Cancer and Fertility: Exploring Uncertainty Management Strategies of Young Adult Female Survivors.

This study describes young adult female (YA-F) cancer survivors' uncertainty management strategies related to fertility/family building. Cross-sectional data were analyzed (n = 98). Participants reported higher rates of seeking information to reduce fertility-related uncertainty (M = 5.48, ±1.03), than avoiding information (M = 4.77, ±1.29). Controlling for relevant covariates (i.e., reproductive distress, household income, and health literacy), greater avoidance was related to higher reproductive distress (ß = 0.293, p = 0.011) and lower household income (ß = -0.281, p = 0.047). Evidence suggests that some survivors may avoid fertility-related information to manage uncertainty and distress, which may impact family-building success. Fertility avoidance may be an important target of intervention.

Preliminary testing of "roadmap to parenthood" decision aid and planning tool for family building after cancer: Results of a single-arm pilot study.

OBJECTIVE: Many young adult female cancer survivors need to use reproductive medicine, surrogacy, or adoption to have a child. This study pilot tested Roadmap to Parenthood, a web-based, self-guided decision aid and planning tool for family building after cancer (disease agnostic). METHODS: A single-arm pilot study tested feasibility, acceptability, and obtained effect size estimates of the Roadmap tool. Participants, recruited via hospital-based and social media strategies, completed a baseline survey (T1), accessed the Roadmap tool (website), then completed surveys at one- and 3-months (T2 and T3, respectively). Feasibility and acceptability were evaluated with rates of eligibility, enrollment, and survey completion, and feedback. Pairwise t-tests and repeated measures ANOVA evaluated usage effects. Effect size estimates were calculated. RESULTS: Participants (N = 98) averaged 31 years old (SD = 5.61); 71% were nulliparous. Enrollment rate was 73%, T1-T2 completion rate was 80%, and 93% accessed the website. From T1-T2, participants reported improvements in decisional conflict (p < 0.001; Cohen's d = 0.85), unmet information needs (p < 0.001; Cohen's d = 0.70), self-efficacy (p = 0.003; Cohen's d = 0.40), and self-efficacy for managing negative emotions (p = 0.03; Cohen's d = 0.29); effects were sustained at T3. There was no change in reproductive distress (p = 0.22). By T3, 94% reported increased consideration of preparatory actions and 20%-61% completed such actions. CONCLUSIONS: The Roadmap intervention was feasible to conduct, acceptable to users, and led to improvements in key psychosocial outcomes. Future directions will test intervention efficacy in a randomized controlled trial with a larger sample and over a longer period. A web-based tool may help women make decisions about family building after cancer and prepare for potential challenges.

Perceptions of Infertility and Reproductive Concerns in Adolescent and Young Adult Female Cancer Survivors.

This cross-sectional survey study explores the fertility perceptions of adolescent and young adult female cancer survivors (n = 111) and relationships to fertility counseling and reproductive distress. Satisfaction with post-treatment fertility counseling (ß = -0.20, p = 0.04), perceived consequences of cancer-related fertility changes (ß = 0.26, p = 0.03), and understanding of one's reproductive health (ß = -0.22, p = 0.03) correlated with reproductive distress, controlling for covariates (F(10, 88) = 3.50, p < 0.001). Findings suggest that post-treatment counseling may be important to addressing survivors' perceptions of fertility and reproductive potential, which influences levels of distress and to create a greater sense of control on their road to parenthood.

Meta-analytic Techniques to Assess the Association Between N-acetylcysteine and Acute Kidney Injury After Contrast Administration: A Systematic Review and Meta-analysis.

Importance: The most suitable analytic method to systematically analyze numerous trials with contradictory results is unclear. Multiple trials assessing the use of N-acetylcysteine (NAC) for prevention of contrast-induced acute kidney injury (CI-AKI) have had contradictory results with recent trials confirming a lack of benefit. Objective: To systematically review the literature on NAC for the prevention of CI-AKI, and to explore the heterogeneity, publication bias, and small-study effect to determine the most suitable analytic method in a setting where the literature is contradictory. Data Sources: Medline, Embase, and Cochrane Central Register of Controlled Trials databases were used to find randomized clinical trials (RCTs) comparing NAC with any other prophylactic agent or placebo in adults. Study Selection: The search included studies published in English from database inception to January 2020. Two independent reviewers screened the studies, extracted data, and performed the risk of bias assessment. Data Extraction and Synthesis: A meta-analysis was conducted about the effect of NAC on CI-AKI, the need for dialysis, and mortality. Fixed and random effects analyses were also performed. Funnel plots and the trim and fill method were used for assessment of publication bias. Metaregression was performed to explore the heterogeneity and subgroup analysis to examine the association between NAC and CI-AKI when studies were categorized according to sample size and number of events. Results: A total of 101 trials were included in this meta-analysis. The median sample size was 112 (range, 20 to 4993). Twenty-nine trials had a sample size of 200 or more, and only 3 trials had a sample size of 500 or more. Forty-five trials reported the need for kidney replacement therapy, and 41 trials reported mortality as an outcome. NAC seemed to show a benefit, with a pooled OR of 0.72 (95% CI, 0.63-0.82) using random effects model and a pooled OR of 0.82 (95% CI 0.76-0.90) using a fixed effects model. However, there was significant heterogeneity (I2 = 37.6; P < .001) and significant publication bias, which was reduced only when restricting to large RCTs (N ≥ 500). The clinical outcomes (ie, the need for kidney replacement therapy and mortality) revealed little heterogeneity and no publication bias, and each provided a robust neutral summary result. Conclusions and Relevance: In this meta-analysis, NAC was associated with a benefit in the prevention of CI-AKI. However, because of substantial publication bias and other biases, standard meta-analytic techniques resulted in significant heterogeneity and a spurious, or factitious, association, even when using a random effects model. When the analysis was restricted to RCTs with a large sample size to account for publication bias or restricted to trials with clinical outcomes, this issue was reduced and resulted in more robust and neutral effect sizes.

The effects of a primary care low-carbohydrate, high-fat dietary educational intervention on laboratory and anthropometric data of patients with chronic disease: a retrospective cohort chart review.

BACKGROUND: Low-carbohydrate and high-fat (LCHF) diets are shown to have health benefits such as weight loss and improved cardiovascular health. Few studies, however, on LCHF diets have been completed in a real-world primary care setting over an extended period of time. OBJECTIVES: To examine the efficacy of a low-carbohydrate, high-fat dietary educational intervention delivered in a family practice setting on weight, body mass index (BMI), blood pressure, glycated haemoglobin (HbA1c), fasting insulin, estimated glomerular filtration rate (eGFR), and albumin to creatinine ratio (ACR). A secondary objective was to determine whether compliance to the program had an effect on outcomes. METHODS: In this retrospective chart review, we collected laboratory and anthropometric data from an electronic medical record system for patients (n = 122) at least 19 years of age, who attended at least 2 LCHF educational sessions between January 2018 and May 2020. Pre-post mean differences of outcome were analysed using paired sample t-tests. Independent sample t-tests examined the effect of compliance on the outcomes. RESULTS: Statistically significant reductions in weight (3.96 kg [P < 0.001]) and BMI (1.46 kg/m2 [P = 0.001]) were observed. Compared with patients who participated in ≤5 educational visits, patients who participated in >5 visits showed trends towards more clinically significant changes in weight, BMI, systolic blood pressure, diastolic blood pressure, HbA1c, eGFR, and ACR. CONCLUSION: Improvements in weight and BMI indicate the utility of providing LCHF health promotion interventions in primary care settings. Greater compliance to LCHF interventions results in greater improvement in laboratory and anthropometric outcomes, including HbA1c.

Bisphenol a affects neurodevelopmental gene expression, cognitive function, and neuromuscular synaptic morphology in Drosophila melanogaster.

Bisphenol A (BPA) is an environmentally prevalent endocrine disrupting chemical that can impact human health and may be an environmental risk factor for neurodevelopmental disorders. BPA has been associated with behavioral impairment in children and a variety of neurodevelopmental phenotypes in model organisms. We used Drosophila melanogaster to explore the consequences of developmental BPA exposure on gene expression, cognitive function, and synapse development. Our transcriptome analysis indicated neurodevelopmentally relevant genes were predominantly downregulated by BPA. Among the misregulated genes were those with roles in learning, memory, and synapse development, as well as orthologs of human genes associated with neurodevelopmental and neuropsychiatric disorders. To examine how gene expression data corresponded to behavioral and cellular phenotypes, we first used a predator-response behavioral paradigm and found that BPA disrupts visual perception. Further analysis using conditioned courtship suppression showed that BPA impairs associative learning. Finally, we examined synapse morphology within the larval neuromuscular junction and found that BPA significantly increased the number of axonal branches. Given that our findings align with studies of BPA in mammalian model organisms, this data indicates that BPA impairs neurodevelopmental pathways that are functionally conserved from invertebrates to mammals. Further, because Drosophila do not possess classic estrogen receptors or estrogen, this research suggests that BPA can impact neurodevelopment by molecular mechanisms distinct from its role as an estrogen mimic.

Red blood cell transfusion in myelodysplastic syndromes: A systematic review.

Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC transfusions may rapidly increase haemoglobin values, their impact on clinical and health services outcomes in MDS patients has not previously been summarized. We conducted a systematic review of the literature to evaluate risks and benefits of RBC transfusions in MDS patients. We searched electronic databases (MEDLINE, Embase, CENTRAL, CINAHL) from inception through June 4, 2021 to identify studies reporting data on RBC transfusions in MDS patients. Full text publications that assessed RBC transfusions as an intervention and reported at least one clinical, laboratory, or healthcare outcome associated with transfusion were included. Study characteristics, transfusion information and transfusion-related outcomes were extracted and reported. We identified 1243 original studies, of which 38 met eligibility requirements and were included. Fourteen reported on survival following diagnosis of MDS, with the majority reporting poorer survival among patients receiving or requiring more frequent transfusions. Nine reported on transfusion-related iron overload and its complications. Other outcomes included rates of allo/autoimmunization and adverse transfusion reactions, and healthcare costs incurred by patients with a greater transfusion burden. Only two studies reported on symptom relief following transfusion. This review underscores transfusion dependence as a negative prognostic factor for MDS patients and highlights the paucity of evidence surrounding quality of life and symptom-related outcomes following RBC transfusions in this population. Further study of patient-important outcomes associated with transfusion in MDS patients is warranted to improve therapeutic recommendations and inform resource allocation.

A Systematic Review and Meta-analysis of Randomized Controlled Trials Comparing Intraoperative Red Blood Cell Transfusion Strategies.

OBJECTIVE: The objective of this work was to carry out a meta-analysis of RCTs comparing intraoperative RBC transfusion strategies to determine their impact on postoperative morbidity, mortality, and blood product use. SUMMARY OF BACKGROUND DATA: RBC transfusions are common in surgery and associated with widespread variability despite adjustment for casemix. Evidence-based recommendations guiding RBC transfusion in the operative setting are limited. METHODS: The search strategy was adapted from a previous Cochrane Review. Electronic databases were searched from January 2016 to February 2021. Included studies from the previous Cochrane Review were considered for eligibility from before 2016. RCTs comparing intraoperative transfusion strategies were considered for inclusion. Co-primary outcomes were 30-day mortality and morbidity. Secondary outcomes included intraoperative and perioperative RBC transfusion. Meta-analysis was carried out using random-effects models. RESULTS: Fourteen trials (8641 patients) were included. One cardiac surgery trial accounted for 56% of patients. There was no difference in 30-day mortality [relative risk (RR) 0.96, 95% confidence interval (CI) 0.71-1.29] and pooled postoperative morbidity among the studied outcomes when comparing restrictive and liberal protocols. Two trials reported worse composite outcomes with restrictive triggers. Intraoperative (RR 0.53, 95% CI 0.43-0.64) and perioperative (RR 0.70, 95% CI 0.62-0.79) blood transfusions were significantly lower in the restrictive group compared to the liberal group. CONCLUSIONS: Intraoperative restrictive transfusion strategies decreased perioperative transfusions without added postoperative morbidity and mortality in 12/14 trials. Two trials reported worse outcomes. Given trial design and generalizability limitations, uncertainty remains regarding the safety of broad application of restrictive transfusion triggers in the operating room. Trials specifically designed to address intraoperative transfusions are urgently needed.

The EBV-Encoded Oncoprotein, LMP1, Recruits and Transforms Fibroblasts via an ERK-MAPK-Dependent Mechanism.

Latent membrane protein 1 (LMP1), the major oncoprotein encoded by Epstein-Barr virus (EBV), is expressed at widely variable levels in undifferentiated nasopharyngeal carcinoma (NPC) biopsies, fueling intense debate in the field as to the importance of this oncogenic protein in disease pathogenesis. LMP1-positive NPCs are reportedly more aggressive, and in a similar vein, the presence of cancer-associated fibroblasts (CAFs) surrounding "nests" of tumour cells in NPC serve as indicators of poor prognosis. However, there is currently no evidence linking LMP1 expression and the presence of CAFs in NPC. In this study, we demonstrate the ability of LMP1 to recruit fibroblasts in vitro in an ERK-MAPK-dependent mechanism, along with enhanced viability, invasiveness and transformation to a myofibroblast-like phenotype. Taken together, these findings support a putative role for LMP1 in recruiting CAFs to the tumour microenvironment in NPC, ultimately contributing to metastatic disease.

Passive Versus Active Intra-Abdominal Drainage Following Pancreatic Resection: Does A Superior Drainage System Exist? A Systematic Review and Meta-Analysis.

Postoperative pancreatic fistula (POPF) is a major source of morbidity following pancreatic resection. Surgically placed drains under suction or gravity are routinely used to help mitigate the complications associated with POPF. Controversy exists as to whether one of these drain management strategies is superior. The objective was to identify and compare the incidence of POPF, adverse events, and resource utilization associated with passive gravity (PG) versus active suction (AS) drainage following pancreatic resection. MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched from inception to May 18, 2020. Outcomes of interest included POPF, post-pancreatectomy hemorrhage (PPH), surgical site infection (SSI), other major morbidity, and resource utilization. Descriptive qualitative and pooled quantitative meta-analyses were performed. One randomized control trial and five cohort studies involving 10 663 patients were included. Meta-analysis found no difference in the odds of developing POPF between AS and PG (p = 0.78). There were no differences in other endpoints including PPH (p = 0.58), SSI (wound p = 0.21, organ space p = 0.05), major morbidity (p = 0.71), or resource utilization (p = 0.72). The risk of POPF or other adverse outcomes is not impacted by drain management following pancreatic resection. Based on current evidence, a suggestion cannot be made to support the use of one drain over another at this time. There is a trend toward increased intra-abdominal wound infections with AS drains (p = 0.05) that merits further investigation.

Health risk assessment of volatile organic compounds at daycare facilities.

Children are particularly vulnerable to many classes of the volatile organic compounds (VOCs) detected in indoor environments. The negative health impacts associated with chronic and acute exposures of the VOCs might lead to health issues such as genetic damage, cancer, and disorder of nervous systems. In this study, 40 VOCs including aldehydes and ketones, aliphatic hydrocarbons, esters, aromatic hydrocarbons, cyclic terpenes, alcohols, and glycol ethers were identified and qualified in different locations at the University of Missouri (MU) Child Development Laboratory (CDL) in Columbia, Missouri. Our results suggested that the concentrations of the VOCs varied significantly among classrooms, hallways, and playground. The VOCs emitted from personal care and cleaning products had the highest indoor levels (2-ethylhexanol-1, 3-carene, homomenthyl salicylate with mean concentration of 5.15 µg/m3 , 1.57 µg/m3 , and 1.47 µg/m3 , respectively). A cancer risk assessment was conducted, and none of the 95th percentile dose estimates exceeded the age-specific no significant risk levels (NSRL) in all classrooms. Dimensionless toxicity index scores were calculated for all VOCs using a novel web-based framework called Toxicological Prioritization Index (ToxPi), which integrates multiple sources of toxicity data. According to the method, homomenthyl salicylate, benzothiazole, 2-ethylhexyl salicylate, hexadecane, and tridecane exhibited diverse toxicity profiles and ranked as the five most toxic indoor VOCs. The findings of this study provide critical information for policy makers and early education professionals to mitigate the potentially negative health impacts of indoor VOCs in the childcare facilities.

Intraoperative Red Blood Cell Transfusion Decision-making: A Systematic Review of Guidelines.

OBJECTIVES: The objective of this work was to carry out a systematic review of clinical practice guidelines (CPGs) pertaining to intraoperative red blood cell (RBC) transfusions, in terms of indications, decision-making, and supporting evidence base. SUMMARY OF BACKGROUND DATA: RBC transfusions are common during surgery and there is evidence of wide variability in practice. METHODS: Major electronic databases (MEDLINE, EMBASE, and CINAHL), guideline clearinghouses and Google Scholar were systematically searched from inception to January 2019 for CPGs pertaining to indications for intraoperative RBC transfusion. Eligible guidelines were retrieved and their quality assessed using AGREE II. Relevant recommendations were abstracted and synthesized to allow for a comparison between guidelines. RESULTS: Ten guidelines published between 1992 and 2018 provided indications for intraoperative transfusions. No guideline addressed intraoperative transfusion decision-making as its primary focus. Six guidelines provided criteria for transfusion based on hemoglobin (range 6.0-10.0 g/dL) or hematocrit (<30%) triggers. In the absence of objective transfusion rules, CPGs recommended considering other parameters such as blood loss (n = 7), signs of end organ ischemia (n = 5), and hemodynamics (n = 4). Evidence supporting intraoperative recommendations was extrapolated primarily from the nonoperative setting. There was wide variability in the quality of included guidelines based on AGREE II scores. CONCLUSION: This review has identified several clinical practice guidelines providing recommendations for intraoperative transfusion. The existing guidelines were noted to be highly variable in their recommendations and to lack a sufficient evidence base from the intraoperative setting. This represents a major knowledge gap in the literature.

Doubly Protective MOF-Photo-Fabrics: Facile Template-Free Synthesis of PCN-222-Textiles Enables Rapid Hydrolysis, Photo-Hydrolysis and Selective Oxidation of Multiple Chemical Warfare Agents and Simulants.

New materials and chemical knowledge for improved personal protection are among the most pressing needs in the international community. Reported attacks using chemical warfare agents (CWAs,) including organophosphate soman (GD) and thioether mustard gas (HD) are driving research in field-deployable catalytic composites for rapid toxin degradation. In this work, we report simple template-free low temperature synthesis that enables for the first time, a deployable-structured catalytic metal-organic framework/polymer textile composite "MOF-fabric" showing rapid hydrolysis and oxidation of multiple active chemical warfare agents, GD and HD, respectively, and their simulants. Our method yields new zirconium-porphyrin based nano-crystalline PCN-222 MOF-fabrics with adjustable MOF loading and robust mechanical adhesion on low-cost nonwoven polypropylene fibers. Importantly, we describe quantitative kinetic analysis confirming that our MOF-fabrics are as effective as or better than analogous MOF powders for agent degradation, especially for oxidation. Faster oxidation using the MOF-fabrics is ascribed to the composite geometry, where active MOF catalysts are uniformly displayed on the MOF-textile enabling better reactant transport and reactive oxidant generation. Furthermore, we note the discovery of visible photo-activation of GD hydrolysis by a MOF-fabric, which is ascribed to oxidation at the active metal node site, significantly increasing the rate over that observed without illumination. These results provide important new insights into the design of future materials and chemical systems to protect military, first-responders, and civilians upon exposure to complex chemical toxins.

The Effect of Surface Hydroxylation on MOF Formation on ALD Metal Oxides: MOF-525 on TiO2/Polypropylene for Catalytic Hydrolysis of Chemical Warfare Agent Simulants.

Metal-organic framework (MOF) fibrous composites were synthesized in a variety of methods in attempt to incorporate the highly effective reactivity of MOFs into a more facile and applicable format. Recent advances have demonstrated incorporating a metal oxide nucleation surface or reactive layer promotes conformal, well-adhered MOF growth on substrates. These materials have demonstrated promising reactivity in capturing or degrading chemical warfare agents and simulants. Here, we examine the mechanisms for MOF nucleation from metal oxide thin films to explore why some metal oxide sources are better suited for one synthesis mechanism over another. We isolate metal oxide extent of hydroxylation as an indicative factor as to whether the film serves as a nucleation promoter or may be converted directly to the MOF thin films. MOF-525 growth on Al2O3, TiO2, and ZnO coated fibers is demonstrated to corroborate these findings and used to degrade chemical warfare agent simulant dimethyl-4-nitrophenyl phosphate.

Exposure to environmental toxicants and young children's cognitive and social development.

Background Understanding the role of environmental toxicant exposure on children's development is an important area of inquiry in order to better understand contextual factors that shape development and ultimately school readiness among young children. There is evidence suggesting negative links between exposure to environmental toxicants and negative physical health outcomes (i.e. asthma, allergies) in children. However, research on children's exposure to environmental toxicants and other developmental outcomes (cognitive, socioemotional) is limited. Objectives The goal of the current review was to assess the existing literature on the links between environmental toxicants (excluding heavy metals) and children's cognitive, socioemotional, and behavioral development among young children. Methods This literature review highlights research on environmental toxicants (i.e. pesticide exposure, bisphenol A, polycyclic aromatic hydrocarbons, tobacco smoke, polychlorinated biphenyls, flame retardants, phthalates and gas pollutions) and children's development across multiple domains. Results The results highlight the potential risk of exposure to multiple environmental toxicants for young children's cognitive and socioemotional development. Discussion Discussion will focus on the role of environmental toxicants in the cognitive and socioemotional development of young children, while highlighting gaps in the existing literature.

Comparison of Metzenbaum scissors and Y-shaped fasciotome for deep metatarsal fasciotomy for the treatment of proximal suspensory ligament desmopathy in horses.

OBJECTIVE: To quantitate the iatrogenic injury associated with deep plantar metatarsal fasciotomy performed with Metzenbaum scissors compared with a Y-shaped fasciotome. STUDY DESIGN: Experimental ex vivo surgical study. STUDY POPULATION: Cadaveric hind limbs (n = 20) from 10 sound thoroughbred racehorses. METHODS: A plantar metatarsal fasciotomy was performed, extending from the proximal extent of the deep metatarsal fascia, distally. Hind limbs were randomly assigned to 2 groups, undergoing fasciotomy with straight Metzenbaum scissors (n = 10) or a Y-shaped fasciotome (n = 10). Magnetic resonance imaging was performed before and after surgery to identify the maximal depth of any iatrogenic trauma. Gross examination of the surgical site included measuring the length of the incision in the deep metatarsal fascia and localizing iatrogenic trauma sustained by the plantar aspect of the proximal suspensory ligament (PSL) during the procedure. RESULTS: Iatrogenic injury to the PSL was identified in 6 of 10 and 9 of 10 specimens prepared with the fasciotome and Metzenbaum scissors, respectively (P = .03), and was most commonly located in the distal third of the fascial incision. Differences between the length of incision (P = .02) and the maximal depth of signal (P = .03) for incisions created with Metzenbaum scissors or a fasciotome were identified. CONCLUSION: The use of a fasciotome resulted in longer fascial incisions and less severe iatrogenic trauma to the PSL compared with using Metzenbaum scissors. CLINICAL SIGNIFICANCE: A Y-shaped fasciotome may be the preferred surgical instrument for successful desmopathy of the PSL fasciotomy because a greater release of compartmental pressure is possible through a longer incision with minimal iatrogenic trauma to the underlying PSL.

Patient-Centered Outcomes in the Management of Anemia: A Scoping Review.

Anemia is a frequently diagnosed condition that may be a symptom of or complication of many illnesses affecting patients of all demographics. Anemia can lead to both worsened clinical outcomes and reduced quality of life. Patient-reported outcome measures (PROMs) are methodological tools used to capture the impact of disease on patient well-being. Use of PROMs in medical research is becoming more common as it is increasingly recognized that disease outcomes of interest to researchers and clinicians are not always consistent with patients' greatest concerns related to their diseases. We conducted a scoping review to characterize the studies that have evaluated patient-centered outcomes using PROMs in patients undergoing treatment for anemia. We conducted a search of Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies published until January 2017 that investigated an intervention to treat anemia in any patient population and used at least 1 PROM to evaluate patient-centered outcomes. A descriptive synthesis was performed to characterize the PROMs used and to evaluate the quality of patient-centered outcome (PCO) reporting. Of the 3224 studies identified in the initial search, 130 met all eligibility criteria. We found that the population most frequently studied was oncology patients (46.2% of studies). The therapy for anemia evaluated in the most studies was erythropoietin-stimulating agents (77.7% of studies). The most commonly used PROM was the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic Illness Therapy tool (46.9%), and the majority of studies used only 1 PROM tool (53.1%). We found significant variability in the quality of PCO reporting across all included studies. Improved methodologic rigor in the assessment of PCOs in anemia management is needed in future studies.

The Effect of N-Acetylcysteine on Creatinine Measurement: Protocol for a Systematic Review.

BACKGROUND: N-acetylcysteine (NAC) is an antioxidant which can regenerate glutathione and is primarily used for acetaminophen overdose. It is also a potential therapy to prevent iatrogenic acute kidney injury or slow the progression of chronic kidney disease. It has been considered in this context by many studies with mixed results. Notably, a biological-mechanism rationale for a protective effect of NAC has never been adequately reported. Among conflicting reports, there appears to be evidence that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, a systematic review of the literature will be conducted to determine whether there is an effect of NAC on kidney function measured with serum creatinine. OBJECTIVE: To determine the effect of NAC on kidney function. DESIGN: A systematic review and meta-analysis. SETTINGS: Prospective studies, with administration of NAC, in the absence of any other change in kidney function (such as contrast administration or surgery). PATIENTS: Adult humans aged 18 years old or more, either healthy volunteers or with chronic kidney disease, were administered with NAC. Populations having little to no kidney function such as in end-stage kidney disease will be excluded. MEASUREMENTS: Serum creatinine and/or cystatin C measurements before and after NAC administration. METHODS: An information specialist will assist in searching MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify all study types including randomized controlled trials, and prospective cohort studies reporting change in serum creatinine after NAC administration. Two reviewers will independently screen the titles and abstracts of the studies obtained from the search using predefined inclusion criteria and will then extract data from the full texts of selected studies. The weighted mean difference will be calculated for change in creatinine with NAC, using random-effects analysis. Quality assessment will be done with the Cochrane Risk of Bias tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: The outcome of interest is kidney function as reported by either change in serum creatinine and/or serum cystatin C measurement for randomized trials or comparing baseline (pre-NAC dose) values and those following the NAC dose. LIMITATIONS: Possible heterogeneity and publication bias and lack of mechanistic data. CONCLUSIONS: This systematic review will provide a synthesis of current evidence on the effect of NAC on serum creatinine measurement. These findings will provide clinicians with guidelines and serve as a strong research base for future studies in this field. SYSTEMATIC REVIEW REGISTRATION: This review is registered with PROSPERO, CRD42017055984.

CONTEXTE: La N-acétylcystéine (NAC) est un antioxydant capable de régénérer le glutathion et principalement utilisé pour traiter les cas de surdose d'acétaminophène. La NAC pourrait également s'avérer efficace comme traitement préventif de l'insuffisance rénale aiguë iatrogénique ou pour ralentir la progression de l'insuffisance rénale chronique. Cette substance a fait l'objet de plusieurs études dans ce contexte, mais les résultats demeurent mitigés. Notamment, il reste toujours à rapporter adéquatement une justification de l'effet protecteur de la NAC sur la base d'un mécanisme biologique. Parmi les rapports contradictoires, certaines données montreraient que la NAC abaisse artificiellement les valeurs de créatinine sérique mesurées sans améliorer la fonction rénale, potentiellement par interférence de l'essai. À la lumière de ces résultats divergents, une revue systématique de la littérature sera effectuée pour déterminer si la NAC produit un effet sur la fonction rénale mesurée par la créatinine sérique. OBJECTIF: Mesurer l'effet de l'administration de NAC sur la fonction rénale. TYPE D'ÉTUDE: Une revue systématique de la littérature et une méta-analyse. CADRE: Les études prospectives avec administration de NAC sans autres changements dans la fonction rénale; l'administration d'un produit de contraste ou une intervention chirurgicale, par exemple. SUJETS: Des adultes, volontaires sains ou atteints de néphropathie chronique, ayant reçu de la NAC. Seront exclues les populations dont la fonction rénale est faible ou inexistante; notamment, les cas d'insuffisance rénale terminale. MESURES: Des mesures de la créatinine sérique et/ou de la cystatine C faites avant et après l'administration de NAC. MÉTHODOLOGIE: Un documentariste spécialisé assistera les recherches dans les bases de données MEDLINE, EMBASE et Cochrane CENTRAL afin de répertorier tous les types d'essais, y compris les essais contrôlés à répartition aléatoire, et toutes les études de cohorte prospectives faisant état d'une variation de la créatinine sérique à la suite de l'administration de NAC. À l'aide de critères d'inclusion prédéfinis, deux réviseurs seront indépendamment chargés de trier les titres et abrégés des études répertoriées lors de la revue de la littérature. Ils devront ensuite extraire les données des textes des études qui auront été retenues. Une analyse des effets aléatoires sera utilisée pour calculer la moyenne pondérée des écarts pour les variations observées dans les mesures de créatinine en présence de NAC. La qualité des essais aléatoires sera évaluée à l'aide de l'outil Cochrane sur le risque de biais, et celle des études observationnelles sera mesurée avec l'échelle de Newcastle-Ottawa. RÉSULTATS: Le principal résultat d'intérêt est la fonction rénale telle que rapportée soit par un changement dans les mesures de créatinine sérique et/ou de la cystatine C dans les essais à répartition aléatoire, soit en comparant les valeurs mesurées avant et après l'administration d'une dose de NAC. LIMITES: L'hétérogénéité des données, de possibles biais de publication et un manque de données mécanistiques. CONCLUSION: Cette revue systématique offrira une synthèse des données probantes actuelles sur l'effet de la NAC sur les mesures de créatinine sérique. Ces résultats fourniront des lignes directrices aux cliniciens et serviront de bases solides pour les recherches futures dans ce domaine.

Solvothermal Synthesis of MIL-96 and UiO-66-NH2 on Atomic Layer Deposited Metal Oxide Coatings on Fiber Mats.

Metal-organic frameworks (MOFs), which contain reactive metal clusters and organic ligands allowing for large porosities and surface areas, have proven effective in gas adsorption, separations, and catalysis. MOFs are most commonly synthesized as bulk powder, requiring additional processes to adhere them to functional devices and fabrics that risk decreasing the powder porosity and adsorption capacity. Here, we demonstrate a method of first coating fabrics with metal oxide films using atomic layer deposition (ALD). This process creates conformal films of controllable thickness on each fiber, while providing a more reactive surface for MOF nucleation. By submerging the ALD coated fabric in solution during solvothermal MOF synthesis, the MOFs create a conformal, well-adhered coating on the fibers, resulting in a MOF-functionalized fabric, without additional adhesion materials that may block MOF pores and functional sites. Here we demonstrate two solvothermal synthesis methods. First, we form a MIL-96(Al) layer on polypropylene fibers using synthetic conditions that convert the metal oxide to MOF. Using initial inorganic films of varying thicknesses, diffusion of the organic linker into the inorganic allows us to control the extent of MOF loading on the fabric. Second, we perform a solvothermal synthesis of UiO-66-NH2 in which the MOF nucleates on the conformal metal oxide coating on polyamide-6 (PA-6) fibers, thereby producing a uniform and conformal thin film of MOF on the fabric. The resulting materials can be directly incorporated into filter devices or protective clothing and eliminate the maladroit qualities of loose powder.

The EBV-Encoded Oncoprotein, LMP1, Induces an Epithelial-to-Mesenchymal Transition (EMT) via Its CTAR1 Domain through Integrin-Mediated ERK-MAPK Signalling.

The Epstein⁻Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) oncogene can induce profound effects on epithelial growth and differentiation including many of the features of the epithelial-to-mesenchymal transition (EMT). To better characterise these effects, we used the well-defined Madin Darby Canine Kidney (MDCK) epithelial cell model and found that LMP1 expression in these cells induces EMT as defined by characteristic morphological changes accompanied by loss of E-cadherin, desmosomal cadherin and tight junction protein expression. The induction of the EMT phenotype required a functional CTAR1 domain of LMP1 and studies using pharmacological inhibitors revealed contributions from signalling pathways commonly induced by integrin⁻ligand interactions: extracellular signal-regulated kinases/mitogen-activated protein kinases (ERK-MAPK), PI3-Kinase and tyrosine kinases, but not transforming growth factor beta (TGFβ). More detailed analysis implicated the CTAR1-mediated induction of Slug and Twist in LMP1-induced EMT. A key role for β1 integrin signalling in LMP1-mediated ERK-MAPK and focal adhesion kianse (FAK) phosphorylation was observed, and β1 integrin activation was found to enhance LMP1-induced cell viability and survival. These findings support an important role for LMP1 in disease pathogenesis through transcriptional reprogramming that enhances tumour cell survival and leads to a more invasive, metastatic phenotype.