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Repressor Element 1-Silencing Transcription factor (REST) emerges as a metabolism-sensitive transcriptional hub that supports basal mitophagy, mitochondrial quality, and synaptic function in neurons. In Alzheimer's disease, REST becomes mislocalized and functionally impaired, coinciding with early defects in mitochondrial quality control. Activation of the NAD+ -SIRT1 axis enhances REST nuclear activity, restores its mitochondrial and neuroprotective gene programs, and attenuates pathological and cognitive decline in experimental AD models. Our study highlights REST as a promising target to preserve mitochondrial and neuronal function.Abbreviations:Alzheimer's disease, AD; Repressor Element 1-Silencing Transcription factor, REST; Nicotinamide Adenine Dinucleotide, NAD+.
Quadriceps muscle deficits following anterior cruciate ligament (ACL) injury can persist years beyond reconstruction (ACLR), but the underlying molecular mechanisms remain largely unexplored. This study investigated whether persistent muscle deficits following ACLR are associated with defects in hypertrophic signaling pathways in response to acute resistance exercise. Twelve participants (7 females, 5 males; age 26.7 ± 4.1 years; 2.6 ± 1.5 years post-ACL injury) underwent MRI scanning and one-repetition maximum (1RM) testing to determine muscle volume and unilateral leg-press strength in the ACLR versus contralateral control leg. Following a standardized meal and overnight fast, participants performed unilateral leg-press resistance exercise (6 sets of 8 repetitions at 80% 1RM). Vastus lateralis (VL) muscle biopsies were collected from both legs at rest and immediately post-exercise. Immunoblotting assessed phosphorylation status and total protein content of hypertrophic signaling proteins (e.g., mTORC1 pathway). Total knee extensor muscle volume (7.5% deficit; p = 0.037), VL (7.7% deficit; p = 0.031), and rectus femoris (5.8% deficit; p = 0.022) muscle volumes were decreased in the ACLR versus contralateral control leg. Knee extensor (R2 = 0.37; p = 0.036) and VL (R2 = 0.36; p = 0.038) deficits correlated with increased time since injury, with no associated unilateral leg press 1RM strength difference between legs (p = 0.192). Despite main effects of exercise observed for mTORC1 pathway signaling proteins (i.e., decreased p-TSC2 Thr1462; p = 0.002 and p-4E-BP1 Thr37/46; p < 0.0001, and increased p-S6 Ser240/244; p = 0.032), no between-leg differences in mTORC1 signaling were detected at rest or immediately post-exercise under the specific experimental conditions tested. In conclusion, persistent muscle volume deficits following ACLR were less pronounced with increased time since injury but were not associated with detectable differences between legs in unilateral leg-press strength. The lack of detectable between-leg differences in vastus lateralis mTORC1 signaling warrants further investigation at timepoints closer to ACLR and/or later post-exercise. Trial Registration: This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry (ANZCTR; trial registration number 12622001166763).
Voice analysis has emerged as a promising non-invasive approach for monitoring respiratory and systemic health conditions. However, subtle physiological alterations are often difficult to capture using recordings collected at rest. In addition, combining traditional acoustic descriptors with modern self-supervised speech representations may provide complementary information for clinical voice analysis. This study evaluates a generalized screening model integrating stress-induced acoustic analysis with machine learning. We investigate how physical exertion and the fusion of traditional acoustic features with self-supervised learning embeddings (such as wav2vec 2.0 and WavLM) enhance the diagnostic sensitivity of vocal and respiratory signals. Post-Acute Sequelae of SARS-CoV-2 (PASC) is used as a case study to evaluate the proposed framework. Utilizing the DICOPERIA-Voice dataset (n = 154), we collected recordings of sustained vowel phonation (/a/) and voluntary coughing at two clinical moments: resting state and following a physiological stress protocol (six-minute walk and one-minute sit-to-stand tests). We employed a dual-feature extraction strategy, combining traditional acoustic biomarkers with high-dimensional Self-Supervised Learning (SSL) embeddings from wav2vec 2.0, WavLM and HuBERT. Binary classification (PASC vs. Healthy) was performed using Logistic Regression, evaluated via stratified 5-fold cross-validation. Physical exertion significantly improved classification performance and reduced model variability across all tasks. The fusion of acoustic features, WavLM and wav2vec 2.0 achieved peak F1-scores of 82.2% for vowel phonation and 80.8% for coughing both in post-exercise conditions. A cross-task late fusion model aggregation reached the highest overall performance, with an F1-score of 87.7%. Incorporating Self-Supervised Learning representations into acoustic analysis improves the sensitivity of voice-based screening, while post-exercise measurements further enhance the robustness and consistency of classification. Together, these strategies provide a scalable and objective framework for detecting respiratory and vocal sequelae in chronic or post-viral conditions. With further validation, this approach could be integrated into routine functional assessments, offering a rapid, non-invasive adjunct to clinical decision-making.
Expanding a genomics-guided assessment of butterfly taxonomy, we integrate phylogenetic evidence from all protein-coding genes with morphological considerations to refine our understanding of butterfly systematics and discover new taxa. As a result, 2 subgenera, 39 species, and 5 subspecies are proposed as new (type species in original combinations or type localities are listed in parentheses): Erebia (Magda) magdalena uintana Grishin, ssp. n. (USA: Utah, Uintah Co.) in Nymphalidae Rafinesque, 1815; Myselasia rondea Grishin, sp. n. (Brazil: Rondônia), Myselasia pseudocrinon Grishin, sp. n. (Ecuador: Pastaza), Myselasia paramatuta Grishin, sp. n. (Ecuador: Morona-Santiago), Euselasia anapellos Grishin, sp. n. (Peru: Loreto), Ectosemia lavanda Grishin, sp. n. (Brazil: Amazonas), Ectosemia dira Grishin, sp. n. (Peru: Cuzco), Ectosemia attavus cyanea Grishin, ssp. n. (Ecuador: Tungurahua), Mesosemia tinypuncta Grishin, sp. n. (Panama: Chiriquí), Mesosemia parabanda Grishin, sp. n. (Peru: Cuzco), Napaea extraperlata Grishin, sp. n. (Ecuador: Morona-Santiago), Ithomiola (Ithomiola) cuscola Grishin, sp. n. (Peru: Cuzco), Ithomiola (Ithomiola) bolitanos Grishin, sp. n. (Bolivia: La Paz), Ithomiola (Ithomiola) ecuatanos Grishin, sp. n. (Ecuador: Tungurahua), Ithomiola (Ithomiola) tanos cuscanos Grishin, ssp. n. (Peru: Cuzco), Ithomiola (Ithomiola) manchola Grishin, sp. n. (Peru: Madre de Dios), Ithomiola (Ithomiola) triola Grishin, sp. n. (Bolivia: Santa Cruz), Apodemia (Apodemia) estrellada Grishin, sp. n. (Mexico: Sonora), and Synargis corta Grishin, sp. n. (French Guiana: Roura) in Riodinidae Grote, 1895 (1827); Idiospilix Grishin, subgen. n. (Rapala subguttata Elwes, [1893]) in Lycaenidae [Leach], [1815]; and Drephalys (Paradrephalys) cremoreus Grishin, sp. n. (Bolivia: Santa Cruz), Dyscophellus megaporsena Grishin, sp. n. (Northern Argentina), Cecropterus (Murgaria) perichales Grishin, sp. n. (Peru), Cecropterus (Murgaria) guatemalensis Grishin, sp. n. (Guatemala: Petén), Charidia paronia Grishin, sp. n. (Brazil: Rondônia), Quadrus (Quadrus) teelatus Grishin, sp. n. (Venezuela: Aragua), Quadrus (Quadrus) truncatina Grishin, sp. n. (Peru: Junín), Gindanes vittatus Grishin, sp. n. (Brazil: Rondônia), Arteurotia artistella sinalima Grishin, ssp. n. (Mexico: Sinaloa), Bolla (Sebia) azora Grishin, sp. n. (Mexico: Oaxaca), Bolla (Sebia) brennatus Grishin, sp. n. (Panama: Darién), Bolla (Sebia) zuelisa Grishin, sp. n. (Venezuela: Trujillo), Bolla (Uniphylus) martea Grishin, sp. n. (Colombia: Magdalena), Staphylus (Capilla) lemesi Grishin, sp. n. (Venezuela: La Guaira), Anisochoria minorella hermieri Grishin, ssp. n. (Argentina: Salta), Justa Grishin, subgen. n. (Thoressa justini Inoué & Kawazoé, 1969), Isma bulaga Grishin, sp. n. (Philippines: Mindanao), Isma leytatus Grishin, sp. n. (Philippines: Leyte), Decinea buenia Grishin, sp. n. (Bolivia: Santa Cruz), Decinea brocki Grishin, sp. n. (Peru: Cuzco), Zenis parlatus Grishin, sp. n. (Brazil: Rondônia), Zenis doris Grishin, sp. n. (Ecuador: Morona-Santiago), Mucia rustana Grishin, sp. n. (Peru: Cuzco), Mucia castanuza Grishin, sp. n. (Peru: Cuzco), Alerema uniplex Grishin, sp. n. (Bolivia: La Paz), and Racta racteca Grishin, sp. n. (Ecuador: Tungurahua), in Hesperiidae Latreille, 1809. Lacturnea Nazari & Fric, 2025, stat. nov., Huegelia Nazari & Fric, 2025, stat. nov., and Everes Hübner, [1819], stat. rev. are subgenera of Cupido Schrank, 1801 (not genera). The following are new combinations: Ajenorix subguttata (Elwes, [1893]), comb. nov. (not Virachola F. Moore, 1881) and Halpe justini (Inoué & Kawazoé, 1969), comb. nov. (not Thoressa Swinhoe, 1913). The following taxa are species (not subspecies or synonyms of the taxa given in parentheses): Erebia (Magda) avinoffi W. Holland, 1930, stat. rest. (not Erebia (Magda) fasciata Butler, 1868), Myselasia gonzaloi (Salazar & Henao, 2019), stat. nov. (not Myselasia gradata (Stichel, 1927)), Ectosemia attalus (Seitz, 1913), stat. nov. (not Ectosemia eumene (Cramer, 1776)), Ectosemia furia (Stichel, 1910), stat. nov. (not Ectosemia erinnya (Stichel, 1910)), Cupido (Sinocupido) korlana Staudinger, 1901, stat. nov. (not Cupido (Everes) prosecusa duplex (Alphéraky, 1887)), Plebejus (Lycaeides) scudderii (W. H. Edwards, 1861), stat. rest. (not Plebejus (Lycaeides) idas (Linnaeus, 1760); consequently, all North American subspecies formerly assigned to P. idas are treated here as subspecies of P. scudderii), Cecropterus (Cecropterus) capys Godman & Salvin, 1894, stat. rest. (not Cecropterus (Cecropterus) longipennis Plötz, 1882), Cogia terranea (Butler, 1874), stat. rest. (not Cogia calchas (Herrich-Schäffer, 1869)), Halpe raphaeli (Nuyda & Kitamura, 1994), comb. et stat. nov. (not Halpe justini (Inoué & Kawazoé, 1969), comb. nov.), and Potanthus (Potanthus) pavor (De Niceville, 1894), stat. rest. (not Potanthus (Potanthus) euria (Plötz, 1883)). The following taxa are valid subspecies, not species or synonyms: Erebia (Magda) avinoffi semo Grum-Grshimailo, 1899, stat. rev., Satyrium californica helenae M. Fisher, 2009, stat. rest., Cecropterus (Cecropterus) longipennis punctisignatus Bryk, 1953, stat. rest., Bolla (Bolla) nigerrima banosa (Bell, 1937), stat. nov., Staphylus (Capilla) azteca machuca (Schaus, 1913), stat. nov., and Staphylus (Capilla) tyro nicoleae Lemes, 2026, stat. nov. The following taxa are confirmed as valid: Erebia (Magda) mackinleyensis Gunder, 1932, Satyrium californica wapiti M. Fisher, 2006, and Isma bipunctata Elwes & Edwards, 1897. The following taxa are new junior subjective synonyms: Lethina Reuter, 1896 of Parargina Tutt, 1896, Euselasia ella terrea Stichel, 1924 of Myselasia eulione (Hewitson, 1856), Euselasia gradata Stichel, 1927 of Myselasia cucuta (Schaus, 1902), Euselasia pseudomys Callaghan, 1999 of Myselasia rhodon (Seitz, 1913), Euselasia crotopus form. mutator Seitz, 1916 of Erythia micaela (Schaus, 1902), Mesosemia meyi Brévignon, 1997 of Ectosemia eumene (Cramer, 1776), Lycaena gisela Püngeler, 1901 of Cupido (Sinocupido) korlana Staudinger, 1901, stat. nov., and Pamphila orfitus Mabille, 1883 of Potanthus (Potanthus) euria (Plötz, 1883); and the following are revised junior subjective synonyms: Sinocupido lokiangensis Lee, 1963 of Cupido (Sinocupido) korlana Staudinger, 1901 and Staphylus inconstans Bell, 1932 of Staphylus (Capilla) azteca machuca (Schaus, 1913), stat. nov. A confidently resolved phylogeny suggests partitioning the tribe Satyrini Boisduval, 1833 into 13 subtribes and places Llorenteana Viloria & Luis-Martínez, [2019] in Euptychiina Reuter, 1896 (not Ypthimina Reuter, 1896). The following species described from a single specimen are confirmed by genomic sequencing of additional specimens: Phanus centralis Grishin, 2025 (known from El Salvador), Phanus ecutinus Grishin, 2025 (range extended from northwestern Ecuador to Panama), Telegonus (Rhabdoides) elorianus Grishin, 2025 (recorded from southern Brazil and Argentina), and Rhomba pulla Grishin, 2023. Furthermore, we clarify the type locality of Apodemia (Apodemia) apache Grishin, 2026 as USA: Arizona, Apache Co., US-60, 8 mi west of Greens Peak Road, elevation 7000 ft; provide additional evidence for the distinction of Satyrium dryope (W. H. Edwards, 1870) as a species-level taxon that possibly does not form a monophyletic group with Satyrium sylvinus Boisduval, 1852, and demonstrate that both Arteurotia artistella Grishin, 2023 and Arteurotia tractipennis A. Butler & H. Druce, 1872 occur in eastern Chiapas (Mexico) and Guatemala. Lectotypes are designated for 18 taxa: Erebia magdalena Strecker, 1880 (USA: Colorado, Clear Creek Co.), Erebia fasciata Butler, 1868 (Canada: Nunavut, Victoria Is.), Euselasia ella Seitz, 1916 (Bolivia: La Paz, Río Zongo), Euselasia ella terrea Stichel, 1924 (Brazil: Pará, Río Moju), Eurygona cucuta Schaus, 1902 (Venezuela: Táchira, vic. Cúcuta), Eurygona matuta Schaus, 1913 (Costa Rica: Cartago, Juan Viñas), Eurygona micaela Schaus, 1902 (Peru), Euselasia crotopus form. mutator Seitz, 1916 (Peru), Mesosemia eumene form. attalus Seitz, 1913 (French Guiana: Nouveau Chantier), Mesosemia albipuncta Schaus, 1913 (Costa Rica: Limón, Guápiles, La Esperanza), Apodemia multiplaga Schaus, 1902 (Mexico: Veracruz, Rinconada), Lycaena gisela Püngeler, 1901 (China: Xinjiang, Tarim River area vic. Aksu), Lycaena prosecusa v. korlana Staudinger, 1901 (China: Xinjiang, Korla), Eudamus calchas Herrich-Schäffer, 1869 (Brazil: Rio de Janeiro), Nisoniades braco Herrich-Schäffer, 1865 (Cuba), Bolla nigerrima Mabille & Boullet, 1917 (Peru: Puno, Chaquimayo), Anisochoria minorella Mabille, 1898 (Bolivia: La Paz, Río Tanampaya), and Hesperia euria Plötz, 1883 (Java). Neotypes are designated for Papilio eumene Cramer, 1776 (Suriname) and Nisoniades undulatus Herrich-Schäffer, 1865 (Cuba: Matanzas). A full-length COI barcode sequence is provided for every designated lectotype and neotype.
Mitral valve repair (MVr) can alter left ventricular outflow tract (LVOT) geometry and precipitate dynamic LVOT obstruction (LVOTO) in patients with underlying hypertrophic cardiomyopathy (HCM). Cardiac myosin inhibitors are now a Class I recommendation for symptomatic obstructive HCM, yet their role in post-surgical LVOTO remains undefined. A 66-year-old woman with prior MVr developed progressive symptomatic dynamic LVOTO with resting and Valsalva gradients of 33 and 48 mmHg, systolic anterior motion (SAM), and NYHA class II-III symptoms. Mavacamten produced marked gradient reduction to 7 mmHg at rest and with Valsalva, with SAM resolution and symptomatic improvement to NYHA class II. Dose reduction to 2.5 mg led to gradient recurrence; re-escalation to 5 mg restored suppression, suggesting a reproducible dose-dependent effect. Mavacamten effectively reduced dynamic LVOTO despite surgically altered mitral geometry, expanding the therapeutic scope of myosin inhibition to a post-surgical population not well represented in the major trials. Dynamic LVOTO may emerge or progress after mitral valve repair in patients with underlying hypertrophic cardiomyopathy. Mavacamten may provide effective non-surgical suppression of post-repair dynamic LVOTO despite surgically altered mitral geometry.
Open arthroplasty with discectomy is offered for temporomandibular joint (TMJ) intraarticular pain and dysfunction after failed conservative care. Whether human amniotic membrane (HAM) interposition improves outcomes remains unclear. To compare pain, mandibular function, and safety between discectomy plus HAM and discectomy alone. Single-center randomized trial (Treviso Regional Hospital, Italy; 2017 to 2024). Adults with TMJ osteoarthrosis on magnetic resonance imaging and symptoms persisting after 5 hyaluronic acid arthrocenteses were randomized at 1:1 ratio (block randomization and concealed allocation). Reconstructive technique: discectomy plus HAM versus discectomy alone, randomly assigned. Peak pain on a 0 to 10 visual analogue scale (VAS) at rest, phonation, and mastication; maximum interincisal opening (MIO, mm); lateral and protrusive excursions. Secondary: complications. Assessed at baseline (T0) and 12 months (T1). Age, sex, symptom duration, arthrocentesis cycles, unilateral versus bilateral disease, and follow up. Welch t-test, Mann-Whitney U, Fisher's exact test; ANCOVA adjusting for baseline, age, sex, and laterality; P < .05; intention-to-treat. Sixty-two subjects enrolled: 32 HAM (mean age 48.7 [standard deviation [SD] 17.4] years; 26 [81.3%] female) and 24 controls (mean age 60.3 [SD 11.2]; 14 [58.3%] female; P = .02 and P = .08). At T0, peak VAS was comparable at rest (4.38 [SD 1.18] vs 4.58 [SD 1.14]; P = .51) and phonation (6.47 [SD 1.08] vs 6.58 [SD 1.10]; P = .70); mastication was higher in controls (7.58 [SD 1.06] vs 6.53 [SD 1.29]; P = .002). At T1, peak VAS favored HAM at rest (0.88 [SD 0.83] vs 3.67 [SD 1.09]; P < .001), phonation (1.41 [SD 1.04] vs 5.62 [SD 1.13]; P < .001), and mastication (1.41 [SD 1.13] vs 4.58 [SD 0.83]; P < .001). MIO did not differ (34.34 [SD 4.60] vs 35.88 [SD 1.54] mm; P = .09). Right lateral excursion favored HAM (8.12 [SD 1.48] vs 6.08 [SD 0.78] mm; P < .001). Transient facial nerve weakness: 4 (12.5%) HAM versus 6 (25.0%) controls (P = .29); no other complications. HAM interposition yielded clinically meaningful pain reduction and superior excursive and masticatory outcomes at 12 months, with no benefit on MIO and no added morbidity.
Ambulance staff have the highest sickness absence, burnout and turnover intentions in the National Health Service, with work-related stress and anxiety identified as key drivers. Although multiple occupational stressors have been reported, it remains unclear which have the greatest impact. This study examined which work stressors are most strongly associated with mental health, well-being and intention to leave; whether these associations are explained by stress appraisals and mental rest; and which staff are most vulnerable to adverse outcomes. A mixed-methods, explanatory, sequential design, stress audit was conducted in one ambulance service in England. An online survey with ambulance staff (n=420) assessed key stress elements (work stressors, stress appraisals, mental rest) and key outcomes (depression, well-being, intention to leave). Semistructured interviews with staff (n=8) explored the findings of the survey in more depth. Linear regression analyses examined relationships between predictors (eg, stressors) and outcomes (eg, well-being) and analysis of variances and t-tests explored differences between groups (eg, gender). A thematic analysis of qualitative data was conducted. Quantitative and qualitative findings suggest that stress related to manager support (ie, upper management prioritising efficiency over staff needs), workplace demands (ie, organisational demands creating extra burden), poor relationships (eg, with non-peer staff) and constant change had the most negative impact on staff. Low mental rest and threat appraisals (ie, feeling 'overwhelmed' by work demands) were strong predictors of all negative outcomes, alongside cumulative stress exposure and negative emotional responses. Longer tenure, supervisory roles, mixed urban-rural working and male gender were associated with greater risk of poorer outcomes. This study offers a comprehensive and novel insight into the stress experiences of ambulance staff. Findings underscore the need for theoretically-informed, evidence-based interventions that integrate organisational reform and individual support strategies to mitigate sickness absence, safeguard well-being and prevent attrition.
This cross-sectional study aimed to evaluate the distribution of complications in clasp-retained removable partial dentures (C-RPDs) and to investigate the influence of denture design parameters, denture age, and Kennedy and Eichner classifications on complication patterns and patient-reported outcomes. 134 patients wearing 205 metal C-RPDs were included. Biological and mechanical complications were recorded. Denture design parameters (major connector type, clasp type and number, and rest number) were documented. Oral health-related quality of life Oral health-related quality of life (OHRQoL) and patient satisfaction were assessed using the OHIP-14 and a visual analog scale (VAS). Associations between complication patterns, design parameters, denture age, classifications and patient-reported outcomes were statistically analyzed. Mechanical complications were the most frequently observed complications. Mechanical complications and ulcerations were significantly associated with reduced OHRQoL. Denture age demonstrated a significant association with mechanical complications and patient-reported outcomes. Classifications showed limited associations with complications and did not influence patient-reported outcomes. Palatal plate and anteroposterior palatal strap designs were associated with physical pain and reduced speech satisfaction. In the mandible, dentures incorporating both circumferential and bar clasps demonstrated higher satisfaction, whereas the exclusive use of bar clasps was associated with increased physical disability. Higher numbers of rests and clasps were associated with lower overall OHIP-14 scores. Denture age and design characteristics were associated with complication patterns and patient-reported outcomes. Mechanical complications were more frequently observed in older dentures and, together with mucosal ulcerations, were associated with reduced OHRQoL. These findings suggest that individualized design strategies, regular follow-up, and timely maintenance may contribute to better mechanical stability and patient-centered outcomes in C-RPDs.
High-intensity interval training (HIIT) protocols with varied parameters have been investigated to optimise the time spent at high levels of oxygen uptake. However, to date, the physiological and perceptual responses to a long-start approach (i.e., longer initial work phases followed by shorter subsequent phases) have not been investigated. The aim of the study was to compare external load, physiological responses, and rating of perceived exertion (RPE) between a constant work-interval HIIT protocol (HIIT-C) and a long-start strategy (HIIT-LS) in rugby union players. Nine male academy rugby union players (19.9 ± 0.8 years) from a professional team randomly completed both HIIT-C and HIIT-LS in a counterbalanced design. HIIT-C consisted of 2 × 8 repetitions of 30 s work with 15 s passive recovery and 3 min rest between sets. HIIT-LS consisted of 2 × 7 repetitions (3 × 45 s followed by 4 × 30 s), each separated by 15 s passive recovery, with 3 min rest between sets. Exercise intensity was set at 88% and 83% of maximal velocity achieved during the 30-15 Intermittent Fitness Test for HIIT-C and HIIT-LS, respectively. Differences between protocols were assessed using a paired t-test or, when appropriate, a Wilcoxon signed-rank test depending on data distribution. HIIT-LS elicited a greater total distance and distance covered above 7 km h-1 compared to HIIT-C (p < 0.01), despite a lower mechanical work distance (p < 0.05). No differences were observed in time spent ≥90%V˙O2peak (p = 0.25). Perceived exertion was significantly lower following HIIT-LS (p < 0.05). Time spent at high levels of oxygen uptake did not differ between HIIT-LS and HIIT-C. However, HIIT-LS was better tolerated, as reflected by lower perceived exertion, suggesting potential practical benefits for training load management. Future research should investigate the effects of incorporating HIIT-LS into long-term training interventions aimed at improving endurance performance in team-sport athletes.
The décolleté is susceptible to intrinsic aging, photoaging, and mechanical stress (breast movement and weight), resulting in progressive thinning, laxity, and wrinkle formation. Although injectable fillers are increasingly used to improve décolleté appearance, controlled clinical data evaluating effectiveness and effects on breast imaging are limited. To evaluate the safety and effectiveness of diluted calcium hydroxylapatite carboxymethylcellulose (CaHA-CMC; Radiesse®), prepared at a 1:2 ratio with sterile saline, for treating moderate-to-severe décolleté wrinkles. Eligible females were randomized to immediate or delayed treatment. Patients assigned to immediate treatment received up to three diluted Radiesse sessions, with optional retreatment. Patients assigned to delayed treatment remained untreated through Week 24 (primary endpoint) and subsequently received the same treatment regimen without retreatment. Effectiveness was assessed by blinded evaluators using the Merz Assessment Scale (MAS) Décolleté Wrinkles - At Rest. Safety evaluations included adverse events, patient-reported treatment responses, and retrospective review of post-treatment radiographic breast imaging. The Week 24 estimated responder rate (≥1-point improvement on the MAS Décolleté Wrinkles - At Rest) was 71.2% [95% CI: 61.4%, 79.4%] among treated patients compared with 6.3% [95% CI: 1.5%, 22.9%] among untreated controls, demonstrating a statistically significant between-group difference. Treatment was well tolerated, with predominantly transient, mild-to-moderate injection-site reactions. No interference attributable to diluted Radiesse was observed on post-treatment breast imaging. Diluted Radiesse provided clinically meaningful improvement in décolleté wrinkles with a favorable safety profile and no observed impact on breast imaging, supporting its use as a nonpermanent injectable option for décolleté rejuvenation.
High-quality chest compressions are crucial for effective resuscitation, yet maintaining the guideline-recommended rate of 100-120 compressions per minute is challenging, particularly in stressful and noisy prehospital environments. Haptic feedback delivered through wearable technology may offer a reliable alternative to auditory cues by providing tactile rhythm guidance. To evaluate the efficacy of a smartwatch-based haptic feedback system delivering 110 vibrations per minute in improving adherence to the target chest compression rate during simulated adult cardiac arrest, compared with unassisted cardiopulmonary resuscitation (CPR). In this prospective, experimental, simulation-based crossover study, 80 volunteers (paramedic students, intern physicians, emergency medicine residents, and laypersons; n = 20 each) performed one minute of self-paced chest compressions on a Laerdal Little Anne QCPR manikin and, after a five-minute rest, repeated the task with a Samsung Galaxy Watch 5 delivering haptic impulses at 110 bpm. The primary endpoint was the percentage of compressions performed within the 100-120 bpm target range; secondary endpoints were the proportion of participants achieving the target rate and self-reported user experience. The study was designed and is reported in accordance with the Reporting Guidelines for Health Care Simulation Research. Haptic guidance substantially improved the percentage of compressions within the guideline-recommended 100-120 bpm range. The proportion of participants achieving the target compression rate increased from 45.0% at baseline to 93.75% with smartwatch-assisted feedback (McNemar test, p < 0.001). The mean percentage of compressions delivered within the target range rose from 43.55% during unassisted CPR to 90.71% with haptic guidance, and significant within-group improvements were observed across all four professional cohorts. Participant experience was highly positive: 93.75% endorsed the device for real-world clinical use, 95.00% found it useful for CPR training, and 95.00% expressed willingness to use it again. A smartwatch-based haptic metronome significantly improved adherence to the guideline-recommended chest compression rate across all experience levels. Given its high user acceptability and resilience to environmental noise, this wearable technology may provide a practical, low-cost adjunct to improve CPR quality in both training and prehospital settings.
Vitamin A is an essential micronutrient with broad physiological roles. The liver is of central importance in whole-body vitamin A homeostasis, with hepatocytes distributing retinol to the rest of the body by secreting it in complex with RBP4 (Retinol-binding protein 4). The goal of this study was to elucidate homeostatic mechanisms regulating hepatic vitamin A metabolism by specifically blocking retinoic acid (RA) signaling in hepatocytes. Herein, we used Albumin-Cre (AlbCre) mice to conditionally express a dominant negative retinoic acid receptor (Rardn) in hepatocytes, generating AlbCre:Rardn mice. These mice experience a functional block in hepatocyte RA signalling, as evidenced by the suppression of Cyp26a1, a gene that is highly responsive to RA and is exclusively expressed in hepatocytes within the liver. Unexpectedly, we observed increased circulating levels of retinol and RBP4 in AlbCre:Rardn mice, accompanied by increased hepatic expression of RBP4 at the gene and protein level. We then compared the effect of blocking RA signaling in AlbCre:Rardn mice with a more physiological depletion of hepatic retinoid content, using a mouse model of diet-induced vitamin A deficiency. Similar to AlbCre:Rardn mice, hepatic RBP4 protein expression was higher in vitamin A deficient mice. However, this was instead accompanied by no transcriptional change in hepatic Rbp4 and reduced retinol-RBP4 in the plasma, indicating an overall reduction in hepatic retinol-RBP4 secretion. Together, these data provide new insight into factors that modulate circulating retinol-RBP4 levels, and how the liver supplies the rest of the body with vitamin A.
Abnormal beta-band (13-30 Hz) oscillations in the subthalamic nucleus are a well-established biomarker of motor dysfunction in Parkinson's disease. While most prior work has focused on beta activity during rest or sustained movement, far less is known about its transient dynamics during movement preparation-a critical phase in which suppression of beta-band activity (beta desynchronization) is thought to facilitate motor circuit readiness. Here, we delineate subthalamic beta-band activity specifically in the pre-movement initiation window across diverse motor tasks and demonstrate its association with both clinical motor impairment severity and subsequent movement acceleration. We recorded subthalamic nucleus local field potentials and kinematics in sixteen individuals with Parkinson's disease (10 males, 6 females; mean age 57.9 ± 10.5 years) implanted with sensing deep brain stimulation systems (Medtronic Activa® PC+S). While off medication and stimulation, participants performed cued motor tasks, including sit-to-stand, stand-to-walk and wrist flexion-extension. Pre-movement beta desynchronization, quantified as beta power normalized to resting baseline, was extracted and analysed using linear mixed-effects models to determine its relationship with clinical impairment severity and movement acceleration. Across all tasks, we observed robust pre-movement beta desynchronization in the subthalamic nucleus (P < 0.001). Critically, reduced desynchronization was associated with greater motor impairment, particularly bradykinesia (P < 0.001). This association appeared stronger during the more complex stand-to-walk task and was linked to reduced movement acceleration, as measured by acceleration indices (P < 0.05). A strong link between greater pre-movement beta desynchronization, less severe bradykinesia and more vigorous movement suggests that impaired beta modulation reflects disruptions in motor planning, delayed recruitment of motor networks and excessive basal ganglia inhibition. These circuit-level abnormalities likely contribute to the difficulties individuals with Parkinson's disease face in initiating and executing movements, offering valuable insight into the neurophysiological basis of motor dysfunction in Parkinson's disease.
Many daily activities involve series of interrelated movements and thus the capacity to learn new motor sequences is vital for everyday functioning. Although learning new skills is especially prominent throughout childhood, remarkably few studies have examined the neural underpinnings of motor sequence learning (MSL) and memory consolidation in children. Twenty-two children (7-11 years) and 23 adults (18-30 years) underwent functional magnetic resonance imaging while completing two sessions of a MSL task, separated by a 5-h offline period of wakefulness. Analyses of the behavioral data revealed comparable initial learning in children and adults. However, and consistent with previous research, children exhibited superior motor memory consolidation over the 5-h offline epoch. Neuroimaging analyses revealed that children exhibited smaller modulations in brain activity between task and rest epochs in a widespread network, including the sensorimotor cortex, supplementary motor area, cerebellum, putamen, and regions associated with the default mode network. Similar levels of activity during task and rest epochs in the hippocampus, dorsolateral prefrontal cortex and somatosensory cortex were associated with better motor memory consolidation in children. Results potentially suggest that the continued engagement of the developing brain during interleaved rest contributes to the childhood advantage in motor memory consolidation.
To investigate the effects of three full squat (SQ) training volumes, matched for fatigue, on jump performance, muscle strength, neuromuscular adaptations, and muscle hypertrophy. Thirty-six resistance-trained men were randomized into three groups: low (LOW), moderate (MOD), and high (HIG) volume. All groups trained SQ twice a week, with relative intensities increasing from 70% to 85% 1RM over the 8-week training period. The total volume accumulated was 48, 144, and 312 repetitions for LOW, MOD, and HIG, respectively, during the 16 training sessions. To isolate the effect of training volume by minimizing fatigue accumulation across repetitions, short rest periods were inserted between repetitions. The following tests were performed: 1) cross-sectional area (CSA) of vastus lateralis; 2) countermovement jump (CMJ); 3) maximal isometric SQ contraction; 4) progressive loading SQ test; and 5) fatigue SQ test. MOD achieved the greatest gains in the progressive loading SQ test ("group-by-time" interaction: p = 0.02, effect sizes (ES): 0.87, 2.52, and 1.12, for LOW, MOD, and HIG, respectively). HIG showed the greatest increases in the electromyography amplitude during this test ("group-by-time" interaction: p = 0.03, ES: -0.13, 0.52, and 0.88, for LOW, MOD, and HIG). All groups showed significant increases in CSA, without significant differences between them ("group-by-time" interaction: p = 0.34, ES: 0.52, 0.41, and 0.56, for LOW, MOD, and HIG). Short inter-repetition rest periods enabled all training volumes to induce significant hypertrophy, while moderate volumes optimized strength gains and high volumes maximized neuromuscular activation, highlighting volume-specific adaptations in SQ training.
Debate exists on which functional position (supine or standing) should form the basis of radiographic assessment of the native acetabulum. Pelvic tilt (PT) differs between positions influencing radiographic acetabular assessment. This study aims to (1) quantify PT changes from supine to standing amongst volunteers and patients; (2) assess changes in acetabular parameters between the postures; and (3) determine whether changes in acetabular parameters differ according to acetabular morphotype. This is a prospective, consecutive, cohort study of 105 asymptomatic volunteers (53% male; mean age 36.5 ± 13.6 years; body mass index [BMI] 25.0 ± 2.0 kg/m2) and 437 patients presenting to a hip preservation clinic without osteoarthritis (Tonnis ≤1) (40% male; mean age 35.7 ± 8.6 years; BMI 25.0 ± 2.0 kg/m2). All underwent standardized supine and standing anteroposterior pelvic radiographs. PT change was quantified using the sacrofemoral-pubic (SFP) angle. Acetabular morphology was evaluated in detail to characterize morphotype according to the Ottawa classification (lateral dysplasia, anterior dysplasia, posterior dysplasia), pincer or "normal." Changes between supine and standing were compared between cohorts and morphotypes. The mean SFP decreased by -3.7° (IC95% 4.0-3.5) from supine to standing. Acetabular measurements demonstrated no differences in change between volunteers and symptomatic patients when transitioning between supine to standing. Measurements of lateral coverage changed minimally between supine (volunteers: 30.7° ± 6.1°; symptomatics: 27.3° ± 8.3°) and standing (volunteers: 30.3° ± 5.7°; symptomatics: 26.1° ± 8.1°), whereas measurements reflecting anteroposterior coverage changed significantly (ΔAWI volunteers: -0.10 ± 0.08 and symptomatics: -0.09 ± 0.07; p < 0.001 and ΔPWI volunteers: 0.09 ± 0.08 and symptomatics: 0.09 ± 0.07; p < 0.001). Patients with anterior dysplasia demonstrated smaller ΔSFP (-1.5° ± 2.5° vs. -3.7° ± 2.9°; p = 0.004) compared with the rest of the cohort. By contrast, posterior dysplasia showed greater ΔSFP (-4.5° ± 2.7° vs. -3.6° ± 2.9°; p = 0.128) than the rest. Groups demonstrated comparable changes in PT and acetabular parameters between positions. The magnitude and direction of change was associated with acetabular morphology uncoupling compensatory mechanisms. Standing radiographs may be preferred to supine, as they account for compensatory mechanisms. Level II, diagnostic. See Instructions for Authors for a complete description of levels of evidence.
Enterolithiasis-formation of stone concretions within the gastrointestinal tract-is an uncommon and underrecognized cause of intermittent abdominal symptoms and acute bowel obstruction. Primary (true) enteroliths originate within the bowel lumen and are usually associated with focal stasis from anatomic or inflammatory pathology; idiopathic primary enterolithiasis (no identifiable predisposing lesion) is exceptionally rare. We present a case that illustrates diagnosis by contrast-enhanced CT and successful nonoperative management of extensive idiopathic enterolithiasis. A 52-year-old woman presented with a 2-month history of intermittent, crampy lower abdominal pain that increased in frequency over the week before presentation. She had no prior abdominal surgery, no history of inflammatory or ischemic bowel disease, and no systemic symptoms. On examination she was hemodynamically stable with a soft, non-tender abdomen and normal laboratory tests. Contrast-enhanced abdominal CT demonstrated numerous discrete intraluminal calcifications within the large bowel consistent with multiple enteroliths but no bowel dilatation, obstruction, perforation, or underlying stricture/diverticulum. Given the clinical stability and absence of obstructive complications, she was treated conservatively with bowel rest, intravenous (IV) isotonic fluids, and analgesia. Over the following days, her pain resolved, and she passed multiple firm, stone-like fragments per rectum. Compositional analysis of a retrieved specimen showed a predominance of calcium salts (calcium phosphate and calcium carbonate) with minor magnesium ammonium phosphate and calcium oxalate. She remained asymptomatic at the 2-month outpatient follow-up with no further intervention. In carefully selected, hemodynamically stable patients without evidence of complete obstruction or ischemia, conservative management (bowel rest, IV fluids, close observation) can permit spontaneous passage of even multiple enteroliths and avoid surgery. Contrast-enhanced CT is essential for diagnosis and assessment of complications, and thorough evaluation to exclude underlying causes is recommended to guide follow-up and prevent recurrence.
Although the use of laser Doppler perfusion imaging has a potential application to monitor internal load associated to exercise, its use in sport science is scarce and the relatively long scanning time required for each region of interest may constrain its use. The aim of this study was to evaluate the effect of running on skin perfusion five hours after exercise across different regions of interest in the lower limbs, and to examine the relationship between these perfusion responses and changes in other physiological and environmental outcomes. A total of 22 volunteers were divided into two groups: an exercise group, which performed a 50-min outdoor run between measurements, and a control group. Skin perfusion (laser Doppler perfusion imaging device, moorLDI2) and skin temperature (infrared thermography, Flir E54) in 6 regions of interest (anterior thigh, anterior knee, anterior leg, posterior thigh, posterior knee and posterior leg), heart rate and heart rate variability (Polar H10) and estimated core temperature (heat flux, Calera Research) were measured before and 5 hours after running in an outdoor temperature of 28 -31 °C. The exercise group presented a higher increase of skin perfusion than the control group for the anterior thigh (95%CI[7, 58%], p=0.02 and ES = 1.0), anterior leg (95%CI[1, 79%], p=0.04 and ES = 0.3), and posterior thigh (95%CI[8, 56%], p<0.01 and ES = 0.5). A regression model obtained (R2 = 0.22) showed how a greater increase in skin perfusion was associated with a higher maximum estimated core temperature during exercise, a higher variation of estimated core temperature at rest and a higher variation of skin temperature. The posterior leg was one of the ROIs with the greatest skin perfusion increase. In conclusion, the anterior thigh can be considered the most appropriate region for evaluating post-exercise skin perfusion responses following aerobic running under warm environmental conditions. These responses are primarily related to the thermal stress generated by the exercise and the environmental conditions.
To investigate the analgesic efficacy, impact on quadriceps muscle strength, and safety of continuous adductor canal block (CACB) versus continuous femoral nerve block (CFNB) in patients undergoing open reduction and internal fixation (ORIF) of patellar fractures, and to provide evidence for selecting the optimal perioperative analgesic regimen in clinical practice. A total of 80 patients scheduled for primary unilateral ORIF of patellar fractures at our hospital from August 2018 to May 2019 were enrolled in this randomized controlled trial. Patients were randomly allocated to the CACB group (experimental group) or CFNB group (control group) at a 1:1 ratio using a computer-generated random number table, with 40 patients in each group. Ultrasound-guided nerve block catheterization was performed before anesthesia induction in both groups, with an initial bolus of 20 mL 0.2% ropivacaine. Postoperative patient-controlled analgesia (PCA) with 0.175% ropivacaine was administered in both groups. The primary outcome was quadriceps muscle strength at 2 h, 12 h, 24 h, and 48 h postoperatively. Secondary outcomes included intraoperative sufentanil consumption, Visual Analogue Scale (VAS) pain scores at rest and during 45° active knee flexion at multiple postoperative time points, rate of rescue analgesia, incidence of adverse events, and patient satisfaction with analgesia. There were no significant differences in baseline demographic and clinical characteristics between the two groups (all P > 0.05). No significant differences were found in intraoperative sufentanil consumption, VAS scores at rest and during movement at all postoperative time points, or rescue analgesia rate between the two groups (all P > 0.05). Quadriceps muscle strength at 2 h, 12 h, 24 h, and 48 h postoperatively was significantly higher in the CACB group than in the CFNB group (all P < 0.001). The total incidence of adverse events was significantly lower in the CACB group (17.5%) than in the CFNB group (32.5%, P = 0.045), and patient satisfaction with analgesia was significantly higher in the CACB group (P = 0.048). Ultrasound-guided CACB yields comparable analgesic efficacy compared with CFNB in patients undergoing ORIF of patellar fractures; CACB resulted in significantly less impairment of quadriceps muscle strength than CFNB, with fewer adverse events and higher patient satisfaction. CACB creates favorable conditions for early postoperative functional rehabilitation, aligns with ERAS principles, and is a safe and effective regional analgesic technique worthy of further clinical validation and consideration in appropriate patient populations undergoing patellar fracture surgery. This trial was registered with ChiCTR (ChiCTR1800017828) on August 16, 2018.
Kinesthetic motor imagery (KMI) likely involves forward model-based prediction of the somatosensory consequences of imagined actions, as suggested by sensory attenuation observed during KMI. As visual motor imagery (VMI) and KMI have been suggested to share partially overlapping neural mechanisms, we hypothesized that VMI may also engage forward model-based prediction. Here, we tested this hypothesis by examining sensory attenuation during VMI using a force-matching task. In this task, a reference force was applied to the relaxed left index finger during rest, motor execution, KMI, or VMI involving right index finger pressing, and participants then reproduced its magnitude. In Experiment 1, the right index finger was positioned directly above the left index finger, allowing prediction of somatosensory input to the left index finger via forward models. Sensory attenuation, defined as a reduction in the reproduced force relative to the rest condition, was observed during KMI and VMI. In Experiment 2, which served as a control condition to rule out the possibility that sensory attenuation was driven by differences in cognitive demands, the right index finger was positioned 250 mm to the right of the left index finger. In this configuration, forward models would not predict finger contact, whereas cognitive demands were comparable to those in Experiment 1. No sensory attenuation was observed during KMI or VMI. Therefore, the sensory attenuation observed in Experiment 1 was not attributable to differences in cognitive demands across conditions. These findings suggest that VMI may recruit forward models to predict the sensory consequences of imagined movements.