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Stem Cell Research Jun 2024Friedreich's ataxia (FRDA) is a rare neurodegenerative disease caused by an expansion of a GAA repeat sequence within the Frataxin (FXN) gene. Prominent regions of...
Generation of genetically modified Friedreich's ataxia induced pluripotent stem cell lines and isogenic control lines carrying an inducible neurogenin-2 expression cassette.
Friedreich's ataxia (FRDA) is a rare neurodegenerative disease caused by an expansion of a GAA repeat sequence within the Frataxin (FXN) gene. Prominent regions of neurodegeneration include sensory neurons within the dorsal root ganglia. Here we present a set of genetically modified FRDA induced pluripotent stem cell (iPSC) lines that carry an inducible neurogenin-2 (NGN2) expression cassette. Exogenous expression of NGN2 in iPSC derived neural crest progenitors efficiently generates functionally mature sensory neurons. These cell lines will provide a streamlined source of FRDA iPSC sensory neurons for studying both disease mechanism and screening potential therapeutics.
PubMed: 38936158
DOI: 10.1016/j.scr.2024.103477 -
The Journal of Hand Surgery Jun 2024To compare the biomechanical properties of adjunctive dorsal spanning plate (DSP) fixation with traditional K-wire fixation of perilunate dislocations in a cadaveric...
PURPOSE
To compare the biomechanical properties of adjunctive dorsal spanning plate (DSP) fixation with traditional K-wire fixation of perilunate dislocations in a cadaveric model.
METHODS
Fourteen fresh-frozen cadaveric wrists underwent simulated perilunate injury. The specimens were randomly allocated to either K-wire fixation versus K-wire and DSP fixation. Scapholunate (SL) ligament repair was performed in all specimens. The constructs were tested using a robot cyclically and to failure. Fluoroscopic images were obtained of the specimens prior to simulated injury, after fixation, after 10 and 100 loading cycles, and at construct failure. Differences in carpal alignment parameters (SL interval, SL angle, lunotriquetral interval, and capitolunate angle) and load to failure were recorded.
RESULTS
There were no statistically significant differences between the two group's carpal alignment parameters after fixation. Specimens fixated with K-wires and DSP required significantly higher loads to achieve construct failure. The only significant difference between the two groups' carpal alignment parameters was SL interval change at failure.
CONCLUSIONS
Compared with K-wire fixation alone, adjunctive DSP fixation resulted in significantly increased loads to failure and decreased change in SL interval at the time of failure.
CLINICAL RELEVANCE
Adjunctive DSP may be a useful technique in the polytraumatized patient in whom providing back a weight-bearing extremity may be advantageous in the rehabilitation process.
PubMed: 38934992
DOI: 10.1016/j.jhsa.2024.04.016 -
Indian Journal of Dental Research :... Jan 2024This case report presents a rare combination of congenital anomalies in an otherwise healthy male infant born at 36 weeks. The infant was diagnosed with congenital...
RATIONALE
This case report presents a rare combination of congenital anomalies in an otherwise healthy male infant born at 36 weeks. The infant was diagnosed with congenital maxillomandibular synechia, ectrodactyly, and ankyloglossia superior syndrome (ASS).
PATIENT CONCERNS
Inability to open the mouth completely, feeding challenges, and a cleft palate. The infant was stabilized through successful positive pressure ventilation via a face mask at birth and enteral feeding was initiated via a feeding gastrostomy.
EXAMINATION
Diagnostic tests revealed a midline palatal cleft, hypoplastic jaws, persistent metopic suture, and a bony fusion at the midline.
TREATMENT
Sectioning of the bony spur along the midline and achieving a mouth opening of 2 cm post-manipulation. The patient is under follow-up, with future treatment plans including cleft palate correction at 12 months and potential frontomandibular and lower jaw advancement depending on growth trajectories.
TAKEAWAY LESSONS
This case underscores the complexity of managing multiple congenital anomalies and the need for individualized treatment plans.
Topics: Humans; Male; Cleft Palate; Tongue; Palate, Hard; Infant, Newborn; Abnormalities, Multiple; Maxilla; Ankyloglossia; Jaw Abnormalities; Mandible
PubMed: 38934763
DOI: 10.4103/ijdr.ijdr_961_23 -
Equine Veterinary Journal Jun 2024Surgical treatment options for horses with overriding dorsal spinous processes include interspinous ligament desmotomy and partial spinous process ostectomy. The impact...
BACKGROUND
Surgical treatment options for horses with overriding dorsal spinous processes include interspinous ligament desmotomy and partial spinous process ostectomy. The impact of spinal surgery on the three-dimensional biomechanics of the equine thoracolumbar spine and the epaxial musculature is unclear.
OBJECTIVES
To investigate the influence of interspinous ligament desmotomy and cranial wedge ostectomy on the biomechanics of the equine thoracolumbar spine and the paraspinal Musculi multifidi.
STUDY DESIGN
Ex-vivo experiments.
METHODS
Twelve equine thoracolumbar spine specimens were mounted in a custom-made mechanical test rig. Based on computed tomographic imaging, distances between dorsal spinous processes and the spinal range of motion (lateral bending, axial rotation, flexion, extension) were compared before and after desmotomy and cranial wedge ostectomy performed at two or five surgical sites. Anatomical dissection was subsequently conducted to document surgical trauma to the Musculi multifidi following desmotomy.
RESULTS
The distance between spinous processes in neutral position did not increase significantly after desmotomy (median preoperative = 7.2 mm, interquartile range [IQR] = 3.6 mm; median postoperative = 7.4 mm, IQR = 3.7 mm; p = 0.09), but increased significantly after ostectomy (median preoperative = 8.8 mm, IQR = 4.2 mm; median postoperative = 13 mm, IQR = 6.1 mm; p < 0.001). Both surgical procedures significantly increased the rotational spinal range of motion (p = 0.001), particularly at the level T14/T15 (median preoperative = 6.4°, IQR = 3.2°; median postoperative = 8.2°, IQR = 3.5°; increase = 28.1%; p = 0.02). Musculi multifidi injury was evident at all desmotomy sites.
MAIN LIMITATIONS
Ex-vivo study with limited sample size.
CONCLUSIONS
Neither interspinous ligament desmotomy nor cranial wedge ostectomy resulted in an increased range of motion during flexion, extension or lateral bending but both procedures influenced the rotational component of the equine thoracolumbar spinal mobility.
PubMed: 38934728
DOI: 10.1111/evj.14123 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2024In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that...
In addition to metabolic and cardiovascular disorders, obesity is associated with cognitive deficits in humans and animal models. We have previously shown that obesogenic high-fat and sugar diet intake during adolescence (adoHFSD) impairs hippocampus (HPC)-dependent memory in rodents. These results were obtained in males only and it remains to evaluate whether adoHFSD has similar effect in females. Therefore, here, we investigated the effects of adoHFSD consumption on HPC-dependent contextual fear memory and associated brain activation in male and female mice. Exposure to adoHFSD increased fat mass accumulation and glucose levels in both males and females but impaired contextual fear memory only in males. Compared with females, contextual fear conditioning induced higher neuronal activation in the dorsal and ventral HPC (CA1 and CA3 subfields) as well as in the medial prefrontal cortex in males. Also, adoHFSD-fed males showed enhanced c-Fos expression in the dorsal HPC, particularly in the dentate gyrus, and in the basolateral amygdala compared with the other groups. Finally, chemogenetic inactivation of the dorsal HPC rescued adoHFSD-induced memory deficits in males. Our results suggest that males are more vulnerable to the effects of adoHFSD on HPC-dependent aversive memory than females, due to overactivation of the dorsal HPC.
Topics: Animals; Fear; Male; Female; Hippocampus; Diet, High-Fat; Obesity; Sex Characteristics; Mice; Memory; Mice, Inbred C57BL; Prefrontal Cortex
PubMed: 38934712
DOI: 10.1093/cercor/bhae254 -
Neural Regeneration Research Jun 2024Successful polyethylene glycol fusion (PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to: (1) rapidly restore...
Successful polyethylene glycol fusion (PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to: (1) rapidly restore electrophysiological continuity; (2) prevent distal Wallerian Degeneration and maintain their myelin sheaths; (3) promote primarily motor, voluntary behavioral recoveries as assessed by the Sciatic Functional Index; and, (4) rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex (e.g., toe twitch) or voluntary behaviors. The preceding companion paper describes sensory terminal field reorganization following PEG-fusion repair of sciatic nerve transections or ablations; however, sensory behavioral recovery has not been explicitly explored following PEG-fusion repair. In the current study, we confirmed the success of PEG-fusion surgeries according to criteria (1-3) above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats. Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws. Dorsal von Frey filament test was a more reliable method than plantar von Frey filament test to assess mechanical nociceptive sensitivity following sciatic nerve transections. Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex. Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats. Following sciatic transection, all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury. However, PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats. Furthermore, PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recovery compared with those without Sciatic Functional Index recovery, suggesting a correlation between successful pPEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries. This correlation was independent of the sex or strain of the rat. Furthermore, our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths. No chronic hypersensitivity developed in any rat up to 12 weeks. All these data suggest that PEG-fusion repair of transection peripheral nerve injuries could have important clinical benefits.
PubMed: 38934383
DOI: 10.4103/NRR.NRR-D-23-01846 -
Stereotactic and Functional Neurosurgery Jun 2024In tremor syndromes, pharmacological therapy is the primary treatment, but deep brain stimulation (DBS) is used when it is insufficient. We explore the use of DBS,...
INTRODUCTION
In tremor syndromes, pharmacological therapy is the primary treatment, but deep brain stimulation (DBS) is used when it is insufficient. We explore the use of DBS, focusing on the globus pallidus internus for dystonia and the ventral intermediate nucleus (VIM) for tremor conditions. We introduce the posterior subthalamic area (PSA) as a potential target, suggesting its efficacy in tremor reduction, particularly in rare tremor syndromes. We aim to evaluate the efficacy and safety of double targeting the VIM and PSA in rare tremor conditions, highlighting the limited existing data on this.
METHODS
Between 2019 and 2023, 22 patients with rare tremor syndromes were treated with bilateral DBS of the VIM and PSA. This case series consisted of 7 isolated head tremor, 1 hepatic encephalopathic tremor due to Abernethy syndrome, 2 voice tremor, 4 dystonic tremor, and 8 Holmes tremor (2 multiple sclerosis, 2 cerebellar insult, and 4 posttraumatic) patients. Patients' preoperative and 12-month postoperative tremor scores were compared, and the optimum VIM and PSA stimulation areas were investigated.
RESULTS
There was a significant reduction in the mean TRS score from 3.70 (±0.57) to 0.45 (±0.68) after 12 months of surgery. Specific outcomes for different indications were observed: for head tremor, 6 of 7 patients showed a reduction in TRS scores to 0 points; the vocal tremor patients demonstrated improvement; this change was not statistically significant, which is likely to be due to the low number of patients in this subgroup; the dystonic tremor patients showed either complete tremor abolition or a reduction in TRS scores; the Holmes tremor patients showed an 80% reduction in TRS scores; and the hepatic encephalopathy tremor and Abernethy syndrome patients showed a 75% improvement in TRS scores. The stimulation parameters converged on the VIM and dorsal PSA. Complications included the need for electrode repositioning, infections requiring electrode removal and re-implantation, dysarthria, and stimulation-induced ataxia, which was resolved by adjusting the stimulation parameters.
DISCUSSION
The literature on DBS for rare tremors is limited. Double targeting of the VIM and PSA appears to produce promising improvements on the outcomes reported in the existing literature on VIM-only DBS. The proximity of the VIM and PSA allows for flexible electrode placement, contributing to the potential success of the dual-target approach. We also discuss the theoretical advantages of targeting the PSA based on the distribution of tremor circuits, emphasizing the need for further research and electrophysiological studies.
PubMed: 38934181
DOI: 10.1159/000539162 -
Frontiers in Veterinary Science 2024A spayed, 8-year-old female Poodle, weighing 5.7 kg, was presented with the chief complaint of vision impairment. Vision assessment, including pupillary light...
Case report: Unilateral papilledema in a dog with a large suprasellar mass and suspected intracranial hypertension: insights from funduscopy, optical coherence tomography, and magnetic resonance imaging.
A spayed, 8-year-old female Poodle, weighing 5.7 kg, was presented with the chief complaint of vision impairment. Vision assessment, including pupillary light reflexes, menace response, dazzle reflex, and maze navigation in photopic and scotopic circumstances, revealed a negative response in both eyes except for positive direct pupillary light reflex in the right eye and positive consensual pupillary light reflex from the right eye to the left eye. Systemic evaluation, including neurologic status, blood profile, and thoracic radiographs, did not reveal any abnormalities. Complete ophthalmic examinations, ocular ultrasonography, and electroretinography did not identify a cause of blindness. Upon funduscopy, the left eye exhibited an increased optic disk diameter, blurred optic disk borders, and loss of the physiologic pit, as well as an increase in vascular tortuosity. In the right eye, there were multifocal depigmented areas in the non-tapetal fundus and several pigmented spots surrounded by a region of dull tapetal reflection in the tapetal fundus. The optical coherence tomography revealed severe anterior deformation of the optic nerve head and Bruch's membrane in the peripapillary region of the left eye. Magnetic resonance imaging revealed an irregular, broad-based suprasellar mass, with features suggestive of intracranial hypertension, including dorsal displacement of third ventricles, a rightward shift of the falx cerebri, -tentorial herniation, perilesional edema, flattening/protrusion of the posterior sclera, and lager optic nerve sheath diameter in left side than right side. This is the first comprehensive report that describes unilateral papilledema in a dog with a brain tumor, using advanced ophthalmic and neuro-imaging modalities.
PubMed: 38933701
DOI: 10.3389/fvets.2024.1372802 -
Frontiers in Pharmacology 2024Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are...
Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia. We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture. Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir Medium dried flowers (NC1) and Cannabixir THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%-89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values. Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.
PubMed: 38933665
DOI: 10.3389/fphar.2024.1395951 -
Cureus May 2024A smooth, red, oval, or rhomboid patch on the dorsal midline is the classic presentation of median rhomboid glossitis (MRG), a rare and benign lesion of the tongue. MRG...
A smooth, red, oval, or rhomboid patch on the dorsal midline is the classic presentation of median rhomboid glossitis (MRG), a rare and benign lesion of the tongue. MRG is still not fully understood, which presents diagnostic hurdles and calls for additional clinical investigation. It is frequently associated with candidal infections. We describe a case of a 42-year-old man who initially appeared to have either mechanical irritation or thermal injury related to a painless patch on the dorsum surface of the tongue. We document a case of MRG that was consulted for a standard dental examination in this case report. This article also highlights a dentist's need to identify the lesion and provide appropriate education for the patient.
PubMed: 38933609
DOI: 10.7759/cureus.61182