Background Beige adipocytes comprise a unique thermogenic cell type in the white adipose tissue (WAT) of rodents and humans, and play a critical role in energy homeostasis. In this scenario, ...recruitment of beige cells has been an important focus of interest for the development of novel therapeutic strategies to treat obesity. PPARgamma activation by full agonists (thiazolidinediones, TZDs) drives the appearance of beige cells, a process so-called browning of WAT. However, this does not translate into increased energy expenditure, and TZDs are associated with weight gain. Partial PPARgamma agonists, on the other hand, do not induce weight gain, but have not been shown to drive WAT browning. The present study was designed to investigate the effects of GQ-16 on BAT and on browning of WAT in obese mice. Methods Male Swiss mice with obesity and hyperglycemia induced by high fat diet were treated with vehicle, rosiglitazone (4 mg/kg/d) or the TZD-derived partial PPARgamma agonist GQ-16 (40 mg/kg/d) for 14 days. Fasting blood glucose, aspartate aminotransferase, alanine aminotransferase and lipid profile were measured. WAT and brown adipose tissue (BAT) depots were excised for determination of adiposity, relative expression of Ucp-1, Cidea, Prdm16, Cd40 and Tmem26 by RT-qPCR, histological analysis, and UCP-1 protein expression analysis by immunohistochemistry. Liver samples were also removed for histological analysis and determination of hepatic triglyceride content. Results GQ-16 treatment reduced high fat diet-induced weight gain in mice despite increasing energy intake. This was accompanied by reduced epididymal fat mass, reduced liver triglyceride content, morphological signs of increased BAT activity, increased expression of thermogenesis-related genes in interscapular BAT and epididymal WAT, and increased UCP-1 protein expression in interscapular BAT and in epididymal and inguinal WAT. Conclusion This study suggests for the first time that a partial PPARgamma agonist may increase BAT activity and induce the expression of thermogenesis-related genes in visceral WAT. General Significance These findings suggest that PPARgamma activity might be modulated by partial agonists to induce WAT browning and treat obesity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Myofibrillar myopathy (MFM) is characterized by nonhyaline lesions (foci of myofibrillar destruction) and hyaline lesions (cytoplasmic inclusions composed of compacted myofibrillar residues) on light ...and electron microscopy. Immunocytochemistry demonstrates the abnormal expression of desmin and numerous other proteins. The clinical, laboratory, and histologic features of MFM are heterogeneous, making a diagnosis difficult.
We diagnosed eight patients with MFM over the preceding 3 years. MFM was inherited in an autosomal dominant pattern in one patient, developed sporadically in five patients, and was induced by an experimental chemotherapy, Elinafide (Knoll, Parsippany, NJ), in two patients. Age at onset ranged from 14 to 64 years. The pattern of weakness was variable but involved proximal and distal muscles. Five patients had evidence of a cardiomyopathy. Electromyography demonstrated muscle membrane instability and small, polyphasic motor unit potentials. Serum creatine kinase levels were normal to moderately elevated (<10x normal). Light and electron microscopy demonstrated the characteristic pattern of nonhyaline and hyaline lesions and the associated abnormalities on immunocytochemistry.
Patients demonstrate a wide spectrum of clinical, laboratory, and histologic abnormalities. Chemotherapy-induced MFM has abnormalities on immunocytochemistry similar to the those of hereditary and sporadic cases. The pathogenesis of MFM is likely heterogeneous. However, MFM is distinctive in that it can preferentially affect distal muscles and has a frequent association with cardiomyopathy. The cardiomyopathy may be amenable to treatment with pacemaker insertion or cardiac transplantation.
The rimmed vacuoles within muscle in inclusion‐body myositis (IBM) are structures of uncertain origin. Two hypotheses have been proposed for their formation: that they develop as a consequence of ...abnormal lysosomal function or in association with the breakdown of myonuclei. We tested the latter hypothesis by studying muscle samples from 14 patients with IBM and 18 controls using immunohistochemistry for nuclear membrane proteins, examining semithin sections, and performing electron microscopy. We found that in IBM muscle vacuoles were immunoreactive for the inner nuclear membrane proteins emerin and lamin A/C. Myonuclei with fragmented or focally absent nuclear membranes were present in immunohistochemical and electron microscopy studies. The association of nuclear membrane proteins with rimmed vacuoles confirms the hypotheses that rimmed vacuoles in IBM form in association with myonuclear pathology and that IBM differs from other inflammatory myopathies in that abnormalities of myonuclei are more prominent. Muscle Nerve, 2006
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A new data acquisition system (DAQ) for bulk
μ
SR and low-energy
μ
SR (LE-
μ
SR) has been developed at PSI. It is based on commercial and in-house VME modules, and on the MIDAS DAQ software library. ...The system is able to cope with the different needs of the various PSI
μ
SR spectrometers, which was not possible with the existing CAMAC and ORTEC's pTA-clock based DAQ systems. The VME clock is a 64-channel CAEN V1190 TDC, using the CERN HPTDC chip, with programmable time resolution of 25, 100, 200 or 800
ps. The TDC onboard memory is continuously read through the VME bus by standard PC's or dedicated servers, using a 1-Gbit/s SIS3100/1100 VME–PCI interface. Detector rates are independently monitored using a 32-channel SIS3820 scaler module. In-house developed modules comprise an 8-channel constant fraction discriminator CFD950, a CD950 clock divider, an 8-channel linear fan-out SP950, a 16-channel NIM-ECL level converter LC950, and a programmable coincidence module FC950. All modules feature a superior performance compared to commercially available devices which allows their use also in the planned high-field
μ
SR spectrometer where a time resolution of about 100
ps is envisaged. A special external hardware logic is no longer required, since the system can deal with a rate total of 5
MHz which is sufficient for
μ
SR spectrometers with high event rate in their active veto systems.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
(CH3)2CHNH3Cu(ClxBr1-x)3 abbreviated IPACu(ClxBr1-x)3 is a mixed system of spin-gap compounds IPACuCl3 and IPACuBr3. This mixed system is reported by macroscopic measurements to show a magnetic order ...when the value of x is between the quantum critical points (QCPs) 0.44 and 0.87. We have investigated microscopically the ground state of the samples x 0.40, 0.45 and 0.50 which are located near the QCP of xc 0.44, by Muon Spin Relaxation (μSR) and NMR measurements. For x 0.40, μSR measurements in zero and longitudinal fields have shown that the spin fluctuation shows a significant slowing down with decreasing temperature, although the magnetic order does not appear down to T 15 mK, indicating that the ground state is an exotic one rather than a gapped one. For x 0.45 and 0.50, μSR and NMR measurements do not show any magnetic order at low temperatures, indicating that the QCP is larger than the reported value of xc 0.44.
Sporadic inclusion body myositis (s-IBM) is characterized by late onset of slowly progressive weakness that involves the quadriceps and volar forearm muscles early in the course of the disease. There ...are hereditary forms of inclusion body myopathy (h-IBM) that histologically resemble s-IBM. The lack of inflammation on biopsy and the different ages at onset and patterns of muscle weakness distinguish s-IBM from h-IBM. We report twin brothers with the typical clinical and histologic features of s-IBM. The occurrence of s-IBM in these twins suggests the possibility of a genetic susceptibility to developing s-IBM.
A discussion linking theory and practice in second language instruction focuses on ways of providing opportunities for meaningful interaction in language classrooms. The first part lays a theoretical ...foundation, looking at: the variety and evolution of instructional approaches from grammar-based to communicative; the classroom as environment for language acquisition; principles of the interactive approach; the episode hypothesis of learning and selection of appropriate materials; and the role of the affective domain. Part 2 explores a variety of classroom teaching methods and activities, including: Total Physical Response and the role of the audio-motor unit of commands; the natural language approach and its extensions; use of jazz chants, music, and poetry; storytelling, role play, and drama; games; and affective activities. Part 3 addresses practical issues of classroom management, instructional materials, placement tests, and instruction linking content areas and language learning. The fourth part contains descriptions of existing English-as-a-Second-Language and foreign language programs, and the fifth part presents related readings on how language is shaped, the notional syllabus, communicative methodology, second language acquisition theories, providing input for acquisition, the learning-development relationship, personality factors, testing approaches, and language proficiency, bilingualism, and academic achievement. A substantial bibliography and index are included. (MSE)
Highlights • Overall, many patients improved in strength over time and corticosteroid use was reduced. • No difference was found between typically used immunosuppressants in dermatomyositis. • There ...is a 5% mortality rate in dermatomyositis due to infections.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
The aim of the survey was to assess the incidence of anastomotic leaks (AL) and to identify risk factors predicting incidence and gravity of AL after low anterior resection (LAR) for ...rectal cancer performed by colorectal surgeons of the Italian Society of Colorectal Surgery (SICCR)
Methods
Information about patients with rectal cancers less than 12 cm from the anal verge who underwent LAR during 2005 was collected retrospectively. AL was classified as grade I to IV according to gravity. Fifteen clinical variables were examined by univariate and multivariate analyses. Further analysis was conducted on patients with AL to identify factors correlated with gravity
Results
There were 520 patients representing 64% of LAR for rectal cancer performed by SICCR members. The overall rate of AL was 15.2%. Mortality was 2.7% including 0.6% from AL. The incidence of AL was correlated with higher age (
p
<0.05), lower (<20 per year) centre case volume (
p
<0.05), obesity (
p
<0.05), malnutrition (
p
<0.01) and intraoperative contamination (
p
<0.05), and was lower in patients with a colonic J-pouch reservoir (
p
<0.05). In the multivariate analysis age, malnutrition and intraoperative contamination were independent predictors. The only predictor of severe (grade III/IV) AL was alcohol/smoking habits (
p
<0.05) while the absence of a diverting stoma was borderline significant (
p
<0.07)
Conclusion
Our retrospective survey identified several risk factors for AL. This survey was a necessary step to construct prospective interventional studies and to establish benchmark standards for outcome studies
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This article presents the steps and considerations that led to the development of the European Centre for Disease Prevention and Control s (ECDC) long-term strategy for the surveillance of ...communicable diseases in the European Union (EU) for the years 2008 to 2013. Furthermore, it outlines the key features of the strategy that was approved by the ECDC s Management Board in December 2007.
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