Neuroimaging of posttraumatic stress disorder in adults and youth: progress over the last decade on three leading questions of the field.

Almost three decades have passed since the first posttraumatic stress disorder (PTSD) neuroimaging study was published. Since then, the field of clinical neuroscience has made advancements in understanding the neural correlates of PTSD to create more efficacious treatment strategies. While gold-standard psychotherapy options are available, many patients do not respond to them, prematurely drop out, or never initiate treatment. Therefore, elucidating the neurobiological mechanisms that define the disorder can help guide clinician decision-making and develop individualized mechanisms-based treatment options. To this end, this narrative review highlights progress made in the last decade in adult and youth samples on three outstanding questions in PTSD research: (1) Which neural alterations serve as predisposing (pre-exposure) risk factors for PTSD development, and which are acquired (post-exposure) alterations? (2) Which neural alterations can predict treatment outcomes and define clinical improvement? and (3) Can neuroimaging measures be used to define brain-based biotypes of PTSD? While the studies highlighted in this review have made progress in answering the three questions, the field still has much to do before implementing these findings into clinical practice. Overall, to better answer these questions, we suggest that future neuroimaging studies of PTSD should (A) utilize prospective longitudinal designs, collecting brain measures before experiencing trauma and at multiple follow-up time points post-trauma, taking advantage of multi-site collaborations/consortiums; (B) collect two scans to explore changes in brain alterations from pre-to-post treatment and compare changes in neural activation between treatment groups, including longitudinal follow up assessments; and (C) replicate brain-based biotypes of PTSD. By synthesizing recent findings, this narrative review will pave the way for personalized treatment approaches grounded in neurobiological evidence.

Parent Psychopathology and Behavioral Effects on Child Brain-Symptom Networks in the ABCD Study.

OBJECTIVE: Parents play a notable role in the development of child psychopathology. In this study, we investigated the role of parent psychopathology and behaviors on child brain-symptom networks to understand the role of intergenerational transmission of psychopathology. Few studies have documented the interaction of child psychopathology, parent psychopathology, and child neuroimaging. METHOD: We used the baseline cohort of the Adolescent Brain Cognitive Development Study (N = 7,151, female-at-birth = 3,619, aged 9-11 years) to derive brain-symptom networks using sparse canonical correlation analysis with the Child Behavior Checklist and resting-state functional magnetic resonance imaging. We then correlated parent psychopathology symptoms and parental behaviors with child brain-symptom networks. Finally, we used the significant correlations to understand, using the mediation R package, whether parent behaviors mediated the effect of parent psychopathology on child brain connectivity. RESULTS: We observed 3 brain-symptom networks correlated with externalizing (r = 0.19, internalizing (r = 0.17), and neurodevelopmental symptoms (r = 0.18). These corresponded to differences in connectivity between the default mode-default mode, default mode-control, and visual-visual canonical networks. We further detected aspects of parental psychopathology, including personal strength, thought problems, and rule-breaking symptoms to be associated with child brain connectivity. Finally, we found that parental behaviors and symptoms mediate each other's relationship to child brain connectivity. CONCLUSION: The current study suggests that positive parental behaviors can relieve potentially detrimental effects of parental psychopathology, and vice versa, on symptom-correlated child brain connectivity. Altogether, these results provide a framework for future research and potential targets for parents who experience mental health symptoms to help mitigate potential intergenerational transmission of mental illness.

Children of trauma survivors: Influences of parental posttraumatic stress and child-perceived parenting.

BACKGROUND: Research has established a negative association between parental posttraumatic stress symptoms (PTSS), including subthreshold symptoms, and child physical and behavioral health outcomes. Such intergenerational transmission of risk has multiple possible mechanisms, including lack of positive parenting, increased negative parenting, shared environmental and contextual risks, and potential biological components such as shared genetics or even transmission of epigenetic risk. METHOD: This study examined 93 parent-child dyads (n = 171 participants total) from a mixed Urban-Suburban US metropolitan area to investigate the relations between parental PTSS and child-perceived parenting and child PTSS. We sought to examine interactions between parental PTSS and parenting on child PTSS. RESULTS: We found an association between parent and child PTSS, consistent with prior literature showing increased risk for children of trauma survivors. Interestingly, we found effects of positive parenting on diminished child PTSS symptoms only in parents without PTSS, whereas the effect of positive parenting on buffering child symptoms was absent in parents with PTSS. LIMITATIONS: The present findings are tempered by the use of self-report data to assess parent and child PTSS, which is not as reliable as clinician assessment of symptoms. Further, the use of survey data limits what is known about the extent of trauma exposure in parents and children, and different measures were used to assess PTSS in parents and kids, which limits comparability of these reported symptoms. DISCUSSION: Limitations notwithstanding, findings suggest joint attention paid to parenting practices and to a parent's recovery, even from subthreshold symptoms of PTSS, as two different but important ways to support trauma survivor parents in their efforts to most optimally parent and protect their children from intergenerational risk.

Prevalence of Skeletal Fluorosis in Northern Tanzania: A Follow-Up Study.

OBJECTIVES: Skeletal fluorosis is a metabolic bone disease caused by excessive exposure to fluoride, predominantly through contamination of drinking water. This study aimed to identify all cases of skeletal fluorosis in Tindigani village situated in Northern Tanzania. This was done following changes in drinking water sources after a previous prevalence study in 2009 in this population. METHODS: In a door-to-door cross-sectional study of Tindigani village, a sample of residents was assessed for skeletal fluorosis and dental fluorosis. Diagnosis of skeletal fluorosis was based on pre-defined angles of deformity of the lower limbs. Dental fluorosis was diagnosed and graded using the Thylstrup and Fejerskov Index. Samples from current drinking water sources underwent fluoride analysis. RESULTS: Tindigani village had a population of 1,944 individuals. Of the 1,532 individuals who were screened, 45 had skeletal fluorosis, giving a prevalence of 3.3% (95% CI=2.4, 4.3). Dental fluorosis was present in 82.5% of those examined (95% CI=79.8, 85.3). Dental fluorosis was present in all individuals with skeletal fluorosis and at higher grades than in the rest of the population. Drinking water samples were collected from 28 sources. These included piped, surface, well, and borehole water sources. Fluoride concentrations ranged from 0.45-38.59 mg/L of fluoride. CONCLUSIONS: Skeletal fluorosis is an ongoing but preventable health problem in the current population. The delivery of sustainable low fluoride piped water to this community would be of clear health benefit. This has been addressed at a local level.

A proof-of-concept study of vicarious extinction learning and autonomic synchrony in parent-child dyads and posttraumatic stress disorder.

Though threat-extinction models continue to inform scientific study of traumatic stress, knowledge of learning and extinction as mechanisms linking exposure to psychopathology remains critically limited among youth. This proof-of-concept study advances the study of threat-extinction in youth by determining feasibility of electrodermal stimulation (EDS), vicarious extinction learning via their parent, and social threat learning in pediatric PTSD (pPTSD). Typically developing (TD) and PTSD-diagnosed youth in 45 mother-child dyads completed an extinction learning paradigm. The use of EDS was first investigated in a cohort of TD youth (n = 20) using a 2-day paradigm without vicarious extinction, while direct (for TD and pPTSD) and vicarious (for pPTSD) extinction were investigated in a 3-day paradigm (n = 25). Threat acquisition and extinction were monitored using skin-conductance response (SCR) and behavioral expectations of EDS. Using Bayesian modeling to accommodate this pilot sample, our results demonstrate: (1) EDS-conditioning to be highly feasible and well-tolerated across TD and trauma-exposed youth, (2) Successful direct and vicarious extinction learning in trauma-exposed youth, and (3) PTSD-associated patterns in extinction learning and physiological synchrony between parent-child dyads. In summary, these novel approaches have the potential to advance translational studies in the mechanistic understanding of parent-child transmission of risk and youth psychopathology.

Changing epidemiology of human enteroviruses (HEV) in a hand, foot and mouth disease outbreak in Vellore, south India.

PURPOSE: Hand Foot and mouth disease (HFMD) is a major childhood exanthematous disease causing outbreaks that have become a major public health threat in recent years. In Vellore district of Tamil Nadu, south India, occasional outbreaks are common among the paediatric age group, most commonly in those under 5years of age (U5s). CoxsackieA6, A4, A5, A9, A10, B2 and B5 are the common serotypes causing outbreaks. This study aimed to identify the molecular serotype of the causative agent, co-circulating in this region. METHODS: Adapting the WHO case definition, cases during an HFMD outbreak between October and December 2017, were identified by a clinical criterion of fever, mouth ulcers and rash in the extremities. Vesicle fluid from these lesions were collected in viral transport medium and transported cold to the Clinical Virology laboratory of a tertiary care hospital in Vellore. Identification of the causative agent was undertaken by two real time PCRs (EV1 and EV2) followed by sequencing the VP1-2C region and constructing a phylogenetic tree. RESULTS: Among the 31 HFMD patients included in this study, 23 (74.2%) were U5s, 3 (9.7%) were between 6 and 15 years and the remaining 5 (16.1%) were adolescents (>15 â€‹yrs). The outbreak ran a mild clinical course, with 22(71%) patients having fever as a prodromal symptom. Papulovesicular lesions characteristic of HFMD were present on all 31 (100%) patients' palms and soles, buttocks of 19 (61.3%), oral mucosa of 12 (38.7%), and all over the body in 4 (12.9%) patients. Coxsackie A6(75%) and Coxsackie A16(25%) were the pathogens associated with this outbreak. CONCLUSIONS: Changing epidemiology of HFMD was seen in this outbreak since; other serotypes apart from the classical Coxsackievirus serotypes causing HFMD outbreak were also found co-circulating. EV1 PCR was a better screening assay than EV2 PCR in this region. Continued surveillance and molecular serotyping are necessary for HFMD outbreaks in any region.

Screening for delirium and dementia in older hospitalised adults in Zambia.

Delirium prevalence and aetiology in older people in hospital or community settings in sub-Saharan Africa (SSA) is largely unknown. Cognitive screening tools designed for high-income countries (HICs) may be inappropriate due to cultural and educational differences, and delirium-specific measures lack validation in this context. The 'Identification and Intervention for Dementia in Elderly Africans' (IDEA) screen is a low-literacy tool developed and validated for dementia and delirium screening in Tanzania and Nigeria. This study aims to determine the prevalence and aetiology of delirium and dementia in older hospitalised patients in Zambia and to assess the utility of the IDEA screen for identification of major cognitive impairment in this setting. This was a blinded 4-month validation study which took place February-June 2015. Consecutive inpatient admissions of a rural mission hospital aged ≥60 years were administered the IDEA screen onadmission. Individuals were evaluated for dementia or delirium based on clinical examination, notes review and the Confusion Assessment Method. Delirium aetiological factors were recorded and classified (infectious/non-infectious). Of 136 patients recruited, dementia, delirium and major cognitive impairment were identified in 37 (27.2%), 45 (33.1%) and 62 (45.6%) respectively. Diagnostic accuracy of the IDEA screen for dementia and delirium was 0.661-0.795 (AUROC). Of those with delirium, 18 (40%) were classified infectious and 26 (57.8%) were classified non-infectious aetiologies. Dementia and delirium prevalence in older Zambian inpatients is comparable tohigh-income countries. The IDEA screen ispotentially clinically useful in this setting though diagnostic accuracy was lower than in initial validation studies. Non-infectious diseases are more highly represented amongst delirium precipitants than anticipated.

Immigrant Asian Indian Mothers' Experiences With Pregnancy, Childbirth, and Infant Care in the United States.

INTRODUCTION: The purpose of the study was to explore experiences of immigrant Asian Indian women with pregnancy, childbirth, and infant care in the United States. METHODOLOGY: This study employed a qualitative descriptive approach using semi-structured interviews and followed COREQ (COnsolidated criteria for REporting Qualitative research) guidelines for reporting qualitative research. Nine immigrant Asian Indian mothers residing in the mid-Atlantic region of the United States participated in the study. RESULTS: Four themes emerged: experiencing cultural differences during the perinatal period in the United States, choosing the best perinatal practices for maternal and infant care, recognizing family as the main support system, and having positive experiences with health care providers. DISCUSSION: Findings of this study shed light on the need for culturally appropriate care, including proper assessment of Asian Indian mothers' sociocultural aspects and cultural preferences and provision of support and information needed during the perinatal period.

The impact of childhood maltreatment on adaptive emotion regulation strategies.

OBJECTIVE: Childhood maltreatment is a potent known risk factor for psychopathology, accounting for nearly 30% of the risk for mental illness in adulthood. One mechanism by which maltreatment contributes to psychopathology is through impairments in emotion regulation. However, the impact of childhood maltreatment on adaptive regulation strategies remains unclear, particularly across positive and negative emotions. METHODS: Using Mechanical Turk, we recruited a cross-sectional sample of 207 adults (21-69 years) with and without childhood maltreatment exposure to complete an emotion regulation task where they were shown positive and negative emotional pictures and were instructed to reappraise or accept their emotions, alongside a non-instruction comparison condition. Participants rated their emotional intensity following each image, as well as perceived effectiveness of each strategy at the end of each block. We first investigated the impact of image valence and strategy use on the intensity of post-image emotions, followed by interacting both maltreatment exposure and severity with valence and strategy. FINDINGS: Surprisingly, maltreated individuals showed significantly higher emotional intensity compared to non-maltreated individuals, specifically toward positive images (F(2,194.6) = 5.01, p < 0.01). When examining strategy, the use of acceptance to regulate negative emotions was equally effective across all levels of maltreatment severity (F(2,194.6) = 15.93, p < 0.001), while reappraisal was effective only at lower maltreatment levels. CONCLUSION: These findings suggest that experiences of childhood maltreatment exert differential impacts on the ability to regulate positive and negative emotions using key adaptive regulation strategies, which has implications for both psychopathology risk and treatment interventions.

Evaluation of a low-resource screening strategy for ophthalmic pathologies and associated neurological morbidity in an older Tanzanian HIV-positive population.

Globally, 43 million people are living with HIV, 90% in developing countries. Increasing life expectancy with combination antiretroviral therapy (cART) results in chronic complications, including HIV-associated neurocognitive disorders (HAND) and eye diseases. HAND screening is currently challenging. Our aim was to evaluate clinical utility of retinopathy as a screening measure of HAND in older cART-treated individuals in Tanzania and feasibility of smartphone-based retinal screening in this low-resource setting. A cross-sectional systematic sample aged ≥ 50-years attending routine HIV follow-up in Tanzania were comprehensively assessed for HAND by American Academy of Neurology criteria and received ophthalmic assessment including smartphone-based retinal imaging. HAND and ophthalmic assessments were independent and blinded. Diagnostic accuracy was evaluated by AUROC curves. Of 129 individuals assessed, 69.8% were visually impaired. Thirteen had retinopathy. HAND prevalence was 66.7%. Retinopathy was significantly associated with HAND but HIV-disease factors (CD4, viral load) were not. Diagnostic accuracy of retinopathy for HAND was poor (AUROC 0.545-0.617) but specificity and positive predictive value were high. We conclude that ocular pathology and HAND appear highly prevalent in this low-resource setting. Although retinal screening cannot be used alone identify HAND, prioritization of individuals with abnormal retinal screening is a potential strategy in low-resource settings.

Longitudinal hippocampal circuit change differentiates persistence and remission of pediatric posttraumatic stress disorder.

BACKGROUND: Previous studies have identified functional brain abnormalities in pediatric posttraumatic stress disorder (pPTSD) suggesting altered frontoparietal-subcortical function during emotion processing. However, little is known about how the brain functionally changes over time in recovery versus the persistence of pPTSD. METHODS: This longitudinal study recruited 23 youth with PTSD and 28 typically developing (TD) youth (ages: 8.07-17.99). Within the PTSD group, nine remitted by the 1-year follow-up (Remit) while the remaining 14 persisted (PTSD). At each visit, youth completed an emotional processing task in which they viewed threat and neutral images during functional magnetic resonance imaging (fMRI). Voxelwise activation analyses using linear mixed-effects regression were conducted using a group (TD, Remit, PTSD) by time (baseline, follow-up) by valence (threat, neutral) design. Based on activation findings, a subsequent analysis of hippocampal functional connectivity was performed using a similar model. RESULTS: PTSD youth showed significantly increasing hippocampal activation to threatening images compared to TD youth, while the Remit group showed more similar patterns to TD youth. Subsequent hippocampal functional connectivity analyses reveal the Remit group showed increasing functional connectivity between the hippocampus and visual cortex (V4) while viewing threat stimuli. CONCLUSIONS: These findings represent one of the first preliminary reports of functional brain substrates of persistence and remission in pPTSD. Notably, increased hippocampal activation to threat and decreased connectivity in the hippocampal-V4 network over time may contribute to persistence in pPTSD. These findings suggest potential biomarkers that could be utilized to advance the treatment of pediatric PTSD.

Low levels of frailty in HIV-positive older adults on antiretroviral therapy in northern Tanzania.

There are over 3 million people in sub-Saharan Africa (SSA) aged 50 and over living with HIV. HIV and combined antiretroviral therapy (cART) exposure may accelerate the ageing in this population, and thus increase the prevalence of premature frailty. There is a paucity of data on the prevalence of frailty in an older HIV + population in SSA and screening and diagnostic tools to identify frailty in SSA. Patients aged ≥ 50 were recruited from a free Government HIV clinic in Tanzania. Frailty assessments were completed, using 3 diagnostic and screening tools: the Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and Brief Frailty Instrument for Tanzania (B-FIT 2). The 145 patients recruited had a mean CD4 + of 494.84 cells/µL, 99.3% were receiving cART and 72.6% were virally suppressed. The prevalence of frailty by FFP was 2.758%. FFP frailty was significantly associated with female gender (p = 0.006), marital status (p = 0.007) and age (p = 0.038). Weight loss was the most common FFP domain failure. The prevalence of frailty using the B-FIT 2 and the CFS was 0.68%. The B-FIT 2 correlated with BMI (r = - 0.467, p = 0.0001) and CD4 count in females (r = - 0.244, p = 0.02). There is an absence of frailty in this population, as compared to other clinical studies. This may be due to the high standard of HIV care at this Government clinic. Undernutrition may be an important contributor to frailty. It is unclear which tool is most accurate for detecting the prevalence of frailty in this setting as levels of correlation are low.

Potential Socioeconomic Effects of the COVID-19 Pandemic on Neural Development, Mental Health, and K-12 Educational Achievement.

The Novel Coronavirus (COVID-19) pandemic can affect more than a child's biological health. Lack of in-person schooling and increased stress can affect neurodevelopment, mental health, and later life outcomes, especially for students who are from low socioeconomic status (SES) households. Insights from neuroscience on child development reveal potential neural mechanisms and educational outcomes likely disrupted by the pandemic-and how this will disproportionally affect low-SES children. Three policies can combat these educational and emotional effects: increased access to online resources, investments in social-emotional health, and increased access to summer/out-of-school learning. Integrating the traditionally separate fields of neuroscience and educational research will be critical for developing and assessing the most impactful policies to improve the well-being and educational achievement of our most disadvantaged children.

The Association between Foveal Floor Measurements and Macular Hole Size.

PURPOSE: Determining which factors influence idiopathic macular hole (MH) size is important because it is a major prognostic indicator of treatment success. Foveal pit morphologic features are highly symmetrical within individuals and may influence idiopathic MH size. Using a series of patients with unilateral idiopathic MHs, we examined the foveal floor size of the fellow eye to evaluate its relationship with idiopathic MH size and postoperative outcomes. DESIGN: Retrospective observational study. PARTICIPANTS: Two hundred forty-one participants with a unilateral idiopathic MH treated with surgery and a fellow eye with no ocular pathologic features. METHODS: Both eyes underwent spectral-domain (SD) OCT imaging at the time of surgery. Minimum linear diameter (MLD) and base diameter (BD) defined idiopathic MH size. Foveal floor width (FFW) and minimal foveal thickness defined foveal pit morphologic features of the fellow eye. MAIN OUTCOME MEASURES: Baseline characteristics, SD OCT measurements, and preoperative variables were compared to determine their relationship with idiopathic MH size and postoperative visual acuity (VA) in logarithm of the minimum angle of resolution units. RESULTS: Foveal floor width was correlated with MLD (r = 0.36; P ≤ 0.001) and BD (r = 0.30; P ≤ 0.001), but not postoperative VA. Minimum linear diameter correlated with preoperative VA (r = 0.49; P ≤ 0.0001) and postoperative VA (r = 0.54; P ≤ 0.0001). A 2-stage regression model was developed to predict postoperative VA (r2 = 0.28): preoperative VA (ß = 0.36; P = 0.002) explained 13% of variability and MLD (ß = 0.29; P = 0.002), and idiopathic MH duration (ß = 0.23; P = 0.004) explained a further 16%. CONCLUSIONS: Foveal floor width of the fellow eye in patients with a unilateral idiopathic MH was correlated significantly with idiopathic MH size and may explain some of the variability in idiopathic MH size observed between individuals. However, FFW could not predict postoperative vision.

Determinants of vitreomacular traction width: associations with foveal floor width and vitreoretinal interface changes.

To investigate the relationship between vitreomacular traction (VMT) width, foveal floor width (FFW) and other anatomical characteristics between eyes of patients with VMT. Retrospective observational study of unilateral and bilateral VMT cases from two specialist ophthalmic centres in the United Kingdom (UK) between 2016 and 2018. For unilateral VMT cases: VMT width in the affected eye and FFW in the non-affected fellow eye were measured. In bilateral VMT cases: VMT width in both eyes was measured. In all cases, the presence of any associated inner or outer retinal, and vitreoretinal interface (VRI) changes, including epiretinal membrane, was also documented. 88 patients fulfilled the study criteria: 57 having unilateral and 31 bilateral VMT. For unilateral VMT cases, log (VMT) width was significantly correlated with FFW (r = 0.347, p = 0.008). Using stepwise linear regression, FFW (p = 0.004) and VRI changes (p = 0.03) were both significantly associated with VMT width with a R2 of 0.21. In bilateral VMT cases, there was strong positive correlation between log (VMT) width (r = 0.88, p < 0.001), and the presence of any VRI (r = 0.90, p < 0.001) or outer retinal changes (r = 0.50, p < 0.001) between the two eyes. These findings suggest that individual variations in foveal morphology as measured by the FFW, along with the presence of vitreoretinal interface changes, are associated with the extent of VMT width. VMT width, VRI and outer retinal changes were also highly correlated between eyes in bilateral VMT, suggesting that individual patient factors, which may be genetic or acquired, determine their presence and extent.

The effect of maternal dietary fat content and n-6:n-3 ratio on offspring growth and hepatic gene expression in the rat.

n-6 Fatty acids have been shown to exert pro-adipogenic effects, whereas n-3 fatty acids work in opposition. Increasing intakes of linoleic acid (LA; n-6) v. α-linolenic acid (ALA; n-3) in Western diets has led to the hypothesis that consumption of this diet during pregnancy may be contributing to adverse offspring health. This study investigated the effects of feeding a maternal dietary LA:ALA ratio similar to that of the Western diet (9:1) compared with a proposed 'ideal' ratio (about 1:1·5), at two total fat levels (18 v. 36 % fat, w/w), on growth and lipogenic gene expression in the offspring. Female Wistar rats were assigned to one of the four experimental groups throughout gestation and lactation. Offspring were culled at 1 and 2 weeks of age for sample collection. Offspring of dams consuming a 36 % fat diet were approximately 20 % lighter than those exposed to an 18 % fat diet (P < 0·001). Male, but not female, liver weight at 1 week was approximately 13 % heavier and had increased glycogen (P < 0·05), in offspring exposed to high LA (P < 0·01). Hepatic expression of lipogenic genes suggested an increase in lipogenesis in male offspring exposed to a 36 % fat maternal diet and in female offspring exposed to a low-LA diet, via increases in the expression of fatty acid synthase and sterol regulatory element-binding protein. Sexually dimorphic responses to altered maternal diet appeared to persist until 2 weeks of age. In conclusion, whilst maternal total fat content predominantly affected offspring growth, fatty acid ratio and total fat content had sexually dimorphic effects on offspring liver weight and composition.

SKA-31, an activator of Ca2+-activated K+ channels, improves cardiovascular function in aging.

Aging represents an independent risk factor for the development of cardiovascular disease, and is associated with complex structural and functional alterations in the vasculature, such as endothelial dysfunction. Small- and intermediate-conductance, Ca2+-activated K+ channels (KCa2.3 and KCa3.1, respectively) are prominently expressed in the vascular endothelium, and pharmacological activators of these channels induce robust vasodilation upon acute exposure in isolated arteries and intact animals. However, the effects of prolonged in vivo administration of such compounds are unknown. In our study, we hypothesized that such treatment would ameliorate aging-related cardiovascular deficits. Aged (∼18 months) male Sprague Dawley rats were treated daily with either vehicle or the KCa channel activator SKA-31 (10 mg/kg, intraperitoneal injection; n = 6/group) for 8 weeks, followed by echocardiography, arterial pressure myography, immune cell and plasma cytokine characterization, and tissue histology. Our results show that SKA-31 administration improved endothelium-dependent vasodilation, reduced agonist-induced vascular contractility, and prevented the aging-associated declines in cardiac ejection fraction, stroke volume and fractional shortening, and further improved the expression of endothelial KCa channels and associated cell signalling components to levels similar to those observed in young male rats (∼5 months at end of study). SKA-31 administration did not promote pro-inflammatory changes in either T cell populations or plasma cytokines/chemokines, and we observed no overt tissue histopathology in heart, kidney, aorta, brain, liver and spleen. SKA-31 treatment in young rats had little to no effect on vascular reactivity, select protein expression, tissue histology, plasma cytokines/chemokines or immune cell properties. Collectively, these data demonstrate that administration of the KCa channel activator SKA-31 improved aging-related cardiovascular function, without adversely affecting the immune system or promoting tissue toxicity.

The impact of exposure to cafeteria diet during pregnancy or lactation on offspring growth and adiposity before weaning.

Exposure to maternal obesity during early-life can have adverse consequences for offspring growth and adiposity. We aimed to assess the relative contributions of exposure to maternal obesity, induced by a highly varied cafeteria diet, during pregnancy and lactation on these measures in rat offspring prior to weaning. Female Wistar rats were fed either a control (C) or cafeteria diet (O) for 8 weeks before mating, throughout pregnancy and lactation. Offspring were cross-fostered at birth to a dam on the same (CC,OO) or alternate diet prior to birth (CO,OC). Feeding a cafeteria diet based on 40 different foods, was associated with a sustained period of elevated energy intake before birth and during lactation (up to 1.7-fold), through increased sugar, total fat and saturated fat intake, and lower protein consumption. Cafeteria fed dams sustained greater weight than animals fed a control chow diet and greater perirenal adiposity by the end of lactation. Exposure to obesity during pregnancy was associated with lower offspring birth weight and body weight in early-postnatal life. In contrast, exposure during lactation alone reduced offspring weight but increased adiposity in male CO offspring before weaning. This research highlights that exposure to maternal obesity during lactation alone can programme adiposity in a sex specific manner.