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Annals of Agricultural and... Jun 2024The NAA10 gene encodes N-alpha-acetyltransferase 10 which plays an important role in cell growth, differentiation, DNA damage, metastasis, apoptosis, stress response and... (Review)
Review
The NAA10 gene encodes N-alpha-acetyltransferase 10 which plays an important role in cell growth, differentiation, DNA damage, metastasis, apoptosis, stress response and autophagy. Defects in the NAA10 gene correlate with the diagnosis of NAA10-related syndrome (Ogden syndrome). The most common symptoms of NAA10-related syndrome are: global developmental delay, non-verbal or limited speech, autism spectrum disorder, feeding difficulties, motor delay, muscle tone disturbances, and long QT syndrome. To-date, there are about 100 patients who have been reported with this condition. The case report presents the clinical study of a girl aged 4 years and 3 months diagnosed with Ogden syndrome. She had many characteristic features of the disorder, as well as precocious puberty. This girl represents the case of a patient with p.Arg83Cys mutation in NAA10 gene as well as precocious puberty.
Topics: Humans; Female; Puberty, Precocious; N-Terminal Acetyltransferase A; N-Terminal Acetyltransferase E; Child, Preschool; Mutation
PubMed: 38940118
DOI: 10.26444/aaem/171758 -
Clinical and Translational Radiation... Jul 2024Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional...
PURPOSE
Preoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1).
METHODS
Eligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers.
RESULTS
Thirteen patients of median age 65 years (range 41-77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1-10) and from SRS to neurosurgery was 1 day (0-5). The median prescribed dose was 16 Gy (14-19) to a median planning target volume of 12.7 cm (5.9-26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed.
CONCLUSION
In patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.
PubMed: 38938931
DOI: 10.1016/j.ctro.2024.100798 -
Chinese Journal of Traumatology =... Jun 2024To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures.
PURPOSE
To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures.
METHODS
A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18-65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American orthopedic foot and ankle society score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test.
RESULTS
During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, preoperative complications with diabetes, smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American orthopedic foot and ankle society score revealed no significant difference between dislocation and no-dislocation patients.
CONCLUSION
Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
PubMed: 38937167
DOI: 10.1016/j.cjtee.2024.06.001 -
IEEE Transactions on Neural Systems and... Jun 2024Robotic rehabilitation has been shown to match the effects of conventional physical therapy on motor function for patients with neurological diseases. Rehabilitation...
Robotic rehabilitation has been shown to match the effects of conventional physical therapy on motor function for patients with neurological diseases. Rehabilitation robots have the potential to reduce therapists' workload in time-intensive training programs as well as perform actions that are not replicable by human therapists. We investigated the effects of one such modality that cannot be achieved by a human therapist: assistance and resistance within the electromechanical delay between muscle activation and muscle contraction during arm extension. We found increased muscle activation when providing robotic assistance within this electromechanical delay. Assistance provided within this delay moves the participant's arm quicker than their own muscle and increases the subsequent peak voluntary muscle activation compared to normal arm extension by 68.97 ± 80.05% (SE = 0.021; p = 0.007). This is surprising since all previous literature shows that muscle activation either decreases or does not change when participants receive robotic assistance. As a consequence, traditional robotic rehabilitation incrementally reduces assistance as the patient improves to maintain levels of muscle activation which is suggested to be important for neuronal repair. The present result may enable therapists to no longer have to choose between providing assistance or increasing muscle activation. Instead, therapists may be able to provide assistance while also increasing muscle activation.
PubMed: 38935467
DOI: 10.1109/TNSRE.2024.3419688 -
Journal of Neurochemistry Jun 2024Deregulated cyclin-dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous...
Deregulated cyclin-dependent kinase 5 (Cdk5) activity closely correlates with hyperphosphorylated tau, a common pathology found in neurodegenerative diseases. Previous postmortem studies had revealed increased Cdk5 immunoreactivity in amyotrophic lateral sclerosis (ALS); hence, we investigated the effects of Cdk5 inhibition on ALS model mice and neurons in this study. For the in vitro study, motor neuron cell lines with wild-type superoxide dismutase 1 (SOD1) or SOD1 and primary neuronal cultures from SOD1 transgenic (TG) mice or non-TG mice were compared for the expression of proteins involved in tau pathology, neuroinflammation, apoptosis, and neuritic outgrowth by applying Cdk5-small interfering RNA or Cdk5-short hairpin RNA (shRNA). For the in vivo study, SOD1 mice and non-TG mice were intrathecally injected with adeno-associated virus 9 (AAV9)-scramble (SCR)-shRNA or AAV9-Cdk5-shRNA at the age of 5 weeks. Weight and motor function were measured three times per week from 60 days of age, longevity was evaluated, and the tissues were collected from 90-day-old or 120-day-old mice. Neurons with SOD1 showed increased phosphorylated tau, attenuated neuritic growth, mislocalization of SOD1, and enhanced neuroinflammation and apoptosis, all of which were reversed by Cdk5 inhibition. Weights did not show significant differences among non-TG and SOD1 mice with or without Cdk5 silencing. SOD1 mice treated with AAV9-Cdk5-shRNA showed significantly delayed disease onset, delayed rotarod failure, and prolonged survival compared with those treated with AAV9-SCR-shRNA. The brain and spinal cord of SOD1 mice intrathecally injected with AAV9-Cdk5-shRNA exhibited suppressed tau pathology, neuroinflammation, apoptosis, and an increased number of motor neurons compared to those of SOD1 mice injected with AAV9-SCR-shRNA. Cdk5 inhibition could be an important mechanism in the development of a new therapeutic strategy for ALS.
PubMed: 38934222
DOI: 10.1111/jnc.16160 -
Cureus Jun 2024Although rare, acute compartment syndrome may develop as a simple elbow dislocation after reduction without initial motor, sensory, or peripheral circulatory...
Although rare, acute compartment syndrome may develop as a simple elbow dislocation after reduction without initial motor, sensory, or peripheral circulatory abnormalities. This report describes a rare case of this condition. Acute compartment syndrome remains a potential complication, even in a simple elbow dislocation without apparent initial abnormalities, and should be explained to patients. A peripheral nerve block during reduction may mask symptoms and delay recognition of acute compartment syndrome. This case highlights the importance of vigilant monitoring for acute compartment syndrome following reduction of simple elbow dislocations, especially when a peripheral nerve block is used during reduction.
PubMed: 38933345
DOI: 10.7759/cureus.63145 -
Neurology. Clinical Practice Jun 2024Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients...
BACKGROUND AND OBJECTIVES
Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020.
METHODS
This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected.
RESULTS
Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH ( = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH ( = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up.
DISCUSSION
This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned.
CLASSIFICATION OF EVIDENCE
This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort.
PubMed: 38932995
DOI: 10.1212/CPJ.0000000000200298 -
Autism Research : Official Journal of... Jun 2024Autistic children vary in symptoms, co-morbidities, and response to interventions. This study aimed to identify clusters of autistic children with a distinct pattern of...
Autistic children vary in symptoms, co-morbidities, and response to interventions. This study aimed to identify clusters of autistic children with a distinct pattern of attaining early developmental milestones (EDMs). The clustering of 5836 autistic children was based on the attainment of 43 gross motor, fine motor, language, and social developmental milestones during the first 3 years of life as recorded in baby wellness visits. K-means cluster analysis detected four EDM clusters: mild (n = 1686); moderate (n = 1691); severe (n = 2265); and global (n = 194). The most prominent cluster differences were in the language domain. The global cluster showed earlier and greater developmental delay across domains, unique early gross motor delays, and more were born preterm via cesarean section. The severe cluster had poor language development prominently in the second year of life, and later fine motor delays. Moderate cluster had mainly language delays in the third year of life. The mild cluster mostly passed milestones. EDM clusters differed demographically, with higher socioeconomic status in mild cluster and lowest in global cluster. However, the severe cluster had more immigrant and non-Jewish mothers followed by the moderate cluster. The rates of parental concerns and provider developmental referrals were significantly higher in the global, followed by the severe, moderate, and mild EDM clusters. Autistic children's language and motor delay in the first 3 years can be grouped by common magnitude and onset profiles as distinct groups that may link to specific etiologies (like prematurity or genetics) and specific intervention programs. Early autism screening should be tailored to these different developmental profiles.
PubMed: 38932567
DOI: 10.1002/aur.3177 -
Sensors (Basel, Switzerland) Jun 2024This article investigates the causes of occasional flight instability observed in Unmanned Aerial Vehicles (UAVs). The issue manifests as unexpected oscillations that...
This article investigates the causes of occasional flight instability observed in Unmanned Aerial Vehicles (UAVs). The issue manifests as unexpected oscillations that can lead to emergency landings. The analysis focuses on delays in the Extended Kalman Filter (EKF) algorithm used to estimate the drone's attitude, position, and velocity. These delays disrupt the flight stabilization process. The research identifies two potential causes for the delays. First cause is magnetic field distrurbances created by UAV motors and external magnetic fields (e.g., power lines) that can interfere with magnetometer readings, leading to extended EKF calculations. Second cause is EKF fusion step implementation of the PX4-ECL library combining magnetometer data with other sensor measurements, which can become computionally expensive, especially when dealing with inconsistent magnetic field readings. This can significantly increase EKF processing time. The authors propose a solution of moving the magnetic field estimation calculations to a separate, lower-priority thread. This would prevent them from blocking the main EKF loop and causing delays. The implemented monitoring techniques allow for continuous observation of the real-time operating system's behavior. Since addressing the identified issues, no significant problems have been encountered during flights. However, ongoing monitoring is crucial due to the infrequent and unpredictable nature of the disturbances.
PubMed: 38931611
DOI: 10.3390/s24123826 -
Materials (Basel, Switzerland) Jun 2024Stainless steel grade 430 is a type of soft magnetic electromagnetic material with rapid magnetization and demagnetization properties. Considering the delay phenomenon...
Stainless steel grade 430 is a type of soft magnetic electromagnetic material with rapid magnetization and demagnetization properties. Considering the delay phenomenon during operation, this study selected 430 stainless steel as the material and explored various metallurgical methods such as magnetic annealing and the addition of Mo as well as increasing the Si content to investigate the microstructure, mechanical behavior, and magnetic properties of each material, aiming to improve the magnetic properties of 430 stainless steel. Experimental results showed that the four electromagnetic steel materials (430F, 430F-MA, 434, and KM31) had equiaxed grain matrix structures, and excellent tensile and elongation properties were observed for each specimen. Additionally, the magnetic properties of the 430F specimen were similar under the DC and AC-10 Hz conditions. According to the hysteresis curves under different AC frequencies (10, 100, 1000 Hz), both magnetic annealing and the addition of Mo could reduce the Bm, Br, and Hc values of the raw 430F material. Increasing the Si content resulted in a decrease in Hc values and an increase in Bm and Br values.
PubMed: 38930368
DOI: 10.3390/ma17122998