Evaluating the Clinical Relevance of Antibodies against Non-Human Leukocyte Antigen in Kidney Transplantation.

Introduction: Kidney transplantation is the preferred modality of kidney replacement therapy for eligible patients with end-stage kidney disease (ESKD), given that it has been found to reduce mortality rates, improve quality of life, and is cost-effective compared to dialysis. Recent advancements in human leukocyte antigen (HLA) typing and donor-specific antibody (DSA) detection have helped to reduce the risk of rejection, but antibody-mediated rejection (AMR) can still occur without DSA. Previous studies suggest that rejection can be attributed to antibodies against Non-Human Leucocyte Antigens (non-HLAs). We aimed to acquire further understanding of the prevalence and distribution of non-HLA antibodies in our local population and attempt to correlate these findings with graft outcomes, as well as assess whether non-HLA antibodies can be utilized to determine graft impairment and dysfunction. Methods: We conducted a retrospective study involving kidney transplant recipients between January 2010 and December 2020. All included individuals were aged over 18 and underwent kidney-alone transplants; were ABO- and HLA-compatible; and were matched at A, B, and DR loci (mismatch 0:0:0). HLA testing was negative at the time of transplantation. The samples from both cases of early graft rejection and the control group were tested for non-HLA antibodies using One Lambda LABScreenTM, Autoantibody kit groups 1, 2, and 3, as well as the Immucor LIFECODES non-HLA autoantibody assay. Results: A total of 850 kidney transplant recipients were included, in which 12 patients experienced early graft rejection within the first month post transplant and 18 patients who did not experience graft rejection were selected as study controls. Our study reported no correlation between the total burden of non-HLA antibodies and early rejection, most likely as the result of a small sample size. Nevertheless, a sub-analysis revealed that specific high-frequency pre-transplant non-HLA antibodies such as GSTT, CXCL11, CXCL10, and HNR, detected by LIFECODES, were associated with rejection (Fisher's exact test with Bonferroni correction, p < 0.001). Most pre-transplant non-HLA antibody levels were reduced after transplantation, which was attributed to immunosuppression. Conclusion: The 'high frequency' non-HLA antibodies displayed an association with graft rejection, though the overall associations between the burden of non-HLA antibodies and rejection episodes remain inconclusive. Further work is needed to establish the rebound phenomenon of non-HLA antibodies, the development of de novo non-HLA antibodies in the long run, and their implications on graft survival.

Long-term outcome after neonatal intervention for congenital critical aortic stenosis.

BACKGROUND: This study explored long-term outcome and functional status of patients born with critical aortic stenosis (CAS) following neonatal surgical or catheter interventions. METHODS: A 40-year retrospective review of all consecutive patients within a large, single-center referral unit who required neonatal (<30 days) intervention for CAS. Additional detailed evaluation of surviving patients >7 years age was performed, with clinical assessment, objective cardiopulmonary exercise testing and state-of-the-art characterization of myocardial function (advanced echocardiography and cardiac MRI). RESULTS: Between 1970 and 2010, ninety-six neonates underwent CAS intervention (mean age 9 ± 7.5 days). Early death occurred in 19 (19.8%) and late death in 10 patients. Overall survival at 10 and 30 years was 70.1% and 68.5%, freedom from reintervention was 41.8% and 32.9% respectively. Among the 25 long-term survivors available for detailed assessment (median age 15.7 ± 6.4 years), 55% exhibited impaired peak oxygen uptake. Mean left ventricle (LV) ejection fraction was 65 ± 11.2%, with a mean LV end-diastolic volume z-score of 0.02 ± 1.4. Mean LV outflow tract Vmax was 2.3 ± 1.02 m/s. CAS patients had reduced LV longitudinal and increased radial strain (p = 0.003, p < 0.001 respectively). Five patients had severe LV diastolic dysfunction associated with endocardial fibroelastosis (EFE) (p = 0.0014). CONCLUSION: Despite high early mortality rate, long-term survival of patients with CAS is reasonable at the expense of high reintervention rate. With successful intervention, there remained long-term clinical and subclinical LV myocardial impairment, of which EFE was one marker. Long-term follow-up of all CAS patients is crucial, involving detailed myocardial functional assessment to help elucidate physiology and optimise management.

Beyond scale-free networks: integrating multilayer social networks with molecular clusters in the local spread of COVID-19.

This study evaluates the scale-free network assumption commonly used in COVID-19 epidemiology, using empirical social network data from SARS-CoV-2 Delta variant molecular local clusters in Houston, Texas. We constructed genome-informed social networks from contact and co-residence data, tested them for scale-free power-law distributions that imply highly connected hubs, and compared them to alternative models (exponential, log-normal, power-law with exponential cutoff, and Weibull) that suggest more evenly distributed network connections. Although the power-law model failed the goodness of fit test, after incorporating social network ties, the power-law model was at least as good as, if not better than, the alternatives, implying the presence of both hub and non-hub mechanisms in local SARS-CoV-2 transmission. These findings enhance our understanding of the complex social interactions that drive SARS-CoV-2 transmission, thereby informing more effective public health interventions.

Relationship of insomnia to sexual function and sexual satisfaction: Findings from the sleep and sex survey II.

OBJECTIVE: Research suggests that healthy sleep is a key component of sexual function. When evaluating sexual function, however, poor sleep is often overlooked as a contributing factor. This cross-sectional survey expands prior work by exploring relationships among insomnia severity, sexual satisfaction, and sexual function with an updated battery of measures for the Sleep and Sex Survey. METHOD: The sample (N = 1266) consisted of 618 men, 648 women recruited via Prolific, an online survey platform. The Sleep and Sex Survey II included measures addressing insomnia, fear of sleep, nightmares, sexual function, sexual satisfaction, sexual activity, depression, anxiety, posttraumatic stress, and alcohol use. RESULTS: Recent sexual activity was correlated with better sleep, lower anxiety, and lower scores on a posttraumatic stress disorder screener. Insomnia severity was negatively correlated with sexual satisfaction (r = 0.22, p < .001) and the presence of insomnia was associated with higher rates of sexual dysfunction in women (53.8% vs. 31.8%; p < .001) and men (22.7% vs. 12.5%; p = .036). In regression analyses, after accounting for depression and anxiety, insomnia had a statistically significant association with sexual function for women (ß = 0.12; p < .01) but not men (ß = 0.11; p = .60). CONCLUSION: Findings support a relationship of insomnia to sexual function and satisfaction with some gender differences. Future work may be enhanced by assessing these relationships in a gender diverse population including objective sleep measures and addressing contributing mechanisms. Clinically, findings support the assessment of sleep when evaluating patients for sexual dysfunction.

Predictors of HIV Molecular Cluster Membership and Implications for Partner Services.

Public health surveillance data used in HIV molecular cluster analyses lack contextual information that is available from partner services (PS) data. Integrating these data sources in retrospective analyses can enrich understanding of the risk profile of people in clusters. In this study, HIV molecular clusters were identified and matched to information on partners and other information gleaned at the time of diagnosis, including coinfection with syphilis. We aimed to produce a more complete understanding of molecular cluster membership in Houston, Texas, a city ranking ninth nationally in rate of new HIV diagnoses that may benefit from retrospective matched analyses between molecular and PS data to inform future intervention. Data from PS were matched to molecular HIV records of people newly diagnosed from 2012 to 2018. By conducting analyses in HIV-TRACE (TRAnsmission Cluster Engine) using viral genetic sequences, molecular clusters were detected. Multivariable logistic regression models were used to estimate the association between molecular cluster membership and completion of a PS interview, number of named partners, and syphilis coinfection. Using data from 4,035 people who had a viral genetic sequence and matched PS records, molecular cluster membership was not significantly associated with completion of a PS interview. Among those with sequences who completed a PS interview (n = 3,869), 45.3% (n = 1,753) clustered. Molecular cluster membership was significantly associated with naming 1 or 3+ partners compared with not naming any partners [adjusted odds ratio, aOR: 1.27 (95% confidence interval, CI: 1.08-1.50), p = .003 and aOR: 1.38 (95% CI: 1.06-1.81), p = .02]. Alone, coinfection with syphilis was not significantly associated with molecular cluster membership. Syphilis coinfection was associated with molecular cluster membership when coupled with incarceration [aOR: 1.91 (95% CI: 1.08-3.38), p = .03], a risk for treatment interruption. Enhanced intervention among those with similar profiles, such as people coinfected with other risks, may be warranted.

The memory sources of dreams: serial awakenings across sleep stages and time of night.

Memories of waking-life events are incorporated into dreams, but their incorporation is not uniform across a night of sleep. This study aimed to elucidate ways in which such memory sources vary by sleep stage and time of night. Twenty healthy participants (11 F; 24.1 ± 5.7 years) spent a night in the laboratory and were awakened for dream collection approximately 12 times spread across early, middle, and late periods of sleep, while covering all stages of sleep (N1, N2, N3, REM). In the morning, participants identified and dated associated memories of waking-life events for each dream report, when possible. The incorporation of recent memory sources in dreams was more frequent in N1 and REM than in other sleep stages. The incorporation of distant memories from over a week ago, semantic memories not traceable to a single event, and anticipated future events remained stable throughout sleep. In contrast, the relative proportions of recent versus distant memory sources changed across the night, independently of sleep stage, with late-night dreams in all stages having relatively less recent and more remote memory sources than dreams earlier in the night. Qualitatively, dreams tended to repeat similar themes across the night and in different sleep stages. The present findings clarify the temporal course of memory incorporations in dreams, highlighting a specific connection between time of night and the temporal remoteness of memories. We discuss how dream content may, at least in part, reflect the mechanisms of sleep-dependent memory consolidation.

Characterization of sleep among deaf individuals.

OBJECTIVES: Numerous health disparities are documented in deaf population research, but few empirical sleep assessments exist for this under-served population, despite knowledge that sleep contributes to physical and mental health disparities. We sought to document subjective and objective sleep in deaf adults with cross-sectional and prospective measures. METHODS: Twenty deaf participants completed validated sleep and mental health questionnaires, 2-weeks of nightly sleep diaries and continuous wrist-worn actigraphy monitoring, and 1-week of nightly, reduced-montage EEG recordings. RESULTS: Questionnaire data suggest high prevalence of insomnia (70%), poor sleep (75%), daytime sleepiness (25%) and nightmares (20%) among participants. Strong correlations were found between depression and sleep quality, fear of sleep, and insomnia severity (p's < .005). Objective sleep assessments suggest elevated wake after sleep onset and low sleep efficiency and sleep duration. CONCLUSIONS: The prevalence of sleep disturbance recorded from self-report and objective sleep measures provides preliminary evidence of sleep health disparity among deaf adults.

Impact of molecular sequence data completeness on HIV cluster detection and a network science approach to enhance detection.

Detection of viral transmission clusters using molecular epidemiology is critical to the response pillar of the Ending the HIV Epidemic initiative. Here, we studied whether inference with an incomplete dataset would influence the accuracy of the reconstructed molecular transmission network. We analyzed viral sequence data available from ~ 13,000 individuals with diagnosed HIV (2012-2019) from Houston Health Department surveillance data with 53% completeness (n = 6852 individuals with sequences). We extracted random subsamples and compared the resulting reconstructed networks versus the full-size network. Increasing simulated completeness was associated with an increase in the number of detected clusters. We also subsampled based on the network node influence in the transmission of the virus where we measured Expected Force (ExF) for each node in the network. We simulated the removal of nodes with the highest and then lowest ExF from the full dataset and discovered that 4.7% and 60% of priority clusters were detected respectively. These results highlight the non-uniform impact of capturing high influence nodes in identifying transmission clusters. Although increasing sequence reporting completeness is the way to fully detect HIV transmission patterns, reaching high completeness has remained challenging in the real world. Hence, we suggest taking a network science approach to enhance performance of molecular cluster detection, augmented by node influence information.

The Relationship Between Dreams and Subsequent Morning Mood Using Self-Reports and Text Analysis.

While material from waking life is often represented in dreams, it is less clear whether and how dreams impact waking life. Here, we assessed whether dream mood and content from home diaries predict subsequent waking mood using both subjective self-reports and an objective automated word detection approach. Subjective ratings of dream and morning mood were highly correlated within participants for both negative and positive valence, suggesting that dream mood persists into waking. Text analyses revealed similar relationships between affect words in dreams and morning mood. Moreover, dreams referencing death or the body were related to worse morning mood, as was first-person singular pronoun usage (e.g., "I"). Dreams referencing leisure or ingestion, or including first-person plural pronouns (e.g., "we"), were related to better morning mood. Together, these results suggest that subjective experiences during sleep, while often overlooked, may be an important contributor to waking mood. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00080-8.

Effects of sleep on positive, negative and neutral valenced story and image memory.

During sleep, emotional memories are preferentially strengthened. However, most studies on sleep and emotional memory focus on comparing negative valence with neutral valence stimuli. This study compared the sleep-dependent memory effects for stories and images, each comprising negative, neutral, and positive stimuli. It was hypothesized that a sleep effect would be seen for negatively and positively valenced stimuli. A novel story memory task (comprising three stories), and photographs from the Nencki Affective Picture database were presented for learning to 61 healthy adults (ages 18-25). They were tested for memory on the two tasks immediately, and then again after either a 2-hr nap (n = 31; 17 women, 14 men) or 2-hr wake period (n = 30; 13 women, 17 men). At second testing, the sleep condition had significantly better recall compared to the wake condition on both tasks. There was a relationship with valence only for the story task, with better performance for the sleep condition on the negatively and positively valenced texts, but not on the neutral text. There were no significant relationships between memory measures and sleep-stage duration and EEG power variables. The story memory findings support the hypothesis that memory consolidation prioritizes emotional memory, whether positively or negatively valenced.

Dreaming of the sleep lab.

The phenomenon of dreaming about the laboratory when participating in a sleep study is common. The content of such dreams draws upon episodic memory fragments of the participant's lab experience, generally, experimenters, electrodes, the lab setting, and experimental tasks. However, as common as such dreams are, they have rarely been given a thorough quantitative or qualitative treatment. Here we assessed 528 dreams (N = 343 participants) collected in a Montreal sleep lab to 1) evaluate state and trait factors related to such dreams, and 2) investigate the phenomenology of lab incorporations using a new scoring system. Lab incorporations occurred in over a third (35.8%) of all dreams and were especially likely to occur in REM sleep (44.2%) or from morning naps (48.4%). They tended to be related to higher depression scores, but not to sex, nightmare-proneness or anxiety. Common themes associated with lab incorporation were: Meta-dreaming, including lucid dreams and false awakenings (40.7%), Sensory incorporations (27%), Wayfinding to, from or within the lab (24.3%), Sleep as performance (19.6%), Friends/Family in the lab (15.9%) and Being an object of observation (12.2%). Finally, 31.7% of the lab incorporation dreams included relative projections into a near future (e.g., the experiment having been completed), but very few projections into the past (2.6%). Results clarify sleep stage and sleep timing factors associated with dreamed lab incorporations. Phenomenological findings further reveal both the typical and unique ways in which lab memory elements are incorporated de novo into dreaming. Identified themes point to frequent social and skillful dream scenarios that entail monitoring of one's current state (in the lab) and projection of the self into dream environments elaborated around local space and time. The findings have implications for understanding fundamental dream formation mechanisms but also for appreciating both the advantages and methodological pitfalls of conducting laboratory-based dream collection.

Local Neuronal Synchronization in Frequent Nightmare Recallers and Healthy Controls: A Resting-State Functional Magnetic Resonance Imaging Study.

Nightmares are highly dysphoric dreams that are well-remembered upon awakening. Frequent nightmares have been associated with psychopathology and emotional dysregulation, yet their neural mechanisms remain largely unknown. Our neurocognitive model posits that nightmares reflect dysfunction in a limbic-prefrontal circuit comprising medial prefrontal and anterior cingulate cortices, hippocampus, and amygdala. However, there is a paucity of studies that used brain imaging to directly test the neural correlates of nightmares. One such study compared the regional homogeneity (ReHo) of resting-state functional magnetic resonance imaging blood-oxygen level-dependent signals between frequent nightmare recallers and controls. The main results were greater regional homogeneity in the left anterior cingulate cortex and right inferior parietal lobule for the nightmare recallers than for the controls. In the present study, we aimed to document the ReHo correlates of frequent nightmares using several nightmare severity measures. We acquired resting-state functional magnetic resonance imaging data from 18 frequent nightmare recallers aged 18-35 (3 males and 15 females) and 18 age- and sex-matched controls, as well as retrospective and prospective disturbed dreaming frequency estimates and scores on the Nightmare Distress Questionnaire. While there were inconsistent results for our different analyses (group comparisons, correlational analyses for frequency estimates/Nightmare Distress scores), our results suggest that nightmares are associated with altered ReHo in frontal (medial prefrontal and inferior frontal), parietal, temporal and occipital regions, as well as some subcortical regions (thalamus). We also found a positive correlation between retrospective disturbed dreaming frequency estimates and ReHo values in the hippocampus. These findings are mostly in line with a recent SPECT study from our laboratory. Our results point to the possibility that a variety of regions, including but not limited to the limbic-prefrontal circuit of our neurocognitive model, contribute to nightmare formation.

Methodological synthesis of Bayesian phylodynamics, HIV-TRACE, and GEE: HIV-1 transmission epidemiology in a racially/ethnically diverse Southern U.S. context.

This study introduces an innovative methodological approach to identify potential drivers of structuring HIV-1 transmission clustering patterns between different subpopulations in the culturally and racially/ethnically diverse context of Houston, TX, the largest city in the Southern United States. Using 6332 HIV-1 pol sequences from persons newly diagnosed with HIV during the period 2010-2018, we reconstructed HIV-1 transmission clusters, using the HIV-TRAnsmission Cluster Engine (HIV-TRACE); inferred demographic and risk parameters on HIV-1 transmission dynamics by jointly estimating viral transmission rates across racial/ethnic, age, and transmission risk groups; and modeled the degree of network connectivity by using generalized estimating equations (GEE). Our results indicate that Hispanics/Latinos are most vulnerable to the structure of transmission clusters and serve as a bridge population, acting as recipients of transmissions from Whites (3.0 state changes/year) and from Blacks (2.6 state changes/year) as well as sources of transmissions to Whites (1.8 state changes/year) and to Blacks (1.2 state changes/year). There were high rates of transmission and high network connectivity between younger and older Hispanics/Latinos as well as between younger and older Blacks. Prevention and intervention efforts are needed for transmission clusters that involve younger racial/ethnic minorities, in particular Hispanic/Latino youth, to reduce onward transmission of HIV in Houston.

Testing the theory of Differential Susceptibility to nightmares: The interaction of Sensory Processing Sensitivity with the relationship of low mental wellbeing to nightmare frequency and nightmare distress.

Propensity to have nightmares has been theorised in terms of diathesis-stress models, with this propensity being seen as negative or even pathological. In contrast, a recent model proposes that nightmare propensity is due to Differential Susceptibility to stimuli, where high susceptibility can be beneficial in positive environments but detrimental in negative environments. This susceptibility to stimuli is assessed as the biobehavioural trait Sensory Processing Sensitivity, which refers to a greater responsivity to internal and external stimuli, and an increased depth of cognitive and emotional processing. To test the Differential Susceptibility Framework for nightmares, 137 participants (females = 104, males = 33; mean age = 33.66 years), recruited from a student population and social media sites, were divided into high (n = 39), medium (n = 59) and low (n = 39) Sensory Processing Sensitivity categories based on their score on the Highly Sensitive Person Scale. Low mental wellbeing and the presence of minor psychiatric problems, measured by the General Health Questionnaire, was found to be significantly correlated with nightmare frequency for the high and medium SPS groups (rs = .29 and .28, respectively), but not for the low Sensory Processing Sensitivity group (r = .19). General Health Questionnaire score was also significantly correlated with trait nightmare distress, for the high Sensory Processing Sensitivity group only (r = .32). These findings in favour of the Differential Susceptibility Framework have aetiology and treatment implications for nightmares that differ from diathesis-stress models.

Frontal Brain Activity and Subjective Arousal During Emotional Picture Viewing in Nightmare Sufferers.

Nightmares are intensely negative dreams that awaken the dreamer. Frequent nightmares are thought to reflect an executive deficit in regulating arousal. Within a diathesis-stress framework, this arousal is specific to negative contexts, though a differential susceptibility framework predicts elevated arousal in response to both negative and positive contexts. The current study tested these predictions by assessing subjective arousal and changes in frontal oxyhemoglobin (oxyHB) concentrations during negative and positive picture-viewing in nightmare sufferers (NM) and control subjects (CTL). 27 NM and 27 CTL subjects aged 18-35 rated subjective arousal on a 1-9 scale following sequences of negative, neutral and positive images; changes in oxyHB were measured by Near-Infrared Spectroscopy (NIRS) using a 2 × 4 template on the frontal pole. Participants also completed the Highly Sensitive Person Scale, a trait marker for differential susceptibility; and completed a dream diary reporting negative and positive dream emotionality. The NM group had higher trait sensitivity, yet higher ratings of negative but not positive emotion in diary dreams. NM compared to CTL subjects reported higher subjective arousal in response to picture-viewing regardless of valence. Dysphoric dream distress, measured prospectively, was negatively associated with frontal activation when viewing negative pictures. Results suggest NM sufferers are highly sensitive to images regardless of valence according to subjective measures, and that there is a neural basis to level of trait and prospective nightmare distress. Future longitudinal or intervention studies should further explore positive emotion sensitivity and imagery in NM sufferers.

Dream engineering: Simulating worlds through sensory stimulation.

We explore the application of a wide range of sensory stimulation technologies to the area of sleep and dream engineering. We begin by emphasizing the causal role of the body in dream generation, and describe a circuitry between the sleeping body and the dreaming mind. We suggest that nearly any sensory stimuli has potential for modulating experience in sleep. Considering other areas that might afford tools for engineering sensory content in simulated worlds, we turn to Virtual Reality (VR). We outline a collection of relevant VR technologies, including devices engineered to stimulate haptic, temperature, vestibular, olfactory, and auditory sensations. We believe these technologies, which have been developed for high mobility and low cost, can be translated to the field of dream engineering. We close by discussing possible future directions in this field and the ethics of a world in which targeted dream direction and sleep manipulation are feasible.

Dream lucidity is associated with positive waking mood.

Lucid dreaming is a unique phenomenon with potential applications for therapeutic interventions. Few studies have investigated the effects of lucidity on an individual's waking mood, which could have valuable implications for improving psychological wellbeing. The current experiment aims to investigate whether the experience of lucidity enhances positive waking mood, and whether lucidity is associated with dream emotional content and subjective sleep quality. 20 participants were asked to complete lucid dream induction techniques along with an online dream diary for one week, which featured a 19-item lucidity questionnaire, and subjective ratings of sleep quality, dream emotional content, and waking mood. Results indicated that higher lucidity was associated with more positive dream content and elevated positive waking mood the next day, although there was no relationship with sleep quality. The results of the research and suggestions for future investigations, such as the need for longitudinal studies of lucidity and mood, are discussed.

Nurturing the digital baby: Open innovation for development and optimization.

The primary aim around developing and optimizing an electronic health record is to improve patient care and population health. The objective of this study is to design and evaluate an action research approach for the optimization of the design of a summary page artefact within an electronic health record for newborn healthcare. An action research approach was chosen for its participatory democratic process for developing practical knowledge and solutions. Collaborative workshops lead by an independent graphic facilitator with a 'bottom up' approach, involving self-selected motivated members from multidisciplinary healthcare teams, were designed and conducted. To evaluate this approach, insights were drawn from behavioural and design science paradigms to demonstrate that knowledge and understanding of the design problem and its solution were acquired in building the optimized summary page artefact. Information system development for healthcare requires consideration not just of what we do but how and why we do things. Our analysis demonstrates that action design research represents an agile and lean approach for successful optimization and implementation of information system development in healthcare.