Search

A right aortic arch with an isolated left innominate artery from the pulmonary artery is an exceedingly rare congenital cardiac malformation. We describe the management and complex surgical timing considerations in two such cases, successfully operated on day 4 and 7 months of age, including the use of cranial ultrasound as a helpful tool to guide decision-making. We also describe the first reported association of this defect with a 4q25 deletion encompassing the LEF1 gene.

Ectopic calcification disorders, including Generalized Arterial Calcification of Infancy (GACI) and Pseudoxanthoma Elasticum are rare but impactful on individuals, healthcare and society, with significant associated morbidity, mortality and healthcare costs. Available therapies are not curative and focus on reducing extracellular calcification to limit progression of the arteriopathy that is responsible for much of the morbidity and, in the case of GACI, significant early mortality (approximately 50% in infancy). In this article, current and emerging medical approaches are reviewed and critiqued, including dietary manipulation, phosphate binders, bisphosphonates, tissue nonspecific alkaline phosphatase inhibitors, ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) enzyme replacement, allele-specific therapies, gene therapies, and antibody targeted treatment. Available therapies may limit further arterial calcification, but in GACI in particular, significant calcification can be present at birth, contributing to high infant mortality. This highlights the need for new approaches that aim to reverse established calcification, rather than merely slow its progression. Recently, a promising new class of antibody-targeted nanoparticle therapeutics has emerged that can reverse established arterial calcification in animals, restoring arterial elasticity. In one realization, nanoparticles carry established chelators, such as ethylenediaminetetraacetic disodium acid, to sites of arterial damage, concentrating the impact of the chelator where it is needed and limiting off-target effects. Such drugs would complement existing and emerging therapies, such as ENPP1 enzyme replacement, that slow or prevent progression of calcification, by offering an opportunity to “reset” arterial health in ectopic calcification disorders. At present, ectopic calcification disorders are challenging to treat effectively and carry a high burden of morbidity and mortality, particularly in GACI. Recent drug developments offer good reason to be hopeful for a new era of effective therapeutics that may reverse established arterial disease as well as halt its progression.

Objectives Improving medical student placements relies on being able to reliably evaluate how students experience clinical learning environments. The Undergraduate Clinical Education Environment Measure (UCEEM) is an increasingly used validated tool designed to allow such evaluations. This study aims to further characterize how the UCEEM relates to qualitative evaluation. methods Students on placement at one hospital were invited to complete the UCEEM before and after the implementation of an innovative new placement structure. Additionally, focus groups were employed to collect qualitative data on their experiences. a novel protocol to triangulate the output of the UCEEM with the qualitative data was developed. Results The UCEEM showed good internal consistency (Cronbach's Alpha 0.79-0.91) and internal correlation. Implementation of the intervention created significant improvements in the overall UCEEM scores ( P = .008) and in the “Learning in and through work and quality of supervision” ( P = .048), “Preparedness for student entry” ( P = .033) and “Workplace interaction patterns and student inclusion” ( P = .039) domains. The triangulation of qualitative data with UCEEM output showed that the UCEEM allowed evaluation of some perceptions not reached through open questioning. However, mixed interpretations of UCEEM items by students led to the conflation of themes and challenges in deriving the meaning behind the score. This appeared to be the case for 14 of the 24 UCEEM items. Conclusion This investigation adds to the literature supporting the UCEEM as a validated tool. It also elucidates the limitations and relationships to qualitative data that investigators need to be aware of in its use.

Background Greater body mass index is associated with cardiovascular remodeling in adolescents. However, body mass index cannot differentiate between adipose and nonadipose tissues. We examined how visceral and subcutaneous adipose tissue are linked with markers of early cardiovascular remodeling, independently from nonadipose tissue. Methods and Results Whole‐body magnetic resonance imaging was done in 82 adolescents (39 overweight/obese; 36 female; median age, 16.3 [interquartile range, 14.4–18.1] years) to measure body composition and cardiovascular remodeling markers. Left ventricular diastolic function was assessed by echocardiography. Waist, waist:height ratio, and body mass index z scores were calculated. Residualized nonadipose tissue, subcutaneous adipose tissue, and visceral adipose tissue variables, uncorrelated with each other, were constructed using partial regression modeling to allow comparison of their individual contributions in a 3‐compartment body composition model. Cardiovascular variables mostly related to nonadipose rather than adipose tissue. Nonadipose tissue was correlated positively with left ventricular mass (r=0.81), end‐diastolic volume (r=0.70), stroke volume (r=0.64), left ventricular mass:end‐diastolic volume (r=0.37), and systolic blood pressure (r=0.35), and negatively with heart rate (r=−0.33) (all P

Robots are becoming increasingly sophisticated in the execution of complex tasks. However, an area that requires development is the ability to act in dynamically changing environments. To advance this, developments have turned towards understanding the human brain and applying this to improve robotics. The present study used electroencephalogram (EEG) data recorded from 54 human participants whilst they performed a two-choice task. A build-up of motor activity starting around 400 ms before response onset, also known as the lateralized readiness potential (LRP), was observed. This indicates that actions are not simply binary processes but rather, response-preparation is gradual and occurs in a temporal window that can interact with the environment. In parallel, a robot arm executing a pick-and-place task was developed. The understanding from the EEG data and the robot arm were integrated into the final system, which included cell assemblies (CAs)—a simulated spiking neural network—to inform the robot to place the object left or right. Results showed that the neural data from the robot simulation were largely consistent with the human data. This neurorobotics study provides an example of how to integrate human brain recordings with simulated neural networks in order to drive a robot.

This work explores the process of adapting the segmented attractor network to a lifelong learning setting. Taking inspirations from Hopfield networks and content-addressable memory, the segmented attractor network is a powerful tool for associative memory applications. The network's performance as an associative memory is analyzed using multiple metrics. In addition to the network's general hit rate, its capability to recall unique memories and their frequency is also evaluated with respect to time. Finally, additional learning techniques are implemented to enhance the network's recall capacity in the application of lifelong learning. These learning techniques are based on human cognitive functions such as memory consolidation, prediction, and forgetting.

Many currently available hardware implementations of the unsupervised self-organizing feature map (SOFM) algorithm utilize complementary metal–oxide–semiconductor (CMOS)-only circuits that often compromise key behaviors of the SOFM algorithm due to complexity. We propose a neuromorphic architecture harnessing the unique properties of ferroelectric field-effect transistors (FeFETs) and gated-resistive random access memory (RRAM) for in-memory computing to implement the SOFM algorithm. The FeFET-based synapse, organized in a novel circuit, is able to compute the input-weight Euclidean error in memory via the saturation drain current. The self-decaying states of the gated-RRAM allow for a self-decaying neighborhood and learning rate implementation to allow for convergence and lifelong learning. This novel architecture is able to successfully cluster benchmarks (RGB colors and MNIST handwritten digits) and real-life datasets, such as COVID-19 patient chest X-rays completely unsupervised. The architecture also demonstrates a significant amount of robustness to device variability and damaged neurons. In addition, the proposed architecture is completely parallelized and provides a power-efficient platform for implementing the SOFM algorithm.

As commercial geospatial intelligence data becomes more widely available, algorithms using artificial intelligence need to be created to analyze it. Maritime traffic is annually increasing in volume, and with it the number of anomalous events that might be of interest to law enforcement agencies, governments, and militaries. This work proposes a data fusion pipeline that uses a mixture of artificial intelligence and traditional algorithms to identify ships at sea and classify their behavior. A fusion process of visual spectrum satellite imagery and automatic identification system (AIS) data was used to identify ships. Further, this fused data was further integrated with additional information about the ship’s environment to help classify each ship’s behavior to a meaningful degree. This type of contextual information included things such as exclusive economic zone boundaries, locations of pipelines and undersea cables, and the local weather. Behaviors such as illegal fishing, trans-shipment, and spoofing are identified by the framework using freely or cheaply accessible data from places such as Google Earth, the United States Coast Guard, etc. The pipeline is the first of its kind to go beyond the typical ship identification process to help aid analysts in identifying tangible behaviors and reducing the human workload.

Abstract Background The cell-surface attachment protein (Env) of the HERV-K(HML-2) lineage of endogenous retroviruses is a potentially attractive tumour-associated antigen for anti-cancer immunotherapy. The human genome contains around 100 integrated copies (called proviruses or loci) of the HERV-K(HML-2) virus and we argue that it is important for therapy development to know which and how many of these contribute to protein expression, and how this varies across tissues. We measured relative provirus expression in HERV-K(HML-2), using enriched RNA-Seq analysis with both short- and long-read sequencing, in three Mantle Cell Lymphoma cell lines (JVM2, Granta519 and REC1). We also confirmed expression of the Env protein in two of our cell lines using Western blotting, and analysed provirus expression data from all other relevant published studies. Results Firstly, in both our and other reanalysed studies, approximately 10% of the transcripts mapping to HERV-K(HML-2) came from Env-encoding proviruses. Secondly, in one cell line the majority of the protein expression appears to come from one provirus (12q14.1). Thirdly, we find a strong tissue-specific pattern of provirus expression. Conclusions A possible dependency of Env expression on a single provirus, combined with the earlier observation that this provirus is not present in all individuals and a general pattern of tissue-specific expression among proviruses, has serious implications for future HERV-K(HML-2)-targeted immunotherapy. Further research into HERV-K(HML-2) as a possible tumour-associated antigen in blood cancers requires a more targeted, proteome-based, screening protocol that will consider these polymorphisms within HERV-K(HML-2). We include a plan (and necessary alignments) for such work.

There is growing evidence that speakers recruit inhibitory control in situations of high within-language interference, e.g., when selecting from among competing lexical entries or when tailoring utterances to the communicative needs of the addressee. However, little is known about the types of cognitive control mechanisms that are involved in the speech production process. This study examines the relative contribution of various forms of interference arising at different stages of information processing as well as their control to object naming under conditions of prepotent and underdetermined competition. Eighty-nine unimpaired native English speakers completed three inhibitory control tasks (arrow flanker, Simon arrow and anti-saccade) and two object naming tasks (picture-word interference, PWI, and name agreement, NA). Analyses of mean RT and RT distribution (delta plots) showed that only the flanker effect was a significant predictor of the PWI but not NA effect, while the remaining inhibitory measures made no significant contribution to either the PWI or NA effect. Participants with smaller flanker effects, indicative of better resolution of representational conflict, were faster to name objects in the face of competing stimuli. The pattern of results suggests that delays in production can be an outcome of inefficient resolution of interference traced to intermediate rather than late stages of processing, at least as far as the PWI task is concerned.

IntroductionCardiovascular disease (CVD) is more common in women who have had pregnancy complications such as spontaneous pregnancy loss. We used cross-sectional data from the UK Biobank Imaging Enhancement Study to determine whether pregnancy loss is associated with cardiac or vascular remodelling in later life, which might contribute to this increased risk.MethodsPregnancy history was reported by women participating in UK Biobank between 2006 and 2010 at age 40-69 years using a self-completed touch-screen questionnaire. Associations between self-reported spontaneous pregnancy loss and cardiovascular measures, collected in women who participated in the Imaging Enhancement Study up to the end of 2015, were examined. Cardiac structure and function were assessed by magnetic resonance (CMR) steady-state free precession imaging at 1.5 Tesla. Carotid intima-media thickness (CIMT) measurements were taken for both common carotid arteries using a CardioHealth Station. Statistical associations with CMR and carotid measures were adjusted for age, BMI and other cardiovascular risk factors.ResultsData were available on 2660 women of whom 111 were excluded because of pre-existing cardiovascular disease and 30 had no pregnancy information available. Of the remaining 2519, 446 were nulligravid and 2073 had a history of pregnancies, of whom 622 reported at least one pregnancy loss (92% miscarriages and 8% stillbirths) and 1451 reported no pregnancy loss. No significant differences in any cardiac or carotid parameters were evident in women who reported pregnancy loss compared to other groups (Table 1).ConclusionWomen who self-report pregnancy loss do not have significant differences in cardiac structure, cardiac function, or carotid structure in later life to explain their increased cardiovascular risk. This suggests any cardiovascular risks associated with pregnancy loss operate through other disease mechanisms. Alternatively, other characteristics of pregnancy loss, which we were not able to take account of, such as timing and number of pregnancy losses may be required to identify those at greatest cardiovascular risk.

An amendment to this paper has been published and can be accessed via the original article.

Endomucin is expressed by endothelial cells that line postcapillary venules—the site of leukocyte recruitment during inflammation. Zahr et al.show that endomucin is an anti-adhesive molecule that is downregulated by the cytokine TNF-a and thereby helps in the transition from a quiescent to a pro-adhesive inflamed endothelium.

Early-onset obesity is known to culminate in type 2 diabetes, arterial hypertension and subsequent cardiovascular disease. The role of sodium (Na+) homeostasis in this process is incompletely understood, yet correlations between Na+ accumulation and hypertension have been observed in adults. We aimed to investigate these associations in adolescents. A cohort of 32 adolescents (13−17 years), comprising 20 obese patients, of whom 11 were hypertensive, as well as 12 age-matched controls, underwent 23Na-MRI of the left lower leg with a standard clinical 3T scanner. Median triceps surae muscle Na+ content in hypertensive obese (11.95 mmol/L [interquartile range 11.62−13.66]) was significantly lower than in normotensive obese (13.63 mmol/L [12.97−17.64]; p = 0.043) or controls (15.37 mmol/L [14.12−16.08]; p = 0.012). No significant differences were found between normotensive obese and controls. Skin Na+ content in hypertensive obese (13.33 mmol/L [11.53−14.22] did not differ to normotensive obese (14.12 mmol/L [13.15−15.83]) or controls (11.48 mmol/L [10.48−12.80]), whereas normotensive obese had higher values compared to controls (p = 0.004). Arterial hypertension in obese adolescents is associated with low muscle Na+ content. These findings suggest an early dysregulation of Na+ homeostasis in cardiometabolic disease. Further research is needed to determine whether this association is causal and how it evolves in the transition to adulthood.

Background: Early life nutrition may affect individuals’ susceptibility to adult non-communicable diseases (NCD). Psychological stress is a well-recognised NCD risk factor. Recent evidence suggests that impaired foetal nutrition alters neuro-endocrine pathways, and hypothalamic-pituitary-adrenal axis feedback systems, resulting in abnormal stress responses, and NCD risk. This study aims to examine adolescent cortisol and cardiovascular stress responses in relation to maternal nutrition and contemporaneous NCD risk markers. Methods: The study sample will be drawn from three well-established birth cohorts in India; the Parthenon cohort, Mysore (N=550, age~20y), the SARAS KIDS prenatal intervention cohort, Mumbai (N=300, age~10-12y) and the Pune Rural Intervention in Young Adults/ PRIYA cohort, Pune (N=100, age~22y). We will perform the ‘Trier Social Stress Test (TSST)’, a well-accepted stress-test module which involves participants performing 5-minutes each of public speaking and mental arithmetic tasks in front of unfamiliar ‘judges’ (stressor). Repeated measures of salivary cortisol and autonomic cardiovascular outcomes relative to the stressor will be assessed. Measures of psychological stress, cognitive function, blood pressure, glucose-insulin metabolism and depression will be carried out. Mechanistic studies including DNA methylation in gluco-corticoid receptor (NR3C1) and 11β-HSD2 gene loci and neuroimaging will be carried out in a subsample. Qualitative interviews and focus group discussions in a subsample of the Parthenon cohort will explore the perception of stress and stressors among the youth. We will convert repeated measures into time-weighted averages before analysis. We will carry out multivariable regression analysis to test the associations. We will further refine the analyses using the mixed-model regression and conditional analyses for the association with repeated measures. Ethics and dissemination: This study has been approved by the research ethics committee of CSI Holdsworth Memorial Hospital, Mysore. The findings will be disseminated locally and at international meetings, and reports will be submitted to open access peer reviewed journals.

Interoception, the process by which the nervous system senses, interprets, and integrates signals originating from within the body, has become major research topic for mental health and in particular for mind-body interventions. Interoceptive awareness here is defined as the conscious level of interoception with its multiple dimensions potentially accessible to self-report. The Multidimensional Assessment of Interoceptive Awareness (MAIA) is an 8-scale state-trait questionnaire with 32 items to measure multiple dimensions of interoception by self-report and was published in November 2012. Its numerous applications in English and other languages revealed low internal consistency reliability for two of its scales. This study's objective was to improve these scales and the psychometrics of the MAIA by adding three new items to each of the two scales and evaluate these in a new sample. Data were collected within a larger project that took place as part of the Live Science residency programme at the Science Museum London, UK, where visitors to the museum (N = 1,090) completed the MAIA and the six additional items. Based on exploratory factor analysis in one-half of the adult participants and Cronbach alphas, we discarded one and included five of the six additional items into a Version 2 of the MAIA and conducted confirmatory factor analysis in the other half of the participants. The 8-factor model of the resulting 37-item MAIA-2 was confirmed with appropriate fit indices (RMSEA = 0.055 [95% CI 0.052-0.058]; SRMR = 0.064) and improved internal consistency reliability. The MAIA-2 is public domain and available (www.osher.ucsf.edu/maia) for interoception research and the evaluation of clinical mind-body interventions.

Long-standing results in urban studies have shown correlation of population and population density to a city’s pace of life, empirically tested by examining whether individuals in bigger cities walk faster, spend less time buying stamps, or make greater numbers of telephone calls. Contemporary social media presents a new opportunity to test these hypotheses. This study examines whether users of the social media platform Twitter in larger and denser American cities tweet at a faster rate than their counterparts in smaller and sparser ones. Contrary to how telephony usage and productivity scale superlinearly with city population, the total volume of tweets in cities scales sublinearly. This is similar to the economies of scale in city infrastructures like gas stations. When looking at individuals, however, greater population density is associated with faster tweeting. The discrepancy between the ecological correlation and individual behavior is resolved by noting that larger cities have sublinear growth in the number of active Twitter users. This suggests that there is a more concentrated core of more active users that may serve an information broadcast function for larger cities, an emerging group of “town tweeters” as it were.

ABSTRACT The pathogenic species of Cryptococcus are a major cause of mortality owing to severe infections in immunocompromised as well as immunocompetent individuals. Although antifungal treatment is usually effective, many patients relapse after treatment, and in such cases, comparative analyses of the genomes of incident and relapse isolates may reveal evidence of determinative, microevolutionary changes within the host. Here, we analyzed serial isolates cultured from cerebrospinal fluid specimens of 18 South African patients with recurrent cryptococcal meningitis. The time between collection of the incident isolates and collection of the relapse isolates ranged from 124 days to 290 days, and the analyses revealed that, during this period within the patients, the isolates underwent several genetic and phenotypic changes. Considering the vast genetic diversity of cryptococcal isolates in sub-Saharan Africa, it was not surprising to find that the relapse isolates had acquired different genetic and correlative phenotypic changes. They exhibited various mechanisms for enhancing virulence, such as growth at 39°C, adaptation to stress, and capsule production; a remarkable amplification of ERG11 at the native and unlinked locus may provide stable resistance to fluconazole. Our data provide a deeper understanding of the microevolution of Cryptococcus species under pressure from antifungal chemotherapy and host immune responses. This investigation clearly suggests a promising strategy to identify novel targets for improved diagnosis, therapy, and prognosis. IMPORTANCE Opportunistic infections caused by species of the pathogenic yeast Cryptococcus lead to chronic meningoencephalitis and continue to ravage thousands of patients with HIV/AIDS. Despite receiving antifungal treatment, over 10% of patients develop recurrent disease. In this study, we collected isolates of Cryptococcus from cerebrospinal fluid specimens of 18 patients at the time of their diagnosis and when they relapsed several months later. We then sequenced and compared the genomic DNAs of each pair of initial and relapse isolates. We also tested the isolates for several key properties related to cryptococcal virulence as well as for their susceptibility to the antifungal drug fluconazole. These analyses revealed that the relapsing isolates manifested multiple genetic and chromosomal changes that affected a variety of genes implicated in the pathogenicity of Cryptococcus or resistance to fluconazole. This application of comparative genomics to serial clinical isolates provides a blueprint for identifying the mechanisms whereby pathogenic microbes adapt within patients to prolong disease.

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1-deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG.

OBJECTIVE: Active anxiety disorders have lasting detrimental effects on pregnant mothers and their offspring but it is unknown if historical, non-active, maternal anxiety disorders have similar effects. Anxiety-related conditions, such as reduced autonomic cardiac control, indicated by reduced heart rate variability (HRV) could persist despite disorder resolution, with long-term health implications for mothers and children. The objective in this study is to test the hypotheses that pregnant mothers with a history of, but not current anxiety and their children have low HRV, predicting anxiety-like offspring temperaments. METHODS: The participants in this case-control study consist of 56 women during their first trimester and their offspring (15 male, 29 female). Women had a history of an anxiety disorder (n=22) or no psychopathology (n=34) determined using the Mini-International Neuropsychiatric Interview. The main outcome measures were indices of autonomic cardiac control including root mean square of successive differences (RMSSD) and high frequency (HF) variability. Children's fearfulness was also assessed using the Laboratory Temperament Assessment Battery (Lab-TAB)-Locomotor Version. RESULTS: HRV was lower in women and children in the past anxiety group compared to controls. HRV measures for mothers and children were positively correlated in the anxiety group only. In all children, low HRV measures at 2-4 months were associated with a higher chance of fearful behavior at 9-10 months. CONCLUSIONS: Pregnant women with previous but not current anxiety and their children have low HRV. Children with low HRV tend to show more fearfulness. These findings have implications for identifying children at risk of anxiety disorders and point to possible underlying mechanisms of child psychopathology.

Obesity and mental stress are potent risk factors for cardiovascular disease but their relationship with each other is unclear. Resilience to stress may differ according to adiposity. Early studies that addressed this are difficult to interpret due to conflicting findings and limited methods. Recent advances in assessment of cardiovascular stress responses and of fat distribution allow accurate assessment of associations between adiposity and stress responsiveness. We measured responses to the Montreal Imaging Stress Task in healthy men (N = 43) and women (N = 45) with a wide range of BMIs. Heart rate (HR) and blood pressure (BP) measures were used with novel magnetic resonance measures of stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and arterial compliance to assess cardiovascular responses. Salivary cortisol and the number and speed of answers to mathematics problems in the task were used to assess neuroendocrine and cognitive responses, respectively. Visceral and subcutaneous fat was measured using T(2) (*)-IDEAL. Greater BMI was associated with generalised blunting of cardiovascular (HR:β = -0.50 bpm x unit(-1), P = 0.009; SV:β = -0.33 mL x unit(-1), P = 0.01; CO:β = -61 mL x min(-1) x unit(-1), P = 0.002; systolic BP:β = -0.41 mmHg x unit(-1), P = 0.01; TPR:β = 0.11 WU x unit(-1), P = 0.02), cognitive (correct answers: r = -0.28, P = 0.01; time to answer: r = 0.26, P = 0.02) and endocrine responses (cortisol: r = -0.25, P = 0.04) to stress. These associations were largely determined by visceral adiposity except for those related to cognitive performance, which were determined by both visceral and subcutaneous adiposity. Our findings suggest that adiposity is associated with centrally reduced stress responsiveness. Although this may mitigate some long-term health risks of stress responsiveness, reduced performance under stress may be a more immediate negative consequence.

Glaucoma, the most frequent optic neuropathy, is a leading cause of blindness worldwide. Death of retinal ganglion cells (RGCs) occurs in all forms of glaucoma and accounts for the loss of vision, however the molecular mechanisms that cause RGC loss remain unclear. The pro-apoptotic molecule, Fas ligand, is a transmembrane protein that can be cleaved from the cell surface by metalloproteinases to release a soluble protein with antagonistic activity. Previous studies documented that constitutive ocular expression of FasL maintained immune privilege and prevented neoangeogenesis. We now show that FasL also plays a major role in retinal neurotoxicity. Importantly, in both TNFα triggered RGC death and a spontaneous model of glaucoma, gene-targeted mice that express only full-length FasL exhibit accelerated RGC death. By contrast, FasL-deficiency, or administration of soluble FasL, protected RGCs from cell death. These data identify membrane-bound FasL as a critical effector molecule and potential therapeutic target in glaucoma.

Adverse fetal environments are associated with depression, reduced cognitive ability and increased stress responsiveness in later life, but underlying mechanisms are unknown. Environmental pressures on the fetus, resulting from variations in placental function and maternal nutrition, health and stress might alter neurodevelopment, promoting the development of some brain regions over others. As asymmetry of cerebral activity, with greater right hemisphere activity, has been associated with psychopathology, we hypothesized that regional specialization during fetal life might be reflected persistently in the relative activity of the cerebral hemispheres. We tested this hypothesis in 140 healthy 8-9 year-old children, using tympanic membrane temperature to assess relative blood flow to the cerebral hemispheres at rest and following psychosocial stress (Trier Social Stress Test for Children). Their birth weight and placental weight had already been measured when their mothers took part in a previous study of pregnancy outcomes. We found that children who had a smaller weight at birth had evidence of greater blood flow to the right hemisphere than to the left hemisphere (r = -.09, P = .29 at rest; r = -.18, P = .04 following stress). This finding was strengthened if the children had a relatively low birth weight for their placental weight (r = -.17, P = .05 at rest; r = -.31, P = .0005 following stress). Our findings suggest that lateralization of cerebral activity is influenced persistently by early developmental experiences, with possible consequences for long-term neurocognitive function.

During the coronavirus disease 2019 (COVID-19) pandemic, clinical staff learned how to manage patients enduring extended stays in an intensive care unit (ICU). COVID-19 patients requiring critical care in an ICU face a high risk of experiencing prolonged intensive care (PIC). The use of invasive mechanical ventilation in individuals with severe acute respiratory distress syndrome can cause numerous complications that influence both short-term and long-term morbidity and mortality. Those risks underscore the importance of proactively addressing functional complications. Mitigating secondary complications unrelated to the primary pathology of admission is imperative in minimizing the risk of PIC. Therefore, incorporating strategies to do that into daily ICU practice for both COVID-19 patients and those critically ill from other conditions is significantly important. [ABSTRACT FROM AUTHOR]

During the coronavirus disease 2019 (COVID-19) pandemic, clinical staff learned how to manage patients enduring extended stays in an intensive care unit (ICU). COVID-19 patients requiring critical care in an ICU face a high risk of experiencing prolonged intensive care (PIC). The use of invasive mechanical ventilation in individuals with severe acute respiratory distress syndrome can cause numerous complications that influence both short-term and long-term morbidity and mortality. Those risks underscore the importance of proactively addressing functional complications. Mitigating secondary complications unrelated to the primary pathology of admission is imperative in minimizing the risk of PIC. Therefore, incorporating strategies to do that into daily ICU practice for both COVID-19 patients and those critically ill from other conditions is significantly important.

Obesity has become increasingly prevalent in the intensive care unit, presenting a significant challenge for healthcare systems and professionals, including rehabilitation teams. Caring for critically ill patients with obesity involves addressing complex issues. Despite the well-established and safe practice of early mobilization during critical illness, in rehabilitation matters, the diverse clinical disturbances and scenarios within the obese patient population necessitate a comprehensive understanding. This includes recognizing the importance of metabolic support, both non-invasive and invasive ventilatory support, and their weaning processes as essential prerequisites. Physiotherapists, working collaboratively with a multidisciplinary team, play a crucial role in ensuring proper assessment and functional rehabilitation in the critical care setting. This review aims to provide critical insights into the key management and rehabilitation principles for obese patients in the intensive care unit.