Sex-Specific ADNP/NAP (Davunetide) Regulation of Cocaine-Induced Plasticity.

Cocaine use disorder (CUD) is a chronic neuropsychiatric disorder estimated to effect 1-3% of the population. Activity-dependent neuroprotective protein (ADNP) is essential for brain development and functioning, shown to be protective in fetal alcohol syndrome and to regulate alcohol consumption in adult mice. The goal of this study was to characterize the role of ADNP, and its active peptide NAP (NAPVSIPQ), which is also known as davunetide (investigational drug) in mediating cocaine-induced neuroadaptations. Real time PCR was used to test levels of Adnp and Adnp2 in the nucleus accumbens (NAc), ventral tegmental area (VTA), and dorsal hippocampus (DH) of cocaine-treated mice (15 mg/kg). Adnp heterozygous (Adnp +/-)and wild-type (Adnp +/-) mice were further tagged with excitatory neuronal membrane-expressing green fluorescent protein (GFP) that allowed for in vivo synaptic quantification. The mice were treated with cocaine (5 injections; 15 mg/kg once every other day) with or without NAP daily injections (0.4 µg/0.1 ml) and sacrificed following the last treatment. We analyzed hippocampal CA1 pyramidal cells from 3D confocal images using the Imaris x64.8.1.2 (Oxford Instruments) software to measure changes in dendritic spine density and morphology. In silico ADNP/NAP/cocaine structural modeling was performed as before. Cocaine decreased Adnp and Adnp2 expression 2 h after injection in the NAc and VTA of male mice, with mRNA levels returning to baseline levels after 24 h. Cocaine further reduced hippocampal spine density, particularly synaptically weaker immature thin and stubby spines, in male Adnp+/+) mice while increasing synaptically stronger mature (mushroom) spines in Adnp+/-) male mice and thin and stubby spines in females. Lastly, we showed that cocaine interacts with ADNP on a zinc finger domain identical to ketamine and adjacent to a NAP-zinc finger interaction site. Our results implicate ADNP in cocaine abuse, further placing the ADNP gene as a key regulator in neuropsychiatric disorders. Ketamine/cocaine and NAP treatment may be interchangeable to some degree, implicating an interaction with adjacent zinc finger motifs on ADNP and suggestive of a potential sex-dependent, non-addictive NAP treatment for CUD.

Acute Aerobic Exercise Intensity on Working Memory and Vigilance After Nap Deprivation: Effects of Low-Intensity Deserve Attention.

Background: Napping deprivation in habitual nappers leads to cognitive impairment. The ameliorative effect of acute aerobic exercise has been demonstrated for this post-cognitive impairment. However, it is still unclear which intensity of aerobic exercise is the most effective and how long this improvement can be sustained. Methods: Fifty-eight healthy adults with a chronic napping habit were randomly assigned to four intervention groups after undergoing nap deprivation: a sedentary control group, a low-intensity exercise group (50-59% maximum heart rate, HRmax), a moderate-intensity exercise group (60-69% HRmax), and a high-intensity exercise group (70-79% HRmax). Working memory (N-back task), vigilance (Psychomotor Vigilance Task, PVT), and response inhibitory capacity (Go/NoGo task) were measured. Results: Regression analyses showed a quadratic trend between exercise intensity and working memory reaction time and accuracy (F =3.297-5.769, p < 0.05, R2 =10.7-18.9%). The effects of exercise were optimal at low-intensity. There was a significant quadratic trend between exercise intensity and PVT lapse (F =4.314, p =0.042, R² =7.2%). The effect of exercise increased with higher intensity. Prolonged observation found that the effect of low-intensity exercise on working memory was maintained for 2 hours. Conclusion: The effect of low-intensity exercise might be underestimated. Low-intensity exercise significantly improved working memory performance, and the effects could be maintained throughout the afternoon. In contrast, the effects of high-intensity exercise were unlikely to be maintained and might even have negative effects. Future researchers can broaden the categories of participants to enhance the external validity and collect diverse physiological indicators to explore related physiological mechanisms.

Validation of intrinsic capacity and healthy sleep pattern in middle-aged and older adults: a longitudinal Chinese study assessing healthy ageing.

OBJECTIVES: Intrinsic capacity (IC), a multidimensional construct encompassing mental and physical capacities, has been established in the aging framework by the World Health Organization. However, the detailed relationship between IC and Chinese sleep patterns (nighttime sleep and post-lunch naps) remains inadequately elucidated. METHODS: Participants in this study were individuals aged ≥45 years residing in China, included in the China Health and Retirement Longitudinal Study (CHARLS). We analyzed 4 years of CHARLS data from the first wave (May 2011-March 2012) to the second wave (July 2015-January 2016). Data from these waves were utilized for longitudinal analysis. Self-reported data included nighttime sleep and nap duration, along with other baseline characteristics. The IC evaluation involved physical examinations and blood tests. Initially, linear regression was used to assess the relationship between total sleep duration, nighttime sleep duration, nap duration, and IC change between the two waves that were determined by marginal effects (ME) and their corresponding 95% confidence intervals (CIs). Regression splines were employed to explore potential nonlinear associations. Subgroup and sensitivity analyses were conducted to investigate the heterogeneity of IC change under specific conditions and the robustness of our results. Mediation analysis was performed to identify potential factors mediating the relationship between sleep patterns and IC change. RESULTS: Both excessive (>10 h) (total, ME: -1.12; 95% CI: -1.61, -0.64; nighttime, ME: -1.44; 95% CI: -2.29, -0.59) and insufficient (<6 h) sleep duration (total, ME: -0.43; 95% CI: -0.68, -0.18; nighttime, ME: -0.50; 95% CI: -0.73, -0.27) negatively impacted IC change. Moderate naps (≤60 min) mitigated the decline in IC change (ME: 0.28; 95% CI: 0.07, 0.49). IC values decreased at the slowest rate when nap time constituted one-seventh of total sleep time. The onset of dyslipidemia partially mediated the association between naps (≤60 min) and IC change (P = 0.02). CONCLUSIONS: These findings suggest that maintaining a healthy sleep pattern of 6-8 h of nighttime or total sleep, along with a post-lunch nap of ≤60 min, helps preserve optimal IC or delay its decline. This is particularly beneficial for cognitive, psychological, and locomotion performance among middle-aged and older adults.

4d-2p-4f Gradient Orbital Coupling Enables Tandem Catalysis for Simultaneous Abatement of N2O and CO on Atomically Dispersed Rh/CeO2 Catalyst.

N2O and CO coexist in various industrial and mobile sources. The synergistic reaction of N2O and CO to generate N2 and CO2 has garnered significant research interest, but it remains extremely challenging. Herein, we constructed an atomically dispersed Rh-supported CeO2 catalyst with asymmetric Rh-O-Ce sites through gradient Rh 4d-O 2p-Ce 4f orbital coupling. This design effectively regulates the 4f electron states of Ce and promotes the electron filling of the O 3π* antibonding orbital to facilitate N-O bond cleavage. Near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) reveals that CO reacts with the surface-adsorbed O* generated by N2O decomposition through self-tandem catalysis, accelerating the rate-limiting step in N2O decomposition and activating the synergistic reaction of N2O and CO at temperatures as low as 115 °C. This work can guide the development of high-performance catalysts using the strategy of high-order orbital hybridization combined with the tandem concept to achieve versatile catalytic applications.

[Causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus: a two-sample bidirectional Mendelian randomization study].

OBJECTIVE: To explore the causal relationship between sleep phenotype and idiopathic normal pressure hydrocephalus (iNPH) using two-sample bidirectional Mendelian randomization. METHODS: The exposure data including 8 sleep phenotypes used in this study were obtained from GWAS catalog, FinnGenR10 and MRCIEU GWAS. The outcome data for idiopathic normal-pressure hydrocephalus were obtained from FinnGen R10. We used the inverse-variance weighted (IVW) method to perform the principal analyses. Cochrane Q-statistics test was used to assess the heterogeneity and MR Egger­intercept test performed to evaluate the pleiotropy for sensitivity analyses. RESULTS: IVW result showed that frequent daytime nap was associated with higher odds of iNPH (OR=3.3393, 95 CI% : 1.0646-10.4742, P=0.0270). Cochrane Q-statistics test and MR Egger­intercept test showed that the MR analysis had no pleiotropy or heterogeneity (P > 0.05). The external validation reproduced this result (OR=2.5660, 95 CI% : 1.1680-5.6373, P=0.0189; OR=4.0424, 95 CI% : 1.5709-10.4024, P=0.0038). Reverse Mendelian randomization suggested that iNPH did not have significant impact on sleep phenotype. CONCLUSION: The frequency of daytime naps is causally associated with iNPH, and reducing the frequency of weekly daytime naps can reduce the risk of iNPH in the elderly population.

How to quantify sleepiness during an attempt to sleep?

Background. Sleepiness assessment tools were mostly developed for detection of an elevated sleepiness level in the condition of sleep deprivation and several medical conditions. However, sleepiness occurs in various other conditions including the transition from wakefulness to sleep during an everyday attempt to get sleep.Objective. We examined whether objective sleepiness indexes can be implicated in detection of fluctuations in sleepiness level during the polysomnographically-monitored attempt to sleep, i.e. in the absence of self-reports on perceived sleepiness level throughout such an attempt.Approach. The polysomnographic signals were recorded in the afternoon throughout 106 90 min napping attempts of 53 university students (28 females). To calculate two objective sleepiness indexes, the electroencephalographic (EEG) spectra were averaged on 30 s epochs of each record, assigned to one of 5 sleep-wake stages, and scored using either the frequency weighting curve for sleepiness substate of wake state or loadings of each frequency on the 2nd principal component of variation in the EEG spectrum (either sleepiness score or PC2 score, respectively).Main results. We showed that statistically significant fluctuations in these two objective sleepiness indexes during epochs assigned to wake stage can be described in terms of the changes in verbally anchored levels of subjective sleepiness assessed by scoring on the 9-step Karolinska Sleepiness Scale.Significance. The results afford new opportunities to elaborate importance of intermediate substates between wake and sleep states for sleep-wake dynamics in healthy individuals and patients with disturbed sleep.

A colorimetric sensor based on multiple elements doped carbon dot nanozyme for rapid detection of 1-naphthol in human urine samples.

The residual carbaryl in crops can cause serious damage to the human kidney and nervous system after entering the human body, which may be metabolized to 1-naphthol (1-NAP) and excreted through urine. 1-NAP is often used as the biomarker for carbaryl exposure, so the intake or leakage of carbaryl can be monitored by detecting the concentration of 1-NAP. Herein, Co, N, P ternary co-doped carbon dots (CoNP-CDs) derived from vitamin B12 were synthesized by a facile hydrothermal method. CoNP-CDs exhibited oxidase-like activity and excellent peroxidase-like activity, which was attributed to the Fenton-like reaction of Co2+/Co3+ and the presence of pyrrole N and P elements, which together provided multiple active sites for chromogenic substrates. Due to the dual enzyme-like activity of CoNP-CDs, hydroxyl radicals (OH) and superoxide radicals (O2-) were generated during the catalytic process, which could rapidly oxidize colorless 3,3',5,5'-tetramethyl benzidine (TMB) to blue oxidation products (oxTMB). The α-carbon in 1-NAP can be attacked by OH, and the catalytic oxidation process of TMB can be inhibited by the consumption of OH, so that the blue color of the solution became lighter. Based on this principle, a smartphone-assisted colorimetric sensing platform was constructed for the detection of 1-NAP, and which resulted in a linear range of 1.07-37.3 µM and a visual detection limit of 0.68 µM. Moreover, the colorimetric sensing system showed satisfactory recoveries in the detection of human urine samples. The colorimetric sensing system owned the advantages of fast response, strong selectivity and simple operation, and provided a potential strategy for the on-site detection of 1-NAP.

Association between nighttime sleep duration, nap time, and mild cognitive impairment in Chinese older adults: a cross-sectional study.

OBJECTIVE: This study aims to investigate the relationship between midday nap time, nighttime sleep duration, and mild cognitive impairment (MCI) in Chinese older adults and determine the recommended sleep duration to provide a scientific basis for preventing and managing MCI in this population. METHODS: Utilizing the 2020 China Health and Retirement Longitudinal Study database, the demographic data, health status, and lifestyle information of the study participants were collected. A total of 5,314 valid samples were included in the analysis. Logistic regression and restricted cubic spline plots were employed to explore the relationship between sleep patterns and MCI. RESULTS: In the cross-sectional analysis, a linear relationship was observed between midday nap duration and MCI among Chinese elderly. The probability of MCI was lowest among those who napped for less than 30 min at noon. Compared with individuals who napped for30-90 min, those who did not nap were more likely to have MCI (OR = 1.30, 95% CI: 1.05-1.60). Older adults with napping duration < 30 min (OR = 0.73, 95% CI:0.56-0.95) also exhibited lower probability of MCI when compared those without napping habit, Nighttime sleep duration exhibited a U-shaped relationship with MCI. Individuals with less than approximately 6 h of nighttime sleep showed a gradual decrease in the probability of MCI with increasing sleep duration, whereas those with more than 7.5 h demonstrated an increase in the probability of MCI with longer sleep duration. Older adults who slept less than 6 h at night (OR = 1.22, 95% CI: 1.01 ~ 1.46) or more than 8 h (OR = 1.78, 95% CI: 1.35-2.33) were more likely to develop MCI compared with those who slept 6 to 8 h. CONCLUSION: After controlling for potential confounding variables, both nighttime sleep duration and midday nap duration exhibited a nonlinear "U"-shaped relationship with MCI among the elderly. The probability of depression was lower with a nap duration of approximately 60 min, and the optimal nighttime sleep duration was 6-8 h, with around 7 h providing the greatest cognitive benefits.

In vitro observation of histone-hexamer association with and dissociation from the amino-terminal region of budding yeast Mcm2, a subunit of the replicative helicase.

During DNA replication, core histones that form nucleosomes on template strands are evicted and associate with newly synthesized strands to reform nucleosomes. Mcm2, a subunit of the Mcm2-7 complex, which is a core component of the replicative helicase, interacts with histones in the amino-terminal region (Mcm2N) and is involved in the parental histone recycling to lagging strands. Herein, the interaction of Mcm2N with histones was biochemically analyzed to reveal the molecular mechanisms underlying histone recycling by Mcm2N. With the addition of Mcm2N, a histone hexamer, comprising a H3-H4 tetramer and a H2A-H2B dimer, was excised from the histone octamer to form a complex with Mcm2N. The histone hexamer, but not H3-H4 tetramer was released from Mcm2N in the presence of Nap1, a histone chaperone. FACT, another histone chaperone, stabilized Mcm2N-histone hexamer complex to protect from Nap1-dependent dissociation. This study indicates cooperative histone transfer via Mcm2N and histone chaperones.

Results of two cross-sectional database analyses regarding nap-induced modulations of tinnitus.

The influence of naps on tinnitus was systematically assessed by exploring the frequency, clinical and demographic characteristics of this phenomenon. 9,724 data from two different tinnitus databases (Tinnitus Hub: n = 6115; Tinnitus Research Initiative (TRI): n = 3627) were included. After separate analysis of the databases, these results were then compared with each other. In the Tinnitus Hub survey database, a total of 31.1% reported an influence on tinnitus by taking a nap (26.9% in the TRI database), with much more frequent worsening after a nap than improvement (23.0% a little or a lot worse; TRI: 17.7% worse; 8.1% a little or a lot better; TRI: 9.2% better). The influence of napping on tinnitus was associated in both databases with other clinical features, such as the dependence of tinnitus on night quality, stress and somatosensory maneuvers. The present study confirms the clinical observation that more tinnitus sufferers report worsening after a nap than tinnitus sufferers reporting an improvement. It was consistently shown that tinnitus sufferers reporting nap-induced modulation of tinnitus also report more frequently an influence of night sleep on their tinnitus. Further clinical and polysomnographic research is warranted to better understand the interaction between sleep and tinnitus.

Molluscum contagiosum virus protein MC089 inhibits interferon regulatory factor 3 activation.

Molluscum contagiosum virus (MCV) is a human-specific poxvirus that causes a highly common but mild infection characterized by distinctive and persistent papular skin lesions. These lesions can persist for long periods without an effective clearance response from the host. MCV, like all poxviruses, encodes multiple known immunosuppressive proteins which target innate immune signalling pathways involved in viral nucleic acid sensing, interferon production and inflammation which should trigger antiviral immunity leading to clearance. Two major families of transcription factors responsible for driving the immune response to viruses are the NF-κB and the interferon regulatory factor (IRF) families. While NF-κB broadly drives pro-inflammatory gene expression and IRFs chiefly drive interferon induction, both collaborate in transactivating many of the same genes in a concerted immune response to viral infection. Here, we report that the MCV protein MC089 specifically inhibits IRF activation from both DNA- and RNA-sensing pathways, making it the first characterized MCV inhibitor to selectively target IRF activation to date. MC089 interacts with proteins required for IRF activation, namely IKKε, TBKBP1 and NAP1. Additionally, MC089 targets RNA sensing by associating with the RNA-sensing adaptor protein mitochondrial antiviral-signalling protein on mitochondria. MC089 displays specificity in its inhibition of IRF3 activation by suppressing immunostimulatory nucleic acid-induced serine 396 phosphorylation without affecting the phosphorylation of serine 386. The selective interaction of MC089 with IRF-regulatory proteins and site-specific inhibition of IRF3 phosphorylation may offer a tool to provide novel insights into the biology of IRF3 regulation.

Cardiac arrest in adult cardiology patients receiving anaesthetic care: analysis from the 7th National Audit Project (NAP7) of the Royal College of Anaesthetists.

BACKGROUND: The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest because of existing knowledge gaps in this important topic. This applies in particular to cardiology patients receiving anaesthetic care, because numbers, types and complexity of minimally invasive interventional procedures requiring planned and unplanned anaesthesia in the cardiac intervention suite is increasing. METHODS: We analysed collected data to determine the epidemiology, clinical features, management and outcomes of peri-operative cardiac arrest in adult patients receiving anaesthetic care for cardiology procedures. RESULTS: There were 54 reports of peri-operative cardiac arrest in adult patients receiving anaesthetic care for cardiology procedures, accounting for 54/881 (6.1%) of all reports to NAP7. The estimated incidence (95%CI) of cardiac arrests in this group was 1/450 or 0.22 (0.17-0.29)%. These patients were older than other adult patients in the NAP7 population, with a notably high proportion of patients of Asian ethnicity when compared with the remaining NAP7 cohort (9/54, 17% vs. 35/709, 5%). Rates of extracorporeal membrane oxygenation cardiopulmonary resuscitation were low (3/53, 6%). A common theme was that of logistical issues and teamworking, with reporters commenting on the difficulties of remote and/or unfamiliar locations and communication issues between specialties, on occasion resulting in poor teamworking and a lack of focus. The NAP7 panel review identified several other common themes which included: cardiogenic shock; late involvement of anaesthesia in the case; and transcatheter aortic valve implantation. CONCLUSION: Cardiology procedures requiring anaesthesia care account for < 1% of anaesthesia activity but generate 6% of all peri-operative cardiac arrests. The incidence of cardiac arrest was disproportionately high in cardiological procedures requiring anaesthetic care. The nature of the cardiac arrest reports to NAP7 indicate that logistical and human factors in multidisciplinary teams in the cardiac intervention suite merit addressing to improve care.

Objectively Measured Sleep Duration and Health-Related Quality of Life in Older Adults with Metabolic Syndrome: A One-Year Longitudinal Analysis of the PREDIMED-Plus Cohort.

The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [ß-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [ß-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Integration of single-cell sequencing with machine learning and Mendelian randomization analysis identifies the NAP1L1 gene as a predictive biomarker for Alzheimer's disease.

Background: The most effective approach to managing Alzheimer's disease (AD) lies in identifying reliable biomarkers for AD to forecast the disease in advance, followed by timely early intervention for patients. Methods: Transcriptomic data on peripheral blood mononuclear cells (PBMCs) from patients with AD and the control group were collected, and preliminary data processing was completed using standardized analytical methods. PBMCs were initially segmented into distinct subpopulations, and the divisions were progressively refined until the most significantly altered cell populations were identified. A combination of high-dimensional weighted gene co-expression analysis (hdWGCNA), cellular communication, pseudotime analysis, and single-cell regulatory network inference and clustering (SCENIC) analysis was used to conduct single-cell transcriptomics analysis and identify key gene modules from them. Genes were screened using machine learning (ML) in the key gene modules, and internal and external dataset validations were performed using multiple ML methods to test predictive performance. Finally, bidirectional Mendelian randomization (MR) analysis, regional linkage analysis, and the Steiger test were employed to analyze the key gene. Result: A significant decrease in non-classical monocytes was detected in PMBC of AD patients. Subsequent analyses revealed the inherent connection of non-classical monocytes to AD, and the NAP1L1 gene identified within its gene module appeared to exhibit some association with AD as well. Conclusion: The NAP1L1 gene is a potential predictive biomarker for AD.

Atomic Force Microscopy Characterization of Reconstituted Protein-DNA Complexes.

Atomic force microscopy is a high-resolution imaging technique useful for observing the structures of biomolecular complexes. This approach provides a straightforward method to characterize the binding behavior of different chromatin architectural proteins and to analyze the increasingly complex structural units assembled on the DNA. The protocol describes the preparation, AFM imaging, and structural analysis of chromatin that is reconstituted in vitro using purified proteins and DNA. Here, we describe the successful application of the method on the chromatin architectural proteins of the archaeon Sulfolobus solfataricus.

Effects of post-learning nap in the recognition memory for faces in habitual nappers.

This study investigated the effects of diurnal nap in the recognition memory for faces in habitual nappers. Thirty volunteers with habitual midday napping (assigned as the sleep group) and 28 non-nappers (assigned as the wake group) participated in this study. Participants were instructed to memorize faces, and subsequently to perform two recognition tasks before and after nap/wakefulness, i.e., an immediate recognition and a delayed recognition. There were three experimental conditions: same faces with the same view angle (S-S condition); same faces with a different view angle (22.5°) (S-D condition); and novel faces (NF condition). A mixed repeated-measures ANOVA revealed that the sleep group exhibited significantly longer reaction times (RT) following their nap compared to those of the wake group; no significant between-group differences were observed in accuracy or sensitivity (d'). Furthermore, both groups were more conservative in the delayed recognition task compared to the immediate recognition task, but the sleep group was more conservative after their nap (vs pre-nap), reflected by the criterion (ß, Ohit/Ofalse alarm). Further stepwise regression analysis revealed a positive relationship between duration of stage N3 sleep and normalized RT difference before/after nap on the S-S condition. These findings suggest that an immediate nap following face learning is associated with memory reorganization during N3 sleep in habitual nappers, rendering the memories not readily accessible.

Anaesthesia associates' clinical activity, case mix, supervision and involvement in peri-operative cardiac arrest: analysis from the 7th National Audit Project.

BACKGROUND: We analysed the clinical practice of anaesthesia associates in the UK, as reported to the 7th National Audit Project of the Royal College of Anaesthetists, and compared these with medically qualified anaesthetists. METHODS: We included data from our baseline survey, activity survey and case registry as with other reports from the project. RESULTS: Among 197 departments of anaesthesia, 52 (26%) employed anaesthesia associates. Of 10,009 responding anaesthesia care providers, 71 (< 1%) were anaesthesia associates, of whom 33 (47%) reporting working nights or weekends (compared with 97% of medically qualified anaesthetists in training and > 90% of consultants). Anaesthesia associates reported less training and confidence in managing peri-operative cardiac arrest and its aftermath compared with medically qualified anaesthetists. Anaesthesia associates were less directly involved in the management and the aftermath of peri-operative cardiac arrest than medically qualified anaesthetists, and the psychological impacts on professional and personal life appeared to be less. Among 24,172 cases, anaesthesia associates attended 432 (2%) and were the senior anaesthesia care provider in 63 (< 1%), with indirect supervision in 27 (43%). Anaesthesia associates worked predominantly in a small number of surgical specialties during weekdays and working daytime hours. Complication rates were low in cases managed by anaesthesia associates, likely reflecting case mix. However, activity and registry case mix data show anaesthesia associates do manage high-risk cases (patients who are older, comorbid, obese and frail) with the potential for serious complications. Registry cases included higher risk cases with respect to the clinical setting and patient factors. CONCLUSION: Anaesthesia associates work in enhanced roles, relative to the scope of practice at qualification agreed by organisations. Recent changes mean the Royal College of Anaesthetists and Association of Anaesthetists do not currently support an enhanced scope of practice.

Sleep duration and the risk of new-onset arthritis in middle-aged and older adult population: results from prospective cohort study in China.

Background: The pain and sleep disorders caused by arthritis are health issues that have been re-emphasized with the aging population. However, the majority of research on arthritis and sleep disorders has focused on cases that have already been diagnosed with arthritis. This research aims to explore the correlation between sleep duration and new-onset arthritis in middle-aged and older adult individuals. Methods: Utilizing data from the China Health and Retirement Longitudinal Study from baseline (2011) to the Wave 3 follow-up (2018), we conducted a 7-year longitudinal investigation targeting populations with valid sleep questionnaire records and without arthritis. Sleep duration was assessed from nighttime sleep and daytime nap records. The new-onset of arthritis was determined based on self-reported diagnosis. We employed different logistic regression models to consider the potential impact of sleep duration on arthritis and conducted mediation analyses to assess the involvement of BMI in the association between sleep duration and the new-onset risk of arthritis. Results: Out of the 6,597 individuals analyzed in the cohort, 586 (8.9%) were diagnosed with new-onset arthritis. Median sleep duration was notably shorter in the new-onset arthritis group (6.63 vs. 6.41 h, p < 0.05). There was a notable negative correlation found between new-onset risk of arthritis and sleep duration, with each Interquartile Range (IQR) increment in sleep leading to a 16% risk reduction (OR: 0.864; 95% CI: 0.784-0.954). Stratified analyses revealed BMI as a potential modifier in the sleep-arthritis relationship (P for interaction = 0.05). Mediation analyses further showed that about 3.5% of the association was mediated by BMI. Additionally, the inclusion of sleep duration improved the arthritis predictive power of our model, with an IDI of 0.105 (0.0203, 0.1898) and an NRI of 0.0013 (0.0004, 0.0022) after adding sleep duration to the basic model. Conclusion: In the middle-aged and older adult demographic of China, increased sleep duration is associated with a decreased new-onset risk of arthritis, with BMI potentially playing a role in mediating this connection.

How Do Thermophiles Organize Their Genomes?

All cells must maintain the structural and functional integrity of the genome under a wide range of environments. High temperatures pose a formidable challenge to cells by denaturing the DNA double helix, causing chemical damage to DNA, and increasing the random thermal motion of chromosomes. Thermophiles, predominantly classified as bacteria or archaea, exhibit an exceptional capacity to mitigate these detrimental effects and prosper under extreme thermal conditions, with some species tolerating temperatures higher than 100°C. Their genomes are mainly characterized by the presence of reverse gyrase, a unique topoisomerase that introduces positive supercoils into DNA. This enzyme has been suggested to maintain the genome integrity of thermophiles by limiting DNA melting and mediating DNA repair. Previous studies provided significant insights into the mechanisms by which NAPs, histones, SMC superfamily proteins, and polyamines affect the 3D genomes of thermophiles across different scales. Here, I discuss current knowledge of the genome organization in thermophiles and pertinent research questions for future investigations.

Drug Inspector as an antibiotic Steward: challenges and recommendations to implement national action plan of Pakistan on antimicrobial resistance.

BACKGROUND: Despite significant measures, low- and middle-income countries (LMICs), including Pakistan, struggle to curtail non-prescription antibiotic sales, enforce regulations, and implement National Action Plan (NAP) against antimicrobial resistance (AMR). NAP Pakistan entails drug inspectors (DIs) to ensure prescription-based sales of antibiotics. This study seeks to understand the perspective of DIs regarding antimicrobial sales without prescription, underlying factors, and policy implementation status. METHODS: A qualitative study employing a semi-structured interview guide using in-depth interviews with purposively selected 17 DIs was conducted. Interviews were transcribed verbatim, and data were analyzed following a thematic analysis framework utilizing MAXQDA 2022 software. RESULTS: Five main themes emerged after data analysis: (1) drug inspector - the regulator of the antimicrobial armamentarium, (2) the policy context, (3) awareness regarding AMR, (4) barriers to combatting AMR, and (5) the way forward: strategies and recommendations. CONCLUSION: A weak regulatory framework, low level of awareness, quackery, vested interests, and socio-economic factors augment inappropriate antibiotic utilization. Opting for better policies and strengthening the DI fraternity as outlined in NAP Pakistan is recommended. Recognizing drug inspectors as effective surveilling units and mobilizing field force against irrational antibiotic utilization is the need of the hour and requires policy reformation.