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Acta Neuropathologica Communications Jun 2024Down syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and...
Down syndrome (DS) is a common genetic condition caused by trisomy of chromosome 21. Among their complex clinical features, including musculoskeletal, neurological, and cardiovascular disabilities, individuals with DS have an increased risk of developing progressive dementia and early-onset Alzheimer's disease (AD). This dementia is attributed to the increased gene dosage of the amyloid-β (Aβ) precursor protein gene, the formation of self-propagating Aβ and tau prion conformers, and the deposition of neurotoxic Aβ plaques and tau neurofibrillary tangles. Tau amyloid fibrils have previously been established to adopt many distinct conformations across different neurodegenerative conditions. Here, we report the characterization of brain samples from four DS cases spanning 36-63 years of age by spectral confocal imaging with conformation-specific dyes and cryo-electron microscopy (cryo-EM) to determine structures of isolated tau fibrils. High-resolution structures revealed paired helical filament (PHF) and straight filament (SF) conformations of tau that were identical to those determined from AD cases. The PHFs and SFs are made of two C-shaped protofilaments, each containing a cross-β/β-helix motif. Similar to filaments from AD cases, most filaments from the DS cases adopted the PHF form, while a minority (approximately 20%) formed SFs. Samples from the youngest individual with no documented dementia had sparse tau deposits. To isolate tau for cryo-EM from this challenging sample we used a novel affinity-grid method involving a graphene oxide surface derivatized with anti-tau antibodies. This method improved isolation and revealed that primarily tau PHFs and a minor population of chronic traumatic encephalopathy type II-like filaments were present in this youngest case. These findings expand the similarities between AD and DS to the molecular level, providing insight into their related pathologies and the potential for targeting common tau filament folds by small-molecule therapeutics and diagnostics.
Topics: Humans; Down Syndrome; tau Proteins; Cryoelectron Microscopy; Middle Aged; Alzheimer Disease; Female; Adult; Male; Neurofibrillary Tangles; Brain
PubMed: 38867338
DOI: 10.1186/s40478-024-01806-y -
Journal of Experimental Orthopaedics Jul 2024No report has proven how tibial and femoral joint-line inclinations affect thigh and shank motion, respectively, according to Kellgren-Lawrence grade in motion analysis...
PURPOSE
No report has proven how tibial and femoral joint-line inclinations affect thigh and shank motion, respectively, according to Kellgren-Lawrence grade in motion analysis with a sufficient sample size. Therefore, this study aimed to evaluate the motion of the thigh and shank individually from the ground and the relative motion between bones in a large-sample motion analysis to determine the differences between normal and osteoarthritic knees and examine the effects of tibial and femoral joint-line inclination on motion according to osteoarthritis (OA) grade.
METHODS
Of 459 participants with healthy knees and varus knee OA undergoing three-dimensional gait analysis, 383 (218 females and 165 males) with an average age of 68 ± 13 years were selected. Gait analysis was performed using a motion-capture system. The six degrees of freedom motion parameters of the knee in the Grood and world coordinate systems and the joint-line inclination in the standing radiographs were measured.
RESULTS
Osteoarthritic knees demonstrated a relative motion different from that of normal knees, with responsibility for the thigh in the sagittal and rotational planes and the thigh and shank in the coronal plane. The involvement of joint-line inclination in motion was mainly on the tibial side, and the effect was minimal in normal knees.
CONCLUSIONS
The details of the relative motion of both the thigh and shank can be clarified by analysing individual motions to determine the responsible part. The tibial joint-line affected knee motion: however, the effect was minimal in normal knees. This finding implies that if physical ability can be improved, the negative effects of deformity in osteoarthritic knees may be compensated for.
LEVEL OF EVIDENCE
Level Ⅱ.
PubMed: 38863941
DOI: 10.1002/jeo2.12040 -
Vascular Specialist International Jun 2024This study aims to examine predisposing anatomic factors and subsequent post-decompression functional outcomes among high-intensity athletes with thoracic outlet...
PURPOSE
This study aims to examine predisposing anatomic factors and subsequent post-decompression functional outcomes among high-intensity athletes with thoracic outlet syndrome (TOS).
MATERIALS AND METHODS
A single-institution retrospective review was performed on a prospective database of patients with TOS from 2018 to 2023 who had undergone operative decompression for TOS. Demographics, TOS characteristics, predisposing anatomy, operative details, and postoperative outcomes were examined. The primary outcome was postoperative return to sport. Secondary outcomes included vascular patency.
RESULTS
A total of 13 patients who were engaged in high-demand athletic activity at the time of their diagnosis were included. Diagnoses included 8 (62%) patients with venous TOS, 4 (31%) patients with neurogenic TOS, and 1 (8%) patient with arterial TOS. Mixed vascular and neurogenic TOS was observed in 3 (23%) patients. The mean age of the cohort was 30 years. Abnormal scalene structure was observed in 12 (92%) patients, and abnormal bone structures were noted in 4 (27%) patients; 2 (15%) with cervical ribs and 3 (23%) patients with clavicular abnormalities. Prior ipsilateral upper extremity trauma was reported in 4 (27%) patients. Significant joint hypermobility was observed in 8 (62%) patients with a median Beighton score of 6. Supraclavicular cervical and/or first rib resection with scalenectomy was performed in all patients. One case of postoperative pneumothorax was treated non-operatively. Ten (77%) patients returned to sport. Duplex ultrasonography showed subclavian vein patency in all 8 patients with venous TOS and wide patency with no drop in perfusion indices in the patient with arterial TOS.
CONCLUSION
Athletes with TOS who required operative intervention had a high incidence of musculoskeletal aberrations and joint hypermobility. Supraclavicular decompression was associated with a high success rate, with overall good functional outcomes and good likelihood of patients returning to preoperative high-intensity athletics.
PubMed: 38858178
DOI: 10.5758/vsi.240011 -
Rheumatology Advances in Practice 2024To investigate the hypotheses that in patients with SSc, the temperature gradient between the dorsum of the foot and toes (distal-dorsal difference [DDD]) is 'more...
OBJECTIVES
To investigate the hypotheses that in patients with SSc, the temperature gradient between the dorsum of the foot and toes (distal-dorsal difference [DDD]) is 'more negative' (toes cooler) than in healthy controls, is greatest along the first (great) toe and that the severities of thermographic abnormalities in the feet and hands are correlated.
METHODS
Thermographic images of the dorsum of each hand and foot were captured using a thermal camera attached to an iPhone in 40 patients with SSc and 20 healthy controls. DDDs along the fingers (index, middle, ring and little) and toes (great toe and 'others') were measured.
RESULTS
There was a non-significant trend for the great toes to be colder in patients with SSc than in controls. The mean great toe DDD was more negative in patients (right: -2.89°C, left: -2.91°C, mean: -2.90°C) than in controls (right: -2.36°C, left: -2.42°C, mean: -2.39°C) ( = 0.37 for mean values). Patients' great toes were colder than 'other' (lesser) toes (right: -2.58°C, left: -2.63°C), although not significantly. In patients with SSc, finger and great toe temperature gradients were correlated ( = 0.406, ρ = 0.01).
CONCLUSION
Our findings suggest that the great toe is the coldest in patients with SSc and that patients with the coldest fingers tend to have the coldest toes. Severe RP symptoms in the hands should prompt podiatry assessment and foot care education. Mobile phone thermography is a convenient tool for assessing the digital vasculature but first requires validation in larger studies with a longitudinal component.
PubMed: 38855628
DOI: 10.1093/rap/rkae068 -
Cureus May 2024Researching Waardenburg syndrome (WS) underscores its rarity and complex symptomatology, presenting as a congenital disorder predominantly inherited in an autosomal...
Researching Waardenburg syndrome (WS) underscores its rarity and complex symptomatology, presenting as a congenital disorder predominantly inherited in an autosomal dominant pattern. It exhibits incomplete penetrance, which results in a wide range of clinical manifestations, with variable phenotypic presentations within the same family as well. The most commonly found features are facial abnormalities, hypopigmentation of the skin, heterochromia iridis, and conductive deafness. Adding to the eccentricities of this syndrome are its four subtypes, each presenting with its specific clinical features, which helps in delineating the subtype. A mutated paired box 3 () gene manifests as type 1 Waardenburg, which is characterized by sideways displacement of the inner angles of the eyes (i.e., dystopia canthorum), widely spaced eyes, congenital sensorineural hearing impairment, and patchy pigmentation of the iris, skin, and hair. Due to insufficient research, it has been difficult to isolate all the genetic mutations responsible for type 2, but its phenotype is very similar to type 1 with minor differences. Type 3 is characterized by musculoskeletal abnormalities. Waardenburg-Shah syndrome (type 4), which is associated with Hirschsprung disease, is the rarest subtype and is caused by genetic mutations in the endothelin receptor type B (), endothelin-3 (), or sex-determining region Y (SRY) box 10 () gene. We present a case series of this unique subtype that presented with a typical history of constipation due to Hirschsprung disease and had phenotypic manifestations of white forelock, heterochromia iridis, and bilateral sensorineural hearing loss (SNHL). In parallel with a positive 1° family history of a white forelock, we reflect on the fundamentals of this unique syndrome, as well as its management protocols, highlighting the importance of genetic counseling and cultivation of a high index of suspicion for its diagnosis.
PubMed: 38854277
DOI: 10.7759/cureus.59858 -
Journal of Neurosurgery. Spine Jun 2024There are limited data about the influence of the lumbar paraspinal muscles on the maintenance of sagittal alignment after pedicle subtraction osteotomy (PSO) and the...
OBJECTIVE
There are limited data about the influence of the lumbar paraspinal muscles on the maintenance of sagittal alignment after pedicle subtraction osteotomy (PSO) and the risk factors for sagittal realignment failure. The authors aimed to investigate the influence of preoperative lumbar paraspinal muscle quality on the postoperative maintenance of sagittal alignment after lumbar PSO.
METHODS
Patients who underwent lumbar PSO with preoperative lumbar MRI and pre- and postoperative whole-spine radiography in the standing position were included. Spinopelvic measurements included pelvic incidence, sacral slope, pelvic tilt, L1-S1 lordosis, T4-12 thoracic kyphosis, spinosacral angle, C7-S1 sagittal vertical axis (SVA), T1 pelvic angle, and mismatch between pelvic incidence and L1-S1 lordosis. Validated custom software was used to calculate the percent fat infiltration (FI) of the psoas major, as well as the erector spinae and multifidus (MF). A multivariable linear mixed model was applied to further examine the association between MF FI and the postoperative progression of SVA over time, accounting for repeated measures over time that were adjusted for age, sex, BMI, and length of follow-up.
RESULTS
Seventy-seven patients were recruited. The authors' results demonstrated significant correlations between MF FI and the maintenance of corrected sagittal alignment after PSO. After adjustment for the aforementioned parameters, the model showed that the MF FI was significantly associated with the postoperative progression of positive SVA over time. A 1% increase from the preoperatively assessed total MF FI was correlated with an increase of 0.92 mm in SVA postoperatively (95% CI 0.42-1.41, p < 0.0001).
CONCLUSIONS
This study included a large patient cohort with midterm follow-up after PSO and emphasized the importance of the lumbar paraspinal muscles in the maintenance of sagittal alignment correction. Surgeons should assess the quality of the MF preoperatively in patients undergoing PSO to identify patients with severe FI, as they may be at higher risk for sagittal decompensation.
PubMed: 38848601
DOI: 10.3171/2024.3.SPINE231052 -
BMC Musculoskeletal Disorders Jun 2024Patient-specific aiming devices (PSAD) may improve precision and accuracy of glenoid component positioning in total shoulder arthroplasty, especially in degenerative... (Comparative Study)
Comparative Study
Experimental guide wire placement for total shoulder arthroplasty in glenoid models: higher precision for patient-specific aiming guides compared to standard technique without learning curve.
BACKGROUND
Patient-specific aiming devices (PSAD) may improve precision and accuracy of glenoid component positioning in total shoulder arthroplasty, especially in degenerative glenoids. The aim of this study was to compare precision and accuracy of guide wire positioning into different glenoid models using a PSAD versus a standard guide.
METHODS
Three experienced shoulder surgeons inserted 2.5 mm K-wires into polyurethane cast glenoid models of type Walch A, B and C (in total 180 models). Every surgeon placed guide wires into 10 glenoids of each type with a standard guide by DePuy Synthes in group (I) and with a PSAD in group (II). Deviation from planned version, inclination and entry point was measured, as well as investigation of a possible learning curve.
RESULTS
Maximal deviation in version in B- and C-glenoids in (I) was 20.3° versus 4.8° in (II) (p < 0.001) and in inclination was 20.0° in (I) versus 3.7° in (II) (p < 0.001). For B-glenoid, more than 50% of the guide wires in (I) had a version deviation between 11.9° and 20.3° compared to ≤ 2.2° in (II) (p < 0.001). 50% of B- and C-glenoids in (I) showed a median inclination deviation of 4.6° (0.0°-20.0°; p < 0.001) versus 1.8° (0.0°-4.0°; p < 0.001) in (II). Deviation from the entry point was always less than 5.0 mm when using PSAD compared to a maximum of 7.7 mm with the standard guide and was most pronounced in type C (p < 0.001).
CONCLUSION
PSAD enhance precision and accuracy of guide wire placement particularly for deformed B and C type glenoids compared to a standard guide in vitro. There was no learning curve for PSAD. However, findings of this study cannot be directly translated to the clinical reality and require further corroboration.
Topics: Humans; Arthroplasty, Replacement, Shoulder; Learning Curve; Bone Wires; Glenoid Cavity; Models, Anatomic; Shoulder Joint
PubMed: 38844899
DOI: 10.1186/s12891-024-07549-0 -
Journal of Clinical Imaging Science 2024Many clinicians use radiological imaging in efforts to locate and diagnose the cause of their patient's pain, relying on X-rays as a leading tool in clinical evaluation.... (Review)
Review
Many clinicians use radiological imaging in efforts to locate and diagnose the cause of their patient's pain, relying on X-rays as a leading tool in clinical evaluation. This is fundamentally flawed because an X-ray represents a "snapshot" of the structural appearance of the spine and gives no indication of the current function of the spine. The health and well-being of any system, including the spinal motion segments, depend on the inter-relationship between structure and function. Pain, tissue damage, and injury are not always directly correlated. Due to such a high incidence of abnormalities found in asymptomatic patients, the diagnostic validity of X-rays can be questioned, especially when used in isolation of history and/or proper clinical assessment. The utility of routine X-rays is, therefore, questionable. One may posit that their application promotes overdiagnosis, and unvalidated treatment of X-ray findings (such as changes in postural curvature), which may mislead patients into believing these changes are directly responsible for their pain. A substantial amount of research has shown that there is no association between pain and reversed cervical curves. Accuracy can also be questioned, as X-ray measurements can vary based on the patient's standing position, which research shows is influenced by an overwhelming number of factors, such as patient positioning, patient physical and morphological changes over time, doctor interreliability, stress, pain, the patient's previous night's sleep or physical activity, hydration, and/or emotional state. Furthermore, research has concluded that strong evidence links various potential harms with routine, repeated X-rays, such as altered treatment procedures, overdiagnosis, radiation exposure, and unnecessary costs. Over the past two decades, medical boards and health associations worldwide have made a substantial effort to communicate better "when" imaging is required, with most education around reducing radiographic imaging. In this review, we describe concerns relating to the high-frequency, routine use of spinal X-rays in the primary care setting for spine-related pain in the absence of red-flag clinical signs.
PubMed: 38841311
DOI: 10.25259/JCIS_5_2024 -
SA Journal of Radiology 2024Fibrous dysplasia (FD) is a rare, non-inherited, congenital bone disorder which may be monostotic or polyostotic. The polyostotic form may rarely present in syndromic...
UNLABELLED
Fibrous dysplasia (FD) is a rare, non-inherited, congenital bone disorder which may be monostotic or polyostotic. The polyostotic form may rarely present in syndromic forms when associated with extra-skeletal manifestations. Mazabraud syndrome is a rare syndrome consisting of polyostotic FD presenting with intramuscular myxomas. McCune-Albright syndrome is recognised by polyostotic FD, precocious puberty and 'café au lait' spots. This report describes an adult patient with Mazabraud syndrome and a child with McCune-Albright syndrome.
CONTRIBUTION
Radiographic findings are typical with bowing deformities, sclerotic, lucent or mixed lesions and bony expansion, often with endosteal scalloping. MRI is often non-contributory and may actually mimic a more aggressive process. Early detection and correct diagnosis allow for early preventative treatment and rehabilitation to prevent devastating neurological sequelae and disability.
PubMed: 38840825
DOI: 10.4102/sajr.v28i1.2877 -
Spine Deformity Jun 2024The Spinal Appearance Questionnaire (SAQ) is a widely validated tool for assessing perceptions of spinal deformity in adolescent idiopathic scoliosis (AIS) patients....
PURPOSE
The Spinal Appearance Questionnaire (SAQ) is a widely validated tool for assessing perceptions of spinal deformity in adolescent idiopathic scoliosis (AIS) patients. This study aimed to develop and validate a Greek version of the SAQ (GR-SAQ).
METHODS
A cross-cultural adaptation of the SAQ following international guidelines was performed. Internal consistency and test-retest reliability were evaluated. Convergent validity was assessed by correlating the GR-SAQ with the Appearance domain of Scoliosis Research Society-22 (SRS-22) and the Cobb angle with the Trunk Shift domain of GR-SAQ. Divergent validity was examined through the relationship between GR-SAQ, patient characteristics, and clinical measures including Cobb angle, DIERS Formetric 4D angle, and scoliometer readings.
RESULTS
The study included 61 AIS patients (52 females, 13.91 ± 2.57 years, 25.33 ± 10.14° Cobb angle). GR-SAQ exhibited good internal consistency (Cronbach's α = 0.794) and excellent test-retest reliability (ICC = 0.931, 95%CI: 0.880-0.960). Correlations between GR-SAQ and SRS-22 showed a low-to-moderate negative correlation (r = -0.351, p = 0.006). The Trunk Shift domain moderately correlated with the Cobb Angle (r = 0.393, p = 0.002). Divergent validity analyses did not demonstrate statistical significance (p > 0.05).
CONCLUSION
The GR-SAQ is a valid and reliable tool for evaluating spinal deformity perception in Greek AIS patients.
PubMed: 38833190
DOI: 10.1007/s43390-024-00907-x