Radiologic-histopathologic correlation of fatty island sign with fat necrosis in atypical lipomatous tumor and lipoma.

AIM: This study aimed to assess the imaging features of atypical lipomatous tumors (ALTs) and lipoma with fat necrosis. METHODS: This study included patients with histopathologically proven fat necrosis within adipocytic tumors who underwent preoperative imaging. Magnetic resonance imaging (MRI) and/or computer tomography (CT) findings of fat necrosis associated with lipomatous tumors were retrospectively reviewed, emphasizing the "fatty island sign (FIS)." FISs were defined as well-demarcated, focal fat-containing areas surrounded by more thickened septa compared with other intratumoral septa. Imaging findings of FIS were compared between ALT and lipoma. RESULTS: Fat necrosis was histopathologically confirmed in 17 patients (6 ALTs and 11 lipomas). Among them, 18 FISs were observed in 10 lesions (59%). Multiple FISs within a lesion were observed in 4 (40%) patients. The median maximum diameter of the FISs was 37 mm. Hypointense areas within FISs relative to the subcutaneous fat on T1- and T2-weighted images were observed in 8 (80%) and 9 (90%), respectively, whereas hyperintense areas within FISs on fat-suppressed T2-weighted images were observed in 2 (20%). Nonfatty solid components within FISs were observed in 2 (20%). On CT, increased fat attenuation and pure fat attenuation within FISs were observed in 6 (86%) and 1 (14%), respectively. The imaging findings of FIS were not significantly different between ALT and lipoma. CONCLUSION: FISs were observed in 59% of the histologically proven ALT and lipoma patients with fat necrosis. The hypointense areas relative to the subcutaneous fat on T1- and T2-weighted images and increased fat attenuation on CT were usually observed within FISs.

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence.

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.

Respiratory Sarcopenia and Sarcopenic Respiratory Disability: Concepts, Diagnosis, and Treatment.

The condition of muscle fiber atrophy and weakness that occurs in respiratory muscles along with systemic skeletal muscle with age is known as respiratory sarcopenia. The Japanese Working Group of Respiratory Sarcopenia of the Japanese Association of Rehabilitation Nutrition narratively reviews these areas, and proposes the concept and diagnostic criteria. We have defined respiratory sarcopenia as "whole-body sarcopenia and low respiratory muscle mass followed by low respiratory muscle strength and/or low respiratory function." Respiratory sarcopenia can be caused by various factors such as aging, decreased activity, undernutrition, disease, cachexia, and iatrogenic causes. We have also created an algorithm for diagnosing respiratory sarcopenia. Respiratory function decreases with age in healthy older people, along with low respiratory muscle mass and strength. We have created a new term, "Presbypnea," meaning a decline in respiratory function with aging. Minor functional respiratory disability due to aging, such as that indicated by a modified Medical Research Council level 1 (troubled by shortness of breath when hurrying or walking straight up hill), is an indicator of presbypnea. We also define sarcopenic respiratory disability as "a disability with deteriorated respiratory function that results from respiratory sarcopenia." Sarcopenic respiratory disability is diagnosed if respiratory sarcopenia is present with functional disability. Cases of respiratory sarcopenia without functional disability are diagnosed as "at risk of sarcopenic respiratory disability." Functional disability is defined as a modified Medical Research Council grade of 2 or more. Rehabilitation nutrition, treatment that combines rehabilitation and nutritional management, may be adequate to prevent and treat respiratory sarcopenia and sarcopenic respiratory disability.

QTL analysis for early growth in an intercross between native Japanese Nagoya and White Plymouth Rock chicken breeds using RAD sequencing-based SNP markers.

An F2 population of 239 chickens was obtained by an intercross between Nagoya (NAG), a native Japanese breed with low growth, and White Plymouth Rock (WPR), a Western breed with high growth. Using SNP markers obtained by restriction site-associated DNA sequencing, genome-wide QTL analysis was performed and it revealed three QTL for early postnatal growth in the F2 population at genome-wide 5% significance levels. The most highly significant QTL affecting body weights at 2-4 weeks of age and weight gains at 2-3 and 0-4 weeks was located on GGA4 between 34.0 and 65.6 Mb with LOD scores of 3.9-5.9 and it explained 4.9-9.9% of the total variance of the traits. The analysis provided evidence for significant QTL on GGA2 between 105.6 and 125.2 Mb (LOD = 4.6) and on GGA1 between 51.1 and 61.6 Mb (LOD = 4.0) which had effects on body weight at 3 weeks and body weight gain at 0-1 week respectively. These two genomic regions explained 6.6 and 6.9% of the phenotypic F2 variance of the corresponding traits respectively. The allele derived from WPR at all QTL increased the corresponding traits. Neither sex-specific nor epistatic QTL was detected. The results showed that the GGA4 QTL affecting multiple traits is a key locus responsible for early growth in our chicken cross, suggesting that this QTL may make a great contribution to genetic improvement of growth performance of the NAG breed with a low growth rate.

Assignment of Dental Hygienists Improves Outcomes in Japanese Rehabilitation Wards: A Retrospective Cohort Study.

OBJECTIVES: To clarify the effectiveness of ward-assigned dental hygienists (DHs) on rehabilitation outcomes in rehabilitation wards. DESIGN: Retrospective cohort study. SETTING: The registry data from the Japanese Rehabilitation Nutrition Database. PARTICIPANTS: 656 patients with hip fracture or stroke admitted to convalescent rehabilitation wards. MEASUREMENTS: The main outcome measures were the Functional Independence Measure (FIM), the Food Intake Level Scale (FILS), and the home discharge rate. Patients were divided into two groups based on the ward setting: with an assigned DH (DH group) and without an assigned DH (NDH group). Clinical characteristics and outcomes were compered between the groups. Between-facility differences were adjusted by generalized estimating equation. We performed post-hoc power analysis to confirm that there were enough samples included in this study to detect a significant difference. RESULTS: Of 656 patients (mean age, 77 years; 57.1% female; 65.5% stroke) from 10 facilities, 454 patients (69.2%) from 4 facilities were in the DH group. FIM score at discharge (107 vs 90, P<0.001), percentage improvement in FILS score from admission to discharge (44.5% vs 22.8%, P<0.001) and home discharge rate (72.5% vs 61.4%, P<0.001) were significantly higher in the DH group than in the NDH group. After multivariate analysis, the FIM score at discharge (P=0.007), FILS score at discharge (P=0.024), and home discharge rate (P=0.007) were significantly higher in the DH group than in the NDH group. CONCLUSIONS: ADL and swallowing function were significantly improved at discharge and the home discharge rate was higher among patients in rehabilitation wards with DHs. Having a ward-assigned DH may lead to better rehabilitation outcomes in rehabilitation wards.

Rehabilitation Nutrition for Iatrogenic Sarcopenia and Sarcopenic Dysphagia.

Sarcopenia is a very important issue in rehabilitation medicine and nutritional care. The prevalence of sarcopenia in older people is approximately 50% in the rehabilitation setting, and also approximately 15% of inpatients without sarcopenia upon admission developed sarcopenia during hospitalization. There is a concern that secondary sarcopenia may occur iatrogenically during hospitalization. Iatrogenic sarcopenia is defined as sarcopenia caused by the activities of medical staff including doctors, nurses, or other health care professionals in healthcare facilities. Iatrogenic sarcopenia is categorized into activity-related, nutrition-related and disease-related-iatrogenic sarcopenia. Especially in acute phase hospitals, concentrating on the treatment of diseases with less attention to nutrition and activity is more likely to cause iatrogenic sarcopenia. Sarcopenic dysphagia is also an important aspect in rehabilitation medicine and nutritional care. Sarcopenic dysphagia is characterized by swallowing difficulty because of a loss of mass and function in whole-body skeletal and swallowing muscles. Sarcopenic dysphagia can be diagnosed using a 5-step algorithm for the condition. Iatrogenic sarcopenia and sarcopenic dysphagia are affected by nutrition, activity and diseases in a complex manner. Therefore, treatment of iatrogenic sarcopenia and sarcopenic dysphagia requires comprehensive interventions through nutrition management and rehabilitation. Rehabilitation nutrition is effective for preventing and treating iatrogenic sarcopenia and sarcopenic dysphagia. Rehabilitation nutrition can be practiced more effectively and comprehensively by using the rehabilitation nutrition care process, which is a systematic problem-solving method. Further research is required to verify the efficacy of rehabilitation nutrition for preventing or improving iatrogenic sarcopenia and/or sarcopenic dysphagia.

Relationship between the length of the forefoot bones and performance in male sprinters.

Although recent studies have reported that the forefoot bones are longer in sprinters than in non-sprinters, these reports included a relatively small number of subjects. Moreover, while computer simulation suggested that longer forefoot bones may contribute to higher sprint performance by enhancing plantar flexor moment during sprinting, the correlation between forefoot bone length and sprint performance in humans has not been confirmed in observational studies. Thus, using a relatively large sample, we compared the length of the forefoot bones between sprinters and non-sprinters. We also examined the relationship between forefoot bone length and performance in sprinters. The length of forefoot bones of the big and second toes in 36 well-trained male sprinters and 36 male non-sprinters was measured using magnetic resonance imaging. The length of forefoot bones in the big and second toes was significantly longer in sprinters than in non-sprinters. After dividing the sprinters into faster and slower groups according to their personal best time in the 100-m sprint, it was found that the forefoot bone length of the second toe, but not that of the big toe, was significantly longer in faster group than in slower group. Furthermore, the forefoot bone length of the second toe correlated significantly with the personal best time in the 100-m sprint. This study supported evidence that the forefoot bones are longer in sprinters than in non-sprinters. In addition, this is the first study to show that longer forefoot bones may be advantageous for achieving superior sprint performance in humans.

Energy saving system with high effluent quality for municipal sewage treatment by UASB-DHS.

An up-flow anaerobic sludge blanket (UASB) - down-flow hanging sponge (DHS) was applied to Japanese municipal sewage treatment, and its treatability, energy consumption, and sludge production were evaluated. The designed sewage load was 50 m(3)/d. The sewage typically had a chemical oxygen demand (COD) of 402 mg/L, a suspended solids (SS) content of 167 mg/L, and a temperature of 17-29 °C. The UASB and DHS exhibited theoretical hydraulic retention times of 9.7 and 2.5 h, respectively. The entire system was operated without temperature control. Operation was started with mesophilic anaerobic digested sludge for the UASB and various sponge media for the DHS. Continuous operational data suggest that although the cellulose decomposition and methanogenic process in the UASB are temperature sensitive, stable operation can be obtained by maintaining a satisfactory sludge volume index and sludge concentration. For the DHS, the cube-type medium G3-2 offers superior filling rates, biological preservation and operational execution. The SS derived from the DHS contaminated the effluent but could be removed by optional sand filtration. A comparison with conventional activated sludge (CAS) treatment confirmed that this system is adequate for municipal sewage treatment, with an estimated energy requirement and excess sludge production approximately 75 and 85% less than those of CAS, respectively.

Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma.

OBJECTIVE: To improve medulloblastoma proton therapy. Although considered ideal for proton therapy, there are potential disadvantages. Expected benefits include reduced radiation-induced cancer and circulatory complications, while avoiding small brain volumes of dose in-homogeneity when compared with conventional X-rays. Several aspects of proton therapy might contribute to reduced tumour control due to (a) the use of more homogenous dose levels which can result in under-dosage, (b) differences in relative biological effectiveness (RBE) between that prescription RBE of 1.1 and the RBE of brain and spinal cord (likely to exceed 1.1) and in medulloblastoma cells (where RBE is likely to be below 1.1). Such changes, although speculative for RBE, might result in potential underdosage of tumour cells and a higher bio-effect in brain tissue. METHODS: Dose distributions for X-ray and proton treatment are compared, with allocation of likely RBE values for fast growing medullolastoma cells and stable central nervous system tissue. RESULTS: These physical and radiobiological factors are shown to combine to give a higher risk of tumour recurrence with further risks on tumour control when dose reduction schedules used for X-ray therapy are replicated for proton therapy for "low-risk" patients. CONCLUSION: The dose distributions and prescribed doses of proton therapy, taking into account RBE, in children and adults with medulloblastoma, need to be reconsidered.

Growth suppression and mitotic defect induced by JNJ-7706621, an inhibitor of cyclin-dependent kinases and aurora kinases.

Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, endoreduplication, and apoptosis. In the present study, we further investigated the molecular mechanisms underlying these effects. The inhibitor arrested various cells at G2 phase at low concentration, and at both G1 and G2 phases at high concentration. JNJ-7706621 did not prevent localization of Aurora A to the spindle poles, but did inhibit other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase. Similarly, the drug did not prevent localization of Aurora B to the kinetochore, but did inhibit other chromosomal passenger proteins such as Survivin and INCENP. In the cells exposed to JNJ-7706621 after nocodazole release, Aurora B, INCENP, and Survivin became relocated to the peripheral region of chromosomes, but Plk1 and Prc1 were localized on microtubules in later mitotic phase. Treatment of nocodazole-synchronized cells with JNJ-7706621 was able to override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation. Injection of the drug significantly inhibited the growth of TC135 Ewing's sarcoma cells transplanted into athymic mice by cell cycle arrest and apoptosis. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at multiple points, suggesting that it could be useful for cell cycle analysis and therapy of various cancers, including Ewing's sarcoma.

Temporal-spatial expression of presenilin 1 and the production of amyloid-beta after acute spinal cord injury in adult rat.

Regulated intramembrane proteolysis (RIP) is one of the signaling pathways mediating information transfer from the extracellular to the intracellular domain. gamma-Secretase is an aspartyl protease of the RIP that cleaves the intramembrane region of type I integral membrane proteins, such as amyloid precursor protein (APP). Presenilin 1 (PS1) is the catalytic subunit of gamma-secretase and PS1 mutations cause Alzheimer's disease, spastic paraplegia and spinal cord atrophy. The biological function of PS1 in the spinal cord has not been fully elucidated. Thus, to clarify the involvement of RIP in spinal cord injury, we examined the expression of PS1, APP and amyloid-beta protein (Abeta) following rat spinal cord hemisection. Western blot analysis showed that PS1, APP and Abeta levels increased 1 day after spinal cord hemisection. Immunohistochemistry showed an increased number of PS1 immunopositive cells about 1mm from the lesion site. PS1, APP and Abeta double staining with cell-type specific markers showed colocalization of PS1 with axons in the white matter of the lesioned side. These findings suggest that RIP signaling occurs following rat spinal cord injury. In the future, the control of RIP may offer a new strategy for the treatment of spinal cord injury.

Reduction of oxidative stress marker levels by anti-TNF-alpha antibody, infliximab, in patients with rheumatoid arthritis.

OBJECTIVE: The aim of this study was to evaluate the effects of anti-TNF-alpha antibody, infliximab, on oxidative stress markers representing DNA damage, lipid peroxidation, and glycoxidation. METHODS: Twenty-three RA patients underwent infliximab treatment and were analyzed for 30 weeks. Six patients who experienced side effects and one patient who had a reduced efficacy of infliximab were discontinued the infliximab treatment at 30-54 weeks. Sixteen patients were analyzed for 54 weeks. The levels of serum total, urinary total, and free pentosidine, which is an advanced glycation end-product (AGE), and of urinary 15-Isoprostane F2t and 8-hydroxy-deoxy guanosine (8-OHdG) were determined at baseline and at 14, 30, and 54 weeks after initial treatment with infliximab. RESULTS: Serum total, urinary total, and free pentosidine levels were reduced at 54 weeks after initial infliximab treatment. Urinary 15-Isoprostane F2t and 8-OHdG levels were also reduced at 14, 30, and 54 weeks. Urinary 8-OHdG levels in RA patients correlated with CRP and the Disease Activity Score of 28 joints. CONCLUSION: In RA patients, infliximab plays an essential role as an anti-oxidative agent against AGE formation, oxidative DNA damage and lipid peroxydation.

Restoration of elbow function by intercostal nerve transfer for obstetrical paralysis with co-contraction of the biceps and the triceps.

Among the conservatively treated patients with obstetrical paralysis after delivery in the vertex presentation, cross reinnervation sometimes occurs in the course of their recovery and co-contraction of multiple muscles impairs smooth upper limb motion. Such co-contraction of the biceps and the triceps inhibits normal elbow motion, making it impossible to use the elbow effectively in daily activities, despite adequate strength in these muscles. To overcome biceps/triceps co-contraction, we performed intercostal nerve transfer to the musculocutaneous nerve for three patients of age 11 months, 6 years and 9 years, respectively, and to the motor branches of the triceps for two patients of age 4 and 14 year-old, respectively. During the average follow-up period of 5.6 (range 1-11.5) years, the power of the reinnervated muscle improved to more than M3, and smooth motion of the elbow independently of shoulder motion was restored.

Detection of an isoform of alpha(1)-antitrypsin in serum samples from foals with gastric ulcers.

The objective of this study was to find serum indicators of gastric ulcers in foals. By using two-dimensional electrophoresis of serum proteins, three distinct spots were detected in samples from foals with gastric ulcers detected endoscopically. One of them appeared with high frequency and was identified by partial digestion with trypsin and subsequent nano-electrospray ionisation-tandem mass spectrometry (nanoesi-ms/ms) analysis as an alpha(1)-antitrypsin. Western blot analysis, using an antibody against human alpha(1)-antitrypsin, revealed at least two bands, of molecular weight 58 kDa and 55 kDa, in the sera. The 55 kDa band was detected in 44 of 47 serum samples from foals with gastric ulcers, but in only three of 22 serum samples from healthy foals.

Mechanical fragmentation and transportation of calcium phosphate substrate by filopodia and lamellipodia in a mature osteoclast.

The functions of filopodia and lamellipodia in mature osteoclasts are not well known in the process of bone resorption. We investigated the function of filopodial/lamellipodial movement in mature osteoclasts by video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy. Mature osteoclasts, which were isolated from Japanese white rabbits, were cultured on calcium phosphate (CP)-coated quartz coverslips to observe filopodial/lamellipodial movement and the formation of CP-free areas precisely. Filopodia broke the CP substrate into pieces and transported them to the cell body by capturing them at the tip. Lamellipodia destroyed the CP substrate, and transported it to the cell body by capturing small particles in a mass. This study suggests two functions of filopodia and lamellipodia in mature osteoclasts, i.e., the mechanical fragmentation of the CP substrate and the transportation of the CP particles to the cell body.

Restoration of shoulder function and elbow flexion by nerve transfer for poliomyelitis-like paralysis caused by enterovirus 71 infection.

We report the case of an eight-month-old girl who presented with a poliomyelitis-like paralysis in her left upper limb caused by enterovirus 71 infection. She recovered useful function after nerve transfers performed six months after the onset of paralysis. Early neurotisation can be used successfully in the treatment of poliomyelitis-like paralysis in children.

Electric polarization, magnetoelectric effect, and orbital state of a layered iron oxide with frustrated geometry.

A layered iron oxide RFe2O4 (R denotes rare-earth-metal elements) is an exotic dielectric material with charge-order (CO) driven electric polarization and magnetoelectric effect caused by spin-charge coupling. In this paper, a theory of electronic structure and dielectric property in RFe2O4 is presented. Charge frustration in paired-triangular lattices allows a charge imbalance without inversion symmetry. Spin frustration induces reinforcement of this polar CO by a magnetic ordering. We also analyze an orbital model for the Fe ion which does not show a conventional long-range order.

Emerinopathy and laminopathy clinical, pathological and molecular features of muscular dystrophy with nuclear envelopathy in Japan.

Mutations in the genes for nuclear envelope proteins of emerin (EMD) and lamin A/C (LMNA) are known to cause Emery-Dreifuss muscular dystrophy (EDMD) and limb girdle muscular dystrophy (LGMD). We compared clinical features of the muscular dystrophy patients associated with mutations in EMD (emerinopathy) and LMNA (laminopathy) in our series. The incidence of laminopathy was slightly higher than that of emerinopathy. The age at onset of the disease in emerinopathy was variable and significantly older than in laminopathy. The initial symptom of emerinopathy was also variable, whereas nearly all laminopathy patients presented initially with muscle weakness. Calf hypertrophy was often seen in laminopathy, underscoring the importance of mutation screening for LMNA in childhood muscular dystrophy with calf hypertrophy. The clinical spectrum of emerinopathy is actually wider than previously known including EDMD, LGMD, conduction defects with minimal muscle/joint involvement, and their intermittent forms. Pathologically, no marked difference was observed between emerinopathy and laminopathy. Increased number and variation in size of myonuclei were detected. More precise observations using electron microscopy is warranted to characterize the detailed nuclear changes in nuclear envelopathy.

The relationship between pre-operative symptoms, operative findings and postoperative complications in schwannomas.

This study presents a retrospective review of the management of schwannomas in the limbs and examines the relationship between pre-operative clinical examination, operative findings and postoperative neurological complications. Eighteen tumours with a histological diagnosis of schwannoma in 17 patients who underwent surgery between 1998 and 2004 were the basis of this study. Enucleation of the tumour was possible in 14 cases. None of these patients had neurological complications pre-operatively but eight had mild neurological complications postoperatively. The complications consisted of sensory deficit in five cases, motor weakness in one and both in two. Enucleation of the tumours was impossible in four cases. These schwannomas originated in the brachial plexus in three cases and the ulnar nerve in the proximal arm in one case. Tumours with pre-operative symptoms and masses located at a proximal site in the limb were more likely to be impossible to enucleate completely.

Real-time PCR quantification of nitrite reductase (nirS) genes in a nitrogen removing fluidized bed reactor.

Molecular approaches were applied to identify and enumerate denitrifying bacteria subsisting in a fluidized bed reactor (FBR). The FBR was continuously operated as a unit for the removal of nitrogen from the effluents of domestic sewage treatment plant, with an additional supply of methanol as a carbon source. By denaturing gradient gel electrophoresis (DGGE) and sequence analysis of 16S ribosomal RNA genes, Thauera group was found to be dominant among the denitrifying bacteria in the FBR sludge. Oligonucleotide probe THA155 for fluorescence in situ hybridization (FISH) was newly designed for specifically targeting the Thauera group. However, the THA155 signal obtained from the sludge was only 0.9-5.7% of the DAPI-stained total cells. The real-time polymerase chain reaction (PCR) targeting the sequences of nitrite reductase (NIR) gene, a key enzyme of denitrification processes, was performed to quantify the cells of denitrifying bacteria cells including the Thauera group in FBR sludge. An excellent correlation was obtained between the numbers of nirS genes and the activity of denitrifiers in the FBR sludge.