Importance of Bilateral Hip Assessments in Unilateral Lower-Limb Amputees: A Retrospective Review Involving Older Veterans.

Background/Objectives: This study aimed to evaluate bone mineral density (BMD) discordance and its implications in veterans with unilateral lower-limb amputation, emphasizing the need for comprehensive hip assessments. Methods: Data were collected from 84 male veterans, and BMD was measured using dual-energy X-ray absorptiometry (DXA) at the lumbar spine, intact hip, and amputated hip. Results: The T-scores for the lumbar spine, intact hip, and amputated hip were -0.27 ± 1.69, -0.25 ± 1.20, and -1.07 ± 1.33, respectively. Osteoporosis and osteopenia were present in 19% and 34.6% of patients, respectively. Osteopenia and osteoporosis were most prevalent in the hips on the amputated side (32.1% and 13.1%, respectively), followed by the lumbar spines (22.6% and 8.3%) and the hips on the intact side (17.9% and 2.4%). BMD discordance between the lumbar spine and hip was found in 47.6% of participants, while discordance between both hips was observed in 39.3%. Transfemoral amputees had significantly lower BMD at the amputated hip compared to transtibial amputees (-2.38 ± 1.72 vs. -0.87 ± 1.16, p < 0.001). Conclusions: Veterans with unilateral lower-limb amputation exhibit a high prevalence of osteoporosis and significant BMD discordance, particularly between both hips. These findings underscore the necessity for bilateral hip assessments to ensure the accurate diagnosis and effective management of osteoporosis in this population.

Association between eyeball asymmetry and offset of openings in optic nerve head canal assessed by posterior polar eyeball topography.

We investigated three-dimensional (3D) eyeball protrusion and its association with the offset between the lamina cribrosa (LC) and Bruch's membrane opening (BMO). 3D-MRI scans were taken from 93 subjects (186 eyes). An ellipsoid was fitted along the posterior 2/3 contour of each eyeball. Eyeball asymmetry with focal bulging was determined by the existence of an adjacent outward protrusion/reciprocal inward depression pair, and the angular deviation of the outermost protruded point (OPP) was measured from the nasal side of the fovea-BMO axis. The LC/BMO offset was evaluated by measuring the central retinal vascular trunk (CRVT) location from the BMO center: (1) the angular deviation and (2) the offset index as the ratio between the CRVT-BMO center distance and the BMO radius in the same direction. Seventy-nine eyes (42%) were classified as having eyeball asymmetry, which had a more superior LC/BMO offset (P < 0.001) and a larger offset index (P = 0.002). In those eyes, the angular deviation of the OPP showed a significant correlation with that of the LC/BMO offset (r = -0.724, P < 0.001), as did protrusion depth with the offset index (r = 0.291, P = 0.009). The presence of eyeball asymmetry was associated with superior LC/BMO offset (P = 0.004) and larger offset index (P = 0.009). Superior LC/BMO offset was associated with older age (P < 0.001), shorter axial length (P < 0.001) and inferior location of OPP (P < 0.001). The location and extent of focal bulging were closely associated with those of LC/BMO offset. This indicates that focal bulging during expansion might be associated with diverse directionality of LC/BMO offset.

Impaired cognitive flexibility and disrupted cognitive cerebellum in degenerative cerebellar ataxias.

There is a clinically unmet need for a neuropsychological tool that reflects the pathophysiology of cognitive dysfunction in cerebellar degeneration. We investigated cognitive flexibility in degenerative cerebellar ataxia patients and aim to identify the pathophysiological correlates of cognitive dysfunction in relation to cerebellar cognitive circuits. We prospectively enrolled degenerative cerebellar ataxia patients with age-matched healthy controls who underwent 3 T 3D and resting-state functional MRI. All 56 participants were evaluated with the Scale for Assessment and Rating of Ataxia and neuropsychological tests including the Wisconsin Card Sorting Test, Trail Making Test, Montreal Cognitive Assessment and Mini-Mental State Examination. From MRI scans, we analysed the correlation of whole-brain volume and cortico-cerebellar functional connectivity with the Wisconsin Card Sorting Test performances. A total of 52 participants (29 ataxia patients and 23 healthy controls) were enrolled in this study. The Wisconsin Card Sorting Test scores (total error percentage, perseverative error percentage, non-perseverative error percentage and categories completed), Trail Making Test A and Montreal Cognitive Assessment were significantly impaired in ataxia patients (P < 0.05) compared to age-matched healthy controls. The Wisconsin Card Sorting Test error scores showed a significant correlation with the ataxia score (P < 0.05) controlling for age and sex. In volumetric analysis, the cerebellar right crus I, II, VIIb and VIII atrophy correlated with non-perseverative error percentage in the ataxia group. In functional connectivity analysis, the connectivity between crus I, II and VIIb of the cerebellum and bilateral superior parietal and superior temporal gyrus was significantly altered in ataxia patients. The functional connectivity between left crus II and VIIb of the cerebellum and dorsolateral prefrontal and superior frontal/parietal cortices showed a positive correlation with perseverative error percentage. The connectivity between left crus VIIb and pontine nucleus/middle cerebellar peduncle showed a significant negative correlation with non-perseverative error percentage in the ataxia group. The impaired cognitive flexibility represented by the Wisconsin Card Sorting Test was significantly impaired in degenerative cerebellar ataxia patients and correlated with disease severity. The Wisconsin Card Sorting Test performance reflects hypoactivity of the cognitive cerebellum and disrupted cortico-cerebellar connectivity in non-demented patients with degenerative cerebellar ataxia.

Malignancy risk of indeterminate lymph node at the central compartment in patients with thyroid cancer and concomitant sonographic thyroiditis.

BACKGROUND: To evaluate the malignancy risk of sonographic (US) indeterminate lymph node (LN)s at the central compartment in thyroid cancer patients with US-thyroiditis (ST). METHODS: Among the central compartments of suspicious, indeterminate, and probably benign LN US categories, the malignancy rates were compared between ST and non-US-thyroiditis (non-ST) groups. Those of indeterminate category were compared with suspicious and probably benign categories. RESULTS: At 531 central compartments from 349 patients, the malignancy rate was lower in ST group (34.4% [44/128]) than non-ST group (43.4% [175/403]), although statistically not significant (p = 0.08). The malignancy rate of indeterminate category in ST group (35.7% [5/14]) was lower than non-ST group (71.9% [23/32]) (p = 0.047). Within ST group, the malignancy rate of indeterminate category (35.7% [5/14]) did not differ from probably benign category (29.1% [30/103]) (p = 0.756), but was lower than suspicious category (81.8% [9/11]) (p = 0.042). CONCLUSIONS: The malignancy risk of US indeterminate LNs at the central compartment in thyroid cancer patients with US thyroiditis was lower than that in patients without US thyroiditis.

Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates.

In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis.

Manipulating solid-state spin concentration through charge transport.

Solid-state defects are attractive platforms for quantum sensing and simulation, e.g., in exploring many-body physics and quantum hydrodynamics. However, many interesting properties can be revealed only upon changes in the density of defects, which instead is usually fixed in material systems. Increasing the interaction strength by creating denser defect ensembles also brings more decoherence. Ideally one would like to control the spin concentration at will while keeping fixed decoherence effects. Here, we show that by exploiting charge transport, we can take some steps in this direction, while at the same time characterizing charge transport and its capture by defects. By exploiting the cycling process of ionization and recombination of NV centers in diamond, we pump electrons from the valence band to the conduction band. These charges are then transported to modulate the spin concentration by changing the charge state of material defects. By developing a wide-field imaging setup integrated with a fast single photon detector array, we achieve a direct and efficient characterization of the charge redistribution process by measuring the complete spectrum of the spin bath with micrometer-scale spatial resolution. We demonstrate a two-fold concentration increase of the dominant spin defects while keeping the T2 of the NV center relatively unchanged, which also provides a potential experimental demonstration of the suppression of spin flip-flops via hyperfine interactions. Our work paves the way to studying many-body dynamics with temporally and spatially tunable interaction strengths in hybrid charge-spin systems.

Efficacy of Imaging Methods in the Detection and Diagnosis of Cerebrospinal Fluid Rhinorrhea.

OBJECTIVE: To assess the diagnostic efficacy of various imaging methods in patients with suspected cerebrospinal fluid (CSF) rhinorrhea. DATA SOURCES: The PubMed, EMBASE, SCOPUS, Web of Science, Cochrane Trials, and Google Scholar databases were searched up to December 2021. REVIEW METHODS: Diagnostic accuracy was compared among seven radiological methods: computed tomography (CT), CT cisternography (CTC), magnetic resonance imaging (MRI), magnetic resonance cisternography (MRC), CT + MRI, radionuclide cisternography, and intrathecal gadolinium (Gd)-MRC. Sensitivity, specificity, and accuracy were used as outcomes of the analysis. Both a traditional pairwise meta-analysis and a network meta-analysis were performed. RESULTS: Twenty-three trials were included in the analysis. The results of a network meta-analysis performed on a network consisting of seven diagnostic methods showed that all imaging modalities had greater diagnostic accuracy than CT, with the exception of CTC, which had lower sensitivity. Only intrathecal Gd-MRC was significantly superior to other imaging methods with regard to sensitivity and accuracy. Gd-MRC also showed the greatest surface under the cumulative ranking curve values for all of the outcomes (sensitivity: 0.9200; specificity: 0.8364; accuracy: 0.8920). CONCLUSION: This network meta-analysis demonstrates that intrathecal Gd-MRC is the most useful diagnostic method to detect CSF rhinorrhea. Laryngoscope, 133:1281-1287, 2023.

Implant selection for successful reverse total shoulder arthroplasty

Reverse total shoulder arthroplasty (RTSA) emerged as a new concept of arthroplasty that does not restore normal anatomy but does restore function. It enables the function of the torn rotator cuff to be performed by the deltoid and shows encouraging clinical outcomes. Since its introduction, various modifications have been designed to improve the outcome of the RTSA. From the original cemented baseplate with peg or keel, a cementless baseplate was designed that could be fixed with central and peripheral screws. In addition, a modular-type glenoid component enabled easier revision options. For the humeral component, the initial design was an inlay type of long stem with cemented fixation. However, loss of bone stock from the cemented stem hindered revision surgery. Therefore, a cementless design was introduced with a firm metaphyseal fixation. Furthermore, to prevent complications such as scapular notching, the concept of lateralization emerged. Lateralization helped to maintain normal shoulder contour and better rotator cuff function for improved external/internal rotation power, but excessive lateralization yielded problems such as subacromial notching. Therefore, for patients with pseudoparalysis or with risk of subacromial notching, a medial eccentric tray option can be used for distalization and reduced lateralization of the center of rotation. In summary, it is important that surgeons understand the characteristics of each implant in the various options for RTSA. Furthermore, through preoperative evaluation of patients, surgeons can choose the implant option that will lead to the best outcomes after RTSA.

Efficacy of non-invasive diagnostic methods in the diagnosis and screening of oral cancer and precancer / Eficácia de métodos diagnósticos não invasivos no diagnóstico e triagem de lesões pré-malignas e malignas na cavidade oral; revisão sistemática e meta-análise

Abstract Introduction: Traditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a single method and a single alternative, while multiple diagnostic options and the ranking thereof were methodologically not possible. Objective: To evaluate the diagnostic values of various methods in patients with oral potential malignant disease by performing a network meta-analysis. Methods: Two authors independently searched the databases (MEDLINE, SCOPUS, the Cochrane Register of Controlled Trials, and Google scholar) up to June 2020 for studies comparing the diagnostic accuracy of various tools (autofluorescence, chemiluminescence, cytology, narrow band imaging, and toluidine blue) with visual examination or other tools. The outcomes of interest for this analysis were sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Both a standard pairwise meta-analysis and network meta-analysis were conducted. Results: Treatment networks consisting of six interventions were defined for the network metaanalysis. The results of traditional meta-analysis showed that, among six methods, narrow band imaging showed higher sensitivity, specificity, negative predictive value, positive predictive value, and accuracy compared to visual examination. The results of network meta-analysis showed that autofluorescence, chemiluminescence, and narrow band imaging had higher sensitivity compared with visual examination, and that chemiluminescence and narrow band imaging had higher negative predictive value compared with visual examination. However, autofluorescence and chemiluminescence had lower specificity compared with visual examination. There were no significant differences in positive predictive value and accuracy among the six interventions. Conclusion: This study demonstrated that narrow banding imaging has superiority in terms of sensitivity and negative predictive value compared with the other five tested agents.

Resumo Introdução: Metanálises tradicionais sobre a precisão diagnóstica de lesões orais têm sido conduzidas, mas são inerentemente limitadas a comparações pareadas diretas entre um único método e uma única opção, enquanto múltiplas opções de diagnóstico e suas classificações ainda não foram metodologicamente possíveis. Objetivo: Avaliar os valores diagnósticos de vários métodos em pacientes com doença oral potencialmente maligna e fazer uma metanálise de rede. Método: Dois autores pesquisaram independentemente os bancos de dados (Medline, Scopus, Cochrane Register of Controlled Trials e Google Scholar) até junho de 2020 para estudos que comparassem a precisão diagnóstica de várias ferramentas (autofluorescência, quimioluminescência, citologia, imagem de banda estreita e cloreto de tolônio) com exame visual ou outras ferramentas. Os resultados de interesse para esta análise foram sensibilidade, especificidade, valor preditivo negativo, valor preditivo e precisão. Tanto uma metanálise pareada padrão quanto uma metanálise de rede foram conduzidas. Resultados: Redes de tratamento compostas por seis intervenções foram definidas para a metanálise de rede. Os resultados da metanálise tradicional mostraram que, entre seis métodos, a imagem de banda estreita apresentou maior sensibilidade, especificidade, valor preditivo negativo, valor preditivo e precisão em comparação ao exame visual. Os resultados da metanálise de rede mostraram que a autofluorescência, a quimioluminescência e a imagem de banda estreita obtiveram maior sensibilidade em comparação com o exame visual e que a quimioluminescência e a imagem de banda estreita apresentaram maior valor preditivo negativo em comparação com o exame visual. Entretanto, a autofluorescência e a quimioluminescência mostraram especificidade inferior em comparação com o exame visual. Não houve diferenças significativas no valor preditivo e na precisão entre as seis intervenções. Conclusão: Este estudo demonstrou que a imagem de banda estreita demonstra superioridade em termos de sensibilidade e valor preditivo negativo em comparação com os outros cinco agentes testados.

Malignancy risk stratification of thyroid nodules according to echotexture and degree of hypoechogenicity: a retrospective multicenter validation study.

Various risk stratification systems show discrepancies in the ultrasound lexicon of nodule echotexture and hypoechogenicity. This study aimed to determine the malignancy risk of thyroid nodules according to their echotexture and degree of hypoechogenicity. From June to September 2015, we retrospectively evaluated 5601 thyroid nodules with final diagnoses from 26 institutions. Nodules were stratified according to the echotexture (homogeneous vs. heterogeneous) and degree of hypoechogenicity (mild, moderate, or marked). We calculated the malignancy risk according to composition and suspicious features. Heterogeneous hypoechoic nodules showed a significantly higher malignancy risk than heterogeneous isoechoic nodules (P ≤ 0.017), except in partially cystic nodules. Malignancy risks were not significantly different between homogeneous versus heterogeneous nodules in both hypoechoic (P ≥ 0.086) and iso- hyperechoic nodules (P ≥ 0.05). Heterogeneous iso-hyperechoic nodules without suspicious features showed a low malignancy risk. The malignancy risks of markedly and moderately hypoechoic nodules were not significantly different in all subgroups (P ≥ 0.48). Marked or moderately hypoechoic nodules showed a significantly higher risk than mild hypoechoic (P ≤ 0.016) nodules. The predominant echogenicity effectively stratifies the malignancy risk of nodules with heterogeneous echotexture. The degree of hypoechogenicity could be stratified as mild versus moderate to marked hypoechogenicity.

Delayed Cerebral Toxoplasmosis in a Kidney Transplant Patient: a Case Report.

Cerebral toxoplasmosis is often life-threatening in an immunocompromised patient due to delayed diagnosis and treatment. Several differential diagnoses could be possible only with preoperative brain images of cerebral toxoplasmosis which show multiple rim-enhancing lesions. Due to the rarity of cerebral toxoplasmosis cases in Korea, the diagnosis and treatment are often delayed. This paper concerns a male patient whose cerebral toxoplasmosis was activated 21 years post kidney transplantation. Brain open biopsy was decided to make an exact diagnosis. Cerebral toxoplasmosis was confirmed by immunohistochemistry and PCR analyses of the tissue samples. Although cerebral toxoplasmosis was under control with medication, the patient did not recover clinically and died due to sepsis and recurrent gastrointestinal bleeding.

Hydrophobic and Hydrogel-Based Methods for Passive Tissue Clearing.

Optical tissue clearing enables the precise imaging of cellular and subcellular structures in whole organs and tissues without the need for physical tissue sectioning. By combining tissue clearing with confocal or lightsheet microscopy, 3D images can be generated of entire specimens for visualization and large-scale data analysis. Here we demonstrate two different passive tissue clearing techniques that are compatible with immunofluorescent staining and lightsheet microscopy: PACT, an aqueous hydrogel-based clearing method, and iDISCO+, an organic solvent-based clearing method.

A deep learning-based automatic analysis of cardiovascular borders on chest radiographs of valvular heart disease: development/external validation.

OBJECTIVES: Cardiovascular border (CB) analysis is the primary method for detecting and quantifying the severity of cardiovascular disease using posterior-anterior chest radiographs (CXRs). This study aimed to develop and validate a deep learning-based automatic CXR CB analysis algorithm (CB_auto) for diagnosing and quantitatively evaluating valvular heart disease (VHD). METHODS: We developed CB_auto using 816 normal and 798 VHD CXRs. For validation, 640 normal and 542 VHD CXRs from three different hospitals and 132 CXRs from a public dataset were assigned. The reliability of the CB parameters determined by CB_auto was evaluated. To evaluate the differences between parameters determined by CB_auto and manual CB drawing (CB_hand), the absolute percentage measurement error (APE) was calculated. Pearson correlation coefficients were calculated between CB_hand and echocardiographic measurements. RESULTS: CB parameters determined by CB_auto yielded excellent reliability (intraclass correlation coefficient > 0.98). The 95% limits of agreement for the cardiothoracic ratio were 0.00 ± 0.04% without systemic bias. The differences between parameters determined by CB_auto and CB_hand as defined by the APE were < 10% for all parameters except for carinal angle and left atrial appendage. In the public dataset, all CB parameters were successfully drawn in 124 of 132 CXRs (93.9%). All CB parameters were significantly greater in VHD than in normal controls (all p < 0.05). All CB parameters showed significant correlations (p < 0.05) with echocardiographic measurements. CONCLUSIONS: The CB_auto system empowered by deep learning algorithm provided highly reliable CB measurements that could be useful not only in daily clinical practice but also for research purposes. KEY POINTS: • A deep learning-based automatic CB analysis algorithm for diagnosing and quantitatively evaluating VHD using posterior-anterior chest radiographs was developed and validated. • Our algorithm (CB_auto) yielded comparable reliability to manual CB drawing (CB_hand) in terms of various CB measurement variables, as confirmed by external validation with datasets from three different hospitals and a public dataset. • All CB parameters were significantly different between VHD and normal control measurements, and echocardiographic measurements were significantly correlated with CB parameters measured from normal control and VHD CXRs.

Efficacy of non-invasive diagnostic methods in the diagnosis and screening of oral cancer and precancer.

INTRODUCTION: Traditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a single method and a single alternative, while multiple diagnostic options and the ranking thereof were methodologically not possible. OBJECTIVE: To evaluate the diagnostic values of various methods in patients with oral potential malignant disease by performing a network meta-analysis. METHODS: Two authors independently searched the databases (MEDLINE, SCOPUS, the Cochrane Register of Controlled Trials, and Google scholar) up to June 2020 for studies comparing the diagnostic accuracy of various tools (autofluorescence, chemiluminescence, cytology, narrow band imaging, and toluidine blue) with visual examination or other tools. The outcomes of interest for this analysis were sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Both a standard pairwise meta-analysis and network meta-analysis were conducted. RESULTS: Treatment networks consisting of six interventions were defined for the network meta-analysis. The results of traditional meta-analysis showed that, among six methods, narrow band imaging showed higher sensitivity, specificity, negative predictive value, positive predictive value, and accuracy compared to visual examination. The results of network meta-analysis showed that autofluorescence, chemiluminescence, and narrow band imaging had higher sensitivity compared with visual examination, and that chemiluminescence and narrow band imaging had higher negative predictive value compared with visual examination. However, autofluorescence and chemiluminescence had lower specificity compared with visual examination. There were no significant differences in positive predictive value and accuracy among the six interventions. CONCLUSION: This study demonstrated that narrow banding imaging has superiority in terms of sensitivity and negative predictive value compared with the other five tested agents.

Delayed Cerebral Toxoplasmosis in a Kidney Transplant Patient: a Case Report

Cerebral toxoplasmosis is often life-threatening in an immunocompromised patient due to delayed diagnosis and treatment. Several differential diagnoses could be possible only with preoperative brain images of cerebral toxoplasmosis which show multiple rim-enhancing lesions. Due to the rarity of cerebral toxoplasmosis cases in Korea, the diagnosis and treatment are often delayed. This paper concerns a male patient whose cerebral toxoplasmosis was activated 21 years post kidney transplantation. Brain open biopsy was decided to make an exact diagnosis. Cerebral toxoplasmosis was confirmed by immunohistochemistry and PCR analyses of the tissue samples. Although cerebral toxoplasmosis was under control with medication, the patient did not recover clinically and died due to sepsis and recurrent gastrointestinal bleeding.

Navigating the Light-Sheet Image Analysis Software Landscape: Concepts for Driving Cohesion From Data Acquisition to Analysis.

From the combined perspective of biologists, microscope instrumentation developers, imaging core facility scientists, and high performance computing experts, we discuss the challenges faced when selecting imaging and analysis tools in the field of light-sheet microscopy. Our goal is to provide a contextual framework of basic computing concepts that cell and developmental biologists can refer to when mapping the peculiarities of different light-sheet data to specific existing computing environments and image analysis pipelines. We provide our perspective on efficient processes for tool selection and review current hardware and software commonly used in light-sheet image analysis, as well as discuss what ideal tools for the future may look like.

Spleen tyrosine kinase facilitates neutrophil activation and worsens long-term neurologic deficits after spinal cord injury.

BACKGROUND: Spinal cord injury elicits widespread inflammation that can exacerbate long-term neurologic deficits. Neutrophils are the most abundant immune cell type to invade the spinal cord in the early acute phase after injury, however, their role in secondary pathogenesis and functional recovery remains unclear. We have previously shown that neutrophil functional responses during inflammation are augmented by spleen tyrosine kinase, Syk, a prominent intracellular signaling enzyme. In this study, we evaluated the contribution of Syk towards neutrophil function and long-term neurologic deficits after spinal cord injury. METHODS: Contusive spinal cord injury was performed at thoracic vertebra level 9 in mice with conditional deletion of Syk in neutrophils (Sykf/fMRP8-Cre). Hindlimb locomotor recovery was evaluated using an open-field test for 35 days following spinal cord injury. Long-term white matter sparing was assessed using eriochrome cyanide staining. Blood-spinal cord barrier disruption was evaluated by immunoblotting. Neutrophil infiltration, activation, effector functions, and cell death were determined by flow cytometry. Cytokine and chemokine expression in neutrophils was assessed using a gene array. RESULTS: Syk deficiency in neutrophils improved long-term functional recovery after spinal cord injury, but did not promote long-term white matter sparing. Neutrophil activation, cytokine expression, and cell death in the acutely injured spinal cord were attenuated by the genetic loss of Syk while neutrophil infiltration and effector functions were not affected. Acute blood-spinal cord barrier disruption was also unaffected by Syk deficiency in neutrophils. CONCLUSIONS: Syk facilitates specific neutrophil functional responses to spinal cord injury including activation, cytokine expression, and cell death. Long-term neurologic deficits are exacerbated by Syk signaling in neutrophils independent of acute blood-spinal cord barrier disruption and long-term white matter sparing. These findings implicate Syk in pathogenic neutrophil activities that worsen long-term functional recovery after spinal cord injury.

Passive Clearing and 3D Lightsheet Imaging of the Intact and Injured Spinal Cord in Mice.

The spinal cord contains a diverse array of sensory and motor circuits that are essential for normal function. Spinal cord injury (SCI) permanently disrupts neural circuits through initial mechanical damage, as well as a cascade of secondary injury events that further expand the spinal cord lesion, resulting in permanent paralysis. Tissue clearing and 3D imaging have recently emerged as promising techniques to improve our understanding of the complex neural circuitry of the spinal cord and the changes that result from damage due to SCI. However, the application of this technology for studying the intact and injured spinal cord remains limited. Here, we optimized the passive CLARITY technique (PACT) to obtain gentle and efficient clearing of the murine spinal cord without the need for specialized equipment. We demonstrate that PACT clearing enables 3D imaging of multiple fluorescent labels in the spinal cord to assess molecularly defined neuronal populations, acute inflammation, long-term tissue damage, and cell transplantation. Collectively, these procedures provide a framework for expanding the utility of tissue clearing to enhance the study of spinal cord neural circuits, as well as cellular- and tissue-level changes that occur following SCI.

Differences in Brain Morphology between Hydrocephalus Ex Vacuo and Idiopathic Normal Pressure Hydrocephalus.

OBJECTIVE: The distinction between idiopathic normal pressure hydrocephalus (iNPH) and hydrocephalus ex vacuo caused by encephalic volume loss remains to be established. This study aims to investigate radiological parameters as clinically useful tools to discriminate iNPH from hydrocephalus ex vacuo caused by Alzheimer's disease (AD). METHODS: A total of 54 patients with ventriculomegaly (iNPH, 25; hydrocephalus ex vacuo, 29) were recruited in this study. Consequently, nine radiological parameters were compared between iNPH and hydrocephalus ex vacuo using magnetic resonance imaging (MRI). RESULTS: A small callosal angle (CA), the Sylvian fissure dilatation, and absence of narrowing of superior parietal sulci discriminated the iNPH group from the hydrocephalus ex vacuo group (p<0.05). The final binary logistic regression model included narrowing of superior parietal sulci, degrees of the CA, and height of the Sylvian fissure after controlling for age and global Clinical Dementia Rating (CDR). The composite score made from these three indicators (narrowing of superior parietal sulci, degrees of the CA, and height of the Sylvian fissure) was statistically different between iNPH and hydrocephalus ex vacuo. CONCLUSION: The narrowing of the CA, dilatation of the Sylvain fissure, and narrowing of superior parietal sulci may be used as radiological key indices and noninvasive tools for the differential diagnosis of iNPH from hydrocephalus ex vacuo.

Cochlear duct length and cochlear distance on preoperative CT: imaging markers for estimating insertion depth angle of cochlear implant electrode.

OBJECTIVES: Preoperative estimation of the insertion depth angle of cochlear implant (CI) electrodes is essential for surgical planning. The purpose of this study was to determine the cochlear size using preoperative CT and to investigate the correlation between cochlear size and insertion depth angle in morphologically normal cochlea. METHODS: Thirty-five children who underwent CI were included in this study. Cochlear duct length (CDL) and the diameter of the cochlear basal turn (distance A/B) on preoperative CT and the insertion depth angle of the CI electrode on postoperative radiographs were independently measured by two readers. Correlation between cochlear size and insertion depth angle was evaluated. Interobserver agreement was calculated using the intraclass correlation coefficient (ICC). RESULTS: The mean CDL, distance A, and distance B of 70 ears were 36.20 ± 1.57 mm, 8.67 ± 0.42 mm, and 5.73 ± 0.32 mm, respectively. The mean insertion depth angle was 431.45 ± 38.42°. Interobserver agreements of CDL, distance A/B, and insertion depth angle were fair to excellent (ICC 0.864, 0.862, 0.529, and 0.958, respectively). Distance A (r = - 0.7643) and distance B (r = - 0.7118) showed a negative correlation with insertion depth angle, respectively (p < 0.0001). However, the correlation between CDL and insertion depth angle was not statistically significant (r = - 0.2333, p > 0.05). CONCLUSIONS: The CDL and cochlear distance can be reliably obtained from preoperative CT. Distance A can be used as a predictive marker for estimating insertion depth angle during CI surgery.