Long-term survival in a patient with Virchow’s lymph node metastasis of cecal cancer

Abstract

The patient was a 53-year-old male with a chief complaint of bloody stool. To treat the cecal colon cancer, right hemicolectomy was performed. Histological examination showed moderately differentiated adenocaricinoma, SE, N3, H0, P0, M0 Stage IIIb by Japanese Classification of the Colorectal Carcinoma. After the operation, the patient received a chemotherapy with 6 cycles of Capecitabine regimen. After 1 year later, computed tomography detected swelling of Virchow's lymph node and tumor in the thyroid gland. By fine-needle aspiration cytology, thyroid gland tumor was diagnosed as papillary cancer and Virchow's lymph node was detected adenocarcinoma which was metastasis of cecal cancer. Total thyroidectomy and cervical lymph node dissection were performed. After the operation, the patient received chemotherapy with 6 cycles of FOLFOX regimen. And the patient had taken UFT/LV for 30 months. Now he has no recurrence and keeps his quality of life high. He has been alive for 80 months since the first operation. Virchow lymph node dissection can be one of the options of treatment of metastasis.

http://ift.tt/2wl9AGt

Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia

Summary

Objective

Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30–40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency.

Methods

Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABA_A) antagonist used to provoke generalized seizures as a "second hit."

Results

LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection.

Significance

Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology.

http://ift.tt/2x2DNau

Breast cancer subtype discrimination using standardized 4-IHC and digital image analysis

Abstract

Breast cancer is a heterogeneous disease. Surrogate classification of intrinsic subtypes of invasive carcinomas by combined immunohistochemistry for estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 (4-IHC) has increased steadily since the 2011 St Gallen symposium, due to its rapid subtyping of tumors at a reasonable cost. An important step in improving 4-IHC reproducibility and reliability will be to provide reference values from the routine use of standardized 4-IHC followed by image analysis. The aims of the current study were (1) to analyze invasive breast carcinomas using standardized 4-IHC and quantitative image analysis and (2) to compare the results obtained in the classification of biological subtypes using current Ki67 and PR threshold values proposed by different authors to sub-classifying the luminal A-like and the luminal B-like (HER2-negative) subtypes. Five hundred twenty-one tumors were analyzed by standardized immunohistochemistry, with automatic image analysis, and HER2 FISH technique. Positivity for ER was found in 82.7% and for PR in 70.1% of cases. Using the Allred scoring system, hormone receptor results showed a bimodal distribution, particularly for ER. HER2 positivity was found in 15.7% of cases, and the mean Ki67 score was 32.3%. Using the most recently proposed surrogate definitions for the classification of luminal breast cancer subtypes, the percentages of different subtypes that we found were similar to those published with genomic platforms: 40.7% luminal A-like, 32.4% luminal B-like/HER2-negative, 9.8% luminal B-like/HER2-positive, 6.0% HER2-positive, and 11.1% triple negative. Standardized 4-IHC with automatic image analysis constitutes a low-cost method for surrogate definitions of biological subtypes of breast cancer that delivers accurate results in a day.

http://ift.tt/2vOoIKR

Cognitive or Cognitive-Motor Executive Function Tasks? Evaluating Verbal Fluency Measures in People with Parkinson’s Disease

Introduction. Executive function deficits are observed in people with Parkinson's disease (PD) from early stages and have great impact on daily living activities. Verbal fluency and oral diadochokinesia involve phonarticulatory coordination, response inhibition, and phonological processing and may also be affected in people with PD. This study aimed to describe the performance of PD patients and an age- and education-matched control group on executive function, verbal fluency, and oral diadochokinesia tests and to investigate possible relationships between them. Methods. Forty people with PD and forty controls were evaluated with Trail Making Test (TMT, executive function) and phonemic/semantic verbal fluency and oral diadochokinesia (/pataka/) tests. Groups were compared by ANOVA and relationships were investigated by Pearson tests. Results. People with PD showed longer times in parts A and B of TMT. They also said fewer words in phonemic/semantic verbal fluency tests and less syllables in the diadochokinesia test. Oral diadochokinesia strongly correlated to parts A and B of TMT and to phonemic verbal fluency. Conclusion. Oral diadochokinesia was correlated to executive function and verbal fluency. The cognitive-motor interaction in verbal fluency and oral diadochokinesia must be considered not to overestimate the cognitive or motor impairments in people with PD.

http://ift.tt/2x2bzN4

Low-grade albuminuria is associated with poor memory performance in the nondemented Chinese elderly with type 2 diabetes

Abstract

Recent studies have correlated cognitive function with albuminuria. We investigated the association between low-grade albuminuria and cognitive performance in nondemented elderly with type 2 diabetes in Fuzhou, China. Between January, 2013 and December, 2014, a retrospective study was performed in 815 patients with type 2 diabetes (398 female and 417 male patients), ages ≥60 years, with normal urinary albumin to creatinine ratios (UACR <30 mg/g). Patients were stratified into tertiles based on UACR levels (lowest tertile, UACR <5.8 mg/g; highest tertile, UACR ≥18.1 mg/g). Cognitive function was measured using the Mini Mental State Examination. UACR tertiles correlated directly (p < 0.05) with age, duration of diabetes, systolic blood pressure (SBP), and pulse wave velocity (PWV). Patients in the second and highest tertiles performed significantly worse on memory and language than those in the lowest UACR tertile (p < 0.05). The association between UACR and memory loss was stronger in patients younger than 70 years of age and in those with a history of diabetes for less than 10 years. Low-grade albuminuria is associated with poor memory performance, especially in the youngest old (60–69 years) and in those with shorter duration of diabetes (< 10 years). Type 2 diabetics with urinary albumin excretion in the upper normal range were also at risk for declining memory performance.

http://ift.tt/2x1LVrE

Hair ethyl glucuronide is a highly accurate biomarker of chronic excessive alcohol use in patients with alcoholic cirrhosis

http://ift.tt/2ws7J1z

Reputation Management and Content Control: An Analysis of Radiation Oncologists’ Digital Identities

The authors identified all Medicare-participating radiation oncologists in the United States and Puerto Rico and developed a customized Google-based search engine. Up tothe top 10 search results for each physician were extracted and categorized. Results for academic and nonacademic radiation oncologists were compared. Most radiation, oncologists lacked self-controlled online content in the first page of Google search results. Strategies for radiation oncologists to improve their digital presence are discussed.

http://ift.tt/2vO4Qrj

Toward Analog Neural Computation

Abstract

Computationalism about the brain is the view that the brain literally performs computations. For the view to be interesting, we need an account of computation. The most well-developed account of computation is Turing Machine computation, the account provided by theoretical computer science which provides the basis for contemporary digital computers. Some have thought that, given the seemingly-close analogy between the all-or-nothing nature of neural spikes in brains and the binary nature of digital logic, neural computation could be a species of digital computation. A few recent authors have offered arguments against this idea; here, I review recent findings in neuroscience that further cement the implausibility of this view. However, I argue that we can retain the view that the brain is a computer if we expand what we mean by "computation" to include analog computation. I articulate an account of analog computation as the manipulation of analog representations based on previous work on the difference between analog and non-analog representations, extending a view originally articulated in Shagrir (Stud Hist Philos Sci 41(3):271–279, 2010). Given that analog computation constitutes a significant chapter in the history of computation, this revision of computationalism to include analog computation is not an ad hoc addition. Brains may well be computers, but of the analog kind, rather than the digital kind.

http://ift.tt/2fUE0bo

Interactive problem-solving sessions in an introductory bioscience course engaged students and gave them feedback, but did not increase their exam scores

Abstract

Active learning, including the promotion of student interactivity in lectures, has been found to improve student engagement and performance in university science classes. This letter describes the use of Pearson's Learning Catalytics to run regular, formatively-assessed problem-solving sessions as part of the semi-flipped redesign of an introductory level university bioscience course. Students found the problem solving sessions more engaging than a traditional lecture, and felt that they were receiving better feedback on their progress in the course. Their participation in the problem solving sessions was strongly associated with their performance in the course's summative assessments, making it possible to identify and assist probable poor performers early in the course. Other measures of student engagement with the course were not improved, and neither were their average exam grades when compared with their grades in a course which had not been redesigned. Possible reasons for this are discussed.

http://ift.tt/2v2xn9M

EM Nerd-The Case of the Elemental Truancy

Much has been written regarding the benefits of apneic oxygenation. The physiological underpinnings are sound with minimal logistical and resource based costs. As such it has enjoyed widespread adoption throughout the Emergency Medicine and Critical Care world. Despite its popularity, the evidence supporting its use has been less inspirational. Recently, a meta-analysis published in Annals […]

EMCrit by Rory Spiegel.

http://ift.tt/2wkfM1i

Hunting for agile prey: trophic specialisation in leptophryid amoebae (Vampyrellida, Rhizaria) revealed by two novel predators of planktonic algae

Abstract

Vampyrellid amoebae (Vampyrellida, Rhizaria) are widespread in freshwater, marine and terrestrial ecosystems and consume a wide range of eukaryotes, e.g. algae, fungi and micrometazoa. Environmental sequences indicate that only a small fraction of their genetic diversity is phenotypically characterised, emphasising the need to further explore unknown vampyrellids and their interactions with prey organisms. This study tests the prey range specificity of three vampyrellid amoebae with 49 strains of three common groups of freshwater algae (Zygnematophyceae, Euglenophyceae and Volvocales), and documents specific interactions by time-lapse microscopy. Two of the amoebae, here introduced as the novel genera Arachnomyxa and Planctomyxa based on morphology and SSU rRNA gene comparisons, display a complementary prey range and consume motile algae, namely Volvocales and Euglenophyceae, respectively. This reveals the existence of specialised 'plankton feeders' in the vampyrellid family Leptophryidae, contrasting with the strikingly broad prey range of Leptophrys vorax. The distinct autecological characteristics found in this group of morphologically rather indistinct amoebae contributes to our knowledge about the vastly understudied vampyrellid amoebae. Furthermore, time-lapse observations suggest that euglenoid movements exerted by the sluggish species of the 'Euglena deses group' as a reaction to vampyrellid contact may serve as an effective defence against microbial predators.

http://ift.tt/2wrQ2iQ

Micropredator niche differentiation between bulk soil and rhizosphere of an agricultural soil depends on bacterial prey

Abstract

Predation is a fundamental mechanism of all food webs, but its drivers and organismic connectivities, especially at microbial level, are still poorly understood. Specifically, competitive carbon flows in the presence of multiple micropredators, as well as trophic links within and between microbial kingdoms have rarely been resolved. Here, using maize-planted agricultural soil as a model system, we have investigated the predation of amended bacterial prey by both prokaryotic and eukaryotic micropredators. We have queried how soil compartment (rhizosphere vs. bulk soil) and nature of prey (Gram-positive vs. Gram-negative) influence predation outcomes. We added ¹³C-labelled biomass of Pseudomonas putida and Arthrobacter globiformis to soil microcosms and found that P. putida was consumed much more rapidly. Bacteria and microeukaryotes specifically responsive to the biomass amendments were identified by rRNA-SIP. Amongst the bacteria, only a few myxobacteria sequestered C from A. globiformis, whereas a considerable diversity of predatory bacteria incorporated C derived from P. putida. Diverse groups of heterotrophic protists, especially amoeba incl. Glaeseria, Hartmanella and Vahlkampfia spp., were observed to incorporate ¹³C from both amendments, but with pronounced niche differentiation between rhizosphere and bulk soil. This provides novel insights into niche partitioning between bacterial and eukaryotic micropredators in soil, driven by the nature of bacterial prey itself, but also by soil compartments.

http://ift.tt/2v24RF5

Diagnostic implications of TERT promoter mutation status in diffuse gliomas in a routine clinical setting

Abstract

IDH (isocitrate dehydrogenase) gene mutations are present in most diffuse low-grade gliomas and define the clinico-pathological core of the respective morphologically defined entities. Conversely, according to the 2016 WHO classification, the majority of glioblastomas belong to the IDH-wildtype category, which is defined by exclusion. TERT (telomerase reverse transcriptase gene) promoter mutations have been suggested as a molecular marker for primary glioblastomas. We analyzed molecular, histopathological, and clinical profiles of a series of 110 consecutive diffuse gliomas (WHO grades II-IV) diagnosed at our institution, in which TERT promoter mutation analysis had been performed as part of diagnostic work-up. A diagnostic algorithm based on IDH, TERT, ATRX, H3F3A, and 1p19q co-deletion status resulted in a consistent molecular classification with only 14 (13%) marker-negative tumors. TERT promoter mutations were present in 77% of IDH-wildtype tumors. The TERT/IDH-wildtype category was highly enriched for tumors with unconventional clinical or histological features. Molecular classes were associated with distinct rates of MGMT promoter methylation. We conclude that, in a routine diagnostic setting, TERT promoter mutations define a relatively homogeneous core group among IDH-wildtype diffuse gliomas that includes the majority of primary glioblastomas as well as their putative precursor lesions.

http://ift.tt/2wkd4ZE

O201 Interhemispheric processing in hyperkinetic movement disorders

changes in interhemispheric connectivity have been recently studied in Huntington's Disease (HD), although their significance and temporal relation with clinical features are still debated. We studied interhemispheric connectivity in healthy volunteers, early HD and in patients with idiopathic dystonia.

http://ift.tt/2vcsGJM

P225 Effect of 30, 50 and 100Hz tetha burst stimulation on healthy individuals

Continuous tetha burst stimulation (cTBS) protocol mainly consists of 3 stimulus bursts repeating every 200ms at 50Hz and It has been interpreted that cTBS had inhibitory effects on human motor cortex. On the other hand, there are some reports that 50Hz cTBS had variability within and between subjects on cortical excitability. In addition, little was known about the effect of different cTBS modalities. The objective of this study is to investigate the effects of 50Hz, 30Hz and 100Hz cTBS on motor cortical excitability healthy subjects.

http://ift.tt/2uT826e

P303 Transcranial direct current stimulation over parietal cortex and associative memory

Memory enhancement is one of the most challenging issues in neurorehabilitation. Memory functions are affected by different neurological conditions as well as by normal aging. Recent data suggest that it may be possible to improve performance on some of the memory tests by physiological modulation of the activity within a neural loop which plays crucial role in formation and maintenance of the associative memory and which consists of the hippocampus and the lateral parietal cortex.

http://ift.tt/2vbUspL

P233 Local and distant dysregulation of synchronization around interictal spikes in bects

High Density electroencephalography is the reference non-invasive technique to investigate the dynamics of neuronal networks in Benign Epilepsy with Centro-Temporal Spikes (BECTS). Analysis of local dynamic changes surrounding Interictal Epileptic Spikes (IES) might improve our knowledge of the mechanisms that propel neurons to the hypersynchronization of IES. Transient distant changes in the dynamics of neurons populations may also interact with neuronal networks involved in various functions that are impaired in BECTS patients.

http://ift.tt/2v1DYBr

P267 Swallowing and brainstem reflexes before and after mandibular sagittal split osteotomy

To study the electrophysiological parameters of swallowing and related brainstem reflexes before and after bilateral mandibular sagittal split osteotomy in patients with mandibular dentoskeletal deformities.

http://ift.tt/2wrYaQz

P319 Differences in adrenergic components of baroreflex response to valsalva maneuver in patients with postural tachycardia syndrome and healthy subjects

To evaluate differences in recently developed, non-standard adrenergic baroreflex sensitivity (BRS) indices between patients with postural tachycardia syndrome (PoTS) and healthy controls (HC).

http://ift.tt/2v1DUBH

P286 Visual and brainstem auditory evoked potentials abnormalities in the patients with systemic lupus erythematosus

Lupus erythematosus (SLE) is a systemic disease with possible nervous system involvement, regarded as unfavorable prognostic factor. Evoked potentials (EP) are electrophysiological markers of disturbed central nervous system (CNS) function, even in subclinical stage of CNS disorders. The purpose of the study was to evaluate parameters of EP in the patients with SLE with or without neuropsychiatric manifestation (NPSLE).

http://ift.tt/2wrPj14

P250 Simultaneous recording of cervical and ocular vestibular-evoked myogenic potentials

To increase clinical application by reducing the testing time for recording vestibular-evoked myogenic potentials (VEMPs), we evaluated whether a simultaneous recording of ocular and cervical VEMPs after monaural and binaural stimulation can be achieved without a loss in diagnostic sensitivity and specificity.

http://ift.tt/2v1DSK5

P216 The efficacy of repetitive transcranial magnetic stimulation in treating patients with chronic daily headache

Headache is the most prevalent pain disorder, affecting around 66% of the global population. This study aimed to investigate the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left DLPFC in treating patients with primary chronic daily headaches (chronic tension type headache and chronic migraine).

http://ift.tt/2ws5Vpo

P311 The effectiveness of the complex repetitive peripheral magnetic stimulation (rPMS) in treatment of lumbosacral radiculopathy

In the modern society the low back pain (LBP) is the most common cause of temporary disability with estimated life time prevalence as high as 23–80% (Pedisic et al., 2013). LBP with radiculopathy is considered as the most unfavorable prognostic risk factor for the development of chronic pain syndrome and low quality of life (Konstantinou et al., 2013). The aim of this study is to evaluate the short-term efficacy of repetitive peripheral magnetic stimulation (rPMS) in the treatment of lumbosacral radiculopathy.

http://ift.tt/2v1LfBc

P295 Effects of functional electric stimulation and task specific training on gait recovery in patients with stroke: Randomized controlled trial

This work was designed to assess the effects of functional electrical stimulation (FES) combined with task specific training on gait recovery in stroke patients.

http://ift.tt/2ws8uYD

P277 The effects of sex hormone fluctuations in menstrual cycle on the EEG delta response

It is clear that reproductive hormones modulate the brain activity and development in human. Studies about how the reproductive hormones fluctuations alter the brain waves during menstrual cycle are insufficient. The objective in this study to explore if reproductive hormones fluctuations in the menstrual and luteal phase of cycle alter the EEG delta response.

http://ift.tt/2v1D4Vl

P259 Object dropping in Carpal Tunnel Syndrome: Clinical and electrophysiological features

Some patients with Carpal Tunnel Syndrome (CTS) complain of dropping objects. In this study, the clinical and electrophysiological features of CTS patients with (wOD) and without object dropping (w/oOD) were compared.

http://ift.tt/2wrR2Uh

P242 Dynamic time warping distance based connectivity: A new method for resting-state FMRI functional connectivity analysis

Traditionally resting-state networks are analysed with methods implying zero-lag linear dependence between brain regions, i.e. functional connectivity strength between voxel pairs is characterized by the correlation-coefficient of the two measured signal. It is known that the shape and timing of hemodynamic response function differs between brain regions and this introduces artefacts in linear measures.

http://ift.tt/2v2maWK

O208 Evidence by direct current stimulation (tDCS) of cerebellum involvement in pain perception and modulation in humans

cerebellum is involved in a wide number of integrative functions; its role in pain processing has been scarcely investigated. We tried to clarify this aspect using transcranial cerebellar direct current stimulation (tcDCS) and studying changes in perceptive threshold (PT), pain intensity (VAS) and laser evoked potentials (LEPs) responses (N1 and N2/P2).

http://ift.tt/2wrChAy

P315 Simple correlation analysis reveals falsely interpreted interictal spikes correlated to artefactual sources: A simultaneous EEG–fMRI study

Simultaneous EEG–fMRI is increasingly used in presurgical evaluation of epilepsy patients. The MR environment causes massive gradient artefacts and cardioballistic artefacts (BCG) to the recorded EEG signal, which must be corrected for, to make the reading of the EEG possible. This study aims to see, whether residual artefacts could disturb the specialist interpreting the EEG, even after apparently successful correction of the artefacts via widely accepted methods.

http://ift.tt/2v1JFPK

P307 TMS-based cortical mapping in double-arm transplantation

The re-adaptation process that the brain exhibits as a response to the environmental modifications resulting from prolonged or sudden limb loss can be described as a part of brain plasticity. In some cases, due to neurons synaptic interaction with neighboring neurons, motor-sensory representation of a hand can be replaced. In this study, it is aimed to develop neurophysiologic approaches for identification and discovery of structural and functional, transient and permanent plastic changes in arm-transplant cases.

http://ift.tt/2wrIqwH

P299 Motor mapping with navigated transcranial magnetic stimulation: Does more stimuli increase the accuracy?

Motor mapping with navigated transcranial magnetic stimulation (nTMS) is widespread technique that is used both in the preoperative planning and as a sign of neuroplasticity changes. But there is no generally accepted mapping protocol. The aim of our study was to estimate the relation between mapping parameters accuracy and the number of stimuli.

http://ift.tt/2v1M64F

P291 Non-invasive detection of fast ripples in low-noise EEG recordings

Ripples (80–250Hz) and fast ripples (FR, 250–500Hz) are characterized by poor signal-to-noise ratio, which reduces their visibility in non-invasive recordings. While ripples are observed in scalp EEG, FR detection has been restricted to invasive recordings. We tested the detectability of FR in the scalp EEG of epilepsy patients, recorded with a low-noise amplifier, and quantified their specificity for the prospective epileptogenic zone (EZ).

http://ift.tt/2wrSIgd

P281 The neurophysiological mechanisms linking stuttering and normal speech

This study examined underlying neurophysiological mechanisms of developmental stuttering – facilitation in the motor cortex during speech preparation served as analogue to the speech planning process.

http://ift.tt/2v1ZR3v

B-acute lymphoblastic leukemia/lymphoma (B-ALL) with precedent or concurrent myelodysplastic syndrome (MDS) with deletion 5q

Abstract

Progression to acute leukemia is an inherited feature of myelodysplastic syndrome (MDS). While majority of acute leukemia cases in this setting is acute myeloid leukemia (AML), rare cases of acute B-lymphoblastic leukemia/lymphoma (B-ALL) also exist. Therefore, detection of increased blasts in a patient with MDS should not be equated with a diagnosis of AML; full immunophenotyping of blasts is required. Previous reports indicate that dysplastic myeloid cells and B-lymphoblasts belong to the same clone. However, dysplastic myeloid cells and B-lymphoblasts could be clonally unrelated. Decitabine in addition to hyperCVAD (fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate and cytarabine) could be a good treatment option in this particular clinical setting.

http://ift.tt/2vSRVmt

A specific antibody to detect transcription factor T-Pit: a reliable marker of corticotroph cell differentiation and a tool to improve the classification of pituitary neuroendocrine tumours

http://ift.tt/2vSSQU1

Dissection of the Mouse Pancreas for Histological Analysis and Metabolic Profiling

This video article provides a detailed demonstration of the procedures required to successfully remove the pancreas from a mouse by dissection for histological analysis and metabolic profiling.

http://ift.tt/2wc9dNH

Isolation of a fluoroglycofen-degrading KS-1 strain and cloning of a novel esterase gene fluE

Abstract

The bacterium KS-1, capable of degrading fluoroglycofen, was isolated from sludge collected at a herbicide factory. The isolate was identified as Lysinibacillus sp. according to its phenotypic features and 16S rDNA phylogeny. KS-1 degraded 85.25% of the fluoroglycofen (50 mg L⁻¹) within 3 days of incubation. The optimum temperature and pH for fluoroglycofen degradation were 30°C and 7.0, respectively. Furthermore, Zn²⁺ and Cu²⁺ could significantly decrease the degradation rate. Three degradation products, which appeared during KS-1-mediated fluoroglycofen metabolism, were identified as deethyl-fluoroglycofen, acifluorfen and decarboxylate-acifluorfen. The fluE gene, which encodes a novel esterase that catalyzes the cleavage of carboxyl ester bonds of fluoroglycofen, was cloned from the KS-1 strain. Sequence alignment reveals that FluE shares 30%–40% amino acid sequence identity with members of the hormone sensitive lipase family. FluE was expressed in Escherichia coli BL21 and purified by Ni-NTA affinity chromatography. Purified FluE could efficiently hydrolyze fluoroglycofen and short-chain p-nitrophenol esters. However, no lipolytic activity was observed with esters containing acyl chains longer than 10 carbon atoms, thereby indicating that this enzyme is an esterase.

http://ift.tt/2unwnM4

Southern promises: a snapshot of the microbiology research landscape in South America based on bibliometric data

Abstract

Scientists have a single currency for productivity and impact: published articles. In an effort to map the global research landscape in microbiology, and to obviate the current lack of bibliometric analysis in the field, FEMS—the Federation of European Microbiological Societies—generated a dataset encompassing an exhaustive, worldwide list of microbiology studies for 2013–14, which further includes information as author affiliation, funding agency and number of citations. The manually curated database is useful in assessing the impact and regional productivity of microbiology research at different levels. Here, the data for microbiology research in South America are presented and discussed in detail. Based on the analysis, it emerged that despite great degrees of variation between number of published articles among the countries, a more levelled research productivity was observed when considering further dimensions like population size or number of research institutes. Normalised productivity and impact increase in countries with a 'central research hub', i.e. an institute or university producing a substantial portion of the national output (15% or more). From these observations, a possible strategy to increase impact and productivity in (microbiology) research for emerging countries is outlined.

http://ift.tt/2x10go0

Identification of biosynthetic gene clusters from metagenomic libraries using PPTase complementation in a Streptomyces host

Abstract

The majority of environmental bacteria are not readily cultured in the lab, leaving the natural products they make inaccessible using culture-dependent discovery methods. Cloning and heterologous expression of DNA extracted from environmental samples (environmental DNA, eDNA) provides a means of circumventing this discovery bottleneck. To facilitate the identification of clones containing biosynthetic gene clusters, we developed a model heterologous expression reporter strain Streptomyces albus::bpsA ΔPPTase. This strain carries a 4΄-phosphopantetheinyl transferase (PPTase)-dependent blue pigment synthase A gene, bpsA, in a PPTase deletion background. eDNA clones that express a functional PPTase restore production of the blue pigment, indigoidine. As PPTase genes often occur in biosynthetic gene clusters (BGCs), indigoidine production can be used to identify eDNA clones containing BGCs. We screened a soil eDNA library hosted in S. albus::bpsA ΔPPTase and identified clones containing non-ribosomal peptide synthetase (NRPS), polyketide synthase (PKS) and mixed NRPS/PKS biosynthetic gene clusters. One NRPS gene cluster was shown to confer the production of myxochelin A to S. albus::bpsA ΔPPTase.

http://ift.tt/2tvkloH

Pseudomonas aeruginosa Trent and zinc homeostasis

Abstract

Pseudomonas aeruginosa is a Gram-negative pathogen and the major cause of mortality in patients with cystic fibrosis. The mechanisms that P. aeruginosa strains use to regulate intracellular zinc have an effect on infection, antibiotic resistance and the propensity to form biofilms. However, zinc homeostasis in P. aeruginosa strains of variable infectivity has not been compared. In this study, zinc homeostasis in P. aeruginosa Trent, a highly infectious clinical strain, was compared to that of a laboratory P. aeruginosa strain, ATCC27853. Trent was able to tolerate higher concentrations of additional zinc in rich media than ATCC27853. Further, pre-adaptation to additional zinc enhanced the growth of Trent at non-inhibitory concentrations but the impact of pre-adaption on the growth of ATCC27853 under the same conditions was minimal. The results establish clear differences in zinc-induced responses in Trent and ATCC27853, and how zinc homeostasis can be a promising target for the development of novel antimicrobial strategies for P. aeruginosa infection in cystic fibrosis patients.

http://ift.tt/2uOAdCJ

Surveying the expanding prokaryotic Rubisco multiverse

Abstract

The universal, but catalytically modest, CO₂-fixing enzyme Rubisco is currently experiencing intense interest by researchers aiming to enhance crop photosynthesis. These efforts are mostly focused on the highly conserved hexadecameric enzyme found in land plants. In comparison, prokaryotic organisms harbor a far greater diversity in Rubisco forms. Recent work towards improving our appreciation of microbial Rubisco properties and harnessing their potential is surveyed. New structural models are providing informative glimpses into catalytic subtleties and diverse oligomeric states. Ongoing characterization is informing us about the conservation of constraints, such as sugar phosphate inhibition and the associated dependence on Rubisco activase helper proteins. Prokaryotic Rubiscos operate under a far wider range of metabolic contexts than the photosynthetic function of higher plant enzymes. Relaxed selection pressures may have resulted in the exploration of a larger volume of sequence space than permitted in organisms performing oxygenic photosynthesis. To tap into the potential of microbial Rubiscos, in vivo selection systems are being used to discover functional metagenomic Rubiscos. Various directed evolution systems to optimize their function have been developed. It is anticipated that this approach will provide access to biotechnologically valuable enzymes that cannot be encountered in the higher plant Rubisco space.

http://ift.tt/2uO2KIR

Fat Body Organ Culture System in Aedes Aegypti, a Vector of Zika Virus

The fat body is the central metabolic organ in insects. We present a live organ culture system that enables the user to study the responses of isolated fat body tissue to various stimuli.

http://ift.tt/2wcmt51

Lymph node targeting strategies to improve vaccination efficacy.

Lymph node targeting strategies to improve vaccination efficacy.

J Control Release. 2017 Aug 14;:

Authors: Jiang H, Wang Q, Sun X

Abstract
With the rapid development of nanotechnology as well as growing interest in immunotherapy, a great number of vaccine delivery vehicles have been explored in order to elicit potent adaptive immune responses against various infections or tumors. Recent studies have shown that targeting vaccine to antigen-presenting cells (APCs) within lymph nodes is an effective strategy for improving antigen-specific adaptive immune response. However, the characteristics of vaccine vehicles, such as size, surface charge and the degree of PEGylation, affect lymph node transfer and subsequent APC uptake, leading to different levels of immune responses. Thus, a comprehensive review of barriers, difficulties and corresponding strategies in lymph node targeting is important. In this review, we summarize the critical factors that affect lymph node delivery and survey recently reported successful vaccine carriers, which may be helpful for the rational design of vaccine vehicles.

PMID: 28818619 [PubMed - as supplied by publisher]

http://ift.tt/2vb1efz

Modified rapid immunohistochemical staining for intraoperative diagnosis of malignant brain tumors

Abstract

Rapid immunohistochemistry (R-IHC) has been developing mainly as a support technique in the rapid diagnosis of central nervous system tumors; however, there have been problems regarding instability in specimen preparation and immunostaining. To overcome the weakness of this technology, the instability of immunostaining, we developed a modified R-IHC. This was achieved by switching to 4% paraformaldehyde as the fixative solution and utilizing a commercially available Polymer Refine Detection Kit, as a high-sensitivity kit, in place of the secondary antibodies. In this study, we tested the modified R-IHC by evaluating rapid immunostaining on new staining items in 94 brain tumor removal cases, which took place at Tokyo Women's Medical University from 2014 to 2015. The results showed that, based on GFAP and p53 markers, the modified method obtained a higher stability in specimens than the standard rapid immunostaining method. It also achieved stainability on the same level as that of a permanent specimen. The modified method tested 86.6% (46/53) and 82.8% (24/29) in pHH3 and ATRX, respectively, in the percentage of correct classification (PCC) against the permanent specimens, and 100% (7/7) in the PCC against malignant lymphomas and gliomas that used CD20/CD3 for discrimination. We concluded that the modified R-IHC method indicated a higher stainability and PCC against the permanent specimens in comparison to the standard method in GFAP, p53, CD20/CD3, pHH3, and ATRX.

http://ift.tt/2uS3j4u

Adherence to the 2015 Dutch dietary guidelines and risk of non-communicable diseases and mortality in the Rotterdam Study

Abstract

We aimed to evaluate the criterion validity of the 2015 food-based Dutch dietary guidelines, which were formulated based on evidence on the relation between diet and major chronic diseases. We studied 9701 participants of the Rotterdam Study, a population-based prospective cohort in individuals aged 45 years and over [median 64.1 years (95%-range 49.0–82.8)]. Dietary intake was assessed at baseline with a food-frequency questionnaire. For all participants, we examined adherence (yes/no) to fourteen items of the guidelines: vegetables (≥200 g/day), fruit (≥200 g/day), whole-grains (≥90 g/day), legumes (≥135 g/week), nuts (≥15 g/day), dairy (≥350 g/day), fish (≥100 g/week), tea (≥450 mL/day), ratio whole-grains:total grains (≥50%), ratio unsaturated fats and oils:total fats (≥50%), red and processed meat (<300 g/week), sugar-containing beverages (≤150 mL/day), alcohol (≤10 g/day) and salt (≤6 g/day). Total adherence was calculated as sum-score of the adherence to the individual items (0–14). Information on disease incidence and all-cause mortality during a median follow-up period of 13.5 years (range 0–27.0) was obtained from data collected at our research center and from medical records. Using Cox proportional-hazards models adjusted for confounders, we observed every additional component adhered to was associated with a 3% lower mortality risk (HR 0.97, 95% CI 0.95; 0.98), lower risk of stroke (HR 0.95, 95% CI 0.92; 0.99), chronic obstructive pulmonary disease (HR 0.94, 95% CI 0.91; 0.98), colorectal cancer (HR 0.90, 95% CI 0.84; 0.96), and depression (HR 0.97, 95% CI 0.95; 0.999), but not with incidence of coronary heart disease, type 2 diabetes, heart failure, lung cancer, breast cancer, or dementia. These associations were not driven by any of the individual dietary components. To conclude, adherence to the Dutch dietary guidelines was associated with a lower mortality risk and a lower risk of developing some but not all of the chronic diseases on which the guidelines were based.

http://ift.tt/2wZUeEp

Interim analysis of a phase II trial evaluating the safety and efficacy of capecitabine plus oxaliplatin (XELOX) as adjuvant therapy in Japanese patients with operated stage III colon cancer

Abstract

Purpose

Adjuvant oxaliplatin plus oral capecitabine (XELOX) is recommended for patients with curatively resected colon cancer. However, its safety and tolerability in Asian patients is unclear; therefore, we evaluated the safety and efficacy of adjuvant XELOX in Japanese patients with curatively resected stage III colon cancer (MCSCO-1024) and present the interim safety data.

Methods

This prospective, multi-center, open-label, single-arm phase II study recruited patients with curatively resected stage III colon cancer. The protocol was a 120-min intravenous infusion of oxaliplatin (130 mg/m²) on day 1 and oral capecitabine (2000 mg/m²/day) in two divided doses for 14 days of a 3-week cycle, for a total of eight cycles (24 weeks). The primary endpoint was the 3-year disease-free survival, and secondary endpoints were the treatment completion rate, safety profile (rate and severity of adverse events), and correlation of adverse events, such as peripheral sensory neuropathy (PSN), with the administration period of oxaliplatin, etc.

Results

From November 2011 to August 2014 (34 months), 196 patients were enrolled. Safety was analyzed in 190 patients. The median total doses of capecitabine and oxaliplatin were 215,586.9 and 777.2 mg/m², respectively, while the median relative dose intensities were 82.5 and 76.0%, respectively. The overall treatment completion rate was 73.7%. The most frequent treatment-related adverse event was PSN (88.4%), while the most frequent grade ≥3 treatment-related adverse events were neutropenia (12.6%), PSN (6.3%), diarrhea (4.2%), and thrombocytopenia (4.2%). There were no treatment-related deaths.

Conclusions

Adjuvant XELOX is tolerable for Japanese patients with Stage III colon cancer.

http://ift.tt/2v0tySw

[Molecularly-Targeted Therapy of Spinocerebellar Ataxia Type 1 by HMGB1].

[Molecularly-Targeted Therapy of Spinocerebellar Ataxia Type 1 by HMGB1].

Brain Nerve. 2017 Aug;69(8):925-932

Authors: Fujita K, Okazawa H

Abstract
Spinocerebellar ataxia type 1 (SCA1) is an untreatable neurodegenerative disease. We reported a decrease in HMGB1 levels in the nucleus of cerebellar neurons in mouse SCA 1. The decrease in this DNA architectural protein leads to the impairment of DNA repair and transcription, the two essential nuclear functions, and eventually causes neurodegeneration. We have designed a gene therapy using AAV-HMGB1 and tested it using the mouse model. Based on the results of these proof of concept (POC) studies, we are now preparing GMP-level AAV vector and designing human clinical trials.

PMID: 28819076 [PubMed - in process]

http://ift.tt/2wbFi8G

Effect of processing methods on the nutritional content of three traditional vegetables leaves: Amaranth, black nightshade and jute mallow

Abstract

The study assessed changes in nutritional content of some commonly consumed traditional vegetables subjected to postharvest processes. Amaranth (Amaranthus cruentus L.), black nightshade (Solanum scabrum Mill.) and jute mallow (Corchorus olitorius L.) leaves used as vegetables were subjected to blanching, boiling and drying. The proximate composition and β-carotene content of fresh and processed leaves were determined. Amaranth, black nightshade and jute mallow leaves had 25.21%, 39.74% and 29.18% of protein, respectively. The β-carotene levels were 16.40, 25.25 and 27.74 mg/100 g for black nightshade amaranth and jute mallow leaves, respectively. The ash content was 10.57% for black nightshade, 12.40% for jute mallow and 16.33% for amaranth. Processing methods caused decreases of β-carotene and crude lipid content. Boiling for 30 min or more resulted in large loss of β-carotene. Drying under shade resulted in less loss of β-carotene than drying in cabinet at 50 and 60°C.

This article evaluates the common processing methods effects on nutritional content of three traditional vegetables (Amaranthus cruentus, Solanum scabrum, Corchorus olitorius) leaf and leaf products. Traditional vegetables constitute a major dietary source of micronutrients. Nutrient concentration of processed traditional African vegetables is dependent on the type of processing used. Shorter cooking times, cooking in less water, and using the cooking water as a part of the diet should be considered in consumption of processed vegetables to maximize product quality and nutrition. Results of this study will help to promote utilization and consumption of these traditional vegetables, which are neglected plant with great nutritional potentials.

http://ift.tt/2vb8Leg

Influence of physicochemical parameters on storage stability: Microbiological quality of fresh unpasteurized fruit juices

Abstract

Fresh juices rich in health and nutritional benefits are valued for their fresh flavor, taste, and aroma. These juices' quality however is affected by factors like temperature, light, and microbiological contamination significantly changing physicochemical parameters and storage stability. Physicochemical and microbiological analyses of passion fruit, pineapple, and mango juices in dark and light bottles at 24°C and 4°C were conducted in Kampala, Uganda for 12 days. Physicochemical parameters significantly reduced (p < .05) storage stability of fresh juices, while no significant changes (p > .05) were observed for the microbiological analyses. pH values ranged from 3.0 to 4.2 (dark) bottles and 2.9 to 4.0 (light) bottles for juices at 24°C and 4°C. °Brix values were from 1.0 to 5.5 for dark and clear bottles at 24°C and 4°C. TTA (%) values ranged from 1.1 to 7.2 (dark) bottles and 1.1 to 7.4 for (light) bottles at 24°C and 4°C. Ascorbic acid content ranged from 3.5 to 61.0 mg/ 100 ml and 5.5 to 56.7 mg/100 ml for juices in dark and clear bottles, respectively. total plate counts ranged from 1.3 × 10___ to 3.3 × 10⁷ CFU/ml (dark bottles at 24°C) to 3.5 × 10³ to 3.3 × 10⁸ CFU/ml (dark bottles at 4°C). For juices in light bottles, total plate counts ranged from 1.8 × 10___ to 8.0 × 10⁷ CFU/ml (24°C) and 2.7 × 10___ to 1.5 × 10⁸ CFU/ml (4°C). High microbial loads suggest the use of poor processing techniques and lack of good hygiene which lower quality and reduce storage stability of juices. Storage temperature greatly reduces physicochemical parameters both at ambient and refrigeration temperatures. This implies that temperature control for unpasteurized juices is critical in order to inhibit microorganism metabolic activities which accelerate biodeterioration leading to spoilage and short shelf life. Fresh unpasteurized juices stored at 24°C and 4°C may safely be consumed within 1 and 2 days, respectively.

Storage temperature significantly reduces physicochemical parameters of fresh unpasteurized fruit juices shortening storage life. The high microbial loads observed accelerated spoilage of the juices reducing storage life. High microbial loads suggest the absence of good manufacturing practices and poor processing techniques.

http://ift.tt/2uRuVHc

Effects of cooking techniques on fatty acid and oxylipin content of farmed rainbow trout (Oncorhynchus mykiss)

Abstract

The aim of this study was to investigate the effect of various cooking techniques on the fatty acid and oxylipin content of farmed rainbow trout. Rainbow trout is an excellent source of long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFA) which have beneficial health effects. Fillets of 2-year-old farmed rainbow trout were baked, broiled, microwaved, or pan-fried in corn (CO), canola (CaO), peanut (PO), or high oleic sunflower oil (HOSO). Fatty acids and oxidized lipids were extracted from these samples and their respective raw fillet samples. Fatty acid content was determined using gas chromatography and oxylipin content by mass spectroscopy. The values obtained from each cooking method were compared to those obtained from the respective raw fillets using paired t tests. PUFA content was not altered when samples were baked, broiled, microwaved, or pan-fried in CO or CaO. Pan-frying in PO reduced α-linolenic acid (18:3n-3), eicosadienoic acid (20:2n-6), and dihomo-γ-linolenic acid (20:3n-6), while pan-frying in HOSO reduced 18:3n-3, eicosapentaenoic acid (20:5n-3), docosapentaenoic acid (22:5n-3), docosahexaenoic acid (22:6n-3), linoleic acid (18:2n-6), 18:3n-6, 20:2n-6, 20:3n-6, docosatrienoic acid (22:2n-6), and adrenic acid (22:4n-6) compared to raw fish. Cooking decreased the omega-6 (n-6) PUFA-derived oxylipins, but caused no change in 20:5n-3 or 22:6n-3-derived oxylipins of the fillets. In conclusion, pan-frying was the only cooking method to alter the fatty acid content of the fillets, while observed changes in oxylipin content varied by cooking method. As the physiological impact of oxylipins is currently unknown, these results suggest that the cooking methods which optimize the consumption of n-3 PUFA from rainbow trout are baking, broiling, microwaving, or pan-frying in CO, CaO, or PO.

The cooking of farmed rainbow trout affects its fatty acid and oxylipin content depending on the cooking technique used. Pan-frying in oils results in significant changes.

http://ift.tt/2vai1iJ

Effect of soy protein isolate on the functional, pasting, and sensory acceptability of cassava starch-based custard

Abstract

Fortification of custard powder (CP) with protein from cheap sources such as soybean could potentially improve its nutritive value but may alter its functional and sensory properties. This study was therefore conducted to determine the effect of soy protein isolate (SPI) inclusion (0%–20%) on some functional and sensory properties of cassava starch-based CP. Functional, pasting, and sensory acceptability were determined using standard methods. Increase in soy protein isolate significantly (p < .05) decreased dispersibility, packed bulk density, swelling power, peak, trough, breakdown, final, and setback viscosities, but increased least gelation concentration, water absorption capacity, and solubility index. This study further showed that despite increasing addition of SPI up to 20%, sensory acceptability of the cassava starch-based CP formulations did not differ significantly, and most of them had very similar acceptability when compared to that of corn starch-based CP.

Soy protein isolate inclusion in cassava starch-based custard powder had marked effect on the functional and pasting properties of cassava starch-based custard powder and the custard powder was accepted by the sensory panelists up to 20% soy protein isolate inclusion.

http://ift.tt/2uRuVqG

Comparative Study between Biologic Plating and Intramedullary Nailing for the Treatment of Subtrochanteric Fractures: Is Biologic Plating using LCP-DF Superior to Intramedullary Nailing?

Publication date: Available online 19 August 2017
Source:Injury
Author(s): Won Chul Shin, Nam Hoon Moon, Jae Hoon Jang, Hee Jin Lee, Kuen Tak Suh
BackgroundThe objective of this study is to evaluate the outcome measures of subtrochanteric fractures between biologic plating and intramedullary nailing and determine if biologic plating is superior to intramedullary nailing.MethodsBetween March 2009 and December 2015, 81 patients with subtrochanteric fractures were enrolled (52 males and 29 females; 31 treated with biologic plating and 50 with intramedullary nailing). Biologic plating was conducted consecutively between May 2011 and March 2013 and intramedullary nailing was performed for the rest of period. Perioperative outcomes including operation time and blood loss during the operation; postoperative radiologic outcomes including union, time to union, coronal alignment, and shortening of the femur; and clinical outcomes including walking ability and pain were evaluated. The biologic plating group was compared with the intramedullary nailing group as a historical control.ResultsNo significant differences were identified for bony union and time to union between the two different fixation methods Coronal alignment was significantly better in the biologic plating group than in the intramedullary nailing group (p<0.016). Postoperative coronal alignment was the only risk factor associated with the nonunion of subtrochanteric fractures (unadjusted OR: 1.915, 95% CI: 0.190 − 19.273; adjusted OR: 0.042, 95% CI: 0.000 − 21.517; p=0.320).ConclusionSurgical outcomes using LCP-DF are comparable to those using intramedullary nailing. Further clinical studies with a larger sample size are required to show the advantage of biologic plating for the treatment of subtrochanteric fractures.



http://ift.tt/2uRm08I

Carotid Artery Stenosis: Medical Therapy, Surgery, and Stenting

Abstract

Purpose of Review

The purpose of the study was to update the recent information pertaining to carotid artery stenosis risk stratification and treatment.

Recent Findings

Current decision-making related to carotid artery stenosis is based on clinical trials that are outdated. Medical therapy has improved considerably in the past two decades, and this has reduced the stroke rate for both symptomatic and asymptomatic carotid stenoses. In recent community-based studies, the stroke risk with asymptomatic stenosis has been < 1% per year. For asymptomatic carotid stenosis, new trials such as CREST 2 and ECST 2 will determine whether revascularization has any benefit beyond aggressive medical management. For symptomatic patients, carotid endarterectomy is associated with a lower periprocedural stroke rate compared to carotid stenting. Age greater than 70 years is also associated with an increased risk for carotid stenting patients.

Summary

Clinicians should consider a variety of clinical and radiologic variables in reaching treatment decisions for patients with carotid stenosis. Both symptomatic and asymptomatic patients should receive optimal medical therapy.

http://ift.tt/2fUeSS2

Setting up of the Indian HIPEC Registry: A Registry for Indian Patients with Peritoneal Surface Malignancies

Abstract

There are various registries for patients with peritoneal metastases (PM) that aid pooling of data and generate evidence that dictates current clinical practice. This manuscript describes the setting up of the Indian HIPEC registry that was set up with a similar goal by a group of Indian surgeons. This is a registry for patients with PM treated with CRS and HIPEC in India. It also acts as a database for storing treatment-related information. Patients with PM from colorectal ovarian, gastric, appendiceal tumors, and other rare peritoneal tumors/metastases from rare tumors are enrolled in the registry. A coordinator updates the disease status of patients on a yearly basis. A private organization maintains the database. A non-disclosure agreement is signed between the company and each surgeon contributing to the registry to maintain confidentiality. For enrolling patients, securing institutional permission depends on the requirement of each institute; patient consent is mandatory. Data entry can be prospective or retrospective. To propose and conduct a study, the approval of a scientific committee linked to the registry is required. The Indian HIPEC registry is a practical database for Indian surgeons. There is no regulatory body that mandates collection and publication of scientific data in India. The onus is on each surgeon to capture valuable information pertaining to these common and rare diseases that could contribute to the existing scientific knowledge and guide the treatment of these patients in the future. The next challenge will be to enter data into the registry.

http://ift.tt/2wZp14f

A prospective study of palonosetron for prevention of chemotherapy-induced nausea and vomiting in malignant lymphoma patients following highly emetogenic chemotherapy

Abstract

Background

Chemotherapy-induced nausea and vomiting (CINV) is a troublesome issue in chemotherapy for cancer patients. A second-generation 5HT₃ receptor antagonist (5HT₃RA), palonosetron, is effective and safe for the prevention of CINV in breast cancer patients treated with cyclophosphamide and anthracycline, but there is little data for malignant lymphoma. We conducted a prospective phase 2 study at a single institution to clarify the efficacy and safety of palonosetron in lymphoma patients.

Methods

Chemotherapy-naïve lymphoma patients who were treated with highly emetogenic chemotherapy (HEC) received a single intravenous bolus of palonosetron, 0.75 mg/body, before chemotherapy on day 1 during the first course of chemotherapy. The occurrence of CINV was assessed using the Multinational Association for Supportive Care in Cancer (MASCC) antiemesis tool, which was recorded by patients during the first course of chemotherapy.

Results

A total of 59 patients were enrolled, and 49 patients were eligible and evaluated. The complete response (CR) rate was 93.9% (95% confidence interval 83.1–98.7%) at 0–120 h post-chemotherapy. The proportion of patients who developed nausea of any grade and vomiting at 0–120 h post-chemotherapy was 34.7 and 6.1%, respectively. Although treatment-related adverse events were observed in 36 (73.5%) patients, these were mild and they recovered by the next cycle of chemotherapy.

Conclusion

The present study demonstrated that a single dose of palonosetron was highly effective and safe for the prevention of CINV in lymphoma patients.

http://ift.tt/2fTANJ3

Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease

Abstract

Progranulin, a secreted glycoprotein, is encoded in humans by the single GRN gene. Progranulin consists of seven and a half, tandemly repeated, non-identical copies of the 12 cysteine granulin motif. Many cellular processes and diseases are associated with this unique pleiotropic factor that include, but are not limited to, embryogenesis, tumorigenesis, inflammation, wound repair, neurodegeneration and lysosome function. Haploinsufficiency caused by autosomal dominant mutations within the GRN gene leads to frontotemporal lobar degeneration, a progressive neuronal atrophy that presents in patients as frontotemporal dementia. Frontotemporal dementia is an early onset form of dementia, distinct from Alzheimer's disease. The GRN-related form of frontotemporal lobar dementia is a proteinopathy characterized by the appearance of neuronal inclusions containing ubiquitinated and fragmented TDP-43 (encoded by TARDBP). The neurotrophic and neuro-immunomodulatory properties of progranulin have recently been reported but are still not well understood. Gene delivery of GRN in experimental models of Alzheimer's- and Parkinson's-like diseases inhibits phenotype progression. Here we review what is currently known concerning the molecular function and mechanism of action of progranulin in normal physiological and pathophysiological conditions in both in vitro and in vivo models. The potential therapeutic applications of progranulin in treating neurodegenerative diseases are highlighted.

http://ift.tt/2uRmdsi

Glymphatic MRI in idiopathic normal pressure hydrocephalus

Abstract

The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer's disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T₁-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging.

http://ift.tt/2vaupPN

Biallelic mutations in the homeodomain of NKX6-2 underlie a severe hypomyelinating leukodystrophy

Abstract

Hypomyelinating leukodystrophies are genetically heterogeneous disorders with overlapping clinical and neuroimaging features reflecting variable abnormalities in myelin formation. We report on the identification of biallelic inactivating mutations in NKX6-2, a gene encoding a transcription factor regulating multiple developmental processes with a main role in oligodendrocyte differentiation and regulation of myelin-specific gene expression, as the cause underlying a previously unrecognized severe variant of hypomyelinating leukodystrophy. Five affected subjects (three unrelated families) were documented to share biallelic inactivating mutations affecting the NKX6-2 homeobox domain. A trio-based whole exome sequencing analysis in the first family detected a homozygous frameshift change [c.606delinsTA; p.(Lys202Asnfs*?)]. In the second family, homozygosity mapping coupled to whole exome sequencing identified a homozygous nucleotide substitution (c.565G>T) introducing a premature stop codon (p.Glu189*). In the third family, whole exome sequencing established compound heterozygosity for a non-conservative missense change affecting a key residue participating in DNA binding (c.599G>A; p.Arg200Gln) and a nonsense substitution (c.589C>T; p.Gln197*), in both affected siblings. The clinical presentation was homogeneous, with four subjects having severe motor delays, nystagmus and absent head control, and one individual showing gross motor delay at the age of 6 months. All exhibited neuroimaging that was consistent with hypomyelination. These findings define a novel, severe form of leukodystrophy caused by impaired NKX6-2 function.

http://ift.tt/2uRsowC

Prevention of Exposure Keratopathy in Critically Ill Patients: A Single-Center, Randomized, Pilot Trial Comparing Ocular Lubrication With Bandage Contact Lenses and Punctal Plugs.

Objectives: To compare the effectiveness of bandage contact lenses and punctal plugs with ocular lubricants in preventing corneal damage in mechanically ventilated and sedated critically ill patients. Design: Single-center, prospective, randomized, pilot study. Setting: Sixteen-bed, general ICU at a tertiary academic medical center. Patients: Adults admitted to the ICU and anticipated to require mechanical ventilation and continuous sedation for greater than or equal to 4 days. Interventions: Patients were randomized to receive eye care with ocular lubricants (n = 38), bandage contact lenses (n = 33), or punctal plugs (n = 33). The bandage contact lenses were changed every 4 days, whereas the punctal plugs remained in situ for the entire study. Measurements and Main Results: The primary endpoint was the presence or absence of corneal damage as assessed by the grade of keratopathy. Patients were examined by an ophthalmologist blinded to the study group every 4 days and at the time of withdrawal from the study, due to cessation of sedation, discharge from the ICU, or death. The mean duration of the study was 8.6 +/- 6.2 days. The grade of keratopathy in the ocular lubricant group increased significantly in both eyes (p = 0.01 for both eyes) while no worsening was noted in either the lens or punctal plugs groups. In a post hoc analysis of patients with an initially abnormal ophthalmic examination, significant healing of keratopathy was noted in the lens group (p = 0.02 and 0.018 for left and right eyes, respectively) and in the right eye of the plugs group (p = 0.005); no improvement was noted in the ocular lubricant group. Conclusions: Compared with ocular lubrication, bandage contact lenses and punctal plugs were more effective in limiting keratopathy, and their use, particularly of bandage contact lenses, was associated with significant healing of existing lesions. Copyright (C) by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

http://ift.tt/2vawviF

Antibiotic Combination Therapy for Patients With Gram-Negative Septic Shock.

No abstract available

http://ift.tt/2uRorI8