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Lymphoma has been reported to worsen the prognosis of COVID-19 partly because it disturbs the normal production of antibodies. We treated a man with mantle cell lymphoma treated with rituximab, who developed severe COVID-19 with viral shedding that lasted for 78 days. He stayed in the intensive care unit for 28 days and did not respond to any treatment against COVID-19. His increased oxygen demand at rest eventually resolved despite the absence of anti-SARS-CoV-2-IgG. This case illustrates that recovery from COVID-19 can occur without antibody production, and that even patients with an inability to produce antibodies can recover from severe COVID-19. It also illustrates that lymphoma patients who develop severe COVID-19 while on rituximab therapy can recover from a prolonged viral shedding state if the acute lung injury can be overcome. [ABSTRACT FROM AUTHOR]

Interleukin-19 suppresses microglia/macrophage antigen presentation, T helper 17 cell expansion and subsequent inflammation in the central nervous system, resulting in improvement in experimental autoimmune encephalomyelitis. Keywords: antigen presentation; macrophage; microglia; multiple sclerosis; T helper 17 cell EN antigen presentation macrophage microglia multiple sclerosis T helper 17 cell 148 149 2 09/02/21 20210801 NES 210801 Interleukin-19 serves as a negative feedback regulator to limit the pro-inflammatory response of macrophages and microglia in autocrine/paracrine manners. These data showed that IL-19 plays a pivotal role in the suppression of MS pathogenesis by inhibiting microglia/macrophage antigen presentation, Th17 cell expansion and subsequent inflammation in the CNS. [Extracted from the article]

Objectives Soluble oligomeric amyloid β ( oAβ) directly causes synaptic dysfunction and neuronal death, which are involved in the pathogenesis of Alzheimer's disease. In contrast, several lines of evidence have shown that glia-mediated excitotoxicity is also involved in the disease progression of Alzheimer's disease. However, it is still unclear how oAβ induces glia-mediated excitotoxicity. Therefore, we tried to clarify the mechanism of oAβ-induced glia-mediated excitotoxicity using mouse primary cultures. Methods Glial glutamate production was assessed using a colorimetric assay kit. Glial production of tumor necrosis factor-α ( TNF-α) was evaluated using a specific enzyme-linked immunosorbent assay kit. Microglial survival was examined using the MTS assay. mRNA and protein expression levels of excitatory amino acid transporter 2 were determined using quantitative polymerase chain reaction and western blotting, respectively. Results We showed that oAβ-stimulation induces glutamate release from astrocyte/microglia co-cultures, but not from single culture of astrocytes or microglia. oAβ increased TNF-α release from astrocytes, but not from microglia, and the astrocyte-derived TNF-α enhanced glutamate release from microglia. TNF-α elongated microglial survival and triggered sustained microglial glutamate release in a positive feedback mechanism through TNF-α receptor 1. Furthermore, treatment of oAβ decreased astrocytic expression of excitatory amino acid transporter 2, which plays a pivotal role in homeostasis of the extracellular glutamate level. Conclusions The present findings suggest that oAβ contributes to glia-mediated excitotoxicity through the two-hit mechanism by suppressing astrocytic glutamate uptake through excitatory amino acid transporter 2 and enhancing microglial glutamate release, and triggers chronic glial neuroinflammation through the TNF-α/ TNF-α receptor 1 positive feedback loop in Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Activated microglia can exert either neurotoxic or neuroprotective effects, and they play pivotal roles in the pathogenesis and progression of various neurological diseases. In this study, we used cDNA microarrays to show that interleukin-19 (IL-19), an IL-10 family cytokine, is markedly upregulated in activated microglia. Furthermore, we found that microglia are the only cells in the nervous system that express the IL-19 receptor, a heterodimer of the IL-20Rα and IL-20Rβ subunits. IL-19 deficiency increased the production of such pro-inflammatory cytokines as IL-6 and tumor necrosis factor-α in activated microglia, and IL-19 treatment suppressed this effect. Moreover, in a mouse model of Alzheimer’s disease, we observed upregulation of IL-19 in affected areas in association with disease progression. Our findings demonstrate that IL-19 is an anti-inflammatory cytokine, produced by activated microglia, that acts negatively on microglia in an autocrine manner. Thus, microglia may self-limit their inflammatory response by producing the negative regulator IL-19. [ABSTRACT FROM AUTHOR]

Background and study aim. Although focal cancer occasionally coexists with gastric hyperplastic polyps, previous studies have reported that white light endoscopy (WLE) and biopsy sampling cannot effectively predict the coexistence of cancer. The aim of this study was to elucidate efficacious predictors for cancer coexistence. Patients and methods. This retrospective single academic center study analyzed consecutive patients with gastric polyps diagnosed as hyperplastic before endoscopic resection. Using an image catalog of WLE and magnifying endoscopy combined with narrow band imaging (ME-NBI) performed as part of the preresection work-up, three endoscopists independently assessed the coexistence of cancer and the presence of predefined ME-NBI findings in the microvasculature (MV) and fine mucosal structure (FMS). Results. Twelve of 64 gastric polyps (19%) resected from 51 patients enrolled in the study showed the coexistence of neoplasia. Polyps with coexisting neoplasia were significantly larger than those without (22.6 ± 10.1 vs. 15.5 ± 7.7 mm, respectively). Multivariate analysis of factors significantly associated with the coexistence of neoplasia identified lesion size and three specific endoscopic findings, that is, WLE diagnosis of cancer coexistence, ME-NBI findings of abnormal MV and micrification (size reduction) of the FMS. Combining lesion size (≥20 mm) and ME-NBI findings of FMS micrification had a diagnostic accuracy of 100% sensitivity and 58% specificity for coexisting neoplasia. However, combinations of WLE diagnosis and any other criteria could not achieve a diagnostic sensitivity of 100%. Conclusion. ME-NBI enhances the prediction of cancer coexistence in gastric hyperplastic polyps, with lesion size (≥20 mm) and FMS micrification the most effective predictive findings. [ABSTRACT FROM AUTHOR]

Abstract: Peripheral blood cytopenia such as anemia, leukopenia with neutropenia and thrombocytopenia is frequently observed in cats infected with feline immunodeficiency virus (FIV). Although previous studies report that cytopenia has been observed in FIV-infected symptomatic cats, yet the asymptomatic cats also present cytopenia occasionally. In the present study, hematological and virological analyses in FIV-infected asymptomatic cats were carried out to understand the prevalence and pathogenesis of peripheral blood cytopenia in FIV infection. Hematological abnormalities were detected in 24 of 50 FIV-infected asymptomatic cats (48%) in which no other cause of cytopenia than FIV infection was observed. Anemia only, neutropenia only, thrombocytopenia only, bicytopenia and pancytopenia were observed in 10%, 10%, 6%, 14% and 8%, respectively. Bone marrow (BM) examination was performed in 8 FIV-infected asymptomatic cats with peripheral blood cytopenia. Myeloid dysplasia was observed in 4 cats with neutropenia of which 2 cats with concurrent thrombocytopenia presented morphological abnormalities of megakaryocytes. FIV-infected BM cells in the 8 cats were analyzed by PCR and immunocytochemistry. Lobulated mononuclear cells in BM were infected with FIV in 5 cats with neutropenia of which 2 cats with concurrent thrombocytopenia showed FIV-infected megakaryocytes. Parts of isolated stromal cells from BM were infected with FIV in all the 8 cats. Present results suggest that FIV infection of BM cells can cause peripheral blood cytopenia and myelodysplasia even if the cat is asymptomatic. Such FIV-related hematological abnormalities are supposed to be diagnosed as FIV-myelopathy. [Copyright &y& Elsevier]

The article presents the case study of a successful rehabilitation of an elderly man after hip fracture (HF) who had ipsilateral above-elbow amputation. He was admitted to a hospital due to exacerbation of chronic obstructive pulmonary disease in which during his admission, he had a fall-related hip fracture. The researchers devised a special upper-limb prosthesis so that he could hold an ipsilateral crutch to enable appropriate acute-phase rehabilitation for HF.

Summary Background: The principal long-term complication after total hip arthroplasty (THA) has been aseptic fixation failure. Many hip prostheses and operative techniques have been developed to improve outcomes, but few measures have been taken to cope with poor bone quality or hip structure. We assessed risk factors for aseptic fixation failure after THA.Methods: We assessed, by multivariate analysis, survival of 405 primary Charnley THAs to identify risk factors for aseptic fixation failures. We also investigated risk factors for development of rapid polyethylene wear (penetration depth of the femoral head into the socket polyethylene [> OR =]2 mm/year)Findings: In the entire series of 405 THAs, with use of radiographic fixation failure or revision for a loose socket as the endpoint, development of rapid polyethylene wear and the preoperative diagnosis of atrophic osteoarthrosis (defined by scarce osteophyte formation) were identified as risk factors for socket loosening (p[≤ OR =]0.02). A medullary canal with an unfavourable geometry (a stovepipe canal, Noble's canal-flare index <3.0) was the only risk factor for femoral fixation failure (p[≤ OR =]6.7x10[SUP 3]). The only variable related to development of rapid polyethylene wear was the type of steel used in the femoral prosthesis--Ortron 90 prostheses significantly lowered the rate of development of rapid wear from 12.7% to 0.4%. In the 248 THAs in which these femoral prostheses were used, socket survival was affected only by the preoperative diagnosis of atrophic osteoarthrosis (for radiographic fixation failure and revision, p=4.0x10[SUP -5] and p=0.042, respectively). [ABSTRACT FROM AUTHOR]

Between January and May in 2018, 17 male cases of hepatitis A were reported in Yokohama, Japan. Of these, 14 identified as men who have sex with men. The viral sequence in this outbreak was same as that of the recent European and Taiwanese outbreaks strain. [ABSTRACT FROM AUTHOR]

Pigmented villonodullar synovitis (PVS) occurs in two forms: diffuse PVS and localized pigmented villonodular synovitis. In this report, a 40-year-old woman presented with a history of recurrent episodes of knee locking and pain. Arthroscopy revealed a nodular pedunculated mass occupying the area anterior to the intercondylar notch of the femur. Histological examination of the tissue confirmed the diagnosis of PVS. After surgery, the patient’s symptoms of pain and recurrent locking promptly resolved. [ABSTRACT FROM AUTHOR]

Background: This study aimed to clarify how SARS-CoV-2 RNAemia is related to COVID-19 critical condition development and mortality in comparison with other predictive markers and scoring systems. Methods: This is a retrospective cohort study conducted at Yokohama Municipal Citizen's Hospital and National Institute of Infectious Diseases. We recruited adult patients with COVID-19 admitted between March 2020 and January 2021. We compared RNAemia with clinical status on admission including scoring systems such as the 4C Mortality, CURB-65, and A-DROP, as well as the Ct value of the nasopharyngeal PCR, in predicting COVID-19 mortality and critical condition development. Results: Of the 92 recruited patients (median age, 58; interquartile range, 45–71 years), 14 (14.9%) had RNAemia. These patients had an older age (median, 68 years vs. 55.5 years; p = 0.011), higher values of lactated dehydrogenase (median, 381 U/L vs. 256.5 U/L, p < 0.001), C-reactive protein (median, 10.9 mg/dL vs. 3.8 mg/dL; p < 0.001), D-dimer (median, 2.07 μg/mL vs. 1.28 μg/mL; p = 0.015), lower values of lymphocyte (median, 802/μL vs. 1007/μL, p = 0.025) and Ct of the nasopharyngeal PCR assay (median, 20.59 vs. 25.54; p = 0.021) than those without RNAemia. Univariate analysis showed RNAemia was associated with mortality (odds ratio [OR], 18.75; 95% confidence interval [CI], 3.92–89.76; area under the receiver operating characteristic curve [AUC], 0.7851; p = 0.002) and critical condition (OR, 72.00; 95% CI, 12.98–399.29; AUC, 0.8198; p < 0.001). Plus, multivariate analysis also revealed the association of RNAemia with critical condition (adjusted OR, 125.71; 95% CI, 11.47–1377.32; p < 0.001). Conclusion: On-admission SARS-CoV-2 RNAemia is a potent predictive marker of COVID-19 critical condition and mortality. The adjusted OR for critical condition was as high as 125.71. [ABSTRACT FROM AUTHOR]

This investigation examined the clinical implications of mild vertebral fractures in older community-dwelling residents. Focusing on the locomotion health of older individuals, the earlier reported Obuse study enrolled 415 randomly sampled Japanese residents aged between 50 and 89 years, 411 of whom underwent X-ray evaluations for pre-existing vertebral fractures. A blinded assessment of vertebral fractures based on Genant's criteria was conducted on the T5-L5 spine for rating on a severity scale. Grade 1 mild fractures were not linked to age in males, but increased with aging in females. Female participants had fewer Grade 1 and 2 fractures (P = 0.003 and 0.035, respectively) but more Grade 3 fractures (P = 0.013) than did males independently of age (Grade 1, 2, and 3: 25%, 16%, and 9% in females and 40%, 22%, and 6% in males, respectively). Weak negative correlations were observed between the number of fractures and bone mineral density in females for all fracture grades (Spearman's rho: 0.23 to 0.36, P < 0.05). Our study showed that Grade 1 mild vertebral fractures in males lacked pathological significance, while in females they potentially indicated fragility fractures and were related to poor lumbopelvic alignment. [ABSTRACT FROM AUTHOR]

Alexander disease (AxD) is an intractable neurodegenerative disorder caused by GFAP mutations. It is a primary astrocyte disease with a pathological hallmark of Rosenthal fibres within astrocytes. AxD astrocytes show several abnormal phenotypes. Our previous study showed that AxD astrocytes in model mice exhibit aberrant Ca2+ signals that induce AxD aetiology. Here, we show that microglia have unique phenotypes with morphological and functional alterations, which are related to the pathogenesis of AxD. Immunohistochemical studies of 60TM mice (AxD model) showed that AxD microglia exhibited highly ramified morphology. Functional changes in microglia were assessed by Ca2+ imaging using hippocampal brain slices from Iba1-GCaMP6-60TM mice and two-photon microscopy. We found that AxD microglia showed aberrant Ca2+ signals, with high frequency Ca2+ signals in both the processes and cell bodies. These microglial Ca2+ signals were inhibited by pharmacological blockade or genetic knockdown of P2Y12 receptors but not by tetrodotoxin, indicating that these signals are independent of neuronal activity but dependent on extracellular ATP from non-neuronal cells. Our single-cell RNA sequencing data showed that the expression level of Entpd2 , an astrocyte-specific gene encoding the ATP-degrading enzyme NTPDase2, was lower in AxD astrocytes than in wild-type astrocytes. In situ ATP imaging using the adeno-associated virus vector GfaABC1D ATP1.0 showed that exogenously applied ATP was present longer in 60TM mice than in wild-type mice. Thus, the increased ATP level caused by the decrease in its metabolizing enzyme in astrocytes could be responsible for the enhancement of microglial Ca2+ signals. To determine whether these P2Y12 receptor-mediated Ca2+ signals in AxD microglia play a significant role in the pathological mechanism, a P2Y12 receptor antagonist, clopidogrel, was administered. Clopidogrel significantly exacerbated pathological markers in AxD model mice and attenuated the morphological features of microglia, suggesting that microglia play a protective role against AxD pathology via P2Y12 receptors. Taken together, we demonstrated that microglia sense AxD astrocyte dysfunction via P2Y12 receptors as an increase in extracellular ATP and alter their morphology and Ca2+ signalling, thereby protecting against AxD pathology. Although AxD is a primary astrocyte disease, our study may facilitate understanding of the role of microglia as a disease modifier, which may contribute to the clinical diversity of AxD. [ABSTRACT FROM AUTHOR]

A large COVID-19 outbreak occurred on the cruise ship Diamond Princess in February 2020. Little information has been reported about the clinical characteristics of the patients. This single-center, retrospective, observational study was conducted in Yokohama, Japan. We included symptomatic patients who were infected on the ship and admitted to our hospital between 5 and 19 February 2020. All the cases were confirmed with SARS-CoV-2 infection by polymerase chain reaction (PCR). We confirmed 17 cases. The average age was 69 years; 10 patients were Asian and 7 were Caucasian. Eleven patients had one or more chronic diseases. The major symptoms were cough and fever. Chest computed tomography (CT) scans found bilateral ground-glass opacities predominantly in the peripheral area, which were similar to reports from cases in China. C-reactive protein (CRP) levels were higher in severe and critical cases than in mild to moderate cases. The moderate to severe cases reached symptomatic resolution; one of the three critical cases resulted in death due to multiple organ failure. SARS-CoV-2 was detected by PCR at an average of 7 days after symptomatic resolution. Cough and fever, increased blood CRP levels, and CT findings of bilateral ground-glass opacities predominantly in the peripheral lung were characteristic of the COVID-19 cases in this study. These findings were compatible with those of previous reports. [ABSTRACT FROM AUTHOR]

Baloxavir marboxil is a new anti-influenza drug, but data on the clinical efficacy of a combination treatment of baloxavir and peramivir is scarce. We conducted a single-center retrospective analysis comparing the mortality of a combination of baloxavir and peramivir (B & P, n = 10) and peramivir without baloxavir (P-mono, n = 132) in hospitalized adults with influenza A between 2011 and 2019 in Yokohama City, Japan. Sequencing analysis was conducted in the B & P group to check the I38 mutation in polymerase acidic protein which is associated with baloxavir resistance. The 30-day mortality rates were 0 (0%) in the B & P group and 6 (4.5%) in the P-mono group, respectively, which was not statistically significant. The I38 mutation was not detected before and after the combination treatment. A combination treatment of baloxavir and peramivir might be more effective than peramivir without baloxavir and prevent the emergence of baloxavir resistance in hospitalized adults with influenza A. [ABSTRACT FROM AUTHOR]

Objective: A pathological excitatory action of the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) has been observed in epilepsy. Blocking the Cl− importer NKCC1 with bumetanide is expected to reduce the neuronal intracellular Cl− concentration ([Cl−]i) and thereby attenuate the excitatory GABA response. Accordingly, several clinical trials of bumetanide for epilepsy were conducted. Although NKCC1 is expressed in both neurons and glial cells, an involvement of glial NKCC1 in seizures has not yet been reported. Astrocytes maintain high [Cl−]i with NKCC1, and this gradient promotes Cl− efflux via the astrocytic GABAA receptor (GABAAR). This Cl− efflux buffers the synaptic cleft Cl− concentration to maintain the postsynaptic Cl− gradient during intense firing of GABAergic neurons, thereby sustaining its inhibitory action during seizure. In this study, we investigated the function of astrocytic NKCC1 in modulating the postsynaptic action of GABA in acute seizure models. Methods: We used the astrocyte‐specific conditional NKCC1 knockout (AstroNKCC1KO) mice. The seizurelike events (SLEs) in CA1 pyramidal neurons were triggered by tetanic stimulation of stratum radiatum in acute hippocampus slices. The SLE underlying GABAAR‐mediated depolarization was evaluated by applying the GABAAR antagonist bicuculline. The pilocarpine‐induced seizure in vivo was monitored in adult mice by the Racine scale. The SLE duration and tetanus stimulation intensity threshold and seizure behavior in AstroNKCC1KO mice and wild‐type (WT) mice were compared. Results: The AstroNKCC1KO mice were prone to seizures with lower threshold and longer duration of SLEs and larger GABAAR‐mediated depolarization underlying the SLEs, accompanied by higher Racine‐scored seizures. Bumetanide reduced these indicators of seizure in AstroNKCC1KO mice (which still express neuronal NKCC1), but not in the WT, both in vitro and in vivo. Significance: Astrocytic NKCC1 inhibits GABA‐mediated excitatory action during seizures, whereas neuronal NKCC1 has the converse effect, suggesting opposing actions of bumetanide on these cells. [ABSTRACT FROM AUTHOR]

Adult spinal deformity (ASD) patients often complain of walking discomfort. However, dynamic balance evaluation methods of gait in ASD have not been well established. Case series study. Characterize the gait of ASD patients using a novel two-point trunk motion measuring device. Sixteen ASD patients scheduled for surgery and 16 healthy control subjects. Trunk swing width and track length of the upper back and sacrum. Gait analysis was performed using a two-point trunk motion measuring device on 16 ASD patients and 16 healthy control subjects. Three measurements were taken for each subject, and the coefficient of variation was determined to compare measurement accuracy between the ASD and control groups. Trunk swing width and track length were measured in three dimensions for comparisons between the groups. The relationship among output indices, sagittal spinal alignment parameters, and quality of life (QOL) questionnaire scores was examined as well. No significant difference was found for the precision of the device between the ASD and control groups. Compared with controls, the walking style of ASD patients tended to have larger right-left swing of the trunk (+14.0 cm and +23.3 cm at the sacrum and upper back, respectively), larger horizontal plane movement of the upper body (+36.4 cm), less vertical movement (-5.9 cm and -8.2 cm up-down swing at the sacrum and upper back, respectively), and longer gait cycle (+0.13 sec). Regarding QOL in ASD patients, greater right-left/front-back swing of the trunk, greater movement in the horizontal plane, and longer gait cycle were associated with lower QOL scores. Conversely, greater vertical movement was associated with higher QOL. ASD patients had unique gait characteristics, the intensity of which were associated with diminished QOL. The two-point trunk motion measuring device may be reliable and useful for the clinical assessment of balance during gait in ASD patients. [ABSTRACT FROM AUTHOR]

A 49-year-old woman underwent anatomic double-bundle anterior cruciate ligament reconstruction using a hamstring tendon. Due to knee osteoarthritis progression, total knee arthroplasty was performed 13 years after the surgery. The anteromedial (AM) bundle was composed partly of tendon-like tissue and partly of scar-like tissue. In the tendon-like part of the AM bundle, the collagen fibers were slightly loose and showed a low-frequency crimp structure with an ovoid cell shape. In contrast, the collagen arrangement in the scar-like part was irregular, edematous, and sparsely cell-dense, with an ovoid cell shape. The posterolateral bundles were generally composed of spindle-shaped cells, and the collagen was arranged in tight cohesion and had well-demarcated bundles with normal crimping. Within the tibial tunnel, the graft was mainly connected to the surrounding lamellar bone on the posterior sides, with sparser connections on the anterior and medial/lateral side. The findings of this long-term case provide valuable information to enable understanding of multiple-folded hamstring tendons. Level of evidence V. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effects of a new remnant-preserving double-bundle anterior cruciate ligament reconstruction (ACLR) technique, focused on avoiding remnant damage and preserving continuity of remnants, on graft maturity using magnetic resonance imaging (MRI). Methods: A total of 169 patients were divided into three groups: 41 in the preservation group, 70 in the resection group, and 58 in the absent group. In the preservation group, rather than passing the graft through the remnant tissue, the graft was reconstructed such that the anteromedial and posterolateral bundles sandwiched the remnant to avoid damage to the remnant and maintain its continuity. Based on 1-year postoperative MRI, the grafts were divided into three regions: distal, middle, and proximal. The signal/noise quotient (SNQ) of each region of interest was calculated to evaluate the signal intensity of the graft and was compared among the three groups. Additionally, to identify factors influencing graft maturity, a multiple regression analysis was performed with SNQ as the dependent variable and patient demographics, bone morphology, and surgical factors as independent variables. Results: In a three-group comparison of mean SNQs, the distal region was 3.3 ± 3.4, 8.9 ± 8.3, and 9.0 ± 8.6 (p < 0.001), the middle region was 5.3 ± 3.7, 10.9 ± 11.1, and 11.3 ± 10.2 (p < 0.001), and the proximal region was 6.8 ± 4.5, 11.1 ± 8.8, and 11.7 ± 10.8 (p = 0.017), in order of the preservation, resection, and absent groups, respectively. That indicated that the remnant-preserving ACLR was more hypointense than ACLR with remnant resection or absent in all three regions. Multiple regression analysis showed that remnant preservation remained the relevant factor affecting SNQ of the graft at the distal and middle levels. Conclusion: The new remnant-preserving anatomic double-bundle ACLR had significantly better graft maturity, measured by SNQ on MRI, than the remnant resection and absent groups. The remnant procedure was the relevant factor affecting graft maturity. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced lung cancer tend to experience dyspnea. Pulmonary rehabilitation has been reported as a method for relieving dyspnea. However, exercise therapy imposes a high burden on patients, and it is difficult to sustain in many cases. Inspiratory muscle training (IMT) imposes a relatively low burden on patients with advanced lung cancer; however, its benefits have not been demonstrated. Methods: We retrospectively analyzed 71 patients who were hospitalized for medical treatment. The participants were divided into an exercise therapy group and an IMT load + exercise therapy group. Changes in maximal inspiratory pressure (MIP) and dyspnea were examined using a two-way repeated measures analysis of variance. Results: MIP variations significantly increase in the IMT load group, with significant differences between baseline and week 1, between week 1 and week 2, and between baseline and week 2. The analysis also showed that the variations in dyspnea decreased in the IMT load + exercise therapy group with significant differences between baseline and week 1 and between baseline and week 2. Conclusions: The results show that IMT is useful and has a high persistence rate in patients with advanced lung cancer who present dyspnea and cannot perform high-intensity exercise therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated major vascular injury risk in distal femoral osteotomy (DFO) via the subvastus approach and examined the relationship between the posterior border of the vastus medialis (VM) and the superficial femoral artery (SFA) and vein (SFV). Methods: Eighty limbs from 80 patients were evaluated using lower extremity computed tomographic venography. The positional relationship between the VM, SFA, and SFV was evaluated by measuring the angle between each structure and the horizontal reference point (VMA: VM angle, FAA (femoral arterial angle), FVA (femoral venous angle) and the distance between VM and the SFA and SFV (VMAD: VM-arterial distance, VMVD: VM-venous distance) in each axial slice (0/10/20/30/40 mm) proximal to the level of the superior patellar margin. The proximity of the posterior border of the VM and the SFA/SFV as a vertical distance, measured between the slice of the superior border of the patella and the slice where the posterior border of the VM contacted the SFA was evaluated. Single and multiple regression analyses were performed using the vertical distance as the objective variable. Results: As the slice shifted proximally, the VMA significantly increased (24.9 ± 8.5, 36.3 ± 8.8, 47.4 ± 11.8, 59.9 ± 14, 70.3 ± 13.7 degrees, respectively, p < 0.001 between all slices) and moved posteromedially from a medial direction. FAA (94.2 ± 7, 86.9 ± 9.2, 78.4 ± 9.7, 71.4 ± 9.8, 66.6 ± 10.5 degree, respectively, p < 0.001 between all slices) and FVA (100.6 ± 4.9, 98.3 ± 5.9, 93.7 ± 7.5, 88 ± 9.2, 81.1 ± 10.5 degrees, respectively, p < 0.001 between all slices) decreased and moved from a posterolateral to a posteromedial direction, while VMAD (35.4 ± 7.8, 24.1 ± 7.3, 14.3 ± 6, 8.4 ± 7, 6.2 ± 6.3 mm, respectively, p < 0.001 between all slices) and VMVD significantly decreased (42.7 ± 7.3, 32 ± 7.4, 22.4 ± 6.8, 14.5 ± 10.6, 8.7 ± 7.1 mm, respectively, p < 0.001 between all slices). The average vertical distance was 36 ± 9.3 mm (range 18.6–61.5 mm). The body height and the patellar length significantly affected the vertical distance. Conclusion: The posterior border of the VM shifted posteromedially from distal to proximal and contacted the SFA at an average of 36 mm from the suprapatellar border. Surgeons should be aware of the risk of major vascular injury during exposure and osteotomy. Level of evidence: Case series, Level IV. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship between heart rate variability (HRV), a parameter of the autonomic nervous system activity (ANSA), and postoperative delirium and postoperative events. This retrospective cohort study included elderly patients aged 65 years or older who were admitted to the intensive care unit (ICU) after cardiovascular surgery. ANSA was measured using HRV parameters for 1 h at daytime and 1 h at night-time before ICU discharge. The primary endpoint was the effect of HRV parameters and delirium on mortality and readmission rates within 1 year after discharge, and the secondary endpoint was the association between HRV parameters and delirium. Cox proportional hazards models were used to examine the association between HRV parameters and postoperative events by adjusting for delirium and pre and postoperative information. A total of 71 patients, 39 without delirium and 32 with delirium, met the inclusion criteria. The incidence of death and readmission within 1 year was significantly higher in the delirium group and in the group with higher daytime HF (high frequency power) and r-MSSD (square root of the squared mean of the difference of successive NN intervals), parameters of the parasympathetic nervous system activity (PNSA), than that in other groups. Furthermore, the delirium group had significantly higher HF and r-MSSD than the nondelirium group. Even after adjusting for confounding factors in the multivariate analysis, a trend of higher daytime HF and r-MSSD was observed, indicating a significant effect on the occurrence of combined events within 1 year of discharge. ICU delirium has been associated with higher daytime HF and r-MSSD, parameters of PNSA. ICU delirium was a prognostic factor, and increased daytime PNSA may worsen the prognosis of elderly patients after cardiovascular surgery. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effectiveness and clinical outcomes of inpatient rehabilitation for patients with severe COVID-19 in Japan. Methods: Patients with severe COVID-19 who underwent rehabilitation during hospitalization were included. The Medical Research Council (MRC) score and short physical performance battery (SPPB), such as physical function assessment and the intensive care unit (ICU) mobility scale, the functional status score for the ICU, and Barthel index as activities of daily living (ADLs) were evaluated at admission and discharge or transfer from the hospital. The correlation between SPPB at discharge and each factor at admission were also analyzed. Furthermore, the prevalence of sarcopenia was evaluated by defining SPPB of <9 points at discharge as sarcopenia. Results: The median age of the total of 23 patients was 59 years (interquartile range (IQR): 47–67), 73.9% were male, and the median PaO2/FiO2 at admission was 172.0 (IQR: 123.0–209.0). All physical function and ADL parameters were significantly improved from the time of admission to discharge (p = 0.014 for the MRC score and p < 0.001 for all others). Moreover, SPPB at discharge significantly correlated with WBC (Spearman's rho = −0.473, p = 0.041), C-reactive protein (Spearman's rho = −0.468, p = 0.044), and exhibited a significant trend with PaO2/FiO2 (Spearman's rho = 0.429, p = 0.067) and age (Spearman's rho = 0.409, p = 0.083). Although the median Barthel index at discharge was 90 points, 47% of patients had sarcopenia as defined by an SPPB of <9 points. Conclusions: Early rehabilitation for patients with severe COVID-19 improved physical function and ADLs during hospitalization. However, 47% of patients had the same level of sarcopenia at discharge. [ABSTRACT FROM AUTHOR]

Objectives Fingolimod ( FTY) is a new oral drug for multiple sclerosis. It acts as a functional antagonist for sphingosine 1-phosphate receptor ( S1 PR). After phosphorylateion by sphingosine kinase in vivo, FTY binds to S1 PR on lymphocytes to downregulate S1 PR, thereby preventing lymphocyte egress from lymphoid tissues to reduce infiltration of autoreactive lymphocytes into the central nervous system. FTY easily passes through the blood-brain barrier and directly affects cells in the central nervous system. Recently, we have shown that FTY exerts neuroprotective effects by suppressing pro-inflammatory functions of glial cells and by upregulating neuroprotective functions of neuronal and glial cells in vitro. In the present study, we examined whether FTY exerts neuroprotective effects in vivo in the chronic phase of experimental autoimmune encephalomyelitis ( EAE). Methods Myelin oligodendrocyte glycoprotein-induced EAE mice were orally treated with FTY (1 mg/kg/day) or vehicle (water) once a day starting at the disease peak (15 days after immunization). To evaluate gliosis and axonal damage, the lumbar spinal cords were examined immunohistochemically at 28 days after immunization. Results FTY treatment starting at disease peak improved the severity of symptoms, and reduced gliosis and axonal damage in the spinal cord, as assessed by glial staining and formation of neuritic bead/spheroid. Conclusions FTY exerts protective effects on axonal impairments during the chronic phase of EAE. The neuroprotective effect of FTY could synergistically suppress pathology of multiple sclerosis with its immunosuppressive effect. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of a new remnant preservation technique with a focus on remnant continuity on postoperative femoral and tibial tunnel enlargement after anatomical double-bundle anterior cruciate ligament reconstruction (ACLR).Methods: A total of 150 knees were divided into three groups: Preservation Group (Group P: 49 knees), wherein the remnant continuity remained after tunnel creation; Resection Group (Group R: 47 knees), wherein the remaining remnant was resected, and Absent Group (Group A: 54 knees), wherein the remnant had no femoral attachment before tunnel creation. In Group P, the remnant maintained continuity, and the anteromedial (AM) and posterolateral (PL) bundles were positioned anterior and posterior to the remnant, respectively. Computed tomographic scans were performed at 1 week and 1 year after surgery, and the cross-sectional area of each tunnel aperture was measured. Tunnel enlargement was compared among the three groups by one-way analysis of variance (ANOVA) and the Bonferroni test. Univariate and multivariate logistic analyses were performed to identify the risk factors for tunnel enlargement in demographic and radiographic data.Result: For femoral AM tunnels, the tunnel enlargement of Group P was significantly smaller than Groups R and A (p < 0.001), femoral PL (p < 0.001 vs. R and A), tibial AM (p < 0.001 vs. R, 0.002 vs. A), and tibial PL (p < 0.001 vs. R, 0.002 vs. A). There was no significant difference between Groups R and A. Multivariate logistic analysis showed that remnant preservation was a significant factor in reducing tunnel enlargement in the femoral AM, femoral PL, tibial AM, and tibial PL.Conclusion: The new remnant-preserving anatomical double-bundle ACLR, which preserves the continuity of the remnant, prevented all bone tunnel enlargement at 1 year postoperatively.Level Of Evidence: Level III. [ABSTRACT FROM AUTHOR]

Background: Early rehabilitation allows patients to better perform the activities of daily living after hospital discharge. A specialized physical therapist has been assigned as part of the early rehabilitation, but the effectiveness of the program remains unclear. We investigated how early rehabilitation provided by a specialized physical therapist affects ADL in patients with sepsis. Methods: This was a retrospective cohort study. This study's subjects were sepsis patients who entered the advanced emergency critical care center of Shinshu University Hospital between April 2014 and March 2020. Electronic medical records were reviewed to obtain information on demographic characteristics, severity score, primary source of infection, therapeutic medication, the number of days after hospital admittance until rehabilitation begins, length of hospital stay, discharge to home, and an assessment of daily living activities for each patient. The patients were divided into two groups based on whether they were treated before or after a specialized physical therapist had been hired by the advanced emergency critical care center. Results: Assigning a physical therapist to a patient significantly shortened the number of days until rehabilitation began. In a multivariable model, the strongest predictors of return to independent living after hospital discharge were (1) assigning a specialized physical therapist (odds ratio = 2.40; 95% confidence interval = 1.09–5.79; P = 0.050) and (2) the number of days until rehabilitation started (odds ratio = 0.24; 95% confidence interval = 0.08–0.76; P = 0.014). Conclusions: Assigning a specialized physical therapist to sepsis patients at an advanced emergency critical care center significantly shortened the number of days until a patient can begin rehabilitation after hospital admittance and improved activities of daily living after hospital discharge. Trial registration: Trial registration [University Hospital Medical Information Network Clinical Trials Registry, number UMIN000040570 (2020/5/28).] [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the risk of medial tibial cortical perforation in unicompartmental knee arthroplasty (UKA) due to peg positions on the tibial tray of the Persona Partial Knee (PPK). Methods: Preoperative CT images of 60 patients and 60 osteoarthritic knees (30 male and 30 female patients) were used. A tibial multiplanar reconstruction (MPR) image was reconstructed in preoperative planning software, and the implant was placed in a virtual osteotomy plane. In addition to PPK, Zimmer Unicompartmental Knee (ZUK) and TRIBRID (TBD) were used for evaluation. The horizontal distances from the medial tibial cortex to the anterior and posterior pegs (APCD/PPCD, respectively) were measured under neutral, 3-degree varus, 3-degree valgus and 2 mm distal positions. The differences between implants under the same positions and between positions using the same implants were compared. The percentage of total cases with APCD/PPCD of less than 3 mm and the perforation risk rate were calculated. Results: The APCD of PPK was significantly shorter at all positions except for the varus position of TBD. The PPCD of PPK was significantly shorter at all positions compared to ZUK and TBD. There were no cases with an APCD of less than 3 mm. Except for varus positions, the perforation risk rate of PPCD was significantly higher for PPK than the other two implants. Conclusion: The posterior pegs of the PPK are located more medially than the other two implants, which may result in perforation of the medial tibial cortex during implantation. Surgeons should consider the risk involved in the type of implant used. [ABSTRACT FROM AUTHOR]

The neurodegenerative processes that underlie Alzheimer's disease are mediated, in part, by soluble oligomeric amyloid β, a neurotoxic protein that inhibits hippocampal long-term potentiation, disrupts synaptic plasticity, and induces the production of reactive oxygen species. Here we show that the sphingosine-1-phosphate (S1P) receptor (S1PR) agonist fingolimod phosphate (FTY720-P)-a new oral drug for multiple sclerosis-protects neurons against oligomeric amyloid β-induced neurotoxicity. We confirmed that primary mouse cortical neurons express all of the S1P receptor subtypes and FTY720-P directly affects the neurons. Treatment with FTY720-P enhanced the expression of brain-derived neurotrophic factor (BDNF) in neurons. Moreover, blocking BDNF-TrkB signaling with a BDNF scavenger, TrkB inhibitor, or ERK1/2 inhibitor almost completely ablated these neuroprotective effects. These results suggested that the neuroprotective effects of FTY720-P are mediated by upregulated neuronal BDNF levels. Therefore, FTY720-P may be a promising therapeutic agent for neurodegenerative diseases, such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

The article presents the conducted study to determine the effect of gabapentin (GBP) on brain hyperactivity that are linked to pain and sleep disturbance among patients with chronic pain, including neuropathic pain. In the study conducted on mice, the functional magnetic resonance imaging (fMRI) and electroencephalogram/electromyogram (EEG/EMG) were used. Neuropathic pain is the pain due to lesions or diseases of the sensory transmission pathways in the peripheral or central nervous system.

Bone morphogenetic proteins (BMPs) that have the potential to elicit new bonein vivo have been used in a tissue-engineering approach for the repair of bone injuries and bone defects. Although it is now possible to generate large amounts of recombinant human (rh) BMPs for medical use, the major challenge remains in the development of optimal local delivery systems for these proteins. Here we describe the development of a synthetic biodegradable polymer, poly-D,L-lactic acid -- p-dioxanone -- polyethylene glycol block copolymer (PLA-DX-PEG). This polymer exhibits promising degradation characteristics for BMP delivery systems and good biocompatibility under test conditions. PLA-DX-PEG/rhBMP-2 composite implants induced ectopic new bone formation effectively when testedin vivo, and can repair large bone defects orthotopically. This polymeric delivery system represents an advance in the technology for the enhancement of bone repair. [ABSTRACT FROM AUTHOR]

Background: Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. Collagen from animal sources has previously been the preferred carrier material in animal experiments. More recently, synthetic biodegradable polymers have been tested as a delivery vehicle for osteoinductive agents. In earlier studies performed in our laboratory, it was found that the polylactic acid homopolymers (PLA650) and poly-D,L-lactic acid-polyethylene glycol block copolymers (PLA650-PEG200) are viscous liquids that can be used as BMP delivery systems. Methods: To obtain new PLA-PEG polymers that exhibit greater plasticity, the molecular sizes of PLA and PEG segments in the copolymer chains were increased. Plastic PLA-PEG polymers with various molecular sizes and PLA/PEG ratios were synthesized, mixed with recombinant human (rh) BMP-2, and implanted into the dorsal muscles of mice for 3 weeks to evaluate their capacity to elicit new bone formation. To compare the plastic PLA-PEG polymer with the liquid PLA650-PEG200 polymer, these two polymers were combined with rhBMP-2, implanted, and harvested after 3 weeks. Bone mineral content (BMC), bone area, and bone mineral density (BMD) of the ectopic new bone were measured by means of single energy X-ray absorptiometry (SXA). Results: All of the PLA6,500-PEG3,000 implants with 10 or 20 microg of rhBMP-2 showed new bone formation. In contrast, little or no bone formation was seen in other plastic PLA-PEG implants with rhBMP-2. Control implants that lacked rhBMP-2 did not show new bone formation. Radiographic and histologic examinations showed that the PLA6,500-PEG3,000 implants with rhBMP-2 harvested 3 weeks after implantation had normal bone characteristics with hematopoietic marrow and osseous trabeculae. SXA analysis showed that the values for bone mineral content (BMC), bone area, and bone mineral density (BMD) of new bone resulting from the use of plastic PLA6,500-PEG3,000 polymers with rhBMP-2 were significantly higher than those obtained with the liquid PLA650-PEG200 polymers (p < 0.001 for each of the three values). Conclusions: These results indicate that the PLA6,500-PEG3000 block copolymer with plastic properties works effectively as a BMP delivery system. These data suggest that the total molecular size and ratio of PLA size to PEG size is an essential factor in determining the efficacy of a BMP delivery system. After implantation, it is possible that the PLA6,500-PEG3,000 pellets might have absorbed tissue fluids and become swollen, resulting in bone formation that exceeded the size of the original implants. This expansion characteristic is a potentially beneficial property, given the intended practical application of the polymer in the repair of bone defects. Clinical Relevance: New synthetic biodegradable delivery systems will play an important role in the clinical applications of rhBMPs in which local formation of bone via an osteoinductive graft material is needed. Further pre-clinical and clinical work is necessary to establish the safety of these implants before they are adopted for widespread clinical use. [ABSTRACT FROM AUTHOR]

Low back pain (LBP) is one of the main etiologies of disability in daily life. In the face of LBP increases in super-aged societies, there are serious concerns of escalating medical costs and deteriorations in the social economy. It is therefore important to identify the factors associated with LBP for prompt preventative and therapeutic measures. This study investigated the prevalence of LBP and the impact of subject-specific factors on LBP development in Japanese community-dwelling older adults. We established eight groups based on age (50's, 60's, 70's, and 80's) and gender after random sampling from a resident registry. A total of 411 participants (201 male and 210 female) were enrolled for a whole-spine lateral radiographic examination and dual-energy X-ray absorptiometry. All subjects were evaluated for the presence and degree of LBP. We analyzed the impact of clinical factors on LBP using multivariate analysis. Fifty-three (12.9%) participants (23 (11.4%) male and 30 (14.3%) female) were found to have LBP. The prevalence of LBP tended to increase with age, and similar results were found between genders. In univariate analysis, the subject-related factors of the sagittal vertebral axis, pelvic incidence minus lumbar lordosis (PI-LL) mismatch, and aging had significant associations with LBP. PI-LL mismatch was a significant independent factor in multivariate analysis. In conclusion, this study identified LBP prevalence and subject-specific factors on a general population basis. Multivariate analysis revealed PI-LL mismatch as an independent factor associated with LBP in the healthy community-dwelling elderly. [ABSTRACT FROM AUTHOR]

Background: Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is widely used as a patient-based evaluation tool for lumbar spine disease in Japan. However, there are currently few established JOABPEQ reference values for the general population. This study proposes population-based reference values for JOABPEQ using a randomly sampled Japanese cohort.Methods: Registered citizens of 50-89 years old were targeted for this survey. We established 8 groups based on age (50's, 60's, 70's, and 80's) and gender (male and female) after random sampling from the basic resident registry of Obuse town in 2014. A total of 414 participants (202 males and 212 females) were enrolled for calculations of average JOABPEQ scores for each age and gender group. We also evaluated for correlations between JOABPEQ domain scores and visual analogue scale (VAS) scores for low back pain.Results: Median reference JOABPEQ scores stratified by age and gender were determined in this study. Lumbar function, walking ability, and social life function deteriorated significantly with age in both genders, with remarkable declines for the social life function domain. VAS scores for low back pain were not significantly correlated with JOABPEQ item scores.Conclusions: This first resident cohort of Japanese individuals determined median JOABPEQ scores by age and gender, which might serve as reference values for future studies. [ABSTRACT FROM AUTHOR]

HLA‐A, ‐C, ‐B, and ‐DRB1 genotypes were analyzed in 178 Japanese COVID‐19 patients to investigate the association of HLA with severe COVID‐19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA‐DRB1*09:01 and severe COVID‐19 (odds ratio [OR], 3.62; 95% CI, 1.57–8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID‐19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID‐19. [ABSTRACT FROM AUTHOR]

The article discusses development of fingolimod, oral drug for treatment of multiple sclerosis that is suggested to suppresses pro-inflammatory effects and improve neuroprotective effects in astrocytes. Topics discussed include action on lymphocytes, reverse transcription polymerase chain reactions and intercellular adhesion molecule-1. IL Interleukin, histocompatibility complex and tumor necrosis factor are mentioned.

Osteoporosis may increase fracture risk and reduce healthy quality of life in older adults. This study aimed to identify an assessment method using physical performance tests to screen for osteoporosis in community dwelling individuals. A total of 168 women aged 50–89 years without diagnosed osteoporosis were randomly selected from the resident registry of a cooperating town for the evaluation of physical characteristics, muscle strength, and several physical performance tests. The most effective combinations of evaluation items to detect osteoporosis (i.e., T-score ≤ −2.5 at the spine or hip) were selected by multivariate analysis and cutoff values were determined by likelihood ratio matrices. Thirty-six women (21.4%) were classified as having osteoporosis. By analyzing combinations of two-step test (TST) score and body mass index (BMI), osteoporosis could be reliably suspected in individuals with TST ≤ 1.30 and BMI ≤ 23.4, TST ≤ 1.32 and BMI ≤ 22.4, TST ≤ 1.34 and BMI ≤ 21.6, or TST < 1.24 and any BMI. Setting cut-off values for TST in combination with BMI represents an easy and possibly effective screening tool for osteoporosis detection in resident health exams. [ABSTRACT FROM AUTHOR]

Abstract An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19). However, data regarding myeloid cell expansion have been collected in Europe, where the mortality rate by COVID-19 is greater than those in other regions including Japan. Thus, characteristics of COVID-19-induced myeloid cell subsets remain largely unknown in the regions with low mortality rates. Here, we analyzed cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis, using blood samples from Japanese COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, but not other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Contrary to previous studies in Europe, this subset selectively expanded in survivors of severe cases and subsided before discharge, but such transient expansion was not observed in non-survivors in Japanese cohort. Analysis of plasma cytokine/chemokine levels revealed positive correlation of PMN-MDSC frequencies with IL-8 levels, indicating the involvement of IL-8 on recruitment of PMN-MDSCs to peripheral blood following the onset of severe COVID-19. Our data indicate that transient expansion of the PMN-MDSC subset results in improved clinical outcome. Thus, this myeloid cell subset may be a predictor of prognosis in cases of severe COVID-19 in Japan. [ABSTRACT FROM AUTHOR]

Background: To determine normative values for the QuickDASH questionnaire in the elderly Japanese population and their associated factors. Methods: Three-hundred and eighty-one residents between 50 and 89 years of age were randomly selected from residents of a town in Japan. All participants completed a QuickDASH questionnaire. A multivariate analysis was performed to identify associated factors. Results: Males and females aged 70–79 and 80–89 showed significantly higher QuickDASH scores than the 50–59 age groups. Females aged 50 to 59 showed significantly higher QuickDASH scores than males aged 50–59. Motion pain or tenderness at the shoulder and side pinch strength showed a significant effect on QuickDASH scores. Conclusions: The mean QuickDASH score was 5.7. As an associated factor for the QuickDASH, aging, female, and shoulder disorders were confirmed. [ABSTRACT FROM AUTHOR]

A 93‐year‐old woman was admitted with a 10‐day history of cough and prostration. Thoracic computed tomography revealed extensive ground‐glass opacities in both the lungs. The polymerase chain reaction test of sputum for severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) was positive. She was treated with antiviral agents and steroid pulse therapy. However, her oxygen saturation gradually declined, and she died 10 days after hospitalization. The most important autopsy finding was fuzzily segmented diffuse alveolar damage (DAD) that expanded from the subpleural to the medial area. No remarkable changes were observed in organs other than the lungs. Therefore, pneumocytes were suggested as the primary target for SARS‐CoV‐2, which might explain why coronavirus infectious disease‐19 is a serious condition. Thus, early treatment is essential to prevent viral replication from reaching a level that triggers DAD. [ABSTRACT FROM AUTHOR]

Background: Locomotive syndrome (LoS) is defined as the loss of mobility due to age-related impairment of motor organs. The purpose of this study was to evaluate the prevalence and severity of LoS, muscular strength and balancing ability, and prevalence of sarcopenia in relation to the presence of LoS according to sex and age groups ranging between 50 and 89 years.Methods: Male and female participants between the ages of 50-89 were randomly selected in the resident registry of a cooperating town. Calls for participation continued until approximately 50 consenting participants were successfully recruited for each age group and sex. A total of 413 participants (203 male and 210 female) were enrolled for undergoing a LoS risk test and measuring their physical function. Physical function was compared to participants with or without LoS.Results: A total of 312 patients (75.5%) were diagnosed as LoS, of which 144 (46.2%) were male and 168 (53.8%) were female. The severity of LoS for the 312 patients were 210 (67.3%) for stage 1 and 102 (32.7%) for stage 2. The prevalence of LoS in males were 37, 59, 91, and 100% in the 50s, 60s, 70s, and 80s age strata, respectively. The prevalence of LoS in females were 71, 62, 89, and 98% in the 50s, 60s, 70s, and 80s age strata, respectively. The prevalence of sarcopenia was significantly higher as the age strata in males grew higher. Knee extension strength was significantly lower for participants in their 50s and females in addition to females in their 60s with LoS. The 31 patients diagnosed as sarcopenia included 29 (93.5%) with LoS, 11 (35.4%) classified as LoS stage 1, and 18 (58.1%) classified as stage 2.Conclusions: The prevalence of LoS was high in participants over 70 years of age. In males, the prevalence of sarcopenia was higher as the age strata grew higher. Patients with LoS exhibited lower knee extension strength. We believe that some measures to prevent or improve LoS may require exercise to increase the muscle strength of the lower limbs. [ABSTRACT FROM AUTHOR]

Introduction: Fragility fractures can cause delayed wound healing after tooth extraction, which contributes to an increased risk of osteomyelitis of the jaw. We evaluated whether a history of fragility fracture was associated with increased risk of delayed wound healing after tooth extraction in older adults in Japan.Materials and Methods: Of 5352 people aged 50-89 years in the 2014 basic resident registry of the town of Obuse, the present study included 376 subjects (190 men and 186 women) who completed a structured questionnaire and measurement of the bone mineral densities (BMDs) of the bilateral femoral neck. Delayed wound healing after tooth extraction was self-reported. Fragility fractures were confirmed via examination of hospital medical records. Logistic regression analyses adjusted for age and gender were used to evaluate association of clinical variables with delayed would healing after tooth extractions. Odds ratios (ORs) and the 95% confidence intervals (CIs) of all possible associated variables for the presence of delayed wound healing were calculated.Results: Subjects with a history of fragility fractures had a significantly higher risk of delayed wound healing compared with those without previous fragility fractures (OR 2.68; 95% CI 1.11-6.46, p = 0.028). This association still remained after adjusted for all other variables (OR 2.70; 95% CI 1.10-6.60, p = 0.030). Delayed wound healing was not significantly associated with the BMD of the femoral neck.Conclusions: History of fragility fracture may be associated with increased risk of delayed wound healing after tooth extraction in Japanese men and women aged 50-89 years. [ABSTRACT FROM AUTHOR]

Case. We report a rare case of prefemoral fat pad impingement syndrome that was caused by a hyperplasia of the normal suprapatellar fat pad. Pain and catching were observed in the proximal-lateral patellofemoral joint, and MRI imaging confirmed a hyperplasic mass in the same area. Although conservative treatment showed no signs of improvement, symptoms improved after an arthroscopic excision of the mass. Conclusion. Prefemoral fat pad impingement syndrome is related to patellar motion and should be considered as one of the underlying causes of anterior knee pain (AKP). Surgeons should recognize that a small hyperplasia composed of normal adipose tissue can cause AKP. [ABSTRACT FROM AUTHOR]

The article discusses the role of astrocytic eotaxin (CCL11) on the production of microglial reactive oxygen species and in aging-related neuronal dysfunction. Topics discussed include CCL11's pathological role in allergic diseases, the study which identifies astrocytes as the primary source of CCL11 in the central nervous system (CNS), and the role of systemic inflammation to CCL11 production.

Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Because synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. To elucidate this, we conducted in vivo 2-photon calcium imaging of neuron and astrocyte activity in the ipsilateral S1 after a peripheral nerve injury. We found that cross-callosal inputs enhanced the activity of both S1 astrocytes and inhibitory neurons, whereas activity of excitatory neurons decreased. When local inhibitory circuits were blocked, astrocyte-dependent spine plasticity and allodynia were revealed. Thus, we propose that cortical astrocytes prime the induction of spine plasticity and mirror image pain after peripheral nerve injury. Moreover, this result suggests that cortical synaptic rewiring could be sufficient to cause allodynia on the uninjured periphery. [ABSTRACT FROM AUTHOR]

By combining video laryngoscopy and fiberoptic bronchoscopy, awake intubation can be performed more safely. [ABSTRACT FROM AUTHOR]

Abstract: Genu recurvatum deformity is rare, usually resulting from injury to the anterior part of the proximal tibial growth plate. However, a small group of cases have no known cause. We describe brothers with the same type of this deformity on the same side. The degree of deformity differed between them, but deformities began at the same age in both (17 years) and progressed over a short period. There was no history of trauma, or other orthopaedic or genetic disorders. These features strongly suggested involvement of heritable risk factors. [Copyright &y& Elsevier]

A multiplex analysis for profiling the expression of candidate microRNAs (miRNAs), which are small noncoding RNAs that function as key post-transcriptional regulators, may lead to a better understanding of the complex machinery of neuropathic pain. In the present study, we performed a miRNA array analysis using tissues of the dorsal root ganglion (DRG), a primary site for pain processing, obtained from mice with partial sciatic nerve ligation. Among 1135 total miRNAs, 26 miRNAs showed up-regulation (more than 2-fold change) and only 4 miRNAs showed down-regulation (less than 0.5-fold change) in the DRG of nerve-ligated mice. In a RT-qPCR assay, the levels of miR-21, miR-431, and miR-511-3p were significantly increased on the ipsilateral side of the DRG from 3 to 7 days after sciatic nerve ligation. These elevations were almost absent in IL-6 knockout mice. Furthermore, the expression level of miR-21, but not those of miR-431 or miR511-3p, was significantly increased in exosomes extracted from blood of nerve-ligated mice. These findings suggest that the increased expression of IL-6-regulated miR-21, miR-431, and miR-511-3p in the DRG and increased exosomal miR-21 extracted from blood after sciatic nerve ligation may play at least a partial role in neuropathic pain. Synapse 70:317-324, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]