Co-Cultures of Oophila Amblystomatis Between Ambystoma Maculatum and Ambystoma Gracile Hosts Show Host-Symbiont Fidelity

A unique symbiosis occurs between embryos of the spotted salamander (Ambystoma maculatum) and a green alga (Oophila amblystomatis). Unlike most vertebrate host-symbiont relationships, which are ectosymbiotic, A. maculatum exhibits both an ecto- and an endo-symbiosis, where some of the green algal cells living inside egg capsules enter embryonic tissues as well as individual salamander cells. Past research has consistently categorized this symbiosis as a mutualism, making this the first example of a “beneficial” microbe entering vertebrate cells. Another closely related species of salamander, Ambystoma gracile, also harbors beneficial Oophila algae in its egg capsules. However, our sampling within the A. gracile range consistently shows this to be a strict ectosymbiotic interaction—with no sign of tissue or presumably cellular entry. In this study we swapped cultured algae derived from intracapsular fluid of different salamander hosts to test the fidelity of tissue entry in these symbioses. Both A. maculatum and A. gracile embryos were raised in cultures with their own algae or algae cultured from the other host. Under these in vitro culture conditions A. maculatum algae will enter embryonic A. maculatum tissues. Additionally, although at a much lower frequency, A. gracile derived algae will also enter A. maculatum host tissues. However, neither Oophila strain enters A. gracile hosts in these co-culture conditions. These data reveal a potential host-symbiont fidelity that allows the unique endosymbiosis to occur in A. maculatum, but not in A. gracile. However, preliminary trials in our study found that persistent endogenous A. maculatum algae, as opposed to the cultured algae used in subsequent trials, enters host tissues at a higher frequency. An analysis of previously published Oophila transcriptomes revealed dramatic differences in gene expression between cultured and intracapsular Oophila. These include a suite of genes in protein and cell wall synthesis, photosynthesis, central carbon metabolism suggesting the intracapsular algae are assimilating ammonia for nitrogen metabolism and may be undergoing a life-cycle transition. Further refinements of these co-culture conditions could help determine physiological differences between cultured and endogenous algae, as well as rate-limiting cues provided for the alga by the salamander

Emotion regulation strategies in bipolar disorder: A systematic and critical review

Background Theoretical frameworks emphasise associations between interpretations and responses to affect and bipolar disorder (BD). This review (PROSPERO CRD42016043801) investigated which emotion regulation (ER) strategies have been applied to BD, are elevated in BD compared to clinical and non-clinical controls, and are associated with clinical and functional outcomes in BD Methods Search terms relating to emotion regulation, coping and bipolar disorder were entered into Embase, MedLine and PsycInfo. Quantitative studies investigating relationships between ER strategies and BD were eligible for this narrative synthesis Results A large volume of research (n = 47) investigated specific ER strategies in BD. Maladaptive strategies such as rumination and dampening were elevated in BD compared to controls and these particular strategies had a detrimental impact on outcomes such as mood symptoms. BD had a similar profile of ER strategies to unipolar depression, but there was limited comparison to other clinical groups. People with BD did not generally have deficits in using adaptive strategies, as evidenced by comparisons with controls and experimental studies Limitations Methodological heterogeneity and a lack of ecologically valid ER assessments Conclusions Empirical literature is critiqued in line with contemporary theories of BD and of emotion regulation more generally, in order to inform future research recommendations. This includes investigation of the importance of context in the impact of ER strategies, and discrepancies between trait and state use of ER strategies, particularly through experience sampling

Feasibility of Cell Phone Surveys in People with Mental Illness Experiencing Homelessness During COVID-19

People experiencing homelessness (PEH) may be at increased risk for negative physical and mental health outcomes in the context of community spread of COVID-19. Research into the impacts of COVID-19 on this vulnerable population can be affected by inaccessibility and poor engagement resulting in minimal representation in population-based survey data. The increased use of mobile phone technology (mHealth) to provide medical and psychiatric care during the COVID-19 pandemic could provide an effective platform for gathering data from this hard-to-reach group. This paper examines feasibility, via review of the barriers and facilitators, of using a mobile phone intervention to administer a series of surveys. Data collected via mHealth includes health behaviors and health awareness, access to services, and mental health symptoms in the context of the COVID-19 pandemic among a sample of 30 PEH. At the end of the six month study, 11 (36.7%) participants completed the full study protocol while 19 (63.3%) partially completed the study. There was a significant difference in completion rates based on whether participants were unsheltered-homeless or sheltered-homeless. The study was rated highly by fully compliant participants in measures of acceptability and usability. Applying principles learned in this pilot study to develop feasible, usable and acceptable means of data gathering through the use of mHealth, can have wider ramifications outside of COVID-19

A guide to behavioural experiments in bipolar disorder

Behavioural experiments are an important component of cognitive-behavioural therapy. However, there exists little up-to-date guidance on how to conduct these in people with a diagnosis of bipolar disorder. This paper provides recommendations on how to conduct behavioural experiments in this population. The aim is to upskill and empower clinicians to conduct behavioural experiments. The paper combines the expertise of senior clinicians working in the United Kingdom. The article starts by providing general advice on conducting behavioural experiments in people with bipolar disorder. It then offers specific examples of behavioural experiments targeting cognitions around the uncontrollability and danger of affective states, and related behavioural strategies, which have been implicated in the maintenance of bipolar mood swings. The article finishes by providing examples of behavioural experiments for non-mood related difficulties that commonly occur with bipolar experiences including perfectionistic thinking, need for approval, and intrusive memories. Behavioural experiments offer a useful therapeutic technique for instigating cognitive and behavioural change in bipolar disorder. Conducted sensitively and collaboratively, in line with people's recovery-focused goals, behavioural experiments can be used to overcome mood- and non-mood related difficulties

Gender-specific effects of HIV protease inhibitors on body mass in mice

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p \u3c 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p \u3c 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p \u3c 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol

ParkIndex: Validation and Application of a Pragmatic Measure of Park Access and Use

Composite metrics integrating park availability, features, and quality for a given address or neighborhood are lacking. The purposes of this study were to describe the validation, application, and demonstration of ParkIndex in four diverse communities. This study occurred in Fall 2018 in 128 census block groups within Seattle(WA), Brooklyn(NY), Raleigh(NC), and Greenville County(SC). All parks within a half-mile buffer were audited to calculate a composite park quality score, and select households provided data about use of proximal parks via an online, map-based survey. For each household, the number of parks, total park acreage, and average park quality score within one half-mile were calculated using GIS. Logistic regression was used to identify a parsimonious model predicting park use. ParkIndex values (representing the probability of park use) were mapped for all study areas and after scenarios involving the addition and renovation/improvement of parks. Out of 360 participants, 23.3% reported visiting a park within the past 30 days. The number of parks (OR = 1.36, 95% CI = 1.15–1.62), total park acreage (OR = 1.13, 95% CI = 1.07–1.19), and average park quality score (OR = 1.04, 95% CI = 1.01–1.06) within one half-mile were all associated with park use. Composite ParkIndex values across the study areas ranged from 0 to 100. Hypothetical additions of or renovations to study area parks resulted in ParkIndex increases of 22.7% and 19.2%, respectively. ParkIndex has substantial value for park and urban planners, citizens, and researchers as a common metric to facilitate awareness, decision-making, and intervention planning related to park access, environmental justice, and community health

Understanding the role of neutrophils in chronic inflammatory airway disease

Airway neutrophilia is a common feature of many chronic inflammatory lung diseases and is associated with disease progression, often regardless of the initiating cause. Neutrophils and their products are thought to be key mediators of the inflammatory changes in the airways of patients with chronic obstructive pulmonary disease (COPD) and have been shown to cause many of the pathological features associated with disease, including emphysema and mucus hypersecretion. Patients with COPD also have high rates of bacterial colonisation and recurrent infective exacerbations, suggesting that neutrophil host defence mechanisms are impaired, a concept supported by studies showing alterations to neutrophil migration, degranulation and reactive oxygen species production in cells isolated from patients with COPD. Although the role of neutrophils is best described in COPD, many of the pathological features of this disease are not unique to COPD and also feature in other chronic inflammatory airway diseases, including asthma, cystic fibrosis, alpha-1 anti-trypsin deficiency, and bronchiectasis. There is increasing evidence for immune cell dysfunction contributing to inflammation in many of these diseases, focusing interest on the neutrophil as a key driver of pulmonary inflammation and a potential therapeutic target than spans diseases. This review discusses the evidence for neutrophilic involvement in COPD and also considers their roles in alpha-1 anti-trypsin deficiency, bronchiectasis, asthma, and cystic fibrosis. We provide an in-depth assessment of the role of the neutrophil in each of these conditions, exploring recent advances in understanding, and finally discussing the possibility of common mechanisms across diseases

What does it mean to age well with bipolar disorder?

Background: Bipolar disorder is characterised by episodes of mania and depression that cause significant impairment and disruptions to people’s lives. This diagnosis has been linked to increased rates of suicide, reduced lifespan, and increased mortality, although there is limited research exploring the challenges faced by people with bipolar disorder as they age. It is possible that there is an important interaction effect between ageing and bipolar disorder that exacerbates the difficulties faced by this group, meaning further attention and support is required. This thesis investigated the challenges faced by older adults with bipolar disorder and explored their preferences, priorities, and needs in later life. Knowledge gathered from four studies helped to identify potential adaptations to care that can be used to improve quality of life in this population and enable them to age well with bipolar disorder. Methods: A range of methods were used to complete this thesis. First, a systematic review and narrative synthesis of 23 papers reporting on 19 studies was completed to investigate the prevalence and predictors of physical health comorbidities in older adults with bipolar disorder. Second, a qualitative study consisting of photo elicitation interviews with 17 participants used reflexive thematic analysis to analyse data and explore what it means to age well for older adults with bipolar disorder. Third, 16 biographical narrative interviews were analysed using narrative analysis to understand the changing care and care needs of older adults with bipolar disorder. Finally, a multilevel analysis of seven waves from The English Longitudinal Study of Ageing data was completed to examine quality of life in older adults with bipolar mood states and assess the predictors of quality of life in this group. Results: Ageing with bipolar disorder was associated with an increased prevalence of certain physical health comorbidities such as cardiovascular disease and some forms of cancer. To age well, participants highlighted the importance of lifelong learning to improve their understanding and management of bipolar disorder and find balance in later life. This learning also helped participants to feel confident in taking an active role in treatment decisions which enabled them to regain agency. Finding a sense of belonging, feeling accepted and building upon strengths all supported older adults with bipolar disorder to age well. Furthermore, giving back to others, such as helping younger age groups with bipolar disorder, allowed participants to develop confidence and self-worth. Participants indicated that there was a disconnect between the care they desired and the care that they currently received from services. Older adults with bipolar disorder appeared to have unique and changing care needs that were often neglected. To improve support, services should attempt to offer care that is consistent and facilitates the development of trusting relationships with professionals. The range of issues faced by this population was found to result in poorer quality of life that appeared to be partly driven by loneliness. Conclusions: Older adults with bipolar disorder face unique challenges and changing care needs that mean treatments require adaptation to improve outcomes in this group. At present, treatments appear to focus on symptom reduction, although participants indicated that treatments prioritising connection and consistency of care are desired. Further attention is required to understand the difficulties associated with ageing whilst experiencing bipolar disorder, to improve care and reduce the inequalities currently experienced by this population

Efficacy of a ML336 Derivative Against Venezuelan and Eastern Equine Encephalitis Viruses

Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV). We report findings from in vitro assessments of four analogs of ML336, and in vivo screening of three of these new derivatives, BDGR-4, BDGR-69 and BDGR-70. The optimal dosing for maximal protection was observed at 12.5 mg/kg/day, twice daily for 8 days. BDGR-4 was tested further for prophylactic and therapeutic efficacy in mice challenged with VEEV Trinidad Donkey (TrD). Mice challenged with VEEV TrD showed 100% and 90% protection from lethal disease when treated at 24 and 48 h post-infection, respectively. We also measured 90% protection for BDGR-4 in mice challenged with Eastern equine encephalitis virus. In additional assessments of BDGR-4 in mice alone, we observed no appreciable toxicity as evaluated by clinical chemistry indicators up to a dose of 25 mg/kg/day over 4 days. In these same mice, we observed no induction of interferon. Lastly, the resistance of VEEV to BDGR-4 was evaluated by next-generation sequencing which revealed specific mutations in nsP4, the viral polymerase