Anxiety in late-life depression: Associations with brain volume, amyloid beta, white matter lesions, cognition, and functional ability.

OBJECTIVES: Late-life depression (LLD) is common and frequently co-occurs with neurodegenerative diseases of aging. Little is known about how heterogeneity within LLD relates to factors typically associated with neurodegeneration. Varying levels of anxiety are one source of heterogeneity in LLD. We examined associations between anxiety symptom severity and factors associated with neurodegeneration, including regional brain volumes, amyloid beta (Aß) deposition, white matter disease, cognitive dysfunction, and functional ability in LLD. PARTICIPANTS AND MEASUREMENTS: Older adults with major depression (N = 121, Ages 65-91) were evaluated for anxiety severity and the following: brain volume (orbitofrontal cortex [OFC], insula), cortical Aß standardized uptake value ratio (SUVR), white matter hyperintensity (WMH) volume, global cognition, and functional ability. Separate linear regression analyses adjusting for age, sex, and concurrent depression severity were conducted to examine associations between anxiety and each of these factors. A global regression analysis was then conducted to examine the relative associations of these variables with anxiety severity. RESULTS: Greater anxiety severity was associated with lower OFC volume (ß = -68.25, t = -2.18, p = .031) and greater cognitive dysfunction (ß = 0.23, t = 2.46, p = .016). Anxiety severity was not associated with insula volume, Aß SUVR, WMH, or functional ability. When examining the relative associations of cognitive functioning and OFC volume with anxiety in a global model, cognitive dysfunction (ß = 0.24, t = 2.62, p = .010), but not OFC volume, remained significantly associated with anxiety. CONCLUSIONS: Among multiple factors typically associated with neurodegeneration, cognitive dysfunction stands out as a key factor associated with anxiety severity in LLD which has implications for cognitive and psychiatric interventions.

Water, Water Everywhere, but Every Drop Unique: Challenges in the Science to Understand the Role of Contaminants of Emerging Concern in the Management of Drinking Water Supplies.

The protection and management of water resources continues to be challenged by multiple and ongoing factors such as shifts in demographic, social, economic, and public health requirements. Physical limitations placed on access to potable supplies include natural and human-caused factors such as aquifer depletion, aging infrastructure, saltwater intrusion, floods, and drought. These factors, although varying in magnitude, spatial extent, and timing, can exacerbate the potential for contaminants of concern (CECs) to be present in sources of drinking water, infrastructure, premise plumbing and associated tap water. This monograph examines how current and emerging scientific efforts and technologies increase our understanding of the range of CECs and drinking water issues facing current and future populations. It is not intended to be read in one sitting, but is instead a starting point for scientists wanting to learn more about the issues surrounding CECs. This text discusses the topical evolution CECs over time (Section 1), improvements in measuring chemical and microbial CECs, through both analysis of concentration and toxicity (Section 2) and modeling CEC exposure and fate (Section 3), forms of treatment effective at removing chemical and microbial CECs (Section 4), and potential for human health impacts from exposure to CECs (Section 5). The paper concludes with how changes to water quantity, both scarcity and surpluses, could affect water quality (Section 6). Taken together, these sections document the past 25 years of CEC research and the regulatory response to these contaminants, the current work to identify and monitor CECs and mitigate exposure, and the challenges facing the future.

Functional NADPH oxidase 2 in T cells amplifies salt-sensitive hypertension and associated renal damage.

Infiltrating T cells in the kidney amplify salt-sensitive (SS) hypertension and renal damage, but the mechanisms are not known. Genetic deletion of T cells (SSCD247-/-) or of the p67phox subunit of NADPH oxidase 2 (NOX2; SSp67phox-/-) attenuates SS hypertension in the Dahl SS rat. We hypothesized that reactive oxygen species produced by NOX2 in T cells drive the SS phenotype and renal damage. T cells were reconstituted by adoptively transferring splenocytes (∼10 million) from the Dahl SS (SS→CD247) rat, the SSp67phox-/- rat (p67phox→CD247), or only PBS (PBS→CD247) into the SSCD247-/- rat on postnatal day 5. Animals were instrumented with radiotelemeters and studied at 8 wk of age. There were no detectable differences in mean arterial pressure (MAP) or albuminuria between groups when rats were maintained on a low-salt (0.4% NaCl) diet. After 21 days of high-salt diet (4.0% NaCl), MAP and albuminuria were significantly greater in SS→CD247 rats compared with p67phox→CD247 and PBS→CD247 rats. Interestingly, there was no difference between p67phox→CD247 and PBS→CD247 rats in albuminuria or MAP after 21 days. The lack of CD3+ cells in PBS→CD247 rats and the presence of CD3+ cells in rats that received the T cell transfer demonstrated the effectiveness of the adoptive transfer. No differences in the number of CD3+, CD4+, or CD8+ cells were observed in the kidneys of SS→CD247 and p67phox→CD247 rats. These results indicate that reactive oxygen species produced by NOX2 in T cells participates in the amplification of SS hypertension and renal damage.NEW & NOTEWORTHY Our current work used the adoptive transfer of T cells that lack functional NADPH oxidase 2 into a genetically T cell-deficient Dahl salt-sensitive (SS) rat model. The results demonstrated that reactive oxygen species produced by NADPH oxidase 2 in T cells participate in the amplification of SS hypertension and associated renal damage and identifies a potential mechanism that exacerbates the salt-sensitive phenotype.

Renal histaminergic system and acute effects of histamine receptor 2 blockade on renal damage in the Dahl salt-sensitive rat.

Histamine is involved in the regulation of immune response, vasodilation, neurotransmission, and gastric acid secretion. Although elevated histamine levels and increased expression of histamine metabolizing enzymes have been reported in renal disease, there is a gap in knowledge regarding the mechanisms of histamine-related pathways in the kidney. We report here that all four histamine receptors as well as enzymes responsible for the metabolism of histamine are expressed in human and rat kidney tissues. In this study, we hypothesized that the histaminergic system plays a role in salt-induced kidney damage in the Dahl salt-sensitive (DSS) rat, a model characterized with inflammation-driven renal lesions. To induce renal damage related to salt sensitivity, DSS rats were challenged with 21 days of a high-salt diet (4% NaCl); normal-salt diet (0.4% NaCl)-fed rats were used as a control. We observed lower histamine decarboxylase and higher histamine N-methyltransferase levels in high-salt diet-fed rats, indicative of a shift in histaminergic tone; metabolomics showed higher histamine and histidine levels in the kidneys of high-salt diet-fed rats, whereas plasma levels for both compounds were lower. Acute systemic inhibition of histamine receptor 2 in the DSS rat revealed that it lowered vasopressin receptor 2 in the kidney. In summary, we established here the existence of the local histaminergic system, revealed a shift in the renal histamine balance during salt-induced kidney damage, and provided evidence that blockage of histamine receptor 2 in the DSS rat affects water balance and urine concentrating mechanisms.NEW & NOTEWORTHY Histamine is a nitrogenous compound crucial for the inflammatory response. The knowledge regarding the renal effects of histamine is very limited. We showed that renal epithelia exhibit expression of the components of the histaminergic system. Furthermore, we revealed that there was a shift in the histaminergic tone in salt-sensitive rats when they were challenged with a high-salt diet. These data support the notion that histamine plays a role in renal epithelial physiological and pathophysiological functions.

Association of Major Depressive Disorder with remotely administered measures of cognition and subjective report of cognitive difficulties across the adult age spectrum.

BACKGROUND: Major depressive disorder (MDD) has increasing prevalence with age. Both objective measures of cognitive dysfunction and subjective report of cognitive difficulties related to MDD are often thought to worsen with increasing age. However, few studies have directly evaluated these characteristics across the adult lifespan. METHODS: Participants included 23,594 adults completing objective and subjective measures of cognition on an online research registry. Linear regression including interactions of age group with depression was used to evaluate the association of self-reported MDD with measures of cognition in three age groups: 21-40 years; 41-60 years; 61+ years. RESULTS: MDD (n = 2127) demonstrated poorer objective cognitive performance and greater subjective ratings of cognitive difficulties across all domains assessed compared to non-depressed individuals (ND; n = 21,467). Significant interactions of age group and MDD status with objective and subjective measures of cognition were observed for both middle age and older adults when compared to young adults but few significant differences between middle-aged and older adults were evident. LIMITATIONS: This study relied on self-report of MDD diagnosis, utilized remotely administered and unsupervised measures of cognition, and the sample was not diverse. CONCLUSIONS: The magnitude of association between MDD and cognitive correlates appears to plateau in middle age. Our results suggest that increased rates of dementia are not due to greater cognitive consequence of MDD in older adults and that age effects, and not greater effects of depression, may lead to increased diagnosis of MDD based on subjective report of cognitive symptoms.

Freshwater Environmental Risk Assessment of Down-the-Drain Octinoxate Emissions in the United States.

Organic ultraviolet (UV) filters are used in a variety of cosmetic and personal care products (CPCPs), including sunscreens, due to their ability to absorb solar radiation. These UV filters can be washed down the drain through bathing, cleansing, or the laundering of clothing, therefore UV filters can enter the freshwater environment via wastewater treatment plant effluent, and so a freshwater risk assessment is necessary to establish the environmentally safe use of these important CPCP ingredients. In the present study, an environmental safety assessment for a UV filter of regulatory concern, octinoxate, was conducted. An established risk assessment framework designed specifically for CPCPs released to the freshwater environment in the United States was used for the assessment. A distribution of predicted environmental concentrations (PECs) representative of conditions across the region was calculated using the spatially resolved probabilistic exposure model iSTREEM. A review of available hazard data was conducted to derive a predicted no-effect concentration (PNEC). The safety assessment was conducted by comparing the PEC distribution to the PNEC. A substantial margin of safety was found between the 90th percentile PEC, which is representative of the reasonable worst-case environmental exposure, and the PNEC. Owing to this finding of negligible risk, further refinement of the risk assessment through the generation of experimental data or refinement of conservative assumptions is not prioritized. These results are critical for demonstrating the environmental safety of UV filters in the US freshwater environment and will help guide future work. Environ Toxicol Chem 2022;41:3116-3124. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Impact of bedding on Dahl salt-sensitive hypertension and renal damage.

Salt-sensitive hypertension, increases in blood pressure in response to increased salt intake, is associated with an increased risk of morbidity, mortality, and end-organ damage compared with salt-resistant hypertension. The Dahl salt-sensitive (SS) rat mimics the phenotypic characteristics observed in human hypertension when rats are challenged with a high-salt diet. Our previous work demonstrated that environmental factors, such as dietary protein, alter the severity of salt sensitivity in Dahl SS rats and should be an important consideration in experimental design. The present study investigated how the bedding on which animals were maintained (wood vs. corncob) could impact the SS phenotype in the Dahl SS rat. Animals that were maintained on corncob bedding exhibited a significant attenuation in blood pressure and renal end-organ damage in response to a high-salt diet compared with animals maintained on wood bedding. This attenuation was associated with an improvement in renal function and reduction in immune cell infiltration into the kidneys of Dahl SS rats maintained on corncob bedding. These results indicate that the type of bedding impacts the SS phenotype in the Dahl SS rat and that the bedding used in experiments can be a confounding factor to consider during data interpretation and experimental design.NEW & NOTEWORTHY Results from our present study demonstrate the profound effect of animal bedding on the severity of salt-sensitive hypertension, renal damage, and inflammation in Dahl salt-sensitive rats. This study highlights the important consideration that should be given to environmental factors, namely, the type of bedding in animal facilities, in experimental design and data interpretation.

Do You Know How to Assess Risks Posed by Over-the-Counter Vitamin A Supplements?

Dietary supplements are regulated as foods by the US Food and Drug Administration (FDA) and, despite their potentially harmful effects, are not subject to labeling rules that apply to prescription medications. This commentary responds to a case about vitamin A supplement safety. The commentary compares regulation of vitamin A-derivative prescription medications, such as isotretinoin, to regulation of high-dose vitamin A supplements, illuminating both products' potential for causing birth defects. Label analysis is key to educating patients about risks of vitamin A-containing supplements. The commentary also suggests the need for more FDA oversight of the dietary supplement industry.

Impact of Continuous Renal Replacement Therapy on Bivalirudin Dosing in Pediatric Extracorporeal Membrane Oxygenation.

There is an increasing interest in the use of bivalirudin for pediatric extracorporeal membrane oxygenation (ECMO) anticoagulation. However, dosing is not well described in those requiring continuous renal replacement therapy (CRRT). We aimed to determine whether CRRT affects bivalirudin dosing in pediatric ECMO patients. Children ≤18 years of age placed on ECMO and anticoagulated with bivalirudin for ≥24 hours from January 2019 to May 2020 were included. Bivalirudin doses were collected for 144 hours from initiation of bivalirudin or CRRT. Analysis was performed to determine whether CRRT, age, or weight affected bivalirudin dosing. Thirty-one children were included, and 11 (35%) required concomitant CRRT. There was no difference in age (median 9.1 versus 3.2 months, p = 0.15) or days on ECMO (median 11 versus 9, p = 0.7) between those who did or did not receive CRRT. The mean bivalirudin dosing was similar in patients who did or did not require CRRT (median and IQR: 0.13 mg/kg/hour [0.08-0.26] versus 0.15 mg/kg/hour [0.11-0.22], respectively, p = 0.13). Younger age ( p < 0.001) and lower weight ( p < 0.001) were associated with higher bivalirudin dosing. In our study, bivalirudin dosing did not differ if the patient required CRRT while on ECMO.

Acne Supplements Sold Online.

INTRODUCTION: As no centralized database of acne supplements is available, we aimed to provide an overview of these products, with a focus on safety. OBJECTIVES: The objectives of this study were to document the number, formulation, contents, and marketing strategies utilized by acne supplements sold online. METHODS: An online search was conducted between March and May 2020. Products were included in the study if they used the terms: "whitehead", "blackhead", or "acne". Data were extracted from the website, box, and Supplement Facts label. RESULTS: 49 products were identified, which contained 146 unique ingredients. These included vitamins, minerals, food extracts, botanical extracts, amino acids, animal products, and distinct microbial strains. Few (4.1%) products were tested by third parties. CONCLUSIONS: This survey of acne supplements available online raised concerns regarding lack of warning labels, teratogenicity, exceedingly large levels of vitamins and minerals, and lack of third-party testing. Given the limited regulation and oversight of dietary supplements, it is imperative that physicians educate patients on the potential risks of these products.

Assembled and annotated 26.5 Gbp coast redwood genome: a resource for estimating evolutionary adaptive potential and investigating hexaploid origin.

Sequencing, assembly, and annotation of the 26.5 Gbp hexaploid genome of coast redwood (Sequoia sempervirens) was completed leading toward discovery of genes related to climate adaptation and investigation of the origin of the hexaploid genome. Deep-coverage short-read Illumina sequencing data from haploid tissue from a single seed were combined with long-read Oxford Nanopore Technologies sequencing data from diploid needle tissue to create an initial assembly, which was then scaffolded using proximity ligation data to produce a highly contiguous final assembly, SESE 2.1, with a scaffold N50 size of 44.9 Mbp. The assembly included several scaffolds that span entire chromosome arms, confirmed by the presence of telomere and centromere sequences on the ends of the scaffolds. The structural annotation produced 118,906 genes with 113 containing introns that exceed 500 Kbp in length and one reaching 2 Mb. Nearly 19 Gbp of the genome represented repetitive content with the vast majority characterized as long terminal repeats, with a 2.9:1 ratio of Copia to Gypsy elements that may aid in gene expression control. Comparison of coast redwood to other conifers revealed species-specific expansions for a plethora of abiotic and biotic stress response genes, including those involved in fungal disease resistance, detoxification, and physical injury/structural remodeling and others supporting flavonoid biosynthesis. Analysis of multiple genes that exist in triplicate in coast redwood but only once in its diploid relative, giant sequoia, supports a previous hypothesis that the hexaploidy is the result of autopolyploidy rather than any hybridizations with separate but closely related conifer species.

Pediatric BehÒ«et disease: Update in diagnosis and management.

BehÒ«et disease is a multisystem inflammatory disease and variable vessel vasculitis involving primarily the oral and genital mucosa, skin, and eyes. Diagnosis is challenging due to the lack of a specific diagnostic test and overlap with other autoinflammatory diseases. Treatment of pediatric BehÒ«et disease aims to reduce inflammation and prevent future flares. The goal of this review is to provide guidance on the diagnostic workup and multidisciplinary approach of pediatric BehÒ«et disease and review evidence-based treatment strategies for patients with refractory mucocutaneous manifestations.

Coral Ecotoxicological Data Evaluation for the Environmental Safety Assessment of Ultraviolet Filters.

There is growing interest in the environmental safety of ultraviolet (UV) filters found in cosmetic and personal care products (CPCPs). The CPCP industry is assessing appropriate environmental risk assessment (ERA) methods to conduct robust environmental safety assessments for these ingredients. Relevant and reliable data are needed for ERA, particularly when the assessment is supporting regulatory decision-making. In the present study, we apply a data evaluation approach to incorporate nonstandard toxicity data into the ERA process through an expanded range of reliability scores over commonly used approaches (e.g., Klimisch scores). The method employs an upfront screening followed by a data quality assessment based largely on the Criteria for Reporting and Evaluating Ecotoxicity Data (CRED) approach. The method was applied in a coral case study in which UV filter toxicity data was evaluated to identify data points potentially suitable for higher tier and/or regulatory ERA. This is an optimal case study because there are no standard coral toxicity test methods, and UV filter bans are being enacted based on findings reported in the current peer-reviewed data set. Eight studies comprising nine assays were identified; four of the assays did not pass the initial screening assessment. None of the remaining five assays received a high enough reliability score (Rn ) to be considered of decision-making quality (i.e., R1 or R2). Four assays were suitable for a preliminary ERA (i.e., R3 or R4), and one assay was not reliable (i.e., R6). These results highlight a need for higher quality coral toxicity studies, potentially through the development of standard test protocols, to generate reliable toxicity endpoints. These data can then be used for ERA to inform environmental protection and sustainability decision-making. Environ Toxicol Chem 2021;40:3441-3464. © 2021 Personal Care Products Council. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Risk of Birth Defects From Vitamin A "Acne Supplements" Sold Online.

BACKGROUND: Dietary supplements are popular among US consumers and claim to address a variety of conditions, including acne. Acne supplements containing vitamin A are of particular interest, due to the potentially teratogenic effects of vitamin A doses over 10,000 IU. OBJECTIVE: This study examined dosage, pregnancy risks, and labeling of vitamin A-containing acne supplements available online. METHODS: An Internet search of acne supplements sold online was conducted between March and May 2020. Supplement labels and websites were analyzed for vitamin A content and pregnancy warnings, and then divided into categories based on dosage and teratogenic risk. RESULTS: A total of 49 acne supplements was found, and of these 26 (53%) contain vitamin A. Three supplements are likely teratogenic, 4 contain vitamin A doses exceeding the daily level of intake that meets the nutritional needs of most people, and 15 have an unknown teratogenic risk. Among the 6 supplements with over 10,000 IU vitamin A, 2 have no pregnancy warning at all, including the supplement with the highest vitamin A dose found in this study. CONCLUSIONS: Dietary supplements are not subject to the same stringent regulations as drugs, and as such, consumers may be unaware of pregnancy risks. Furthermore, FDA requirements on labeling of vitamin A supplements may lead to consumer confusion regarding dosage. As such, we encourage stricter labeling requirements for vitamin A-containing supplements, including pregnancy warnings for high-dose supplements and clearer dosage labeling.

National scale down-the-drain environmental risk assessment of oxybenzone in the United States.

Organic ultraviolet (UV) filters are used in cosmetic and personal care products (CPCPs) and over-the-counter (OTC) sunscreens, due to their ability to absorb solar radiation. When OTC and CPCP ingredients are washed down the drain, they can then enter freshwaters that receive wastewater treatment plant effluents. This paper presents a freshwater environmental safety assessment of a key UV filter, oxybenzone, used in OTC sunscreens and CPCPs in the United States. Exposure was characterized using iSTREEM® , a spatially resolved aquatic exposure model developed for chemicals disposed of down the drain. iSTREEM® provides a comprehensive exposure assessment of oxybenzone concentrations in United States receiving waters through predicted environmental concentration (PEC) distributions representative of conditions across the region. A review of available hazard data was used to derive a predicted no-effect concentration (PNEC) using aquatic toxicity data and assessment factors. A safety assessment was conducted by comparing the PEC distribution with the PNEC. The results indicate that oxybenzone is of low concern and there is a significant margin of safety as the 90th percentile PEC is two orders of magnitude below the PNEC. These results are instrumental in demonstrating the environmental safety of key organic UV filters in the U.S. freshwater environment and will help prioritize future work. Integr Environ Assess Manag 2021;17:951-960. © 2021 Personal Care Products Council. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Physical and psychological impacts of handwashing and personal protective equipment usage in the COVID-19 pandemic: A UK based cross-sectional analysis of healthcare workers.

The COVID-19 pandemic has necessitated intensified handwashing and mask usage for healthcare staff. A retrospective cross-sectional study was performed primarily to investigate the potential skin damage and secondary impacts on wellbeing of staff resulting from these practices. Additionally the availability and uptake of occupational health services and moisturisers in the work place was also assessed. The survey was distributed to NHS staff between April and May 2020 and asked questions regarding skin damage, impact on wellbeing and availability and utilisation of occupational health input and moisturisers. Of the 211 responders, 167 washed their hands more than ten times per shift. Three quarters of these reported cracks or fissures in one or more regions of their hands, most frequently to the back of the hands or web spaces. Amongst the 157 staff who wore FFP3 masks, redness of the nasal area was most frequently reported with 8% reporting facial blisters. 36% of staff reported a substantial impact on one or more aspects of their wellbeing. Only 7% of respondents had received specialist advice, yet a quarter (26%) had made or anticipated needing changes to their occupational duties. The majority (63%) felt they required no specialist input, despite 38% of these reporting a substantial detriment to their wellbeing. Handwashing and face mask use is resulting in skin damage amongst healthcare workers during the COVID-19 pandemic, with associated detriment to wellbeing. Healthcare services need to take action to implement measures to prevent, reduce and treat damage including promotion of available specialist support.

A Critical Review of Organic Ultraviolet Filter Exposure, Hazard, and Risk to Corals.

There has been a rapid increase in public, political, and scientific interest regarding the impact of organic ultraviolet (UV) filters to coral reefs. Such filters are found in sunscreens and other consumer products and enter the aquatic environment via direct (i.e., recreational activities, effluents) or indirect (i.e., land runoff) pathways. This review summarizes the current state of the science regarding the concentration of organic UV filters in seawater and sediment near coral reef ecosystems and in coral tissues, toxicological data from early and adult life stages of coral species, and preliminary environmental risk characterizations. Up to 14 different organic UV filters in seawater near coral reefs have been reported across 12 studies, with the majority of concentrations in the nanograms per liter range. Nine papers report toxicological findings from no response to a variety of biological effects occurring in the micrograms per liter to milligrams per liter range, in part given the wide variations in experimental design and coral species and/or life stage used. This review presents key findings; scientific data gaps; flaws in assumptions, practice, and inference; and a number of recommendations for future studies to assess the environmental risk of organic UV filters to coral reef ecosystems. Environ Toxicol Chem 2021;40:967-988. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Is anticoagulation with bivalirudin comparable to heparin for pediatric extracorporeal life support? Results from a high-volume center.

There is a paucity of data regarding the use of direct thrombin inhibitors such as bivalirudin for children on extracorporeal life support (ECLS). We sought to compare the outcomes of children on ECLS anticoagulated with bivalirudin versus heparin. Patients transitioned from heparin to bivalirudin were treated as a separate group. A single-institution, retrospective review of all consecutive children (neonate to 18 years) placed on ECLS in the cardiac or pediatric intensive care units was performed (June 2018-December 2019). Data collected included demographics, anticoagulation strategy, number of circuit interventions, blood product use on ECLS, survival to decannulation, and survival to discharge. Fifty-four children were placed on ECLS for a total of 56 runs. Demographics and venovenous versus venoarterial ECLS were similar. The bivalirudin group had longer median duration of support compared to the heparin group--11.0 days [IQR 6.2, 23.1] versus 3.3 days [2.1, 6.2], P < .001. Patients switched from heparin to bivalirudin had a similar duration of support (10.3 days [8.3, 18.3]) as those on bilvalirudin alone. However, there was no difference in red blood cell, fresh frozen plasma, or platelet transfusions. There was no difference in the number of circuit interventions, survival to decannulation or discharge. The freedom to first circuit intervention was longer with bivalirudin compared to heparin. Our data suggest that even with longer pediatric ECLS runs on bivalirudin, there were no differences in the outcomes between the heparin and bivalirudin groups, with longer freedom from first circuit intervention with bivalirudin. While this is the largest reported series comparing children on ECLS anticoagulated with heparin versus bivalirudin, larger studies are needed to determine the optimal anticoagulation strategy for this diverse and complicated group of children.

The relationship of frailty and disability with suicidal ideation in late life depression.

OBJECTIVES: Frailty and disability are commonly found in Late Life Depression (LLD) and have been associated with increased depression severity, health comorbidities and mortality. Additionally, physical frailty has been associated with suicide in later life, independent of presence of a mood disorder. The objective of our study was to assess the associations of physical frailty and functional disability with suicidal ideation, controlling for depression severity and demographic factors, in an older depressed sample. METHODS: This study used data from community-dwelling older adults with major depression. Eligible participants were ≥ 65 years old, completed measures of depression symptom severity (Hamilton Depression Rating Scale-24 item; HDRS-24), current suicidal ideation (Geriatric Suicide Ideation Scale; GSIS), and physical frailty/functional capacity measures. RESULTS: Participants were 88 older adults with a mean age of 71.5 (SD = 6.0) and 66% of the sample was female. Poorer performance on frailty measures of gait speed (B = .239, p = .003) and muscle weakness (B = -.218, p = .01) were significantly associated with higher levels of suicidal ideation, independent of depression severity and demographic factors. Functional disability was also significantly related to suicide ideation, specifically impairment in financial capacity (B = -.290, p = .008), social interaction (B = .408, p < .001), and communication skills (B = .373, p = .001). CONCLUSION: Our findings show that, in LLD, frailty and functional disability are significantly associated with higher levels of suicide ideation, independent of depression symptom severity.