共找到 20 条结果
A 30-year-old man patient presented with the progressive weakness and pain in the back, arms and legs, sensory loss, facial weakness, diplopia, difficulty of speech and swallowing since 4 months. MRI revealed syringomyelia and syringocephaly involving medulla (syringobulbia), pons (syringopontia) and midbrain (syringomesencephaly) with intrasyringeal hemorrhage.
The neurological examination has evolved from rudimentary clinical observations in ancient civilizations to a structured and indispensable tool in modern medical diagnostics. Early contributions from Hippocratic medicine emphasized the brain as the seat of cognition and introduced systematic observation of neurological signs. In the 19th century, figures such as Jean-Martin Charcot, Wilhelm Erb, William Gowers, and Joseph Babinski established the foundations of the modern neurological exam through anatomoclinical correlations, standardization of reflex assessment, and structured clinical reasoning. Throughout the 20th century, seminal textbooks-such as those by Mills, McKendree, DeJong, and Wartenberg-helped consolidate and disseminate neurological semiology globally. More recently, evidence-based approaches, exemplified by Steven McGee's work, have introduced statistical rigor to bedside examinations. Despite advances in neuroimaging and electrophysiology, examinations remain a cornerstone of clinical neurology, guiding diagnosis, promoting cost-effective care, and reinforcing the doctor-patient relationship.
Neurologists often encounter medically refractory epileptic patients, who manage to suppress focal motor seizures by means of various types of sensorimotor stimulation. The aim of this article is to provide a critical evaluation of the historical investigations of such abatement methods. Peripheral therapies for epilepsies have been recommended since antiquity, but it was not until the nineteenth century that physicians mentioned patients reporting being able to stop seizures by sensorimotor mechanisms. Both the reports of patients and the analysis of the various methods used became more accurate with the descriptions by physicians such as Louis Odier (1748-1817) and Théodore Herpin (1799-1865). John Hughlings Jackson (1835-1911) and William Richard Gowers (1845-1915) provided a more solid theoretical framework for (somato)sensory interventions by developing new insights into brain control of movement sequences that are well within the range of current hypotheses. In more recent studies, individual reports of successful inhibition of seizures continue to appear. The wide array of historical studies of peripheral sensory stimulation methods offers a valuable source of information for future research that may potentially lead to new therapeutic avenues and to greater effectiveness in the management of the disease burden.
In 1885, William Gowers proposed that epilepsy is a progressive disease, based on clinical evidence before any effective treatments were available. His long-standing hypothesis has been summarized with the statement "seizures beget seizures." Whether this is the case and related questions about seizure-induced modification and damage of brain circuits are of fundamental importance for neurobiological understanding of epilepsy, development of effective treatment strategies, clinical management, and prognostication. Consensus about progression and seizure-induced damage has remained controversial. Here, we critically review these long-standing questions, incorporating perspectives about perceived inconsistencies in past studies, potential implications of recent longitudinal imaging and cognitive studies, and emphasize experimental and clinical gaps that have proved challenging. Answers to these questions are important for development of management strategies to achieve prompt effective acute control of seizures and prevention of their potential recurrence and long-term comorbidities.
Surgical services were poorly prepared for the COVID-19 pandemic, leading to widescale disruption to elective activity. This study aimed to identify actionable priorities to strengthen pandemic preparedness of surgical and hospital systems. This study pooled data from three international, prospective cohort studies including patients who had a positive SARS-CoV-2 test result in the seven days before or within 30 days after surgery. Patients were included across four pandemic time periods: Period 1 (January-May 2020), Period 2 (June-July 2020), Period 3 (October 2020), and Period 4 (December-March 2022). The primary outcome measure was 30-day postoperative mortality. Hierarchical logistic regression models were developed to explore association between pandemic periods (primary analysis) and hospital-level preparedness (secondary analysis) on 30-day postoperative mortality. Hospital preparedness was classified in to poorly-, moderately-, and highly-prepared tertiles based on Surgical Preparedness Index (SPI) score. A total of 31,751 patients were included from 1589 hospitals and 102 countries. From Period 1 through to Period 4 there was a decrease in the proportion of patients aged ≥70 years and with ASA grades 3-5.30-day postoperative mortality fell from Period 1 (18.4% [1378/7502]), Period 2 (9.9% [219/2234], adjusted odds ratio (aOR) 0.65, 95% confidence interval (CI) 0.53-0.78), Period 3 (10.5% [246/2427], aOR 0.60, 95% CI 0.50-0.71), through to Period 4 (5.8% [1132/19,588], aOR 0.33, 95% CI 0.30-0.37). During Period 4, SARS-CoV-2 vaccinated patients had lower mortality compared to unvaccinated patients (4.9% [603/12,361] versus 7.4% [529/7178], aOR 0.49, 95% CI 0.42-0.57). Compared to poorly-prepared hospitals (11.2% [1019/9071]), moderately-prepared (9.4% [857/9071], aOR 0.84, 95% CI 0.75-0.94) and highly-prepared hospitals (5.8% [530/9071], aOR 0.70, 95% CI 0.62-0.80) had lower mortality. Postoperative mortality decreased over the course of the COVID-19 pandemic and was lower in better prepared hospitals. Hospitals are critical national infrastructure and strengthening their preparedness by developing formal pandemic plans, establishing patient and procedure prioritisation protocols, and ring-fencing surgical beds would ensure safer surgical care during future pandemics. National Institute for Health and Care Research, United Kingdom.
Accurately measuring compound binding affinities is key to driving the pharmaceutical development process. Rigorous physics-based in silico approaches, particularly alchemical free energy methods, have become a gold-standard tool for estimating compound affinity changes. Here we present the results of a large-scale precompetitive collaborative assessment of relative binding free energy (RBFE) calculations generated by 15 pharmaceutical companies. We evaluate an open-source and MIT-licensed RBFE protocol from the Open Free Energy (OpenFE) ecosystem across both public and blinded private datasets, encompassing over 1,700 ligands in total. For the public dataset, the weighted RMSE across the 58 systems was 1.731.531.96 kcal/mol, with 10 of the systems reaching sub-kcal/mol accuracy. For the private dataset, the weighted RMSE across the 37 systems was 2.441.943.06 kcal/mol, with only 2 of the systems reaching sub-kcal/mol accuracy, reflecting the increased complexity of real-world drug discovery. The protocol's performance was system-dependent, with no single dominant error source, indicating that accuracy is primarily influenced by input quality and transformation type. Overall, these benchmark results are encouraging and indicate that OpenFE is ready for large-scale industrial applications, with an "out-of-the-box" accuracy that approaches that of commercial solutions. While comparison against published FEP+ results, which were obtained after manual parameter optimization, shows comparable ranking statistics, a gap remains in error statistics, for which we outline possible paths toward improvement. The protocol meets key criteria required for production use in an industrial setting: it shows robust performance, generates reproducible results, and achieves both sufficient throughput and rapid convergence.
Low-dose computed tomography (LDCT) employed in lung cancer screening (LCS) programmes is increasing in uptake worldwide. LCS programmes herald a generational opportunity to simultaneously detect cancer and non-cancer-related early-stage lung disease, yet these efforts are hampered by a shortage of radiologists to interpret scans at scale. Here, we present TANGERINE, a computationally frugal, open-source vision foundation model for volumetric LDCT analysis. Designed for broad accessibility and rapid adaptation, TANGERINE can be fine-tuned off the shelf for a wide range of disease-specific tasks with limited computational resources and training data. The model is pretrained using self-supervised learning on more than 98,000 thoracic LDCT scans, including the United Kingdom's largest LCS initiative to date and 27 public datasets. By extending a masked autoencoder framework to three-dimensional imaging, TANGERINE provides a scalable solution for LDCT analysis, combining architectural simplicity, public availability, and modest computational requirements. TANGERINE demonstrates superior computational and data efficiency in a retrospective multi-dataset analysis: it converges rapidly during fine-tuning, requiring significantly fewer graphics processing unit hours than models trained from scratch, and achieves comparable or superior performance using only a fraction of the fine-tuning data. The model achieves strong performance across 14 disease classification tasks, including lung cancer and multiple respiratory diseases, and generalises robustly across diverse clinical centres. TANGERINE's accessible, open-source, lightweight design lays the foundation for rapid integration into next-generation medical imaging tools, enabling lung cancer screening programmes to pivot from a singular focus on lung cancer detection toward comprehensive respiratory disease management in high-risk populations. Lung cancer screening uses low-dose chest scans to find cancer early, but these scans can also reveal other diseases before symptoms appear. Interpreting large numbers of scans is challenging due to the limited number of radiologists worldwide. We introduce TANGERINE, an efficient and easy-to-use, open-source AI model that can analyse three-dimensional chest scans efficiently and accurately. The model learns patterns from thousands of scans and can then be adapted to detect lung diseases using only small amounts of new data. TANGERINE performs as well as, or better than, more complex systems while using less computing power. Its open-source design provides a foundation for future tools that could make advanced scan analysis more accessible, supporting earlier diagnosis and improved lung health worldwide.
Lung cancer is the leading cause of cancer-related death worldwide. Low-dose CT (LDCT) screening improves outcomes by detecting early-stage cancers as pulmonary nodules. As most are benign, diagnosing these nodules is challenging and often requires surveillance imaging. The aim of this study is to assess the frequency of cancer progression in a lung cancer screening study as measured by tumour stage (T-stage). SUMMIT is a prospective cohort study assessing implementation of lung cancer screening with LDCT in a high-risk population. Screen-detected lung cancers with clinical tumour stage cT1a-c at time of referral were included. Upstaging was defined as an increase in T-stage from referral to treatment. The date of death was obtained from the National Cancer Registration and Analysis Service. Cox proportional hazards analysis with adjustment for age, sex, Charlson Comorbidity Index and pack years was used to assess mortality between groups. 390 screen-detected cancers were stage cT1a-c at time of referral. Upstaging occurred more frequently in cT1a (n=48, 56%) compared with cT1b (n=83, 38%) or cT1c (n=34, 40%), p=0.01. The proportion of part-solid nodules was similar between groups (upstaged-N=47, 27%, vs not upstaged-N=45, 21%, p=0.19). 43% of tumours increased T-stage from referral to first treatment (n=165). In participants upstaged, time from referral to treatment was longer (upstaged: 84 days, 46-298 vs not upstaged: 72 days, 43-211, p=0.04). Adjusted overall survival analyses showed an association between upstaging and mortality (HR 1.68, 95% CI 1.13 to 2.51, p=0.01). Tumour upstaging occurred in nearly half of early-stage cases in a lung cancer screening population. Tumour upstaging was associated with longer time to treatment and poorer outcomes in this population. NCT03934866.
Neuronal function depends on mitochondria, but little is known about their organization across neurons. Using an electron microscopy Drosophila connectome, we uncovered quantitative rules governing the morphology and positioning of hundreds of thousands of mitochondria across thousands of neurons. We discovered that mitochondrial morphological features are specific to cell and neurotransmitter type, which provides fingerprints to identify neurons. Mitochondria are positioned with 2- to 3-micrometer precision relative to synaptic and structural features, with systematic differences across neuron types and compartments. Mitochondrial localization correlates with regional activity and postsynaptic targets. Analysis of a mouse visual cortex connectome confirms cell type-specific morphology and identifies partially divergent positioning rules. These results establish mitochondria as circuit-embedded organelles whose distribution links subcellular architecture to brain connectivity.
This position statement is intended to synthesize and interpret current consensus and salient developments regarding the relationship between obesity and physical activity. It draws from the latest evidence and guidelines to update and share the World Obesity Federation's stance with policymakers, healthcare professionals, public health stakeholders, and civil society organizations. This statement identifies the critical role of physical activity in the prevention and management of obesity, highlights the lived experience of people with obesity, summarizes global recommendations, and considers the emerging connections between obesity, climate change, and physical activity.
Cannabis use has increased worldwide, with over 188 million users annually. In Spain, past-year prevalence among people aged 15-64 is 10.6%. Dual use of cannabis and tobacco is common, increasing health risks and complicating cessation. This study examines consumption patterns and cannabis withdrawal severity among dual users undergoing treatment for cannabis use disorder (CUD). A cross-sectional study was conducted in substance use treatment programs in Catalonia, Spain. Participants were cannabis users initiating CUD treatment. A questionnaire collected sociodemographic data, cannabis and tobacco use characteristics (e.g., number of spliffs, tobacco amount), nicotine dependence, motivation to quit, and cannabis withdrawal symptoms. Hierarchical cluster analysis using Gower's distance identified behavioral patterns among participants. Data from 94 participants seeking CUD treatment were included. Daily tobacco use was reported by 91.5%, with a mean Fagerström score of 4.2/10. Most participants (88.1%) co-used cannabis with tobacco, and 75.8% experienced cannabis withdrawal symptoms, with women reporting greater severity. Cluster analysis revealed two profiles: Cluster 1 (71.0%) included mostly older males with higher motivation to quit and fewer withdrawal symptoms; Cluster 2 (29.0%) was younger, more sex-balanced, and showed higher nicotine dependence, and more severe withdrawal symptoms. Co-use of cannabis and tobacco is highly prevalent among individuals entering CUD treatment. Higher nicotine dependence is associated with more severe withdrawal symptoms. Older males with higher motivation and fewer withdrawal symptoms may have better prognosis, highlighting motivation as cessation predictor. Findings underscore the need to enhance motivation to quit both substances and integrated treatment.Trial registration number. The DuCATA project has been registered at Clinicaltrials.gov under the identifier [NCT05512091].
BACKGROUND: Spinal muscular atrophy (SMA) is a rare autosomal recessive genetic disorder characterized by severe neurological and muscular degeneration, often leading to severe disability or death. Its complex clinical manifestations frequently result in misdiagnosis or missed diagnosis. Type IV SMA primarily affects adults, rarely impacting normal lifespan or maximum motor capacity, and is clinically uncommon. However, SMA presenting with pseudohypertrophy of the gastrocnemius muscle and near-complete loss of motor function is extremely rare and has not been previously reported. We hereby report what we believe to be the first case of Type IV SMA caused by SMN1 deletion presenting with pseudohypertrophy of the gastrocnemius muscle. CASE PRESENTATION: A 51-year-old man presented with progressive weakness in all four limbs over 16 years, which worsened over the past two months, leaving him unable to walk. Examination strongly suggested a diagnosis of SMA type IV. He was found to have a homozygous deletion of the SMN1 gene at exon 7, located on 5q13.2. Muscle strength in the biceps brachii and triceps brachii of both upper limbs was grade IV, with weakened grip strength in both hands. Grade III muscle strength in the quadriceps of both lower limbs, Grade IV muscle strength in the tibialis anterior, gastrocnemius, and extensor hallucis longus muscles, bilateral knee reflexes and Achilles reflexes (+), right Hoffmann’s sign (+), bilateral Babinski signs (+), and Gower’s sign (+). Multiple disc herniations with degeneration in the cervical spine. Multiple muscle atrophy of the thoracic wall. Electromyography of the limbs shows neurogenic changes. However, symptoms such as pseudohypertrophy of the gastrocnemius muscle and almost complete loss of motor function are rare, suggesting a poor prognosis. CONCLUSION: This rare case highlights that pseudohypertrophy of the gastrocnemius muscle may be a rare manifestation of type IV spinal muscular atrophy, and clinical differential diagnosis should be made with PMD and other diseases.
This randomized controlled trial investigated the effectiveness of supervised lumbopelvic stabilization and urotherapy on factors associated with lower urinary tract symptoms in children with Duchenne Muscular Dystrophy and lower urinary tract dysfunction (LUTD). The study included 32 children aged 5-12 years, who were ambulatory and had a Dysfunctional Voiding and Incontinence Symptom Scale (DVISS) of 8.5 or higher. Lower urinary tract symptoms were assessed using the DVISS, a three-day bladder diary, and a nocturnal enuresis diary. Bowel symptoms were assessed with a seven-day bowel diary. Moreover, physical performance tests, the strength of pelvis-related muscle groups, and participation in activities of daily living were evaluated using validated measurement tools. Participants were randomized into two groups: the active control group (n:16, weight:25.81±9.53 kg, height:121.25±18.22 cm) received only urotherapy, while the treatment group (n:16, weight:25.88±9.67 kg, height: 122.69±16.63 cm) additionally performed lumbopelvic stabilization-based exercises for eight weeks under the supervision of a physiotherapist. Urotherapy significantly reduced LUTD severity (p < 0.001), enuresis frequency (p = 0.014), and the number of symptoms associated with LUTD (p = 0.001). However, adding lumbopelvic stabilization exercises conferred no superiority over urotherapy alone (p > 0.05). Supervised lumbopelvic stabilization improved functional mobility (p < 0.003), muscle strength (p < 0.05), and participation in activities of daily living (p < 0.049). However, neither urotherapy nor lumbopelvic stabilization training had a significant effect on Gower's time or daytime voiding frequency (p > 0.05). Both interventions were effective in improving bladder and bowel outcomes in children with Duchenne Muscular Dystrophy and LUTD, with no superiority observed on lower urinary tract symptoms.
Genetic testing using targeted panels or comprehensive genome sequencing is the current standard for diagnosing Duchenne muscular dystrophy (DMD), identifying pathogenic variants in up to 98% of cases. We report a 5-year-old male presenting with delayed motor milestones, frequent falls, and difficulty climbing stairs due to generalized muscle weakness. Laboratory studies revealed markedly elevated CK (13,041 U/L) and chronic transaminase elevation. Clinical examination demonstrated Gower's sign, calf pseudohypertrophy, neuromuscular scoliosis, and cognitive impairment. Initial neuromuscular gene panel testing identified several variants of uncertain significance, and muscle biopsy showed markedly reduced dystrophin labeling. Follow-up short-read DMD sequencing with deletion/duplication analysis at Age 11 remained negative. Given persistently negative findings, we utilized optical genome mapping (Bionano Genomics) and long-read sequencing (Oxford Nanopore Technologies) to identify potential structural variants. Both methods independently detected a novel inversion identified to span 31 kb and encompassing exons 68-73 of the DMD gene (ChrX: 31,171,362-31,202,982), classified as pathogenic. This case highlights a clinically definitive diagnosis of DMD missed by standard genetic testing. Our findings demonstrate that Optical Genome Mapping and Long-Read Sequencing provide complementary, high-resolution tools for identifying previously unidentified structural variants and should be considered in unresolved cases prior to invasive procedures such as muscle biopsy.
Premature neonates are particularly vulnerable and therefore require rigorous monitoring of analytes such as glucose and lactate. Traditionally, this is achieved through invasive, intermittent blood sampling, which is painful and may cause potential complications. To address this issue, we have developed a noninvasive perfusable skin sampling patch designed to collect analytes from low-volume thermoregulatory sweat without the need for external sweat induction. This can be combined with microfluidic biosensor analysis technologies to detect skin glucose and lactate levels. We were able to demonstrate the potential of this technology for noninvasive measurement of glucose and lactate in premature neonates. Our results showed that skin glucose levels correlated well with time-matched blood glucose measurements. Lactate skin measurements did not correlate with blood measurements, indicating a more complex relationship. In addition, we successfully measured skin glucose levels in healthy adults, which correlated with blood glucose levels for each individual. In contrast with the neonate measurements, the relationship between blood and skin glucose varies between individual adults. We successfully carried out proof-of-concept experiments to detect glucose in real-time in both neonates and in healthy adults by connecting the sampling patch to a continuous analysis system. These results provide the groundwork for subsequent large-scale clinical trials intended to validate the system reliability and clinical applicability within health care contexts, particularly neonatal intensive care units.
Phase-based X-ray microtomography is a powerful technique capable of quantitative volumetric imaging of lung tissue in health and disease. The maximum sample size is however limited by the fixed sizes of detectors and optical elements. Thus while high-resolution imaging can offer valuable microscale insights, it can be difficult to interpret without the context of the surrounding tissue. We propose a multi-contrast and multi-scale approach, combined with an offset geometry to extend the field-of-view (FOV). FOV limitations make it a challenge to simultaneously achieve high spatial-resolution and image large samples. Our method doubles the possible FOV achievable for a given spatial-resolution, in a way compatible with multiple scales and imaging systems. Multi-contrast whole sample volumetric images are acquired using a beam-tracking X-ray phase-contrast imaging(XPCI) system. Following this, a section of the same sample is imaged at higher resolution using an X-ray microscope with propagation-based imaging. The FOV of both methods is doubled using an offset center-of-rotation geometry, followed by weighted analytical reconstruction. We present exemplary multi-contrast reconstructions of resected human lung tissue at 10.5 μ m $\umu{\rm m}$ voxel size across a 4.3 cm horizontal FOV, and at 450 nm voxel size for a 2.7 mm section of the same sample. This enables the visualization of a range of features, from the macro to the cellular scale. We demonstrate a versatile method to image large samples without sacrificing spatial-resolution. This method is directly compatible with complementary implementations of XPCI, and is easily adapted to a range of other systems.
The most frequent type of aura preceding the migraine headache is the visual one. The visual perception of the migraineur can be variegated, the most common being a zig-zag pattern of luminous lines, the complete denomination of this phenomenon being "fortification spectra of Vauban". We investigated on original sources about the origin of this complex denomination and more in detail about the eponym and the priority on the construction of the Reinassance fortification. This kind of visual aura was compared to Reinassance fortifications by John Fothergill. (1712-1780). In 1870 Hubert Airy, reporting on his own attack of migraine with aura, compared the visual disturbance to a fortified town with its bastions of a colourful appearance. Moreover, realising the illusory nature of these images, he called them "fortification spectra". Later on, William Gowers (1845-1915), with reference to ".its projecting and reintrant angles bearing resemblance to the plan which the French engineer Vauban first described as the most effective for the defence of a fortress.", introduced the term "fortification of Vauban", that since then has been largely used. Historically, these kinds of fortifications were first developed in early sixteen century in Italy by Michele Sanmicheli (1484-1559), a Venetian military engineer, when medieval tall courtains and circular towers were substituted with low and thicker walls and polygonal bastions, to face the destroying power of the new mobile siege guns. Only later Sébastien Le Prestre De Vauban (1633-1707), at the service of Louis XIV, the Sun King, greatly contributed to the development of this branch of military engineering. With reference to the visual aura, the eponym "fortifications spectra of Vauban" should be substituted for that "of Sanmicheli".
Thyroid dysfunction is typically associated with systemic metabolic disturbances and may also present as thyroid myopathy. Understanding this relationship is crucial for recognizing its clinical manifestations and guiding appropriate management. This report describes the case of a 29-year-old male who presented with unusual swelling in his right leg along with persistent stiffness in his calf muscles. Physical examination revealed striking diffuse pseudo-hypertrophy of the calf muscles, accompanied by a positive Gowers' sign, indicating underlying muscular weakness. Laboratory investigations confirmed classic features of hypothyroidism, including markedly low triiodothyronine (T3) and thyroxine (T4) levels, elevated thyroid-stimulating hormone (TSH), and increased muscle enzyme levels. Remarkably, following the initiation of levothyroxine therapy, the patient exhibited a dramatic and progressive improvement in symptoms. The clinical picture was consistent with Hoffman syndrome, a rare manifestation of hypothyroid myopathy marked by visibly enlarged calf muscles and progressive muscle weakness. This rapid response underscores the importance of early diagnosis and timely treatment, which can lead to a full recovery even in cases with such rare presentations. Overall, this case serves as a reminder that thyroid disorders may occasionally manifest in unexpected ways, and with prompt intervention, patients can achieve significant clinical improvement.