Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial.

INTRODUCTION: Trials of effectiveness of treatment options for depression in dementia are an important priority. METHODS: Randomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease. RESULTS: Three hundred thirty-six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized to adapted PATH or treatment as usual. Mean age 77.0 years, 39.0% males, mean Mini-Mental State Examination 21.6, mean CSDD 12.9. For primary outcome (CSDD at 6 months), no statistically significant benefit with adapted PATH on the CSDD (6 months: -0.58; 95% CI -1.71 to 0.54). The CSDD at 3 months showed a small benefit with adapted PATH (-1.38; 95% CI -2.54 to -0.21) as did the EQ-5D (-4.97; 95% CI -9.46 to -0.48). DISCUSSION: An eight-session course of adapted PATH plus two booster sessions administered within NHS dementia services was not effective treatment for depression in people with mild and moderate dementia. Future studies should examine the effect of more intensive and longer-term therapy.

Fauna Associated with American Alligator (Alligator mississippiensis) Nests in Coastal South Carolina, USA.

Crocodilians are considered to be "ecosystem engineers" because their modification of habitats provides opportunities for feeding, drinking, breeding, and other vital life activities to a wide variety of other animals. One such habitat modification is the construction of nest mounds during the breeding season by most crocodilian species, including American alligators (Alligator mississippiensis). While many reports exist describing wildlife associated with alligator nests, no studies have quantified faunal associates and their corresponding behaviors while visiting nests. To address this data gap, we used automated game cameras to monitor wildlife and their behaviors at alligator nests during the egg incubation period (June-September) in coastal South Carolina, USA (2016-2021). We documented a total of 81 species (79 vertebrates and 2 invertebrates) at 78 alligator nests representing six taxonomic groups, including 48 birds (59.2%), 9 mammals (11.1%), 19 reptiles (23.4%), 3 amphibians (3.7%), 1 malacostracan (1.2%), and 1 insect (1.2%). Collectively, faunal associates primarily used alligator nests for feeding/foraging (51.8%), traveling (29.3%), and loafing (19.9%) and to a much lesser extent basking, burrowing/shelter, breeding, and nesting. However, trends in alligator nest use varied among faunal associate groups (birds, mammals, reptiles, amphibians, etc.), subgroups (e.g., passerines, raptors, wading birds, and waterfowl), and species. Several novel behaviors by some nest associates were also noted during the study, including the first observations of Virginia oppossum (Didelphis virginiana) opening and predating nests, bobcat (Lynx rufus) consuming alligator hatchlings, and Carolina wren (Thryothorus ludovicianus) feeding on the contents of a recently predated alligator egg. The results of this study indicate that a diverse assemblage of vertebrates (and some invertebrates) use alligator nest sites in coastal South Carolina for a variety of life activities during the egg incubation period, and the proportion of the behaviors exhibited varies among animal groups and species. This study provides a first step for investigations regarding the net impacts of alligator nest-faunal associate interactions and ultimately the greater ecological role of alligators and other crocodilians.

Relationships between maternally-transferred mercury and hatchling development, behavior, and survival in the American alligator (Alligator mississippiensis).

Mercury is a toxic and pervasive environmental contaminant that can be transferred from mother to offspring during development. Consequences of maternally-transferred mercury have been observed in vertebrate taxa, including reduced clutch viability, reduced offspring size, and behavioral alterations. These sublethal effects have been assumed to decrease survivorship, though this is seldom assessed. Here, we examined how maternally-transferred mercury interacts with incubation temperature to influence reproductive success, offspring behavior, and subsequent survival in the American alligator (Alligator mississippiensis). We collected nine clutches of eggs from a mercury contaminated reservoir on the Savannah River Site, South Carolina, and incubated eggs at either female- or male-promoting temperatures. Clutch-averaged mercury in egg yolk was high relative to other studies in crocodilians and ranged from 0.248 to 0.554 ppm compared to 0.018-0.052 ppm at a site with low levels of mercury contamination; mercury levels in hatchling blood ranged from 0.090 to 0.490 ppm (x¯ = 0.240 ppm, n = 158). We found few, mostly negligible correlations between life history traits and mercury but noted a positive relationship with egg mass, possibly mediated by correlated maternal effects such as resource provisioning. Incubation temperature exerted strong effects on hatchling phenotypes, with warmer, male-promoting temperatures producing larger and bolder hatchlings. Presumptive females, produced from cooler incubation temperatures, spent more time in warm areas during behavior trials. Hatchlings were released 10-15 days post-hatch and surveyed over eight months to assess survival. Survivorship was positively correlated with hatchling size and negatively correlated with proportional time spent in warm areas. Presumptive females had much lower survival, and overall survivorship for the eight-month period was 0.185-0.208, depending on the modelling approach. Our study suggests that, within the range of concentrations we observed, incubation temperature has a stronger effect on offspring behavior and survival than maternally-transferred mercury pollution in American alligators.

Quantifying Circulating IgY Antibody Responses against Select Opportunistic Bacterial Pathogens and Correlations with Body Condition Factors in Wild American Alligators, Alligator mississippiensis.

Little is known about the disease ecology of American alligators (Alligator mississippiensis), and especially how they respond immunologically to emerging infectious diseases and zoonotic pathogens. In this study, we examined serum samples collected from wild alligators in Florida (2010-2011) and South Carolina (2011-2012, 2014-2017) for antibody responses to multiple bacteria. Immunoglobulin Y (IgY) was purified from serum to generate a mouse monoclonal antibody (mAb AMY-9) specific to the IgY heavy chain. An indirect ELISA was then developed for quantifying antibody responses against whole cell Escherichia coli,Vibrio parahaemolyticus, Vibrio vulnificus, Mycobacterium fortuitum, Erysipelothrix rhusiopthiae, and Streptococcus agalactiae. In Florida samples the primary differences in antibody levels were between January-March and late spring through summer and early fall (May-October), most likely reflecting seasonal influences in immune responses. Of note, differences over the months in antibody responses were confined to M. fortuitum, E. rhusiopthiae, V. vulnificus, and E. coli. Robust antibody responses in SC samples were observed in 2011, 2014, and 2015 against each bacterium except E. coli. All antibody responses were low in 2016 and 2017. Some of the highest antibody responses were against V. parahaemolyticus, M. fortuitum, and E. rhusiopthiae. One SC alligator estimated to be 70+ years old exhibited the highest measured antibody response against V. parahaemolyticus and M. fortuitum. By combining data from both sites, we show a clear correlation between body-mass-indices (BMI) and antibody titers in all six of the bacteria examined. Our study provides a critical antibody reagent and a proof-of-concept approach for studying the disease ecology of alligators in both the wild and in captivity.

Evidence of determinate growth in an American alligator (Alligator mississippiensis) based on long-term recapture and osteohistological confirmation.

Despite the general perception that crocodilians exhibit indeterminate growth, recent long-term field studies and laboratory investigations have independently suggested that growth in these animals is determinate. In this study, we had the unique opportunity to examine skeletal growth in a wild adult American alligator (Alligator mississippiensis) based on change in body length measurements (snout-vent length) in the field and confirm these findings using osteohistological analyses (presence/absence of an external fundamental system [EFS]) of long bones. The alligator was captured and measured five times over 7 years and exhibited no discernable growth during that period, suggesting skeletal maturity had been attained at or prior to its first capture. Our field assessment of determinate growth in this alligator was osteohistologically confirmed by the presence of an EFS in the animal's humerus, femur, tibia, and fibula. To our knowledge, this study is the first to report determinate growth in a wild crocodilian using both field and laboratory methods, providing further evidence of this growth pattern in crocodilians.

Acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder: the FACTOID feasibility study.

BACKGROUND: Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking. OBJECTIVES: To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters. DESIGN: Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention. SETTING: Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community. PARTICIPANTS: Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder. INTERVENTION: Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants' homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter. MAIN OUTCOME MEASURES: The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life. RESULTS: Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility. LIMITATIONS: Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London. CONCLUSIONS: There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12268776. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 54. See the NIHR Journals Library website for further project information.

Generalised anxiety disorder, characterised by a tendency to worry, is the most common anxiety disorder among older people. Those with this condition may experience other difficulties, including increased distress and disability, poorer coping and reduced quality of life. Medication and talking therapy are usually offered as forms of treatment, but many do not find them helpful. Guidance is lacking on how to help older people manage generalised anxiety disorder when it does not respond to such treatments. We developed a 16-session intervention specifically for older people with treatment-resistant generalised anxiety disorder. This was based on acceptance and commitment therapy: a form of talking therapy that helps people to learn how to best live with distressing experiences while still doing things that really matter to them. It may be particularly suited to older people because many older people experience difficulties with chronic ill health and other problems that cannot be easily improved with conventional talking therapies. We developed our intervention by asking 15 older people about their experiences of treatment-resistant generalised anxiety disorder and treatments they have received for it, as well as what might help or hinder their engagement with talking therapy. We combined their guidance with advice from 36 clinicians to ensure that our intervention was tailored to the needs of this population. We then asked the same 15 older people, our Service User Advisory Group and academic clinicians about how we could optimise our intervention. We also conducted an online survey of service users and clinicians to clarify what care older people with generalised anxiety disorder are typically offered and receive. We tested how acceptable our intervention was to 37 older people with treatment-resistant generalised anxiety disorder, and how feasible it was to deliver within the NHS. We found evidence that it was acceptable to participants, that it could be delivered within the NHS and that its value for money could be tested in a larger study. We also found evidence suggestive of improvements in anxiety, depression and coping. There were some limitations of our study. However, overall, our results suggest that we should conduct a larger study to find out whether or not our intervention is helpful for older people with treatment-resistant generalised anxiety disorder.

Incubation Temperature and Maternal Resource Provisioning, but Not Contaminant Exposure, Shape Hatchling Phenotypes in a Species with Temperature-Dependent Sex Determination.

AbstractThe environment experienced during embryonic development is a rich source of phenotypic variation, as environmental signals have the potential to both inform adaptive plastic responses and disrupt normal developmental programs. Environment-by-embryo interactions are particularly consequential for species with temperature-dependent sex determination, a mode of sex determination common in non-avian reptiles and fish, in which thermal cues during a discrete period of development drive the formation of either an ovary or a testis. Here we examine the impact of thermal variation during incubation in combination with developmental exposure to a common endocrine-disrupting contaminant on fitness-related hatchling traits in the American alligator (Alligator mississippiensis), a species with temperature-dependent sex determination. Using a factorial design, we exposed field-collected eggs to five thermal profiles (three constant temperatures, two fluctuating temperatures) and two environmentally relevant doses of the pesticide metabolite dichlorodiphenyldichloroethylene; and we quantified incubation duration, sex ratios, hatchling morphometric traits, and growth (9-10 days post-hatch). Whereas dichlorodiphenyldichloroethylene exposure did not generally affect hatchling traits, constant and fluctuating temperatures produced diverse phenotypic effects. Thermal fluctuations led to subtle changes in incubation duration and produced shorter hatchlings with smaller heads when compared to the constant temperature control. Warmer, male-promoting incubation temperatures resulted in larger hatchlings with more residual yolk reserves when compared to cooler, female-promoting temperatures. Together, these findings advance our understanding of how complex environmental factors interact with developing organisms to generate phenotypic variation and raise questions regarding the mechanisms connecting variable thermal conditions to responses in hatchling traits and their evolutionary implications for temperature-dependent sex determination.

Acceptance and commitment therapy for late-life treatment-resistant generalised anxiety disorder: a feasibility study.

BACKGROUND: Generalised anxiety disorder (GAD) is the most common anxiety disorder in older people. First-line management includes pharmacological and psychological therapies, but many do not find these effective or acceptable. Little is known about how to manage treatment-resistant generalised anxiety disorder (TR-GAD) in older people. OBJECTIVES: To examine the acceptability, feasibility and preliminary estimates of the effectiveness of acceptance and commitment therapy (ACT) for older people with TR-GAD. PARTICIPANTS: People aged ≥65 years with TR-GAD (defined as not responding to GAD treatment, tolerate it or refused treatment) recruited from primary and secondary care services and the community. INTERVENTION: Participants received up to 16 one-to-one sessions of ACT, developed specifically for older people with TR-GAD, in addition to usual care. MEASUREMENTS: Co-primary outcomes were feasibility (defined as recruitment of ≥32 participants and retention of ≥60% at follow-up) and acceptability (defined as participants attending ≥10 sessions and scoring ≥21/30 on the satisfaction with therapy subscale). Secondary outcomes included measures of anxiety, worry, depression and psychological flexibility (assessed at 0 and 20 weeks). RESULTS: Thirty-seven participants were recruited, 30 (81%) were retained and 26 (70%) attended ≥10 sessions. A total of 18/30 (60%) participants scored ≥21/30 on the satisfaction with therapy subscale. There was preliminary evidence suggesting that ACT may improve anxiety, depression and psychological flexibility. CONCLUSIONS: There was evidence of good feasibility and acceptability, although satisfaction with therapy scores suggested that further refinement of the intervention may be necessary. Results indicate that a larger-scale randomised controlled trial of ACT for TR-GAD is feasible and warranted.

Negative bias in interpretation and facial expression recognition in late life depression: A case control study.

OBJECTIVES: While cognitive bias in younger adults with depression has been extensively researched, there have been relatively few investigations of the presence of cognitive bias in late life depression (LLD). This exploratory study aimed to ascertain whether negative cognitive bias exists across a range of cognitive domains in participants with LLD. METHODS/DESIGN: Participants were 19 patients with LLD and 19 matched non-depressed older adults. Participants completed standardised tests to assess bias in facial expression recognition, attention, recall of adjectives and interpretation. RESULTS: LLD participants were slower to identify surprised faces, and more likely to create negative statements in the interpretation task. There was no evidence of negative bias in memory or attention, but participants with LLD performed more poorly on the recall task. CONCLUSIONS: This study provides new evidence of negative bias in interpretation in LLD, but the findings are not consistent with a global cognitive bias Further work is needed to investigate cognitive bias in LLD. It may be that interventions which target negative interpretation biases, such as cognitive bias modification, could be helpful in treating LLD.

18FDG PET-CT in sporadic Creutzfeldt-Jakob disease, correlated with MRI and histology.

We present a case of sporadic Creutzfeldt-Jakob disease with profoundly abnormal 18fluoro-deoxy-glucose positron emission tomography with computed tomography (FDG PET-CT) at an early stage, and correlate this with the clear findings at magnetic resonance imaging and also postmortem histology. Prion diseases are rare but important causes of cognitive impairment. The role of FDG PET-CT is discussed, along with other investigations such as electroencephalography and cerebro-spinal fluid analyses.

Spatial and temporal variation in nest temperatures forecasts sex ratio skews in a crocodilian with environmental sex determination.

Species displaying temperature-dependent sex determination (TSD) are especially vulnerable to the effects of a rapidly changing global climate due to their profound sensitivity to thermal cues during development. Predicting the consequences of climate change for these species, including skewed offspring sex ratios, depends on understanding how climatic factors interface with features of maternal nesting behaviour to shape the developmental environment. Here, we measure thermal profiles in 86 nests at two geographically distinct sites in the northern and southern regions of the American alligator's (Alligator mississippiensis) geographical range, and examine the influence of both climatic factors and maternally driven nest characteristics on nest temperature variation. Changes in daily maximum air temperatures drive annual trends in nest temperatures, while variation in individual nest temperatures is also related to local habitat factors and microclimate characteristics. Without any compensatory nesting behaviours, nest temperatures are projected to increase by 1.6-3.7°C by the year 2100, and these changes are predicted to have dramatic consequences for offspring sex ratios. Exact sex ratio outcomes vary widely depending on site and emission scenario as a function of the unique temperature-by-sex reaction norm exhibited by all crocodilians. By revealing the ecological drivers of nest temperature variation in the American alligator, this study provides important insights into the potential consequences of climate change for crocodilian species, many of which are already threatened by extinction.

Post-Transcriptional Mechanisms Respond Rapidly to Ecologically Relevant Thermal Fluctuations During Temperature-Dependent Sex Determination.

An organism's ability to integrate transient environmental cues experienced during development into molecular and physiological responses forms the basis for adaptive shifts in phenotypic trajectories. During temperature-dependent sex determination (TSD), thermal cues during discrete periods in development coordinate molecular changes that ultimately dictate sexual fate and contribute to patterns of inter- and intra-sexual variation. How these mechanisms interface with dynamic thermal environments in nature remain largely unknown. By deploying thermal loggers in wild nests of the American alligator (Alligator mississippiensis) over two consecutive breeding seasons, we observed that 80% of nests exhibit both male- and female-promoting thermal cues during the thermosensitive period, and of these nests, all exhibited both male- and female-promoting temperatures within the span of a single day. These observations raise a critical question-how are opposing environmental cues integrated into sexually dimorphic transcriptional programs across short temporal scales? To address this question, alligator embryos were exposed to fluctuating temperatures based on nest thermal profiles and sampled over the course of a daily thermal fluctuation. We examined the expression dynamics of upstream genes in the temperature-sensing pathway and find that post-transcriptional alternative splicing and transcript abundance of epigenetic modifier genes JARID2 and KDM6B respond rapidly to thermal fluctuations while transcriptional changes of downstream effector genes, SOX9 and DMRT1, occur on a delayed timescale. Our findings reveal how the basic mechanisms of TSD operate in an ecologically relevant context. We present a hypothetical hierarchical model based on our findings as well as previous studies, in which temperature-sensitive alternative splicing incrementally influences the epigenetic landscape to affect the transcriptional activity of key sex-determining genes.

Nonlinear patterns in mercury bioaccumulation in American alligators are a function of predicted age.

Mercury is a widespread, naturally occurring contaminant that biomagnifies in wetlands due to the methylation of this element by sulfate-reducing bacteria. Species that feed at the top trophic level within wetlands are predicted to have higher mercury loads compared to species feeding at lower trophic levels and are therefore often used for mercury biomonitoring. However, mechanisms for mercury bioaccumulation in sentinel species are often poorly understood, due to a lack of long-term studies or an inability to differentiate between confounding variables. We examined mercury bioaccumulation patterns in the whole blood of American alligators (Alligator mississippiensis) from a long-term mark-recapture study (1979-2017) in South Carolina, USA. Using a growth model and auxiliary information on predicted age at first capture, we differentiated between age- and size-related variation in mercury bioaccumulation, which are often confounded in alligators due to their determinate growth pattern. Contrary to predictions that the oldest or largest individuals were likely to have the highest mercury concentrations, our best-supported model indicated a peak in mercury concentration at 30-40 years of age, depending on the sex, and lower concentrations in the youngest and oldest animals. To evaluate the robustness of our findings, we re-analyzed data from a previously published study of mercury in alligators sampled at Merritt Island National Wildlife Refuge in Florida. Unlike the South Carolina data, the data from Florida contained minimal auxiliary information regarding age, yet the best supported model similarly indicated a peaked rather than increasing relationship between mercury and body size, a less-precise indicator of age. These findings highlight how long-term monitoring can differentiate between confounding variables (e.g., age and size) to better elucidate complex relationships between contaminant exposure and demographic factors in sentinel species.

Optimising the acceptability and feasibility of acceptance and commitment therapy for treatment-resistant generalised anxiety disorder in older adults.

BACKGROUND: generalised anxiety disorder (GAD) is common in later life with a prevalence of 3-12%. Many only partially respond to cognitive behavioural therapy or pharmacotherapy and can be classified as treatment resistant. These patients experience poor quality of life, and are at increased risk of comorbid depression, falls and loneliness. Acceptance and commitment therapy (ACT) is an emerging therapy, which may be particularly suited to this population, but has not been tailored to their needs. OBJECTIVES: to optimise the acceptability and feasibility of ACT for older adults with treatment-resistant GAD. DESIGN: a person-based approach to ground the adapted ACT intervention in the perspectives and lives of those who will use it. METHODS: first, we conducted qualitative interviews with 15 older adults with GAD and 36 healthcare professionals to develop guiding principles to inform the intervention. Second, we consulted service users and clinical experts and interviewed the same 15 older adults using 'think aloud' techniques to enhance its acceptability and feasibility. RESULTS: in Stage 1, older adults' concerns and needs were categorised in four themes: 'Expert in one's own condition', 'Deep seated coping strategies', 'Expert in therapy' and 'Support with implementation'. In Stage 2, implications for therapy were identified that included an early focus on values and ACT as a collaborative partnership, examining beliefs around 'self as worrier' and the role of avoidance, validating and accommodating individuals' knowledge and experience and compensating for age-related cognitive changes. DISCUSSION: Our systematic approach combined rigour and transparency to develop a therapeutic intervention tailored to the specific needs of older adults with treatment-resistant GAD.

The impact of maternally derived dioxins on embryonic development and hepatic AHR signaling in a long-lived apex predator.

Dioxins and related contaminants are highly pervasive in aquatic systems and elicit deleterious effects in exposed organisms. Because dioxins exhibit a proclivity to bioaccumulate, long-lived predatory species are particularly vulnerable to their persistence in the environment. We have previously reported elevated expression of CYP1A2, a biomarker of dioxin exposure, in American alligator embryos collected from the Tom Yawkey Wildlife Center (YWC). This coastal population inhabits a system with historical dioxin contamination associated with industrial activities. Herein, we utilize ecological attributes of the alligator to address the persistence of dioxins and furans in yolk and their potential to drive changes in hepatic function. Specifically, we assess variation in expression of AHR signaling components in embryos and its connection to contaminant levels in matched yolk samples. Compared to a reference population, TEQ levels and total penta-, hexa-, octa-substituted CDDs were elevated at YWC. Contrary to predictions, TEQ levels were not significantly related to hepatic AHR1B or CYP1A2 expression. However, a significant association was detected between expression of both factors and embryo:yolk mass ratios, wherein decreasing embryo mass was negatively associated with CYP1A2 but positively associated with AHR1B. These findings suggest that variation in embryonic metabolism and developmental progression likely influence AHR signaling and dioxin toxicity in alligators and potentially other oviparous species. While dioxin concentrations observed in alligators in this study are lower than historical values reported for other wildlife species inhabiting this system, they indicate the continued presence and possible long-term influence of these contaminants in a high trophic status species.

AHR and CYP1A expression link historical contamination events to modern day developmental effects in the American alligator.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that initiates a transcriptional pathway responsible for the expression of CYP1A subfamily members, key to the metabolism of xenobiotic compounds. Toxic planar halogenated aromatic hydrocarbons, including dioxin and PCBs, are capable of activating the AHR, and while dioxin and PCB inputs into the environment have been dramatically curbed following strict regulatory efforts in the United States, they persist in the environment and exposures remain relevant today. Little is known regarding the effects that long-term chronic exposures to dioxin or dioxin-like compounds might have on the development and subsequent health of offspring from exposed individuals, nor is much known regarding AHR expression in reptilians. Here, we characterize AHR and CYP1A gene expression in embryonic and juvenile specimen of a long-lived, apex predator, the American alligator (Alligator mississippiensis), and investigate variation in gene expression profiles in offspring collected from sites conveying differential exposures to environmental contaminants. Both age- and tissue-dependent patterning of AHR isoform expression are detected. We characterize two downstream transcriptional targets of the AHR, CYP1A1 and CYP1A2, and describe conserved elements of their genomic architecture. When comparisons across different sites are made, hepatic expression of CYP1A2, a direct target of the AHR, appears elevated in embryos from a site associated with a dioxin point source and previously characterized PCB contamination. Elevated CYP1A2 expression is not persistent, as site-specific variation was absent in juveniles originating from field-collected eggs but reared under lab conditions. Our results illustrate the patterning of AHR gene expression in a long-lived environmental model species, and indicate a potential contemporary influence of historical contamination. This research presents a novel opportunity to link contamination events to critical genetic pathways during embryonic development, and carries significant potential to inform our understanding of potential health effects in wildlife and humans.

Perfluorinated alkyl acids in plasma of American alligators (Alligator mississippiensis) from Florida and South Carolina.

The present study aimed to quantitate 15 perfluoroalkyl acids (PFAAs) in 125 adult American alligators at 12 sites across the southeastern United States. Of those 15 PFAAs, 9 were detected in 65% to 100% of samples: perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), perfluorododecanoic acid, perfluorotridecanoic acid (PFTriA), perfluorotetradecanoic acid, perfluorohexanesulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS). Males (across all sites) showed significantly higher concentrations of 4 PFAAs: PFOS (p = 0.01), PFDA (p = 0.0003), PFUnA (p = 0.021), and PFTriA (p = 0.021). Concentrations of PFOS, PFHxS, and PFDA in plasma were significantly different among the sites in each sex. Alligators at both Merritt Island National Wildlife Refuge (FL, USA) and Kiawah Nature Conservancy (SC, USA) exhibited some of the highest PFOS concentrations (medians of 99.5 ng/g and 55.8 ng/g, respectively) in plasma measured to date in a crocodilian species. A number of positive correlations between PFAAs and snout-vent length were observed in both sexes, suggesting that PFAA body burdens increase with increasing size. In addition, several significant correlations among PFAAs in alligator plasma may suggest conserved sources of PFAAs at each site throughout the greater study area. The present study is the first to report PFAAs in American alligators, to reveal potential PFAA hot spots in Florida and South Carolina, and to provide a contaminant of concern when assessing anthropogenic impacts on ecosystem health. Environ Toxicol Chem 2017;36:917-925. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Patient safety in community dementia services: what can we learn from the experiences of caregivers and healthcare professionals?

Objectives: this study aims to explore how patient safety in community dementia services is understood by caregivers, and healthcare professionals. Methods: cross-sectional analysis of guided one-to-one interviews with 10 caregivers, and 10 healthcare professionals. Results: caregivers and healthcare professionals identified a range of issues including medication errors, mis-communication between professionals, unclear service pathways and the effects of stress on caregivers' behaviour. Caregivers and professionals differed in their attitudes to balancing safety with patient autonomy and who is responsible for managing safety. Conclusions: this article helps to define the nature of safety issues in the context of community care for people with dementia. In contrast to hospital medicine, where the ideal treatment world is safe with all risks managed or minimised, in dementia some risks are actively taken in the interests of promoting autonomy. Caregivers' views differ from those of health professionals but both parties see potential for collaborative working to manage risk in this context, balancing the promotion of autonomy with the minimisation of potential harm.