Physiological Challenges Research Articles

Convolutional neural network for classification of eight types of arrhythmia using 2D time\u2013frequency feature map from standard 12-lead electrocardiogram

Electrocardiograms (ECGs) are widely used for diagnosing cardiac arrhythmia based on the deformation of signal shapes due to changes in various heart diseases. However, these abnormal signs may not be observed in some 12 ECG channels, depending on the location, the heart shape, and the type of cardiac arrhythmia. Therefore, it is necessary to closely and comprehensively observe ECG records acquired from 12 channel electrodes to diagnose cardiac arrhythmias accurately. In this study, we proposed a clustering algorithm that can classify persistent cardiac arrhythmia as well as episodic cardiac arrhythmias using the standard 12-lead ECG records and the 2D CNN model using the time–frequency feature maps to classify the eight types of arrhythmias and normal sinus rhythm. The standard 12-lead ECG records were provided by China Physiological Signal Challenge 2018 and consisted of 6877 patients. The proposed algorithm showed high performance in classifying persistent cardiac arrhythmias; however, its accuracy was somewhat low in classifying episodic arrhythmias. If our proposed model is trained and verified using more clinical data, we believe it can be used as an auxiliary device for diagnosing cardiac arrhythmias.

Utilizing 3D Arterial Spin Labeling to Identify Cerebrovascular Leak and Glymphatic Obstruction in Neurodegenerative Disease.

New approaches are required to successfully intervene therapeutically in neurodegenerative diseases. Addressing the earliest phases of disease, blood brain barrier (BBB) leak before the accumulation of misfolded proteins has significant potential for success. To do so, however, a reliable, noninvasive and economical test is required. There are two potential methods of identifying the BBB fluid leak that results in the accumulation of normally excluded substances which alter neuropil metabolism, protein synthesis and degradation with buildup of misfolded toxic proteins. The pros and cons of dynamic contrast imaging (DCI or DCE) and 3D TGSE PASL are discussed as potential early identifying methods. The results of prior publications of the 3D ASL technique and an overview of the associated physiologic challenges are discussed. Either method may serve well as reliable physiologic markers as novel therapeutic interventions directed at the vasculopathy of early neurodegenerative disease are developed. They may serve well in addressing other neurologic diseases associated with either vascular leak and/or reduced glymphatic flow.

Silencing of Aquaporin Homologue Accumulates Uric Acid and Decreases the Lifespan of the Asian Citrus Psyllid, Diaphorina citri (Hemiptera: Liviidae).

Simple SummaryThe use of RNA interference has become increasingly popular for investigating insect physiology, testing the functionality of insect genes and as a potential control strategy. Hemiptera include many vectors for destructive plant diseases. A major characteristic of the order of Hemiptera is feeding on the phloem sap of their plant hosts. Phloem feeders face high osmotic stress between the gut lumen and hemolymph due to the high level of sucrose in phloem sap. Targeting the osmoregulation mechanisms in Diaphorina citri Kuwayama, which transmits ‘Candidatus Liberibacter asiaticus’, the putative causal agent of Huanglongbing in citrus may lead to an effective control strategy. Herein we downregulate the expression of aquaporin, representing a major mechanism of osmoregulation, by RNA interference.The Asian citrus psyllid, Diaphorina citri Kuwayama is devastating the citrus industry worldwide. It transmits ‘Candidatus Liberibacter asiaticus’, the pathogen of Huanglongbing in citrus. RNA interference is an excellent tool for functional genomics and for screening target genes for pest control. Herein, we silenced the aquaporin (AQP) gene (DcAQP) homologue in D. citri to study its functionality and whether it could be a good target for a control strategy. AQP is an integral membrane channel protein that aids in the rapid flux of water and other small solutes that move across the lipid membrane. In Hemiptera, it is well established that AQP plays important roles in adjusting to physiological challenges including (1) regulating osmotic stress between the gut lumen and hemolymph after imbibing large quantities of a low nitrogen, sugar-rich liquid diet; (2) avoiding or preventing dehydration and desiccation; and (3) surviving at elevated temperatures. The dsRNA-DcAQP was applied twice to nymphs of the 4th and 5th instars through a soaking technique. Silencing AQP caused a significant increase in nymph mortality. Emerged adults showed malformations and a shorter lifespan. Silencing DcAQP provoked alterations in some metabolites and increased the uric acid content in emerged adults. DcAQP could be a useful target to control D. citri.

63 The “Brighton Connector”: A Simple, Reproducible and Cost-Effective Technique for Bilateral Antegrade Cerebral Perfusion During Aortic Arch Surgery

Abstract Aim Surgery of the aortic arch presents significant technical and physiological challenges. Selective antegrade cerebral perfusion (SACP) during arch surgery has been shown to improve mortality and neurological outcomes in these patients. At our centre, we aimed to develop a safe, reliable, and cost-effective technique to provide bilateral antegrade cerebral perfusion without the need of another pump head. Method We developed our system using equipment that is included in the accessory packaging for the Sorin Xtra cell saver system, which is readily available in cardiac surgical units nationwide, but often discarded as it is not required. An EOPA arterial return cannula and the TRUE FLOW RDB SACP cannula were joined using our novel connection. Results A single surgeon has used the “Brighton Connector” for 6 patients in the last two years. All patients made a satisfactory recovery with a 0% rate of mortality or permanent neurological deficit. Conclusions All components in our circuit are already approved for use in cardiac theatres, and the connection tubing would normally be discarded, making our method cost neutral. We demonstrate through a case series that mortality and neurological outcomes are good and comparable with other techniques.

Transcriptome profiling reveals differential gene expression in the rumen of Hu lambs at different developmental stages

The development of the rumen is a critical physiological challenge in newborn ruminants. However, the molecular mechanism underlying different stages of rumen development in sheep remains poorly understood. Here, RNA sequencing and bioinformatics analysis were performed to compare the transcription profiles of rumen development at 7, 28 and 56 days of birth (D7, D28 and D56). We identified 1246, 2257 and 627 differentially expressed genes (DEGs) between D7 and D28, between D7 and D56, between D28 and D56, respectively. Also, 70 DGEs were co-expressed at these three time points. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated most DEGs mainly related to transporter activity, channel activity and metabolism pathways. Noteworthy, the expression levels of most genes (CA4, CA9, CA12 and CA14) in nitrogen metabolic pathways were negatively correlated with the papilla length and width, but the papilla length and width were positively correlated with the expression of genes (PLA2G3, SLC26A9, SLC34A3) in ion transport pathway, suggesting that these genes may be involved in nitrogen metabolic and ion transport pathway and thus affect rumen development. These results provide new insight into the changes in RNA expression at different time points of rumen development in Hu sheep.

High-speed functional photoacoustic microscopy using a water-immersible two-axis torsion-bending scanner

Optical-resolution photoacoustic microscopy (OR-PAM) can provide functional, anatomical, and molecular images at micrometer level resolution with an imaging depth of less than 1 mm in tissue. However, the imaging speed of traditional OR-PAM is often low due to the point-by-point mechanical scanning and cannot capture time-sensitive dynamic information. In this work, we demonstrate a recent effort in improving the imaging speed of OR-PAM, using a newly developed water-immersible two-axis scanner. Driven by water-compatible electromagnetic actuation force, the new scanning mirror employs a novel torsion-bending mechanism to achieve fast 2D scanning. The torsion scanning along the fast-axis works in the resonant model, and the bending scanning along the slow-axis operate at the quasi-static mode. The scanning speed and scanning range along the two axes can be independently adjusted. Steered by the two-axis torsion-bending scanning mirror immersed in water, the focused excitation light and the generated acoustic wave can be confocally aligned over the entire imaging area. Thus, a high imaging speed can be achieved without sacrificing the detection sensitivity. Equipped with the torsion-bending scanner, the high-speed OR-PAM system has achieved a cross-sectional frame rate of 400 Hz, and a volumetric imaging speed of 1 Hz over a field of view of 1.5 × 2.5 mm2. We have also demonstrated high-speed OR-PAM of the hemodynamic changes in response to pharmaceutical and physiological challenges in small animal models in vivo. We expect the torsion-bending scanner based OR-PAM will find matched biomedical studies of tissue dynamics.

Integrating thermal tolerance, water balance and morphology: An experimental study on dung beetles.

The impacts of extreme and rising mean temperatures due to climate change can pose significant physiological challenges for insects. An integrated approach that focuses on mechanisms of body temperature regulation, water balance and morphology may help to unravel the functional traits underpinning thermoregulation strategies and the most relevant trade-offs between temperature and water balance regulation. Here, we focused on four species of tunneler dung beetles as important providers of ecosystem services. In this experimental research, we first quantified two traits related to desiccation resistance and tolerance via experimental tests, and subsequently defined two levels of resistance and tolerance (i.e. low and high) according to significant differences among species. Second, we identified morphological traits correlated with water balance strategies, and we found that desiccation resistance and tolerance increased with small relative size of spiracles and wings. High levels of desiccation tolerance were also correlated with small body mass. Third, by integrating thermal tolerance with functional traits based on desiccation resistance and desiccation tolerance, we found that the species with the highest survival rates under elevated temperatures (Euoniticellus fulvus) was characterized by low desiccation resistance and high desiccation tolerance. Our results suggest shared physiological and morphological responses to temperature and desiccation, with potential conflicts between the need to regulate heat and water balance. They also highlighted the sensitivity of a large species such as Geotrupes stercorarius to warm and arid conditions with potential implications for its geographic distribution and the provisioning of ecosystem services under a climate change scenario.

Structural changes to the brood pouch of male pregnant seahorses (Hippocampus abdominalis) facilitate exchange between father and embryos.

Embryonic growth and development require efficient respiratory gas exchange. Internal incubation of developing young thus presents a significant physiological challenge, because respiratory gas diffusion to embryos is impeded by the additional barrier of parental tissue between the embryo and the environment. Therefore, live-bearing species exhibit a variety of adaptations facilitating respiratory gas exchange between the parent (usually the mother) and embryos. Syngnathid fishes are the only vertebrates to exhibit male pregnancy, allowing comparative studies of the biology and evolution of internal incubation of embryos, independent of the female reproductive tract. Here, we examine the fleshy, sealed, seahorse brood pouch, and provide the first quantification of structural changes to this gestational organ across pregnancy. We used histological analysis and morphometrics to quantify the surface area for exchange across the brood pouch epithelium, and the structure of the vascular bed of the brood pouch. We show dramatic remodelling of gestational tissues as pregnancy progresses, including an increase in tortuosity of the gestational epithelium, an increase in capillary density, and a decrease in diffusion distance between capillaries and the pouch lumen. These changes produce an increased surface area and expansion of the vascular bed of the placenta that likely facilitates respiratory gas exchange. These changes mirror the remodelling of gestational tissue in viviparous amniotes and elasmobranchs, and provide further evidence of the convergence of adaptations to support pregnancy in live-bearing animals.

Convolutional squeeze-and-excitation network for ECG arrhythmia detection

Automatic detection of arrhythmia through an electrocardiogram (ECG) is of great significance for the prevention and treatment of cardiovascular diseases. In Convolutional neural network, the ECG signal is converted into multiple feature channels with equal weights through the convolution operation. Multiple feature channels can provide richer and more comprehensive information, but also contain redundant information, which will affect the diagnosis of arrhythmia, so feature channels that contain arrhythmia information should be paid attention to and given larger weight. In this paper, we introduced the Squeeze-and-Excitation (SE) block for the first time for the automatic detection of multiple types of arrhythmias with ECG. Our algorithm combines the residual convolutional module and the SE block to extract features from the original ECG signal. The SE block adaptively enhances the discriminative features and suppresses noise by explicitly modeling the interdependence between the channels, which can adaptively integrate information from different feature channels of ECG. The one-dimensional convolution operation over the time dimension is used to extract temporal information and the shortcut connection of the Se-Residual convolutional module in the proposed model makes the network easier to optimize. Thanks to the powerful feature extraction capabilities of the network, which can effectively extract discriminative arrhythmia features in multiple feature channels, so that no extra data preprocessing including denoising in other methods are need for our framework. It thus improves the working efficiency and keeps the collected biological information without loss. Experiments conducted with the 12-lead ECG dataset of the China Physiological Signal Challenge (CPSC) 2018 and the dataset of PhysioNet/Computing in Cardiology (CinC) Challenge 2017. The experiment results show that our model gains great performance and has great potential in clinical.

Maternal morphine intake during pregnancy and lactation affects the circadian clock of rat pups

Early-life morphine exposure causes a variety of behavioural and physiological alterations observed later in life. In the present study, we investigated the effects of prenatal and early postnatal morphine on the maturation of the circadian clockwork in the suprachiasmatic nucleus and the liver, and the rhythm in aralkylamine N-acetyltransferase activity in the pineal gland. Our data suggest that the most affected animals were those born to control, untreated mothers and cross-fostered by morphine-exposed dams. These animals showed the highest mesor and amplitude in the rhythm of Per2, Nr1d1 but not Per1 gene expression in the suprachiasmatic nuclei (SCN) and arrhythmicity in AA-NAT activity in the pineal gland. In a similar pattern to the rhythm of Per2 expression in the SCN, they also expressed Per2 in a higher amplitude rhythm in the liver. Five of seven specific genes in the liver showed significant differences between groups in their expression. A comparison of mean relative mRNA levels suggests that this variability was caused mostly by cross-fostering, animals born to morphine-exposed dams that were cross-fostered by control mothers and vice versa differed from both groups of natural mothers raising offspring. Our data reveal that the circadian system responds to early-life morphine administration with significant changes in clock gene expression profiles both in the SCN and in the liver. The observed differences between the groups suggest that the dose, timing and accompanying stress events such as cross-fostering may play a role in the final magnitude of the physiological challenge that opioids bring to the developing circadian clock.

Multi-label correlation guided feature fusion network for abnormal ECG diagnosis

Electrocardiographic (ECG) abnormalities are the most intuitive manifestation in the clinical diagnosis of cardiovascular disease. Although significant progress has been achieved in diagnosing ECG abnormalities, current convolutional neural network (CNN) based methods still show a relatively high rate of misdiagnosis. On the one hand, the ECG data an abnormality imbalance problem. On the other hand, the previous work did not consider the multi-label correlations of the ECG abnormalities. The main objective of this paper is to design an ECG abnormal event detection model based on multi-label correlation guided feature fusion. First, the proposed method calculates the correlation of different ECG abnormality labels on the basis of their frequency and Bayesian conditional probability and divides the ECG abnormalities into groups of different levels. The first-level ECG abnormalities are those that have the highest frequency and the second-level abnormalities are those that have a higher probability of other ECG abnormalities given the first-level ECG abnormalities, and so on. Then, the feature fusion strategy uses the multi-label correlation to guide the fusion of features of different levels. Specifically, the features of the first-level ECG signals are integrated into the features of the second-level ECG signals and the features of the former two-level ECG signals are integrated into the features of the third-level ECG signals. Furthermore, a multi-scale receptive field fusion module is proposed to enhance the multi-scale representation ability of the features. To evaluate the performance of the proposed method, it is validated against the 1st China physiological signal challenge dataset, and it achieved better results compared with other state-of-the-art methods. This proposed method achieves a precision score of 0.816, a sensitivity score of 0.845 and an F1-score of 0.827, which are better than other methods. The comparative analysis shows that the proposed method demonstrates the effectiveness in abnormal ECG diagnosis.

Effect of bio-banding on physiological and technical-tactical key performance indicators in youth elite soccer

ABSTRACT Bio-banding has been introduced to reduce the impact of inter-individual differences due to biological maturation among youth athletes. Existing studies in youth soccer have generally examined the pilot-testing application of bio-banding. This is the first study that investigated whether bio-banded (BB) versus chronological age (CA) competition affects reliable physiological and technical-tactical in-game key performance indicators (KPIs) using a randomized cross-over repeated measures design. Sixty-five youth elite soccer players from the under-13 (U13) and under-14 (U14) age category and with maturity offsets (MO) between −2.5 and 0.5 years, competed in both a BB and CA game. For statistical analysis, players were divided into four sub-groups according to CA and MO: U13MOlow (CA ≤ 12.7, MO ≤ −1.4), U13MOhigh (CA ≤ 12.7, MO > −1.4), U14MOlow (CA > 12.7, MO ≤ −1.4), U14MOhigh (CA > 12.7, MO > −1.4). The two-factor mixed ANOVA revealed significant (p < .05) interactions between competition format and sub-group for the KPIs high accelerations ( = .176), conquered balls ( = .227) and attack balls ( = .146). Especially, U13MOhigh (i.e. early maturing players) faced a higher physiological challenge by having more high accelerations (|d| = 0.6) in BB games. Notably, U14MOlow (i.e. late maturing players) had more opportunities to show their technical-tactical abilities during BB games with more conquered balls (|d| = 1.1) and attack balls (|d| = 1.6). Affected KPIs indicate new challenges and learning opportunities during BB competition depending on a player’s individual maturity status. Bio-banding can beneficially be applied to enhance the talent development of youth elite soccer players.

Engineering of benzoxazinoid biosynthesis in Arabidopsis thaliana: Metabolic and physiological challenges

Plant specialised metabolites constitute a layer of chemical defence. Classes of the defence compounds are often restricted to a certain taxon of plants, e.g. benzoxazinoids (BX) are characteristically detected in grasses. BXs confer wide-range defence by controlling herbivores and microbial pathogens and are allelopathic compounds. In the crops maize, wheat and rye high concentrations of BXs are synthesised at an early developmental stage. By transfer of six Bx-genes (Bx1 to Bx5 and Bx8) it was possible to establish the biosynthesis of 2,4-dihydroxy-1,4-benzoxazin-3-one glucoside (GDIBOA) in a concentration of up to 143 nmol/g dry weight in Arabidopsis thaliana. Our results indicate that inefficient channeling of substrates along the pathway and metabolisation of intermediates in host plants might be a general drawback for transgenic establishment of specialised metabolite biosynthesis pathways. As a consequence, BX levels required for defence are not obtained in Arabidopsis. We could show that indolin-2-one (ION), the first specific intermediate, is phytotoxic and is metabolised by hydroxylation and glycosylation by a wide spectrum of plants. In Arabidopsis, metabolic stress due to the enrichment of ION leads to elevated levels of salicylic acid (SA) and in addition to its intrinsic phytotoxicity, ION affects plant morphology indirectly via SA. We could show that Bx3 has a crucial role in the evolution of the pathway, first based on its impact on flux into the pathway and, second by C3-hydroxylation of the phytotoxic ION. Thereby BX3 interferes with a supposedly generic detoxification system towards the non-specific intermediate.

Cervical to Petrous Carotid Artery High-Flow Bypass for Carotid Artery Pseudoaneurysm Through Zygomatic Approach: 2-Dimensional Operative Video

Pseudoaneurysms of the cervical internal carotid artery may generate grave risk from catastrophic rupture, thromboembolic stroke, or mass effect. They have many causes, including malignancy, infection, and iatrogenic and most commonly blunt or penetrating trauma.1 These aneurysms require treatment to eliminate their risk. Treatment options include trapping, with or without revascularization, or endovascular stenting. Trapping without revascularization requires evaluation of the cerebral collateral under a physiological challenge, which is usually done with a balloon occlusion test, which is not applicable in this lesion.2 Occluding the carotid without revascularization carries the risk of delayed ischemia and aneurysm formation.3,4 Carotid stenting has been applied in the treatment of these lesions5,6; however, the extent of the lesion in our patient from the carotid bifurcation to the petrous carotid makes endovascular treatment challenging. We present a patient with a delayed post-traumatic pseudoaneurysm of the carotid artery that extended from the bifurcation to the petrous carotid who was treated with trapping and high-flow saphenous vein bypass from the proximal cervical internal carotid to the petrous carotid. Adequate exposure of the petrous carotid to perform anastomosis requires a thorough knowledge of the anatomy and surgical nuances, which we demonstrate here through a zygomatic approach.7 The patient consented to the procedure and publication of imaging. Image at 2:28 from Al-Mefty O, Operative Atlas of Meningiomas, © LWW, 1997, with permission.

Skeletal muscle histidine-containing dipeptide contents are increased in freshwater turtles (C. picta bellii) with cold-acclimation

Freshwater turtles found in higher latitudes can experience extreme challenges to acid-base homeostasis while overwintering, due to a combination of cold temperatures along with the potential for environmental hypoxia. Histidine-containing dipeptides (HCDs; carnosine, anserine and balenine) may facilitate pH regulation in response to these challenges, through their role as pH buffers. We measured the HCD content of three tissues (liver, cardiac and skeletal muscle) from the anoxia-tolerant painted turtle (C. picta bellii) acclimated to either 3 or 20 °C. HCDs were detected in all tissues, with the highest content shown in the skeletal muscle. Turtles acclimated to 3 °C had more HCD in their skeletal muscle than those acclimated to 20 °C (carnosine = 20.8 ± 4.5 vs 12.5 ± 5.9 mmol·kg DM−1; ES = 1.59 (95%CI: 0.16–3.00), P = 0.013). The higher HCD content shown in the skeletal muscle of the cold-acclimated turtles suggests a role in acid-base regulation in response to physiological challenges associated with living in the cold, with the increase possibly related to the temperature sensitivity of carnosine's dissociation constant.

Abstract P373: The Occurrence Of Neurovascular And Adipose Neuropathy In The Genetically Diverse Het3 Mouse With Aging

Energy homeostasis and adipose tissue metabolism are regulated in large part through peripheral sympathetic nerve innervation of metabolically important tissues and organs. This neural communication from the brain to adipose tissues results in release of the neurotransmitter norepinephrine that regulates energy expenditure through modulation of lipolysis, adipogenesis, ‘browning’ (development of brown adipocytes in white adipose depots), and non-shivering thermogenesis. Subcutaneous white adipose tissue (scWAT) is an energy storing tissue that is highly plastic, responding to metabolic need by changing mass and cellularity, as well as responding to challenges (including cold temperature, exercise, fasting) by modifying neural activity and metabolism. Within scWAT lies a dense bed of nerves and blood vessels that are integrated closely, and in large part, rely on one another to function properly. Even if not directly innervating the blood vessels themselves (as is the case with capillaries), neurites that appear to innervate single adipocytes use these blood vessels as scaffolding to traverse the tissue. We have recently demonstrated that under pathological conditions (obesity and aging), scWAT innervation decreases through a process termed ‘adipose neuropathy’. With advanced age the small fiber peripheral nerve endings in adipose die back, including reducing contact with adipose-resident blood vessels (as observed previously in the C57BL6/J mouse). This likely poses a physiological challenge for metabolism and for vascular or adipose tissue health and function. For this work, we compared C57BL6/J mice with the more genetically diverse HET3 mouse model, established for the NIA’s Intervention Testing Program to more accurately represent the variability of age-related mortality/morbidity. We investigated incidence of peripheral neuropathy with aging (skin, scWAT muscle) as well as changes to the neurovascular supply of scWAT across several ages in both males and females. We also investigated the anti-aging drug Rapamycin as a potential means to prevent or reduce adipose neuropathy. We found that HET3 mice display a reduced neuropathy phenotype compared to inbred C56BL6/J mice. Importantly, the nerve die-back around blood vessels was not observed in the HET3 model. However, male HET3 mice did reveal neuropathic phenotypes by 62wks of age, characterized by decreased mechanoreception in hind paw skin, reduced NMJ occupation, and decreased expression of the Schwann cell marker Sox10 in scWAT. Female HET3 mice appeared to have increased protection from neuropathy until advanced age (126wks) when they began to show stronger phenotypes than males (excluding Sox10 analysis.) Despite its success as a longevity treatment in mice, rapamycin had little to no effect on reducing or preventing the onset of adipose neuropathy.

Investigating the effect of relationship satisfaction on postpartum women’s health-related quality of life in Burkina Faso: a cross-sectional analysis

IntroductionThe period following childbirth poses physiological, physical, social and psychological challenges to women that may affect their quality of life. Few studies in Africa have explored women’s health-related quality of...

Paediatric Airway

The paediatric airway has always been a challenge to both the novice and the experienced airway manager. In this review, we have addressed the challenges of a paediatric airway, especially for the occasional paediatric anaesthesiologist. Children are not small adults and present unique anatomical, physiological and emotional challenges. It is imperative to be aware of these differences and adequately prepare to manage the normal or difficult airway appropriately. In this review, we have analysed recent publications in indexed journals detailing airway challenges in paediatrics and their management. Recent advances and recommendations include the usage of microcuffed tubes, various sizes of supraglottic airways and multiple paediatric-airway friendly videoscopes. Awareness of the differences and how to manage them efficiently is the key to delivery of a safe anaesthetic in small children.

Childhood sexual abuse history amplifies the link between disease burden and inflammation among older adults with HIV

As they age, people living with HIV (PLWH) experience greater rates of inflammation-related health conditions compared to their HIV-negative peers. Because early life adversity can exaggerate proinflammatory effects of later physiological challenges, inflammation may be higher among PLWH with these combined risks, which could inform intervention approaches to mitigate multimorbidity. In this cross-sectional analysis, we investigated individual and combined effects of childhood sexual abuse (CSA) history and physiological burden (Veterans Aging Cohort Study Index scores) on serum cytokine and C-reactive protein (CRP) levels among PLWH. Participants (n ​= ​131; age 54 and older) were patients at an outpatient HIV clinic who completed a psychosocial survey and biomedical research visit as part of a larger study. 93% were virally suppressed, and 40% reported experiencing sexual abuse in childhood. Composite cytokine levels (summarizing IL-6, TNF-α, IFN-γ), CRP, and disease burden did not differ significantly between those who had a history of CSA and those who did not. Participants with greater disease burden had higher composite cytokine levels (r ​= ​0.29, p ​= ​0.001). The disease burden by CSA interaction effect was a significant predictor of composite cytokine levels (but not CRP), and remained significant after controlling for age, sex, race, BMI, anti-inflammatory medication use, selective serotonin reuptake inhibitor use, depressive symptoms, and smoking status (F(1, 114) ​= ​5.68, p ​= ​0.02). In follow-up simple slopes analysis, greater disease burden was associated with higher cytokine levels among those with CSA history (b ​= ​0.03, SE ​= ​0.008, p<0.001), but not among those without CSA history. Further, in the context of greater disease burden, individuals with a CSA history tended to have higher cytokine levels than those without a CSA history (b ​= ​0.38, SE ​= ​0.21, p ​= ​0.07). These data suggest that the physiological sequelae of childhood trauma may persist into older age among those with HIV. Specifically, links between physiological burden and inflammation were stronger among survivors of CSA in this study. The combined presence of CSA history and higher disease burden may signal a greater need for and potential benefit from interventions to reduce inflammation, an area for future work.

Adolescent female rats prone to the activity based anorexia (ABA) paradigm have altered hedonic responses and cortical astrocyte density compared to resistant animals

ObjectiveAnhedonia, which in part involves the lack of pleasure in consuming palatable food, is a long-lasting symptom observed in patients both when acutely ill and when long term recovered from Anorexia Nervosa. The neurocircuitry underlying this phenomenon is not well understood. Here we use the preclinical activity-based anorexia (ABA) model in adolescent female rats to assess the impact of excessive exercise, limited food intake and acute weight loss, on adolescent female rat orofacial responding to intraoral sucrose, as measured by the taste reactivity test (TRT). Animals were identified as either prone or resistant to this paradigm based on a weight loss criterion. Measures of food intake, running wheel activity, taste reactivity and medial prefrontal cortex astrocyte expression were compared across groups. MethodsAdolescent female rats implanted with an intraoral catheter were given a TRT using 1 M (M) sucrose at baseline, max weight loss (25% weight loss from start of ABA or 7 full days on the paradigm) or 10 days recovered from the ABA paradigm. Animals were sacrificed after the final TRT and astrocyte density was measured via immunohistochemistry. ResultsAnimals resistant to the ABA paradigm ran less than prone animals during the ABA period. Additionally, we found that resistant animals displayed more cumulative ‘liking’ responses to sucrose compared to prone animals at maximum weight loss. Finally, we found prone animals 10-days recovered from ABA had reduced medial prefrontal cortex astrocyte density compared to levels in resistant animals. DiscussionRats presented with the physiological challenge of the ABA paradigm either adapt their behavior to stabilize their body weight (i.e. resistant), or rapidly lose weight (i.e. prone). Furthermore, we found that prone animals have reduced orofacial responding to 1 M sucrose at maximum weight loss compared to responses in resistant animals, and this anhedonia-like behavior may be a result of reduced astrocyte density that affects cortical function.