Investigation of the effectiveness of intermittent electromagnetic field stimulation for early internal cartilaginous ossification in prechondrocytic ATDC5 cells.

Pulsed electromagnetic field (PEMF) stimulation has been widely applied clinically to promote bone healing; however, its detailed mechanism of action, particularly in endochondral ossification, remains elusive, and long-term stimulation is required for its satisfactory effect. The aim of this study was to investigate the involvement of the mammalian target of rapamycin (mTOR) pathway in chondrocyte differentiation and proliferation using a mouse prechondroblast cell line (ATDC5), and establish an efficient PEMF stimulation strategy for endochondral ossification. The changes in cell differentiation (gene expression levels of aggrecan, type II collagen, and type X collagen) and proliferation (cellular uptake of bromodeoxyuridine [BrdU]) in ATDC5 cells in the presence or absence of rapamycin, an mTOR inhibitor, was measured. The effects of continuous and intermittent PEMF stimulation on changes in cell differentiation and proliferation were compared. Rapamycin significantly suppressed the induction of cell differentiation markers and the cell proliferation activity. Furthermore, only intermittent PEMF stimulation continuously activated the mTOR pathway in ATDC5 cells, significantly promoting cell proliferation. These results demonstrate the involvement of the mTOR pathway in chondrocyte differentiation and proliferation and suggest that intermittent PEMF stimulation could be effective as a stimulus for endochondral ossification during fracture healing process, thereby reducing stimulation time.

Magnetic resonance imaging findings in patients with dropped head syndrome.

BACKGROUND: Dropped head syndrome (DHS) is difficult to diagnose only by clinical examination. Although characteristic images on X-rays of DHS have been studied, changes in soft tissue of the disease have remained largely unknown. Magnetic resonance imaging (MRI) is useful for evaluating soft tissue, and we therefore performed this study with the purpose of investigating the characteristic signal changes of DHS on MRI by a comparison with those of cervical spondylosis. METHODS: The study involved 35 patients diagnosed with DHS within 6 months after the onset and 32 patients with cervical spondylosis as control. The signal changes in cervical extensor muscles, interspinous tissue, anterior longitudinal ligament (ALL) and Modic change on MRI were analyzed. RESULTS: Signal changes of cervical extensor muscles were 51.4% in DHS and 6.3% in the control group, those of interspinous tissue were 85.7% and 18.8%, and those of ALL were 80.0% and 21.9%, respectively, suggesting that the frequency of signal changes of cervical extensor muscles, interspinous tissue and ALL was significantly higher in the DHS group (p < 0.05). The presence of Modic change of acute phase (Modic type I) was also significantly higher in the DHS group than in the control group (p < 0.001). CONCLUSION: MRI findings of DHS within 6 months after the onset presented the characteristic signal changes in cervical extensor muscles, interspinous tissue, ALL and Modic change. Evaluation of MRI signal changes is useful for an objective evaluation of DHS.

A novel diagnostic examination for dropped head syndrome (DHS) (Prone position cervical extension test; DHS test).

BACKGROUND: Dropped head syndrome (DHS) is followed by severe cervical extension muscle weakness that results in chin-on chest deformity. However, maintaining a neutral cervical position can be temporarily possible, and the diagnosis of DHS might sometimes be difficult. The purpose of the present study is to examine a novel clinical test (DHS test) as the diagnostic utility for objective evaluation that focuses on cervical extension condition in the prone position. METHODS: One hundred subjects were diagnosed with isolated neck extensor myopathy (INEM)-DHS at our hospital (17 men and 83 women, mean age 75.0 ± 8.5 years), and 62 subjects were enrolled as age-matched controls. The DHS test consisted of three examinations; the first was "Ceiling gazing test" in standing position, the second was horizontal gazing in "Sphinx prone position test", and the third was horizontal gazing in "Hands and knees prone position test". We investigated the sensitivity and specificity of the DHS test for DHS. RESULTS: The patients showing positive in the INEM-DHS group were 63/100 in Ceiling gaze test, 73/100 in the Sphinx prone position test, and 91/100 in the Hands and knees prone position test. In the control group, 0/62 patients presented positive in the Ceiling gaze test, 4/62 in the Sphinx prone position test, and 0/62 in the Hands and knees prone position test. Sensitivity and specificity of the DHS test were 63.0%/100%, 73.0%/93.5%, and 91.0%/100% in the Ceiling gaze test, Sphinx position prone position test, and Hands and knees prone position test, respectively. CONCLUSION: The prone position cervical extension test (DHS test) would be useful as a novel objective diagnostic tool for INEM-DHS.

In vivo creep and wear performance of vitamin-E-diffused highly crosslinked polyethylene in total hip arthroplasty.

INTRODUCTION: An acetabular liner thickness of around 6 mm remains the "gold standard" in total hip arthroplasty. Some surgeons have been recommending the use of the thickest possible liner because contact stress and strain in articulating surfaces decrease with increasing the wall thickness. The purpose of this study was to determine whether in vivo creep and wear performance could be enhanced using a thicker liner over the standard thickness in vitamin-E-diffused highly crosslinked polyethylene (HXLPE). MATERIALS AND METHODS: One hundred and twenty-two hips were allocated to age-matched, sex-matched, and body mass index-matched two subgroups implanted either with a 6.8- or 8.9-mm-thick vitamin-E-diffused HXLPE liner against 28-mm cobalt-chrome femoral head, and followed-up for 7 years. Linear and volumetric penetration of femoral head into the liners attributed to creep and wear were analyzed for each group. RESULTS: Compressive creep strain generated at the initial 6 months was significantly larger in the 6.8-mm group (2.6%) than in the 8.9-mm group (2.2%). The linear steady-state wear observed after 2 years was 0.0019 and 0.0015 mm/year, whereas the volumetric steady-state wear was 0.54 and 0.45 mm3/years in the 6.8- and 8.9-mm-thick groups, respectively. Although less strain in the thicker group resulted in a slightly less wear, it did not reach significant differences in the steady-state wear rates between the groups. CONCLUSION: No clinical significance for using a thicker liner over the standard thickness (6.8 mm → 8.9 mm) was confirmed in the vitamin-E-diffused HXLPE according to the 7-year follow-up. The wear rates for both thicknesses were very low enough to prevent osteolysis, and no mechanical failure was observed at any follow-up interval. Nevertheless, since the significantly higher strain was seen in the thinner liner, further follow-up is needed to compare the longer term wear and the incidence of osteolysis and component fracture.

Immune-Nutritional Status as a Novel Prognostic Predictor of Bell's Palsy.

INTRODUCTION: The prognosis of Bell's palsy, idiopathic facial nerve palsy (FNP), is usually predicted by electroneuronography in subacute phase. However, it would be ideal to establish a reliable and objective examination applicable in acute phase to predict the prognosis of FNP. Immune-nutritional status (INS) calculated from peripheral blood examination is recently reported as the prognostic factor in various disease. However, the validity of INS as the prognostic factor in Bell's palsy is not well known. Thus, we conducted a retrospective study to investigate the usefulness of INS as prognostic predictors of Bell's palsy. METHODS: We reviewed the medical records of 79 patients with Bell's palsy and divided into two groups as "complete recovery" and "incomplete recovery" groups. Clinical features such as severity of FNP and INS, including neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), prognostic nutritional index (PNI), and controlling nutrition status (CONUT) score, were assessed. RESULTS: In univariate analysis, statistically significant differences were observed in clinical score of facial movement, NLR, LMR, PNI, and CONUT score at the initial examination between the two groups (p < 0.05). Furthermore, in multivariate analysis, statistically significant differences were also observed in facial movement score and PNI at the initial examination (p < 0.05). CONCLUSION: Immune and nutritional condition play important roles in the pathogenesis of Bell's palsy, suggesting that INS would be one of the useful prognostic factors in Bell's palsy.

Risk factors for preoperative nasal carriage of methicillin-resistant bacteria in total hip and knee arthroplasty patients.

BACKGROUND: The present study aimed to identify risk factors for preoperative nasal carriage of resistant bacteria - MRSA methicillin-resistant Staphylococcus (S.) aureus, MRSE (methicillin-resistant Staphylococcus epidermidis), and MRCNS (methicillin-resistant coagulase negative staphylococci) in total hip and knee arthroplasty (THA and TKA) patients. METHODS: Nasal cultures were obtained from 538 patients before THA (262 primary and 26 revision) and TKA (241 primary and 9 revision). These were classified either as methicillin-resistant bacteria (group MR) or methicillin-susceptible bacteria (including culture-negative) (group MS). Patient characteristics were compared between these groups using logistic regression models. RESULTS: The resistant bacteria were preoperatively present in 33.1% (178 patients) among all patients. MRSE, MRCNS, and MRSA were detected in 27.5% (148 patients), 3.7% (20 patients), and 1.9% (10 patients). In the unadjusted comparisons of the patient characteristics between the groups MR and MS, a significant difference was found in the percentages of diabetic patients (15.2% vs. 9.2%, P = 0.04); the association remained after the multivariable adjustment for possible risk factors (P < 0.001). In addition, the diabetic patients in the group MR showed a higher percentage of receiving insulin injection than those in the group MS (25.9% vs. 6.1%, P = 0.063), and their mean levels of HbA1c were significantly higher in the group MR than the MS (6.8% vs. 6.4%, P = 0.03). CONCLUSIONS: We identified diabetes as a risk factor for the preoperative nasal carriage of resistant bacteria. Our results suggest that, in order to prevent a surgical site infection (SSI), extra care should be taken in performing joint arthroplasties for diabetic patients, especially using insulin and with high HbA1c levels (≥6.6%) prior to the surgical procedures.

Glucose-dependent aerobic glycolysis contributes to recruiting viral components into HIV-1 particles to maintain infectivity.

The cellular environment affects optimal viral replication because viruses cannot replicate without their host cells. In particular, metabolic resources such as carbohydrates, lipids, and ATP are crucial for viral replication, which is sensitive to cellular metabolism. Intriguingly, recent studies have demonstrated that human immunodeficiency virus type 1 (HIV-1) infection induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis in CD4+ T cells to produce the virus efficiently. However, the importance of aerobic glycolysis in maintaining the quality of viral components and viral infectivity has not yet been fully investigated. Here, we show that aerobic glycolysis is necessary not only to override the inhibitory effect of virion-incorporated glycolytic enzymes, but also to maintain the enzymatic activity of reverse transcriptase and the adequate packaging of envelope proteins into HIV-1 particles. To investigate the effect of metabolic remodeling on the phenotypic properties of HIV-1 produced by infected cells, we replaced glucose with galactose in the culture medium because the cells grown in galactose-containing medium are forced to carry out oxidative metabolism instead of aerobic glycolysis. We found that the packaging levels of glyceraldehyde 3-phosphate dehydrogenase, alpha-enolase and pyruvate kinase muscle type 2, which decrease HIV-1 infectivity by packaging into viral particles, are increased in progeny viruses produced by the cells grown in galactose-containing medium. Furthermore, we found that the entry and reverse transcription efficiency of the progeny viruses were reduced, which was caused by a decrease in the enzymatic activity of reverse transcriptase in the viral particles and a decrease in the packaging levels of envelope proteins and reverse transcriptase. These results indicate that the aerobic glycolysis environment in HIV-1-infected cells may contribute to the quality control of viruses.

Prostaglandin E2 induces dual-specificity phosphatase-1, thereby attenuating inflammatory genes expression in human osteoarthritic synovial fibroblasts.

Characteristic features of osteoarthritis (OA) are joint pain and cartilage degeneration. The degeneration is caused by excess induction of matrix metalloproteinases (MMPs) and the pain is caused by nerve growth factor (NGF)-dependent nerve invasion into synovial tissue in addition to nociceptive pain by prostaglandin (PG)E2. The objective of this study was to clarify the suppressive mechanism of PGE2 on the regulation of MMPs and NGF by focusing on mitogen-activated protein kinases (MAPKs) and their endogenous phosphatase, dual-specificity phosphatase (DUSP)-1 in human synovial fibroblasts. PGE2 strongly increased DUSP-1 and suppressed IL-1ß-induced MAPKs phosphorylation. Inhibition of MAPKs by selective inhibitors differentially regulated the IL-1ß-induced expression of MMPs and NGF expression. IL-1ß-induced MAPKs phosphorylation was prolonged and enhanced in DUSP-1 knockdown cells and the expression of MMPs and NGF was also increased. This study revealed that PGE2 has novel biological activity that suppresses NGF and MMPs expression by inducing DUSP-1 expression.

Use of residual neural network for the detection of ossification of the posterior longitudinal ligament on plain cervical radiography.

Ossification of the posterior longitudinal ligament (OPLL) causes serious problems, such as myelopathy and acute spinal cord injury. The early and accurate diagnosis of OPLL would hence prevent the miserable prognoses. Plain lateral radiography is an essential method for the evaluation of OPLL. Therefore, minimizing the diagnostic errors of OPLL on radiography is crucial. Image identification based on a residual neural network (RNN) has been recognized to be potentially effective as a diagnostic strategy for orthopedic diseases; however, the accuracy of detecting OPLL using RNN has remained unclear. An RNN was trained with plain lateral cervical radiography images of 2,318 images from 672 patients (535 images from 304 patients with OPLL and 1,773 images from 368 patients of Negative). The accuracy, sensitivity, specificity, false positive rate, and false negative rate of diagnosis of the RNN were calculated. The mean accuracy, sensitivity, specificity, false positive rate, and false negative rate of the model were 98.9%, 97.0%, 99.4%, 2.2%, and 1.0%, respectively. The model achieved an overall area under the curve of 0.99 (95% confidence interval, 0.97-1.00) in which AUC in each fold estimated was 0.99, 0.99, 0.98, 0.98, and 0.99, respectively. An algorithm trained by an RNN could make binary classification of OPLL on cervical lateral X-ray images. RNN may hence be useful as a screening tool to assist physicians in identifying patients with OPLL in future setting. To achieve accurate identification of OPLL patients clinically, RNN has to be trained with other cause of myelopathy.

DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1ß-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells.

The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1ß (IL-1ß). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1ß is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1ß-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1ß-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1ß-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1ß-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression.

Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration.

BACKGROUND: A protein exhibiting more than one biochemical function is termed a moonlighting protein. Glycolytic enzymes are typical moonlighting proteins, and these enzymes control the infection of various viruses. Previously, we reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and alpha-enolase (ENO1) are incorporated into human immunodeficiency virus type 1 (HIV-1) particles from viral producer cells and suppress viral reverse transcription independently each other. However, it remains unclear whether these proteins expressed in viral target cells affect the early phase of HIV-1 replication. RESULTS: Here we show that the GAPDH expression level in viral target cells does not affect the early phase of HIV-1 replication, but ENO1 has a capacity to suppress viral integration in viral target cells. In contrast to GAPDH, suppression of ENO1 expression by RNA interference in the target cells increased viral infectivity, but had no effect on the expression levels of the HIV-1 receptors CD4, CCR5 and CXCR4 and on the level of HIV-1 entry. Quantitative analysis of HIV-1 reverse transcription products showed that the number of copies of the late products (R/gag) and two-long-terminal-repeat circular forms of viral cDNAs did not change but that of the integrated (Alu-gag) form increased. In contrast, overexpression of ENO1 in viral target cells decreased viral infectivity owing to the low viral integration efficiency. Results of subcellular fractionation experiments suggest that the HIV integration at the nucleus was negatively regulated by ENO1 localized in the nucleus. In addition, the overexpression of ENO1 in both viral producer cells and target cells most markedly suppressed the viral replication. CONCLUSIONS: These results indicate that ENO1 in the viral target cells prevents HIV-1 integration. Importantly, ENO1, but not GAPDH, has the bifunctional inhibitory activity against HIV-1 replication. The results provide and new insights into the function of ENO1 as a moonlighting protein in HIV-1 infection.

Relationship between cervical and global sagittal balance in patients with dropped head syndrome.

BACKGROUND: DHS is characterized by chin-on-chest deformity and devastatingly impedes activities of daily living in affected individuals. There is a paucity of literature about the pathophysiology of DHS including knowledge about spinal sagittal alignment. We conducted this study to clarify the relationship between cervical sagittal alignment and global sagittal balance in DHS. METHODS: This is a retrospective radiographic study of a case series of DHS. Forty-one patients with diagnosed DHS were enrolled. Measurements were made using lateral standing radiograph. RESULTS: C2-C7 sagittal vertical axis (SVA) was estimated as 52.0 ± 2.4 mm. Among sagittal parameters, C7-S1 SVA positively correlated with C2-C7 angle (C2-C7 A) (r = 0.33). For the correlations between C7 and S1 SVA and C2-C7 A, both logistic and linear regression models were used to determine the threshold for C2-C7 A value responsible for global sagittal balance. C2-C7 A of - 15.0 and 6.0 were predicted by logistic and linear regression models and were considered responsible for the occurrence of global positive imbalance. Therefore, we divided into two groups, namely, cervical kyphosis group (C type) and diffuse kyphosis group (D type) by median value of C2-C7 A. Enlarged thoracic kyphosis and global positive imbalance were observed in D type compared to C type. CONCLUSION: C2-C7 A exhibited correlations with cervical balance and also with global balance. There should be various type of thoraco-lumbar alignment in DHS. These slides can be retrieved under Electronic Supplementary Material.

The factors related to the poor ADL in the patients with osteoporotic vertebral fracture after instrumentation surgery.

PURPOSE: Osteoporotic vertebral fracture (OVF) with nonunion or neurological deficit may be a candidate for surgical treatment. However, some patients do not show improvement as expected. Therefore, we conducted a nationwide multicenter study to determine the predictors for postoperative poor activity of daily living (ADL) in patients with OVF. METHODS: We retrospectively reviewed the case histories of 309 patients with OVF who underwent surgery. To determine the factors predicting postoperative poor ADL, uni- and multivariate statistical analyses were performed. RESULTS: The frequency of poor ADL at final follow-up period was 9.1%. In univariate analysis, preoperative neurological deficit (OR, 4.1; 95% CI, 1.8-10.3; P < 0.001), perioperative complication (OR, 3.4; P = 0.006), absence of preoperative bone-modifying agent (BMA) administration (OR, 2.7; P = 0.03), and absence of postoperative recombinant human parathyroid hormone (rPTH) administration (OR, 3.9; P = 0.006) were significantly associated. In multivariate analysis, preoperative neurological deficit (OR, 4.6; P < 0.001), perioperative complication (OR, 3.4; P = 0.01), and absence of postoperative rPTH administration (OR, 3.9; P = 0.02) showed statistical significance. CONCLUSIONS: Preoperative neurological deficit, perioperative complication, and absence of postoperative rPTH administration were considered as predictors for postoperative poor ADL in patients with OVF. Neurological deficits and complications are often inevitable factors; therefore, rPTH is an important option for postoperative treatment for OVF. These slides can be retrieved under Electronic Supplementary Material.

Intermittent pulsed electromagnetic field stimulation activates the mTOR pathway and stimulates the proliferation of osteoblast-like cells.

Pulsed electromagnetic fields (PEMFs) have been shown to be a noninvasive physical stimulant for bone fracture healing. However, PEMF stimulation requires a relatively long period of time and its mechanism of action has not yet been fully clarified. Recently, the mammalian target of rapamycin (mTOR) pathway has been shown to be involved in bone formation. This study aimed to investigate the effects of PEMFs on osteoblastic MC3T3-E1 cells by examining various cellular responses including changes in the mTOR pathway. Continuous PEMF stimulation induced a transient phosphorylation of the mTOR pathway, whereas intermittent PEMF stimulation (1 cycle of 10 min stimulation followed by 20 min of stimulation pause) revitalized the reduced phosphorylation. Moreover, PEMF stimulation stimulated cell proliferation (bromodeoxyuridine incorporation) rather than differentiation (alkaline phosphatase activity), with a more notable effect in the intermittently stimulated cells. These results suggest that intermittent PEMF stimulation may be effective in promoting bone fracture healing by accelerating cell proliferation, and in shortening stimulation time. Bioelectromagnetics. 2019;40:412-421. © 2019 Bioelectromagnetics Society.

Impact of pelvic incidence on change in lumbo-pelvic sagittal alignment between sitting and standing positions.

PURPOSE: Lumbo-pelvic sagittal alignment is affected by pelvic incidence (PI), and the PI represents the compensatory capacity of lumbo-pelvic sagittal alignment. The purpose of this study was to analyze changes in lumbo-pelvic sagittal alignment between the standing and sitting positions and to analyze its association with PI. METHODS: This study included 253 subjects (160 men and 93 women; age 53.6 ± 7.4 years). The subjects were divided into three groups (younger age group (YG), from 20 to 49 years; middle age group, from 50 to 69 years, and older age group (OG), of 70 years and above). Lumbar lordotic angle (LL), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), and the associations between the changes in LL (∆LL), SS (∆SS), PT (∆PT), and PI were analyzed. RESULTS: In the YG, the amount of change in LL, SS, and PT was larger than in the OG. These parameters correlated with age in the standing position but not in the sitting position. On the other hand, in all groups, there were positive correlations between PI and changes between the standing and sitting positions. Multiple logistic regression analysis demonstrated that ∆LL = 3.81 - 0.72 × PT + 0.52 × PI, ∆SS = - 4.50 - 5.3 × PT + 0.34 × PI, and ∆PT = - 9.1 + 3.5 × PT - 0.21 × PI. CONCLUSIONS: Change in lumbo-pelvic parameters between the sitting and standing positions correlated with PI. These slides can be retrieved under Electronic Supplementary Material.

Differences in cervical sagittal alignment between the standing and sitting positions.

BACKGROUND: Sagittal spinal alignment has mainly analyzed in the standing position. According to previous studies, there are significant differences in lumbopelvic alignment between the standing and sitting positions and cervical alignment is affected by lumbopelvic alignment. In this study, therefore, we hypothesized that cervical sagittal alignments are different between the standing and sitting positions. METHODS: A total of 108 patients with spinal degenerative diseases underwent whole spine radiography. Cervical lordosis (CL), C2-7 SVA, T1S, C7-S1 SVA, TK, LL, SS, PT, and PI were measured in the standing and sitting positions. Patients were classified into 3 groups according to the changes in CL (ΔCL, CL in the sitting position - CL in the standing position); ΔCL < -3° (Decreased group: DG; 28.7%), -3° ≤ ΔCL ≤ 3° (Unchanged group: UG; 41.7%), and ΔCL > 3° (Increased group: IG; 29.6%). RESULTS: The parameters of the UG in the standing position were closer to the ideal alignment (SRS-Schwab classification). In the DG, CL, T1S, and C7-S1 SVA in the standing position were significantly higher than in the UG. In the IG, PI-LL in the standing position was significantly higher than in the UG. In the sitting position, pelvis was rotated posteriorly (decrease in SS and increase in PT) and lumbar lordosis was flattened (decrease in LL) in all groups, and C2-7 SVA was significantly higher in the DG than in the UG. CONCLUSIONS: CL was different between the standing and sitting positions in 58.3% of individuals. However, patients with good spinal sagittal alignment appeared to not undergo any changes in cervical alignment. Our results suggest the possibility that patients who had a positive imbalance and large PI-LL mismatch in the standing position had decreased CL and increased CL, respectively, when in the sitting position.

Overview of dropped head syndrome (Combined survey report of three facilities).

BACKGROUND: Dropped head syndrome (DHS) is a low prevalence and the clinical features remain unclear. The purpose of the present study was to clarify the general overview of DHS. METHODS: The subjects were 67 consecutive DHS patients (17 men and 50 women; average age 72.9 ± 10.2 years) presenting difficulty of horizontal gaze in up-right position. The patients' background, global spinal alignment, clinical findings and treatment were analyzed. RESULTS: The peak population of DHS was 75-79-year-old females. The comorbidities included Parkinson's disease in 9 cases, minor trauma in 9 cases, post-cervical operation in 3 cases, mental depression in 3 cases, malignant tumor in 3 cases, diabetes mellitus in 2 cases and rheumatoid arthritis in 2 cases. The C2-C7 cervical coronal vertical axis was distributed more to the right side (2.6 ± 12.8 mm). Regarding sagittal alignment, 24 cases (35.8%) showed negative balanced DHS (N-DHS) and 43 cases (64.2%) showed positive balanced DHS (P-DHS). There were significant differences in C2-C7 angle, T1S, LL and PI-LL between the two groups. Cervical or back pain was present in 62 cases (92.5%), and average numerical rating scale was 3.0 ± 2.6. Fourteen cases (20.9%) recovered (average 11.3 months), but 29 cases (43.3%) did not recover without surgery. Twenty-four cases (35.8%) underwent surgery, 20 for cervical spine and 4 for thoraco-lumbar spine, and horizontal gaze difficulty was improved in all patients post-surgery. CONCLUSION: DHS was mainly observed in elderly women. About 20% of DHS patients recovered without surgical treatment. DHS was accompanied by scoliosis in 37.3% of the cases.

Bacille Calmette-Guérin (BCG) spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy: a case report and literature review.

BACKGROUND: Although intravesical bacille Calmette-Guérin (BCG) therapy is accepted as an effective treatment for bladder cancer, serious complications may occur in rare cases. To date, only 4 cases have been reported in which the patient developed a combination of mycotic aortic aneurysm and BCG spondylitis. Accurate diagnosis of BCG spondylitis is important because it is an iatrogenic disease, and its treatment is different from usual tuberculous spondylitis. However, distinguishing BCG spondylitis from usual tuberculous spondylitis is very difficult and takes a long time. In this study, we were able to suspect BCG spondylitis at an early stage from the result of the interferon-gamma release assay (IGRA). CASE PRESENTATION: We encountered a case of BCG spondylitis with adjacent mycotic aortic aneurysm after intravesical BCG therapy in a 76-year-old man. We performed a 2-stage operation to obtain spine stabilization and replace the aneurysm with a synthetic graft. We started multidrug therapy with antituberculosis medication, excluding pyrazinamide, because the patient's history of BCG therapy, negative IGRA, and positive of tuberculosis-polymerase chain reaction (Tb-PCR) suggested that the pathogenic bacteria of the spondylitis was BCG. Eventually the bacterial strain was identified as BCG by PCR-based genomic deletion analysis. CONCLUSIONS: BCG infection should be considered in patients who have been treated with BCG therapy, even if the treatment was performed several months to several years previously. In the case of a patient with a history of BCG therapy, a positive Tb-PCR result and negative IGRA result probably suggest BCG infections, if the possibility of false-negative IGRA result can be excluded.

Virion-Packaged Pyruvate Kinase Muscle Type 2 Affects Reverse Transcription Efficiency of Human Immunodeficiency Virus Type 1 by Blocking Virion Recruitment of tRNALys3.

Human immunodeficiency virus type 1 (HIV-1) recruits diverse cellular factors into viral particles during its morphogenesis, which apparently play roles in modulating its infectivity. In our study, proteomic techniques demonstrated that a key glycolytic protein, pyruvate kinase muscle type 2 (PKM2), is incorporated into viral particles. Here, we show that virion-packaged PKM2 significantly reduces viral infectivity by affecting the incorporation level of a cellular tRNALys3 into virions. Enhanced expression of PKM2 in HIV-1-producing cells led to a higher incorporation level of PKM2 into progeny virions without affecting the viral maturation process. Compared with the control virus, the high-level-PKM2-packaging virus showed decreased levels of both reverse transcription products and cellular tRNALys3 packaging, suggesting that the shortage of intravirion tRNALys3 suppresses reverse transcription efficiency in target cells. Interestingly, the enhanced expression of PKM2 also suppressed the virion recruitment of other nonpriming cellular tRNAs such as tRNALys1,2 and tRNAAsn, which are known to be selectively packaged into virions, without affecting the steady level of the cytoplasmic pool of those tRNAs in producer cells, suggesting that PKM2 specifically impedes the selective incorporation of tRNAs into virions. Taken together, our findings indicate that PKM2 is a vital host factor that negatively affects HIV-1 infectivity by targeting the tRNALys3-mediated initiation of reverse transcription in target cells.