ATLAS: Mapping ATtention's Location And Size to probe five modes of serial and parallel search.

Conventional visual search tasks do not address attention directly and their core manipulation of 'set size' - the number of displayed items - introduces stimulus confounds that hinder interpretation. However, alternative approaches have not been widely adopted, perhaps reflecting their complexity, assumptions, or indirect attention-sampling. Here, a new procedure, the ATtention Location And Size ('ATLAS') task used probe displays to track attention's location, breadth, and guidance during search. Though most probe displays comprised six items, participants reported only the single item they judged themselves to have perceived most clearly - indexing the attention 'peak'. By sampling peaks across variable 'choice sets', the size and position of the attention window during search was profiled. These indices appeared to distinguish narrow- from broad attention, signalled attention to pairs of items where it arose and tracked evolving attention-guidance over time. ATLAS is designed to discriminate five key search modes: serial-unguided, sequential-guided, unguided attention to 'clumps' with local guidance, and broad parallel-attention with or without guidance. This initial investigation used only an example set of highly regular stimuli, but its broader potential should be investigated.

Epigenetic control of multiple genes with a lentiviral vector encoding transcriptional repressors fused to compact zinc finger arrays.

Gene silencing without gene editing holds great potential for the development of safe therapeutic applications. Here, we describe a novel strategy to concomitantly repress multiple genes using zinc finger proteins fused to Krüppel-Associated Box repression domains (ZF-Rs). This was achieved via the optimization of a lentiviral system tailored for the delivery of ZF-Rs in hematopoietic cells. We showed that an optimal design of the lentiviral backbone is crucial to multiplex up to three ZF-Rs or two ZF-Rs and a chimeric antigen receptor. ZF-R expression had no impact on the integrity and functionality of transduced cells. Furthermore, gene repression in ZF-R-expressing T cells was highly efficient in vitro and in vivo during the entire monitoring period (up to 10 weeks), and it was accompanied by epigenetic remodeling events. Finally, we described an approach to improve ZF-R specificity to illustrate the path toward the generation of ZF-Rs with a safe clinical profile. In conclusion, we successfully developed an epigenetic-based cell engineering approach for concomitant modulation of multiple gene expressions that bypass the risks associated with DNA editing.

Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells.

Nucleobase editors represent an emerging technology that enables precise single-base edits to the genomes of eukaryotic cells. Most nucleobase editors use deaminase domains that act upon single-stranded DNA and require RNA-guided proteins such as Cas9 to unwind the DNA prior to editing. However, the most recent class of base editors utilizes a deaminase domain, DddAtox, that can act upon double-stranded DNA. Here, we target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers (ZFs). We also identify a broad variety of Toxin-Derived Deaminases (TDDs) orthologous to DddAtox that allow us to fine-tune properties such as targeting density and specificity. TDD-derived ZF base editors enable up to 73% base editing in T cells with good cell viability and favorable specificity.

Post-mortem formation of ethanol: Is 1-propanol a reliable marker? A proof-of-concept study using an in vitro putrefactive environment setup.

Ethanol is the psychoactive substance identified most frequently in post-mortem specimens. Unfortunately, interpreting post-mortem ethanol concentrations can be difficult because of post-mortem alcohol redistribution and the possibility of post-mortem alcohol neogenesis. Indeed, in the time interval between death and sample collection, the decedent may be exposed to non-controlled environments for an extended period, promoting microbial colonization. Many authors report that in the presence of carbohydrates and other biomolecules, various species of bacteria, yeast, and fungi can synthesize ethanol and other volatile substances in vitro and in vivo. The aim of this study was to study the impact of several variables on microbial ethanol production as well as develop a mathematical model that could estimate the microbial-produced ethanol in correlation with the most significant consensual produced higher alcohol, 1-propanol. An experimental setup was developed using human blood samples and cadaveric fragments incubated under strictly anaerobic conditions to produce a novel substrate, "cadaveric putrefactive blood" mimicking post-mortem corpse conditions. The samples were analyzed daily for ethanol and 1-propanol using an HS-GC-FID validated method. The formation of ethanol was evaluated considering different parameters such as putrefactive stage, blood glucose concentration, storage temperature, and storage time. Statistical analysis was performed using the Mann-Whitney non-parametric test and simple linear regression. The results indicate that the early putrefactive stage, high blood glucose concentration, high temperature, and time of incubation increase microbial ethanol production. In addition, the developed mathematical equation confirms the feasibility of using 1-propanol as a marker of post-mortem ethanol production.

Preeclampsia-Associated Cardiovascular Risk Factors 6 Months and 2 Years After Pregnancy: The P4 Study.

BACKGROUND: Increased cardiovascular risk following preeclampsia is well established and there are signs of early cardiovascular aging 6 months postpartum. This study assessed whether blood pressure (BP) and other cardiovascular measures are abnormal 2 years postpartum in the same cohort to determine ongoing risk markers. METHODS: Six months and 2 years postpartum, BP was measured using sphygmomanometry, 24-hour ambulatory BP monitoring, and noninvasive central BP. Anthropometric measures, blood, and urine biochemistry were performed. Cross-sectional comparisons between preeclampsia and normotensive pregnancy (NP) groups and longitudinal comparisons within each group were made at 6 months and 2 years. RESULTS: Two years postpartum, 129 NP, and 52 preeclampsia women were studied who also had 6 months measures. At both time points, preeclampsia group had significantly higher BP (office BP 2 years, 112±12/72±8 versus 104±9/67±7 mm Hg NP; [P<0.001]; mean ambulatory BP monitoring 116±9/73±8 versus 106±8/67±6 mm Hg NP; [P<0.001]). No significant BP changes noted 6 months to 2 years within either group. Office BP thresholds of 140 mm Hg systolic and 90 mm Hg diastolic classified 2% preeclampsia and 0% NP at 2 years. American Heart Association 2017 criteria (above normal, >120/80 mm Hg) classified 25% versus 8% (P<0.002), as did our reference range threshold of 122/79 mm Hg. American Heart Association criteria classified 60% post-preeclampsia versus 16% after NP with above-normal ambulatory BP monitoring (P<0.001). Other cardiovascular risk markers more common 2 years post-preeclampsia included higher body mass index (median 26.6 versus 23.1, P=0.003) and insulin resistance. CONCLUSIONS: After preeclampsia, women have significantly higher BP 6 months and 2 years postpartum, and have higher body mass index and insulin-resistance scores, increasing their future cardiovascular risk. Regular cardiovascular risk screening should be implemented for all who have experienced preeclampsia.

Superhydrophobic Surface Modification of Polymer Microneedles Enables Fabrication of Multimodal Surface-Enhanced Raman Spectroscopy and Mass Spectrometry Substrates for Synthetic Drug Detection in Blood Plasma.

Microneedles are widely used substrates for various chemical and biological sensing applications utilizing surface-enhanced Raman spectroscopy (SERS), which is indeed a highly sensitive and specific analytical approach. This article reports the fabrication of a nanoparticle (NP)-decorated microneedle substrate that is both a SERS substrate and a substrate-supported electrospray ionization (ssESI) mass spectrometry (MS) sample ionization platform. Polymeric ligand-functionalized gold nanorods (Au NRs) are adsorbed onto superhydrophobic surface-modified polydimethylsiloxane (PDMS) microneedles through the control of various interfacial interactions. We show that the chain length of the polymer ligands dictates the NR adsorption process. Importantly, assembling Au NRs onto the micrometer-diameter needle tips allows the formation of highly concentrated electromagnetic hot spots, which provide the SERS enhancement factor as high as 1.0 × 106. The micrometer-sized area of the microneedle top and high electromagnetic field enhancement of our system can be loosely compared with tip-enhanced Raman spectroscopy, where the apex of a plasmonic NP-functionalized sharp probe produces high-intensity plasmonic hot spots. Utilizing our NR-decorated microneedle substrates, the synthetic drugs fentanyl and alprazolam are analyzed with a subpicomolar limit of detection. Further analysis of drug-molecule interactions on the NR surface utilizing the Langmuir adsorption model suggests that the higher polarizability of fentanyl allows for a stronger interaction with hydrophilic polymer layers on the NR surface. We further demonstrate the translational aspect of the microneedle substrate for both SERS- and ssESI-MS-based detection of these two potent drugs in 10 drug-of-abuse (DOA) patient plasma samples with minimal preanalysis sample preparation steps. Chemometric analysis for the SERS-based detection shows a very good classification between fentanyl, alprazolam, or a mixture thereof in our selected 10 samples. Most importantly, ssESI-MS analysis also successfully identifies fentanyl or alprazolam in these same 10 DOA plasma samples. We believe that our multimodal detection approach presented herein is a highly versatile detection technology that can be applicable to the detection of any analyte type without performing any complicated sample preparation.

Inducible CRISPR-targeted "knockdown" of human gut Bacteroides in gnotobiotic mice discloses glycan utilization strategies.

Understanding how members of the human gut microbiota prioritize nutrient resources is one component of a larger effort to decipher the mechanisms defining microbial community robustness and resiliency in health and disease. This knowledge is foundational for development of microbiota-directed therapeutics. To model how bacteria prioritize glycans in the gut, germfree mice were colonized with 13 human gut bacterial strains, including seven saccharolytic Bacteroidaceae species. Animals were fed a Western diet supplemented with pea fiber. After community assembly, an inducible CRISPR-based system was used to selectively and temporarily reduce the absolute abundance of Bacteroides thetaiotaomicron or B. cellulosilyticus by 10- to 60-fold. Each knockdown resulted in specific, reproducible increases in the abundances of other Bacteroidaceae and dynamic alterations in their expression of genes involved in glycan utilization. Emergence of these "alternate consumers" was associated with preservation of community saccharolytic activity. Using an inducible system for CRISPR base editing in vitro, we disrupted translation of transporters critical for utilizing dietary polysaccharides in Phocaeicola vulgatus, a B. cellulosilyticus knockdown-responsive taxon. In vitro and in vivo tests of the resulting P. vulgatus mutants allowed us to further characterize mechanisms associated with its increased fitness after knockdown. In principle, the approach described can be applied to study utilization of a range of nutrients and to preclinical efforts designed to develop therapeutic strategies for precision manipulation of microbial communities.

The MothersBabies Study, an Australian Prospective Cohort Study Analyzing the Microbiome in the Preconception and Perinatal Period to Determine Risk of Adverse Pregnancy, Postpartum, and Child-Related Health Outcomes: Study Protocol.

The microbiome has emerged as a key determinant of human health and reproduction, with recent evidence suggesting a dysbiotic microbiome is implicated in adverse perinatal health outcomes. The existing research has been limited by the sample collection and timing, cohort design, sample design, and lack of data on the preconception microbiome. This prospective, longitudinal cohort study will recruit 2000 Australian women, in order to fully explore the role of the microbiome in the development of adverse perinatal outcomes. Participants are enrolled for a maximum of 7 years, from 1 year preconception, through to 5 years postpartum. Assessment occurs every three months until pregnancy occurs, then during Trimester 1 (5 + 0-12 + 6 weeks gestation), Trimester 2 (20 + 0-24 + 6 weeks gestation), Trimester 3 (32 + 0-36 + 6 weeks gestation), and postpartum at 1 week, 2 months, 6 months, and then annually from 1 to 5 years. At each assessment, maternal participants self-collect oral, skin, vaginal, urine, and stool samples. Oral, skin, urine, and stool samples will be collected from children. Blood samples will be obtained from maternal participants who can access a study collection center. The measurements taken will include anthropometric, blood pressure, heart rate, and serum hormonal and metabolic parameters. Validated self-report questionnaires will be administered to assess diet, physical activity, mental health, and child developmental milestones. Medications, medical, surgical, obstetric history, the impact of COVID-19, living environments, and pregnancy and child health outcomes will be recorded. Multiomic bioinformatic and statistical analyses will assess the association between participants who developed high-risk and low-risk pregnancies, adverse postnatal conditions, and/or childhood disease, and their microbiome for the different sample types.

The effects of the (fentanyl-fueled) drug overdose epidemic on medicolegal death investigation in the United States.

The evolving opioid epidemic in the United States, fueled by illicit fentanyl, has greatly increased deaths from illicit drug use. These nonnatural deaths require formal death investigation. The National Association of Medical Examiners states in its Forensic Autopsy Performance Standards that autopsy remains a necessary component for proper investigation of suspected acute overdose deaths. If a death investigation office lacks adequate resources to investigate all deaths under its jurisdiction while meeting expected standards, then that office may be forced to consider altering its protocols for investigation by changing the types of deaths investigated or the extent of its investigations. Drug death investigations take longer to complete because novel illicit drugs and mixtures of drugs complicate toxicological analyses, prolonging a family's wait for completion of a death certificate and autopsy report. Public health agencies must also wait for results, but some agencies have developed mechanisms for rapid notification of preliminary results to allow timely deployment of public health resources. The increased deaths have strained the resources of medicolegal death investigation systems throughout the United States. Given the significant workforce shortage of forensic pathologists, newly trained forensic pathologists are too few to meet the demand. Nevertheless, forensic pathologists (and all pathologists) must make time to present their work and themselves to medical students and pathology trainees to encourage an understanding of the importance of quality medicolegal death investigation and autopsy pathology and to provide a model that can encourage interest in a career in forensic pathology.

Oogenesis in Caenorhabditis elegans.

BACKGROUND: The nematode, Caenorhabditis elegans has proven itself as a valuable model for investigating metazoan biology. C. elegans have a transparent body, an invariant cell lineage, and a high level of genetic conservation which makes it a desirable model organism. Although used to elucidate many aspects of somatic biology, a distinct advantage of C. elegans is its well annotated germline which allows all aspects of oogenesis to be observed in real time within a single animal. C. elegans hermaphrodites have two U-shaped gonad arms which produce their own sperm that is later stored to fertilise their own oocytes. These two germlines take up much of the internal space of each animal and germ cells are therefore the most abundant cell present within each animal. This feature and the genetic phenotypes observed for mutant worm gonads have allowed many novel findings that established our early understanding of germ cell dynamics. The mutant phenotypes also allowed key features of meiosis and germ cell maturation to be unveiled. SUMMARY: This review will focus on the key aspects that make C. elegans an outstanding model for exploring each feature of oogenesis. This will include the fundamental steps associated with germline function and germ cell maturation and will be of use for those interested in exploring reproductive metazoan biology. KEY MESSAGES: Since germ cell biology is highly conserved in animals, much can be gained from study of a simple metazoan like C. elegans. Past findings have enhanced understanding on topics that would be more laborious or challenging in more complex animal models.

Establishing Minimal Clinically Important Difference in Sleep Outcomes after Spinal Cord Stimulation in Patients with Chronic Pain Disorders.

INTRODUCTION: As one of the most common medical conditions for which patients seek medical care, chronic pain can be debilitating. The relationship between chronic pain and sleep is thought to be bidirectional, suggesting that treatment of one can be beneficial to the other. There is mounting evidence that spinal cord stimulation (SCS) improves aspects of sleep. How meaningful that is to patients' lives has not been ascertained. OBJECTIVE: The aim of the current study was to further elucidate the effect of SCS on sleep by examining the relationship between pain outcome measures with the insomnia severity index (ISI) and to establish the minimally clinical important difference (MCID), which is defined as the smallest noticeable change that an individual perceives as clinically significant. MATERIALS AND METHODS: We prospectively collected ISI, Epworth sleepiness scale (ESS), Numerical Rating Scale, McGill Pain Questionnaire-Short Form, Oswestry Disability Index, Beck Depression Inventory, and Pain Catastrophizing Scale data both pre- and postoperatively for chronic pain patients who underwent SCS placement and had long-term outcomes. The ISI is a well-studied questionnaire used to assess an individual's level of insomnia. RESULTS: We correlated the ESS and ISI with pain outcome measures in sixty-four patients at a mean follow-up of 9.8 ± 2.9 months. The ISI showed correlations with disability as measured through the Oswestry Disability Index (p = 0.014) and depression as measured through the Beck Depression Inventory (p = 0.024). MCID values for the ISI were calculated using both anchor- and distribution-based methods. The minimal detectable change method resulted in an MCID of 2.4 points, standard error of measurement resulted in an MCID of 2.6 points, and the change difference resulted in an MCID of 2.45. The receiver operating characteristic method yielded an MCID of 0.5-point change with an area under the curve of 0.61. CONCLUSION: This study successfully established MCID ranges for the ISI outcome measure to help gauge improvement in insomnia after SCS. The ISI has ample evidence of its validity in assessment of insomnia, and MCID values of 2.4-2.6 correlate with improvement in disability and depression in our patients.

Float like a Butterfly: Comparison between Off and On-Ice Torso Kinematics during the Butterfly Stance in Ice Hockey Goalkeepers.

In ice hockey, the butterfly style/stance is a technique distinguished by the goalkeepers (goalie) dropping to their knees to block attempts to score. Although this goalie style has been around for many years, comparisons between on and off-ice attire has not been undertaken. Therefore, this preliminary study compared differences in torso acceleration and energy expenditure by way of the Metabolic Equivalent of Task (MET) during off-ice and on-ice butterfly stances/saves. Seven participants each performed 8 on-ice butterfly saves/stances whilst wearing full hockey attire followed by 8 off-ice butterfly stances without wearing full hockey attire whilst torso acceleration was collected. The off-ice movement significantly increased vertical torso acceleration (p < 0.01, d > 0.90) with increased MET, compared to on-ice motion. Despite no significant difference in anteroposterior and mediolateral torso kinematics, vector magnitudes were significantly greater (p < 0.01, d > 0.90) when the stance was performed off-ice. The increased vertical acceleration observed when goalies performed the movement off-ice could be due to a failure to maintain adequate posture without the support of the external load. The results of this study may help inform off-ice training interventions for ice hockey goalkeeping.

Desformylflustrabromine (dFBr), a positive allosteric modulator of α4ß2 nicotinic acetylcholine receptors decreases voluntary ethanol consumption and preference in male and female Sprague-Dawley rats.

Alcohol use disorder is a medical condition that impacts millions of individuals worldwide. Although there are a few pharmacotherapeutic options for alcohol-dependent individuals; there is a need for the development of novel and more effective therapeutic approaches. Alcohol and nicotine are commonly co-abused, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Desformylflustrabromine (dFBr), a positive allosteric modulator of the α4ß2 nAChRs has been shown to reduce nicotine intake, compulsive-like behavior and neuropathic pain in animal models. dFBr has also been previously shown to cross the blood-brain-barrier. We have recently shown that dFBr can attenuate the response to an acute, hypnotic dose of ethanol, via ß2 nAchR. Here, we have investigated the effect of dFBr in modulating ethanol consumption using the intermittent access two-bottle choice (IA2BC) model of voluntary ethanol consumption in male and female Sprague Dawley rats. We show that dFBr selectively reduced ethanol but not sucrose consumption in the IA2BC model. Furthermore, dFBr decreased preference for ethanol in both male and female rats. No rebound increase in ethanol intake was observed after the washout period after dFBr treatment. The ability of dFBr to decrease ethanol consumption, along with its previously demonstrated ability to decrease nicotine self-administration in rodents, suggest that dFBr is an attractive therapeutic candidate to target both nicotine and alcohol abuse.

Stubborn Exercise Responders-Where to Next?

There is a wide variance in the magnitude of physiological adaptations after resistance or endurance training. The incidence of "non" or "poor" responders to training has been reported to represent as high as 40% of the project's sample. However, the incidence of poor responders to training can be ameliorated with manipulation of either the training frequency, intensity, type and duration. Additionally, global non-response to cardio-respiratory fitness training is eliminated when evaluating several health measures beyond just the target variables as at least one or more measure improves. More research is required to determine if altering resistance training variables results in a more favourable response in individuals with an initial poor response to resistance training. Moreover, we recommend abandoning the term "poor" responders, as ultimately the magnitude of change in cardiorespiratory fitness in response to endurance training is similar in "poor" and "high" responders if the training frequency is subsequently increased. Therefore, we propose "stubborn" responders as a more appropriate term. Future research should focus on developing viable physiological and lifestyle screening tests that identify likely stubborn responders to conventional exercise training guidelines before the individual engages with training. Exerkines, DNA damage, metabolomic responses in blood, saliva and breath, gene sequence, gene expression and epigenetics are candidate biomarkers that warrant investigation into their relationship with trainability. Crucially, viable biomarker screening tests should show good construct validity to distinguish between different exercise loads, and possess excellent sensitivity and reliability. Furthermore "red flag" tests of likely poor responders to training should be practical to assess in clinical settings and be affordable and non-invasive. Early identification of stubborn responders would enable optimization of training programs from the onset of training to maintain exercise motivation and optimize the impact on training adaptations and health.

Corrigendum: The P4 Study: Postpartum Maternal and Infant Faecal Microbiome 6 Months After Hypertensive Versus Normotensive Pregnancy.

[This corrects the article DOI: 10.3389/fcimb.2022.646165.].

Gut Microbiome and Metabolome Variations in Self-Identified Muscle Builders Who Report Using Protein Supplements.

Muscle builders frequently consume protein supplements, but little is known about their effect on the gut microbiota. This study compared the gut microbiome and metabolome of self-identified muscle builders who did or did not report consuming a protein supplement. Twenty-two participants (14 males and 8 females) consumed a protein supplement (PS), and seventeen participants (12 males and 5 females) did not (No PS). Participants provided a fecal sample and completed a 24-h food recall (ASA24). The PS group consumed significantly more protein (118 ± 12 g No PS vs. 169 ± 18 g PS, p = 0.02). Fecal metabolome and microbiome were analyzed by using untargeted metabolomics and 16S rRNA gene sequencing, respectively. Metabolomic analysis identified distinct metabolic profiles driven by allantoin (VIP score = 2.85, PS 2.3-fold higher), a catabolic product of uric acid. High-protein diets contain large quantities of purines, which gut microbes degrade to uric acid and then allantoin. The bacteria order Lactobacillales was higher in the PS group (22.6 ± 49 No PS vs. 136.5 ± 38.1, PS (p = 0.007)), and this bacteria family facilitates purine absorption and uric acid decomposition. Bacterial genes associated with nucleotide metabolism pathways (p < 0.001) were more highly expressed in the No PS group. Both fecal metagenomic and metabolomic analyses revealed that the PS group's higher protein intake impacted nitrogen metabolism, specifically altering nucleotide degradation.

The P4 Study: Postpartum Maternal and Infant Faecal Microbiome 6 Months After Hypertensive Versus Normotensive Pregnancy.

OBJECTIVE/HYPOTHESIS: To explore potential differences in faecal microbiome between women, and their infants, who had normotensive pregnancies (NP) and those who had a hypertensive pregnancy (HP), either gestational hypertension (GH) or preeclampsia (PE). METHODS: This is a sub study of P4 (Postpartum Physiology, Psychology, and Paediatrics Study) and includes 18 mother-infant pairs: 10 NP and 8 HP (HP as defined by blood pressure > 140/90mmHg; of which 6 had PE, and 2 GH), six months postpartum. The participating mothers collected stool samples from themselves and their infants. 16S rRNA V3-V4 amplicons were used to study the faecal microbiome. RESULTS: The sample of women and their infants were mostly primiparous (n =16) with vaginal birth (n = 14). At the time of faecal sampling 8 women were using hormonal contraception, and one HP woman remained on an antihypertensive. All women had blood pressure < 130/80mmHg, and 10 had high BMI (> 30). All infants had started solids, 8 were exclusively breastfed, 1 exclusively formula fed and 9 both. Three infants had been exposed to a course of antibiotics. Six months postpartum, there were no significant differences in alpha or beta diversity between the gut microbiota of HP and NP women (P > 0.05). However, a statistically significant difference was detected in alpha diversity between infants following HP and NP, with lower diversity levels in HP infants (P < 0.05). It was also found that at a genus and species level, the gut microbiota of HP women was enriched with Bifidobacterium and Bifididobacterium sp. and depleted in Barnisiella and Barnesiella intestinihominis when compared to NP women (P < 0.05). Similarly, the gut microbiota of infants born from HP was enriched in Streptococcus infantis and depleted in Sutterella, Sutterella sp., Bacteroides sp. and Clostridium aldenense compared to infants born from NP (P < 0.05). DISCUSSION: While our findings are at best preliminary, due to the very small sample size, they do suggest that the presence of hypertension in pregnancy may adversely affect the maternal microbiota postpartum, and that of their infants. Further analysis of postpartum microbiome data from future studies will be important to validate these early findings and provide further evidence about the changes in the microbiota in the offspring of women following hypertensive disorders of pregnancy (HDP), including possible links to the causes of long-term cardiovascular disease, the prevalence of which is increased in women who have experienced HDP.

Depression, anxiety and posttraumatic stress disorder six months following preeclampsia and normotensive pregnancy: a P4 study.

BACKGROUND: Mental health is an integral part of overall health. Mental health disorders following childbirth are common and poor maternal mental health has consequences for both the mother and her infant. Preeclampsia is also relatively common in pregnancy but there is little known about the intersection between these two important conditions. Gaining a better understanding of the psychological consequences following preeclampsia is important, especially the link with depression, anxiety and posttraumatic stress disorder. If women who experience preeclampsia are recognised as being at increased risk of poor mental health, targeted screening in the postpartum period should be implemented. AIMS: To describe the prevalence and symptom severity of depression, anxiety and posttraumatic stress disorder at six months postpartum in women, who had a diagnosis of preeclampsia, compared to those who had normal blood pressure in pregnancy. METHODS: The mental health component of the prospective cohort study, the Postpartum, Physiology, Psychology and Paediatric follow-up study (P4 Study) was used. Women diagnosed with preeclampsia (n = 90) and those who were normotensive during pregnancy (n = 302) completed the Edinburgh Postnatal Depression Scale, General Anxiety Disorder Scale, and the Posttraumatic Stress Diagnostic Scale or Posttraumatic Stress Diagnostic Sclae-5 at six months postpartum. RESULTS: At six months postpartum, depressive scores were similar in both groups but a higher proportion of women from the preeclampsia group scored above the threshold for depression (2% v 7% p = 0.04). There were no differences between the groups in the prevalence or severity of anxiety or PTSD. However, more women in the preeclampsia group reported their birth experience as a traumatic event (1% vs 7%, p = 0.01). On correlation testing and modelling, booking Edinburgh Postnatal Depression Scale score, any mental health history, experiencing birth as traumatic and the General Anxiety Disorder Scale score were independent predictors of postpartum Edinburgh Postnatal Depression Scale scores. CONCLUSION: The postpartum clinical care of women with preeclampsia often focusses on the immediate physical health issues, but these women may also benefit from mental health screening. Targeted screening of preeclamptic women in the postpartum period may lead to more timely referral and initiation of treatment. TRIAL REGISTRATION: Retrospectively registered on 18/11/2013 with the Australian and New Zealand Clinical Trials Registry. Registration Number: ACTRN12613001260718 .

NeuroLISP: High-level symbolic programming with attractor neural networks.

Despite significant improvements in contemporary machine learning, symbolic methods currently outperform artificial neural networks on tasks that involve compositional reasoning, such as goal-directed planning and logical inference. This illustrates a computational explanatory gap between cognitive and neurocomputational algorithms that obscures the neurobiological mechanisms underlying cognition and impedes progress toward human-level artificial intelligence. Because of the strong relationship between cognition and working memory control, we suggest that the cognitive abilities of contemporary neural networks are limited by biologically-implausible working memory systems that rely on persistent activity maintenance and/or temporal nonlocality. Here we present NeuroLISP, an attractor neural network that can represent and execute programs written in the LISP programming language. Unlike previous approaches to high-level programming with neural networks, NeuroLISP features a temporally-local working memory based on itinerant attractor dynamics, top-down gating, and fast associative learning, and implements several high-level programming constructs such as compositional data structures, scoped variable binding, and the ability to manipulate and execute programmatic expressions in working memory (i.e., programs can be treated as data). Our computational experiments demonstrate the correctness of the NeuroLISP interpreter, and show that it can learn non-trivial programs that manipulate complex derived data structures (multiway trees), perform compositional string manipulation operations (PCFG SET task), and implement high-level symbolic AI algorithms (first-order unification). We conclude that NeuroLISP is an effective neurocognitive controller that can replace the symbolic components of hybrid models, and serves as a proof of concept for further development of high-level symbolic programming in neural networks.

Intrauterine exposure to preeclampsia does not impair vascular health in children.

Background and objectives: Preeclampsia is a serious multisystem blood pressure disorder during pregnancy that is associated with increased long-term risk of cardiovascular disease to the mother and offspring. We investigated the vascular health of children exposed to intrauterine preeclampsia. Materials and methods: This was a cross-sectional study of offspring in a prospective cohort of women with complications during pregnancy. Children aged between 2 and 5 years [median age 4.7 (2.8, 5.1) years] exposed to intrauterine preeclampsia (n = 26) or normotensive controls (n = 34), were recruited between July 2020 and April 2021. Vascular health was assessed by measuring aortic intima-media thickness and pulse wave velocity. Univariate generalized linear regression models were used to explore associations between vascular measurements and explanatory variables. Results: Children exposed to preeclampsia had a lower body mass index at assessment (15.5 vs. 16.2 kg/m2, p = 0.04), birth weight (2.90 vs. 3.34 kg, p = 0.004), gestational age at birth (37.5 vs. 39.4 weeks, p < 0.001) and higher frequency of preterm birth (27% vs. 6%, p = 0.02). There were no differences in vascular health between children exposed to preeclampsia vs. controls (mean aortic intima-media thickness 0.575 mm vs. 0.563 mm, p = 0.51, pulse wave velocity 4.09 vs. 4.18 m/s, p = 0.54) and there were no significant associations in univariate analyses. Conclusions: There were no major adverse differences in vascular health which contrasts with existing studies. This suggests exposure to intrauterine preeclampsia may result in a less severe cardiovascular phenotype in young children. While reassuring, longitudinal studies are required to determine if and when exposure to intrauterine preeclampsia affects vascular health in children.