Intergenerational Occurrence of Premature Birth and Reproductive Health in Prematurely-Born Women in the Women's Health Initiative.

OBJECTIVE: To compare reproductive history and postmenopausal health by birth status (preterm vs. full term) in a U.S. longitudinal study of postmenopausal women. Birth status was examined according to region of residence, household, and neighborhood socioeconomic status (SES). METHODS: In the Women's Health Initiative Observational Study, 2271 women were born prematurely (< 37 weeks). ANOVA and Chi-square determined birth status differences of reproductive history, pregnancy, and postmenopausal health. Odds ratios were calculated using either binary logistic or multinomial logistic regression. SES and U.S. region of residence were examined as potential effect modifiers. RESULTS: Preterm-born women compared to term-born women had higher risk of delivering a premature infant (aOR 1.68, 95% CI [1.46, 1.93]), higher odds of later-age first pregnancy (aOR 1.27 95% CI [1.02, 1.58]), longer duration to become pregnant (> 1 year to pregnancy) (aOR 1.10 95% CI [1.01, 1.21]), more miscarriages (aOR 1.23 95% CI [1.11, 1.37]), and more pregnancy complications including hypertension (aOR 1.58 95% CI (1.13, 2.21)], preeclampsia (aOR 1.64 95% CI [1.24, 2.16]), and gestational diabetes (aOR 1.68 95% CI [1.11, 2.53]). Preterm-born women had higher odds of menopause before age 50 (aOR 1.09 95% CI [1.05, 1.14]). Post-menopause, they had higher rates of diabetes (p = .01), hypertension (p = .01), hysterectomy (p = .045), and higher Charlson Comorbidity Index scores (p = .01). CONCLUSIONS: Preterm-born women had higher reproductive and pregnancy risks which when coupled with early menopause, may indicate a shorter childbearing period than term-born women. Guidelines for integration of preterm history in women's health care across the life course are needed to identify and manage their higher risk.

"It's a Postcode Lottery": How Do People Affected by Dementia in Wales Experience Their Diagnosis and Post-Diagnostic Support, and How May These Be Improved?

National dementia strategies are government policies that guide the provision of appropriate support for people living with dementia. These strategies, developed through extensive stakeholder engagement, should be tailored to the cultural and demographic needs of a country. Using a mixed methods survey design, this study explored the aims of the Dementia Action Plan (2018-2022) for Wales (UK) around assessment, diagnosis, and post-diagnostic support, and assessed whether these are being realized. Further, it sought to gain insight from people living with dementia and their carers around how the experience may be improved for others in the future, as the development of the next iteration of the Action Plan is anticipated. Respondents included 71 people, affected by typical and rarer types of dementia, living in both rural and urban areas. Findings suggest both positive and negative experiences, reflecting a 'postcode lottery' of service provision. Attainable recommendations for improvement were made by respondents, which would ultimately likely be cost-effective and reduce strain on formal services. The findings reported in this paper concur with those reported by people living with dementia in other countries, indicating their relevance for policymakers beyond Wales.

Exploring experiential differences in everyday activities - A focused ethnographic study in the homes of people living with memory-led Alzheimer's disease and posterior cortical atrophy.

BACKGROUND: Supporting ageing in place, quality of life and activity engagement are public health priorities for people living with dementia, but little is known about the needs and experiences of community-dwelling people with rarer forms of dementia with lesser known symptoms. Posterior cortical atrophy (PCA) is a rare form of dementia usually caused by Alzheimer's disease but which is characterised by diminished visual processing (rather than a dominant memory problem), which poses challenges for maintaining independence and accessing appropriate support. METHODS: This study used a comparative qualitative design and focussed ethnographic methods to explore experiential differences in activity engagement for 10 people with the most common, memory-led presentation of Alzheimer's disease and 10 people with posterior cortical atrophy within their everyday home environments. RESULTS: While the data collection revealed much rich variation in individual and contextual factors, some tentative high-level differences in the experiences of everyday activities could be drawn out, seemingly attributable to the different diagnoses' differing dominant symptoms. These included people with posterior cortical atrophy being less likely to use environmental cues to initiate activities, and more likely to withhold from asking for support because of preserved insight into the impact of this on carers. This lack of initiation of activities could be misinterpreted as apathy. People with posterior cortical atrophy also were discouraged from engaging in activities by disorientation within the home, and difficulties localising, identifying and manipulating objects. People with the more common, memory-led presentation of Alzheimer's disease exhibited more memory-based difficulties with engaging with activities such as forgetting planned activities, where to locate the items required for an activity and the steps involved. Despite these distinct symptom-led challenges, all participants and their family members demonstrated resourcefulness and resilience in making creative adaptations to support continued engagement in everyday activities, supporting the widely reported management strategies of people with dementia of the Alzheimer's type more generally. CONCLUSIONS: These findings offer helpful insights into some the differing impacts dementia related visual and memory impairments can have on everyday activity engagement, which will be helpful for others navigating these challenges and the health and social care practitioners working with people affected by these conditions. The findings also highlight the vast individual variation in the multitude of individual and contextual factors involved in everyday activity engagement, and suggest important areas for future work utilising methods which are similarly high in ecological validity and accessibility as the home-based focussed ethnographic methods utilised here.

'Talking lines': the stories of diagnosis and support as told by those with lived experience of rare forms of dementia.

BACKGROUND: People living with, or caring for someone with, rare forms of dementia can encounter issues while obtaining a diagnosis and trying to access appropriate support. This can affect their wellbeing, quality of life, social relationships and employment status. This study makes use of an arts-based narrative approach to explore individual accounts of these experiences whilst also exploring how, in telling their stories, those affected by rare forms of dementia might invoke, and situate their stories in relation to, broader cultural narratives around dementia and illness. METHODS: Semi-structured interviews were conducted via video-conferencing software with participants (N = 27), living with, or caring for someone with, a rare forms of dementia. Participants used line drawings to depict their journey from initial symptoms to the present day, followed by prompts to verbally narrate their experiences. All interview transcripts and line drawings were subjected to narrative analysis. Four sets of transcripts and drawings were then subjected to more in-depth analysis. RESULTS: Analysis shed light on the struggles encountered by both care-partners and people with a diagnosis, while navigating a health and social care system that does not always understand their needs. This often led to individuals feeling isolated and unsupported. Accounts also depicted challenges to identity brought on by the process. The moment of diagnosis was also drawn in a complicated light. Individuals found comfort in gaining understanding, but felt fear at recognising upcoming challenges. Participants situated their own accounts against mainstream cultural narratives around what good support for cognitive impairment and dementia might look like, whilst also demonstrating the influential role they took on in pursuing the right care. CONCLUSIONS: The use of line drawing, alongside narrative interviews, allowed participants to tell complicated, sometimes anachronistic, stories about difficult experiences, whilst also reflecting on, and attaching meaning to, them. These stories highlighted pressing gaps in healthcare services and shone a light on the various pieces of collective action individuals were engaged in in order to improve them. Finally, in modelling some elements of the participants' service provision which were working, the narratives pointed to future directions services might move in.

Modulation of prey capture kinematics in relation to prey distance helps predict success.

Predators are not perfect, as some of their prey capture attempts result in failure. Successful attempts may be partly due to predators modulating their capture kinematics in relation to variation in the visual cues of the prey to increase the probability of success. In praying mantises, which have been suggested to possess stereoscopic vision, variation in prey distance has been shown to elicit variation in the probability of an attempt. However, it remains to be examined whether variation in prey distance results in mantises modulating their attempt to successfully capture prey. The goals of this study were to examine these relationships using the praying mantis system. Using 11 adult female Sphodromantis lineola, we recorded 192 prey capture attempts at 1000 Hz with two cameras to examine the 3D kinematics of successful and unsuccessful prey capture attempts. Using a combination of principal component analysis (PCA) and logistic regression, our results show that as prey distance increases, mantises adjust through greater and faster expansion of the forelegs and body (PC1), which significantly predicts capture success. However, PC1 only explains 22% of the variation in all prey capture attempts, suggesting that the other components may be related to additional aspects of the prey. Our results suggest that the distances at which mantises prefer to attempt to capture prey may be the result of their greater probability of successfully capturing the prey. These results highlight the range of motions mantises use when attempting to capture prey, suggesting flexibility in their prey capture attempts in relation to prey position.

Percutaneous decannulation reduces procedure length and rates of groin wound infection in patients on venoarterial extracorporeal membrane oxygenation.

Objective: Open decannulation from femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) carries high risk of morbidity, including groin wound infection. This study evaluated the impact of percutaneous decannulation on rates of groin wound infection in patients decannulated from femoral VA-ECMO. Methods: Between January 1, 2022, and April 30, 2023, 47 consecutive patients received percutaneous femoral VA-ECMO and survived to decannulation. A percutaneous suture-mediated closure device was used for decannulation in patients with relatively smaller arterial cannulas. Patients with larger arterial cannulas or unsuccessful percutaneous closures underwent surgical cutdown and repair of the femoral artery. The primary outcome was arterial site wound infection following decannulation. Results: Among the 47 patients who survived to decannulation from VA-ECMO, 21 underwent percutaneous decannulation and 27 underwent surgical cutdown. One patient underwent 2 VA-ECMO runs, one with percutaneous decannulation and one with surgical cutdown. Percutaneous decannulation was attempted in 22 patients, with 21 of 22 (95.5%) success rate. Decannulation procedure length was significantly shorter in the percutaneous group (79 minutes vs 148 minutes, P = .0001). The percutaneous group had significantly reduced rates of groin wound complications (0% vs 40.7%, P = .001) and groin wound infections (0% vs 22.2%, P = .03) when compared with the surgical cutdown group. Three patients (14.3%) in the percutaneous group experienced vascular complications, including pseudoaneurysm at the distal perfusion catheter site and nonocclusive thrombus of the common femoral artery. Conclusions: Percutaneous decannulation may reduce decannulation procedure length and rate of groin wound infection in patients who survive to decannulation from VA-ECMO.

"I Want to Do Something" - Exploring What Makes Activities Meaningful for Community-Dwelling People Living With Dementia: A Focused Ethnographic Study.

Supporting ageing in place, quality of life, and activity engagement are public health priorities for people with dementia. The importance of maintaining opportunities for meaningful activities has been widely acknowledged for those with dementia in long-term care, but little is known about what makes activities meaningful for, and how they are experienced by, people with different types of dementia in their own homes. This study used focussed ethnographic methods to explore the motivations and meanings of everyday activity engagement within the homes of 10 people with memory-led Alzheimer's disease and 10 people with posterior cortical atrophy. While participants' interactions with their everyday environments were challenged by their diagnoses, they were all finding ways to continue meaning-making via various activities. The main findings are encapsulated in three themes: (1) The fun and the function of activities; (2) Reciprocities of care, and (3) The constitution and continuity of (a changing) self. Ongoing engagement with both fun and functional activities offered participants living with different dementias opportunities to connect with others, to offer care and support (as well as receive it), and to maintain a sense of self and identity. Implications are discussed regarding the development and delivery of tailored interventions and support to enable continued engagement in meaningful activities for people with different types of dementia living in the community.

The Effect of Using a Remote Patient Management Platform in Optimizing Guideline-Directed Medical Therapy in Heart Failure Patients: A Randomized Controlled Trial.

BACKGROUND: Guideline-directed medical therapy (GDMT) remains underutilized in patients with heart failure with reduced ejection fraction, leading to morbidity and mortality. OBJECTIVES: The Medly Titrate (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration) study was an open-label, randomized controlled trial to determine whether remote medication titration for patients with heart failure with reduced ejection fraction was more effective than usual care (UC). METHODS: In this study, 108 patients were randomized to remote GDMT titration through the Medly heart failure program (n = 56) vs UC (n = 52). The primary outcome was the proportion of patients completing GDMT titration at 6 months. Secondary outcomes included the number of clinic visits and time required to achieve titration, patient health outcomes, and health care utilization, including urgent clinic/emergency department visits and hospitalization. RESULTS: At 6 months, GDMT titration was completed in 82.1% (95% CI: 71.2%-90.8%) of patients in the intervention arm vs 53.8% in UC (95% CI: 41.1%-67.7%; P = 0.001). Remote titration required fewer in-person (1.62 ± 1.09 vs 2.42 ± 1.65; P = 0.004) and virtual clinic visits (0.50 ± 1.08 vs 1.29 ± 1.86; P = 0.009) to complete titration. Median time to optimization was shorter with remote titration (3.42 months [Q1-Q3: 2.99-4.04 months] vs 5.47 months [Q1-Q3: 4.14-7.33 months]; P < 0.001). The number of urgent clinic/emergency department visits (incidence rate ratio of remote vs control groups: 0.90 [95% CI: 0.53-1.56]; P = 0.70) were similar between groups, with a reduction in all-cause hospitalization with remote titration (incidence rate ratio: 0.55 [95% CI: 0.31-0.97]; P = 0.042). CONCLUSIONS: Remote titration of GDMT in heart failure with reduced ejection fraction was effective, safe, feasible, and increased the proportion of patients achieving target doses, in a shorter period of time with no excess adverse events compared with UC. (Use of Telemonitoring to Facilitate Heart Failure Mediation Titration [Medly Titrate]; NCT04205513).

Microfluidics produced ATRA-loaded PLGA NPs reduced tuberculosis burden in alveolar epithelial cells and enabled high delivered dose under simulated human breathing pattern in 3D printed head models.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is second only to COVID-19 as the top infectious disease killer worldwide. Multi-drug resistant TB (MDR-TB) may arise because of poor patient adherence to medications due to lengthy treatment duration and side effects. Delivering novel host directed therapies (HDT), like all trans retinoic acid (ATRA) may help to improve drug regimens and reduce the incidence of MDR-TB. Local delivery of ATRA to the site of infection leads to higher bioavailability and reduced systemic side effects. ATRA is poorly soluble in water and has a short half-life in plasma. Therefore, it requires a formulation step before it can be administered in vivo. ATRA loaded PLGA nanoparticles suitable for nebulization were manufactured and optimized using a scalable nanomanufacturing microfluidics (MF) mixing approach (MF-ATRA-PLGA NPs). MF-ATRA-PLGA NPs demonstrated a dose dependent inhibition of Mtb growth in TB-infected A549 alveolar epithelial cell model while preserving cell viability. The MF-ATRA-PLGA NPs were nebulized with the Aerogen Solo vibrating mesh nebulizer, with aerosol droplet size characterized using laser diffraction and the estimated delivered dose was determined. The volume median diameter (VMD) of the MF-ATRA-PLGA NPs was 3.00 ± 0.18 µm. The inhaled dose delivered in adult and paediatric 3D printed head models under a simulated normal adult and paediatric breathing pattern was found to be 47.05 ± 3 % and 20.15 ± 3.46 % respectively. These aerosol characteristics of MF-ATRA-PLGA NPs supports its suitability for delivery to the lungs via inhalation. The data generated on the efficacy of an inhalable, scalable and regulatory friendly ATRA-PLGA NPs formulation provides a foundation on which further pre-clinical testing can be built. Overall, the results of this project are promising for future research into ATRA loaded NPs formulations as inhaled host directed therapies for TB.

'Misdiagnosed and Misunderstood': Insights into Rarer Forms of Dementia through a Stepwise Approach to Co-Constructed Research Poetry.

This study investigated co-constructed research poetry as a way to understand the lived experiences of people affected by rarer dementia and as a means to use poetry to convey those experiences to healthcare professionals. Using mixed methods, 71 people living with rarer dementia and care-partners (stakeholders) contributed to co-constructing 27 poems with professional poets; stakeholders' verbatim words were analysed with descriptive qualitative analysis. Stakeholders were also surveyed and interviewed about their participation. Healthcare professionals (n = 93) were surveyed to elicit their responses to learning through poetry and its acceptability as a learning tool. Poems conveyed a shared narrative of different aspects of lived experience, often owing to atypical symptoms, misunderstandings by professionals, lack of support pathways, and a continuous struggle to adapt. Stakeholder surveys indicated it was a valuable experience to both co-create and respond to the poems, whilst group interviews revealed people's experiences of the research poetry were characterised by reflection on lived experience, curiosity and exploration. Healthcare professionals' responses reinforced poetry's capacity to stimulate cognitive and affective learning specific to rare dementia support and prompt both empathy and critical thinking in practice. As the largest poetry-based study that we are aware of, this novel accessible approach of creating group poems yielded substantial information about the experiences and needs of those affected by rarer dementia and how poetry can contribute to healthcare education and training.

Physiologic benefits of veno-pulmonary extracorporeal membrane oxygenation for COVID-19 ARDS: A single center experience.

BACKGROUND: A subset of patients with COVID-19 acute respiratory distress syndrome (ARDS) require extracorporeal membrane oxygenation (ECMO). Veno-pulmonary (VP) ECMO provides support to the right ventricle and decreased risk of recirculation. METHODS: A retrospective analysis of patients with COVID-19 ARDS and VP ECMO was performed. Patients were separated into groups by indication (1) "right ventricular (RV) failure," (2) "refractory hypoxemia," and (3) "recurrent suck-down events (SDEs)." Pre- and post-configuration vasoactive inotropic scores (VIS), fraction of inspired oxygen (FIO2), and resolution of SDEs were reported. A 90-day mortality was computed for all groups. Patients were also compared to those who underwent conventional venovenous (VV) ECMO. RESULTS: Forty-seven patients underwent VP ECMO configuration, 18 in group 1, 16 in group 2, and 8 in group 3. Ninety-day mortality was 66% for the entire cohort and was 77.8%, 81.3% and 37.5% for groups 1, 2, and 3, respectively. Mean VIS decreased in group 1 (8.3 vs 2.9, p = 0.005), while mean FIO2 decreased in the group 2 and was sustained at 72 h (82.5% vs 52.5% and 47.5%, p < 0.001). Six of the eight (75%) of patients with recurrent SDEs had resolution of these events after configuration to VP ECMO. Patients with VP ECMO spent more days on ECMO (33 days compared to 18 days, p = 0.004) with no difference in mortality (66% compared to 55.1%, p = 0.28). CONCLUSION: VP ECMO in COVID-19 ARDS improves hemodynamics in patients with RV failure, improves oxygenation in patients with refractory hypoxemia and improves the frequency of SDEs.

Advanced Respiratory Support Days as a Novel Marker of Mortality in COVID-19 Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

Emerging evidence suggests prolonged use of noninvasive respiratory support may increase mortality of patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome who require extracorporeal membrane oxygenation (ECMO). Using a database of adults receiving ECMO for COVID-19, we calculated survival curves and multivariable Cox regression to determine the risk of death associated with pre-ECMO use of high-flow nasal oxygen (HFNO), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) days. We investigated the performance of a novel variable, advanced respiratory support days (composite of HFNO, NIV, and IMV days), on Respiratory ECMO Survival Prediction (RESP) score. Subjects (N = 146) with increasing advanced respiratory support days (<5, 5-9, and ≥10) had a stepwise increase in 90 day mortality (32.2%, 57.7%, and 75.4%, respectively; p = 0.002). Ninety-day mortality was significantly higher in subjects (N = 121) receiving NIV >4 days (81.8% vs. 52.4%, p < 0.001). Each additional pre-ECMO advanced respiratory support day increased the odds of right ventricular failure (odds ratio [OR]: 1.066, 95% confidence interval [CI]: 1.002-1.135) and in-hospital mortality (1.17, 95% CI: 1.08-1.27). Substituting advanced respiratory support days for IMV days improved RESP score mortality prediction (area under the curve (AUC) or: 0.64 vs. 0.71). Pre-ECMO advanced respiratory support days were associated with increased 90 day mortality compared with IMV days alone. Adjusting the RESP score for advanced respiratory support days improved mortality prediction.

Venovenous extracorporeal membrane oxygenation after cardiac arrest for acute respiratory distress syndrome caused by Legionella: a case report.

BACKGROUND: Legionella remains underdiagnosed in the intensive care unit and can progress to acute respiratory distress syndrome (ARDS), multiorgan failure and death. In severe cases, venovenous extracorporeal membrane oxygenation (VV-ECMO) allows time for resolution of disease with Legionella-targeted therapy. VV-ECMO outcomes for Legionella are favorable with reported survival greater than 70%. Rapid molecular polymerase chain reaction (PCR) testing of the lower respiratory tract aids in diagnosing Legionella with high sensitivity and specificity. We present a unique case of a patient with a positive COVID-19 test and ARDS who suffered a cardiac arrest. The patient was subsequently cannulated for VV-ECMO, and after lower respiratory tract PCR testing, Legionella was determined to be the cause. She was successfully treated and decannulated from VV-ECMO after eight days. CASE PRESENTATION: A 53-year-old female presented with one week of dyspnea and a positive COVID-19 test. She was hypoxemic, hypotensive and had bilateral infiltrates on imaging. She received supplemental oxygen, intravenous fluids, vasopressors, broad spectrum antibiotics, and was transferred to a tertiary care center. She developed progressive hypoxemia and suffered a cardiac arrest, requiring ten minutes of CPR and endotracheal intubation to achieve return of spontaneous circulation. Despite mechanical ventilation and paralysis, she developed refractory hypoxemia and was cannulated for VV-ECMO. Dexamethasone and remdesivir were given for presumed COVID-19. Bronchoscopy with bronchoalveolar lavage (BAL) performed with PCR testing was positive for Legionella pneumophila and negative for COVID-19. Steroids and remdesivir were discontinued and she was treated with azithromycin. Her lung compliance improved, and she was decannulated after eight days on VV-ECMO. She was discharged home on hospital day 16 breathing room air and neurologically intact. CONCLUSIONS: This case illustrates the utility of rapid PCR testing to diagnose Legionella in patients with respiratory failure and the early use of VV-ECMO in patients with refractory hypoxemia secondary to Legionella infection. Moreover, many patients encountered in the ICU may have prior COVID-19 immunity, and though a positive COVID-19 test may be present, further investigation with lower respiratory tract PCR testing may provide alternative diagnoses. Patients with ARDS should undergo Legionella-specific testing, and if Legionella is determined to be the causative organism, early VV-ECMO should be considered in patients with refractory hypoxemia given reported high survival rates.

"Better Living with Non-memory-led Dementia": protocol for a feasibility randomised controlled trial of a web-based caregiver educational programme.

BACKGROUND: Non-memory-led dementias such as posterior cortical atrophy (PCA), primary progressive aphasia (PPA) and behavioural variant frontotemporal dementia (bvFTD) are low prevalent and often affect individuals under the age of 65. Tailored educational and support resources for caregivers of people living with these dementia phenotypes are scarce and unevenly distributed geographically. Web-based educational programmes are emerging as promising alternatives to improve caregiver self-efficacy and well-being. Here, we present the protocol of a study aiming to assess the feasibility of a co-produced online educational programme for caregivers of people living PCA, PPA and bvFTD: the Better Living with Non-memory-led Dementia programme. METHODS: A randomised controlled feasibility trial will be conducted on a sample of 30 caregivers of people living with PCA, PPA and bvFTD. Participants will be recruited among members of the support organisation Rare Dementia Support (based at UCL in the UK). The intervention group will be given access to an 8-week co-produced web-based educational programme consisting of 6 modules addressing education about PCA, PPA and bvFTD and support strategies for the person with dementia and for the caregiver. The control group will receive treatment as usual (TAU). Feasibility will be measured through feasibility of recruitment, clinical measurement tools and acceptability. Clinical measures will be used to assess preliminary efficacy and data on completion rates, missing data and variability used to decide on measures to be included in a full-scale trial. Allocation ratio will be 2:1 (intervention:control) stratified by diagnosis. Feasibility of recruitment and acceptability will be assessed. Clinical measures will be administered at baseline and 8-week and 3-month post-randomisation. The control group will be offered access to the intervention at the completion of data collection. Participants will be unblinded, and all measures will be self-reported online. DISCUSSION: Online-delivered educational programmes show potential for improving care competency of caregivers and may contribute to overcoming geographical inequalities in local provision of support services. This pilot study will inform a fully powered international trial to determine the effectiveness of Better Living with Non-memory-led Dementia. TRIAL REGISTRATION: This trial has been registered prospectively on the Clinical Trials Registry on 1st September 2022, registration number NCT05525377.

Preterm birth, birthweight, and subsequent risk for depression.

An individual's birthweight, a marker of in utero exposures, was recently associated with certain psychiatric conditions. However, studies investigating the relationship between an individual's preterm birth status and/or birthweight and risk for depression during adulthood are sparse; we used data from the Women's Health Initiative (WHI) to investigate these potential associations. At study entry, 86,925 postmenopausal women reported their birthweight by category (<6 lbs., 6-7 lbs. 15 oz., 8-9 lbs. 15 oz., or ≥10 lbs.) and their preterm birth status (full-term or ≥4 weeks premature). Women also completed the Burnham screen for depression and were asked to self-report if: (a) they had ever been diagnosed with depression, or (b) if they were taking antidepressant medications. Linear and logistic regression models were used to estimate unadjusted and adjusted effect estimates. Compared to those born weighing between 6 and 7 lbs. 15 oz., individuals born weighing <6 lbs. (ßadj = 0.007, P < 0.0001) and ≥10 lbs. (ßadj = 0.006, P = 0.02) had significantly higher Burnam scores. Individuals born weighing <6 lbs. were also more likely to have depression (adjOR 1.21, 95% CI 1.11-1.31). Individuals born preterm were also more likely to have depression (adjOR 1.18, 95% CI 1.02-1.35); while attenuated, this association remained in analyses limited to only those reportedly born weighing <6 lbs. Our research supports the role of early life exposures on health risks across the life course. Individuals born at low or high birthweights and those born preterm may benefit from early evaluation and long-term follow-up for the prevention and treatment of mental health outcomes.

Situating support for people living with rarer forms of dementia.

BACKGROUND: Awareness of a multitude of diseases that can cause neurodegenerative decline and their unique symptom profiles in the dementia care and support sectors remains limited. Obtaining an accurate diagnosis and post-diagnostic care and support is a challenge for many people and their families. As part of a larger study examining multi-component forms of support for people living with rarer dementias, the aim of this present study was to examine how rare dementia was situated within the complex social groupings, their organization and embedded discursive constructions that broadly form dementia care and support delivery. METHODS: Adopting a situational analysis approach, we undertook an examination of public documents and organizational websites within the support sector for people living with dementia in Canada, England, and Wales. We also surveyed professionals to further explore the situation at the point of care and support delivery. Consistent with our approach, data collection and analysis occurred concurrently including the development of a series of analytic maps. RESULTS: Recognizing the complexities within the situation, our findings provided new insights on the situated structures for support action and the discursive representations that illuminate both the limitations of the current support landscape and possibilities for a more flexible and tailored rare dementia support. Alongside, the predominant universal versus tailored support positionings within our data reinforced the complexity from which a promising new social space for people living with rarer dementias is being cultivated. CONCLUSIONS: The social worlds engaged in supportive action with people living with rare dementia are less visible within the shadow of a universally constructed dementia support milieu and appear to be negotiated within this powerful arena. However, their evolving organization and discursive constructions point to an emerging new social space for people living with rarer conditions.

Development of an item pool for a patient reported outcome measure of resilience for people living with dementia.

BACKGROUND AND OBJECTIVES: Policies to support people living with dementia increasingly focus on strengths-based approaches, highlighting the importance of building resilience. This research responds to the lack of a suitable resilience measure for people with dementia. It develops a pool of items to inform a new measure of resilience for this population. METHODS: A conceptual model and associated data informed the item generation of the draft resilience measure. Regular meetings with professionals (n = 7) discussed response-scale formatting, content and face validity, leading to refinement and item reduction. Cognitive interviews with people living with dementia (n = 11) then examined the face and content validity of items and the suitability of response-scale formatting. These two phases informed subsequent revision and further item reduction of the resilience measure. RESULTS: The first item generation exercise led to 140 items. These were independently assessed by the professionals and this refinement reduced the measure to 63 items across 7 domains of the conceptual model (psychological strengths; practical approaches for adapting to life with dementia; continuing with hobbies, interests and activities; strong relationships with family and friends; peer support and education; participating in community activities; the role of professional support services). Cognitive interviews explored the 63 items with people living with dementia. Detailed feedback led to items removed due to difficulty with (a) understanding (N = 7); (b) answering (n = 11); (c) low preference for that item (n = 6); and (d) presence of a preferred item within a cluster of similar questions (n = 4). Items were amended to enhance clarity/conciseness (n = 19) leading to a final 37-item pool. CONCLUSION: Established methods for measurement development included the expertise of people with dementia and led to the generation of a set of items for a new resilience measure that were understandable and acceptable to this target population. This 37-item pool reflects the conceptual understanding of resilience in dementia as being derived across individual, community and societal level resources.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

OBJECTIVE: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. STUDY DESIGN: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case-control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p < 0.05 in the replication cohort. RESULTS: Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis (p = 4.1 × 10-4) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2-1.0; p = 0.039). CONCLUSION: A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. KEY POINTS: · Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay.. · A genetic variant in SERPINE1 is associated with CP or death among ELBW infants.. · The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor..

Glucose metabolism and its role in the maturation and migration of human CD1c+ dendritic cells following exposure to BCG.

Introduction: Tuberculosis (TB) still kills over 1 million people annually. The only approved vaccine, BCG, prevents disseminated disease in children but shows low efficacy at preventing pulmonary TB. Myeloid dendritic cells (mDCs) are promising targets for vaccines and immunotherapies to combat infectious diseases due to their essential role in linking innate and adaptive immune responses. DCs undergo metabolic reprogramming following exposure to TLR agonists, which is thought to be a prerequisite for a successful host response to infection. We hypothesized that metabolic rewiring also plays a vital role in the maturation and migration of DCs stimulated with BCG. Consequently, we investigated the role of glycolysis in the activation of primary human myeloid CD1c+ DCs in response to BCG. Methods/results: We show that CD1c+ mDC mature and acquire a more energetic phenotype upon challenge with BCG. Pharmacological inhibition of glycolysis with 2-deoxy-D-glucose (2-DG) decreased cytokine secretion and altered cell surface expression of both CD40 and CCR7 on BCG-challenged, compared to untreated, mDCs. Furthermore, inhibition of glycolysis had differential effects on infected and uninfected bystander mDCs in BCG-challenged cultures. For example, CCR7 expression was increased by 2-DG treatment following challenge with BCG and this increase in expression was seen only in BCG-infected mDCs. Moreover, although 2-DG treatment inhibited CCR7-mediated migration of bystander CD1C+ DCs in a transwell assay, migration of BCG-infected cells proceeded independently of glycolysis. Discussion: Our results provide the first evidence that glycolysis plays divergent roles in the maturation and migration of human CD1c+ mDC exposed to BCG, segregating with infection status. Further investigation of cellular metabolism in DC subsets will be required to determine whether glycolysis can be targeted to elicit better protective immunity against Mtb.