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Objectives@#This study aimed to quantify the relationship between proximal humeral rotation and the lateral border of the bicipital groove on fluoroscopic imaging. @*Methods@#A composite normal humerus with a marker placed on the lateral border of the bicipital groove was affixed to a custom rotation device at the proximal cut segment. Consecutive fluoroscopic images were captured from −60° to 60° in 5° increments and from −15° to 15° in 1° increments. The index value was calculated by taking the ratio of the distance from the medial boundary of the proximal humerus to the lateral border of the bicipital groove to the distance between the medial and lateral boundaries of the proximal humerus. The correlation between the humeral rotation and the index value was determined. @*Results@#The index value showed a strong positive linear correlation position during internal rotation of the humerus across the entire range (r=0.998, P<0.001), as well as when the humerus was externally rotated, ranging from 15° of internal rotation to 15° of external rotation (r=0.991, P<0.001). @*Conclusion@#The lateral border of the bicipital groove may serve as a useful intraoperative landmark for assessing proximal humeral rotation. This could potentially enhance the outcomes of humeral fracture repair and upper arm arthroplasty.

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The impact of the gut microbiota on glial cell growth and maturation via the gut-brain axis is highlighted herein. Considering that glial activation is crucial for onset and maintenance of neuropathic pain, we assessed the putative involvement of gut microbiota in the pathogenesis of neuropathic pain. Depletion of mouse gut microbiota with chronic antibiotics cocktail treatment prevented nerve injury-induced mechanical allodynia and thermal hyperalgesia both in male and female mice. Furthermore, post-injury treatment with antibiotics cocktail relieved ongoing pain in neuropathic pain-established mice. Upon recolonization of the gut microbiota after cessation of antibiotics, nerve injury-induced mechanical allodynia relapsed. Depletion of gut microbiota accompanied a decrease in nerve injury-induced TNF-α expression in the spinal cord. Notably, nerve injury changed the diversity and composition of the gut microbiome, which was measured by 16 s rRNA sequencing. We then tested if probiotic administration ameliorating dysbiosis affected the development of neuropathic pain after nerve injury. Probiotic treatment for three weeks prior to nerve injury inhibited nerve injury-induced TNF-α expression in the spinal cord and pain sensitization. Our data reveal an unexpected link between the gut microbiota and development and maintenance of nerve injury-induced neuropathic pain, and we propose a novel strategy to relieve neuropathic pain through the gut-brain axis.

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OBJECTIVES: Quantification of monoclonal protein (M-protein) by serum protein electrophoresis (SPE) is indispensable for diagnosing and monitoring monoclonal gammopathies. However, quantification of small and beta migrating M-proteins is challenging because of overlapping non-immunoglobulin and/or polyclonal immunoglobulin protein fractions. We compared a new integration method based on immunosubtraction (IS-CE) using capillary zone electrophoresis (CZE) against the routine method, which includes a combination of perpendicular drop (0.4%), corrected perpendicular drop (1%) and tangent skimming (98.5%). DESIGN & METHODS: The proposed method of M-protein quantification involves calculating the difference in area under the curve between the SPE and a class-specific IS-CE trace. We analyzed the difference in estimated M-protein concentrations obtained with the new method and routine integration methods using 913 samples. For IgA M-proteins at < 10 g/L, the estimated M-protein concentrations were compared with the total IgA concentration. RESULTS: The median M-protein concentration of 913 consecutive samples was 6.2 g/L (IQR 2.1-14.3 g/L). The median and median % difference between the two integration methods was 0.68 g/L (IQR 0.01-1.55 g/L) and 10.9% (IQR 0.18-38.7%), showing a larger estimated M-protein concentration with the new method. More than 25% difference was observed in 38% of the samples and was associated with lower total protein concentration, lower M-protein concentration, IgA and IgM heavy chain isotypes, and beta- or beta-gamma migration. When 161 samples with IgA M-protein < 10 g/L were compared against total IgA concentration, the median bias of the new method was smaller compared to that of the existing method (-0.95 g/L vs. -1.3 g/L, P < 0.0001). CONCLUSIONS: The use of IS based integration using CZE and IS-CE is promising especially for small and beta migrating M-proteins.

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Objective@#To evaluate the feasibility of single-shot whole thoracic time-resolved MR angiography (TR-MRA) to identify the feeding arteries of pulmonary arteriovenous malformations (PAVMs) and reperfusion of the lesion after embolization in patients with multiple PAVMs. @*Materials and Methods@#Nine patients (8 females and 1 male; age range, 23–65 years) with a total of 62 PAVMs who underwent percutaneous embolization for multiple PAVMs and were subsequently followed up using TR-MRA and CT obtained within 6 months from each other were retrospectively reviewed. All imaging analyses were performed by two independent readers blinded to clinical information. The visibility of the feeding arteries on maximum intensity projection (MIP) reconstruction and multiplanar reconstruction (MPR) TR-MRA images was evaluated by comparing them to CT as a reference. The accuracy of TR-MRA for diagnosing reperfusion of the PAVM after embolization was assessed in a subgroup with angiographic confirmation. The reliability between the readers in interpreting the TR-MRA results was analyzed using kappa (κ) statistics. @*Results@#Feeding arteries were visible on the original MIP images of TR-MRA in 82.3% (51/62) and 85.5% (53/62) of readers 1 and 2, respectively. Using the MPR, the rates increased to 93.5% (58/62) and 95.2% (59/62), respectively (κ = 0.760 and 0.792, respectively). Factors for invisibility were the course of feeding arteries in the anteroposterior plane, proximity to large enhancing vessels, adjacency to the chest wall, pulsation of the heart, and small feeding arteries. Thirty-seven PAVMs in five patients had angiographic confirmation of reperfusion status after embolization (32 occlusions and 5 reperfusions).TR-MRA showed 100% (5/5) sensitivity and 100% (32/32, including three cases in which the feeding arteries were not visible on TR-MRA) specificity for both readers. @*Conclusion@#Single-shot whole thoracic TR-MRA with MPR showed good visibility of the feeding arteries of PAVMs and high accuracy in diagnosing reperfusion after embolization. Single-shot whole thoracic TR-MRA may be a feasible method for the follow-up of patients with multiple PAVMs.

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Purpose@#In our previous studies, application of trichloroacetic acid (TCA) to gingival fibroblasts or to canine palatal soft tissue was verified to alter the expression of several genes responsible for cell cycle progression. In order to confirm this effect in a system allowing sequential release of TCA and epidermal growth factor (EGF), expression of various cell cycle genes following the application of the agents, using hydrophobically modified glycol chitosan (HGC)-based nano-controlled release system, was explored in this study. @*Materials and methods@#HGCbased nano-controlled release system was developed followed by loading TCA and EGF. The groups were defined as the control (CON); TCA-loaded nano-controlled release system (EXP1); TCA- and EGF- individually loaded nano-controlled release system (EXP2). At 24- and 48 hr culture, expression of 37 cell cycle genes was analyzed in human gingival fibroblasts. Correlations and the influential genes were also analyzed. @*Results@#Numerous genes such as cyclins (CCNDs), cell division cycles (CDCs), cyclin-dependent kinases (CDKs), E2F transcription factors (E2Fs), extracellular signal-regulated kinases (ERKs) and other cell cycle genes were significantly up-regulated in EXP1 and EXP2. Also, cell cycle arrest genes of E2F4, E2F5, and GADD45G were up-regulated but another cell cycle arrest gene SMAD4 was down-regulated. From the multiple regression analysis, CCNA2, CDK4, and ANAPC4 were determined as the most influential factors on the expression of ERK genes. @*Conclusion@#Application of TCA and EGF, using the HGC-based nano-controlled sequential release system significantly up-regulated various cell cycle progression genes, leading to the possibility of regenerating oral soft tissue via application of the proposed system.

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The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.

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The neurological symptoms of stroke have traditionally provided the foundation for functional mapping of the brain. However, there are many unresolved aspects in our understanding of cerebral activity, especially regarding high-level cognitive functions. This review provides a comprehensive look at the pathophysiology of post-stroke cognitive impairment in light of recent findings from advanced imaging techniques. Combining network neuroscience and clinical neurology, our research focuses on how changes in brain networks correlate with post-stroke cognitive prognosis. More specifically, we first discuss the general consequences of stroke lesions due to damage of canonical resting-state large-scale networks or changes in the composition of the entire brain. We also review emerging methods, such as lesion-network mapping and gradient analysis, used to study the aforementioned events caused by stroke lesions. Lastly, we examine other patient vulnerabilities, such as superimposed amyloid pathology and blood-brain barrier leakage, which potentially lead to different outcomes for the brain network compositions even in the presence of similar stroke lesions. This knowledge will allow a better understanding of the pathophysiology of post-stroke cognitive impairment and provide a theoretical basis for the development of new treatments, such as neuromodulation.

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BACKGROUND@#AND PURPOSE: Similar-sized stroke lesions at similar locations can have different prognoses in clinical practice. Lesion-network mapping elucidates network-level effects of lesions that cause specific neurologic symptoms and signs, and also provides a group-level understanding. This study visualized the effects of stroke lesions on the functional brain networks of individual patients.@*METHODS@#We enrolled patients with ischemic stroke who were hospitalized within 1 week of the stroke occurrence. Resting-state functional magnetic resonance imaging was performed 3 months after the index stroke. For image preprocessing, acute stroke lesions were visually delineated based on diffusion-weighted images obtained at admission, and the lesion mask was drawn using MRIcron software. Correlation matrices were calculated from 280 brain regions using the Brainnetome Atlas, and connectograms were visualized using in-house MATLAB code.@*RESULTS@#We found characteristic differences in connectograms between pairs of patients who had comparable splenial, frontal cortical, cerebellar, and thalamocapsular lesions. Two representative patients with bilateral thalamic infarctions showed significant differences in their reconstructed connectograms. The cognitive function had recovered well at 3 months after stroke occurrence in patients with well-maintained interhemispheric and intrahemispheric connectivities.@*CONCLUSIONS@#This pilot study has visualized the effects of stroke lesions on the functional brain networks of individual patients. Consideration of the neurobiologic mechanisms underlying the differences between their connectograms has yielded new hypotheses about differences in the effects of stroke lesions.

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Cell-to-cell adhesion is important for maintenance of brain structure and function. Abnormal neuronal cell adhesion and loss of its connectivity are considered a main cause of psychiatric disorders such as major depressive disorder (MDD). Various cell adhesion molecules (CAMs) are involved in neuronal cell adhesions and thereby affect brain functions such as learning and memory, cognitive functions, and psychiatric functions. Compared with other CAMs, neuronal growth regulator 1 (Negr1) has a distinct functioning mechanism in terms of its cross-talk with cytokine receptor signaling. Negr1 is a member of the immunoglobulin LON (IgLON) family of proteins and is involved in neuronal outgrowth, dendritic arborization, and synapse formation. In humans, Negr1 is a risk gene for obesity based on a genome-wide association study. More recently, accumulating evidence supports that it also plays a critical role in psychiatric disorders. In this review, we discuss the recent findings on the role of Negr1 in MDD, focusing on its regulatory mechanism. We also provide evidence of putative involvement of Negr1 in other psychiatric disorders based on the novel behavioral phenotypes of Negr1 knockout mice.

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BACKGROUND: Fracture–dislocation of the proximal interphalangeal (PIP) joint of the finger is challenging due to the high risk of stiffness. The purpose of this study is to evaluate the clinical and radiological results of a modified transosseous wiring technique for the management of chronic fracture–dislocations of the PIP joint. METHODS: Ten patients (nine men and one woman; mean age, 38.3 years; range, 21 to 69 years) with neglected fracture–dislocation of the PIP joint were included. The mean duration from injury to operation was 14.7 weeks (range, 3 to 66 weeks). The dorsolateral approach and extension block pinning were used to reduce dislocation. After thorough debridement of the scar tissues in the dorsal dead space and the fracture site, the reduction was maintained with transosseous wiring. Radiologic evaluations of bone union and arthritic changes and clinical evaluations (range of motion of the PIP joint and Disabilities of the Arm, Shoulder and Hand [DASH] score) were performed. The mean follow-up period was 12.9 months (range, 12 to 19 months). RESULTS: All patients demonstrated evidence of radiographic healing within a mean healing time of 6 weeks (range, 4 to 10 weeks); however, one had a widened gap and one had an early arthritic change. The mean range of motion in the PIP joint was 81° (range, 50° to 105°). The mean DASH score was 21.6 (range, 7.5 to 35.8). CONCLUSIONS: For chronic fracture–dislocation of the PIP joint, transosseous wiring with direct curettage and optimal bone purchase can provide satisfying outcome.

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OBJECTIVES@#To investigate the potential clinical use of the spinal instability neoplastic score (SINS) for determining the surgical strategy, especially regarding the need for anterior support.SUMMARY OF LITERATURE REVIEW: The SINS seems to enable an improved qualitative and quantitative assessment of spinal instability in patients with spinal metastasis.@*MATERIALS AND METHODS@#We retrospectively reviewed 69 consecutive patients who underwent surgical treatment for spinal metastasis. We assessed the patients' preoperative status with respect to each component of the SINS. Multiple logistic regression was performed to calculate odds ratios (ORs) representing the associations among SINS, age, Eastern Cooperative Oncology Group performance status, modified Tokuhashi score, as well as the preoperative Nurick grade variables and reconstruction of the anterior spinal column.@*RESULTS@#Among the 6 items in the SINS, those indicating the degree of collapse and alignment had significantly higher scores in those who underwent corpectomy and anterior support (p<0.001). Multiple logistic regression revealed that the total SINS was the only factor significantly associated with predicting whether anterior support should be performed (adjusted OR=1.595). Receiver operating characteristic (ROC) curve analysis suggested that a cut-off value of 10 points on the SINS scale could be used to decide whether anterior support following corpectomy should be performed (AUC=0.706).@*CONCLUSIONS@#The SINS, insofar as it assesses the degree of collapse and alignment, is a potentially useful tool for determining the surgical strategy in patients with spinal metastasis, especially for deciding upon the necessity of additional anterior support procedures.

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BACKGROUND/AIMS@#Nucleotide-binding oligomerization domain 1 (NOD1) is required for primary intestinal epithelial cells (IECs) to respond to natural mucopeptides secreted by gram-negative bacteria. Infection of human IECs with invasive bacteria up-regulates intercellular adhesion molecule-1 (ICAM-1) expression. However, the role of NOD family members in host defense has been largely unknown. The aim of this study was to determine whether there is a functional role for NOD1 in the up-regulation of ICAM-1 expression in invasive bacteria-infected IECs.@*METHODS@#ICAM-1 mRNA expression was compared between controls, Caco-2 or HT29 cells transfected with an empty vector, and IECs stably transfected with a dominant-negative (DN) NOD1. Expression was compared using qualitative reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and flow cytometry after infection with enteroinvasive Escherichia coli O29:NM or Shigella flexneri. Nuclear factor kB (NF-κB) activation was determined by electrophoretic mobility shift assays.@*RESULTS@#DN NOD1 significantly inhibited the up-regulation of ICAM-1 expression in response to an enteroinvasive bacterial infection. The Caco-2 cells transfected with DN NOD1 manifested marked inhibition of NF-kB activation in response to E. coli O29:NM infection.@*CONCLUSIONS@#Signaling through NOD1 may play an essential role in neutrophil trafficking following infection with enteroinvasive bacteria.

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A 66-year-old woman was referred for treatment of incidental detection of two intracranial aneurysms. Time-of-flight MR angiography (TOF MRA) revealed two aneurysms at the M1 segment of the right middle cerebral artery, and clinoid segment of left internal carotid artery, respectively. On digital subtraction angiography, there was a saccular aneurysm on the left internal carotid artery, but the other aneurysm was not detected on the right middle cerebral artery. Based on comprehensive review of imaging findings, organized thrombosed aneurysm was judged as the most likely diagnosis. In the presented report, magnetization transfer (MT) pulse to TOF MRA was used, to differentiate aneurysm-mimicking lesion on TOF MRA. We report that MT technique could be effective in differentiating true aneurysm, from possible T1 high signal artifact on TOF MRA.

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OBJECTIVE: To assess the nutritional status of Korean patients with spinal cord injury (SCI), identify the predictors of undernutrition, and investigate the relationship between undernutrition and clinical outcomes. METHODS: A retrospective study design was used to determine the nutritional status of 130 patients over 19 years old admitted to the rehabilitation hospital of Yonsei University Health System between June 2015 and February 2017. The nutritional status was assessed using the malnutrition universal screening tool (MUST) and the spinal nutrition screening tool (SNST). The relationship between undernutrition and clinical outcomes was examined by comparing a low-risk group with an at-risk group using a t-test. RESULTS: Among the SCI patients, 70 (50.8%) were confirmed with undernutrition based on the MUST scores, while 60 (46.2%) had undernutrition based on the SNST scores. It was found that undernutrition has an effect on functional outcomes. CONCLUSION: We assessed the undernutrition risk in Korean SCI patients, and found that approximately 50% of the patients were at risk of undernutrition. We also found that undernutrition can affect functional recovery.

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Ceruminous adenoma is a benign neoplasm of the ceruminous gland, and its development in human external auditory canal is very rare. Due to the limited number of cases, controversy still exists about nomenclature, classification, diagnosis and its treatment. Recently we experienced a 55 years old woman who was diagnosed with ceruminous adenoma of the external auditory canal, and who was treated with wide excision. So we report this uncommon case in combination with a review of the literature.

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STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To investigate the potential clinical use of the spinal instability neoplastic score (SINS) for determining the surgical strategy, especially regarding the need for anterior support. SUMMARY OF LITERATURE REVIEW: The SINS seems to enable an improved qualitative and quantitative assessment of spinal instability in patients with spinal metastasis. MATERIALS AND METHODS: We retrospectively reviewed 69 consecutive patients who underwent surgical treatment for spinal metastasis. We assessed the patients' preoperative status with respect to each component of the SINS. Multiple logistic regression was performed to calculate odds ratios (ORs) representing the associations among SINS, age, Eastern Cooperative Oncology Group performance status, modified Tokuhashi score, as well as the preoperative Nurick grade variables and reconstruction of the anterior spinal column. RESULTS: Among the 6 items in the SINS, those indicating the degree of collapse and alignment had significantly higher scores in those who underwent corpectomy and anterior support (p<0.001). Multiple logistic regression revealed that the total SINS was the only factor significantly associated with predicting whether anterior support should be performed (adjusted OR=1.595). Receiver operating characteristic (ROC) curve analysis suggested that a cut-off value of 10 points on the SINS scale could be used to decide whether anterior support following corpectomy should be performed (AUC=0.706). CONCLUSIONS: The SINS, insofar as it assesses the degree of collapse and alignment, is a potentially useful tool for determining the surgical strategy in patients with spinal metastasis, especially for deciding upon the necessity of additional anterior support procedures.

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Inorganic amorphous oxide semiconductor (AOS) materials such as amorphous InGaZnO (a-IGZO) possess mechanical flexibility and outstanding electrical properties, and have generated great interest for use in flexible and transparent electronic devices. In the past, however, AOS devices required higher activation energies, and hence higher processing temperatures, than organic ones to neutralize defects. It is well known that one-dimensional nanowires tend to have better carrier mobility and mechanical strength along with fewer defects than the corresponding two-dimensional films, but until now it has been difficult, costly, and impractical to fabricate such nanowires in proper alignments by either "bottom-up" growth techniques or by "top-down" e-beam lithography. Here we show a top-down, cost-effective, and scalable approach for the fabrication of parallel, laterally oriented AOS nanoribbons based on lift-off and nano-imprinting. High mobility (132 cm2/Vs), electrical stability, and transparency are obtained in a-IGZO nanoribbons, compared to the planar films of the same a-IGZO semiconductor.

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PURPOSE: Calcium channel blockers diltiazem and nitrate have been used as selective coronary vasodilators for patients with significant coronary artery spasm (CAS). However, no study has compared the efficacy of diltiazem alone versus diltiazem with nitrate for long-term clinical outcomes in patients with CAS. MATERIALS AND METHODS: A total of 2741 consecutive patients without significant coronary artery disease with positive CAS by acetylcholine (Ach) provocation test between November 2004 and May 2014 were enrolled. Significant CAS was defined as a narrowing of >70% by incremental intracoronary injection of 20, 50, and 100 µg of Ach into the left coronary artery. Patients were assigned to either the diltiazem group (n=842) or the dual group (diltiazem with nitrate, n=1899) at physician discretion. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM analysis, two well-balanced groups (811 pairs, n=1622, C-statistic=0.708) were generated. RESULTS: At 5 years, there were similar incidences in primary endpoints, including mortality, myocardial infarction, revascularization, and recurrent angina requiring repeat coronary angiography between the two groups. Diltiazem alone was not an independent predictor for major adverse cardiovascular events or recurrent angina requiring repeat coronary angiography. CONCLUSION: Despite the expected improvement of endothelial function and the relief of CAS, the combination of diltiazem and nitrate treatment was not superior to diltiazem alone in reducing mortality and cardiovascular events up to 5 years in patients with significant CAS.

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BACKGROUND AND OBJECTIVES: Many patients experience middle ear surgery via retroauricular approach. While not a main interest of the surgery, the change of the auricular shape after surgery has been a subject of complaint by some patients. In this study, we wanted to determine if a change in the auricular shape occurs after middle ear surgery and evaluate the possibility of using reconstruction of posterior auricular muscle as a treatment option for this kind of change. SUBJECTS AND METHOD: Forth patients who received middle ear surgery were enrolled in this study. Retroauricular incision and canal up mastoidectomy were carried out to all patients. The patients were separated into two groups randomly before surgery: one group that had the reconstruction of posterior auricular muscle during surgery, and the other that did not. The average of heights of the helix was compared. Also, patients were asked to fill out a questionnaire about auricular shape before and after surgery. RESULTS: The heights of helix increased about 1.6 mm after surgery; however, the difference of increment as a result of reconstruction of posterior auricular muscle was not statistically significant. Questionnaire about the change of auricular shape after surgery showed that only 8% patients had noticed about the change of auricular shape after surgery. CONCLUSION: Most patients have no complaint about auricular shape after middle ear surgery via retroauricular approach. The average of heights of the helix increases after middle ear surgery. However, the reconstruction of the posterior auricular muscle is not effective for reducing the observed increment of heights of the helix following middle ear surgery via retroauricular approach.

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OBJECTIVE: To determine whether providing education about the disease pathophysiology and drug mechanisms and side effects, would be effective for reducing the use of pain medication while appropriately managing neurogenic pain in spinal cord injury (SCI) patients. METHODS: In this prospective study, 109 patients with an SCI and neuropathic pain, participated in an educational pain management program. This comprehensive program was specifically created, for patients with an SCI and neuropathic pain. It consisted of 6 sessions, including educational training, over a 6-week period. RESULTS: Of 109 patients, 79 (72.5%) initially took more than two types of pain medication, and this decreased to 36 (33.0%) after the educational pain management program was completed. The mean pain scale score and the number of pain medications decreased, compared to the baseline values. Compared to the non-response group, the response group had a shorter duration of pain onset (p=0.004), and a higher initial number of different medications (p<0.001) and certain types of medications. CONCLUSION: This study results imply that an educational pain management program, can be a valuable complement to the treatment of spinal cord injured patients with neuropathic pain. Early intervention is important, to prevent patients from developing chronic SCI-related pain.

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