Citations

AbstractPatients in delirium require trustful communication and re‐orientation. We developed a flyer with positive, re‐orientating suggestions for families of delirious patients in intensive care units. Suggestions include creating a safe environment, interpreting unusual behaviours positively and fostering mental resilience. Additionally, families are encouraged to prioritize their own well‐being, recognizing their crucial role in supporting their loved ones. This flyer offers practical strategies across four key areas: ensuring security and orientation, reframing noises and body experiences, managing agitation and reshaping perceptions. By equipping families with knowledge and tools, this resource aims to promote understanding, resilience and strength to humanize delirium care.

ABSTRACT Background The optimal exercise regimen for alleviating sarcopenia remains uncertain. This study aimed to investigate the efficacy of high‐intensity interval training (HIIT) over moderate‐intensity continuous training (MICT) in ameliorating sarcopenia. Methods We conducted a randomized crossover trial to evaluate plasma proteomic reactions to acute HIIT (four 4‐min high‐intensity intervals at 70% maximal capacity alternating with 4 min at 30%) versus MICT (constant 50% maximal capacity) in inactive adults. We explored the relationship between a HIIT‐specific protein relative to MICT, identified via comparative proteomic analysis, eukaryotic translation elongation factor 1 epsilon 1 (EEF1E1) and sarcopenia in a paired case–control study of elderly individuals (aged over 65). Young (3 months old) and aged (20 months old) mice were randomized to sedentary, HIIT and MICT groups (five sessions/week for 4 weeks; n = 8 for each group). Measurements included skeletal muscle index, hand grip strength, expression of atrophic markers Atrogin1 and MuRF1 and differentiation markers MyoD, myogenin and MyHC‐II via western blotting. We examined the impact of EEF1E1 siRNA and recombinant protein on D‐galactose‐induced myoblast senescence, measuring senescence‐associated β‐galactosidase and markers like p21 and p53. Results The crossover trial, including 10 sedentary adults (32 years old, IQR 31–32) demonstrated significant alterations in the abundance of 21 plasma proteins after HIIT compared with MICT. In the paired case–control study of 84 older adults (84 years old, IQR 69–81; 52% female), EEF1E1 was significantly increased in those with sarcopenia compared to those without (14.68 [95%CI, 2.02–27.34] pg/mL, p = 0.03) and was associated with skeletal muscle index ( R 2 = 0.51, p < 0.001) and hand grip strength ( R 2 = 0.54, p < 0.001). In the preclinical study, aged mice exhibited higher EEF1E1 mRNA and protein levels in skeletal muscle compared to young mice, accompanied by a lower muscle mass and strength, increased cellular senescence and protein degradation markers and reduced muscle differentiation efficiency (all p < 0.05). HIIT reduced EEF1E1 expression and mitigated age‐related muscle decline and atrophy in aged mice more effectively than MICT. Notably, EEF1E1 downregulation via siRNA significantly counteracted D‐galactose‐induced myoblast senescence as evidenced by reduced markers of muscle protein degradation and improved muscle differentiation efficiency (all p < 0.05). Conversely, treatments that increased EEF1E1 levels accelerated the senescence process ( p < 0.05). Further exploration indicated that the decrease in EEF1E1 was associated with increased SIRT1 level and enhanced autophagy. Conclusions This study highlights the potential of HIIT as a promising approach to prevent and treat sarcopenia while also highlighting EEF1E1 as a potential intervention target.

Aggregated α-synuclein (α-SYN) proteins, encoded by the SNCA gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we recapitulated α-SYN pathologies in human induced pluripotent stem cells (iPSCs)–derived cortical organoids generated from patients with LBD with SNCA gene triplication. Single-cell RNA sequencing, combined with functional and molecular validation, identified synaptic and mitochondrial dysfunction in excitatory neurons exhibiting high expression of the SNCA gene, aligning with observations in the cortex of autopsy-confirmed LBD human brains. Furthermore, we screened 1280 Food and Drug Administration–approved drugs and identified four candidates (entacapone, tolcapone, phenazopyridine hydrochloride, and zalcitabine) that inhibited α-SYN seeding activity in real-time quaking-induced conversion assays with human brains, reduced α-SYN aggregation, and alleviated mitochondrial dysfunction in SNCA triplication organoids and excitatory neurons. Our findings establish human cortical LBD models and suggest potential therapeutic drugs targeting α-SYN aggregation for LBD.

BACKGROUND: The supraglottic airway device (SGD) was introduced as a breakthrough in airway management. The Fastrach emerged as the first commercially available intubating SGD, drawing extensive investigation. I-gel is a more recent device that has gained popularity, can be used as an intubating SGD, and replaced Fastrach in many institutions. However, there is uncertainty regarding the comparison between these devices in terms of efficacy for intubation and ventilation, and safety in an airway rescue situation. METHODS: PubMed, EMBASE, Scopus, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing I-gel and Fastrach SGD in adult patients undergoing intubation. The primary outcome was the first-pass success rate for tracheal intubation. Secondary outcomes were tracheal intubation time, SGD insertion time and success, and complications. We computed risk ratios (RRs) to assess binary end points and weighted mean differences (WMDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome and its subgroup analysis ( P < .05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes ( P < .01 was considered statistically significant). RESULTS: This study included a total of 14 RCTs encompassing 1340 patients. The results indicated a significant difference in the first-pass success rate favoring Fastrach (RR, 0.81; 95% CI, 0.67–0.98; P = .03; I² = 91%). In the subgroup analysis, when a flexible scope was utilized through I-gel, providers achieved a better tracheal intubation first-pass success rate (RR, 1.05; 95% CI, 1.01–1.11; P = .03; I² = 0%), compared with the Fastrach. Overall intubation success rates (RR, 0.92; 99% CI, 0.82–1.04; P = .08, I² = 92%) and time (WMD - 1.03 seconds; 99% CI, -4.75 to 2.69; P = .48; I² = 84%) showed no significant difference irrespective of the device used. There was no significant difference regarding device insertion time by the providers (WMD -6.48 seconds; 99% CI, -13.23 to 0.27; P = .01; I 2 = 98%). Success rates of the providers’ initial SGD insertion and complications such as sore throat (RR, 1.01; 99% CI, 0.65–1.57; P = .95, I² = 33%) and blood presence post-SGD removal (RR, 0.89; 99% CI, 0.42–1.86; P = .68, I² = 0%) showed no significant difference. CONCLUSIONS: Based on our findings, a higher first-pass success rate was observed with the use of Fastrach when compared to I-gel. However, the use of I-gel might result in a better intubation success rate with the flexible scope-guided intubation. There are no significant differences in performance in terms of the success rate for intubation overall, time for device insertion, or time to intubation or complications regardless of the device used.

Abstract Isolation of neuron‐derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)‐specific antibodies has been widely used to identify blood biomarkers of CNS disorders. However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single‐EV techniques to establish the neuronal origin and determine the abundance of L1CAM‐positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co‐expressed on single‐EVs with the neuronal proteins β‐III‐tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM‐positive EVs. Levels of L1CAM‐positive EVs carrying the neuronal proteins VAMP2 and β‐III‐tubulin range from 30% to 63%, in contrast to 0.8%–3.9% of L1CAM‐negative EVs. Plasma fluid‐phase L1CAM does not bind to single‐EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.

AbstractThe bond between humans and dogs is precious and has been treasured since ancient times. Dog ownership is linked to numerous health benefits, such as increased physical activity and social functioning and decreased depression and cardiovascular events. However, dogs can transmit zoonotic diseases to humans, many of which present with cutaneous findings. This review summarizes the dermatologic manifestations, transmission routes, diagnosis, and treatment of zoonotic diseases transmitted by dogs, including vector‐borne, bacterial, viral, fungal, and parasitic infections. This review emphasizes the significance of clinicians obtaining a comprehensive exposure history when patients exhibit a rash of unknown origin. Such an approach can provide valuable epidemiological clues related to diagnosing a zoonotic disease transmitted by a pet dog. Furthermore, identifying the dog as an infection source and subsequent veterinary treatment can help prevent recurrent infections in dermatologic patients.