ssDNA reeling is an intermediate step in the reiterative DNA unwinding activity of the WRN-1 helicase.

RecQ helicases are highly conserved between bacteria and humans. These helicases unwind various DNA structures in the 3' to 5'. Defective helicase activity elevates genomic instability and is associated with predisposition to cancer and/or premature aging. Recent single-molecule analyses have revealed the repetitive unwinding behavior of RecQ helicases from Escherichia coli to humans. However, the detailed mechanisms underlying this behavior are unclear. Here, we performed single-molecule studies of WRN-1 Caenorhabditis elegans RecQ helicase on various DNA constructs and characterized WRN-1 unwinding dynamics. We showed that WRN-1 persistently repeated cycles of DNA unwinding and rewinding with an unwinding limit of 25 to 31 bp per cycle. Furthermore, by monitoring the ends of the displaced strand during DNA unwinding we demonstrated that WRN-1 reels in the ssDNA overhang in an ATP-dependent manner. While WRN-1 reeling activity was inhibited by a C. elegans homolog of human replication protein A, we found that C. elegans replication protein A actually switched the reiterative unwinding activity of WRN-1 to unidirectional unwinding. These results reveal that reeling-in ssDNA is an intermediate step in the reiterative unwinding process for WRN-1 (i.e., the process proceeds via unwinding-reeling-rewinding). We propose that the reiterative unwinding activity of WRN-1 may prevent extensive unwinding, allow time for partner proteins to assemble on the active region, and permit additional modulation in vivo.

A randomized controlled trial of propofol-remifentanil total intravenous anesthesia and sevoflurane-fentanyl anesthesia on early postoperative fatigue in patients undergoing laparoscopic colorectal surgery.

PURPOSE: Even after uncomplicated surgery, postoperative fatigue prevalence has been reported to be 30-80% for various surgeries. We evaluated postoperative fatigue according to anesthetic technique in patients who underwent colorectal surgery. METHODS: One hundred thirty patients who underwent colorectal surgery were randomly assigned to either propofol-remifentanil total intravenous anesthesia (propofol-remifentanil group, n = 65) or sevoflurane-fentanyl anesthesia (sevoflurane-fentanyl group, n = 65). The primary outcome was the prevalence of postoperative fatigue, as defined by the Chalder Fatigue Questionnaire (total score ≥ 16), at 24 h postoperatively. Secondary outcomes were early postoperative complications during hospitalization and laboratory examination. RESULTS: The final analyses included 127 patients. The prevalence of postoperative fatigue on the 1st postoperative day was lower in the propofol-remifentanil group than the sevoflurane-fentanyl group: 56.3% (36/64) in the propofol-remifentanil group and 73.0% (46/63) in the sevoflurane-fentanyl group (relative risk [RR] = 0.77, 95% confidence interval [CI] 0.59-1.00; P = 0.048). However, there was no difference between the two groups in postoperative fatigue at postoperative day 3. Other postoperative outcomes including the severity of pain and the incidence of nausea/vomiting were not different between the two groups, but postoperative atelectasis on chest X-ray was higher in the sevoflurane-fentanyl group (2/64 [3.1%] vs. 9/63 [14.3%], P = 0.025). C-reactive protein change from preoperative to postoperative day 1 and 5 was significantly lower in the propofol-remifentanil group (P = 0.044). CONCLUSION: Propofol-remifentanil total intravenous anesthesia was associated with reduced postoperative fatigue at the 1st postoperative day compared with sevoflurane-fentanyl anesthesia. Clinical trial The Korean Clinical Research Registry (study identifier: KCT0006917, principal investigator's name: MiHye Park, date of registration: January 12, 2022).

The association of withholding or continuing angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers on acute kidney injury after non-cardiac surgery.

BACKGROUND: Withholding or continuing angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers peri-operatively in non-cardiac surgery remains controversial as they may result in intra-operative hypotension and postoperative organ damage. METHODS: We included patients prescribed angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers who underwent surgical procedures > 1 h duration under general or spinal anaesthesia from January 2012 to June 2022 in a single centre. We categorised patients by whether these drugs were withheld for 24 h before surgery. We evaluated the association of withholding these drugs before non-cardiac surgery with creatinine concentrations that increased ≥ 26.4 µmol.l-1 in the first 48 postoperative hours (acute kidney injury). We also analysed changes in creatinine concentrations and estimated glomerular filtration rates. RESULTS: Angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers were withheld in 24,285 of 32,933 (74%) patients and continued in 8648 (26%) patients. We used propensity scores for drug discontinuation to match 8631 patient pairs who did or did not continue these drugs: acute kidney injury was recorded for 1791 (21%) patients who continued these drugs vs. 1587 (18%) who did not (OR (95%CI) 1.16 (1.08-1.25), p < 0.001). Intra-operative hypotension was recorded for 3892 (45%) patients who continued drugs vs. 3373 (39%) patients who did not (OR (95%CI) 1.28 (1.21-1.36), p < 0.001). Continuing drugs was independently associated with a mean increase in creatinine of 2.2 µmol.l-1 (p < 0.001) and a mean decrease in estimated glomerular filtration rate of 1.4 ml.min.1.73 m-2 (p < 0.001). CONCLUSIONS: Continuing angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers 24 h before non-cardiac surgery was associated with intra-operative hypotension and postoperative acute kidney injury.

Evaluating the coding accuracy of type 2 diabetes mellitus among patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) describes a spectrum of chronic fattening of liver that can lead to fibrosis and cirrhosis. Diabetes has been identified as a major comorbidity that contributes to NAFLD progression. Health systems around the world make use of administrative data to conduct population-based prevalence studies. To that end, we sought to assess the accuracy of diabetes International Classification of Diseases (ICD) coding in administrative databases among a cohort of confirmed NAFLD patients in Calgary, Alberta, Canada. METHODS: The Calgary NAFLD Pathway Database was linked to the following databases: Physician Claims, Discharge Abstract Database, National Ambulatory Care Reporting System, Pharmaceutical Information Network database, Laboratory, and Electronic Medical Records. Hemoglobin A1c and diabetes medication details were used to classify diabetes groups into absent, prediabetes, meeting glycemic targets, and not meeting glycemic targets. The performance of ICD codes among these groups was compared to this standard. Within each group, the total numbers of true positives, false positives, false negatives, and true negatives were calculated. Descriptive statistics and bivariate analysis were conducted on identified covariates, including demographics and types of interacted physicians. RESULTS: A total of 12,012 NAFLD patients were registered through the Calgary NAFLD Pathway Database and 100% were successfully linked to the administrative databases. Overall, diabetes coding showed a sensitivity of 0.81 and a positive predictive value of 0.87. False negative rates in the absent and not meeting glycemic control groups were 4.5% and 6.4%, respectively, whereas the meeting glycemic control group had a 42.2% coding error. Visits to primary and outpatient services were associated with most encounters. CONCLUSION: Diabetes ICD coding in administrative databases can accurately detect true diabetic cases. However, patients with diabetes who meets glycemic control targets are less likely to be coded in administrative databases. A detailed understanding of the clinical context will require additional data linkage from primary care settings.

Ten-year outcomes of recurrent laryngeal nerve reinnervation for thyroidectomy-related unilateral vocal fold paralysis: A single-surgeon, prospective study.

OBJECTIVES: This study evaluated the long-term outcomes of intraoperative recurrent laryngeal nerve (RLN) reinnervation for managing thyroidectomy-related unilateral vocal fold paralysis (UVFP) over a period of 10 years and assessed the long-term efficacy of this technique. METHODS: This study was conducted between March 2006 and July 2022 at Soonchunhyang University Bucheon Hospital. We enrolled 25 patients who underwent RLN reinnervation via direct neurorrhaphy or ansa cervicalis-to-RLN anastomosis and completed subjective and objective voice measurements over 5 years period. Among these, 10 patients completed voice measurements over 10 years period. RESULTS: Six months post-RLN reinnervation, most subjective voice parameters and some of objective voice parameters showed significant improvement (p < 0.05). Twelve months after the procedure, most parameters demonstrated significant voice improvements. These improvements remained stable in follow-up examinations 10 years post-RLN reinnervation (p < 0.05). CONCLUSIONS: With stable voice outcomes over a decade, primary intraoperative RLN reinnervation provides satisfactory voice outcomes for 10 years postoperatively. Concerning the long-term survival of thyroid cancer patients, primary intraoperative RLN reinnervation is the first recommended voice rehabilitation technique for thyroidectomy related permanent UVFP.

Multiple-Junction-Based Traffic-Aware Routing Protocol Using ACO Algorithm in Urban Vehicular Networks.

The burgeoning interest in intelligent transportation systems (ITS) and the widespread adoption of in-vehicle amenities like infotainment have spurred a heightened fascination with vehicular ad-hoc networks (VANETs). Multi-hop routing protocols are pivotal in actualizing these in-vehicle services, such as infotainment, wirelessly. This study presents a novel protocol called multiple junction-based traffic-aware routing (MJTAR) for VANET vehicles operating in urban environments. MJTAR represents an advancement over the improved greedy traffic-aware routing (GyTAR) protocol. MJTAR introduces a distributed mechanism capable of recognizing vehicle traffic and computing curve metric distances based on two-hop junctions. Additionally, it employs a technique to dynamically select the most optimal multiple junctions between source and destination using the ant colony optimization (ACO) algorithm. We implemented the proposed protocol using the network simulator 3 (NS-3) and simulation of urban mobility (SUMO) simulators and conducted performance evaluations by comparing it with GSR and GyTAR. Our evaluation demonstrates that the proposed protocol surpasses GSR and GyTAR by over 20% in terms of packet delivery ratio, with the end-to-end delay reduced to less than 1.3 s on average.

Comparison of high-flow nasal cannula and conventional nasal cannula during deep sedation for endoscopic submucosal dissection: a randomized controlled trial.

PURPOSE: Adequate oxygenation and airway management during deep sedation can be challenging. We investigated the effect of high-flow nasal cannula (group HF) and conventional nasal cannula (group CO) during sedation for endoscopic submucosal dissection (ESD). METHODS: Patients undergoing ESD with deep sedation were enrolled. The primary outcome was difference in lowest oxygen saturation (SpO2) between the groups. Incidence of hypoxia (SpO2 < 90%), patients with SpO2 < 95%, hypercapnia, and airway interventions; operator satisfaction; and adverse events were recorded. RESULTS: Thirty-two patients in each group completed the study. The mean of minimum SpO2 values was significantly higher in group HF than in group CO (96.8% ± 4.2% vs. 93.3% ± 5.3%, p = 0.005). The incidence of hypoxia was comparable between the groups (4 [12.5%] vs. 6 [18.8%], p = 0.491); however, patients with SpO2 < 95% were significantly less in group HF (5 [15.6%] vs. 18 [56.3%], p = 0.003). Incidence of hypercapnia was higher in group HF than in group CO (14 [46.7%] vs. 5 [16.7%], p = 0.013). Airway rescue interventions were significantly less common in group HF. Satisfaction of operators and post-procedural complications were comparable between the two groups. In multivariable analysis, group CO and higher body mass index were risk factors for airway managements (odds ratio [95% confidence interval]: 6.204 [1.784-21.575], p = 0.004; 1.337 [1.043-1.715], p = 0.022, respectively). CONCLUSIONS: Compared to conventional nasal cannula, high-flow nasal cannula maintained higher minimum SpO2 value during deep sedation with propofol-remifentanil for ESD. TRIAL REGISTRATION: Clinical Trial Registry of the Republic of Korea (KCT0006618, https://cris.nih.go.kr ; registered September 29, 2021; principal investigator: Ji Won Choi).

Comparison of the Influence of Dual-Task Activities on Prefrontal Activation and Gait Variables in Older Adults with Mild Cognitive Impairment during Straight and Curved Walking.

Background and Objectives: Mild cognitive impairment (MCI) is an early stage of dementia in which everyday tasks can be maintained; however, notable challenges may occur in memory, focus, and problem-solving skills. Therefore, motor-cognitive dual-task training is warranted to prevent cognitive decline and improve cognition in aging populations. This study aimed to determine the influence of such dual-task activities during straight and curved walking on the activities of the prefrontal cortex and associated gait variables in older adults with MCI. Materials and Methods: Twenty-seven older adults aged ≥65 years and identified as having MCI based on their scores (18-23) on the Korean Mini-Mental State Examination were enrolled. The participants performed four task scenarios in random order: walking straight, walking straight with a cognitive task, walking curved, and walking curved with a cognitive task. The activation of the prefrontal cortex, which is manifested by a change in the level of oxyhemoglobin, was measured using functional near-infrared spectroscopy. The gait speed and step count were recorded during the task performance. Results: Significant differences were observed in prefrontal cortex activation and gait variables (p < 0.05). Specifically, a substantial increase was observed in prefrontal cortex activation during a dual task compared with that during a resting-state (p < 0.013). Additionally, significant variations were noted in the gait speed and step count (p < 0.05). Conclusions: This study directly demonstrates the impact of motor-cognitive dual-task training on prefrontal cortex activation in older adults with MCI, suggesting the importance of including such interventions in enhancing cognitive function.

Stimuli-Responsive Molecular Duplexes Displaying Duplex-to-Duplex Switching.

Synthetic duplexes with high stabilities have promising potential for mimicking biomolecular functions and developing supramolecular smart materials. Herein, we describe the synthesis and stimuli-responsive properties of molecular duplexes derived from indolocarbazole (I)-pyridine (P) oligomers. These duplexes adopt nonclassical helical structures, stabilized by I-P hydrogen-bonding pairs in anhydrous chlorinated solvents. Notably, the longest duplex 62 (11-mer)2 displays remarkable stability, forming twenty hydrogen bonds; its exchange energy barrier was determined to be ΔG‡ = 22.0 kcal·mol-1 at 75 °C in anhydrous (CDCl2)2. Upon the addition of water, a hydrated duplex 62 (11-mer)2⊃10H2O was formed, with one water molecule inserted between each I-P hydrogen-bonding pair. The Hill coefficient (n) for this process is 6.1, demonstrating extremely positive cooperativity. Conversely, the hydrated duplex 62 (11-mer)2⊃10H2O was completely converted into the original anhydrous duplex 62 (11-mer)2 when the temperature was increased. Interconversion between these two distinct duplexes can be repeatedly carried out by varying the temperature. Furthermore, reversible switching between hetero-duplexes and homo-duplexes was also demonstrated by controlling the temperature, with concomitant changes in the characteristic emission signals.

Comparison of two doses of intrathecal morphine in laparoscopic donor hepatectomy: A randomized double-blinded non-inferiority trial.

BACKGROUND: Intrathecal morphine (ITM) injection is an effective postoperative analgesic strategy in open or laparoscopic donor hepatectomy; however, the optimal dose has not been determined. In this trial, we compared the post-operative analgesic effects of two doses (300 vs. 400 µg) of ITM injections. METHODS: In this prospective randomized non-inferiority trial, 56 donors were divided into either the 300 µg or 400 µg ITM group (n = 28, each). The primary outcome was the resting pain score at 24 h postoperatively. Pain scores, cumulative opioid consumption, and side effects (postoperative nausea and vomiting [PONV]) were compared up to 48 h postoperatively. RESULTS: Fifty-five donors participated in the entire study. The mean resting pain scores at 24 h after surgery were 1.7 ± 1.6 and 1.7 ± 1.1 in the ITM 300 and ITM 400 groups, respectively (mean difference, 0 [95% CI, -.8 to .7], p = .978). The upper limit of the 95% CI was lower than the prespecified non-inferiority margin (δ = 1), indicating that non-inferiority had been established. The incidence of PONV was lower in the ITM 300 group than in the ITM 400 group at 18 (p = .035) and 24 h postoperatively (p = .015). There were no significant differences in the resting and coughing pain scores and cumulative opioid consumption at any time point. CONCLUSION: For laparoscopic donor hepatectomy, preoperative ITM 300 µg exhibited non-inferior postoperative analgesic effects compared to ITM 400 µg, with a lower incidence of PONV.

Remimazolam dose for successful insertion of a supraglottic airway device with opioids: a dose-determination study using Dixon's up-and-down method.

PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine, was recently approved in numerous jurisdictions as an induction drug for general anesthesia. We aimed to determine the doses of remimazolam that would allow placement of a supraglottic airway device (SGD) in 50% and 95% of nonparalyzed patients (ED50 and ED95). METHODS: In this prospective study, 30 American Society of Anesthesiology Physical Status I-II grade female patients scheduled for hysteroscopic surgery were enrolled. Anesthesia was induced with 1 µg·kg-1 of fentanyl and continuous infusion of remimazolam without neuromuscular blockade. An i-gel® SGD was inserted 2.5 min after the start of remimazolam infusion. We used Dixon's up-and-down method and isotonic regression to determine the ED50 and ED95 of remimazolam for insertion of an SGD. RESULTS: Twenty-eight patients were included in the final analysis. The ED50 and ED95 of remimazolam required for successful i-gel insertion were 8.8 mg·kg-1·hr-1 (95% confidence interval [CI], 6.3 to 10.6) and 10.7 mg·kg-1·hr-1 (95% CI, 10.6 to 11.7), respectively. A nonfully relaxed jaw was found in 7/13 patients (54%) in the success group and 14/15 patients (93%) in the failure group (difference in proportions, 40%; 95% CI, 7 to 65; P = 0.02). Bucking or other movements during SGD insertion only occurred in the failure group (11/15, 73%). CONCLUSION: In 95% of nonparalyzed female patients undergoing hysteroscopy, 10.7 mg·kg-1·hr-1 of remimazolam with 1 µg·kg-1 of fentanyl facilitates i-gel insertion. Remimazolam showed a high incidence of poor jaw relaxation and bucking or other movements during SGD insertion. STUDY REGISTRATION: Clinical Trial Registry of the Republic of Korea (KCT0006527, https://cris.nih.go.kr ; registered 1 September 2021; principal investigator: Ji Seon Jeong).

RéSUMé: OBJECTIF: Le remimazolam, une benzodiazépine à action ultra-brève, a récemment été approuvé dans de nombreuses juridictions comme agent d'induction pour l'anesthésie générale. Notre objectif était de déterminer les doses de remimazolam qui permettraient l'insertion d'un dispositif supraglottique (DSG) chez 50 % et 95 % des patients non paralysés (DE50 et DE95). MéTHODE: Dans cette étude prospective, 30 patientes de statut physique I-II selon l'American Society of Anesthesiology devant bénéficier d'une chirurgie hystéroscopique ont été recrutées. L'anesthésie a été induite avec 1 µg·kg−1 de fentanyl et une perfusion continue de remimazolam sans bloc neuromusculaire. Un DSG i-gel® a été inséré 2,5 minutes après l'amorce de la perfusion de remimazolam. Nous avons utilisé la méthode de l'escalier de Dixon et la régression isotonique pour déterminer la DE50 et DE95 de remimazolam pour l'insertion d'un DSG. RéSULTATS: Vingt-huit patientes ont été incluses dans l'analyse. Les DE50 et DE95 du remimazolam requises pour une insertion réussie de l'i-gel était de 8,8 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 6,3 à 10,6) et 10,7 mg·kg−1·h−1 (IC 95 %, 10,6 à 11,7), respectivement. Une mâchoire non complètement détendue a été observée chez 7 patientes sur 13 (54 %) dans le groupe d'intubation réussie et chez 14/15 patientes (93 %) dans le groupe d'échec d'intubation (différence de proportions, 40 %; IC 95 %, 7 à 65; P = 0,02). Le fléchissement ou d'autres mouvements pendant l'insertion du DSG ne se sont produits que dans le groupe d'échec de l'induction (11/15, 73 %). CONCLUSION: Chez 95 % des patientes non paralysées bénéficiant d'une hystéroscopie, 10,7 mg·kg−1·h−1 de remimazolam avec 1 µg·kg−1 de fentanyl ont facilité l'insertion d'un dispositif i-gel. Le remimazolam a montré une incidence élevée de mauvaise relaxation de la mâchoire et de fléchissement ou d'autres mouvements lors de l'insertion du DSG. ENREGISTREMENT DE L'éTUDE: Registre des essais cliniques de la République de Corée (KCT0006527, https://cris.nih.go.kr ; enregistrée le 1er septembre 2021; chercheur principal : Ji Seon Jeong).

Magnetic Properties of Amorphous Ta/CoFeB/MgO/Ta Thin Films on Deformable Substrates with Magnetic Field Angle and Tensile Strain.

Recently, the application of cobalt iron boron (CoFeB) thin films in magnetic sensors has been widely studied owing to their high magnetic moment, anisotropy, and stability. However, most of these studies were conducted on rigid silicon substrates. For diverse applications of magnetic and angle sensors, it is important to explore the properties of ferromagnetic thin films grown on nonrigid deformable substrates. In this study, representative deformable substrates (polyimide (PI), polyethylene naphthalate (PEN), and polydimethylsiloxane (PDMS)), which can be bent or stretched, were used to assess the in-plane magnetic field angle-dependent properties of amorphous Ta/CoFeB/MgO/Ta thin films grown on deformable substrates. The effects of substrate roughness, tensile stress, deformable substrate characteristics, and sputtering on magnetic properties, such as the coercive field (Hc), remanence over saturation magnetization (Mr/Ms), and biaxial characteristics, were investigated. This study presents an unconventional foundation for exploring deformable magnetic sensors capable of detecting magnetic field angles.

Exercise-Induced Fibroblast Growth Factor-21: A Systematic Review and Meta-Analysis.

This systematic review aimed to synthesize and quantify the results of the studies investigating the changes in fibroblast growth factor-21 (FGF-21) induced by exercise. We searched for studies that did not differentiate between patients and healthy adults but compared them before and after exercise and with and without exercise. For quality assessment, the risk-of-bias assessment tool for nonrandomized studies and the Cochrane risk-of-bias tool were used. A quantitative analysis was performed using the standardized mean difference (SMD) and random-effects model in RevMan 5.4. A total of 94 studies were searched in international electronic databases, and after screening, 10 studies with 376 participants were analyzed. Compared with no exercise, there was a significant increase in the FGF-21 levels from before to after exercise (SMD = 1.05, 95% confidence interval (CI), 0.21 to 1.89). The changes in FGF-21 levels in the exercise group showed a significant difference from the levels in the controls. The results of the random-effects model were as follows: SMD = 1.12; 95% CI, -0.13 to 2.37. While the data on acute exercise were not synthesized in this study, FGF-21 levels generally increased after chronic exercise compared with no exercise.

Immediate Effects of Sprinter-Pattern Exercise on the Lordotic Curve and Abdominal Muscle Activity in Individuals with Hyperlordosis.

Background and Objectives: Abdominal muscle exercises with limb movements are more effective for trunk stabilization than traditional exercises involving trunk flexion alone. This study examined the effects of abdominal exercises incorporating sprinter pattern and crunch exercises on changes in the lordotic curve and abdominal muscle activation in individuals with low back pain caused by hyperlordosis resulting from weak abdominal muscles. Materials and Methods: In this single-blind, randomized controlled trial, a total of 40 participants with hyperlordosis were recruited and randomly assigned to perform either sprinter-pattern abdominal exercises or crunch exercises. The participants assigned to each group performed three sets of ten abdominal exercises. The lumbar lordotic angle (LLA) and sacrohorizontal angle (SHA) were assessed prior to and following the intervention, whereas abdominal muscle activity was gauged throughout the intervention period. Changes in the LLA and SHA were measured by radiography. Abdominal muscle activity was measured using electromyography. Results: The LLA and SHA decreased significantly in both groups (p < 0.001), while the sprinter-pattern exercise group showed a statistically significant decrease compared to the crunch exercise group (p < 0.001). In the activity of the abdominal muscles, there was no significant difference in the rectus abdominis muscle between the two groups (p > 0.005). However, a significant difference between the external and internal oblique muscles was observed, and the activities of both muscles were significantly higher in the sprinter-pattern exercise group than in the crunch exercise group (p < 0.005). Conclusions: Abdominal exercise using a sprinter pattern may be effective in reducing lumbar lordosis by strengthening the abdominal muscles in patients with hyperlordosis.

The C-terminal tail of the yeast mitochondrial transcription factor Mtf1 coordinates template strand alignment, DNA scrunching and timely transition into elongation.

Mitochondrial RNA polymerases depend on initiation factors, such as TFB2M in humans and Mtf1 in yeast Saccharomyces cerevisiae, for promoter-specific transcription. These factors drive the melting of promoter DNA, but how they support RNA priming and growth was not understood. We show that the flexible C-terminal tails of Mtf1 and TFB2M play a crucial role in RNA priming by aiding template strand alignment in the active site for high-affinity binding of the initiating nucleotides. Using single-molecule fluorescence approaches, we show that the Mtf1 C-tail promotes RNA growth during initiation by stabilizing the scrunched DNA conformation. Additionally, due to its location in the path of the nascent RNA, the C-tail of Mtf1 serves as a sensor of the RNA-DNA hybrid length. Initially, steric clashes of the Mtf1 C-tail with short RNA-DNA hybrids cause abortive synthesis but clashes with longer RNA-DNA trigger conformational changes for the timely release of the promoter DNA to commence the transition into elongation. The remarkable similarities in the functions of the C-tail and σ3.2 finger of the bacterial factor suggest mechanistic convergence of a flexible element in the transcription initiation factor that engages the DNA template for RNA priming and growth and disengages when needed to generate the elongation complex.

Talonavicular joint mobilization and foot core strengthening in patellofemoral pain syndrome: a single-blind, three-armed randomized controlled trial.

BACKGROUND: Patellofemoral pain syndrome (PFPS) is defined as pain around the patella while performing activities such as squats, running, and climbing steps. One of the inherent risk factors for PFPS is an excessively pronated foot posture. The aim of this study was to investigate the effect of foot intervention, talonavicular joint mobilization (TJM) and foot core strengthening (FCS), on PFPS. METHODS: Forty-eight patients with PFPS (mean age, 21.96 ± 2.34 years; BMI, 22.77 ± 2.95 kg/m2) were enrolled in the study. Participants were randomly assigned in a 1:1:1 ratio to three groups, and received 12 sessions of TJM, FCS, and blended intervention at university laboratory for 4 weeks. The primary outcomes were pain while the secondary outcomes were lower extremity function, valgus knee, foot posture, and muscle activity ratio measured at baseline, after 12 sessions, and at the 4-week follow-up. RESULTS: The two-way repeated-measures ANOVA revealed significant interactions in all groups (p < 0.05). TJM reduced pain more than the FCS at post-test (mean difference, - 0.938; 95% Confidence interval [CI], - 1.664 to - 0.211; p < 0.05), and blended intervention improved lower extremity function (mean difference, 6.250; 95% CI, 1.265 to 11.235; p < 0.05) and valgus knee (mean difference, - 11.019; 95% CI, - 17.007 to - 5.031; p < 0.05) more than the TJM at 4 weeks follow-up. TJM was more effective in post-test (mean difference, - 1.250; 95% CI, - 2.195 to - 0.305; p < 0.05), and TJM (mean difference, - 1.563; 95% CI, - 2.640 to - 0.485; p < 0.05) and blended intervention (mean difference, - 1.500; 95% CI, - 2.578 to - 0.422; p < 0.05) were more effective in foot posture than the FCS in 4 weeks follow-up. Blended intervention displayed greater improvement in muscle activity than the TJM (mean difference, 0.284; 95% CI, 0.069 to 0.500; p < 0.05) and the FCS (mean difference, 0.265; 95% CI, 0.050 to 0.481; p < 0.05) at 4 weeks follow-up. CONCLUSIONS: Our study is a novel approach to the potential impact of foot interventions on patellofemoral pain. Foot intervention including TJM and FCS is effective for pain control and function improvement in individuals with PFPS. TRIAL REGISTRATION: KCT0003176 , 16/08/2018 (retrospectively registered).

SCDNet: A Deep Learning-Based Framework for the Multiclassification of Skin Cancer Using Dermoscopy Images.

Skin cancer is a deadly disease, and its early diagnosis enhances the chances of survival. Deep learning algorithms for skin cancer detection have become popular in recent years. A novel framework based on deep learning is proposed in this study for the multiclassification of skin cancer types such as Melanoma, Melanocytic Nevi, Basal Cell Carcinoma and Benign Keratosis. The proposed model is named as SCDNet which combines Vgg16 with convolutional neural networks (CNN) for the classification of different types of skin cancer. Moreover, the accuracy of the proposed method is also compared with the four state-of-the-art pre-trained classifiers in the medical domain named Resnet 50, Inception v3, AlexNet and Vgg19. The performance of the proposed SCDNet classifier, as well as the four state-of-the-art classifiers, is evaluated using the ISIC 2019 dataset. The accuracy rate of the proposed SDCNet is 96.91% for the multiclassification of skin cancer whereas, the accuracy rates for Resnet 50, Alexnet, Vgg19 and Inception-v3 are 95.21%, 93.14%, 94.25% and 92.54%, respectively. The results showed that the proposed SCDNet performed better than the competing classifiers.

Postoperative Rehabilitation Protocol Following Arthroscopic Rotator Cuff Repair: A Prospective Single-Arm Pragmatic Interventional Study.

Background and Objectives: Rotator cuff tear is the most common cause of shoulder pain. If nonsurgical treatment fails, arthroscopic rotator cuff repair (ARCR) is recommended. Since the standards for rehabilitation after ARCR are not clear, various rehabilitation methods have been suggested. This study intends to investigate the effect on the recovery phase of ARCR patients through a postoperative rehabilitation protocol (PRP) that considers the healing process and rehabilitation trend. Materials and Methods: This single-arm, pragmatic intervention study was conducted on 30 patients, two weeks postoperative day (POD) after ARCR. ARCR patients received intervention for six weeks from POD two-week, and pain intensity and shoulder function were evaluated at two-week intervals until POD 12-week, and range of motion (ROM) was evaluated at POD four-week and eight-week. Results: In this study, all variables improved over time (p < 0.05). As a result of the comparison between time points, a significant improvement was found in shoulder function at POD 6-week. In addition, the effect size had a large effect on ROM (flexion, scaption flexion, abduction, and external rotation) and shoulder function. Conclusions: Management through the PRP based on scientific evidence in the strategy of postoperative rehabilitation of patients with ARCR is effective for pain intensity, ROM, and shoulder function.

Comparison of Core Muscle Asymmetry Using Spine Balance 3D in Patients with Arthroscopic Shoulder Surgery: A STROBE-Compliant Cross-Sectional Study.

Background and Objectives: Joint immobilization after shoulder surgery can cause an imbalance in the periscapular muscles and affect the kinetic chain throughout the body. There is a difference in core muscle stability because of the asymmetry of the lower extremity muscles. However, the difference due to the asymmetry of the upper-extremity muscles has not been studied extensively. The purpose of this study is to investigate the effect of joint immobilization on the symmetry of the core muscles involved in proximal stability for distal mobility. Materials and Methods: Fifty-five patients who underwent arthroscopic shoulder surgery participated in this study. Core muscle asymmetry (CMA) was measured using a body tilt device. The evaluation variables were analyzed according to the surgical site based on the direction of the core muscle ratio and core muscle state ratio. Results: No differences in CMA were found based on the surgical site (p > 0.05). As a result of the additional subanalysis, significant differences in sex and postoperative day were established (p < 0.05). CMA was low during the intensive postoperative rehabilitation period. However, sex-related differences were greater in males than in females. Conclusions: The clinical results suggest that core muscle training is necessary to reduce CMA during rehabilitation after the immobilization period has elapsed.

Bone marrow CX3CR1+ mononuclear cells relay a systemic microbiota signal to control hematopoietic progenitors in mice.

The microbiota regulate hematopoiesis in the bone marrow (BM); however, the detailed mechanisms remain largely unknown. In this study, we explored how microbiota-derived molecules (MDMs) were transferred to the BM and sensed by the local immune cells to control hematopoiesis under steady-state conditions. We reveal that MDMs, including bacterial DNA (bDNA), reach the BM via systemic blood circulation and are captured by CX3CR1+ mononuclear cells (MNCs). CX3CR1+ MNCs sense MDMs via endolysosomal Toll-like receptors (TLRs) to produce inflammatory cytokines, which control the basal expansion of hematopoietic progenitors, but not hematopoietic stem cells, and their differentiation potential toward myeloid lineages. CX3CR1+ MNCs colocate with hematopoietic progenitors at the perivascular region, and the depletion of CX3CR1+ MNCs impedes bDNA influx into the BM. Moreover, the abrogation of TLR pathways in CX3CR1+ MNCs abolished the microbiota effect on hematopoiesis. These studies demonstrate that systemic MDMs control BM hematopoiesis by producing CX3CR1+ MNC-mediated cytokines in the steady-state.