covariate adjustment, CRCI was associated with 2.26 times the odds of prior 30-day vaping (95% CI, 1.24 to 4.11; P = .007). Mediators with significant indirect effects in the CRCI-vaping relationship include depressive symptoms (Center for Epidemiological Studies Depression Scale) and having two or more cancer-related late effects ( P < .05)., Conclusion: CRCI among YACCSs was associated with reports of vaping. Oncologists should screen for vaping behavior if CRCI is apparent. Increasing access to long-term follow-up clinics, addressing physical and mental health issues, and monitoring and educating on vaping and other substance use behaviors is recommended to improve the long-term health of YACCSs.

Background: The National Institutes of Health All of Us (AoU) Research Program is currently building a database of 1million+ adult subjects. With it, we describe the characteristics of those with documented vaccinations., Objectives: To describe the sociodemographic, health status, and lifestyle factors associated with vaccinations., Methods: This is a retrospective study involving data from the AoU program (R2020Q4R2, N = 315,297). Five vaccine cohorts [influenza, hepatitis B (HBV), pneumococcal <65 years old, pneumococcal ≥65 years old, and human papillomavirus (HPV)] were generated based on vaccination history. The influenza cohort comprised participants with documented influenza vaccinations in electronic health records (EHRs) from September 2017 to May 2018. Other vaccine cohorts comprised participants with ≥1 lifetime record(s) of vaccination documented in the EHR by December 2018. The vaccine cohorts were compared to the overall AoU cohort. Descriptive statistics were generated using EHR- and survey-based sociodemographic, health, and lifestyle information. The SAMBA (0.9.0) R package was utilized to adjust for EHR selection and outcome misclassification biases to infer sources of disparity for pneumococcal vaccinations in older adults., Results: Cohort counts were as follows: influenza (n = 15,346), HBV (n = 6323), pneumococcal <65 (n = 15,217), pneumococcal ≥65 (n = 15,100), and HPV (n = 2125). All vaccine cohorts had higher proportions of White and non-Hispanic/Latino participants compared to the overall AoU cohort. The largest differences were found in pneumococcal age ≥65, with 80.2% White participants compared to 52.9% in the overall study population. Multivariable analysis revealed that race/ethnic disparities in pneumococcal vaccination among older adults were explained by biological sex, income, health insurance, and education-related variables., Conclusion: Racial, ethnic, education, and income characteristics differ across the vaccine cohorts among AoU participants. These findings inform future utilization of large health databases in vaccine epidemiology research and emphasize the need for more targeted interventions that address differences in vaccine uptake., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: There is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study., Methods: Newly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF])., Results: We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self-perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10 and IFN-γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function., Conclusion: With the pre-existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (ClinicalTrials.gov Identifier: NCT03476070)., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect that is highly prevalent among cancer patients undergoing chemotherapy. There is a growing use of cryotherapy (CryTx) and compression therapy (ComTx) to prevent CIPN at cancer centers worldwide. In this study, we examined the awareness and recommendation of these modalities and evaluated factors associated with awareness. In addition, we investigated the type of technology utilized, barriers to implementation, and perceived adverse events of CryTx and ComTx., Methods: Active members of the Multinational Association of Supportive Care of Cancer (MASCC) were invited to complete an electronic survey that was sent via SurveyMonkey between September and October 2021. The survey assessed participants' awareness, recommendation, usage, barriers to utilization, and perceived adverse events of CryTx and ComTx. Descriptive statistics and multiple logistic regression were utilized to analyze findings., Results: Out of 184 participants, 70.1% were physicians, 73.4% had over 10 years of practice, and 49.5% were practicing in an outpatient setting. While more than half (63.3%) of participants indicated awareness of CryTx for taxane-induced peripheral neuropathy, less than a quarter (22.8%) indicated recommendation in their practice setting. Factors associated with higher awareness of CryTx for patients receiving taxanes include living in Europe (OR = 2.69, 95% CI [1.28-5.64], p = 0.009), not practicing in an inpatient setting (OR = 3.15, 95% CI [1.45-6.85], p = 0.004), and self-identifying as non-physician (OR = 2.40, 95% CI [1.03-4.37], p = 0.041). Commercial cooling (31.5%) and compression (16.8%) gloves and socks were the most used modalities for CryTx and ComTx, respectively. The most identified barriers to CryTx and ComTx utilization include insufficient evidence (53.5%), logistics (34.8%), and patient discomfort (23.4%). Redness/irritation of skin (27.7%) and numbness/tingling (24.5%) accounted for about half of the perceived adverse events associated with use of CryTx and ComTx., Conclusion: Results of our global survey illustrated that there are varying modes in the delivery of CryTx and ComTx among cancer centers around the world. Education of the utilization of CryTx and ComTx, in addition to efficacy and implementation studies, is needed to close the gap between awareness and implementation in clinical practice., (© 2022. The Author(s).)

Brain-derived neurotrophic factor (BDNF) plays an essential role in neurogenesis and neuroplasticity and may be a key protein in cancer-related cognitive impairment (CRCI). This systematic review assessed the relationship between BDNF biomarkers and neurocognitive outcomes in cancer patients and survivors. A search in PubMed, Scopus, and PsycINFO yielded 638 articles, of which 26 were eligible. Fourteen (54 %) studied BDNF protein levels while 15 (58 %) analyzed BDNF rs6265 polymorphism. Of the nine observational studies reporting BDNF plasma/serum levels, five (56 %) exhibited a positive association between BDNF and cognitive function. One study reported intra-tumoral BDNF levels that were negatively associated with memory. For rs6265, three (20 %) of 15 studies reported an association with cognitive function with inconsistent directions. Among seven neuroimaging studies, three (43 %) demonstrated an effect of BDNF on brain function and structure. These results suggest that BDNF is a potential monitoring biomarker and druggable target for CRCI., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Owing to the limited information regarding potential sources of nickel (Ni) in drinking water, incidences of Ni contamination have not been well elucidated in the literature. However, in recent decades, Ni-containing plumbing materials such as stainless steel pipes, brass fittings, and chrome faucets have gained popularity in drinking water distribution systems. As a result of increased use of such materials, Ni levels in drinking water are expected to rise over time, posing long-term exposure risks to consumers. For the first time, this study employed an intensive sequential sampling, from October 2019 to July 2020, to assess Ni levels in drinking water samples collected from dispensers of elementary schools in Taichung, Taiwan. Of the total 580 sequential samples collected from 58 elementary schools, 45 samples from 17 schools exceeded the Taiwan Environmental Protection Administration (EPA) standard value of 20 μg/L for Ni. Total Ni concentration in 1 L sample, an average of the total Ni concentrations in 10 sequential samples, exceeded in 4 schools. This finding suggests minor Ni contamination in drinking water supplies across the city. The highest Ni concentration was measured in the 1st sequential sample reaching 154 μg/L. Weekend and summer samples exhibited a higher tendency to exceed the standard. Older schools with age above 50 years and schools with a higher student population (≥ 500) were more likely to have Ni contamination. This study showed that drinking water is a potential source of Ni. However, the identification of Ni source, whether within the dispenser or in the distribution system, warrants further research., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Introduction: We conducted a randomized controlled trial evaluating the efficacy and tolerability of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with early breast cancer receiving neo/adjuvant weekly paclitaxel. Methods: Patients were recruited from the National Cancer Centre Singapore and randomized (1:1) to receive either cryotherapy or usual care. Cryotherapy was applied as frozen gloves and socks on all extremities from 15 min before paclitaxel until 15 min post-infusion every cycle. Efficacy was measured by patient-reported outcomes (Patient Neurotoxicity Questionnaire [PNQ] and EORTC QLQ-CIPN20) and electrophysiological assessments. The primary endpoint was PNQ severity at 2 weeks after 12 cycles of weekly paclitaxel. Results: A total of 46 patients were recruited, of which 8 dropped out before paclitaxel treatment, leaving 38 evaluable. There was no significant difference in PNQ severity between cryotherapy and usual care at 2 weeks after paclitaxel treatment (sensory: p = 0.721; motor: p = 1.000). A benefit was observed at 3 months post-paclitaxel based on PNQ (sensory: 14.3 vs. 41.2%, p = 0.078; motor: 0 vs. 29.4%, p = 0.012) and CIPN20 (sensory: β = -3.6, 95%CI = -10.5-3.4, p = 0.308; motor: β = -7.3, 95%CI = -14.6-0, p = 0.051). Additionally, cryotherapy subjects have lower CIPN20 autonomic score (β = -5.84, 95%CI = -11.15 to -0.524, p = 0.031) and higher sympathetic skin response hand amplitudes (β = 0.544, 95%CI = 0.108-0.98, p = 0.014), suggesting possible autonomic benefits from cryotherapy. Temporary interruption with cryotherapy occurred in 80.9% of the subjects due to cold intolerance. Conclusions: There is insufficient evidence that cryotherapy prevents sensory neuropathy which may be due to the high rates of cryotherapy interruption in this study. The autonomic benefits of cryotherapy should be further investigated with appropriate outcome measures. Clinical Trial Registration: ClinicalTrials.gov: NCT03429972., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Ng, Tan, Soh, Tan, Loh, Tan, Ong, Teng, Chan, Chay, Lee, Lai, Beh, Tan, Yap, Lee, Wong, Dent, Lo, Chan and Loh.)

Lead pipe has been banned in the drinking water distribution system in most countries since 1980s. Although water authorities around the world have attempted to replace all remaining lead pipes in service, pipe replacement was often hindered by high cost and lack of access to private premises. Hence, partial replacement has become a common scenario where portions of lead pipes remain in the system. When the lead pipe is connected to two other different metallic materials at both ends, two different galvanic couples can form simultaneously in this three-metal system. The release of lead resulting from galvanic corrosion in such three-metal systems consisting of lead (Pb), copper (Cu) and stainless steel (SS) with three different configurations, namely Cu-SS-Pb, SS-Cu-Pb and Cu-Pb-SS was investigated in this study. The results showed that when the materials are arranged in order of reduction potential as in SS-Cu-Pb configuration, lead release was the highest. A more fluent electron transport across the system was proposed based on the direction and magnitude of galvanic currents measured at each galvanic couple., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lead pipe has been banned for distributing drinking water in the 1980s and partial replacement of lead pipes with stainless steel pipes has been practiced in many Asian countries. Due to the different potentials of lead and stainless steel, galvanic corrosion may take place. The extent of lead release and effects of water chemistry on this process, however, are largely unknown. The objectives of this study are to characterize lead release resulting from galvanic connection between lead and stainless steel, the effects of pH, chloride and sulfate concentrations on this process, and the effectiveness of using orthophosphate to mitigate this problem. The experiments were conducted by connecting aged lead pipes to stainless steel fittings and placing the couple in different water conditions. The results of this study demonstrated that lead release significantly accelerated when lead and stainless steel were galvanically connected and the rate of lead release accelerated with decreasing pH and increasing chloride-to-sulfate mass ratio (CSMR). Orthophosphate could effectively reduce lead release but CSMR needs to be considered since water with a higher CSMR still caused more lead release when galvanic corrosion took place., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Premise plumbing materials such as pipes, valves, fittings, and faucets are made of various materials, including plastic, stainless steel, copper, and brass/bronze. Although lead pipe has been banned for its use in drinking water supply by most countries in the 1980s, lead is still commonly used as an additive in many plumbing materials for its flexibility and malleability. Certified leaching tests for plumbing materials are usually conducted using relatively mild solutions over short periods which may not reveal the true risk of lead exposure when these materials are used. The objective of this study is to investigate the extents of lead release from commonly used premise plumbing materials into drinking water. The maximum lead leaching potential for pluming material was operationally determined using high strength acidic EDTA solutions (pH 4, EDTA = 100 mg/L) for a stagnation time of 3 days for a total period of up to 1 month. Lead leaching from each plumbing material was also evaluated using reconstituted tap water. Brass- and bronze-based plumbing materials were found to release dangerous levels of lead. Surface lead weight percentage obtained using SEM-EDX and lead weight percentages of the material body obtained using strong acid digestion were found to positively correlate with lead release. A re-examination of the appropriateness of current certified leaching tests and a more stringent regulation on the use of lead as an additive for plumbing materials should be considered.

In this study, a sampling campaign with a total of nine sampling events investigating lead in drinking water was conducted at 7 sampling locations in an old building with lead pipes in service in part of the building on the National Taiwan University campus. This study aims to assess the effectiveness of four different sampling methods, namely first draw sampling, sequential sampling, random daytime sampling and flush sampling, in lead contamination detection. In 3 out of the 7 sampling locations without lead pipe, lead could not be detected (<1.1 μg/L) in most samples regardless of the sampling methods. On the other hand, in the 4 sampling locations where lead pipes still existed, total lead concentrations >10 μg/L were consistently observed in 3 locations using any of the four sampling methods while the remaining location was identified to be contaminated using sequential sampling. High lead levels were consistently measured by the four sampling methods in the 3 locations in which particulate lead was either predominant or comparable to soluble lead. Compared to first draw and random daytime samplings, although flush sampling had a high tendency to reduce total lead in samples in lead-contaminated sites, the extent of lead reduction was location-dependent and not dependent on flush durations between 5 and 10 min. Overall, first draw sampling and random daytime sampling were reliable and effective in determining lead contamination in this study. Flush sampling could reveal the contamination if the extent is severe but tends to underestimate lead exposure risk., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Metal sulfides serve as the sinks of toxic heavy metals in anoxic sediments. Once exposed to fluctuations in environmental conditions, dissolution of metal sulfides can occur and release toxic heavy metal ions into water column. In this study, we investigated the effects of dissolved oxygen (DO), pH, salinity and humic acid (HA) on the dissolution of CuS, PbS and ZnS using batch experiments with continuous aeration to simulate the re-suspension of these metal sulfides during a storm event. Experimental results indicated that oxidative dissolution of CuS, PbS and ZnS occurred in the presence of DO. The rate was the fastest for PbS, followed by CuS and ZnS. Soluble metal concentrations also increased with decreasing pH under oxic conditions. Compared to metal sulfides dissolution rates in freshwater without HA, the presence of saline conditions and HA generally accelerated the dissolution of CuS but inhibited the dissolution of PbS and ZnS. A higher saline or HA concentration, however, did not always lead to a stronger enhanced or inhibited dissolution rate, which could be a collective effect resulting from ligand-enhanced dissolution, complexation, and decreased oxygen and proton attacks due to HA adsorption on the metal sulfide surfaces., (Copyright © 2017. Published by Elsevier B.V.)

Introduction: Tension-band wire fixation of patellar fractures is associated with significant hardware-related complications and infection. Braided polyester suture fixation is an alternative option. However, these suture fixations have higher failure rates due to the difficulty in achieving rigid suture knot fixation. The Arthrex syndesmotic TightRope, which is a double-button adjustable loop fixation device utilizing a 4-point locking system using FibreWire, may not only offer stiff rigid fixation using a knotless system, but may also obviate the need for implant removal due to hardware related problems. The aim of our study is to compare the fixation rigidity of patella fractures using Tightrope versus conventional tension-band wiring (TBW) in a cadaveric model., Materials and Methods: TBW fixation was compared to TightRope fixation of transverse patella fractures in 5 matched pairs of cadaveric knees. The knees were cyclically brought through 0-90° of motion for a total of 500 cycles. Fracture gapping was measured before the start of the cycling, and at 50, 100, 200 and 500 cycles using an extensometer. The mean maximum fracture gapping was derived. Failure of the construct was defined as a displacement of more than 3mm, patella fracture or implant breakage., Results: All but one knee from each group survived 500 cycles. The two failures were due to a fracture gap of more than 3mm during cycling. There was no significant difference in the mean number of cycles tolerated. There was no implant breakage. There was no statistical significant difference in mean maximum fracture gap between the TBW and TightRope group at all cyclical milestones after 500 cycles (0.3026±0.4091mm vs 0.3558±0.7173mm, p=0.388)., Conclusions: We found no difference between the TBW and Tightrope fixation in terms of fracture gapping and failure. With possible lower risk of complications such as implant migration and soft tissue irritation, we believe tightrope fixation is a feasible alternative in fracture management of transverse patella fractures., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Nanoscale lead dioxide (nPbO 2(s) ) is a corrosion product formed from the chlorination of lead-containing plumbing materials. This metal oxide nanoparticle (NP) plays a key role in determining lead pollution in drinking water and receiving water bodies. This study uses nPbO 2(s) and medaka fish (Oryzias latipes) as surrogates to investigate the aqueous fate and toxicological risk of metal oxide NPs associated with water matrices. The larvae of medaka were treated with solutions containing nPbO 2(s) or Pb(II) aq in different water matrices for 7-14 days to investigate the in vivo toxic effects of NPs. Ionic strength enhanced aggregation and sedimentation of nPbO 2(s) in water, leading to increased lead contents in fish bodies. However, the presence of dissolved organic matter in water enhanced particle stability and accelerated the lead dissolution, thus changing the bioavailability processes (bioaccessibility) of particles. Oxidative stress response and neurotoxicity in exposed fish was greater for nPbO 2(s) solution with increased salinity than dissolved organic matter. We predict the bioavailability processes and toxicity of nPbO 2(s) in medaka from the aqueous particle behavior under environmentally relevant exposure conditions. Our investigation suggests a toxicological risk of metal oxide NP pollution in the aquatic environment.

In this pilot study, a modified sampling protocol was evaluated for the detection of lead contamination and locating the source of lead release in a simulated premise plumbing system with one-, three- and seven-day stagnation for a total period of 475 days. Copper pipes, stainless steel taps and brass fittings were used to assemble the "lead-free" system. Sequential sampling using 100 mL was used to detect lead contamination while that using 50 mL was used to locate the lead source. Elevated lead levels, far exceeding the World Health Organization (WHO) guideline value of 10 µg · L(-1), persisted for as long as five months in the system. "Lead-free" brass fittings were identified as the source of lead contamination. Physical disturbances, such as renovation works, could cause short-term spikes in lead release. Orthophosphate was able to suppress total lead levels below 10 µg · L(-1), but caused "blue water" problems. When orthophosphate addition was ceased, total lead levels began to spike within one week, implying that a continuous supply of orthophosphate was required to control total lead levels. Occasional total lead spikes were observed in one-day stagnation samples throughout the course of the experiments.

Addition of orthophosphate has been commonly employed to suppress lead levels in drinking water. Its detailed mechanism and time required for it to become effective, however, have not been fully elucidated. In this study, we investigated the mechanistic role of orthophosphate as a corrosion inhibitor in controlling lead release from tetravalent lead corrosion product PbO(2) in chloraminated solutions, a system representing distribution networks experiencing disinfectant changeover from free chlorine to monochloramine. In all experiments with orthophosphate addition of at least 1 mg/L as P, peaking of soluble Pb(II) concentration within the first 24 h was observed before lead concentrations decreased and stabilized at levels lower than 15 μg/L. The variation of soluble Pb(II) concentration could be attributed to the dynamics between the rate of PbO(2) reductive dissolution, primarily induced by monochloramine decomposition, and that of chloropyromorphite (Pb(5)(PO(4))(3)Cl) precipitation, which did not occur until a critical supersaturation ratio of about 2.36 was reached in the solution. Our findings provide insights to how orthophosphate reduces lead levels under drinking water conditions and highlight the potential risk of short-term elevated lead concentrations. Intensive monitoring following the disinfectant changeover may be required to determine the overall lead exposure when using orthophosphate as a corrosion inhibitor.

Lead and its compounds are toxic and can harm human health, especially the intelligence development in children. Accurate measurement of total lead present in drinking water is crucial in determining the extent of lead contamination and human exposure due to drinking water consumption. The USEPA method for total lead measurement (no. 200.8) is often used to analyze lead levels in drinking water. However, in the presence of high concentration of the tetravalent lead corrosion product PbO(2), the USEPA method was not able to fully recover particulate lead due to incomplete dissolution of PbO(2) particles during strong acid digestion. In this study, a new procedure that integrates membrane separation, iodometric PbO(2) measurement, strong acid digestion and ICP-MS measurement was proposed and evaluated for accurate total lead measurement and quantification of different lead fractions including soluble Pb(2+), particulate Pb(II) carbonate and PbO(2) in drinking water samples. The proposed procedure was evaluated using drinking water reconstituted with spiked Pb(2+), spiked particulate Pb(II) carbonate and in situ formed or spiked PbO(2). Recovery tests showed that the proposed procedure and the USEPA method can achieve 93-112% and 86-103% recoveries respectively for samples containing low PbO(2) concentrations (0.018-0.076 mg Pb per L). For samples containing higher concentrations of PbO(2) (0.089-1.316 mg Pb per L), the USEPA method failed to meet the recovery requirement for total lead (85-115%) while the proposed method can achieve satisfactory recoveries (91-111%) and differentiate the soluble Pb(2+), particulate Pb(II) carbonate and PbO(2).