Early Time Research Articles

Looking Beyond Sleep Duration in Understanding Obesity Risk in Adolescents: The Role of Circadian Timing and Misalignment on Adolescent Dietary Outcomes, Physical Activity, and Body Mass Index

Abstract Objectives This study evaluated the differences in obesity-related outcomes across multiple adolescent sleep health domains, including circadian misalignment (CM), circadian timing, and sleep duration. Methods 53 adolescents (aged 14-18; body mass index (BMI) percentile<95%; 53.7% female) completed a cross-sectional study that included baseline assessment of height; weight; demographics; and a 10-day assessment of sleep, physical activity, and dietary outcomes. Sleep duration, sleep timing, and physical activity data were collected from all participants using wrist-worn and waist-worn actigraphs. Dietary intake was measured using the Automated Self-Administered 24-Hour dietary recalls on three randomized days. Circadian timing was measured using dim-light melatonin onset (DLMO), and CM was calculated as the distance of time between DLMO and the average sleep onset time. Participants were categorized into groups (early versus late circadian timing, aligned versus misaligned circadian timing, and adequate sleep versus short sleep), and differences in dietary outcomes, physical activity, and BMI were analyzed using t-tests. Results Adolescents with later DLMO (M = 21:30 ± 1:11) had 0.63 higher BMI and 0.47% less averaged daily percent fat consumption than adolescents with early DLMO. Adolescents with CM (M = 1:42 ± 1:06) consumed 451.77 more averaged daily kcal consumption compared to those with circadian alignment. No statistically significant differences were found in any obesity-related outcome between sleep duration groups. Conclusions Our cross-sectional findings indicate that focusing on sleep timing and circadian alignment, beyond sleep duration, may promote better health outcomes for healthy adolescents. The findings of this study could enhance sleep education and inform clinical models for prevention efforts for pediatric obesity.

Immunologic Profiling of CSF in Subarachnoid Neurocysticercosis Reveals Specific Interleukin-10-Producing Cell Populations During Treatment.

Subarachnoid neurocysticercosis (SANCC) is the most severe form of Taenia solium CNS infection and accounts for the majority of neurocysticercosis-associated mortality. Inflammation is important in the treatment of SANCC because overactivity can lead to serious complications, but excessive suppression may be counterproductive toward parasite eradication. A relative abundance of CSF IL-10 to IL-12 has been associated with increased treatment duration for patients with SANCC, suggesting that IL-10 plays an important role in this disease process. To better understand SANCC immunology and the major sources of IL-10 during anthelmintic treatment, we took an unbiased and comprehensive approach to phenotype the immune cell populations in the CSF and peripheral blood of patients with SANCC. Eight samples of CSF cells collected from 5 patients with SANCC during treatment were evaluated using single-cell RNA sequencing. Matched CSF and peripheral blood mononuclear cells from 4 patients were assessed using flow cytometry. Staining for extracellular and intracellular markers allowed for the characterization of IL-10-producing T cells. The CSF during SANCC contains a diversity of immune cell populations including multiple myeloid and lymphoid populations. Although there were changes in the composition of CSF cells during treatment, the largest population at both early and late time points was CD4+ T cells. Within this population, we identified 3 sources of IL-10 unique to SANCC CSF compared with controls: natural regulatory T cells (nTregs), induced regulatory T cells (iTregs), and Th17 cells. The abundance and phenotype of these IL-10-producing populations differed between CSF and blood in patients with SANCC, but iTregs were the single most productive population in the CSF. During treatment, these IL-10 producers persisted in consistent proportions despite decreases in parasite antigen over time. This profile of immune cell populations in the CSF provides a comprehensive blueprint of the local and systemic immunology associated with SANCC. The identification of IL-10-producing cells in the CSF and peripheral blood deepens our understanding of the immunosuppressive phenotype that deters SANCC treatment success. Finally, the discovery that these IL-10 producers persist throughout treatment highlights the endurance of these populations in the CNS.

Pulse current injection platform with consecutive early-time and intermediate-time high-altitude electromagnetic pulse conducted currents for immunity test of electrical equipment.

High-altitude electromagnetic pulse (HEMP) has attracted considerable attention for its influence on electrical equipment. HEMP is divided into three parts: early time HEMP (E1), intermediate-time HEMP (E2), and late-time HEMP (E3). Most studies focused on E1 alone, while few investigated others. However, the electrical equipment may be disturbed by more than one part since these three parts co-exist in a HEMP environment. The pulse current injection (PCI) test is an effective immunity test method for evaluating the sensitivity and susceptibility of electrical equipment. To investigate the responses of electrical equipment excited by the consecutive E1 and E2 and compare with those under the individual E1 or E2, this paper builds a PCI platform that can carry out PCI tests with the consecutive E1 and E2 conducted current. To output the E1 current and the E2 current consecutively, which exhibit significant differences in the rise time (20ns and 1.5 μs), peak current (2500 and 250A), and full width at half maximum (FWHM, 500-550ns and 3-5ms), an E1&E2 coupler with a fast-closing high-current trigger switch is designed in this paper. Finally, some 10-kV epoxy insulators are tested in the developed platform, which shows the capacity of the proposed platform to test the immunity of electrical equipment with the consecutive E1 and E2 conducted current.

Co-Seismic and Post-Seismic Slip Properties Associated with the 2024 M 7.5 Noto Peninsula, Japan Earthquake Determined by GNSS Observations

Based on GNSS observations, the co-seismic and post-seismic slip of the 2024 Noto Peninsula earthquake and the spatio-temporal pattern of afterslip are investigated in this paper. The co-seismic slip is mainly distributed in the depth range of 2 to 15 km with the maximum value of 5.94 m. Compared with the co-seismic rupture pattern, a shallow afterslip can be observed after the earthquake, and the afterslip patch is formed northeast of the epicenter. The maximum value of afterslip during the post-seismic 180 days is 1.13 m, which is situated at the longitude of 137.53°, latitude of 37.75°, and epth of 5.43 km. The spatio-temporal evolution of afterslip indicates that the fault activity has continued throughout the post-seismic 180 days, and the coverage and magnitude of afterslip have gradually increased. As time goes on, the fault activity tends to weaken, as evidenced by a decrease in slip rate. The daily images of afterslip demonstrate that the fault activity is particularly strong in the early time period following the earthquake. The maximum value of afterslip in the first week accounts for about 18% of that in the post-seismic 180 days, and the maximum slip rate reaches 0.043 m/day. In addition, the Coulomb stress analysis indicates that afterslip and most aftershocks appear in the positive Coulomb stress region, suggesting that co-seismic Coulomb stress changes may be the driving mechanism of afterslip and aftershocks.

Evolution of Chemistry in the envelope of HOt CorinoS (ECHOS). II. The puzzling chemistry of isomers as revealed by the HNCS/HSCN ratio

The observational detection of some metastable isomers in the interstellar medium with abundances comparable to those of the most stable isomer, or even when the stable isomer is not detected, highlights the importance of non-equilibrium chemistry. This challenges our understanding of the interstellar chemistry and shows the need to study isomeric forms of molecular species to constrain chemical processes occurring in the interstellar medium. Our goal is to study the chemistry of isomers through the sulphur isomer pair HNCS and HSCN, since HSCN has been observed in regions where its stable isomer has not been detected, and the observed HNCS/HSCN ratio seems to significantly vary from cold to warm regions. We used the Nautilus time-dependent gas-grain chemical code to model the formation and destruction paths of HNCS and HSCN in different astrochemical scenarios, as well as the time evolution of the HNCS/HSCN ratio. We also analysed the influence of the environmental conditions on their chemical abundances. We present an observational detection of the metastable isomer HSCN in the Class I object B1-a ($N$=(1.1pm 0.6)times 1012 cm$^ $), but not of the stable isomer HNCS, despite HNCS lying 3200 K lower in energy than HSCN. Our theoretical results show an HNCS/HSCN ratio sensitive to the gas temperature and the evolutionary time, with the highest values obtained at early stages ($t$lesssim 10$^4$ yr) and low ($T_ g $lesssim 20 K) temperatures. A more detailed analysis also shows that the main mechanism forming HNCS in young ($t$$<$10$^5$ yr) and cold ($T_ g $$=$10 K) objects at moderate-low densities ($n$$_ H $leq 10$^5$ cm$^ $) is a grain surface reaction (the chemical desorption reaction N$_ solid $+HCS$_ solid $rightarrow HNCS), unlike previous predictions that suggest only gas-phase chemistry for its formation. However, for the formation of its metastable isomer HSCN, over the same time range and physical conditions, we find that both surface and gas-phase reactions (through the ion H$_2$NCS$^+$) play important roles. In warmer ($T_ g $geq 50 K) regions, the formation of this isomer pair is only dominated by gas-phase chemistry through the ions H$_2$NCS$^+$ (mainly at low densities) and HNCSH$^+$ (mainly at high densities). The results suggest a different efficiency of the isomerisation processes depending on the source temperature. The progressive decrease of HNCS/HSCN with gas temperature at early evolutionary times derived from our theoretical results indicates that this ratio may be used as a tracer of cold young objects. This work also demonstrates the key role of grain surface chemistry in the formation of the isomer pair HNCS and HSCN in cold regions, as well as the importance of the ions H$_2$NCS$^+$ and HNCSH$^+$ in warm/hot regions. Since most of the interstellar regions where HSCN is detected are cold regions (starless cores, Class 0/I objects), a larger sample including sources characterised by high temperatures (e.g. hot cores) are needed to corroborate the theoretical results.

Holographic Gubser flow. A combined analytic and numerical study

Gubser flow is an evolution with cylindrical and boost symmetries, which can be best studied by mapping the future wedge of Minkowski space (R3,1) to dS3 × ℝ in a conformal relativistic theory. Here, we sharpen our previous analytic results and validate them via the first numerical exploration of the Gubser flow in a holographic conformal field theory.Remarkably, the leading generic behavior at large de Sitter time is free-streaming in transverse directions and the sub-leading behavior is that of a color glass condensate. We also show that Gubser flow can be smoothly glued to the vacuum outside the future Minkowski wedge generically given that the energy density vanishes faster than any power when extrapolated to early proper time or to large distances from the central axis. We find that at intermediate times the ratio of both the transverse and longitudinal pressures to the energy density converge approximately to a fixed point which is hydrodynamic only for large initial energy densities. We argue that our results suggest that the Gubser flow is better applied to collective behavior in jets rather than the full medium in the phenomenology of heavy ion collisions and can reveal new clues to the mechanism of confinement.

Energy-dependent and Energy-integrated Two-moment General-relativistic Neutrino Transport Simulations of a Hypermassive Neutron Star

We compare two-moment-based energy-dependent and three variants of energy-integrated neutrino transport general-relativistic magnetohydrodynamics simulations of a hypermassive neutron star. To study the impacts due to the choice of the neutrino transport schemes, we perform simulations with the same setups and input neutrino microphysics. We show that the main differences between energy-dependent and energy-integrated neutrino transport are found in the disk and ejecta properties, as well as in the neutrino signals. The properties of the disk surrounding the neutron star and the ejecta in energy-dependent transport are very different from the ones obtained using energy-integrated schemes. Specifically, in the energy-dependent case, the disk is more neutron-rich at early times and becomes geometrically thicker at later times. In addition, the ejecta is more massive and, on average, more neutron-rich in the energy-dependent simulations. Moreover, the average neutrino energies and luminosities are about 30% higher. Energy-dependent neutrino transport is necessary if one wants to better model the neutrino signals and matter outflows from neutron star merger remnants via numerical simulations.

Expert and Novice Teachers’ Cognitive Neural Differences in Understanding Students’ Classroom Action Intentions

Objectives: Teachers’ intention understanding ability reflects their professional insight, which is the basis for effective classroom teaching activities. However, the cognitive process and brain mechanism of how teachers understand students’ action intention in class are still unclear. Methods: This study used event-related potential (ERP) technology to explore the cognitive neural differences in intention understanding ability among teachers with different levels of knowledge and experience. The experiment used the comic strips paradigm to examine the ability of expert and novice teachers to understand students’ normative and non-normative classroom actions under different text prompts (“how” and “why”). Results: The results revealed that in the late time window, expert teachers induced larger P300 and LPC amplitudes when they understood students’ classroom action intentions, while the N250 amplitudes induced by novice teachers in the early time window were significantly larger. In addition, for both types of teachers, when understanding the intentions behind students’ normative actions, the N250 amplitude was the most significant, while the P300 and LPC amplitudes were more significant for non-normative actions. Conclusions: This study found that teachers at varying professional development stages had different time processing processes in intention understanding ability, which supported teachers’ brain electrophysiological activities related to social ability.

The Early Radio Afterglow of Short GRB 230217A

We present the radio afterglow of short gamma-ray burst (GRB) 230217A, which was detected less than 1 day after the gamma-ray prompt emission with the Australia Telescope Compact Array (ATCA) and the Karl G. Jansky Very Large Array. The ATCA rapid-response system automatically triggered an observation of GRB 230217A following its detection by the Neil Gehrels Swift Observatory and began observing the event just 32 minutes postburst at 5.5 and 9 GHz for 7 hr. Dividing the 7 hr observation into three time-binned images allowed us to obtain radio detections with logarithmic central times of 1, 2.8, and 5.2 hr postburst, the first of which represents the earliest radio detection of any GRB to date. The decline of the light curve is consistent with reverse shock emission if the observing bands are below the spectral peak and not affected by synchrotron self-absorption. This makes GRB 230217A the fifth short GRB (SGRB) with radio detections attributed to a reverse shock at early times (<1 day postburst). Following brightness temperature arguments, we have used our early radio detections to place the highest minimum Lorentz factor ( Γmin>50 at ∼1 hr) constraints on a GRB in the radio band. Our results demonstrate the importance of rapid radio follow-up observations with long integrations and good sensitivity for detecting the fast-evolving radio emission from SGRBs and probing their reverse shocks.

Persistent angina following revascularization for chronic coronary syndromes: a systematic review and meta-analysis of randomized controlled trials

Abstract Introduction Recent randomized clinical trials (RCTs) have demonstrated that revascularization plus optimal medical therapy for patients with chronic coronary syndromes (CCS) results in greater reduction in angina than medical therapy alone. However, the frequency of persistent angina following revascularization for CCS is not well understood. Purpose To quantify the frequency of persistent angina following revascularization in contemporary RCTs of revascularization plus medical therapy vs. medical therapy alone among patients with CCS. Methods A literature search through January of 2024 was conducted in PubMed and Cochrane Central Register of Controlled Trials for contemporary RCTs reporting angina frequency following randomization to revascularization plus medical therapy vs. medical therapy alone. The primary outcome of interest was the frequency of persistent angina in the revascularization arms of these studies at early (3-12 months) and late (3-5 years) time points. A random effects model was used to combine results from individual studies. Results From a total of 5287 citations, the search yielded 7 RCTs that met inclusion criteria. These studies randomized 5719 patients to an invasive or revascularization strategy. Revascularization was exclusively by percutaneous coronary intervention (PCI) in 4 studies and by coronary artery bypass grafting or PCI in 3 studies. At the early time point, the combined frequency of persistent angina was 39.6% (95% CI: 30.6-49.4). For the two blinded, sham-controlled studies, the rate of persistent angina was significantly greater at 67.2% (95%CI: 54.9-77.4) compared to 30.5% (95% CI: 23.1-39) in the unblinded studies (P&amp;lt;0.001). In the 5 studies with 3-5 years of follow-up, the frequency of persistent angina was 33.3% (95% CI: 19.2-51.2). Conclusion Persistent angina is common after revascularization for CCS and suggests alternative causes and treatments of residual angina should be considered.

Did the Buddha Teach to Be Called ‘Buddha’?―Focusing on the Meaning of Brāhmaṇa and How Buddhist Authors (re)Formulated His Words to Praise Him―

The attainment of enlightenment by Gautama Buddha is the very beginning of Buddhism as a religious phenomenon. Because of his attainment of enlightenment, he has been remembered as Buddha for centuries, even though it is uncertain whether buddha was the preferred title to remember him by from the earliest times. Previous scholarship has demonstrated that the term buddha was a common noun in the Indian religious context, and it was also employed to refer to his higher disciples. The verses of the Suttanipāta represent a complex corpus rich in many fundamental concepts common to Jain religious thought. Many epithets were introduced by Buddhists to praise their monastic founder as Jains do. Among them, buddha does not seem to be the preferred one among them. Contrarily, by redefining brāhmaṇa, Buddhists participate in the ascetic discourse of praising their master as the one who deserves to be regarded as that ideal. This paper argues that Buddhists advocated their master as a brāhmaṇa, a title that is not only consistent with the teachings of Jains but also one that may have preceded the popularity of Buddha as his most memorable title.

A Machine Learning Approach to Identifying Risk Factors for Long COVID-19

Long-term sequelae of coronavirus disease 2019 (COVID-19) infection are common and can have debilitating consequences. There is a need to understand risk factors for Long COVID-19 to give impetus to the development of targeted yet holistic clinical and public health interventions to reduce its associated healthcare and economic burden. Given the large number and variety of predictors implicated spanning health-related and sociodemographic factors, machine learning becomes a valuable tool. As such, this study aims to employ machine learning to produce an algorithm to predict Long COVID-19 risk, and thereby identify key predisposing factors. Longitudinal cohort data were sourced from the UK’s “Understanding Society: COVID-19 Study” (n = 601 participants with past symptomatic COVID-19 infection confirmed by serology testing). The random forest classification algorithm demonstrated good overall performance with 97.4% sensitivity and modest specificity (65.4%). Significant risk factors included early timing of acute COVID-19 infection in the pandemic, greater number of hours worked per week, older age and financial insecurity. Loneliness and having uncommon health conditions were associated with lower risk. Sensitivity analysis suggested that COVID-19 vaccination is also associated with lower risk, and asthma with an increased risk. The results are discussed with emphasis on evaluating the value of machine learning; potential clinical utility; and some benefits and limitations of machine learning for health science researchers given its availability in commonly used statistical software.

Time dependent changes in protein expression induced by intermittent theta burst stimulation in a cell line

BackgroundIntermittent Theta Burst Stimulation (iTBS), a non-invasive brain stimulation technique, is recognized for its ability to modulate cortical neuronal activity. However, its effects over time and the dynamics following stimulation are less well understood. Understanding the temporal dynamics of iTBS effects is essential for optimizing the timing and frequency of stimulation in therapeutic applications.ObjectiveThis study investigated the temporal changes in protein expression induced by iTBS in Neuro-2a cells.MethodsWe analyzed protein expression in retinoic acid-differentiated Neuro-2a cells at multiple time points — 0.5, 3, 6, 12, and 24 hours post-iTBS — using Western blot and immunocytochemistry techniques.ResultsOur findings reveal a significant early increase in neurotransmitter receptor subunits, neurotrophic factors, and cytoskeletal proteins within the first 0.5 hour following iTBS. Notably, proteins such as mGLuR1, NMDAR1, GABBR2, and β-tubulin III showed substantial increase in expression. However, the effects of iTBS on protein expression was not sustained at later timepoints.ConclusionOur results suggest that iTBS can transiently alter the expression of specific proteins in Neuro-2a cells. Future research should investigate the potential benefits of repeated stimulations within the early time window to refine iTBS interventions, potentially expanding their research and clinical applications.

Blood-brain barrier profile pretreatment is associated with hemorrhagic transformation after endovascular reperfusion.

While advances in endovascular thrombectomy (EVT) have led to high reperfusion rates, most patients treated with EVT do not avoid disability. Post-reperfusion hemorrhagic transformation (HT) is a potential target for improving outcomes. This study examined pretreatment blood-brain barrier (BBB) disruption in tissue that would subsequently become part of the final infarct to evaluate its role in post-EVT HT. This post hoc analysis of the FRAME study, which enrolled patients with anterior large vessel occlusion who received EVT within 6 hours of onset, included patients if they had successful pretreatment MRI perfusion weighted imaging (PWI) and underwent successful EVT. BBB disruption was measured as the percent signal change due to gadolinium leakage on the PWI source images prior to thrombectomy. Mean permeability derangement (MPD) was defined as the average of all voxels in the stroke core that are two standard deviations above normal. The primary outcome was hemorrhagic transformation with parenchymal hematoma (PH). In total, 164 patients were included; mean age was 71 and 48% were female. PH occurred in 57 patients. Median MPD was 13.5% for patients with PH versus 3.6% for patients without (p < 0.0001). Elevated MPD was independently associated with PH with a 20% increased risk of PH for each 5% increase in MPD (OR 1.206; 95% CI 1.037:1.405; p = 0.0147, adjusted for NIHSS and procedure duration). Even in patients who are successfully recanalized in an early time window, pretreatment BBB disruption in regions that go on to infarct is associated with an increased risk of post-EVT HT.

Mesiri: Mephisto Early Supernovae Ia Rapid Identifier

The early time observations of Type Ia supernovae (SNe Ia) play a crucial role in investigating and resolving longstanding questions about progenitor stars and the explosion mechanisms of these events. Colors of supernovae (SNe) in the initial days after the explosion can help differentiate between different types of SNe. However, the use of true color information to identify SNe Ia at the early-time explosion is still in its infancy. The Multi-channel Photometric Survey Telescope (Mephisto) is a photometric survey telescope equipped with three CCD cameras, capable of simultaneously imaging the same patch of sky in three bands (u, g, i or v, r, z), yielding real-time colors of astronomical objects. In this paper, we introduce a new time-series classification tool named Mephisto Early Supernovae Ia Rapid Identifier (Mesiri), which, for the first time, utilizes real-time color information to distinguish early-time SNe Ia from core-collapse supernovae. Mesiri is based on the deep learning approach and can achieve an accuracy of 96.75% ± 0.79%, and AUC of 98.87% ± 0.53% in case of single epoch random observation before the peak brightness. These values reach towards perfectness if additional data points on several night observations are considered. The classification with real-time color significantly outperforms that with pseudo-color, especially at the early time, i.e., with only a few points of observations. The BiLSTM architecture shows the best performance compared to others that have been tested in this work.

Role of Oxide-Derived Cu on the Initial Elementary Reaction Intermediate During Catalytic CO2 Reduction.

The catalytic role of oxide-derived Cu (OD-Cu) in promoting CO2 reduction (CO2R) to C2+ products has been appreciated for decades. However, the dynamic evolution of the surface oxidation states, together with their real correlation to the binding of reaction intermediates, remains unclear due to technical challenges. Here, we show the time-resolved spectroscopic signatures of key OD-Cu-CO2•- intermediates during catalytic CO2 reduction through one electron transfer from nanoseconds to seconds time scale. We generated the initial intermediate CO2•- radicals in the bulk solution and monitored the interfacial reaction kinetics with well-defined OD-Cu (Cu(0), Cu(I), and Cu(II)) nanoparticles. Combined with molecular simulations, transient absorption profiles analysis reveals that Cu(I) induced a faster CO2•- radical coupling reaction than Cu(0), whereas Cu(II) is only reduced to Cu(I) by the CO2•- radical. Furthermore, the newly developed multistep cumulative pulse methodology uncovered the transition in chemical states of mixed OD-Cu during radical coupling reactions. This pulse radiolysis study provides compelling evidence for the beneficial role of subsurface oxides in early time catalytic CO2 transformation.

The impact of viral respiratory infection on surgical outcome of cavopulmonary shunt.

Undetected respiratory infections may adversely affect the intrapulmonary resistance after Stage 2 or Stage 3 Fontan palliation. A few studies describe a higher risk for viral pneumonia during respiratory virus season, but none of them have focused on the effect of symptomatic viral pneumonia on in-hospital clinical course after bidirectional Glenn shunt. We analysed 77 patients who underwent bidirectional Glenn shunt surgery. Six patients were detected with pneumonia and proof of viral ribonucleic acid in tracheal mucus in the very early postoperative time. We compared them retrospectively to the remaining 71 patients regarding preoperative inflammatory signs, mortality, paediatric ICU length of stay, and ventilation time. The infection rate was not seasonal dependent. Ventilation time was significantly elongated in the pneumonia group (558 h ± 634 vs. 8.7 h ± 1.9; p < 0.0001) and so was the paediatric ICU length of stay (29 days ± 26 vs. 3 days±1; p = 0.007). Significantly more patients in the pneumonia group required extracorporeal cardiac life support postoperatively. The mortality was significantly increased in patients with pneumonia. Even subclinical viral pneumonia may cause ventilation-to-perfusion mismatch by raising intrapulmonary resistance. Recorded parameters of postoperative paediatric ICU therapy showed a significant impact of a viral pneumonia on patients after bidirectional Glenn shunt. The respiratory syncytial virus vaccination does not protect these patients from infection with other respiratory viruses. The focus should be put on preoperative diagnosis of pulmonary infections in the vulnerable group of patients with univentricular hearts.

Dynamics of transcription-coupled repair of cyclobutane pyrimidine dimers and (6-4) photoproducts in Escherichia coli

DNA repair processes modulate genotoxicity, mutagenesis, and adaption. Nucleotide excision repair removes bulky DNA damage, and in Escherichia coli, basal excision repair, carried out by UvrA, B, C, and D, with DNA PolI and DNA ligase, occurs genome-wide. In transcription-coupled repair (TCR), the Mfd protein targets template strand (TS) lesions that block RNA polymerase for accelerated repair by the basal repair enzymes. Accelerated repair is also seen with particular adducts. Notably, of the two major UV photoproducts, basal repair of (6-4) photoproducts [(6-4)PPs] is about 10× faster than repair of cyclobutane pyrimidine dimers (CPDs). To better understand repair prioritization in E. coli, we used XR-seq to measure TCR of UV photoproducts genome-wide. With CPDs, we found that TCR occurred at early time points, increased with transcription level, and was Mfd dependent; later, with completion of TS repair, nontranscribed strand (NTS) repair predominated. With (6-4)PP, when analyzing all genes, TCR was not observed; in fact, among the most highly transcribed genes, slightly more repair of (6-4)PPs in the NTS was evident. Thus, the very rapid basal repair of (6-4)PP in the NTS was faster than TCR of (6-4)PPs in the TS. Overall, TCR is of limited importance in (6-4)PP repair, and TCR of CPDs is limited to the TS of more highly transcribed genes. These results are consistent with the significant role of Mfd in mutagenesis and the modest effect of mfd deletion on UV survival and bear upon the response of E. coli to bulky DNA damage.

Successful 24-hour discharge for total knee arthroplasty: importance of timing of surgery and physiotherapy in enhanced recovery after surgery protocol.

The current literature is mixed on which patient factors, if any, predict the rate of successful discharge within 24 h of enhanced recovery after surgery (ERAS) total knee arthroplasty (TKA). This study aimed to investigate the influence of timing of surgery and physiotherapy on the rate of successful 24-h discharge. All 342 patients who underwent ERAS day surgery TKA from August 2020 to July 2021 were followed up prospectively. Patient characteristics and postoperative outcomes, such as number of physiotherapy sessions required before clearance for home, time taken after surgery to ambulate >10 m and length of stay (LOS), were recorded. Patients were grouped based on surgical end time (morning/afternoon/ evening) and time of physiotherapy review (morning/afternoon/evening/morning after). Patients successfully passed ERAS day surgery protocol if they were discharged within 24 h. With regard to the timing of operation, the morning group had the shortest LOS (P = 0.001) and a higher ERAS day surgery pass rate than the afternoon group (P = 0.016). With regard to the timing of physiotherapy, the afternoon group took the shortest time to ambulate >10 m (P < 0.001), had the shortest LOS (P < 0.001) and had a higher ERAS day surgery pass rate as compared to the morning after the operation group (P = 0.005). Patients who ended their operations in the morning and received physiotherapy review in the same afternoon were the most likely to be discharged within 24 h due to early ambulation and adequate time for spinal anaesthesia to wear off.

Sleep timing and the prevalence of hypertension in middle-aged and older populations: the sleep heart health study

ObjectivesSleep characteristics such as duration, continuity, and irregularity are associated with the risk of hypertension. This study aimed to investigate the association between sleep timing (including bedtime, wake-up time, and sleep midpoint) and the prevalence of hypertension.MethodsParticipants were selected from the Sleep Heart Health Study (n = 5504). Bedtime and wake-up times were assessed using sleep habit questionnaires. The sleep midpoint was calculated as the halfway point between the bedtime and wake-up time. Restricted cubic splines and logistic regression analyses were performed to explore the association between sleep timing and hypertension.ResultsA significant nonlinear association was observed between bedtime (Poverall<0.001; Pnonlinear<0.001), wake-up time (Poverall=0.024; Pnonlinear=0.076), sleep midpoint (Poverall=0.002; Pnonlinear=0.005), and the prevalence of hypertension after adjusting for potential confounders. Multivariable logistic regression showed that both late (> 12:00AM and 23:01PM to 12:00AM) and early (≤ 22:00PM) bedtimes were associated with an increased risk of hypertension compared to bedtimes between 22:01PM and 23:00PM. In addition, individuals with late (> 7:00AM) and early (≤ 5:00AM) wake-up times had a higher prevalence of hypertension than those with wake-up times ranging between 5:01AM and 6:00AM. Delaying the sleep midpoint (> 3:00AM) was also associated with an increased risk of hypertension. Furthermore, no significant interaction effect was found in the subgroup analyses stratified by age, sex, or apnea-hypopnea index.ConclusionsOur findings identified a nonlinear association between sleep timing and hypertension. Individuals with both early and late sleep timing had a high prevalence of hypertension.