ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model.

ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model.

Microsurgery. 2015 Dec 30;

Authors: Reichenberger MA, Mueller W, Hartmann J, Diehm Y, Lass U, Koellensperger E, Leimer U, Germann G, Fischer S

Abstract
BACKGROUND: Due to their unique properties, adipose derived stem cells (ADSCs) obtain promising potential to enhance nerve regeneration. The aim of this study was to investigate if fibrin-glue embedded ADSCs were a beneficial adjunct to primary coaptation in a rat sciatic nerve model.
MATERIALS AND METHODS: Fifty male Lewis rats underwent sciatic nerve transection and subsequent epineural suture repair. The treatment group received ADSCs re-suspended in fibrin glue, while the control group received fibrin glue only. After 7, 21, 35, and 63 days, analysis involved axon count, myelin sheath thickness as well as N- and G-ratios. Additionally, muscle weight quotient (operated vs. non-operated site of the same animal) was calculated and compared between treatment and control groups. For co-detection of vital ADSCs, vessel walls, and Schwann cells, immunolabeling was performed with CM-DiI, SMA, and S-100 antibodies, respectively.
RESULTS: ADSCs led to a significant increase of myelinization at day 21 (0.508 ± 0.085 μm vs. 0.381 ± 0.044 μm, P = 0.025) and day 35 (0.872 ± 0.09 µm vs. 0.495 ± 0.078 µm; P = 0.01) after surgery. Axon count was significantly increased at day 21 (420 ± 119 vs. 129 ± 63; P = 0.003) and day 63 (284 ± 137 vs. 111 ± 26; P = 0.046) after surgery. N- and G-ratios were significantly different compared with control indicating enhanced nerve regeneration due to ADSC treatment at each time point (P < 0.05). Muscle weight quotient was significantly higher in the treatment group compared with the control at day 21 (44.01% ± 6.16% vs. 35.03% ± 2.61%; P = 0.014) and day 63 (65.49% ± 2.81% vs. 58.79% ± 4.06%; P = 0.009) after surgery. Co-detection of immunolabeled cells showed vital ADSCs at the neuronal repair site and in close proximity to intraneuronal vessels indicating active participation of ADSCs in the process of nerve regeneration and associated angiogenesis.
CONCLUSION: ADSCs embedded in a fibrin matrix can significantly enhance regeneration of peripheral nerve injuries after primary coaptation. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015.

PMID: 26716599 [PubMed - as supplied by publisher]

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Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate.

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Progressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate.

Ann Neurol. 2015 Oct;78(4):501-14

Authors: Bartsch T, Rempe T, Wrede A, Leypoldt F, Brück W, Adams O, Rohr A, Jansen O, Wüthrich C, Deuschl G, Koralnik IJ

Abstract
Progressive multifocal leukoencephalopathy (PML) has recently been described in psoriasis or multiple sclerosis patients treated with fumaric acid esters (fumarates), who had developed severe and long-standing lymphocytopenia (<500/mm(3) ). We report a psoriasis patient who presented with progressive neurologic dysfunction and seizures after 2.5 years of fumarate therapy. Despite absolute lymphocyte counts remaining between 500-1000/mm(3) , his CD4(+) and CD8(+) T-cell counts were markedly low. MRI showed right hemispheric and brainstem lesions and JC virus DNA was undetectable in his cerebrospinal fluid. Brain biopsy revealed typical features of PML as well as JC virus-infected neurons. Clinicians should consider PML in the differential diagnosis of fumarate-treated patients presenting with brain lesions or seizures even in the absence of severe lymphocytopenia.

PMID: 26150206 [PubMed - indexed for MEDLINE]

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Frontotemporal lobar degeneration with MAPT mutation in an Italian-Polish family. A case report.

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Frontotemporal lobar degeneration with MAPT mutation in an Italian-Polish family. A case report.

Folia Neuropathol. 2014;52(4):457-66

Authors: Wierzba-Bobrowicz T, Lewandowska E, Zaremba J, Berdyński M, Żekanowski C, Stępień T, Felczak P, Tarka S

Abstract
Frontotemporal lobar degeneration (FTLD) with mutations in the MAPT (microtubule-associated protein tau) gene (FTLD with MAPT mutation) is a neurodegenerative disease with various clinical phenotypes. We present an Italian- Polish family with a IVS10+3G>A mutation in the MAPT gene, linked with haplotype H1s in a male proband (Fig. 2, II.2, H1s/H1b diplotype) and his sister (Fig. 2, II.1, the H1s/H1j diplotype). This report presents clinical, neuropathological and genetic testing of the proband and his affected sister, two members of an Italian-Polish family consisting of 25 family members. Their clinical history includes dementia as well as movement and cardiovascular disorders. Magnetic resonance imaging showed frontal and temporal cerebral atrophy. Neuropathological studies of the brain samples showed loss of neurons, gliosis, and the occurrence of neurofibrillary tangles, numerous neuropil threads, coiled bodies and abundant deposits of tau protein, including 3- and 4-repeated isoforms in neurons and glial cells. Only in the male proband brain, there were Pick body-like deposits in granule neurons of the hippocampus. Pathology of vascular walls was found in both cases. Ultrastructurally, the male proband showed clusters of collagen fibers mainly in a pericyte position. Beside the typical neurofibrillary pathology, aggregated gliofilaments and lipofuscin deposits in astroglia are described. Our report suggests that FTLD with IVS10+3G>A MAPT mutation causes damage mainly to the central nervous system and induces neuropathological changes, depending on the haplotypes of MAPT. In the clinical course of this disease, damage of the cardiovascular system may also be observed.

PMID: 25574752 [PubMed - indexed for MEDLINE]

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Methyl-CpG binding protein 2, receptors of innate immunity and receptor for advanced glycation end-products in human viral meningoencephalitis.

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Methyl-CpG binding protein 2, receptors of innate immunity and receptor for advanced glycation end-products in human viral meningoencephalitis.

Folia Neuropathol. 2014;52(4):428-35

Authors: Maslinska D, Laure-Kamionowska M, Maslinski S

Abstract
Inflammation is a normal host defense reaction to infections and tissue injury. In pathology, the process of inflammation is deregulated by various environmental factors, prolonged activation of Toll-like receptors (TLRs), induction of epigenetic machinery or expression of receptors for advanced glycation end-products (RAGE). In the present study, we examined immunoexpression of proteins participating in the above-mentioned mechanisms, in the brain of patients with viral meningoencephalitis. The results showed that depending on the period of the disease, the process of inflammation is deregulated in different ways. In an early period of viral meningoencephalitis, we found numerous so-called microglial nodules which were strongly immunopositive to methyl-CpG protein 2 (MeCP2). This protein is an epigenetic factor important for methylation of DNA; therefore, our results suggest that cells collected in the nodules may participate in modification of the host defense reaction. Moreover, in the early period of viral meningoencephalitis, we found that Purkinje cells of the cerebellum contain TLR3 or TLR9 receptors that can recognize viral pathogens and may activate a self-destructive mechanism in these neurons. In the later (advanced) period of viral meningoencephalitis, despite some of the above observations, RAGE protein was detected in the brain of adult and aging patients. It means that in this period of the disease, the inflammatory process may be deregulated by numerous post-translationally modified proteins that are transported to the brain after binding with activated RAGE. In addition, young patients appeared more susceptible to viral infections than adult and aging patients, because most of them died during the early period of meningoencephalitis.

PMID: 25574748 [PubMed - indexed for MEDLINE]

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Molecular stratification of medulloblastoma: comparison of histological and genetic methods to detect Wnt activated tumours.

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Molecular stratification of medulloblastoma: comparison of histological and genetic methods to detect Wnt activated tumours.

Neuropathol Appl Neurobiol. 2015 Feb;41(2):135-44

Authors: Goschzik T, Zur Mühlen A, Kristiansen G, Haberler C, Stefanits H, Friedrich C, von Hoff K, Rutkowski S, Pfister SM, Pietsch T

Abstract
AIMS: Wnt activation in medulloblastomas is associated with good outcome. Upfront testing and risk-adapted stratification of patients will be done in future clinical studies. In a cohort of 186 paediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup.
METHODS: Nuclear accumulation of β-catenin was analysed by immunohistochemistry (IHC). DNA of FFPE tissue was amplified by PCR for single-strand conformation polymorphism analysis and direct sequencing of CTNNB1 exon 3. Copy number of chromosome 6 was analysed by multiplex ligation-dependent probe amplification and molecular inversion profiling.
RESULTS: Different automated immunostaining systems showed similar results. Twenty-one of 186 samples had nuclear accumulation in ≥5% of cells, 17 samples showed <5% β-catenin positive nuclei. None of these 17 cases had CTNNB1 mutations, but 18 of 21 cases with ≥5% accumulation did, identifying these 18 cases as Wnt-subgroup medulloblastomas. Fifteen of 18 mutated cases showed monosomy 6, 3 had balanced chromosome 6. On the contrary, none of the CTNNB1 wild-type tumours had monosomy 6.
CONCLUSIONS: Standard neuropathological evaluation of medulloblastoma samples should include IHC of β-catenin because tumours with high nuclear accumulation of β-catenin most probably belong to the Wnt subgroup of medulloblastomas. Still, IHC alone may be insufficient to detect all Wnt cases. Similarly, chromosome 6 aberrations were not present in all CTNNB1-mutated cases. Therefore, we conclude that sequencing analysis of CTNNB1 exon 3 in combination with β-catenin IHC (possibly as pre-screening method) is a feasible and cost-efficient way for the determination of Wnt medulloblastomas.

PMID: 24894640 [PubMed - indexed for MEDLINE]

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Gynecomastia and Klinefelter Syndrome.

Gynecomastia and Klinefelter Syndrome.

Eplasty. 2015;15:ic61

Authors: Singer-Granick CJ, Reisler T, Granick M

PMID: 26715949 [PubMed]

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Detecting Residual/Recurrent Head Neck Squamous Cell Carcinomas Using PET or PET/CT: Systematic Review and Meta-analysis.

Detecting Residual/Recurrent Head Neck Squamous Cell Carcinomas Using PET or PET/CT: Systematic Review and Meta-analysis.

Otolaryngol Head Neck Surg. 2015 Dec 29;

Authors: Cheung PK, Chin RY, Eslick GD

Abstract
OBJECTIVE: To evaluate the diagnostic accuracy of positron emission tomography (PET) and PET/computed tomography (CT) for detecting residual and/or recurrent local and regional disease and distant metastases in patients with head and neck squamous cell carcinomas (HNSCCs) following radiotherapy with or without chemotherapy.
DATA SOURCES: A systematic review with no language restrictions was conducted using PREMEDLINE, MEDLINE, EMBASE, and Google Scholar.
REVIEW METHODS: Only prospective studies with histopathological and/or clinical follow-up that assessed the diagnostic accuracy of PET and PET/CT in detecting residual and/or recurrent disease following radiotherapy with or without chemotherapy in patients with HNSCCs were included.
RESULTS: Twenty-seven studies were identified. The pooled sensitivity and specificity of PET and PET/CT for detecting residual or recurrent disease at the primary site was 86.2% and 82.3%, respectively. For residual and recurrent neck disease, the sensitivity and specificity were 72.3% and 88.3%, while for distant metastases, the values were 84.6% and 94.9%.
CONCLUSIONS: PET and PET/CT are highly accurate in detecting residual and/or recurrent HNSCC. PET/CT is more specific than PET alone. Specificity is also greater for scans performed more than 12 weeks after radiotherapy with or without chemotherapy. The authors support the use of PET/CT after 12 weeks posttreatment for the assessment of residual or recurrent disease.

PMID: 26715675 [PubMed - as supplied by publisher]

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Rapid categorization of sound objects in anesthetized rats as indexed by the electrophysiological mismatch response.

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Rapid categorization of sound objects in anesthetized rats as indexed by the electrophysiological mismatch response.

Psychophysiology. 2014 Nov;51(11):1195-9

Authors: Astikainen P, Ruusuvirta T, Näätänen R

Abstract
It is not known whether animals can, similarly to humans, categorize auditory objects based on an abstract rule in combining their physical features. We recorded local-field potentials from the dura above the primary auditory cortex in urethane-anesthetized rats presented with sound series occasionally violating a rule (e.g., "the higher the frequency, the weaker the intensity"). In a separate control condition, the same frequency and intensity levels were applied in the sound objects, but they obeyed no rule. Responses found selectively to the violations of the rule suggest that an abstract rule was represented in the rat brain, enabling auditory categorization.

PMID: 24981508 [PubMed - indexed for MEDLINE]

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Coexistence of Papillary Thyroid Carcinoma With Thyroid MALT Lymphoma in a Patient With Hashimoto's Thyroiditis: A Clinical Case Report.

Coexistence of Papillary Thyroid Carcinoma With Thyroid MALT Lymphoma in a Patient With Hashimoto's Thyroiditis: A Clinical Case Report.

Medicine (Baltimore). 2015 Dec;94(52):e2403

Authors: Shen G, Ji T, Hu S, Liu B, Kuang A

Abstract
Papillary thyroid carcinoma (PTC) is the most common type of thyroid neoplasias; however, primary thyroid gland lymphoma (PTL) is uncommon and their simultaneous occurrence is very rare.Herein, we reported a 25-year-old female patient with Hashimoto's thyroiditis (HT), who developed a small goiter with a palpable 1.2-cm nodule in the right lobe. A fine-needle aspiration (FNA) biopsy revealed atypical follicular epithelial cells and lymphoid cells in a background of lymphocytic thyroiditis. A total thyroidectomy was performed. The pathology showed multicentric papillary thyroid carcinoma, concomitant thyroid mucosa-associated lymphoid tissue (MALT) lymphoma, and Hashimoto's thyroiditis. Postoperatively, he received chemotherapy and radioactive iodine ablation treatment. Nowadays the thyroglobulin of the patient is undetectable, without recurrences at 2 years of follow-up.It is concluded that the PTC and MALT lymphoma can exist concomitantly, especially in patients with HT. For the diagnostic workup and optional management of this rare coexistence, a multidisciplinary approach and close surveillance are needed.

PMID: 26717396 [PubMed - as supplied by publisher]

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External-beam radiotherapy for differentiated thyroid cancer locoregional control: A statement of the American Head and Neck Society.

External-beam radiotherapy for differentiated thyroid cancer locoregional control: A statement of the American Head and Neck Society.

Head Neck. 2015 Dec 30;

Authors: Kiess AP, Agrawal N, Brierley JD, Duvvuri U, Ferris RL, Genden E, Wong RJ, Tuttle RM, Lee NY, Randolph GW

Abstract
The use of external-beam radiotherapy (EBRT) in differentiated thyroid cancer (DTC) is debated because of a lack of prospective clinical data, but recent retrospective studies have reported benefits in selected patients. The Endocrine Surgery Committee of the American Head and Neck Society provides 4 recommendations regarding EBRT for locoregional control in DTC, based on review of literature and expert opinion of the authors. (1) EBRT is recommended for patients with gross residual or unresectable locoregional disease, except for patients <45 years old with limited gross disease that is radioactive iodine (RAI)-avid. (2) EBRT should not be routinely used as adjuvant therapy after complete resection of gross disease. (3) After complete resection, EBRT may be considered in select patients >45 years old with high likelihood of microscopic residual disease and low likelihood of responding to RAI. (4) Cervical lymph node involvement alone should not be an indication for adjuvant EBRT. © 2015 Wiley Periodicals, Inc. Head Neck, 2015.

PMID: 26716601 [PubMed - as supplied by publisher]

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Gynecomastia and Klinefelter Syndrome.

Gynecomastia and Klinefelter Syndrome.

Eplasty. 2015;15:ic61

Authors: Singer-Granick CJ, Reisler T, Granick M

PMID: 26715949 [PubMed]

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Advances in the knowledge of breast Cancer Stem Cells. A Review.

Advances in the knowledge of breast Cancer Stem Cells. A Review.

Histol Histopathol. 2015 Dec 30;0(0):11718

Authors: Schwarz-Cruz Y Celis A, Espinosa M, Maldonado V, Melendez-Zajgla J

Abstract
Much effort has been made by researchers to elucidate the complex biology of breast cancer stem cells (BCSCs), a small subset of breast tumor cells that display stem cell properties, drive tumor initiation, and growth. In recent years, it has been suggested that BCSCs could be responsible for the process of metastasis and the development of drug resistance. These findings make the need to find the distinguishing blend of markers that can recognize only BCSCs of the utmost importance in order to be able to design new targeted therapies. This review will summarize BCSCs' main features as well as the cell surface markers that are currently used to identify them.

PMID: 26715540 [PubMed - as supplied by publisher]

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Recent advances in the development of dual VEGFR and c-Met small molecule inhibitors as anticancer drugs.

Recent advances in the development of dual VEGFR and c-Met small molecule inhibitors as anticancer drugs.

Eur J Med Chem. 2015 Dec 13;108:495-504

Authors: Zhang J, Jiang X, Jiang Y, Guo M, Zhang S, Li J, He J, Liu J, Wang J, Ouyang L

Abstract
Vascular endothelial growth factor receptor (VEGFR) is a very important receptor tyrosine kinase (RTK) that can induce angiogenesis, increase cell growth and metastasis, reduce apoptosis, alter cytoskeletal function, and affect other biologic changes. Moreover, it is identified to be deregulated in varieties of human cancers. Therefore, VEGFR turn out to be a remarkable target of significant types of anticancer drugs in clinical trials. On the other side, c-Met is the receptor of hepatocyte growth factor (HGF) and a receptor tyrosine kinase. Previous studies have shown that c-Met elicits many different signaling pathways mediating cell proliferation, migration, differentiation, and survival. Furthermore, the correlation between aberrant signaling of the HGF/c-Met pathway and aggressive tumor growth, poor prognosis in cancer patients has been established. Recent reports had shown that c-Met/HGF and VEGFR/VEGF (vascular endothelial growth factor) can act synergistically in the progression of many diseases. They were also found to be over expressed in many human cancers. Thus, in a variety of malignancies, VEGFR and c-Met receptor tyrosine kinases have acted as therapeutic targets. With the development of molecular biology techniques, further understanding of the human tumor disease pathogenesis and interrelated signaling pathways known to tumor cells, using a single target inhibitors have been difficult to achieve the desired therapeutic effect. At this point, with respect to the combination of two inhibitors, a single compound which is able to inhibit both VEGFR and c-Met may put forward the advantage of raising anticancer activity. With the strong interest in these compounds, this review represents a renewal of previous works on the development of dual VEGFR and c-Met small molecule inhibitors as novel anti-cancer agents. Newly collection derivatives have been mainly describing in their biological profiles and chemical structures.

PMID: 26717201 [PubMed - as supplied by publisher]

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Serum amyloid A stimulates vascular endothelial growth factor receptor 2 expression and angiogenesis.

Serum amyloid A stimulates vascular endothelial growth factor receptor 2 expression and angiogenesis.

J Physiol Biochem. 2015 Dec 29;

Authors: Lv M, Xia YF, Li B, Liu H, Pan JY, Li BB, Zhang C, An FS

Abstract
Serum amyloid A (SAA), a major acute-phase reactant, modulates angiogenesis in many diseases. Vascular endothelial growth factor receptor 2 (VEGFR2) is the primary angiogenic receptor for vascular endothelial growth factor (VEGF), but the possibility of an interaction between SAA and VEGFR2 has not yet been resolved. Here, we investigated if SAA stimulates the expression of VEGFR2 and promotes angiogenesis in vitro. Human umbilical vein endothelial cells (HUVECs) were stimulated with recombinant SAA (rSAA), and the messenger RNA (mRNA) and protein expression of VEGFR2 was detected by Western blot analysis and quantitative real-time PCR. Formyl peptide receptor-like 1 (FPRL1) agonist (WKYMVm) and antagonist (WRW(4)) and inhibitors of mitogen-activated protein kinases (MAPKs) were used to investigate the mechanism of regulation of VEGFR2.We show that SAA induces VEGFR2 expression in a time- and dose-dependent manner in HUVECs. In addition, SAA promotes tube formation in HUVECs. The effect of SAA on tube formation was shown to be the result of an increase in VEGFR2 expression, which was blocked by the multi-angiokinase receptor inhibitor BIBF1120. These activities of SAA appear to be mediated by FPRL1/MAPK signaling pathways, as they were mimicked by WKYMVm and abrogated by WRW(4) and inhibitors of MAPKs. These observations indicate that SAA induces VEGFR2 expression and promotes tube formation in HUVECs via the FPRL1/MAPK signaling pathway, thus providing a potential target for the control of angiogenesis.

PMID: 26714823 [PubMed - as supplied by publisher]

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Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.

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Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo.

BMC Syst Biol. 2015;9:76

Authors: Field SL, Dasgupta T, Cummings M, Savage RS, Adebayo J, McSara H, Gunawardena J, Orsi NM

Abstract
BACKGROUND: Cytokine-hormone network deregulations underpin pathologies ranging from autoimmune disorders to cancer, but our understanding of these networks in physiological/pathophysiological states remains patchy. We employed Bayesian networks to analyze cytokine-hormone interactions in vivo using murine lactation as a dynamic, physiological model system.
RESULTS: Circulatory levels of estrogen, progesterone, prolactin and twenty-three cytokines were profiled in post partum mice with/without pups. The resultant networks were very robust and assembled about structural hubs, with evidence that interleukin (IL)-12 (p40), IL-13 and monocyte chemoattractant protein (MCP)-1 were the primary drivers of network behavior. Network structural conservation across physiological scenarios coupled with the successful empirical validation of our approach suggested that in silico network perturbations can predict in vivo qualitative responses. In silico perturbation of network components also captured biological features of cytokine interactions (antagonism, synergy, redundancy).
CONCLUSION: These findings highlight the potential of network-based approaches in identifying novel cytokine pharmacological targets and in predicting the effects of their exogenous manipulation in inflammatory/immune disorders.

PMID: 26553024 [PubMed - indexed for MEDLINE]

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IFN-γ Prevents Adenosine Receptor (A2bR) Upregulation To Sustain the Macrophage Activation Response.

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IFN-γ Prevents Adenosine Receptor (A2bR) Upregulation To Sustain the Macrophage Activation Response.

J Immunol. 2015 Oct 15;195(8):3828-37

Authors: Cohen HB, Ward A, Hamidzadeh K, Ravid K, Mosser DM

Abstract
The priming of macrophages with IFN-γ prior to TLR stimulation results in enhanced and prolonged inflammatory cytokine production. In this study, we demonstrate that, following TLR stimulation, macrophages upregulate the adenosine 2b receptor (A2bR) to enhance their sensitivity to immunosuppressive extracellular adenosine. This upregulation of A2bR leads to the induction of macrophages with an immunoregulatory phenotype and the downregulation of inflammation. IFN-γ priming of macrophages selectively prevents the induction of the A2bR in macrophages to mitigate sensitivity to adenosine and to prevent this regulatory transition. IFN-γ-mediated A2bR blockade leads to a prolonged production of TNF-α and IL-12 in response to TLR ligation. The pharmacologic inhibition or the genetic deletion of the A2bR results in a hyperinflammatory response to TLR ligation, similar to IFN-γ treatment of macrophages. Conversely, the overexpression of A2bR on macrophages blunts the IFN-γ effects and promotes the development of immunoregulatory macrophages. Thus, we propose a novel mechanism whereby IFN-γ contributes to host defense by desensitizing macrophages to the immunoregulatory effects of adenosine. This mechanism overcomes the transient nature of TLR activation, and prolongs the antimicrobial state of the classically activated macrophage. This study may offer promising new targets to improve the clinical outcome of inflammatory diseases in which macrophage activation is dysregulated.

PMID: 26355158 [PubMed - indexed for MEDLINE]

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The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity.

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The amino acid sensor GCN2 inhibits inflammatory responses to apoptotic cells promoting tolerance and suppressing systemic autoimmunity.

Proc Natl Acad Sci U S A. 2015 Aug 25;112(34):10774-9

Authors: Ravishankar B, Liu H, Shinde R, Chaudhary K, Xiao W, Bradley J, Koritzinsky M, Madaio MP, McGaha TL

Abstract
Efficient apoptotic cell clearance and induction of immunologic tolerance is a critical mechanism preventing autoimmunity and associated pathology. Our laboratory has reported that apoptotic cells induce tolerance by a mechanism dependent on the tryptophan catabolizing enzyme indoleamine 2,3 dioxygenase 1 (IDO1) in splenic macrophages (MΦ). The metabolic-stress sensing protein kinase GCN2 is a primary downstream effector of IDO1; thus, we tested its role in apoptotic cell-driven immune suppression. In vitro, expression of IDO1 in MΦs significantly enhanced apoptotic cell-driven IL-10 and suppressed IL-12 production in a GCN2-dependent mechanism. Suppression of IL-12 protein production was due to attenuation of IL-12 mRNA association with polyribosomes inhibiting translation while IL-10 mRNA association with polyribosomes was not affected. In vivo, apoptotic cell challenge drove a rapid, GCN2-dependent stress response in splenic MΦs with increased IL-10 and TGF-β production, whereas myeloid-specific deletion of GCN2 abrogated regulatory cytokine production with provocation of inflammatory T-cell responses to apoptotic cell antigens and failure of long-tolerance induction. Consistent with a role in prevention of apoptotic cell driven autoreactivity, myeloid deletion of GCN2 in lupus-prone mice resulted in increased immune cell activation, humoral autoimmunity, renal pathology, and mortality. In contrast, activation of GCN2 with an agonist significantly reduced anti-DNA autoantibodies and protected mice from disease. Thus, this study implicates a key role for GCN2 signals in regulating the tolerogenic response to apoptotic cells and limiting autoimmunity.

PMID: 26261340 [PubMed - indexed for MEDLINE]

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Fucoidan and cancer: a multifunctional molecule with anti-tumor potential.

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Fucoidan and cancer: a multifunctional molecule with anti-tumor potential.

Mar Drugs. 2015 Apr;13(4):2327-46

Authors: Atashrazm F, Lowenthal RM, Woods GM, Holloway AF, Dickinson JL

Abstract
There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed.

PMID: 25874926 [PubMed - indexed for MEDLINE]

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Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer.

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Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer.

Curr Pharm Biotechnol. 2015;16(6):553-63

Authors: Zalazar F, De Luca P, Gardner K, Figg WD, Meiss R, Spallanzani RG, Vallecorsa P, Elguero B, Cotignola J, Vazquez E, De Siervi A

Abstract
Prostate cancer (PCa) still ranks as the second most frequently diagnosed cancer and metastatic castration resistant prostate cancer (CRPC) is a foremost cause of men cancer death around the world. The aim of this work was to investigate the selectivity and efficacy of new drug combinations for CRPC. We combined three compounds: paclitaxel (PTX: taxane that inhibits microtubule polymerization); 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole- 1,3(2H)-dione (CPS49; redox-reactive thalidomide analog with anti-angiogenic properties) and flavopiridol (flavo: semisynthetic flavonoid that inhibits cyclin dependent kinases). We assessed CPS49-flavo or -PTX combinations cytotoxicity in a panel of PCa cell lines and PC3 xenografts. We found that CPS49 enhanced flavo or PTX cytotoxicity in human PCa cell lines while showed resistance in a non-tumor cell line. Furthermore, xenografts generated by inoculation of human prostate carcinoma PC3 cells in nu/nu mice showed that CPS49/flavo administration reduced tumor growth both after 2 weeks of co-treatment and after 1 week of pretreatment with a low dose of flavo followed by 2 weeks of co-treatment. PTX and CPS49 combination did not significantly reduce tumor growth in PC3 xenografts. Histological analysis of xenograft PC3 tumor samples from CPS49/flavo combination showed extensive areas of necrosis induced by the treatment. RT-qPCR array containing 23 genes from PC3 cells or PC3 xenografts exposed to CPS49/flavo combination showed that this treatment shut down the expression of several genes involved in adhesion, migration or invasion. In summary, the antitumor activity of CPS49 or flavopiridol was improved by the combination of these compounds and using half dose of that previously reported. Hence, CPS49-flavo combination is a promising new alternative for PCa therapy.

PMID: 25860066 [PubMed - indexed for MEDLINE]

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Lenalidomide in multiple myeloma.

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Lenalidomide in multiple myeloma.

Expert Rev Anticancer Ther. 2015 May;15(5):491-7

Authors: Kim Y, Schmidt-Wolf IG

Abstract
In the last couple of years major progress has been made in the treatment of multiple myeloma (MM) through the introduction of novel agents like thalidomide, lenalidomide, bortezomib and pomalidomide, mostly in combination with autologous stem cell transplantation. Lenalidomide, a second-generation immunomodulatory agent with antitumor and immunomodulatory effects against MM, in combination with dexamethasone was proven to show significant clinical benefits (overall survival and progression-free survival) in Phase III trials either as induction or as maintenance therapy. With a manageable toxicity profile, lenalidomide seems to be an attractive agent in the treatment of MM. Here, we discuss the present data and research on lenalidomide in the treatment of MM.

PMID: 25843431 [PubMed - indexed for MEDLINE]

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On the stiffness of demineralized dentin matrices

Publication date: Available online 30 December 2015
Source:Dental Materials
Author(s): Heonjune Ryou, Gianluca Turco, Lorenzo Breschi, Franklin R. Tay, David H. Pashley, Dwayne Arola
Resin bonding to dentin requires the use of self-etching primers or acid etching to decalcify the surface and expose a layer of collagen fibrils of the dentin matrix. Acid-etching reduces the stiffness of demineralized dentin from approximately 19GPa–1MPa, requiring that it floats in water to prevent it from collapsing during bonding procedures. Several publications show that crosslinking agents like gluteraladehyde, carbodiimide or grape seed extract can stiffen collagen and improve resin–dentin bond strength.ObjectiveThe objective was to assess a new approach for evaluating the changes in stiffness of decalcified dentin by polar solvents and a collagen cross-linker.MethodsFully demineralized dentin beams and sections of etched coronal dentin were subjected to indentation loading using a cylindrical flat indenter in water, and after treatment with ethanol or ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The stiffness was measured as a function of strain and as a function of loading rate from 1 to 50μm/s.ResultsAt a strain of 0.25% the elastic modulus of the fully demineralized dentin was approximately 0.20MPa. It increased to over 0.90MPa at strains of 1%. Exposure to ethanol caused an increase in elastic modulus of up to four times. Increasing the loading rate from 1 to 50μm/s caused an increase in the apparent modulus of up to three times in both water and ethanol. EDC treatment caused increases in the stiffness in fully demineralized samples and in acid-etched demineralized dentin surfaces in situ.SignificanceChanges in the mechanical behavior of demineralized collagen matrices can be measured effectively under hydration via indentation with cylindrical flat indenters. This approach can be used for quantifying the effects of bonding treatments on the properties of decalcified dentin after acid etching, as well as to follow the loss of stiffness over time due to enzymatic degradation.



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The effect of TiO2 concentration on properties of apatite-mullite glass-ceramics for dental use

Publication date: Available online 30 December 2015
Source:Dental Materials
Author(s): Hawa M. Fathi, Anthony Johnson
ObjectiveThe aim of this study was to evaluate the effect of TiO2 concentration on the properties of apatite-mullite glass-ceramics namely strength and the chemical solubility to comply with the ISO standard recommendations for dental ceramics (BS EN ISO 6872-2008) [1].MethodsTen novel glass-ceramic materials were produced based on the general formula (4.5SiO2-3Al2O3-1.5P2O5-3CaO-CaF2-xTiO2) where x varied from 0.5 to 5wt%. Glass with no TiO2 added (HG1T0.0) was used as a reference. Discs of 12mm diameter and 1.6mm (±0.2mm) thickness were prepared for both biaxial flexural strength (BFS) and chemical solubility testing, in accordance with the BS EN ISO 6872-2008 [1] for dental ceramics. All produced materials were investigated using differential thermal analysis (DTA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Energy dispersive X-ray analysis (EDS) was also carried out on some samples to identify the element composition of samples.ResultsIncreasing the concentration of TiO2 from 0.5wt% to 2wt% significantly (P<0.05) increased the chemical solubility of the material. With the material containing 2.5wt% of TiO2, the solubility significantly reduced (P<0.05) and resulted in a solubility value of 228.3μm/cm² and BFS value of 197.9MPa. Increasing the TiO2 concentration more than 2.5wt%, led to a significant (P<0.05) increase in solubility and a reduction in BFS.ConclusionsTiO2 is an effective agent for improving the durability and the mechanical properties of an apatite-mullite glass-ceramic only up to 2.5wt% concentration.



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Quantitative Susceptibility Mapping of Intracerebral Hemorrhages at Various Stages

Purpose

To investigate the magnetic susceptibility of intracerebral hemorrhages (ICH) at various stages by applying quantitative susceptibility mapping (QSM).

Materials and Methods

Blood susceptibility was measured serially using QSM after venous blood withdrawal from healthy subjects. Forty-two patients who provided written consent were recruited in this Institutional Review Board-approved study. Gradient echo magnetic resonance imaging (MRI) data of the 42 patients (17 females; 64 ± 12 years) with ICH were processed with QSM. The susceptibilities of various blood products within hematomas were measured on QSM.

Results

Blood susceptibility continually increased and reached a plateau 96 hours after venous blood withdrawal. Hematomas at all stages were consistently hyperintense on QSM. Susceptibility was 0.57 ± 0.48, 1.30 ± 0.33, 1.14 ± 0.46, 0.40 ± 0.13, and 0.71 ± 0.31 ppm for hyperacute, acute, early subacute, late subacute, and chronic stages of hematomas, respectively. The susceptibility decrease from early subacute (1.14 ppm) to late subacute (0.4 ppm) was significant (P < 0.01).

Conclusion

QSM reveals positive susceptibility in hyperacute hematomas, indicating that even at their hyperacute stage, deoxyhemoglobin may exist throughout the hematoma volume, not just at its rim, as seen on conventional imaging. QSM also reveals a reduction of susceptibility from early subacute to late subacute ICH, suggesting that methemoglobin concentration decreases at the late subacute stage. J. Magn. Reson. Imaging 2015.

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Signal decay mapping of myocardial edema using dual-contrast fast spin-echo MRI

Purpose

To introduce a dual-contrast fast spin-echo (dcFSE) sequence for signal decay mapping of myocardial edema.

Materials and Methods

After consultation with the Institutional Review Board, 22 acute myocardial infarction (MI) patients were examined with magnetic resonance imaging (MRI) at 1.5T 2 days after revascularization. Edema was evaluated in 16 myocardial segments with an exponential fit for signal decay time (SDT) in dcFSE mapping and T₂ signal intensity ratio for single-contrast FSE. Myocardial viability was evaluated in late gadolinium enhancement (LGE). A control group of 10 volunteers was examined for edema imaging. SDT was compared in segment groups: 1) with LGE in MI, 2) penumbra, 3) remote from LGE, 4) controls. Groups 1/3 and 3/4 were tested on difference. Three phantoms providing similar T₂ but different T₁ relaxation times (low, intermediate, high) were examined with dcFSE and multicontrast spin echo sequence as a reference.

Results

The SDT/T₂ratio for segment groups was 1) 82msec/1.7 in segments with LGE; 2) 65msec/1.6 for penumbra, 3) 62msec/1.7 for remote segments, and 4) 50msec/1.6 in controls. In dcFSE group 1/3 (P < 0.0001) and in group 3/4 (P = 0.0002) SDT was significantly different. In single-contrast FSE the T₂ratio was not significantly different for both tests: 1/3 P = 0.1889; 3/4 P = 0.8879. T₂-overestimation of dcFSE was 23% in low, 29% in intermediate, and 35% in highly T₁ contaminated phantoms.

Conclusion

dcFSE signal decay edema mapping is feasible in volunteers and patients. DcFSE SDT is superior to T₂ratio for detection of high-grade and diffuse myocardial edema. J. Magn. Reson. Imaging 2015.

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Complication rates in sentinel lymph node biopsy for melanoma.

Complication rates in sentinel lymph node biopsy for melanoma.

J Plast Reconstr Aesthet Surg. 2015 Dec 17;

Authors: Smith JR, Wilson AD

PMID: 26715555 [PubMed - as supplied by publisher]

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Volpara™ as a measurement tool for breast volume.

Volpara™ as a measurement tool for breast volume.

J Plast Reconstr Aesthet Surg. 2015 Dec 17;

Authors: Teo I, Whelehan P, Macaskill JE, Vinnicombe S, Munnoch DA, Evans A

PMID: 26715554 [PubMed - as supplied by publisher]

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upper respiratory tract infection; +18 new citations

18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2015/12/31

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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A reversible cause of longitudinally extensive transverse myelopathy: question.

A reversible cause of longitudinally extensive transverse myelopathy: question.

J Clin Neurosci. 2015 Nov;22(11):1809, 1852

Authors: Pinto WB, Souza PV, Oliveira AS

PMID: 26716140 [PubMed]

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Vestibular functions of hereditary hearing loss patients with GJB2 mutations.

Related Articles

Vestibular functions of hereditary hearing loss patients with GJB2 mutations.

Audiol Neurootol. 2015;20(3):147-52

Authors: Tsukada K, Fukuoka H, Usami S

Abstract
OBJECTIVES: Mutations in the GJB2 gene have been of particular interest as it is the most common causative gene for congenital deafness in all populations. Detailed audiological features, including genotype-phenotype correlations, have been well documented. However, in spite of abundant gene as well as protein expression in the vestibular end organs, neither vestibular symptoms nor vestibular functions have yet been elucidated. In the present study, vestibular functions were evaluated in patients diagnosed with GJB2-related deafness.
SUBJECTS AND METHODS: Vestibular functions were evaluated by caloric test and cervical vestibular evoked myogenic potential (cVEMP) testing in 24 patients with biallelic GJB2 mutations.
RESULTS AND DISCUSSION: Twenty-one of 23 patients (91.3%) had normal caloric responses and significantly lower cVEMP amplitudes than the control subjects. In the patients who were able to undergo vestibular testing, the mostly normal reactions to caloric testing indicated that the lateral semicircular canal was intact. However, the majority of GJB2 patients showed low cVEMP reactions, indicating a saccular defect.

PMID: 25824904 [PubMed - indexed for MEDLINE]

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Selective otolith dysfunctions objectively verified.

Related Articles

Selective otolith dysfunctions objectively verified.

J Vestib Res. 2014;24(5-6):365-73

Authors: Manzari L, MacDougall HG, Burgess AM, Curthoys IS

Abstract
Vertigo and vigorous horizontal spontaneous nystagmus in a presenting patient is usually taken to indicate unilaterally reduced horizontal canal function. However here we report results which question that presumption. In three such patients with an acute vestibular syndrome, complete testing of all peripheral vestibular sense organs using new tests of canal and otolith function (vHIT and VEMPs) showed that semicircular canal function was normal, but that there were unilateral otolithic deficits which probably caused their acute syndrome.

PMID: 25564079 [PubMed - indexed for MEDLINE]

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Advances in the knowledge of breast Cancer Stem Cells. A Review.

Advances in the knowledge of breast Cancer Stem Cells. A Review.

Histol Histopathol. 2015 Dec 30;0(0):11718

Authors: Schwarz-Cruz Y Celis A, Espinosa M, Maldonado V, Melendez-Zajgla J

Abstract
Much effort has been made by researchers to elucidate the complex biology of breast cancer stem cells (BCSCs), a small subset of breast tumor cells that display stem cell properties, drive tumor initiation, and growth. In recent years, it has been suggested that BCSCs could be responsible for the process of metastasis and the development of drug resistance. These findings make the need to find the distinguishing blend of markers that can recognize only BCSCs of the utmost importance in order to be able to design new targeted therapies. This review will summarize BCSCs' main features as well as the cell surface markers that are currently used to identify them.

PMID: 26715540 [PubMed - as supplied by publisher]

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Rupture of the sheath of the extensor carpi ulnaris tendon in a patient affected by rheumatoid arthritis

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IJMS, Vol. 17, Pages 56: Redox-Responsive Porphyrin-Based Polysilsesquioxane Nanoparticles for Photodynamic Therapy of Cancer Cells

The development of stimulus-responsive photosensitizer delivery systems that carry a high payload of photosensitizers is of great importance in photodynamic therapy. In this study, redox-responsive polysilsesquioxane nanoparticles (PSilQNPs) built by a reverse microemulsion approach using 5,10,15,20-tetrakis(carboxyphenyl) porphyrin (TCPP) silane derivatives as building blocks, were successfully fabricated. The structural properties of TCPP-PSilQNPs were characterized by dynamic light scattering (DLS)/ζ-potential, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The photophysical properties were determined by UV-vis and fluorescence spectroscopy. The quantity of singlet oxygen generated in solution was measured using 1,3-diphenylisobenzofuran. The redox-responsive release of TCPP molecules was successfully demonstrated in solution in the presence of a reducing agent. The internalization of TCPP-PSilQNPs in cancer cells was investigated using laser scanning confocal microscopy. Phototoxicity experiments in vitro showed that the redox-responsive TCPP-PSilQNPs exhibited an improved phototherapeutic effect on cervical cancer cells compared to a non-responsive TCPP-PSilQNP control material.

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IJMS, Vol. 17, Pages 54: Effects of Iron-Oxide Nanoparticle Surface Chemistry on Uptake Kinetics and Cytotoxicity in CHO-K1 Cells

Superparamagnetic iron-oxide nanoparticles (SPIONs) show great promise for multiple applications in biomedicine. While a number of studies have examined their safety profile, the toxicity of these particles on reproductive organs remains uncertain. The goal of this study was to evaluate the cytotoxicity of starch-coated, aminated, and PEGylated SPIONs on a cell line derived from Chinese Hamster ovaries (CHO-K1 cells). We evaluated the effect of particle diameter (50 and 100 nm) and polyethylene glycol (PEG) chain length (2k, 5k and 20k Da) on the cytotoxicity of SPIONs by investigating cell viability using the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The kinetics and extent of SPION uptake by CHO-K1 cells was also studied, as well as the resulting generation of intracellular reactive oxygen species (ROS). Cell toxicity profiles of SPIONs correlated strongly with their cellular uptake kinetics, which was strongly dependent on surface properties of the particles. PEGylation caused a decrease in both uptake and cytotoxicity compared to aminated SPIONs. Interestingly, 2k Da PEG-modifed SPIONs displayed the lowest cellular uptake and cytotoxicity among all studied particles. These results emphasize the importance of surface coatings when engineering nanoparticles for biomedical applications.

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IJMS, Vol. 17, Pages 49: The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury.

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Clinical Outcome in Acute Ischemic Stroke Patients With Microbleeds After Thrombolytic Therapy: A Meta-Analysis.

Clinical Outcome in Acute Ischemic Stroke Patients With Microbleeds After Thrombolytic Therapy: A Meta-Analysis.

Medicine (Baltimore). 2015 Dec;94(52):e2379

Authors: Cai J, Fu J, Yan S, Hu H, Lin C

Abstract
It remains unclear whether preexisting cerebral microbleeds (CMBs) increase the risks of worse functional outcome after thrombolytic therapy. We performed a systematic review and meta-analysis to assess the risk of unfavorable outcome in patients with acute ischemic stroke and CMBs.We searched EMBASE, PubMed, and Web of Science for relevant studies assessing functional outcome in the patients with CMBs following thrombolytic therapy. Fixed-effects and random-effects models were performed.Five eligible studies including 1974 patients were pooled in meta-analysis. The prevalence of CMBs was 24.3%. The pooled analysis demonstrates odds ratio for preexisting CMBs and the achievement of favorable outcome to be 0.69 (95% CI 0.56-0.86; P = 0.001) with no evidence of statistical heterogeneity (I = 46.7%, P = 0.112).Our meta-analysis of available published data demonstrates an increased risk of worse functional outcome after thrombolytic therapy for acute ischemic stroke in patients with pre-existing CMBs. Future studies are needed to determine whether the risk outweigh the expected benefit of reperfusion therapies.

PMID: 26717385 [PubMed - as supplied by publisher]

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Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy.

Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy.

Radiat Oncol. 2015;10(1):267

Authors: Thieke C, Nicolay NH, Sterzing F, Hoffmann H, Roeder F, Safi S, Debus J, Huber PE

Abstract
INTRODUCTION: We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT).
METHODS: Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC), distant control (DC) and overall survival (OS), measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used.
RESULTS: The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-, 2-, 3-year OS rates were 63, 42, 28 %, the LRC rates were 81, 60, 40 %, and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology.
CONCLUSIONS: Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM.

PMID: 26715491 [PubMed - in process]

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Self-identification and management of hand-foot syndrome (HFS): effect of a structured teaching program on patients receiving capecitabine-based chemotherapy for colon cancer.

Self-identification and management of hand-foot syndrome (HFS): effect of a structured teaching program on patients receiving capecitabine-based chemotherapy for colon cancer.

Support Care Cancer. 2015 Dec 30;

Authors: Murugan K, Ostwal V, Carvalho MD, D'souza A, Achrekar MS, Govindarajan S, Gupta S

Abstract
INTRODUCTION: Capecitabine is an oral prodrug of 5-fluorouracil and is commonly used oral chemotherapeutic drugs for advanced gastric and colorectal cancer. However, hand-foot syndrome (HFS) has high incidence, and once developed, the symptoms significantly impair quality of life (QOL), leading to a reduction in the dosage or discontinuation of the treatment. Effective health education should be offered to patients to promote self-identification and management on how to recognize HFS and use self-management techniques at the very beginning of chemotherapy.
MATERIALS AND METHODS: The present study intended to evaluate the effectiveness of structured teaching program on knowledge related to self-identification and management of HFS among patients receiving chemotherapy for colon cancer at tertiary cancer care center. Participants who fulfilled the criteria were selected using non-probability purposive sampling. The sample selected were 40 participants (20 participants in experimental group and 20 participants in control group).
RESULTS: Among the group of 40 patients, 17 (85 %) participants in the experimental group and 17 (85 %) participants in the control group were receiving capecitabine and oxaliplatin (CAPOX) chemotherapy treatment protocol. Five (25 %) participants in the experimental group and ten (50 %) participants in the control group were receiving drug capecitabine at a dose of 2500 mg. The mean knowledge (knowledge related to self-identification and management of HFS) pretest score was 6.75 and mean knowledge posttest score was 10.25 in the experimental group which was statistically significant (p = 0.000) (p < 0.05). The mean knowledge pretest score of participants was 6.45 and mean knowledge posttest score of participants was 6.75 in the control group which was not statistically significant (p = 0.67) (p > 0.05).
CONCLUSION: The study showed a statistically significant improvement in knowledge scores of participants that occurred due to intervention of structured teaching program. This can be used to assess reduction in incidence of HFS in the future.

PMID: 26715292 [PubMed - as supplied by publisher]

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Screening for Psychosocial Risk in Dutch Families of a Child With Cancer: Reliability, Validity, and Usability of the Psychosocial Assessment Tool.

Screening for Psychosocial Risk in Dutch Families of a Child With Cancer: Reliability, Validity, and Usability of the Psychosocial Assessment Tool.

J Pediatr Psychol. 2015 Dec 29;

Authors: Sint Nicolaas SM, Schepers SA, Hoogerbrugge PM, Caron HN, Kaspers GJ, van den Heuvel-Eibrink MM, Grootenhuis MA, Verhaak CM

Abstract
OBJECTIVE:  The Psychosocial Assessment Tool (PAT) was developed to screen for psychosocial risk in families of a child diagnosed with cancer. The current study is the first describing the cross-cultural adaptation, reliability, validity, and usability of the PAT in an European country (Dutch translation).  METHODS:  A total of 117 families (response rate 59%) of newly diagnosed children with cancer completed the PAT2.0 and validation measures.  RESULTS:  Acceptable reliability was obtained for the PAT total score (α = .72) and majority of subscales (0.50-0.82). Two subscales showed inadequate internal consistency (Social Support α = .19; Family Beliefs α = .20). Validity and usability were adequate. Of the families, 66% scored low (Universal), 29% medium (Targeted), and 5% high (Clinical) risk.  CONCLUSIONS:  This study confirms the cross-cultural applicability, reliability, and validity of the PAT total score. Reliability left room for improvement on subscale level. Future research should indicate whether the PAT can be used to provide cost-effective care.

PMID: 26715054 [PubMed - as supplied by publisher]

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Pilot Study of Neoadjuvant Chemoradiotherapy with Three Cycles of 5-Fluorouracil Plus Leucovorin for Treatment of Locally Advanced Rectal Cancer.

Pilot Study of Neoadjuvant Chemoradiotherapy with Three Cycles of 5-Fluorouracil Plus Leucovorin for Treatment of Locally Advanced Rectal Cancer.

Ann Surg Oncol. 2015 Dec 29;

Authors: Lee SJ, Kang BW, Chae YS, Kim HJ, Park SY, Park JS, Choi GS, Kim JG

Abstract
BACKGROUND: Neoadjuvant concurrent chemoradiotherapy combined with total mesorectal excision is the main treatment for patients with locally advanced rectal cancer (LARC). However, because distant metastasis remains the major challenge in the management of LARC, we proposed an additional one cycle of chemotherapy before surgery to improve systemic control.
METHODS: One hundred sixty-eight patients with clinical stage II and III rectal cancer were enrolled at Kyungpook National University Medical Center (Daegu, Korea) between January 2011 and December 2013 and were considered the study group. In addition, 160 patients were retrospectively reviewed as the historical control group. All the patients underwent total mesorectal excision at 8 weeks after completing the radiotherapy and receiving a total of six cycles of 5-fluorouracil plus leucovorin.
RESULTS: Overall, 155 (96.9 %) of the 168 patients completed their planned six cycles of study treatment. Dose modification at any cycle was observed in 18 patients (10.7 %). The grade 3 to 4 treatment-related toxicity rate was 27.3 %, and the most common grade 3 to 4 hematologic adverse event was neutropenia. With a median follow-up duration of 38 months, the estimated 3-year disease-free survival and OS rates were 79.5 and 86.9 %, respectively.
CONCLUSIONS: Adding one cycle of chemotherapy during the resting period between chemoradiotherapy and surgery was found to be feasible in patients with LARC in terms of the chemotherapy-related adverse events and postoperative complications. These results warrant further investigation in future prospective randomized trials.

PMID: 26714957 [PubMed - as supplied by publisher]

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Two decades of external peer review of cancer care in general hospitals; the Dutch experience.

Two decades of external peer review of cancer care in general hospitals; the Dutch experience.

Cancer Med. 2015 Dec 29;

Authors: Kilsdonk MJ, Siesling S, Otter R, van Harten WH

Abstract
External peer review was introduced in general hospitals in the Netherlands in 1994 to assess and improve the multidisciplinary team approach in cancer care. This paper aims to explore the value, perceived impact, and (future) role of external peer review in cancer care. Semistructured interviews were held with clinicians, oncology nurses, and managers from fifteen general hospitals that participated in three rounds of peer review over a period of 16 years. Interviewees reflected on the goals and expectations, experiences, perceived impact, and future role of external peer review. Transcriptions of the interviews were coded to discover recurrent themes. Improving clinical care and organization were the main motives for participation. Positive impact was perceived on multiple aspects of care such as shared responsibilities, internal prioritization of cancer care, improved communication, and a clear structure and position of cancer care within general hospitals. Establishing a direct relationship between the external peer review and organizational or clinical impact proved to be difficult. Criticism was raised on the content of the program being too theoretical and organization-focussed after three rounds. According to most stakeholders, external peer review can improve multidisciplinary team work in cancer care; however, the acceptance is threatened by a perceived disbalance between effort and visible clinical impact. Leaner and more clinically focused programs are needed to keep repeated peer reviews challenging and worthwhile.

PMID: 26714788 [PubMed - as supplied by publisher]

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MicroRNA Expression in Formalin-fixed Paraffin-embedded Cancer Tissue: Identifying Reference MicroRNAs and Variability.

MicroRNA Expression in Formalin-fixed Paraffin-embedded Cancer Tissue: Identifying Reference MicroRNAs and Variability.

BMC Cancer. 2015;15(1):1024

Authors: Boisen MK, Dehlendorff C, Linnemann D, Schultz NA, Jensen BV, Høgdall EV, Johansen JS

Abstract
BACKGROUND: Archival formalin-fixed paraffin-embedded (FFPE) cancer tissue samples are a readily available resource for microRNA (miRNA) biomarker identification. No established standard for reference miRNAs in FFPE tissue exists. We sought to identify stable reference miRNAs for normalization of miRNA expression in FFPE tissue samples from patients with colorectal (CRC) and pancreatic (PC) cancer and to quantify the variability associated with sample age and fixation.
METHODS: High-throughput miRNA profiling results from 203 CRC and 256 PC FFPE samples as well as from 37 paired frozen/FFPE samples from nine other CRC tumors (methodological samples) were used. Candidate reference miRNAs were identified by their correlation with global mean expression. The stability of reference genes was analyzed according to published methods. The association between sample age and global mean miRNA expression was tested using linear regression. Variability was described using correlation coefficients and linear mixed effects models. Normalization effects were determined by changes in standard deviation and by hierarchical clustering.
RESULTS: We created lists of 20 miRNAs with the best correlation to global mean expression in each cancer type. Nine of these miRNAs were present in both lists, and miR-103a-3p was the most stable reference miRNA for both CRC and PC FFPE tissue. The optimal number of reference miRNAs was 4 in CRC and 10 in PC. Sample age had a significant effect on global miRNA expression in PC (50 % reduction over 20 years) but not in CRC. Formalin fixation for 2-6 days decreased miRNA expression 30-65 %. Normalization using global mean expression reduced variability for technical and biological replicates while normalization using the expression of the identified reference miRNAs reduced variability only for biological replicates. Normalization only had a minor impact on clustering results.
CONCLUSIONS: We identified suitable reference miRNAs for future miRNA expression experiments using CRC- and PC FFPE tissue samples. Formalin fixation decreased miRNA expression considerably, while the effect of increasing sample age was estimated to be negligible in a clinical setting.

PMID: 26714641 [PubMed - in process]

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Schizophrenia and the risk of fractures: a systematic review and comparative meta-analysis.

Related Articles

Schizophrenia and the risk of fractures: a systematic review and comparative meta-analysis.

Gen Hosp Psychiatry. 2015 Mar-Apr;37(2):126-33

Authors: Stubbs B, Gaughran F, Mitchell AJ, De Hert M, Farmer R, Soundy A, Rosenbaum S, Vancampfort D

Abstract
BACKGROUND: People with schizophrenia experience increased rates of osteoporosis and may be at heightened risk of fractures. We conducted a systematic review and meta-analysis to investigate fractures among people with schizophrenia compared to people without mental illness.
METHOD: We systematically searched major electronic databases from inception until October 2014. Articles were included that reported the number of fractures in people with schizophrenia and a control group. Two independent authors conducted searches, completed methodological assessment and extracted data. Data were narratively synthesized, and a random-effects incidence rate ratio (IRR) meta-analysis was performed.
RESULTS: Eight studies were included encompassing 48,384 people with schizophrenia (49.9-75.2 years, 41%-100% female) and 3,945,783 controls. The pooled adjusted rate of fractures per 1000 person-years was 5.54 [95% confidence interval (CI)=4.92-5.57] in people with schizophrenia and 3.48 (95% CI=3.39-3.64) in control participants. The comparative meta-analysis showed that people with schizophrenia experience an increased rate of fractures compared to control participants (IRR 1.72, 95% CI=1.24-2.39, I2=49%; n=168,914). There were insufficient data to conduct moderation analysis, but the narrative review consistently highlighted that antipsychotic medication was an important risk factor for fractures.
CONCLUSION: People with schizophrenia are at significantly increased risk of fractures. Future research is required to understand the mechanisms and should seek to validate fracture prediction algorithms used in the general population. Importantly, there is a need to develop preventative strategies to improve bone health and reduce fracture risk involving the wider multidisciplinary team and incorporating falls-prevention strategies.

PMID: 25666994 [PubMed - indexed for MEDLINE]

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Thyroid hormone receptors are differentially expressed in granulosa and cervical cells of infertile women.

Thyroid hormone receptors are differentially expressed in granulosa and cervical cells of infertile women.

Thyroid. 2015 Dec 30;

Authors: López E, Ortega FJ, Francisco-Busquets E, Sabater-Masdeu M, Álvarez E, Ricart W, Fernández-Real JM

Abstract
BACKGROUND: Thyroid hormones are known to exert an important role in reproduction. The objective of this study is to evaluate the expression of thyroid hormone receptors (TR) in granulosa (GC) and cervical cells (CC) of infertile euthyroid women.
METHODS: In a cross-sectional study, we investigated 31 consecutive infertile and 18 fertile women undergoing oocyte retrieval procedures. The expression of TRα1, TRα2 and TRβ was evaluated in GCs and uterine CC from infertile and fertile euthyroid women. β2 adrenergic receptor (ADRβ2) mRNA levels and the expression of genes linked to fertility such as gremlin-1 (GREM1), hyaluronan synthase 2 (HAS2), and prostaglandin-endoperoxide synthase 2 (PTGS2) were also evaluated.
RESULTS: In GCs, the expression of the thyroid hormone receptor TRα2, which exerts a dominant negative effect, increased with age in all women tested. TRα2 mRNA was increased in infertile vs. fertile women, in parallel to decreased ADRβ2 mRNA. As expected, the expression of genes associated with fertility (i.e. GREM1 and PTGS2) was downregulated in infertile women, in parallel to decreased ADRβ2 mRNA and increased TRα2 mRNA. In uterine CCs, a positive association of ADRβ2 mRNA with TRα1:TRα2 ratio was observed. Importantly, GCs from infertile women whose oocytes did not result in pregnancy had increased expression of TRα2 (p=0.017), and lower ADRβ2 (p=0.008), GREM1 (p=0.003) and PTGS2 (p=0.002) mRNAs than fertile women whose oocytes resulted in pregnancy. Infertile women also showed more TRα2 (p=0.033) mRNA in CCs than fertile women whose oocytes resulted in pregnancy.
CONCLUSIONS: The expression of different markers of intracellular thyroid function is linked to fertility status.

PMID: 26715425 [PubMed - as supplied by publisher]

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Cost-Effectiveness of Diagnostic Lobectomy Versus Observation for Thyroid Nodules Greater than 4 cm.

Cost-Effectiveness of Diagnostic Lobectomy Versus Observation for Thyroid Nodules Greater than 4 cm.

Thyroid. 2015 Dec 30;

Authors: Lee L, Mitmaker EJ, Chabot JA, Lee JA, Kuo JH

Abstract
BACKGROUND: The management of thyroid nodules >4 cm with benign cytology after fine-needle aspiration (FNA) is controversial. FNA is associated with a high false-negative rate in this setting and may result in a delayed diagnosis and management of thyroid cancer. However, the majority of these nodules are benign. Therefore the objective was to determine the cost-utility of observation versus surgical management for thyroid nodules >4 cm with benign cytology after FNA.
METHODS: A microsimulation model comparing routine thyroid lobectomy versus observation for low-risk patients with >4cm thyroid nodules with benign FNA cytology was constructed. Costs, quality-adjusted life years (QALYs), and life-years gained were calculated over a lifetime time horizon from a US Medicare perspective.
RESULTS: The proportion of patients undergoing thyroid lobectomy for benign final pathology was 40% in the observation strategy versus 66% in the surgical strategy (p<0.001). Overall, the surgical strategy was associated with higher lifetime costs compared to the observation strategy (incremental difference: +12992 US$; 95% CI 13042, 13524), but also more QALYs (+0.12 QALYs; 95% CI 0.02, 0.24) and longer life expectancy (+1.67 years; 95% CI 1.00, 2.41). Incremental lifetime costs were lower for patients <55 years versus those >=55 years (+11181 vs +14811, p<0.001). The probability of cost-effectiveness of the surgical strategy was 49% at a $100k/QALY threshold or 65% at a $100k/life-year gained threshold.
CONCLUSIONS: Routine thyroid lobectomy is associated with improved outcomes at an acceptable cost compared to observation for thyroid nodules >4cm with benign cytology after FNA. Surgical resection may be a cost-effective strategy to rule out malignancy in these nodules.

PMID: 26715288 [PubMed - as supplied by publisher]

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Healthcare professionals' perceptions of psychological treatment for chronic pain in Singapore: challenges, barriers, and the way forward.

Healthcare professionals' perceptions of psychological treatment for chronic pain in Singapore: challenges, barriers, and the way forward.

Disabil Rehabil. 2015 Dec 30;:1-9

Authors: Yang SY, Bogosian A, Moss-Morris R, McCracken LM

Abstract
PURPOSE: There are very few studies on healthcare providers' experiences of delivering treatment for chronic pain in a Southeast Asian setting. The aims of this study are to understand the experiences of professionals delivering treatment for people with chronic pain in Singapore and identify possible barriers to psychological treatment for this condition within the broader experiences of these professionals.
METHOD: Healthcare professionals with at least 1-year experience treating chronic pain were recruited and purposefully sampled. Fifteen inductive semi-structured interviews were conducted to explore healthcare professionals' experiences of treating people with chronic pain. Interviews were transcribed verbatim and analysed using thematic analysis.
RESULTS: Four main themes were identified: 'System Barriers', 'Core Beliefs and management of Chronic Pain', 'Engaging Patients in treatment' and 'Creating Awareness for Chronic Pain Management'. Professionals trained in a multidisciplinary approach to pain management were seen as rare. Professionals who could refer patients for psychological treatment do not refer due to costs, and their perception that patients may lack understanding of such a treatment.
CONCLUSION: Reducing barriers in the access to psychological treatment in settings like Singapore will require a multifaceted approach. Implications for Rehabilitation A multifaceted approach is required to reduce barriers to psychological treatment for chronic pain in settings like Singapore. Educating healthcare professionals on the need for a multidisciplinary approach to chronic pain could help in reducing misconceptions and increase understanding of the benefits of psychological approaches. Utilizing both media and technological platforms as a means to facilitate psychological treatment uptake for chronic pain may be a way forward for a technological savvy generation.

PMID: 26714734 [PubMed - as supplied by publisher]

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Rare diseases: matching wheelchair users with rare metabolic, neuromuscular or neurological disorders to electric powered indoor/outdoor wheelchairs (EPIOCs).

Rare diseases: matching wheelchair users with rare metabolic, neuromuscular or neurological disorders to electric powered indoor/outdoor wheelchairs (EPIOCs).

Disabil Rehabil. 2015 Dec 30;:1-10

Authors: De Souza LH, Frank AO

Abstract
PURPOSE: To describe the clinical features of electric powered indoor/outdoor wheelchair (EPIOC) users with rare diseases (RD) impacting on EPIOC provision and seating.
METHOD: Retrospective review by a consultant in rehabilitation medicine of electronic and case note records of EPIOC recipients with RDs attending a specialist wheelchair service between June 2007 and September 2008. Data were systematically extracted, entered into a database and analysed under three themes; demographic, diagnostic/clinical (including comorbidity and associated clinical features (ACFs) of the illness/disability) and wheelchair factors.
RESULTS: Fifty-four (27 male) EPIOC users, mean age 37.3 (SD 18.6, range 11-70) with RDs were identified and reviewed a mean of 64 (range 0-131) months after receiving their wheelchair. Diagnoses included 27 types of RDs including Friedreich's ataxia, motor neurone disease, osteogenesis imperfecta, arthrogryposis, cerebellar syndromes and others. Nineteen users had between them 36 comorbidities and 30 users had 44 ACFs likely to influence the prescription. Tilt-in-space was provided to 34 (63%) users and specialised seating to 17 (31%). Four users had between them complex control or interfacing issues.
CONCLUSIONS: The complex and diverse clinical problems of those with RDs present unique challenges to the multiprofessional wheelchair team to maintain successful independent mobility and community living. Implications for Rehabilitation Powered mobility is a major therapeutic tool for those with rare diseases enhancing independence, participation, reducing pain and other clinical features. The challenge for rehabilitation professionals is reconciling the physical disabilities with the individual's need for function and participation whilst allowing for disease progression and/or growth. Powered wheelchair users with rare diseases with a (kypho) scoliosis require a wheelchair system that balances spine stability and movement to maximise residual upper limb and trunk function. The role of specialised seating needs careful consideration in supporting joint derangements and preventing complications such as pressure sores.

PMID: 26714619 [PubMed - as supplied by publisher]

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Frequency and characteristics of goal attainment following BoNT-A injection for management of spasticity.

Frequency and characteristics of goal attainment following BoNT-A injection for management of spasticity.

Disabil Rehabil. 2015 Dec 30;:1-7

Authors: Mullins D, Winter A, Fini N, Dixon C, Aldous S, Palit M, Holland AE

Abstract
PURPOSE: To determine which Goal Attainment Scale (GAS) goals are commonly achieved in patients with upper limb and/or lower limb spasticity following Botulinum Neurotoxin Type A (BoNT-A) injection.
METHOD: Adults who attended a Spasticity Management Clinic for upper and/or lower limb BoNT-A injection were included in this prospective cohort study. Goals were set by participants and/or carers in conjunction with the therapist using the GAS, prior to injection and reviewed at one month following the injection. Three out of the five categories of goals were passive. Goals were categorised into: mobility/transfers, pain/comfort, upper limb use, hygiene, and cosmesis. The number of responders for the GAS total score, and in each of the GAS categories, was calculated.
RESULTS: Sixty-seven participants were recruited (mean age 51 ± 16 years; range 18-85), 70% had a stroke. Responders for mobility and transfer goals were further post injury or disease onset than non-responders (median 5.9 vs. 1.2 years, p = 0.03). Clients with stroke were less likely than other participants to achieve mobility and transfer goals (p = 0.02). There was a trend for those who achieved mobility and transfer goals to be younger (mean 49 years vs. 55 years, p = 0.06). Although active goals are more commonly identified, passive goals were more likely to be achieved.
CONCLUSIONS: Although active goals are commonly identified by people with spasticity, passive goals were more likely to be achieved following BoNT-A injection. A long duration of spasticity does not preclude patients from achieving mobility and transfer goals. Non-stroke participants were more likely to achieve mobility and transfer goals. Implications for Rehabilitation Patients with chronic spasticity should be considered for BoNT-A as clinically meaningful outcomes can be achieved. When spasticity is present in multiple muscles, the GAS can be an assistive tool to guide clinicians in determining which muscles are a priority for injection, because the client will be more motivated to improve those specific goals. Although carers and patients are more willing to set active goals, these are more difficult to achieve possibly because follow up intervention or independent practise is required.

PMID: 26714558 [PubMed - as supplied by publisher]

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Green near-infrared determination of copper and mancozeb in pesticide formulations

Abstract

A green analytical procedure has been successfully developed for the simultaneous determination of copper and mancozeb in phytosanitary products. The method is based on different direct measurements of diffuse reflectance near-infrared (DR-NIR) spectra. Accuracy of the method has been evaluated by comparison of the obtained copper and mancozeb concentrations with those provided by reference methodologies based on titrimetric procedures. The average relative prediction error was 0.7 and 1.6 % for copper and mancozeb, respectively. The evaluation of the greenness of the DR-NIR procedure provided 100 points, which is the maximum value in the Green Certificate ranking, because of the absence of consumed reagents and waste generation and energy consumption lower than 0.1 kWh.

Graphical abstract

Direct green NIR determination of copper and mancozeb in pesticides

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Evaluation of response after SBRT for liver tumors

Publication date: Available online 30 December 2015
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Raphael Tétreau, Carmen Llacer, Olivier Riou, Emmanuel Deshayes
Stereotactic body radiotherapy (SBRT) has developed over the last few years for the treatment of primary and metastatic hepatic tumors. The tumoral and adjacent peritumoral modifications caused by this radiosurgery limit the evaluation of response by anatomic imaging and dimensional criteria alone, such as with RECIST. This suggests that it is of interest to also take into account the residual enhancement and hyper metabolism of these hepatic targets. We have reviewed the English language literature regarding the response of hepatic lesions treated by SBRT, and found that only seven articles were specifically concerned with this problem.The response of the hepatocellular carcinoma after SBRT has been studied specifically with multiphase enhanced CT-scan. Criteria set by the European Association of Study of the Liver better estimate response at each time point of follow up than RECIST does. Non-enhancement, reflecting tumor necrosis, is additionally an early indicator of response with extended response in time and a best non-enhancement percentage is observed at 12 months. The response after treatment by SBRT of cholangiocarcinoma has not yet generated a specific report.Use of RECIST criteria is also inadequate in the evaluation of response after SBRT for hepatic metastases. Response of liver metastases to SBRT is better assessed with a combination of size and enhancement pattern. The occurrence of a lobulated enhancement during follow up is efficient to predict local progression in a specific, reproducible, and sensitive way. Patients with FDG-avid hepatic metastases are also better evaluated with PET-CT and functional criteria than routine imaging and metric evaluation alone.



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