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Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures.

Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12months postoperatively was defined as a reduction from baseline of at least 15points for ODI, 2.2points for COMI, or 2points for pain severity.

Models were developed and integrated into a web-app ( https//neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age 61.19 (12.36) years]. At externalvalidated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population.HotBalloon-based pulmonary vein isolation (HBPVI) has yielded encouraging clinical results in the treatment of atrial fibrillation (AF). Balloon ablation requires a larger sheath, which raises the concern for a persistent iatrogenic atrial septal defect (iASD). The present study aimed to investigate the incidence, clinical features, and the predictive factors of transthoracic echocardiography (TTE)-detectable iASD after HBPVI. All patients who underwent HBPVI of AF with pre- and post-ablation TTE were retrospectively analyzed. A 17-French steerable deflectable guiding sheath was inserted into the left atrium (LA) after a transseptal puncture, and an 8-French sheath was inserted via a single transseptal hole. In a total of 190 patients, 98 (52%) paroxysmal AF (PAF) and 92 (48%) non-PAF, the iASD was detected in 18 (9.4%) with a mean follow-up period of 12.7 ± 2.5 months after HBPVI. All patients had no clinical symptoms related to iASD. No embolic or heart failure events occurred. In the multivariate analysis, LA volume index and LA procedure time were identified as significant independent predictors of iASD. After HBPVI, TTE-detectable iASD was found in 9.4% of study patients. Larger LA size and longer LA procedure time were predictive factors for the persistence of iASD. All patients with iASD had no clinical symptoms 12 months after HBPVI; however, long-term follow-up may be necessary.This paper studies the reduction of crystallinity degree (CD) of cellulose treated with starch gel (SG), and the correlation of CD with the fermentation efficiency of cellulose to fuel-grade ethanol. Cellulose bioconversion from wood sawdust, consisting of three processes, was conducted in the same batch (one-step). The XRD and TEM analysis revealed 11% reduction in cellulose CD after its treatment with SG. One-step bioconversion process was performed employing two cell factories (CF) of non-engineered S. cerevisiae. CFs contained non- engineered S. cerevisiae cells covered with either SG entrapping Trichoderma reesei or cellulases prepared in the laboratory and immobilized in SG. The consolidated fermentation of treated cellulose resulted in an increase of bioethanol concentration (60-90%) in 2-day fermentation and the maximum ethanol concentration reached was approximately 5 mL/L (3.95 g/L). The fermentation efficiency for grade-fuel ethanol production was improved by cellulose pretreatment using SG to achieve reduced CD.

Previous evidence regarding the impact of exercise interventions on chemotherapy-induced peripheral neuropathy often focuses on lower-extremity functions, such as muscle strength and balance ability, while their effects on upper extremities remain unknown. We aimed to evaluate the efficacy of combined hand exercise intervention on upper-extremity function, symptoms, and quality-of-life in patients with chemotherapy-induced peripheral neuropathy (CIPN).

After screening 341 patients, 42 were randomly assigned to either the intervention (n = 21) or control (n = 21) group. Participants were evaluated at baseline (T0) and after one (T1) and two (T2) chemotherapy cycles. The primary outcome was upper-extremity function measured using the Michigan Hand Outcomes Questionnaire (MHQ) at T2. The intention-to-treat and as-treated populations were compared using a mixed-effect model.

In the intention-to-treat analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference 7.23; 95% confidence interval 0.35-14.10). Similarly, in the as-treated analysis, the decline in activities of daily living of MHQ was significantly suppressed in the intervention group compared with that in the control group at T2 (difference 13.09; 95% confidence interval 5.68-20.49). Pain also significantly improved in the intervention group compared with that in the control group at T2 (difference 13.21; 95% confidence interval - 22.91 to - 3.51).

The combined hand exercise intervention may improve upper-extremity function, such as by suppressing decline in ADL, and reduce pain in patients with CIPN.

The combined hand exercise intervention may improve upper-extremity function, such as by suppressing decline in ADL, and reduce pain in patients with CIPN.Translating particle dose from in vitro systems to relevant human exposure remains a major challenge for the use of in vitro studies in assessing occupational hazard and risk of particle exposure. This study aimed to model the lung deposition and retention of welding fume particles following occupational scenarios and subsequently compare the lung doses to those used in vitro. We reviewed published welding fume concentrations and size distributions to identify input values simulating real-life exposure scenarios in the multiple path particle dosimetry (MPPD) model. The majority of the particles were reported to be below 0.1 μm and mass concentrations ranged between 0.05 and 45 mg/m3. Following 6-h exposure to 5 mg/m3 with a count median diameter of 50 nm, the tracheobronchial lung dose (0.89 µg/cm2) was found to exceed the in vitro cytotoxic cell dose (0.125 µg/cm2) previously assessed by us in human bronchial epithelial cells (HBEC-3kt). However, the tracheobronchial retention decreased rapidly when no exposure occurred, in contrast to the alveolar retention which builds-up over time and exceeded the in vitro cytotoxic cell dose after 1.5 working week. After 1 year, the tracheobronchial and alveolar retention was estimated to be 1.15 and 2.85 µg/cm2, respectively. Exposure to low-end aerosol concentrations resulted in alveolar retention comparable to cytotoxic in vitro dose in HBEC-3kt after 15-20 years of welding. This study demonstrates the potential of combining real-life exposure data with particle deposition modelling to improve the understanding of in vitro concentrations in the context of human occupational exposure.

Poor ergonomics and acute stress can impair surgical performance and cause work-related injuries. Robotic assistance may optimize these psychophysiological factors during UKA. This study compared surgeon physiologic stress and ergonomics during robotic-assisted UKA (rUKA) and conventional UKA (cUKA).

Cardiorespiratory and postural data from a single surgeon were recorded during 30 UKAs, (15 rUKAs, 15 cUKAs). Heart rate (HR), HR variability, respiratory rate (RR), minute ventilation and calorie expenditure were used to measure surgical strain. Intraoperative ergonomics were assessed by measuring flexion/extension/rotation of the neck and lumbar spine, and shoulder abduction/adduction.

Mean operative time was 32.0 ± 7min for cUKA and 45.9 ± 9min for rUKA (p < 0.001). Mean neck flexion was -23.4° ± 13° for rUKA and -49.1° ± 18 for cUKA (p < 0.001), while mean lumbar flexion was -20.3° ± 30° for rUKA and -0.4° ± 68° for cUKA (p = 0.313). Mean lumbar flexion was similar; however, a significantly greater percentage of time was spent in lumbar flexion > 20° during cUKA. Bilateral shoulder abduction was significantly higher for rUKA. Mean calorie expenditure was 154cal for rUKA and 89.1cal for cUKA (p < 0.001). Mean HR was also higher for rUKA (88.7 vs. 84.7, p = 0.019). HR variability was slightly lower for rUKA (12.4) than for cUKA (13.4), although this did not reach statistical significance (p = 0.056). No difference in RR or minute ventilation was observed.

rUKA resulted in less neck flexion but increased shoulder abduction, heart rate, and energy expenditure. The theoretical ergonomic and physiologic advantages of robotic assistance using a handheld sculpting device were not realized in this study.

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Treatment initiation with brolucizumab, a new potent anti-vascular endothelial growth factor (VEGF) agent, is typically performed with three monthly injections (loading dose) and has been well studied in treatment-naïve patients. However, no clinical data are available yet on whether or not anti-VEGF pretreated patients also benefit from a loading dose. In the clinical setting, different heterogeneous treatment patterns are used as no clinical trial has addressed this so far in a head-to-head comparison. Therefore, the FALCON study is investigating whether patients with unsatisfactory response to previous anti-VEGF treatments benefit from a loading dose at the switch to brolucizumab treatment.

FALCON is a 52-week, two-arm, randomized, open-label, multicenter, multinational study in patients with residually active neovascular age-related macular degeneration (nAMD) who will be randomized 11 and started with brolucizumab 6mg loading (three monthly loading doses) or brolucizumab 6mg non-loading (one initial tion-03 Dec 2019.Biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and their recycling after splicing require numerous assembly/recycling factors whose modes of action are often poorly understood. The intrinsically disordered TSSC4 protein has been identified as a nuclear-localized U5 snRNP and U4/U6-U5 tri-snRNP assembly/recycling factor, but how TSSC4's intrinsic disorder supports TSSC4 functions remains unknown. Using diverse interaction assays and cryogenic electron microscopy-based structural analysis, we show that TSSC4 employs four conserved, non-contiguous regions to bind the PRPF8 Jab1/MPN domain and the SNRNP200 helicase at functionally important sites. It thereby inhibits SNRNP200 helicase activity, spatially aligns the proteins, coordinates formation of a U5 sub-module and transiently blocks premature interaction of SNRNP200 with at least three other spliceosomal factors. Guided by the structure, we designed a TSSC4 variant that lacks stable binding to the PRPF8 Jab1/MPN domain or SNRNP200 in vitro. Comparative immunoprecipitation/mass spectrometry from HEK293 nuclear extract revealed distinct interaction profiles of wild type TSSC4 and the variant deficient in PRPF8/SNRNP200 binding with snRNP proteins, other spliceosomal proteins as well as snRNP assembly/recycling factors and chaperones. Our findings elucidate molecular strategies employed by an intrinsically disordered protein to promote snRNP assembly, and suggest multiple TSSC4-dependent stages during snRNP assembly/recycling.

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