Care for Patients, Not for Charts: A Future for Clinical Medical Physics

http://ift.tt/2vrT03G

Re-irradiation using Permanent Interstitial Brachytherapy (PIB): A Potentially Durable Technique for Salvaging Recurrent Pelvic Malignancies

Permanent interstitial brachytherapy (PIB) is an often forgotten and underutilized brachytherapy technique that can be used to manage small volume recurrent gynecologic disease. The primary intent of this type of treatment is to manage local disease, and in nearly all cases, curative doses of radiation can be delivered in a single outpatient procedure. The median time to failure for re-irradiation was not identified in this series suggesting its effectiveness as a form of local therapy.

http://ift.tt/2wRKK0a

Aldehyde dehydrogenase 1 (ALDH1A1) expression by immunohistochemistry is associated with chemo-refractoriness in patients with high-grade ovarian serous carcinoma

Aldehyde dehydrogenase-1A1 (ALDH1A1), CD133, CD44, and CD24 have been reported as cancer stem cell markers in ovarian cancers. The goal of our study was to assess the prognostic significance of these markers in patients with advanced serous ovarian cancer. Formalin-fixed, paraffin-embedded tissues from 347 ovarian cancer were used to construct a microarray. Immunohistochemical studies for ALDH1A1, CD133, CD44, and CD24 were performed and scored semiquantitatively by two pathologists based on intensity and percent of positive immunoreactive cells.

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Pediatric soft tissue tumor of the upper arm with LMNA-NTRK1 fusion

A 6-year-old girl was admitted to our hospital due to the presence of a slow-growing tumor in her right elbow. Biopsy specimens showed a round- to spindle-cell neoplasm with uncertain malignant potential, leading to the decision of surgical resection. Histologically, the resected tumor was encapsulated by fibrous tissue, but focally invaded the surrounding skeletal muscles. The tumor was composed of ganglion-cell-like short spindle cells with lymphocytic infiltration in the collagenous background.

http://ift.tt/2w7I7qe

Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma

Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non-small cell lung carcinoma (NSCLC) patients for treatment with anti-PD-1 or anti-PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC.

http://ift.tt/2xn6aQG

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma

Although most classical Hodgkin lymphomas (CHL) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHL are positive for these antigens. We investigated the utility of J chain and MEF2B in the diagnosis of CHL, NLPHL, PMBL, T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL), and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL (BCLU, DLBCL/CHL) compared to OCT-2 and BOB.1.

http://ift.tt/2w891y9

THYMOMA: A clinicopathological correlation of 1470 cases

We present 1470 surgical resections for thymoma identified in the pathology files of 14 institutions from 11 countries with the purpose to determine and correlate a simplified histological classification of thymoma and pathological staging with clinical outcome. The study population was comprised of 720 men and 750 women between the ages of 12 and 86years (average: 54.8years). Clinically 137 patients (17%) had a history of myasthenia gravis, 31 patients (3.8%) of other autoimmune disease, and 55 (6.8%) patients of another neoplastic process.

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In reply to: letter to the editor entitled: primary pure lymphoepithelioma-like carcinoma of the ureter

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Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas

Abstract

Chordomas are rare, slowly growing, locally aggressive bone neoplasms that arise from embryonic remnants of the notochord, showing dual epithelial-mesenchymal differentiation. The high plasticity probably is the main reason for the high variety in phenotypes of chordoma, from its high heterogeneity on a cellular level to its subtype variations depending on tissue location, with its potential to develop from an inactive quiescent form to an aggressive cancer with extreme adaptability and resistance to drugs and other treatments. Gene expression profiles of formalin-fixed, paraffin-embedded skull chordoma, spine chordoma, and normal tissue specimens were generated and compared. Using strict criteria, we identified 222 differentially expressed transcripts unique to skull base chordoma, 261 unique to spine chordoma, and 192 common to both chordoma subtypes. Further analysis of these three groups of transcripts allowed the selection of three subsets of highly differentially expressed genes as potential biomarkers, disease drivers, and therapeutic targets in both chordoma subtypes. Immunohistochemistry revealed LMX1A to be dominant in skull base chordoma, SALL3 to be unique to spine chordoma, and T to be common to both chordoma subtypes. In both chordoma subtypes, the genes with the highest expression were predominantly development-related genes, mostly transcription factors. Our findings indicate that these developmental genes play important oncogenic roles in chordoma, mainly causing high plasticity and resistance to therapy in both these cancer subtypes but also determining their differentiation status and proliferation activity, pointing to features expected of heterogeneous stem cell-like tissues with similarities to their notochord origins.

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The Effect of Schinus terebinthifolius Raddi (Anacardiaceae) Bark Extract on Histamine-Induced Paw Edema and Ileum Smooth Muscle Contraction

Schinus terebinthifolius Raddi (Anacardiaceae), popularly known as red aroeira, is used in traditional medicine to treat inflammatory, gastric, and respiratory disorders. The aim of this study was to evaluate the antihistaminic activity of S. terebinthifolius (St) bark extract by using in vivo and in vitro experimental models. The effects of St were investigated on contractions induced by histamine, carbachol, and potassium chloride in isolated guinea pig ileum. St was also studied in response to hind paw edema induced by histamine in rats. Experiments revealed that although St (250, 500, and 1,000 µg/mL) reduced the histamine-induced contractions by , , and %, respectively, it did not inhibit contractions induced by carbachol or KCl. The association of St (250 and 500 µg/mL) with hydroxyzine, an H1-antihistamine (0.125 and 0.250 µM), increased the inhibitory effect to and %, respectively. Moreover, St (100, 200, and 400 mg/kg) decreased paw edema from its peak by 33.9, 48.4, and 54.8%, respectively, whereas hydroxyzine (70 mg/kg) inhibited the peak edema by 56.5%. Altogether, the results suggest that the bark extract of S. terebinthifolius has an antihistaminic effect (H1).

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MicroRNA-195 Activates Hepatic Stellate Cells In Vitro by Targeting Smad7

Background and Aim. Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR. The protein expression of Smad7 was detected by Western blot analysis. Results. Enhanced miR-195 and decreased Smad7 were observed in diethylnitrosamine-induced liver fibrotic rats (). Dual luciferase reporter assays showed that the miR-195 mimic significantly suppressed the luciferase activity of a reporter plasmid carrying the binding site of miR-195 on the 3′UTR of Smad7 (). The miR-195 mimics activated HSCs, further elevated miR-195 and α-SMA (), and reduced the Smad7 level (). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and -SMA (), and upregulated the expression of Smad7 (). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7.

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Histological Evidence of the Osseointegration of Fractured Direct Metal Laser Sintering Implants Retrieved after 5 Years of Function

Background. Direct metal laser sintering (DMLS) is an additive manufacturing technique that allows the fabrication of dental implants layer by layer through the laser fusion of titanium microparticles. The surface of DMLS implants is characterized by a high open porosity with interconnected pores of different sizes; therefore, it has the potential to enhance and accelerate bone healing. To date, however, there are no histologic/histomorphometric studies in the literature evaluating the interface between bone and DMLS implants in the long-term. Purpose. To evaluate the interface between bone and DMLS implants retrieved after 5 years of functional loading. Methods. Two fractured DMLS implants were retrieved from the human jaws, using a 5 mm trephine bur. Both the implants were clinically stable and functioned regularly before fracture. The specimens were processed for histologic/histomorphometric evaluation; the bone-to-implant contact (BIC%) was calculated. Results. Compact, mature lamellar bone was found over most of the DMLS implants in close contact with the implant surface; the histomorphometric evaluation showed a mean BIC% of 66.1% (±4.5%). Conclusions. The present histologic/histomorphometric study showed that DMLS implants were well integrated in bone, after 5 years of loading, with the peri-implant bone undergoing continuous remodeling at the interface.

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Monitoring Leiomyoma Response to Uterine Artery Embolization Using Diffusion and Perfusion Indices from Diffusion-Weighted Imaging

Purpose. To investigate the potential of diffusion and perfusion indices (ADC and perfusion fraction ) from DWI at 3.0 T in monitoring treatment response to uterine artery embolization (UAE) at 6-month follow-up. Methods. Twelve female patients with uterine fibroids who underwent 3.0-T pelvic DWI before and 6 months after UAE were included. ADC and perfusion fraction were calculated from DWI. The Wilcoxon signed-rank test and Spearman rank correlation test were used for statistics. Results. Seventeen fibroids were studied. The median ADCs showed a significant increase from 1.20 × 10−3 mm2/s (range, 0.86–1.66 × 10−3 mm2/s) at baseline to 1.56 × 10−3 mm2/s (range, 1.00–1.86 × 10−3 mm2/s) at 6-month follow-up (). Conversely, the median perfusion fraction was significantly decreased after UAE (), with a median pre-UAE value of 14.2% (range, 6.7%–17.6%) and a median post-UAE value of 9.2% (range, 3.2%–14.6%). Significant correlations were found between fibroid volume reduction rate and percentage changes in ADC and perfusion fraction at 6-month follow-up relative to baseline, with values of −0.50 () and 0.55 (), respectively. Conclusion. ADC and perfusion fraction obtained from DWI at 3.0 T may help to evaluate treatment response to UAE.

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The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress

Abstract

Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

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Intravital Microscopy of Monocyte Homing and Tumor-Related Angiogenesis in a Murine Model of Peripheral Arterial Disease

Monocytes are important mediators of arteriogenesis in the context of peripheral arterial disease. Using a basement membrane-like matrix and intravital microscopy, this protocol investigates monocyte homing and tumor-related angiogenesis after monocyte injection in the femoral artery ligation murine model.

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Understanding the value of minimally invasive procedures for the treatment of lumbar spinal stenosis: the case of interspinous spacer devices

Publication date: Available online 25 August 2017
Source:The Spine Journal
Author(s): Stephanie J. Tapp, Brook I. Martin, Tor D. Tosteson, Jon D. Lurie, Milton C. Weinstein, Richard A. Deyo, Sohail K. Mirza, Anna N.A. Tosteson
Background ContextMinimally invasive lumbar spinal stenosis procedures have uncertain long-term value.PurposeThis study sought to characterize factors affecting the long-term cost-effectiveness of such procedures using interspinous spacer devices ("spacers") relative to decompression surgery as a case study.Study DesignModel-based cost-effectiveness analysis.Patient SampleThe Medicare Provider Analysis and Review database for the years 2005-2009 was used to model a group of 65-year-old patients with spinal stenosis who had no previous spine surgery and no contraindications to decompression surgery.Outcome MeasuresCosts, quality-adjusted life years, and cost per quality-adjusted life year gained.MethodsA Markov model tracked health utility and costs over 10 years for a 65-year-old cohort under three care strategies: conservative care, spacer surgery, and decompression surgery. Incremental cost-effectiveness ratios (ICER) reported as cost per quality-adjusted life year (QALY) gained included direct medical costs for surgery. Medicare claims data were used to estimate complication rates, reoperation and related costs within 3 years. Utilities and long-term reoperation rates for decompression were derived from published studies. Spacer failure requiring reoperation beyond 3 years and post-spacer health utilities are uncertain and were evaluated through sensitivity analyses. In the base-case, the spacer failure rate was held constant for years 4-10 (cumulative failure: 47%). In a "worst-case" analysis, the 10-year cumulative reoperation rate was increased steeply (to 90%). Threshold analyses were performed to determine the impact of failure and post-spacer health utility on the cost-effectiveness of spacer surgery.ResultsThe spacer strategy had an ICER of $89,500/QALY gained under base-case assumptions, and remained under $100,000 as long as the 10-yr cumulative probability of reoperation did not exceed 54%. Under worst-case assumptions, the spacer ICER was $482,000/QALY and fell below $100,000 only if post-spacer utility was 0.01 greater than post-decompression utility or the cost of spacer surgery was $1,600 less than the cost of decompression surgery.ConclusionsSpacers may provide a reasonably cost-effective initial treatment option for patients with lumbar spinal stenosis. Their value is expected to improve if procedure costs are lower in outpatient settings where these procedures are increasingly being done. Decision analysis is useful for characterizing the long-term cost-effectiveness potential for minimally invasive spinal stenosis treatments and highlights the importance of complication rates and prospective health utility assessment.



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Dysregulation of LIMK-1/Cofilin-1 pathway: A possible basis for alteration of neuronal morphology in experimental cerebral malaria

ABSTRACT

Objective: Loss of cognition even after survival is the salient feature of cerebral malaria (CM). Currently, the fate of neuronal morphology is not studied at the ultra-structural level in CM. Recent studies suggest that maintenance of neuronal morphology and dendritic spine density (actin dynamics in particular) are essential for proper cognitive functions. LIMK-1/Cofilin-1signaling pathway is known to involve in the maintenance of actin dynamics through regulation of cofilin-1, in executing learning and memory functions.

Methods: Using experimental mouse model, we analyzed the behavioural parameters of CM, asymptomatic mice by performing Rapid Murine Coma Behaviour Scale experiment (RMCBS). We performed Golgi-Cox staining to assess neuronal morphology, dendritic spine density and arborization in the brain cortex subjected to Plasmodium berghei ANKA infection compared to asymptomatic, anemic and control groups. We studied the neural gene expression pattern of LIMK-1, cofilin-1 and β-actin in all the experimental groups by semi-quantitative, quantitative PCR followed by immunoblotting and immunofluorescence.

Results: We observed significant loss of dendritic spine density, abnormal spine morphology, reduced dendritic arborization; extensive dendritic varicosities in the cortical neurons of CM infected brain. Further, these observations correlated with diminished protein levels of LIMK-1, cofilin-1, phospho-cofilin-1 and β-actin in the whole brain lysates as well as formation of actin-cofilin rods in the brain sections of mice symptomatic to CM.

Interpretation: Overall, our findings suggest that the altered neuronal morphology and dysregulation of LIMK-1/cofilin-1 pathway could affect the cognitive outcome after experimental CM. Therefore, this study could help to establish newer therapeutic strategies aiming long-term cognitive impairment after CM. This article is protected by copyright. All rights reserved.

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Isolated non-traumatic, non-aneurysmal convexal subarachnoid hemorrhage in a patient with Evans syndrome

Non-traumatic, spontaneous subarachnoid hemorrhage occurs in approximately 85% of cases where there is a ruptured saccular aneurysm. An additional 10% of cases arise from non-aneurysmal peri-mesencephalic hemo...

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Can brain impermeable BACE1 inhibitors serve as anti-CAA medicine?

Cerebral amyloid angiopathy (CAA) is characterized by the deposition of ß-amyloid peptides (Aß) in and surrounding the wall of microvasculature in the central nervous system, together with parenchymal amyloid ...

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Neuropathy-specific alterations in a Mexican population of diabetic patients

Neuropathy is one of the major complications of type 2 diabetes mellitus. Our first aim was to determine the clinical characteristics of a population of diabetic patients with different types of neuropathy. Ou...

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Acute autonomic neuropathy with severe gastrointestinal symptoms in children: a case series

Acute autonomic neuropathy (AAN) is rare disorder with anecdotal report, especially for childhood onset patients. Misdiagnosis or delays in treatment can always be found in clinical practice. We conducted this...

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Usefulness of intraoperative insular electrocorticography in modified functional hemispherectomy

The insular cortex is not routinely removed in modified functional hemispherectomy due to the risk of injury to the main arteries and to deep structures. Our study evaluates the safety and usefulness of applyi...

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The clinicopathologic spectrum of mature aggressive B cell lymphomas

Abstract

Our understanding of mature aggressive B cell lymphomas has evolved significantly in the last years as reflected in the 2016 update of the WHO lymphoma classification. A main topic of the 2016 European Association for Haematopathology/Society of Hematopathology lymphoma workshop in Basel therefore was the clinicopathological spectrum of mature aggressive B cell lymphomas with the exception of conventional diffuse large B cell lymphoma. In this review, we summarize two sessions dedicated to "high-grade B cell lymphomas, with MYC and BCL2 and/or BCL6 rearrangements (so-called double/triple-hit lymphomas)" and "high-grade B cell lymphomas, NOS" as defined in the 2016 update of the WHO lymphoma classification, Burkitt lymphoma and related neoplasms, and terminally differentiated aggressive B cell lymphomas. One focus was on cases of Burkitt lymphoma with unusual clinical features such as spontaneous regression or association with immunosuppression, and the new provisional category of Burkitt-like lymphoma with 11q aberration. The large numbers of cases submitted for the new high-grade categories with or without genetic "double/triple hit" demonstrated the broad clinical and pathological spectrum of this group and gave ample opportunity for discussion. In this review, current definitions and our understanding of the main high-grade categories, potential problem areas, and suggestions for the immunophenotypic and genetic work-up of these neoplasms are discussed and illustrated by many interesting and challenging cases submitted to the workshop.

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Silkworm (Bombyx mori) has the Capability to Accumulate C20 and C22 Polyunsaturated Fatty Acids

Abstract

Bombyx mori, an insect with significant economic importance in China contains a large amount of lipids among different developmental stages, especially the pupal stage. Silkworms were fed with a base diet and fish oil supplemented diet, and the FA compositions of different strains, life stages, and sexes were determined by GC-MS. No C₂₀ or C₂₂ polyunsaturated fatty acids (PUFAs) were detected in silkworms fed with the base diet. Females accumulated more unsaturated fatty acids (USFAs) than males in the pupal stage, and the relative amount of USFAs decreased from the wandering stage to the moth stage, especially in females, suggesting that silkworms prefer the utilization of USFAs. In addition, when silkworms were fed with a diet supplemented with fish oil, which contained C₂₀ and C₂₂ PUFAs, they accumulated C₂₀ and C₂₂ PUFAs in proportion to the concentration of fish oil added to the diet.

Practical applications: Currently, the main dietary source of C₂₀ and C₂₂ PUFAs is marine fish, however, of which the stocks are declining because of environmental pollution and overfishing. Because of its excellent capability to accumulate C₂₀ and C₂₂ PUFAs, silkworm could be developed as a potential new source of these long-chain FAs by transferring Δ5 and Δ6 desaturases to silkworm or its primary food, mulberry.

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Classification of monovarietal Sardinian Extra Virgin Olive Oils by 1H NMR Metabolomic

Abstract

The chemical composition affects the sensory properties and quality of Extra Virgin Olive Oil (EVOO). In addition, its knowledge can supply valuable information about the cultivar and its geographical origin. The goal of this study is to obtain a protocol in order to be able to recognize the composition of various Sardinian oils and to consequently correlate them with their production areas. High-resolution ¹H NMR spectroscopy was used to analyse 100 (82 training + 18 test sets) samples of EVOO from the Bosana cultivar, collected from different growing areas in Sardinia (Italy). Growth areas were classified on the basis of FAO-UNEP aridity index. NMR data were processed with multivariate statistical analysis. NMR profiling presented a connection between environmental factors of Sardinian cultivation areas and the chemical composition of EVOO. An NMR-based metabolomic approach that used six "one-to-one" OPLS-DA models allowed us to discriminate the different influence of evapotranspiration, solar exposure and altitude on the chemical composition of Bosana EVOO.

Practical applications: Detailed knowledge of NMR spectra pattern variations could have a potential impact on olive oil market. The application of the ¹H NMR metabolomic, based on chemometric models, can be a useful tool in order to certificate the geographical origin of EVOO.

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The effect of aqueous extract of Xinjiang Artemisia rupestris L. (an influenza virus vaccine adjuvant) on enhancing immune responses and reducing antigen dose required for immunity.

The effect of aqueous extract of Xinjiang Artemisia rupestris L. (an influenza virus vaccine adjuvant) on enhancing immune responses and reducing antigen dose required for immunity.

PLoS One. 2017;12(8):e0183720

Authors: Zhang A, Wang D, Li J, Gao F, Fan X

Abstract
Potent adjuvant can improve the effectiveness of vaccines and reduce the antigen doses required for initiating the protective immunity. In this study, we identified that aqueous extract of Artemisia rupestris L. (AEAR) could be employed as an efficient adjuvant for influenza virus vaccine (V) to enhance immune responses and reduce the antigen doses required for initiating immunity, without compromising the immune response. ICR mice were subcutaneously co-administrated with V combined with different concentrations of AEAR demonstrated that 300 μg AEAR could significantly improve hemagglutination inhibition (HI) and increase IgG antibody titers in serum (P<0.05) and the population of CD4+CD44+ and CD8+CD44+ (P<0.05). Next, 300 μg AEAR combined with different doses of V in vivo markedly increased HI and specific IgG antibody level(P<0.05). It also significantly increased the amount of CD4+ and CD8+ T cells, CD4+CD44+ and CD8+CD44+ T cells (P<0.05), improved lymphocyte proliferation, the secretion of CD4+IL-4, CD4+IFN-γ and CD8+IFN-γ (P<0.05), and the killing efficacy of cytotoxic T lymphocyte (CTL) (P<0.05). Furthermore, the combination increased the expression of major histocompatibility complex-II (MHC-II) and co-stimulatory molecules including CD40, CD80, and CD86 on dendritic cells (DCs), and downregulated the expression of CD25+Foxp3+Treg cells (P<0.05). No significant difference was observed between high-dose V and low-dose AEAR-V (10-fold lower) vaccination group (P>0.05), indicating a 10-fold reduction of antigen required for V vaccine administration. In conclusion, this study demonstrated that AEAR, as an adjuvant for influenza vaccine, could stimulate potent humoral and cellular immune responses and reduce the antigen dose required for effective vaccination, which were mediated by promoting DCs activation and repressing Treg expression.

PMID: 28841693 [PubMed - in process]

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Investigation into the quantitative and qualitative characteristics of choroidal melanoma through magnetic resonance imaging and B-scan ultrasound

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Mismatch repair deficient metastatic colon cancer and urothelial cancer: A case report of sequential immune checkpoint therapy

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Deletion of eIF2β lysine stretches creates a dominant negative that affects the translation and proliferation in human cell line: A tool for arresting the cell growth

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Therapeutic implications of bioactive sphingolipids: A focus on colorectal cancer

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Targeted Genome Replacement via Homology-directed Repair in Non-dividing Cardiomyocytes.

Related Articles

Targeted Genome Replacement via Homology-directed Repair in Non-dividing Cardiomyocytes.

Sci Rep. 2017 Aug 24;7(1):9363

Authors: Ishizu T, Higo S, Masumura Y, Kohama Y, Shiba M, Higo T, Shibamoto M, Nakagawa A, Morimoto S, Takashima S, Hikoso S, Sakata Y

Abstract
Although high-throughput sequencing can elucidate the genetic basis of hereditary cardiomyopathy, direct interventions targeting pathological mutations have not been established. Furthermore, it remains uncertain whether homology-directed repair (HDR) is effective in non-dividing cardiomyocytes. Here, we demonstrate that HDR-mediated genome editing using CRISPR/Cas9 is effective in non-dividing cardiomyocytes. Transduction of adeno-associated virus (AAV) containing sgRNA and repair template into cardiomyocytes constitutively expressing Cas9 efficiently introduced a fluorescent protein to the C-terminus of Myl2. Imaging-based sequential evaluation of endogenously tagged protein revealed that HDR occurs in cardiomyocytes, independently of DNA synthesis. We sought to repair a pathological mutation in Tnnt2 in cardiomyocytes of cardiomyopathy model mice. An sgRNA that avoided the mutated exon minimized deleterious effects on Tnnt2 expression, and AAV-mediated HDR achieved precise genome correction at a frequency of ~12.5%. Thus, targeted genome replacement via HDR is effective in non-dividing cardiomyocytes, and represents a potential therapeutic tool for targeting intractable cardiomyopathy.

PMID: 28839205 [PubMed - in process]

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A shorter period of therapy is associated with higher mortality in bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae in a Brazilian centre

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Phacoemulsification with primary implantation of an intraocular lens in patients with uveitis

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Metabolic conditions and breast cancer risk among Los Angeles County Filipina Americans compared with Chinese and Japanese Americans

Abstract

Accumulating evidence suggests that the aggregation of common metabolic conditions (high blood pressure, diabetes, dyslipidemia) is a risk factor for breast cancer. Breast cancer incidence has risen steadily in Asian American women, and whether these metabolic conditions contribute to breast cancer risk in certain Asian American subgroups is unknown. We investigated the role of physician-diagnosed hypertension, high cholesterol, and diabetes separately, and in combination, in relation to the risk of breast cancer in a population-based case-control study of 2,167 Asian Americans diagnosed with breast cancer and 2,035 age and ethnicity matched control women in Los Angeles County. Compared to Asian American women who did not have any of the metabolic conditions, those with 1, 2, or 3 conditions showed a steady increase in risk (respective odds ratios (ORs) were 1.12, 1.42, 1.62; P trend=0.001) with adjustment for covariates including body mass index. Similar significant trends were observed in Filipina Americans (P trend=0.021), postmenopausal women (P trend =0.001), Asian women who were born in the United States (US) (P trend =0.032) and migrants who have lived in the US for at least 20 years (P trend=0.008), but not migrants who lived in the US for <20 years (P trend=0.62). These results suggest that westernization in lifestyle (diet, physical inactivity) and corresponding increase in adiposity have contributed to the rising prevalence of these metabolic conditions, which in turn, are associated with an increase in breast cancer. This article is protected by copyright. All rights reserved.

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Yang-warming method in the treatment of diabetic peripheral neuropathy: an updated systematic review and meta-analysis

Various studies have suggested the effectiveness of Chinese medicine in the treatment of diabetic peripheral neuropathy (DPN). There are several principles and methods in Chinese medicine for the treatment of ...

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Extracorporeal Circulatory Support in Acute Coronary Syndromes: A Systematic Review and Meta-Analysis.

Objectives: Extracorporeal circulatory support is a life-saving technique, and its use is increasing in acute coronary syndromes. A meta-analysis on pooled event rate of short-term mortality and complications of acute coronary syndrome patients treated with extracorporeal circulatory support was performed. Data Sources: Articles were searched in MEDLINE, Cochrane Library, Google Scholar, and Biomed Central. Study Selection: Inclusion criteria were observational studies on acute coronary syndrome patients treated with extracorporeal circulatory support. Primary outcome was short-term mortality. Secondary outcomes were extracorporeal circulatory support-related complications, causes of death, long-term mortality, and bridge therapy. Data Extraction: Sixteen articles were selected. Data about clinical characteristics, acute coronary syndrome diagnosis and treatment, extracorporeal circulatory support setting, outcome definitions, and event rate were retrieved from the articles. Random effect meta-analytic pooling was performed reporting results as a summary point estimate and 95% CI. Data Synthesis: A total of 739 patients were included (mean age, 59.8 +/- 2.9). The event rate of short-term mortality was 58% (95% CI, 51-64%), 6-month mortality was affecting 24% (95% CI, 5-63%) of 1-month survivors, and 1-year mortality 17% (95% CI, 6-40%) of 6-month survivors. The event rates of extracorporeal circulatory support-related complications were acute renal failure 41%, bleeding 25%, neurologic damage in survivors 21%, sepsis/infections 21%, and leg ischemia 12%. Between causes of death, multiple organ failure and brain death affected respectively 40% and 27% of patients. Bridge to ventricular assistance device was offered to 14% of patients, and 7% received a transplant. Conclusions: There is still a high rate of short-term mortality and complications in acute coronary syndrome patients treated with extracorporeal circulatory support . New studies are needed to optimize and standardize extracorporeal circulatory support. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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Delirium and Catatonia in Critically Ill Patients: The Delirium and Catatonia Prospective Cohort Investigation.

Objectives: Catatonia, a condition characterized by motor, behavioral, and emotional changes, can occur during critical illness and appear as clinically similar to delirium, yet its management differs from delirium. Traditional criteria for medical catatonia preclude its diagnosis in delirium. Our objective in this investigation was to understand the overlap and relationship between delirium and catatonia in ICU patients and determine diagnostic thresholds for catatonia. Design: Convenience cohort, nested within two ongoing randomized trials. Setting: Single academic medical center in Nashville, TN. Patients: We enrolled 136 critically ill patients on mechanical ventilation and/or vasopressors, randomized to two usual care sedation regimens. Measurements and Main Results: Patients were assessed for delirium and catatonia by independent and masked personnel using Confusion Assessment Method for the ICU and the Bush Francis Catatonia Rating Scale mapped to Diagnostic Statistical Manual-5 criterion A for catatonia. Of 136 patients, 58 patients (43%) had only delirium, four (3%) had only catatonia, 42 (31%) had both, and 32 (24%) had neither. In a logistic regression model, more catatonia signs were associated with greater odds of having delirium. For example, patient assessments with greater than or equal to three Diagnostic Statistical Manual-5 symptoms (75th percentile) had, on average, 27.8 times the odds (interquartile range, 12.7-60.6) of having delirium compared with patient assessments with zero Diagnostic Statistical Manual-5 criteria (25th percentile) present (p

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