Testing personality-pace-of-life associations via artificial selection: insights from selected lines of rainbow trout on the context-dependence of correlations.

More than a decade of study since the personality pace-of-life syndrome (POLS) hypotheses were first proposed, there is little support for it within species. Lack of experimental control, insufficient sampling in the face of highly labile behavioural and metabolic traits, and context dependency of trait correlations are suggested as reasons. Here, I argue that artificial selection and/or use of existing selected lines represents a powerful but under-used approach to furthering our understanding of the POLS. To illustrate this potential, I conducted a focussed review of studies that compared the behaviour, metabolism, growth and survival of an artificially selected fast-growing rainbow trout relative to wild unselected strains, under varying food and risk conditions in the laboratory and field. Resting metabolic rate, food intake, and behaviours that enhance feeding but increase energy expenditure (activity, aggression, boldness), were all higher in the fast strain in paired contrasts, under all food and risk conditions, both in the laboratory and the field. Fast-strain fish grew faster in almost every food and risk situation except where food was highly limited (or absent), had higher survival under low or zero predation risk, but had lower survival under high risk. Several other traits rarely considered in POLS studies were also higher in the fast strain, including maximum swimming speed, and hormones (growth hormone (GH), thyroid hormone (T3) and insulin-like growth factor (IGF-1)). I conclude: (i) assumptions and predictions of the POLS hypothesis are well supported, and (ii) context-dependency was largely absent, but when present revealed trade-offs between food acquisition and predation risk. This focused review highlights the potential of artificial selection in testing POLS ideas, and will hopefully motivate further studies using other animals.

A selective CutMix approach improves generalizability of deep learning-based grading and risk assessment of prostate cancer.

The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to train an artificial intelligence (AI)-based algorithm to grade prostate cancer in specimens from patients who underwent radical prostatectomy (RP) and to assess the correlation of AI-estimated proportions of different Gleason patterns with biochemical recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS). Training and validation of algorithms for cancer detection and grading were completed with three large datasets containing a total of 580 whole-mount prostate slides from 191 RP patients at two centers and 6218 annotated needle biopsy slides from the publicly available Prostate Cancer Grading Assessment dataset. A cancer detection model was trained using MobileNetV3 on 0.5 mm × 0.5 mm cancer areas (tiles) captured at 10× magnification. For cancer grading, a Gleason pattern detector was trained on tiles using a ResNet50 convolutional neural network and a selective CutMix training strategy involving a mixture of real and artificial examples. This strategy resulted in improved model generalizability in the test set compared with three different control experiments when evaluated on both needle biopsy slides and whole-mount prostate slides from different centers. In an additional test cohort of RP patients who were clinically followed over 30 years, quantitative Gleason pattern AI estimates achieved concordance indexes of 0.69, 0.72, and 0.64 for predicting RFS, MFS, and OS times, outperforming the control experiments and International Society of Urological Pathology system (ISUP) grading by pathologists. Finally, unsupervised clustering of test RP patient specimens into low-, medium-, and high-risk groups based on AI-estimated proportions of each Gleason pattern resulted in significantly improved RFS and MFS stratification compared with ISUP grading. In summary, deep learning-based quantitative Gleason scoring using a selective CutMix training strategy may improve prognostication after prostate cancer surgery.

Minipterional craniotomy for resection of epileptogenic cavernous malformation.

Epilepsy is a common symptom of pediatric cavernous malformations. In medically refractory patients, surgery can achieve high seizure freedom rates with low morbidity. This video depicts the use of a minipterional craniotomy and transsulcal resection of a frontal opercular cavernous malformation in a 13-year-old female with medically intractable epilepsy. At 1-year follow-up, she was evaluated as Engel class I with a significant improvement in her quality of life. Principles of cavernous malformation resection for the treatment of epilepsy are also reviewed. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2441.

Myelin Surfactant Assemblies as Dynamic Pathways Guiding the Growth of Electrodeposited Copper Dendrites.

Self-organization of inorganic matter enables bottom-up construction of materials with target shapes suited to their function. Positioning the building blocks in the growth process involves a well-balanced interplay of the reaction and diffusion. Whereas (supra)molecular structures have been used to template such growth processes, we reasoned that molecular assemblies can be employed to actively create concentration gradients that guide the deposition of solid, wire-like structures. The core of our approach comprises the interaction between myelin assemblies that deliver copper(II) ions to the tips of copper dendrites, which in turn grow along the Cu2+ gradient upon electrodeposition. First, we successfully include Cu2+ ions among amphiphile bilayers in myelin filaments, which grow from tri(ethylene glycol) monododecyl ether (C12E3) source droplets over air-water interfaces. Second, we characterize the growth of dendritic copper structures upon electrodeposition from a negative electrode at the sub-mM Cu2+ concentrations that are anticipated upon release from copper(II)-loaded myelins. Third, we assess the intricate growth of copper dendrites upon electrodeposition, when combined with copper(II)-loaded myelins. The myelins deliver Cu2+ at a negative electrode, feeding copper dendrite growth upon electrodeposition. Intriguingly, the copper dendrites follow the Cu2+ gradient toward the myelins and grow along them toward the source droplet. We demonstrate the growth of dynamic connections among electrodes and surfactant droplets in reconfigurable setups─featuring a unique interplay between molecular assemblies and inorganic, solid structures.

Dynamic Implications of Noncovalent Interactions in Amphiphilic Single-Chain Polymer Nanoparticles.

Single-chain polymer nanoparticles (SCNPs) combine the chemical diversity of synthetic polymers with the intricate structure of biopolymers, generating versatile biomimetic materials. The mobility of polymer chain segments at length scales similar to secondary structural elements in proteins is critical to SCNP structure and thus function. However, the influence of noncovalent interactions used to form SCNPs (e.g., hydrogen-bonding and biomimetic secondary-like structure) on these conformational dynamics is challenging to quantitatively assess. To isolate the effects of noncovalent interactions on SCNP structure and conformational dynamics, we synthesized a series of amphiphilic copolymers containing dimethylacrylamide and monomers capable of forming these different interactions: (1) di(phenylalanine) acrylamide that forms intramolecular ß-sheet-like cross-links, (2) phenylalanine acrylamide that forms hydrogen-bonds but lacks a defined local structure, and (3) benzyl acrylamide that has the lowest propensity for hydrogen-bonding. Each SCNP formed folded structures comparable to those of intrinsically disordered proteins, as observed by size exclusion chromatography and small angle neutron scattering. The dynamics of these polymers, as characterized by a combination of dynamic light scattering and neutron spin echo spectroscopy, was well described using the Zimm with internal friction (ZIF) model, highlighting the role of each noncovalent interaction to additively restrict the internal relaxations of SCNPs. These results demonstrate the utility of local scale interactions to control SCNP polymer dynamics, guiding the design of functional biomimetic materials with refined binding sites and tunable kinetics.

Revealed masks: Facial mimicry after oxytocin administration in forensic psychopathic patients.

Facial mimicry serves as an evolutionarily rooted important interpersonal communication process that touches on the concepts of socialization and empathy. Facial electromyography (EMG) of the corrugator muscle and the zygomaticus muscle was recorded while male forensic psychopathic patients and controls watched morphed angry or happy facial expressions. We tested the hypothesis that psychopathic patients would show weaker short latency facial mimicry (that is, within 600 ms after stimulus onset) than controls. Exclusively in the group of 20 psychopathic patients, we tested in a placebo-controlled crossover within-subject design the hypothesis that oxytocin would enhance short-latency facial mimicry. Compared with placebo, we found no oxytocin-related significant short-latency responses of the corrugator and the zygomaticus. However, compared with 19 normal controls, psychopathic patients in the placebo condition showed significantly weaker short-latency zygomaticus responses to happy faces, while there was a trend toward significantly weaker short-latency corrugator responses to angry faces. These results are consistent with a recent study of facial EMG responses in adolescents with psychopathic traits. We therefore posit a lifetime developmental deficit in psychopathy pertaining short-latency mimicry of emotional facial expressions. Ultimately, this deficit in mimicking angry and happy expressions may hinder the elicitation of empathy, which is known to be impaired in psychopathy.

Long-term effects of the COVID-19 pandemic for patients with cancer.

INTRODUCTION: Long COVID is defined as the continuation of symptoms, unexplainable by alternative diagnosis, longer than four weeks after SARS-CoV-2 infection. These symptoms might hinder daily activities and overall well-being, ultimately impacting quality of life (QoL). Several studies have reported fatigue as the most common symptom, followed by dyspnoea, headache and myalgia. Although it is assumed that long COVID affects 10-20% of SARS-CoV-2 infected individuals, recently numbers up to 60% were described for patients with cancer. This study uncovers the impact of the COVID-19 pandemic on QoL of patients with cancer and how long COVID manifests in this cohort. METHODS: A group of 96 patients with cancer was followed from March 2022 till March 2023. Online questionnaires assessing symptoms associated with long COVID, anxiety and depression (HADS), quality of life (EORTC-QLQ-C30) and cognitive functioning (CFQ) were sent every three months during this period. Furthermore, a semi-structured focus group was organised for qualitative data collection. RESULTS: Overall, these patients reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. Forty nine patients with cancer (51.0%) were infected with SARS-CoV-2 over the course of the study, of which 39 (79.6%) reported long COVID symptoms. The most commonly reported symptoms were myalgia (46.2%), fatigue (38.5%) and disturbed sleep (35.9%) and it was observed that male sex is associated with poor long COVID outcomes. CONCLUSION: While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve.

Since the outbreak in Wuhan (China) at the end of 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has caused instability at various levels of society. While most patients completely recover from their SARS-CoV-2 infection, 10­20% of infected persons and up to 60% of infected patients with cancer develop long COVID. Long COVID is defined as the continuation of symptoms, which cannot be explained by alternative causes, that last longer than four weeks after initial infection. Even though it is generally accepted that patients with cancer are at increased risk of developing severe COVID-19, it is still unclear how long COVID manifests and whether long COVID impacts quality of life in this cohort. Hence, this study observed that patients with cancer reported a negative impact of the enforced COVID-19 restrictions on the emotional and psychological wellbeing. While patients with cancer experience similar long COVID symptoms as healthy controls, the prevalence is remarkably higher possibly due to their compromised immune system and weakened physiological reserve.

Successful Aging Through Financial Empowerment (SAFE): Financial Coaching with Older Adult Victims of Financial Exploitation.

Financial exploitation (FE) of older adults is a growing public health problem. Current estimates of financial exploitation show between 5% and 11% of older adults are victimized each year. This study examined an empowerment-centered financial coaching intervention. Program records and participant baseline and follow-up assessment data were used to detail program dynamics and investigate participant outcomes. Most SAFE participants were very satisfied or satisfied (91%) with the services they received. Participants also reported significantly less stress at the six-month follow-up. These findings demonstrate that empowerment-centered financial coaching interventions can successfully address FE in older adult populations.

Deep learning-based image quality assessment: impact on detection accuracy of prostate cancer extraprostatic extension on MRI.

OBJECTIVE: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm. MATERIALS AND METHODS: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE. RESULTS: A total of 773 consecutive patients (median age 61 [IQR 56-67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67-76%] vs. 63% [95% CI 56-69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62-80%] vs. 75% [95% CI 63-85%]), positive predictive value (44% [95% CI 39-49%] vs. 38% [95% CI 32-43%]), or negative predictive value (89% [95% CI 86-92%] vs. 89% [95% CI 85-93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54-5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63-4.24; P = 0.24). CONCLUSION: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology.

Cervical vertebral and spinal cord injuries in rollover occupants.

BACKGROUND: Rollover crashes continue to be a substantial public health issue in North America. Previous research has shown that the cervical spine is the most injured spine segment in rollovers, but much of the past research has focused on risk factors rather than the actual cervical spine injuries. We sought to examine how different types of cervical spine injuries (vertebral and/or cord injury) vary with different occupant-related factors in rollovers and to compare these with non-rollovers. METHODS: We obtained crash and injury information from the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) for 2005-2015 and Crash Investigation Sampling System (CISS) for 2017-2022. Based on weighted data, we calculated relative risks to assess how occupant sex, seat belt use, ejection status, and fatal outcome relate to the rate of different cervical spine injuries in rollovers and non-rollovers. RESULTS: In NASS-CDS occupants with cervical spine injuries (N = 111,040 weighted cases), about 91.5% experienced at least one vertebral injury whereas only 11.3% experienced a spinal cord injury (most of which had a concomitant vertebral fracture). All types of cervical spine injuries we examined were 3.4-5.2 times more likely to occur in rollovers compared to non-rollovers. These relative risks were similar for both sexes, belted and unbelted, non-ejected, and non-fatal occupants. The number of weighted CISS occupants with cervical spine injuries (N = 42,003) was smaller than in the NASS analysis, but cervical spine injuries remained 6.25 to 6.36 times more likely in rollovers compared to non-rollovers despite a more modern vehicle fleet. CONCLUSIONS: These findings underscore the continued need for rollover-specific safety countermeasures, especially those focused on cervical spine injury prevention, and elucidate the frequency, severity and other characteristics of the specific vertebral and spinal cord injuries being sustained in rollovers. Our findings suggest that countermeasures focused on preventing cervical vertebral fractures will also effectively prevent most cervical spinal cord injuries.

Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model.

Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and trigeminal cells. After CSD, ~11% of the CSF proteome is altered, with up-regulation of proteins that directly activate receptors in the trigeminal ganglion. CSF collected from animals exposed to CSD activates trigeminal neurons in naïve mice in part by CSF-borne calcitonin gene-related peptide (CGRP). We identify a communication pathway between the central and peripheral nervous system that might explain the relationship between migrainous aura and headache.

The Role of Alpha-Synuclein in Synucleinopathy: Impact on Lipid Regulation at Mitochondria-ER Membranes.

The protein alpha-synuclein (αSyn) plays a critical role in the pathogenesis of synucleinopathy, which includes Parkinson's disease and multiple system atrophy, and mounting evidence suggests that lipid dyshomeostasis is a critical phenotype in these neurodegenerative conditions. Previously, we identified that αSyn localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs), temporary functional domains containing proteins that regulate lipid metabolism, including the de novo synthesis of phosphatidylserine. In the present study, we have analyzed the lipid composition of postmortem human samples, focusing on the substantia nigra pars compacta of Parkinson's disease and controls, as well as three less affected brain regions of Parkinson's donors. To further assess synucleinopathy-related lipidome alterations, similar analyses were performed on the striatum of multiple system atrophy cases. Our data show region-and disease-specific changes in the levels of lipid species. Specifically, our data revealed alterations in the levels of specific phosphatidylserine species in brain areas most affected in Parkinson's disease. Some of these alterations, albeit to a lesser degree, are also observed multiples system atrophy. Using induced pluripotent stem cell-derived neurons, we show that αSyn contributes to regulating phosphatidylserine metabolism at MAM domains, and that αSyn dosage parallels the perturbation in phosphatidylserine levels. Our results support the notion that αSyn pathophysiology is linked to the dysregulation of lipid homeostasis, which may contribute to the vulnerability of specific brain regions in synucleinopathy. These findings have significant therapeutic implications.

Exploring and retrieving sequence and metadata for species across the tree of life with NCBI Datasets.

To explore complex biological questions, it is often necessary to access various data types from public data repositories. As the volume and complexity of biological sequence data grow, public repositories face significant challenges in ensuring that the data is easily discoverable and usable by the biological research community. To address these challenges, the National Center for Biotechnology Information (NCBI) has created NCBI Datasets. This resource provides straightforward, comprehensive, and scalable access to biological sequences, annotations, and metadata for a wide range of taxa. Following the FAIR (Findable, Accessible, Interoperable, and Reusable) data management principles, NCBI Datasets offers user-friendly web interfaces, command-line tools, and documented APIs, empowering researchers to access NCBI data seamlessly. The data is delivered as packages of sequences and metadata, thus facilitating improved data retrieval, sharing, and usability in research. Moreover, this data delivery method fosters effective data attribution and promotes its further reuse. This paper outlines the current scope of data accessible through NCBI Datasets and explains various options for exploring and downloading the data.

Association of remoteness and ethnicity with major amputation following minor amputation to treat diabetes-related foot disease.

INTRODUCTION: Minor amputation is commonly needed to treat diabetes-related foot disease (DFD). Remoteness of residence is known to limit access to healthcare and has previously been associated with poor outcomes. The primary aim of this study was to examine the associations between ethnicity and remoteness of residency with the risk of major amputation and death following initial treatment of DFD by minor amputation. A secondary aim was to identify risk factors for major amputation and death following minor amputation to treat DFD. RESEARCH DESIGN AND METHODS: This was a retrospective analysis of data from patients who required a minor amputation to treat DFD between 2000 and 2019 at a regional tertiary hospital in Queensland, Australia. Baseline characteristics were collected together with remoteness of residence and ethnicity. Remoteness was classified according to the 2019 Modified Monash Model (MMM) system. Ethnicity was based on self-identification as an Aboriginal and Torres Strait Islander or non-Indigenous person. The outcomes of major amputation, repeat minor amputation and death were examined using Cox-proportional hazard analyses. RESULTS: A total of 534 participants were included, with 306 (57.3%) residing in metropolitan or regional centres, 228 (42.7%) in rural and remote communities and 144 (27.0%) were Aboriginal or Torres Strait Islander people. During a median (inter quartile range) follow-up of 4.0 (2.1-7.6) years, 103 participants (19.3%) had major amputation, 230 (43.1%) had repeat minor amputation and 250 (46.8%) died. The risks (hazard ratio [95% CI]) of major amputation and death were not significantly higher in participants residing in rural and remote areas (0.97, 0.67-1.47; and 0.98, 0.76-1.26) or in Aboriginal or Torres Strait Islander people (HR 1.44, 95% CI 0.96, 2.16 and HR 0.89, 95% CI 0.67, 1.18). Ischemic heart disease (IHD), peripheral artery disease (PAD), osteomyelitis and foot ulceration (p<0.001 in all instances) were independent risk factors for major amputation. CONCLUSION: Major amputation and death are common following minor amputation to treat DFD and people with IHD, PAD and osteomyelitis have an increased risk of major amputation. Aboriginal and Torres Strait Islander People and residents of remote areas were not at excess risk of major amputation.

CSF Proteomics in Patients With Progressive Supranuclear Palsy.

BACKGROUND AND OBJECTIVES: Identification of fluid biomarkers for progressive supranuclear palsy (PSP) is critical to enhance therapeutic development. We implemented unbiased DNA aptamer (SOMAmer) proteomics to identify novel CSF PSP biomarkers. METHODS: This is a cross-sectional study in original (18 clinically diagnosed PSP-Richardson syndrome [PSP-RS], 28 cognitively healthy controls]), validation (23 PSP-RS, 26 healthy controls), and neuropathology-confirmed (21 PSP, 52 non-PSP frontotemporal lobar degeneration) cohorts. Participants were recruited through the University of California, San Francisco, and the 4-Repeat Neuroimaging Initiative. The original and neuropathology cohorts were analyzed with the SomaScan platform version 3.0 (5026-plex) and the validation cohort with version 4.1 (7595-plex). Clinical severity was measured with the PSP Rating Scale (PSPRS). CSF proteomic data were analyzed to identify differentially expressed targets, implicated biological pathways using enrichment and weighted consensus gene coexpression analyses, diagnostic value of top targets with receiver-operating characteristic curves, and associations with disease severity with linear regressions. RESULTS: A total of 136 participants were included (median age 70.6 ± 8 years, 68 [50%] women). One hundred fifty-five of 5,026 (3.1%), 959 of 7,595 (12.6%), and 321 of 5,026 (6.3%) SOMAmers were differentially expressed in PSP compared with controls in original, validation, and neuropathology-confirmed cohorts, with most of the SOMAmers showing reduced signal (83.1%, 95.1%, and 73.2%, respectively). Three coexpression modules were associated with PSP across cohorts: (1) synaptic function/JAK-STAT (ß = -0.044, corrected p = 0.002), (2) vesicle cytoskeletal trafficking (ß = 0.039, p = 0.007), and (3) cytokine-cytokine receptor interaction (ß = -0.032, p = 0.035) pathways. Axon guidance was the top dysregulated pathway in PSP in original (strength = 1.71, p < 0.001), validation (strength = 0.84, p < 0.001), and neuropathology-confirmed (strength = 0.78, p < 0.001) cohorts. A panel of axon guidance pathway proteins discriminated between PSP and controls in original (area under the curve [AUC] = 0.924), validation (AUC = 0.815), and neuropathology-confirmed (AUC = 0.932) cohorts. Two inflammatory proteins, galectin-10 and cytotoxic T lymphocyte-associated protein-4, correlated with PSPRS scores across cohorts. DISCUSSION: Axon guidance pathway proteins and several other molecular pathways are downregulated in PSP, compared with controls. Proteins in these pathways may be useful targets for biomarker or therapeutic development.

Facing infant cuteness: How nurturing care motivation and oxytocin system gene methylation are associated with responses to baby schema features.

Baby schema features are a specific set of physical features-including chubby cheeks, large, low-set eyes, and a large, round head-that have evolutionary adaptive value in their ability to trigger nurturant care. In this study among nulliparous women (N = 81; M age = 23.60, SD = 0.44), we examined how sensitivity to these baby schema features differs based on individual variations in nurturant care motivation and oxytocin system gene methylation. We integrated subjective ratings with measures of facial expressions and electroencephalography (EEG) in response to infant faces that were manipulated to contain more or less pronounced baby schema features. Linear mixed effects analyses demonstrated that infants with more pronounced baby schema features were rated as cuter and participants indicated greater motivation to take care of them. Furthermore, infants with more pronounced baby schema features elicited stronger smiling responses and enhanced P2 and LPP amplitudes compared to infants with less pronounced baby schema features. Importantly, individual differences significantly predicted baby schema effects. Specifically, women with low OXTR methylation and high nurturance motivation showed enhanced differentiation in automatic neurophysiological responses to infants with high and low levels of baby schema features. These findings highlight the importance of considering individual differences in continued research to further understand the complexities of sensitivity to child cues, including facial features, which will improve our understanding of the intricate neurobiological system that forms the basis of caregiving behavior.

Defluorination of Organofluorine Compounds Using Dehalogenase Enzymes from Delftia acidovorans (D4B).

Organofluorine compounds have been widely used as pharmaceuticals, agricultural pesticides, and water-resistant coatings for decades; however, these compounds are recognized as environmental pollutants. The capability of microorganisms and enzymes to defluorinate organofluorine compounds is both rare and highly desirable to facilitate environmental remediation efforts. Recently, a strain of Delftia acidovorans (D4B) was identified with potential biodegradation activity toward perfluoroalkyl substances (PFAS) and other organofluorine compounds. Genomic analysis found haloacid and fluoroacetate dehalogenases as enzymes associated with Delftia acidovorans. Here, defluorination activity of these enzymes toward different fluorinated substrates was investigated after their recombinant expression and purification from E. coli. Using an electrochemical fluoride probe, 19F NMR, and mass spectrometry to monitor defluorination, we identified two dehalogenases, DeHa2 (a haloacid dehalogenase) and DeHa4 (a fluoroacetate dehalogenase), with activity toward mono- and difluoroacetate. Of the two dehalogenases, DeHa4 demonstrated a low pH optimum compared to DeHa2, which lost catalytic activity under acidic conditions. DeHa2 and DeHa4 are relatively small proteins, operate under aerobic conditions, and remain active for days in the presence of substrates. Significantly, while there have been many reports on dehalogenation of monofluoroacetate by dehalogenases, this study adds to the relatively small list of enzymes reported to carry out enzymatic defluorination of the more recalcitrant disubstituted carbon in an organofluorine compound. Thus, DeHa2 and DeHa4 represent organofluorine dehalogenases that may be used in the future to design and engineer robust defluorination agents for environmental remediation efforts.

Cardiac autonomic function in REM-related obstructive sleep apnoea: insights from nocturnal heart rate variability profiles.

PURPOSE: In light of the reported association between REM-related obstructive sleep apnoea (OSA) and heightened cardiovascular risk, this study aims to compare cardiac autonomic function in patients with REM-OSA and OSA independent of sleep stage. We hypothesized that REM-OSA patients would exhibit higher sympathetic cardiac modulation based on heart rate variability (HRV) profiles. METHODS: HRV was compared between the OSA group (AHI ≥ 5 events/h, n = 252) and the REM-OSA group (AHI ≥ 5 events/h, AHIREM:AHINREM ≥ 2, n = 137). Time- and frequency-domain measures of HRV were analysed during N2 and REM sleep. RESULTS: Clinical characteristics between the two test groups differed significantly, 45% of REM-OSA patients were female, with mild OSA (median, interquartile range (IQR)) AHI of 10 (7) events/h. Only 26% of the OSA cohort were female with moderate OSA (AHI = 17 (20) events/h, p < 0.001). Compared with the OSA group, the low frequency to high frequency ratio (LF:HF) and LF power were lower and HF power was higher in the REM-OSA group during N2 (LF:HF, p = 0.012; LF; p = 0.013; HF, p = 0.007) and in REM sleep (LF:HF, p = 0.002; LF, p = 0.004; HF, p < 0.001). Patient sex and OSA severity had a significant combined effect on average N to N interval, LF power, and LF:HF ratio during N2 and REM sleep (all p < 0.001). CONCLUSION: Contrary to our hypothesis, REM-OSA patients demonstrated consistently higher cardiac vagal modulation, reflecting better cardiac autonomic adaptation. These results were attributed to differences in OSA severity and sex in these two groups, both independently affecting HRV. This study emphasises the need for future research into the underlying pathophysiology of REM-OSA and the potential implications of sex and OSA severity on cardiovascular risk.

High prevalence of obstructive sleep apnea in a surgical aortic valve replacement cohort: an observational study.

Study Objectives: A high prevalence of sleep apnea has been reported among transcatheter aortic valve replacement (AVR) patients; however, the prevalence of sleep apnea in the younger and relatively healthier population of surgical AVR (SAVR) patients is unknown. Methods: We assessed the prevalence of sleep apnea and overall sleep quality in patients having SAVR. Participants aged 50-89 were eligible for recruitment. All participants completed type II HST before SAVR. Sleep apnea was defined as an apnea-hypopnea index (AHI) ≥ 5 events/hour. The current use of positive airway pressure was exclusionary. Results: The 46 participants (32 males/14 females) had a mean age of 66.6 years, body mass index of 30, AHI of 23.5, and obstructive AHI of 22.0. Only four participants had a prior sleep apnea diagnosis, yet all but one had sleep apnea on type II sleep testing. Two-thirds of sleep apnea was moderate or severe (AHI ≥ 15). A quarter of respiratory events were defined by arousals without desaturations. Whereas most sleep parameters resembled those of similarly aged community cohorts, mean percentage of N3 was reduced, accounting for only 3.8% of total sleep time. Conclusions: Type II home sleep testing (HST) revealed a 97.8% prevalence of sleep apnea in this sample, most of which was undiagnosed obstructive sleep apnea. Roughly two-thirds of sleep apnea was moderate or severe. Such a high impact of obstructive sleep apnea among patients with severe aortic valve disease deserves further investigation on potential underlying mechanisms and clinical implications.