Intraosseous carcinoma of the anterior maxilla identified as the occult primary tumour of carcinoma of unknown primary.

Carcinoma of unknown primary (CUP) is defined as lymph node metastasis without a detectable origin until after the initial treatment has been performed. The most common occult primary site in the head and neck, as revealed by a review of the published literature, is the oropharynx. An occult primary site in the oral region is extremely rare. We report a rare case of head and neck CUP (HNCUP) in a 69-year-old female patient, wherein the occult primary lesion was a primary intraosseous carcinoma (PIOC) invading the anterior maxilla. During the course of the initial diagnostic workup, no primary lesion could be identified; however, cervical lymph node metastasis to left levels IB and IIA were observed in the patient. A neck dissection followed by adjuvant radiotherapy was performed. However, the PIOC of the anterior maxilla was identified 6 months after neck treatment and was confirmed as the occult primary tumour of the HNCUP. This case is quite rare and required a comprehensive workup to guide optimal treatment. Careful follow-up or active biopsy should be considered if osteolytic changes are observed in the jaw.

Prevalence of and risk factors for depressive symptoms in non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The presence of depressive symptoms in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an important research topic; however, the prevalence of depressive symptoms and the factors that influence their development are unclear.OBJECTIVE: To analyse the association between CES-D (Center for Epidemiological Studies Depression Scale) scores and clinical parameters such as age, disease duration, pulmonary function, imaging findings, blood data, physical functions, sleep disturbances, respiratory symptoms and health-related quality of life (HRQOL).METHODS: We conducted a cross-sectional retrospective study of 114 patients with NTM-PD at a single centre from March 2016 to January 2021 to evaluate the relationship between CES-D scores and clinical parameters.RESULTS: Participants had a median age of 64 years; 32.5% of them had depressive symptoms. Disease duration, albumin, C-reactive protein, pulmonary function, dyspnoea, exercise capacity, respiratory symptoms, cough-related HRQOL and sleep disturbances were associated with depressive symptoms. Binomial logistic regression analyses indicated that the CES-D score was significantly associated with cough-related HRQOL and sleep disturbances.CONCLUSION: A high percentage of NTM-PD patients in this study experienced depressive symptoms, and these patients had abnormalities of various clinical parameters. Cough-related HRQOL and sleep disturbance had a strong influence on the development of depressive symptoms.

Health-related quality of life associates with clinical parameters in patients with NTM pulmonary disease.

BACKGROUND: Previous studies have shown a reduction in health-related quality of life (HRQoL) in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). However, the causes of this decline and the factors that contribute to it are unknown. This study was conducted to analyse the association between the St George´s Respiratory Questionnaire (SGRQ) and clinical parameters, including age, disease duration, body composition, pulmonary function, chest X-ray findings, blood data and physical function.METHODS: We performed a single-centre, cross-sectional, retrospective study of 101 patients with NTM-PD from December 2016 to October 2019. The relationship between the SGRQ scores and clinical parameters was evaluated.RESULTS: The median patient age was 67.0 years. Pulmonary function, radiological score, albumin levels, C-reactive protein levels and incremental shuttle walk test distance (ISWD) were significantly correlated with the total and component scores on the SGRQ. Multiple regression analysis showed that the SGRQ score was significantly associated with radiological score, pulmonary function and ISWD.CONCLUSION: This study was the first to assess the effect of clinical parameters on the SGRQ in patients with NTM-PD. HRQoL as determined using the SGRQ was associated with the radiological score, pulmonary function and ISWD in patients with NTM-PD.

Imaging of local structures affecting electrical transport properties of large graphene sheets by lock-in thermography.

The distribution of defects and dislocations in graphene layers has become a very important concern with regard to the electrical and electronic transport properties of device applications. Although several experiments have shown the influence of defects on the electrical properties of graphene, these studies were limited to measuring microscopic areas because of their long measurement times. Here, we successfully imaged various local defects in a large area of chemical vapor deposition graphene within a reasonable amount of time by using lock-in thermography (LIT). The differences in electrical resistance caused by the micrometer-scale defects, such as cracks and wrinkles, and atomic-scale domain boundaries were apparent as nonuniform Joule heating on polycrystalline and epitaxially grown graphene. The present results indicate that LIT can serve as a fast and effective method of evaluating the quality and uniformity of large graphene films for device applications.

Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma.

We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification.

Screening for musculoskeletal problems in Japanese schoolchildren: a cross-sectional study nested in a cohort.

OBJECTIVES: To clarify the frequency of musculoskeletal problems in public elementary and junior high school children and to determine the advantages and problems of musculoskeletal examinations. STUDY DESIGN: School-based cross-sectional study nested in a cohort. METHODS: We examined 41,376 public elementary and junior high school children (aged 6-15 years) in Miyazaki, Japan, from 2008 to 2014. Participation was voluntary. Participants received an in-school primary musculoskeletal examination (clinical examination with check items and a questionnaire) and a secondary examination at an orthopaedic outpatient clinic as indicated. Estimated prevalence rates for musculoskeletal problems were calculated from the results of both examinations. RESULTS: The total estimated prevalence of musculoskeletal problems was 8.6%. Prevalence by school grade ranged from 3.2% to 13.7%. Estimated prevalence rates increased as grade increased and were higher in junior high school students than in elementary school students. The secondary examination identified musculoskeletal problems on the back (65.4%), knee (8.1%), ankle or feet (7.3%) and elbow (5.4%). Of those referred for a secondary examination, 44.4% had not reported musculoskeletal complaints on the initial questionnaire. Overall, 69.8% of problems diagnosed in the secondary examination were previously undiagnosed. CONCLUSIONS: School-based musculoskeletal examination enables early detection of abnormal growth and disorders of the locomotive organs and is expected to support children's musculoskeletal growth and development. We recommend musculoskeletal examinations as part of school check-ups in Japan. Our findings suggest musculoskeletal examinations should be conducted for students in higher elementary school grades and for all junior high school students. Evaluation should include both direct clinical examination and questionnaires.

Factors affecting volume change of myocutaneous flaps in oral cancer.

After oral cancer resection with flap reconstruction, the volume of the flap decreases over time. The purpose of this study was to estimate the volume change in myocutaneous flaps and to identify the clinical factors associated with this volume decrease. Postoperative computed tomography scans and magnetic resonance images of 30 patients, obtained at 1, 6, and 12 months after oral cancer resection with myocutaneous flap reconstruction, were reviewed retrospectively. Changes in the volume of the flaps over time were assessed. The residual flap ratio was calculated using the flap volume at 1 month after reconstruction as the denominator. The residual ratios in relation to clinical factors were compared at 6 and 12 months using the Student t-test. Overall, the flap residual ratio was 78.1% (range 64.1-93.9%) at 6 months and 71.4% (range 48.8-87.2%) at 12 months. Hypertension, diabetes mellitus, and postoperative radiotherapy were significantly associated with volume changes at 6 months, and postoperative infection and decreased serum albumin levels were associated with volume changes at both 6 months (P=0.015 and P=0.001, respectively) and 12 months (P=0.026 and P=0.017, respectively). Flap reconstruction must be performed with postoperative flap atrophy in mind in order to preserve optimum speech and swallowing function.

Gate-Tunable Spin-Charge Conversion and the Role of Spin-Orbit Interaction in Graphene.

The small spin-orbit interaction of carbon atoms in graphene promises a long spin diffusion length and the potential to create a spin field-effect transistor. However, for this reason, graphene was largely overlooked as a possible spin-charge conversion material. We report electric gate tuning of the spin-charge conversion voltage signal in single-layer graphene. Using spin pumping from an yttrium iron garnet ferrimagnetic insulator and ionic liquid top gate, we determined that the inverse spin Hall effect is the dominant spin-charge conversion mechanism in single-layer graphene. From the gate dependence of the electromotive force we showed the dominance of the intrinsic over Rashba spin-orbit interaction, a long-standing question in graphene research.

Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma.

BACKGROUND: Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients. METHODS: We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery. RESULTS: The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients. CONCLUSIONS: Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.

Comprehensive safety management and assessment at rugby football competitions.

The present study aims to improve medical systems by designing objective safety assessment criteria for rugby competitions. We evaluated 195 competitions between 2002 and 2011 using an original safety scale comprising the following sections: 1) competence of staff such as referees, medical attendants and match day doctor; 2) environment such as weather, wet bulb globe temperature and field conditions; and 3) emergency medical care systems at the competitions. Each section was subdivided into groups A, B and C according to good, normal or fair degrees of safety determined by combinations of the results.Overall safety was assessed as A, B and C for 110, 78 and 7 competitions, respectively. The assessments of individual major factors were mostly favorable for staff, but the environment and medical care systems were assessed as C in 25 and 70, respectively, of the 195 competitions. Medical management involves not having a match day doctor, but also comprehensive management including preventive factors and responses from the staff, environment and medical-care systems. 6 cases of severe injuries and accidents occurred between 2002 and 2011, which were observed in Grade A competition. These cases revealed better prognosis without obvious impairment, thus confirming the value of the present assessment scale.

Upregulation of non-ß cell-derived vascular endothelial growth factor A increases small clusters of insulin-producing cells in the pancreas.

Pancreatic ß cell-derived vascular endothelial growth factor A (VEGF-A) contributes to normal ß cell function. We therefore hypothesized that non-ß cell-derived VEGF-A may affect its properties in adult mice.We generated transgenic mice expressing human VEGF-A (hVEGF-A) in a visceral smooth muscle cell (SMC)-dominant manner under the control of the transgelin (Tagln/SM22α) promoter via a tamoxifen-induced Cre/loxP recombination system (SM-CreER(T2)/hVEGF mice).SM-CreER(T2)/hVEGF mice received tamoxifen orally followed by microscopic examination of their pancreas 4 weeks after the hVEGF-A induction. The number of clusters of insulin-producing cells (IPCs) in islets, pancreatic ducts, and individual IPCs were counted.The number of small IPC clusters (100-215 µm(2)) in the pancreas increased significantly in SM-CreER(T2)/hVEGF mice compared with SM-CreER(T2)(Ki) mice (473 out of 1 992 counts vs. 199 out of 976 counts, p<0.05), although total IPC area and the number of pancreatic duct IPCs, in proportion to exocrine area, were similar between the 2 groups. Although most small IPC clusters observed in SM-CreER(T2)/hVEGF mice were not accompanied by α and/or δ cells, some were attached to a single or a few α cells. An STZ-induced diabetic state in SM-CreER(T2)/hVEGF mice was slightly ameliorated, with only one point of significance 12 weeks after STZ administration, compared with SM-CreER(T2)(Ki) mice.Upregulation of non-ß cell-derived VEGF-A may alter the composition of pancreatic IPCs by increasing the number of small IPC clusters. These findings provide new information on the role of non-ß cell-derived VEGF-A to IPC regeneration and insulin production.

Angiosarcoma of the oral cavity: a clinicopathological study and a review of the literature.

Soft tissue sarcomas are uncommon in the head and neck. Primary angiosarcomas of the oral cavity area are extremely rare, and have mostly been presented as case reports. This paper presents the clinical and histological features of three such cases. All patients were diagnosed based on the presence of rapidly extending masses involving the tongue, maxillary gingiva, or mandibular gingiva; bone destruction was present in two cases. The resected specimens revealed clustered large, pleomorphic, and spindle-shaped cells with a markedly haemorrhagic background. Tumour cells showed expression of vascular endothelial markers, such a CD31, CD34, and factor VIII-related antigen. Despite undergoing radical surgery, distant metastases developed in all three cases. We also studied the clinicopathological features of a series of oral angiosarcomas. This article therefore reports the clinicopathological features of the three new cases and provides a review of the cases of primary oral angiosarcoma reported during the past 20 years.

Is the prognostic impact of tumor location in patients with surgically resected esophageal squamous cell carcinoma affected by surgical approach?

AIM: The aim of the present study was to clarify differences in node metastasis mode and clinical outcomes based on tumor location in patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Participants comprised 228 patients with ESCC who underwent radical esophagectomy without preoperative supplement therapies. Lymph nodes were harvested from three fields: the neck, thorax, and abdomen. Patients were divided into three groups depending on tumor location [upper esophagus (UE), middle esophagus, or lower esophagus (LE)] and analyzed clinicopathologically. RESULTS: The LE group showed significantly more progressive ESCC in terms of tumor invasion (p = 0.025), node metastasis (p = 0.0071), and TNM stage (p = 0.0043). The LE group revealed a tendency to metastasize to extrathoracic (especially abdominal) nodes (p = 0.0008). Recurrent laryngeal node metastasis was increased in the UE group (p = 0.016). However, no prognostic differences were detected between groups according to tumor location. Likewise, subgroup analyses by surgical approach (open thoracotomy vs. thoracoscopy) and cancer stage (stage I/II, III, and IV) did not reveal any significant prognostic impact of tumor location. CONCLUSION: Lymphatic spread varied by tumor location, but no prognostic impact of tumor location could be detected in patients with ESCC in spite of surgical approach or cancer stage.

PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression.

BACKGROUND: The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown. METHODS: To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer. RESULTS: Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046). CONCLUSION: The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.

Negative-U system of carbon vacancy in 4H-SiC.

Using electron paramagnetic resonance (EPR), energy levels of the carbon vacancy (V(C)) in 4H-SiC and its negative-U properties have been determined. Combining EPR and deep-level transient spectroscopy we show that the two most common defects in as-grown 4H-SiC--the Z(1/2) lifetime-limiting defect and the EH(7) deep defect--are related to the double acceptor (2-|0) and single donor (0|+) levels of V(C), respectively.

Fabrication of three-dimensional nano, micro and micro/nano scaffolds of porous poly(lactic acid) by electrospinning and comparison of cell infiltration by Z-stacking/three-dimensional projection technique.

The use of electrospun extracellular matrix (ECM)-mimicking nanofibrous scaffolds for tissue engineering is limited by poor cellular infiltration. The authors hypothesised that cell penetration could be enhanced in scaffolds by using a hierarchical structure where nano fibres are combined with micron-scale fibres while preserving the overall scaffold architecture. To assess this, we fabricated electrospun porous poly(lactic acid) (PLA) scaffolds having nanoscale, microscale and combined micro/nano architecture and evaluated the structural characteristics and biological response in detail. Although the bioactivity was intermediate to that for nanofibre and microfibre scaffold, a unique result of this study was that the micro/nano combined fibrous scaffold showed improved cell infiltration and distribution than the nanofibrous scaffold. Although the cells were found to be lining the scaffold periphery in the case of nanofibrous scaffold, micro/nano scaffolds had cells dispersed throughout the scaffold. Further, as expected, the addition of nanoparticles of hydroxyapatite (nHAp) improved the bioactivity, although it did not play a significant role in cell penetration. Thus, this strategy of creating a three-dimensional (3D) micro/nano architecture that would increase the porosity of the fibrous scaffold and thereby improving the cell penetration, can be utilised for the generation of functional tissue engineered constructs in vitro.

Intracerebral microinjection of interleukin-4/interleukin-13 reduces ß-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice.

We previously reported that the anti-inflammatory cytokine interleukin (IL)-4 induced selective clearance of oligomeric ß-amyloid (Aß(1-42)) in rat primary type 2 microglial cells. For the present study, we investigated whether IL-4 and IL-13 could activate microglial cells to induce Aß clearance in vivo and improve cognitive deficits in APP23 mice, which are amyloid precursor protein transgenic mice. We administered an intracerebral microinjection of a mixture of IL-4 and IL-13 or of saline vehicle into one hemisphere of APP23 mice and their wild-type littermates, 4.5 and 9 months old, after which we evaluated the effects of these treatments on spatial learning and memory by Morris Water Maze test and on accumulated amounts of Aß. The cytokine injection significantly improved memory deficits of 4.5-month-old APP23 mice, but did not do so in 9-month-old APP23 mice, even though similar Aß reductions were observed in both age groups of APP23 mice in the ipsilateral neocortex. The cytokine injection improved memory impairment of 9-month-old wild-type (WT) mice in the probe trial. Immunohistochemical analysis of the 4.5-month-old APP23 mice revealed the presence of increased numbers of microglial cells at 2 days after the cytokine injection. In addition to induced CD36 expression in the activated microglia, increased expression of neprilysin, mainly in neurons, suggested that the cytokines improved the cognitive deficits via degradation and clearance of intra- and extraneuronal Aß peptides, of buffer-extractable nonplaque form. Double immunostaining also revealed that most of the activated microglia had the M2-like phenotype. This unique mechanism of IL-4/IL-13-induced clearance of Aß may provide an additional strategy to prevent and/or cure Alzheimer's disease at early stage.

Granulocyte and monocyte adsorption apheresis as an effective treatment for Reiter disease.

Reiter disease (RD) is characterized by a triad of sterile arthritis, urethritis and conjunctivitis. The conditions occur concomitantly or sequentially, and are associated with mucocutaneous features such as circinate balanitis and stomatitis. Arthritis usually occurs in attacks followed by recovery, but it sometimes progresses to permanent damage of the affected joints. Because the symptoms of this disorder are attributable to activated neutrophils, we assessed the efficacy of granulocyte and monocyte adsorption apheresis (GCAP) in a 73-year-old man with RD who had skin rashes on his penis, scrotum and right hand, with severe arthralgia. The patient's skin rash and joint pain responded dramatically to five sessions of GCAP delivered at intervals of 5 days. We present a detailed description of the patient and discuss the mechanisms of GCAP, and suggest that GCAP may be useful for treating RD.

Meticillin-resistant Staphylococcus aureus and meticillin-susceptible S. aureus pneumonia: comparison of clinical and thin-section CT findings.

OBJECTIVES: The purpose of this study was to compare the clinical and thin-section CT findings in patients with meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-susceptible S. aureus (MSSA). METHODS: We retrospectively identified 201 patients with acute MRSA pneumonia and 164 patients with acute MSSA pneumonia who had undergone chest thin-section CT examinations between January 2004 and March 2009. Patients with concurrent infectious disease were excluded from our study. Consequently, our study group comprised 68 patients with MRSA pneumonia (37 male, 31 female) and 83 patients with MSSA pneumonia (32 male, 51 female). Clinical findings in the patients were assessed. Parenchymal abnormalities, lymph node enlargement and pleural effusion were assessed. RESULTS: Underlying diseases such as cardiovascular were significantly more frequent in the patients with MRSA pneumonia than in those with MSSA pneumonia. CT findings of centrilobular nodules, centrilobular nodules with a tree-in-bud pattern, and bronchial wall thickening were significantly more frequent in the patients with MSSA pneumonia than those with MRSA pneumonia (p = 0.038, p = 0.007 and p = 0.039, respectively). In the group with MRSA, parenchymal abnormalities were observed to be mainly peripherally distributed and the frequency was significantly higher than in the MSSA group (p = 0.028). Pleural effusion was significantly more frequent in the patients with MRSA pneumonia than those with MSSA pneumonia (p = 0.002). CONCLUSIONS: Findings from the evaluation of thin-section CT manifestations of pneumonia may be useful to distinguish between patients with acute MRSA pneumonia and those with MSSA pneumonia.