Αρχειοθήκη ιστολογίου

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Πέμπτη 7 Απριλίου 2016

Hybrid MR/PET Imaging in Neurology: Present Applications and Prospects for the Future



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Response and tolerability of a single dose of 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer: a multicenter retrospective analysis

Background: Radiolabelled prostate specific membrane antigen (PSMA) ligands represent a true theranostics concept for diagnosis and therapy of relapsed and metastatic prostate cancer patients. The aim of this study was to evaluate response and tolerability of a single dose of 177Lutetium-PSMA-617 (Lu-PSMA) in a large cohort of patients with metastatic castration resistant prostate cancer (mCRPC). Methods: The data of 82 consecutive patients (median age: 73 years, range: 43-87) with metastatic castration resistant prostate cancer who received a single dose of Lu-PSMA (mean: 5.9±0.5 GBq) were retrospectively analyzed. Data was collected at baseline and 8 weeks after therapy. 68Ga-PSMA-11 PET/CT was performed in all patients to verify sufficient PSMA expression. Bone, lymph node, liver and lung metastases were present in 99%, 65%, 17% and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data and prostate specific antigen (PSA) value at baseline and 8 weeks after therapy application. Results: A total of six patients died and two patients dropped out not willing to continue therapy and follow-up. Complete dataset of 74 patients were available for analysis. 47 (64%) of the patients showed a PSA-Decline, of these 23 (31%) had a PSA decline > 50%, 35 (47%) had a stable disease with a PSA decline from <50% to an increase <25% and 17 (23%) showed a progressive disease with a PSA increase >25%. There were no significant changes indicative of toxicity in hemoglobin, white blood cells, creatinine and tubular extraction rates. There was a significant but mild decrease of platelets with a median value still within the normal range. Conclusion: This retrospective multicenter analysis suggests that radioligand therapy with Lu-PSMA is safe, well tolerated and shows considerable response in PSA values. Therefore, it offers an additional therapeutic option for patients with mCRPC. This data may justify further prospective randomized studies to evaluate and prove the clinical benefit in survival and quality of life.



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The Thymidine Phosphorylase Imaging Agent 123I-IIMU Predicts the Efficacy of Capecitabine

Recently, companion diagnostics with nuclear medicine techniques are expected as more suitable means than biopsy for predicting treatment efficacy. The anti-cancer effect of capecitabine, an orally administered chemotherapeutic agent activated by thymidine phosphorylase (TP), positively correlates with tumor TP expression levels. This study aimed to assess whether TP imaging using a radiolabeled uracil derivative, [123I]5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([123I]IIMU), could predict the efficacy of capecitabine treatment. Methods: Sensitivity to doxifluridine, a metabolite of capecitabine and direct substrate for TP, was assessed by WST assays in vitro for three human colon cancer cell lines with different TP expression profiles. The intracellular uptake and retention of [123I]IIMU were evaluated. Mice inoculated with each cell line were treated with capecitabine for 2 weeks, and tumor growth was compared. In vivo distribution studies and single photon emission computed tomography/computed tomography imaging of [123I]IIMU were performed in inoculated mice. Results: In vitro experiments showed a positive correlation between TP expression levels and doxifluridine sensitivity. In vitro studies revealed that intracellular uptake and retention of [123I]IIMU were dependent on TP expression levels. In vivo experiments in inoculated mice showed that [123I]IIMU accumulation in tumor tissue was correlated with TP expression levels and susceptibility to capecitabine treatment. Moreover, single photon emission computed tomography/computed tomography imaging of [123I]IIMU in tumor-inoculated mice showed that [123I]IIMU reflects TP expression levels in tumor tissues. Conclusion: [123I]IIMU could be used as an in vivo companion diagnostic for predicting the efficacy of capecitabine treatment.



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Administered Activities for Pediatric Nuclear Medicine Procedures and the Impact of the 2010 North American Guidelines on General Hospitals in the United States

We sought to describe the practice of pediatric nuclear medicine at general hospitals in the US and to assess the impact of dose awareness campaigns like Image Gently. METHODS: A web-based survey was developed that requested information regarding hospital type, whether they practiced pediatric nuclear medicine, and their method for determining the administered activity for children. The survey invitation was emailed to a sample of general hospitals with more than 300 beds excluding dedicated pediatric, veterans, psychiatric and rehabilitation hospitals. Data were collected for 5 procedures performed in children: 99mTc MDP bone scans, 99mTc MAG3 renograms, 99mTc DMSA renal cortical scans, 99mTc based hepatobiliary scans, and 18F FDG PET scans. The sites reported dosage by weight (MBq/kg), minimum and maximum dosages and the activities that they would administer to 2 hypothetical patients: a 5 year old boy (20 kg, 110 cm tall) and a 10 year old girl (30 kg, 140 cm tall). RESULTS: The invitation was delivered to 196 sites with 121 (61.7%) responding. Eighty-two hospitals (67.8%) performed nuclear medicine in children. All sites scaled administered activity for children, mostly by body weight. Also, 82.4% of sites indicated they were familiar with Image Gently, 57.1% were familiar with the 2010 North American Guidelines for children, and 54.9% altered their protocols because of the Guidelines. The median value for parameters defined by the Guidelines was equal to the Guidelines recommended value for all sites. More than 50% of these sites were compliant with the Guidelines regarding both the acquisition parameters and the administered activities for the two hypothetical patients, particularly sites familiar with the Guidelines. However, there remained a wide variation in practice, sometimes more than a factor of 10, for sites not familiar with the Guidelines. CONCLUSION: Image Gently and the North American Guidelines have had a substantial impact on pediatric nuclear medicine practice in the US. However, a wide variation in practice still exists, particularly for sites not familiar with the Guidelines. Further promotion and dissemination of the Guidelines and best practice is still necessary.



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Anti-3-[18F] FACBC (Fluciclovine) PET-CT of Breast Cancer An Exploratory Study

The purpose of this study is to explore the uptake of the synthetic amino acid analog positron emission tomography (PET) radiotracer anti-3-[18F] FACBC (fluciclovine) in breast lesions with correlation to histologic and immunohistochemical characteristics. Methods: Twelve women with breast lesions underwent 45 minute dynamic PET-CT of the thorax after intravenous administration of 366.3 ±14.8 (337.44 - 394.05) MBq of fluciclovine. Uptake in the primary lesions at 4 representative time points (5, 17, 29, 41 min) after injection were correlated with histologic, imaging, and clinical findings. The significance of differences in maximum standard uptake value (SUVmax) and tumor to background ratios between malignant and benign tissue were calculated. Correlation of activity to histologic and immunohistochemical cancer subtypes were made including Ki-67 intensity and Nottingham Grade (NG). Results: There were 17 breast lesions (4 benign, 13 malignant) including 7/13 invasive ductal, 5/13 invasive lobular, and 1/13 metaplastic carcinomas. There was a significant difference in mean SUVmax ± standard deviation (SD) of malignant (6.15±3.2, 6.01±3.15, 5.68±2.82, and 5.59±2.95) vs benign (1.26±0.57, 1.21±0.53, 1.22±0.57 and 1.11±0.54) lesions at 5, 17, 29 and 41mins respectively (all p≤0.0001). Tumor to background (aorta, normal breast and marrow) ratios were also significantly higher in malignant compared to benign breast lesions (all P≤0.02). Highest fluciclovine activity seems to be present in triple negative and NG3 subtypes. Across time points, quantitative Ki-67 had weak positive correlation with SUVmax [R1=0.48(P = 0.03), R2=0.44(P = 0.03), R3= 0.46(P = 0.03), R4 =0.43(0.06)]. In 7 patients, fluciclovine PET visualized locoregional and distant spread including that of lobular cancer, though identification of hepatic metastases was limited by physiologic background activity. Conclusion: The uptake characteristics of fluciclovine are reflective of the histologic and immunohistochemical characteristics in suspect breast lesions with greater activity in malignant versus benign etiology. The data from this exploratory study may be useful to design future studies utilizing fluciclovine PET for breast tumor imaging as well as for detection of locoregional and distant spread



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Serial quantitative TSPO-targeted PET reveals peak microglial activation up to two weeks after an epileptogenic brain insult.

Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We employed TSPO-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. Methods: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium-pilocarpine. Rats were subjected to [11C]PK11195 PET scans before SE, immediately after SE, at 1, 2, 5, 7, 14, and 22 days, and 14-16 weeks post SE. For data evaluation, brain regions were outlined by co-registration with a standard rat brain atlas, and % injected dose/cc and binding potential (simplified reference tissue model with cerebellar gray matter as reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5 or 14 days post SE. Results: Following SE, increases in [11C]PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as hippocampus, thalamus or piriform cortex, but not in the cerebellum beginning at 2-5 days and persisting at least 3 weeks after SE. Maximal regional signal was observed at 1-2 weeks after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. Principal Conclusion: TSPO-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, anti-epileptogenic therapy.



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Modulation of abnormal metabolic brain networks by experimental therapies in a nonhuman primate model of Parkinsons disease: an application to human retinal pigment epithelial (hRPE) cell implantation

Abnormal covariance pattern of regional metabolism associated with Parkinson's disease (PD) is modulated by dopaminergic pharmacotherapy. Using high resolution FDG PET and network analysis we previously derived and validated a parkinsonism-related metabolic pattern (PRP) in non-human primate models of PD. It is currently not known whether this network is modulated by experimental therapeutics. In this study we examined changes in network activity by striatal implantation of human levodopa-producing retinal pigment epithelial (hRPE) cells in parkinsonian macaques and evaluated its reproducibility in a small test-retest study. Methods: PET FDG scans were acquired in eight healthy macaques and eight macaques with MPTP-induced bilateral nigrostriatal dopaminergic lesions following unilateral putaminal implantation of hRPE cells or sham surgery. PRP activity was measured prospectively in all animals and in a subset of test-retest animals using a network quantification approach. Network activity and regional metabolic values were compared on a hemispheric basis between animal groups and treatment conditions. Results: All individual macaques had sustained clinical improvement after hRPE-implantation compared to the sham surgery. PRP activity was elevated in the untreated MPTP hemispheres relative to those of the normal controls (P < 0.00005) but was reduced (P < 0.05) in the hRPE-implanted hemispheres. The modulation observed in network activity was supported by concurrent local and remote changes in regional glucose metabolism. PRP activity remained unchanged in the untreated MPTP hemispheres versus the sham-operated hemispheres. PRP activity was also stable (P ≥ 0.29) and correlated (R2 ≥ 0.926; P < 0.00005) in the test-retest hemispheres. These findings were highly reproducible across several PRP topographies generated in multiple cohorts of parkinsonian and healthy macaques. Conclusion: We have demonstrated long-term therapeutic effects of hRPE cell implantation in non-human primate models of PD. The implantation of such levodopa-producing cells can concurrently decrease the elevated metabolic network activity in parkinsonian brains on an individual basis. These results parallel the analogous findings reported in patients with PD undergoing levodopa therapy and other symptomatic interventions. With further validation in large samples, FDG PET imaging with network analysis may provide a viable biomarker for assessing treatment response in animal models of PD following experimental therapies.



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Is Tinnitus Treatable?

Tinnitus is one of the most intrusive disorders known in our modern society. It is far more prevalent today than ever before due to the fact that society is noisier than ever before. Construction workers, factory workers and disc jockeys are probably the three occupations most effected by tinnitus. Loud sounds without proper ear protection can cause tinnitus, and once you have it, it usually does not go away. And while there is no cure currently known, the question is: is tinnitus treatable?

Disc Jockeys Beware

If you are in an otherwise quiet room and you hear a hissing or ringing sound that is not coming from anything discernible, it is probably tinnitus. Some sufferers claim that it literally blocks out other sounds, causing them to be virtually deaf. Unfortunately, contemporary disc jockeys, specifically, generally do not wear ear protection and, essentially, live in a loud music environment. In their youthful exuberance for the music and dancing, they tend to ignore the warnings of experienced individuals. It isn't too long before tinnitus sets in and will likely only get worse unless precautions are taken.

Psychological Distress and Memory Loss

The tonality, volume and type of ringing or hissing can vary, but the result is the same: partial deafness. The sound may interfere with watching television and listening to music. Even having a conversation can be frustrating with a constant hissing in your ears. At its worst, severe tinnitus can even cause psychological distress, including depression and anxiety. Some sufferers also experience short-term memory loss.

Again, is tinnitus treatable? The simple answer is yes. However, treatment may not work for everybody.

Successful Treatment is Not Guaranteed

As of yet, there is no known, scientifically accepted, definitive cure, just as there is no definitive universal treatment. Even with successful treatment, there is no guarantee that the hissing or ringing will completely dissipate or disappear and not return. So it is wise to look upon ebooks and other sources that claim to alleviate the symptoms of tinnitus with skepticism and concern. The cure may be out there, but it has yet to be discovered.

"Successful" treatments include:

  • Tinnitus Restraining Therapy
  • Tinnitus Masking
  • Meditation
  • Medication
  • Sound Therapies

The most anticipated cure being examined is stem cell research. Hopefully, the question – "Is tinnitus treatable?" – will be a thing of the past. That being said, it is, in the long run, easier and wiser to prevent tinnitus than to have it treated.

If you have a DJ friend or family member, talk to them; show them this article and other sources that will persuade them to be less careless with their hearing. Their lives will be richer for it.




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Participatory epidemiology at the neotropics: study of diseases of backyard livestock and description of hunting patterns in Uaxactún, Maya Reserve Biosphere, Guatemala

The intention of the following study was to describe the interrelationship between villagers, domestic animals and wildlife at the Community Forestry Concession of Uaxactún, Guatemala by means of participatory...

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Low dose topical tacrolimus in vernal keratoconjunctivitis

Shoughy SS, Jaroudi MO, Tabbara KF

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Nonpharmacologic, nonherbal management of menopause-associated vasomotor symptoms: an umbrella systematic review (protocol)

Vasomotor symptoms such as hot flashes and night sweats are a common concern of perimenopausal and postmenopausal women and are associated with a decreased quality of life. These symptoms can be effectively ma...

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Supporting successful implementation of public health interventions: protocol for a realist synthesis

There is a growing emphasis in public health on the importance of evidence-based interventions to improve population health and reduce health inequities. Equally important is the need for knowledge about how t...

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Barriers and facilitators in providing oral health care to nursing home residents, from the perspective of care aides—a systematic review protocol

Unregulated care aides provide up to 80 % of direct resident care in nursing homes. They have little formal training, manage high workloads, frequently experience responsive behaviours from residents, and are ...

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Detection of Antibodies in Blood Plasma Using Bioluminescent Sensor Proteins and a Smartphone

TOC Graphic

Analytical Chemistry
DOI: 10.1021/acs.analchem.6b00534
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Anti-wrinkle effects of Seungma-Galgeun-Tang as evidenced by the inhibition of matrix metalloproteinase-I production and the promotion of type-1 procollagen synthesis

Seungma-Galgeun-Tang (SMGGT), a traditional herbal medicinal formula, has been used to treat various skin problems such as inflammation and rashes in Korean traditional medicine. In order to clarify the scient...

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Chemical composition, in vitro antioxidant and anti-inflammatory properties of essential oils of four dietary and medicinal plants from Cameroon

In the Cameroonian traditional medicine, plants of the Capparidaceae, Euphorbiaceae and Liliaceae families are used to treat several metabolic diseases. These plants are rich in various compounds belonging to ...

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Outcomes of West Nile encephalitis patients after one year of West Nile encephalitis outbreak in Kerala, India: A follow-up study

Abstract

We reported an acute encephalitis syndrome outbreak in Alappuzha district in Kerala, India during the year 2011. The aetiology was confirmed to be West Nile virus lineage 1. Many encephalitis patients from this outbreak exhibited neurological sequelae post recovery. This study was aimed to assess the clinical outcomes of West Nile encephalitis confirmed case-patients after one-year of acute illness. Forty West Nile virus confirmed encephalitis patients were selected from the 2011 outbreak was included in this study. Out of 40 cases, only 30 survived after 12 months. Among these 30 recovered case-patients, 27 (90%) consented for clinical follow-up and 23 (73.67%) of them consented for assessment of cognitive impairment and deposition of blood sample for antibody testing. The most common symptom observed in these patients was fatigue (25.93%). Other symptoms included dizziness (7.4%), decreased sense of hearing (7.4%) and decreased sense of smell (7.4%). Reduced power in limbs was found in 33.33% of the cases. Most of the patients (23.1%) were dependent on others for normal daily living activities. The patients also had probable risk of poor cognition (29.41%) and dementia (57.14%). None of the patients were positive for WNV specific IgM at 12 months post onset of disease. The study concluded that the long-term sequelae were noticed in WNV positive patients. Prevention effort should be focused on the elderly (≥60 years old) people who have a higher risk of severe sequelae. The state health authorities should create awareness among people in order to prevent the transmission of disease. This article is protected by copyright. All rights reserved



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Etiology, seasonality and clinical characterization of viral respiratory infections among hospitalized children in Beirut, Lebanon

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Abstract

Background

Acute respiratory tract viral infections occur worldwide and are one of the major global burdens of diseases in children. The aim of this study was to determine the viral etiology of respiratory infections in hospitalized children, to understand the viral seasonality in a major Lebanese hospital and to correlate disease severity and the presence of virus.

Methods

Over a one year period, nasal and throat swabs were collected from 236 pediatric patients, aged 16 years old or less and hospitalized for acute respiratory illness. Samples collected were tested for the presence of 17 respiratory viruses using multiplex real-time RT-PCR.

Results

Pathogens were identified in 165 children (70%) and were frequently observed during fall and winter seasons. Co-infection was found in 37% of positive samples. The most frequently detected pathogens were human Rhinovirus (hRV, 23%), Respiratory Syncytial Virus (RSV, 19%), human Bocavirus (hBov, 15%), human Metapneumovirus (hMPV, 10%) and human Adenovirus (hAdV, 10%). A total of 48% of children were diagnosed with bronchiolitis and 25% with pneumonia. While bronchiolitis was often caused by RSV single virus infection and hAdV/hBoV coinfection, pneumonia was significantly associated with hBoV and HP1V1 infections. No significant correlation was observed between a single viral etiology infection and a specific clinical symptom.

Conclusion

This study provides relevant facts on the circulatory pattern of respiratory viruses in Lebanon and the importance of using PCR as a useful tool for virus detection. Early diagnosis at the initial time of hospitalization may reduce the spread of the viruses in pediatric units. This article is protected by copyright. All rights reserved



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Longitudinal analysis of the humoral response to Kaposi's sarcoma-associated herpesvirus after primary infection in children

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ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS)—one of the most common pediatric cancers in sub-Saharan Africa—however, the factors that lead to disease progression are not fully understood. HIV infection, immunosuppression, and high KSHV viral load increase the risk of developing KS, suggesting that the loss of an effective anti-KSHV immune response may be an important risk factor. However, very little is known about the KSHV-specific immune response prior to KS and less is known about the anti-KSHV immune response during the very early stages of infection. We therefore prospectively followed a cohort of 86 Zambian children for two years after primary KSHV seroconversion to characterize the humoral immune response during the early stages of KSHV infection. Plasma, peripheral blood mononuclear cells, and oral swabs were collected from patients every three months and analyzed for KSHV-specific antibodies and presence of viral DNA. We observed an approximately 40% KSHV seropositive rate among infected children at time points after primary seroconversion, indicating that seroreversion is common after primary KSHV infection. At the time of primary KSHV seroconversion HIV-infected ART-naïve children had a more robust KSHV antibody response compared to HIV-infected children taking ART and HIV-uninfected children. Conversely, the longitudinal anti-KSHV antibody response was highly variable and did not correlate with available clinical information, HIV/ART status, or presence of KSHV DNA. Collectively, our data suggest that there is limited impact by the variations in the humoral immune response in young children after infection. This article is protected by copyright. All rights reserved



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The use of computerized echocardiographic simulation improves the learning curve for transesophageal hemodynamic assessment in critically ill patients

Our aim was to evaluate the impact of a computerized echocardiographic simulator on the learning curve for transesophageal echocardiography (TEE) hemodynamic assessment of ventilated patients in the ICU.

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Title page/Editorial Board

Publication date: May 2016
Source:Medical Hypotheses, Volume 90





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Sublobar resection versus lobectomy in Surgical Treatment of Elderly Patients with early-stage non-small cell lung cancer (STEPS): study protocol for a randomized controlled trial

The appropriateness of lobectomy for all elderly patients is controversial. Meanwhile, sublobar resection is associated with reduced operative risk, better preservation of pulmonary function, and a better qual...

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Editorial Board

Publication date: March–April 2016
Source:Médecine & Droit, Volume 2016, Issue 137





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Contents

Publication date: March–April 2016
Source:Médecine & Droit, Volume 2016, Issue 137





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Balance confidence: A predictor of perceived physical function, perceived mobility, and perceived recovery one year following inpatient stroke rehabilitation

Publication date: Available online 6 April 2016
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Caryne Torkia, Krista L. Best, William C. Miller, Janice J. Eng
ObjectiveTo estimate the effect of balance confidence measured at one month post-stroke rehabilitation on perceived physical function, mobility, and stroke recovery 12 months later.DesignLongitudinal study (secondary analysis)SettingMulti-site, community-basedParticipantsCommunity-dwelling individuals (n=69) with stroke living in a home settingMain Outcome MeasuresActivities-specific Balance Confidence scale; the physical function and mobility subscales of the Stroke Impact Scale (SIS) 3.0; and the SIS single-item for perceived recovery.ResultsBalance confidence at one month post-discharge from inpatient rehabilitation predicts perceived physical function (model 1), mobility (model 2), and recovery (model 3) 12 months later adjusting for important covariates. The covariates included in model 1 were age, sex, basic mobility, and depression. The covariates selected for model 2 were age, sex, balance capacity, and anxiety, while the covariates in model 3 were age, sex, walking capacity, and social support. The amount of variance in perceived physical function, perceived mobility, and perceived recovery that balance confidence accounted for was 12%, 9%, and 10% respectively.ConclusionsFollowing discharge from inpatient rehabilitation post-stroke, balance confidence predicts individuals' perceived physical function, mobility, and recovery one year later. There is a need to address balance confidence at discharge from inpatient stroke rehabilitation.



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STAGE-diging: a novel in-gel digestion processing for proteomics samples

Publication date: Available online 6 April 2016
Source:Journal of Proteomics
Author(s): Paolo Soffientini, Angela Bachi
Proteomics based on high-resolution mass spectrometry has become a powerful tool for the analysis of protein abundance, modifications and interactions. New generation mass spectrometers and UPLC are able to cover approximately an entire cell proteome in one run, but sample preparation, in terms of time and sample recovery is still a critical step. Here we present a modification of the in-gel digestion method, called STAGE-diging. This approach was compared with the well-established procedures for sample preparation, both on high and low complexity samples, on quantitative SILAC-based experiments and on two different mass spectrometers. The results show that STAGE-diging reduces sample handling, decreases the analysis time and improves protein identification and quantification. Moreover, shorter instrument time allows performing multiple replicates that produce wider proteome coverage and more accurate quantitation.SignificanceIn our work we detailed the set-up of a novel in-gel digestion processing for proteomics samples, called STAGE-diging. This new method can be applied to samples of different complexity both for qualitative and quantitative proteomics studies. We proved that STAGE-diging streamlines sample preparation as it is easy to use, reduces sample handling and improves protein identification and quantification all with a decreased analysis time. All these benefits make this new method appealing for laboratories handling a large number of samples, where time and reproducibility play a substantial role.

Graphical abstract

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Proteomic biomarkers for psoriasis and psoriasis arthritis

Publication date: Available online 6 April 2016
Source:Journal of Proteomics
Author(s): J. Reindl, J. Pesek, T. Krüger, S. Wendler, S. Nemitz, P. Muckova, R. Büchler, S. Opitz, N. Krieg, J. Norgauer, H. Rhode
Although several new biomarkers have been recently proposed for psoriasis (Ps) and psoriasis arthritis (PsA), nothing is known about their diagnostic sensitivity and specificity, and their routine use. We therefore searched in-depth for new biomarker candidates using a biobank with EDTA-plasma from 158 individuals, patients and healthy controls. Samples from 6 selected pairs (patients against healthy controls) were searched proteomically using a workflow of extensive and precise design that is highly comprehensive. Subsequent verification was performed using ELISA and the entire biobank. By proteomic methods, 208 altered proteins were identified. Of these, 15 biomarker candidates were selected for verification. Of these 15, 4 individual parameters and 11 combinations significantly discriminated between patient and control groups. These individual parameters were Zn-α2-glycoprotein, complement C3, polymeric immunoglobulin receptor, and plasma kallikrein. Significant discrimination was obtained by combinations of 2 or 3 parameters. One combination seemed suitable for diagnosing PsA. Moreover, several candidates desmoplakin, complement C3, polymeric immunoglobulin receptor, and cytokeratin 17, correlated with PASI in all patients. This first comprehensive proteomic study on non-depleted plasma identified several biomarker candidates that have not been described before as well as some known from previous studies.Biological significanceOur non-gel proteomic analysis is based on the highly comprehensive and significantly optimized chromatographic protein pre-fractionation. The method allows a biomarker search in non-depleted plasma. The subsequent verification by ELISA identifies several biomarker-candidates for the unbiased diagnosis of psoriasis and psoriasis arthritis. Four of the identified candidate markers might be used individually. Combinations of several parameters improve the diagnostic sensitivity and specificity. The still not validated candidates form a reserve for further evaluation. Moreover, mass spectrometric data uncover several biomarker-candidates which show diverse protein species of the same protein with opposing changes in the same sample.

Graphical abstract

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How to Build a Vacuum Spring-transport Package for Spinning Rotor Gauges

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Here we describe how to build a robust spring-transport mechanism for a spinning rotor gauge. This device securely immobilizes the rotor and keeps it under vacuum during transportation. We also describe packaging that minimizes the risk of damage during transport. Tests show our design works for typical shocks during transport.

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Titanium scaffold osteogenesis in healthy and osteoporotic rats is improved by the use of low-level laser therapy (GaAlAs)

Abstract

The present study aimed to assess the effects of low-level laser therapy (GaAlAs) on the bone repair process within titanium scaffolds in the femurs of healthy and osteoporotic rats. Fifty-six rats were divided into four groups: group Sh: SHAM animals that received scaffolds; group LSh: SHAM animals that received scaffolds and were subjected to laser therapy; group OV: ovarietomized (OVX) animals that received scaffolds; and group LOV: OVX animals that received scaffolds and were subjected to laser therapy. Thirty days following ovariectomy or sham surgery, scaffolds were implanted in the left femurs of all animals in the study. Immediately after opening the surgical site, the inner part of the surgical cavity was stimulated with low-level laser (GaAlAs). In addition to this procedure, the laser group was also subjected to sessions of low-level laser therapy (LLLT) at 48-h intervals, with the first session performed immediately after surgery. The rats were sacrificed at 2 and 6 weeks, time in which femur fragments were submitted for histological and histomorphometric examination, and skin tissue above the scaffold was submitted to histological analysis. At the end of the study, greater bone formation was observed in the animals submitted to LLLT. At 2 and 6 weeks, statistically significant differences were observed between LSh and Sh groups (p = 0.009 and 0.0001) and LOV and OV (p = 0.0001 and 0.0001), respectively. No statistical difference was observed when assessing the estrogen variable. On the basis of our methodology and results, we conclude that LLLT improves and accelerates bone repair within titanium scaffolds in both ovariectomized and healthy rats, when compared to animals not subjected to radiation.



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In vitro investigation on Ho:YAG laser-assisted bone ablation underwater

Abstract

Liquid-assisted hard tissue ablation by infrared lasers has extensive clinical application. However, detailed studies are still needed to explore the underlying mechanism. In the present study, the dynamic process of bubble evolution induced by Ho:YAG laser under water without and with bone tissue at different thickness layer were studied, as well as its effects on hard tissue ablation. The results showed that the Ho:YAG laser was capable of ablating hard bone tissue effectively in underwater conditions. The penetration of Ho:YAG laser can be significantly increased up to about 4 mm with the assistance of bubble. The hydrokinetic forces associated with the bubble not only contributed to reducing the thermal injury to peripheral tissue, but also enhanced the ablation efficiency and improve the ablation crater morphology. The data also presented some clues to optimal selection of irradiation parameters and provided additional knowledge of the bubble-assisted hard tissue ablation mechanism.



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Correlation of histological and ex-vivo confocal tumor thickness in malignant melanoma

Abstract

The ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) is a novel diagnostic method for fresh tissue examination, which has already shown promising results in the evaluation of healthy skin and different skin tumors. In malignant melanoma, the histological tumor thickness plays an essential role for further treatment strategies. The immediate perioperative measurement of tumor thickness by means of ex-vivo CLSM might accelerate the decision for further operating procedures in malignant melanoma. Ten histologically confirmed malignant melanomas from various donor sites were blindly examined by two investigators via ex-vivo CLSM and conventional light microscopy. The histopathological tumor thickness (HTT) and confocal tumor thickness (CTT) were measured independently and evaluated using correlation curves, Spearman's correlation coefficient, and Bland-Altman plots. Bland-Altman plots for HTT and reflectance-mode CTT, as well as for fluorescence-mode CTT, showed high correlations. Spearman's correlation coefficient of HTT and CTT was 1.00 in FM and RM. The mean difference of RM-CTT and FM-CTT versus HTT was 0.09 ± 0.30 mm and 0.19 ± 0.35 mm. In one case, the HTT was identical to the CTT in both modes. This pilot study shows high conformity of CTT and HTT measured in malignant melanoma underlining the potential of ex-vivo CLSM for perioperative decisions on safety margin excisions of malignant melanoma in the future.



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In vitro evaluation of photodynamic therapy using curcumin on Leishmania majo r and Leishmania braziliensis

Abstract

Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 μg/ml up to 7.8 μg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm2 at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed.



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Effects of low-level laser therapy on bone regeneration of the midpalatal suture after rapid maxillary expansion

Abstract

This study evaluated the effect of low-level laser therapy (LLLT) on bone regeneration at the midpalatal suture (MPS) after rapid maxillary expansion (RME), using cone beam computed tomography. Fourteen 8–14-year-old patients with transverse maxillary deficiency underwent RME with a Hyrax-type expander activated with one full turn after installation and two half turn daily activations until achieving overcorrection. Patients were randomly assigned to either a control group (RME alone, n = 4) or an experimental group (n = 10) in which RME was followed by 12 LLLT sessions (GaAlAs, p = 70 mW, λ = 780 nm, Ø = 0.04 cm2). Two tomographic images of the MPS were obtained—T0, after disjunction and T1, after 4 months. Bone regeneration was evaluated by measuring the optical density (OD) on the tomographic images using InVivo Dental 5.0 software. Data were analyzed by the paired Student's t test (α = 0.05 %). A statistically significant difference between T0 and T1 OD values was observed in the laser-treated group (p = 0.00), but this difference was not significant in the control group (p = 0.20). Intergroup comparison of OD values at T1 revealed higher OD in the laser-treated group (p = 0.05). In conclusion, LLLT had a positive influence on bone regeneration of the midpalatal suture by accelerating the repair process.



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Effect of Er,Cr:YSGG laser on the surface of composite restoratives during in-office tooth bleaching

Abstract

The aim of this in vitro study was to investigate the effect of Er,Cr:YSGG laser on the surface roughness and microhardness of various composite restoratives during in-office tooth bleaching. Five highly viscous composite restoratives and three flowable composite restoratives were investigated. Thirty cylindrical specimens of each material were made using Teflon molds. The specimens of each composite were randomly divided into three groups (n = 10). Group 1 specimens did not receive bleaching treatment, group 2 received a conventional in-office bleaching treatment, and group 3 received a laser-assisted in-office bleaching treatment using an Er,Cr:YSGG laser. Two-way ANOVA was used to determine significant interactions between materials and bleaching methods. One-way ANOVA and Tukey's post hoc test were used to compare the mean surface microhardness and roughness between materials for each treatment group (a = 0.05). Τhere were no significant differences in surface microhardness between the two bleached experimental groups for all the tested composites (p > 0.05). The reduction of surface microhardness after bleaching procedures ranged from 0.72 to 16.93 % for the specimens received conventional treatment and from 1.30 to 11.51 % for those received laser-assisted treatment. Moreover, there were no significant differences in Ra values between the experimental groups (p > 0.05) in all cases. The increase of surface roughness after the bleaching treatments was negligible and was between 0.43 and 4.78 %. The use of Er,Cr:YSGG laser during in-office tooth bleaching treatment did not affect the surface microhardness and roughness of the tested composite restorative materials.



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The picosecond laser for tattoo removal

Abstract

The prevalence of tattoos continues to grow as modern society's stigma towards this form of body art shifts towards greater acceptance. Approximately one third of Americans aged 18–25 and 40 % of Americans aged 26–40 are tattooed. As tattoos continue to rise in popularity, so has the demand for an effective method of tattoo removal such as lasers. The various colors of tattoo inks render them ideal targets for specific lasers using the principle of selective photothermolysis. Traditional laser modalities employed for tattoo removal operate on pulse durations in the nanosecond domain. However, this pulse duration range is still too long to effectively break ink into small enough particles. Picosecond (10−12) lasers have emerged at the forefront of laser tattoo removal due to their shorter pulse lengths, leading to quicker heating of the target chromophores, and consequently, more effective tattoo clearance. Recent studies have cited more effective treatment outcomes using picosecond lasers. Future comparative studies between picosecond lasers of various settings are necessary to determine optimal laser parameters for tattoo clearance.



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Laser and light-based treatments of venous lakes: a literature review

Abstract

Venous lake is a benign vascular malformation commonly seen in elderly patients, typically arising in sun-exposed areas of the body. Patients often seek treatment to prevent recurrent bleeding or because they find the lesion cosmetically unacceptable. Venous lake may negatively affect quality of life, due to the cosmetic disfigurement it can create and the resulting psychological distress. Traditional treatments, such as surgical excision, cryosurgery, sclerotherapy, and electrocoagulation, result in varying degrees of success and can cause discomfort. Laser- and light-based treatment modalities may offer a safe and effective alternative, as numerous studies have shown their benefit in the treatment of venous lakes, particularly with the long-pulsed 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG). Although various types of lasers and lights have been studied, there remains a lack of general consensus as to which one is the superior laser modality. Further studies that establish standardized protocols to compare the results of using different types of laser treatments are warranted.



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Comparison of the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy and ureteroscopic holmium laser lithotripsy in the treatment of obstructive upper ureteral calculi with concurrent urinary tract infections

Abstract

The aim of this study is to compare the clinical efficacy and safety of retroperitoneal laparoscopic ureterolithotomy (RPLU) and ureteroscopic holmium laser lithotripsy (UHLL) as two minimally invasive procedures in managing obstructive upper ureteral calculi with concurrent urinary tract infections (UTI). The retrospective study included 189 patients who underwent unilateral obstructive upper ureteral stones with concurrent UTI from January 2007 to November 2014 at our institution. Patients received RPLU (81 cases) or UHLL (108 cases). All patients received preoperative anti-infection treatment (indwelling ureteral stent and/or preoperative antibiotics). Collected data, including sex, age, stone size, success rate, operation duration, post-operation hospitalization time, and post-operation complications, were compared. All patients were followed up for more than 6 months after surgeries, and no ureterostenosis occurred. The study included 189 patients, 41 (21.7 %) females and 148 (78.3 %) males with a medium age of 52 years (range 22–81 years). All surgeries were successfully performed without conversion to open surgery. Stone size in the RPLU group was larger than that of the UHLL group (16.1 ± 1.4 vs. 10.4 ± 1.6 mm, P = 0.012). Operative duration (P = 0.009) and hospitalization time (P < 0.001) in the UHLL group were significantly shorter than those in the RPLU group, whereas stone clearance rate was significantly higher in the RPLU group (100 vs. 88.9 %, P = 0.002). Of note, postoperative fever was more common in patients treated with UHLL (15 cases) versus RPLU (4 cases) (13.9 vs. 4.9 %, P = 0.043). Moreover, in the UHLL group, three patients without a preoperative indwelling ureteral stent were complicated with sepsis, which was not seen in RPLU group. In our study, the safety and stone clearance rate of RPLU are better than those of UHLL in the treatment of unilateral upper ureteric calculi with concurrent UTI. Preoperative antibiotics and indwelling ureteral stent may reduce the risk of postoperative infections.



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Performance evaluation of a high resolution dedicated breast PET scanner

Purpose:

Early stage breast cancers may not be visible on a whole-body PET scan. To overcome whole-body PET limitations, several dedicated breast positron emission tomography (DbPET) systems have emerged nowadays aiming to improve spatial resolution. In this work the authors evaluate the performance of a high resolution dedicated breast PET scanner (Mammi-PET, Oncovision).

Methods:

Global status, uniformity, sensitivity, energy, and spatial resolution were measured. Spheres of different sizes (2.5, 4, 5, and 6 mm diameter) and various 18 fluorodeoxyglucose (18F-FDG) activity concentrations were randomly inserted in a gelatine breast phantom developed at our institution. Several lesion-to-background ratios (LBR) were simulated, 5:1, 10:1, 20:1, 30:1, and 50:1. Images were reconstructed using different voxel sizes. The ability of experienced reporters to detect spheres was tested as a function of acquisition time, LBR, sphere size, and matrix reconstruction voxel size. For comparison, phantoms were scanned in the DbPET camera and in a whole body PET (WB-PET). Two patients who just underwent WB-PET/CT exams were imaged with the DbPET system and the images were compared.

Results:

The measured absolute peak sensitivity was 2.0%. The energy resolution was 24.0% ± 1%. The integral and differential uniformity were 10% and 6% in the total field of view (FOV) and 9% and 5% in the central FOV, respectively. The measured spatial resolution was 2.0, 1.9, and 1.7 mm in the radial, tangential, and axial directions. The system exhibited very good detectability for spheres ≥4 mm and LBR ≥10 with a sphere detection of 100% when acquisition time was set >3 min/bed. For LBR = 5 and acquisition time of 7 min the detectability was 100% for spheres of 6 mm and 75% for spheres of 5, 4, and 2.5 mm. Lesion WB-PET detectability was only comparable to the DbPET camera for lesion sizes ≥5 mm when acquisition time was >3 min and LBR > 10.

Conclusions:

The DbPET has a good performance for its clinical use and shows an improved resolution and lesion detectability of small lesions compared to WB-PET.



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Study of myocardial cell inhomogeneity of the human heart: Simulation and validation using polarized light imaging

Purpose:

The arrangement or architecture of myocardial cells plays a fundamental role in the heart's function and its change was shown to be directly linked to heart diseases. Inhomogeneity level is an important index of myocardial cell arrangements in the human heart. The authors propose to investigate the inhomogeneity level of myocardial cells using polarized light imaging simulations and experiments.

Methods:

The idea is based on the fact that the myosin filaments in myocardial cells have the same properties as those of a uniaxial birefringent crystal. The method then consists in modeling the myosin filaments of myocardial cells as uniaxial birefringent crystal, simulating the behavior of the latter by means of the Mueller matrix, and measuring the final intensity of polarized light and consequently the inhomogeneity level of myocardial cells in each voxel through the use of crossed polarizers. The method was evaluated on both simulated and real tissues and under various myocardial cell configurations including parallel cells, crossed cells, and cells with random orientations.

Results:

When myocardial cells run perfectly parallel to each other, all the polarized light was blocked by those parallel myocardial cells, and a high homogeneity level was observed. However, if myocardial cells were not parallel to each other, some leakage of the polarized light was observed, thus causing the decrease of the polarized light amplitude and homogeneity level. The greater the crossing angle between myocardial cells, the smaller the amplitude of the polarized light and the greater the inhomogeneity level. For two populations of myocardial cell crossing at an angle, the resulting azimuth angle of the voxel was the bisector of this angle. Moreover, the value of the inhomogeneity level began to decrease from a nonzero value when the voxel was not totally homogeneous, containing for example cell crossing.

Conclusions:

The proposed method enables the physical information of myocardial tissues to be estimated and the inhomogeneity level of a volume or voxel to be quantified, which opens new ways to study the microstructures of the human myocardium and helps understanding how heart diseases modify myocardial cells and change their mechanical properties.



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Denoising of polychromatic CT images based on their own noise properties

Purpose:

Because of high diagnostic accuracy and fast scan time, computed tomography(CT) has been widely used in various clinical applications. Since the CT scan introduces radiation exposure to patients, however, dose reduction has recently been recognized as an important issue in CTimaging. However, low-dose CT causes an increase of noise in the image and thereby deteriorates the accuracy of diagnosis. In this paper, the authors develop an efficient denoising algorithm for low-dose CTimages obtained using a polychromatic x-ray source. The algorithm is based on two steps: (i) estimation of space variant noise statistics, which are uniquely determined according to the system geometry and scanned object, and (ii) subsequent novel conversion of the estimated noise to Gaussian noise so that an existing high performance Gaussian noise filtering algorithm can be directly applied to CTimages with non-Gaussian noise.

Methods:

For efficient polychromatic CTimage denoising, the authors first reconstruct an image with the iterative maximum-likelihood polychromatic algorithm for CT to alleviate the beam-hardening problem. We then estimate the space-variant noise variance distribution on the image domain. Since there are many high performance denoising algorithms available for the Gaussian noise,image denoising can become much more efficient if they can be used. Hence, the authors propose a novel conversion scheme to transform the estimated space-variant noise to near Gaussian noise. In the suggested scheme, the authors first convert the image so that its mean and variance can have a linear relationship, and then produce a Gaussian image via variance stabilizing transform. The authors then apply a block matching 4D algorithm that is optimized for noise reduction of the Gaussian image, and reconvert the result to obtain a final denoised image. To examine the performance of the proposed method, an XCAT phantom simulation and a physical phantom experiment were conducted.

Results:

Both simulation and experimental results show that, unlike the existing denoising algorithms, the proposed algorithm can effectively reduce the noise over the whole region of CTimages while preventing degradation of image resolution.

Conclusions:

To effectively denoise polychromatic low-dose CTimages, a novel denoising algorithm is proposed. Because this algorithm is based on the noise statistics of a reconstructed polychromatic CTimage, the spatially varying noise on the image is effectively reduced so that the denoised image will have homogeneous quality over the image domain. Through a simulation and a real experiment, it is verified that the proposed algorithm can deliver considerably better performance compared to the existing denoising algorithms.



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Analysis of Zebrafish Kidney Development with Time-lapse Imaging Using a Dissecting Microscope Equipped for Optical Sectioning

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The method described here allows time-lapse analysis of organ development in zebrafish embryos by using a fluorescence dissecting microscope capable of performing optical sectioning and simple strategies of readjustment to correct focal and planar drift.

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Improving Quality of Acute Asthma Care in U.S. Hospitals: Changes between 1999-2000 and 2012-2013

Background
Little is known about the longitudinal change in quality of acute asthma care for hospitalized children and adults in the U.S. We investigated whether the concordance of inpatient asthma care with the national guidelines improved over time, identified hospital characteristics predictive of guideline concordance, and determined whether guideline-concordant care is associated with a shorter hospital length-of-stay (LOS).
Methods
Analysis of data from two multicenter chart review studies of hospitalized patients aged 2-54 years with acute asthma during two time periods: 1999-2000 and 2012-2013. Outcomes were guideline concordance at the patient- and hospital-levels, and association of patient composite concordance with hospital LOS.
Results
Analytic cohort for the comparison of guideline concordance comprised 1,634 patients: 834 patients from 1999-2000 versus 800 patients from 2012-2013. Over these ∼15 years, inpatient asthma care became more concordant at the hospital-level, with the mean composite score increasing from 74 to 82 (P<.001 however during wide variability in guideline concordance of acute asthma care remained across hospitals with the greatest variation provision individualized written action plan at discharge was significantly lower midwestern and southern compared to northeastern hospitals. after adjusting for severity patients who received perfectly concordant guidelines had shorter hospital los p=".009).<div">Conclusions

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ICU Telemedicine Co-Management Methods and Length of Stay

Background
Recent studies have identified processes that are associated with more favorable length of stay outcomes when an ICU telemedicine program is implemented. Despite these studies, the relation of the acceptance of ICU telemedicine management services by individual ICUs to length of stay (LOS) outcomes is unknown.
Methods
This is a single ICU telemedicine center study that compares length of stay outcomes among 3 groups of intensivist staffed mixed medical surgical ICUs that used alternative co-management strategies. The proportion of provider orders recorded by an ICU telemedicine provider to all recorded orders were compared among ICUs that used a monitor and notify co-management approach, a direct intervention with timely notification process, and ICUs that used a mix of these two approaches. The primary outcome was acuity adjusted hospital length of stay.
Results
ICUs that used the direct intervention with timely notification strategy had a significantly larger proportion of provider orders recorded by ICU telemedicine physicians than the mixed methods of co-management group, which had a larger proportion than ICUs that used the monitor and notify method (p Conclusions

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Efficacy and safety of PAH-specific therapy in pulmonary arterial hypertension: a meta-analysis of randomized clinical trials

Background
Previous meta-analyses of PAH-specific therapy for pulmonary arterial hypertension (PAH) pooled PAH-specific combination therapy and monotherapy together. The flaw might threaten the authenticity of their findings.
Methods
PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) that evaluated any PAH-specific medications in the treatment of PAH. We calculated odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous data and standardized mean differences for continuous data.
Results
In total, 35 RCTs involving 6,702 patients were included. In monotherapy vs placebo/conventional therapy, significance was obtained in mortality reduction (OR:0.50; 95%CI:0.33-0.76; P=0.001), six-minute walk test (6MWD) (MD:31.10m; 95%CI: 25.40 to 36.80; P Conclusions

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Study of Apatinib in Patients With Differentiated Thyroid Cancer

Condition:   Thyroid Cancer
Intervention:   Drug: Apatinib
Sponsor:   Peking Union Medical College Hospital
Recruiting - verified March 2016

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HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide

The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial.

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Mosquito vectors and the spread of cancer: an overlooked connection?

Abstract

Mosquitoes (Diptera: Culicidae) represent a key threat for millions of humans and animals worldwide, vectoring important pathogens and parasites, including malaria, dengue, filariasis, and Zika virus. Besides mosquito-borne diseases, cancers figure among the leading causes of mortality worldwide. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Notably, there are few contrasting evidences of the relationship between cancer and mosquito-borne diseases, with special reference to malaria. However, analogies at the cellular level for the two diseases were reported. Recently, a significant association of malaria incidence with all cancer mortality in 50 USA states was highlighted and may be explained by the ability of Plasmodium to induce suppression of the immune system. However, it was hypothesized that Anopheles vectors may transmit obscure viruses linked with cancer development. The possible activation of cancer pathways by mosquito feeding events is not rare. For instance, the hamster reticulum cell sarcoma can be transmitted through the bites of Aedes aegypti by a transfer of tumor cells. Furthermore, mosquito bites may influence human metabolic pathways following different mechanisms, leading to other viral infections and/or oncogenesis. Hypersensitivity to mosquito bites is routed by a unique pathogenic mechanism linking Epstein–Barr virus infection, allergy, and oncogenesis. During dengue virus infection, high viral titers, macrophage infiltration, and tumor necrosis factor alpha production in the local tissues are the three key important events that lead to hemorrhage. Overall, basic epidemiological knowledge on the relationships occurring between mosquito vector activity and the spread of cancer is urgently needed, as well as detailed information about the ability of Culicidae to transfer viruses or tumor cells among hosts over time. Current evidences on nanodrugs with multipotency against mosquito-borne diseases and cancers are reviewed, with peculiar attention to their mechanisms of action.



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Intestinal and liver flukes of birds of prey (Accipitriformes, Falconiformes, Strigiformes) from Slovakia: uniform or diverse compound?

Abstract

During 2012–2014 up to 286 birds of the orders Falconiformes (5 species), Accipitriformes (11 species), and Strigiformes (7 species) were examined for trematodes and this represents the first detailed study in Slovakia. A total of 12 trematode species belonging to the families Diplostomidae, Cyathocotylidae, Strigeidae, and Opisthorchiidae were identified. Rare infections were found in falcons where only two species (40 %) and three of 85 examined birds (3.5 %) were infected with a low range of two to four worms of generalists Strigea falconis or Plagiorchis elegans. Contrary to that, ten accipitriformes species (90.9 %) and 63 of 156 bird individuals (40.4 %) were infected with nine flukes: Conodiplostomum perlatum, Conodiplostomum spathula, Neodiplostomum attenuatum, Neodiplostomum spathoides, Parastrigea flexilis, Strigea falconis, Strigea vandenbrokae, Paracoenogonimus ovatus, and Metorchis bilis. S. falconis and N. attenuatum were the most frequent, occurring in parallel in eight and four bird species, in numbers up to 575 and 224. The intensity of infection with other fluke species was low ranging from one to 13 worms. Three owl (Strigiformes) representatives (42.9 %) were exclusive hosts for Neodiplostomum canaliculatum and Strigea strigis, and the proportion of positive and dissected individual birds was 10:45 (22.2 %). Both trematodes occurred in two or three owl species. In conclusion, apparent dissimilarity of trematode load of three unrelated lines of falcons, eagles, and owls was revealed. The present study extends our knowledge on the composition of the trematode fauna in Slovakia as all species except S. falconis and P. elegans that represent new host and species records in Slovakia.



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Epigenomes, Vol. 1, Pages 1: Welcome to the New Journal Epigenomes

We are excited to introduce Epigenomes, a new journal that will serve the growing community of researchers who use omic approaches to dissect the epigenetic mechanisms underlying developmental and pathological processes.[...]

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Effect of Yi Gong San Decoction on Iron Homeostasis in a Mouse Model of Acute Inflammation

We investigated the effect of Yi Gong San (YGS) decoction on iron homeostasis and the possible underlying mechanisms in a mouse model of acute inflammation in this study. Our findings suggest that YGS regulates iron homeostasis by downregulating the level of HAMP mRNA, which may depend on regulation of the IL-6/STAT3 or BMP/HJV/SMAD pathway during acute inflammation.

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