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Exp Clin Endocrinol Diabetes 2017; 125: 1-3
DOI: 10.1055/s-0042-123975

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

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Stereotactic body radiotherapy (SBRT) in recurrent or oligometastatic pancreatic cancer

Abstract

Background

Stereotactic body radiotherapy (SBRT) in pancreatic cancer can be limited by its proximity to organs at risk (OAR). In this analysis, we evaluated the toxicity and efficacy of two different treatment approaches in patients with locally recurrent or oligometastatic pancreatic cancer.

Materials and methods

According to the prescription method, patients were divided in two cohorts (C1 and C2). The planning target volume (PTV) was created through a 4 mm expansion of the internal target volume. In C2, a subvolume was additionally created, a simultaneous integrated protection (SIP), which is the overlap of the PTV with the planning risk volume of an OAR to which we prescribed a reduced dose.

Results

In all, 18 patients were treated (7 with local recurrences, 9 for oligometastases, 2 for both). Twelve of 23 lesions were treated without SIP (C1) and 11 with SIP (C2). The median follow-up was 12.8 months. Median overall survival (OS) was 13.2 (95% confidence interval [CI] 9.8–14.6) months. The OS rates at 6 and 12 months were 87 and 58%, respectively. Freedom from local progression for combined cohorts at 6 and 12 months was 93 and 67% (95% CI 15–36), respectively. Local control was not statistically different between the two groups. One patient in C2 experienced grade ≥3 acute toxicities and 1 patient in C1 experienced a grade ≥3 late toxicity.

Conclusion

The SIP approach is a useful prescription method for abdominal SBRT with a favorable toxicity profile which does not compromise local control and overall survival despite dose sacrifices in small subvolumes.

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Ultrastructural changes in peripheral arteries and nerves in diabetic ischemic lower limbs, by electron microscope

Publication date: Available online 30 January 2017
Source:Alexandria Journal of Medicine
Author(s): Mohamed E. Salem, Abdel-Azzem A. Ismael, Amr Salem, Tarek Salem
BackgroundThe results of "light and electron microscopic study" of the peripheral arteries and nerves biopsies in diabetic neuropathy comparing with biopsies of normal arteries and nerves of traumatic amputation as a control group.Aim of the workTo evaluate the "electron microscopic changes" in the peripheral small arteries and nerves in the diabetic ischemic lower limbs.Patients and methodsFrom January 2015 to June 2016 a total number of 20 patients with diabetic ischemic lower limbs (Diabetic patients group) compared with 20 non diabetic non ischemic persons as (Control group) who undergone traumatic lower limb amputation. All cases were subjected to complete history taking, complete clinical examination, and routine laboratory investigations. "Light and electron microscopic studies" of biopsies from the peripheral small arteries and nerves e.g. digital or posterior tibial arteries and nerves during amputation of diabetic gangrene of the toes, below knee, above knee amputation and from traumatic amputation of the control group.ResultsThe results of an "electron microscopic study" of diabetic peripheral arteries and nerves biopsies, 12 out of 20 cases showed thrombi in small vessels. In some small vessels, masses of fibrin were seen within the lumen. In other vessels, older thrombi were present. 17 out of 20 cases showed endothelial cells hyperplasia in some vessels. The degree of hyperplasia was sufficient to occlude the lumen of the vessels. Some vessels showed degenerate pericytes and endothelial cells which contained large lipid droplets. The peripheral nerves showed patchy demyelination, areas of degeneration and regeneration, areas of infarction and necrosis and collagen fibers deposition. Among the control group, no cases contained thrombi, degenerated vessels, degenerate pericytes or lipid droplets within the endothelial cells.ConclusionThe present study found that the diabetic microangiopathy is the main cause of diabetic neuropathy and diabetic foot lesions.



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Effectiveness of antiangiogenic drugs in glioblastoma patients: a systematic review and meta-analysis of randomized clinical trials

Publication date: Available online 30 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Giuseppe Lombardi, Ardi Pambuku, Luisa Bellu, Miriam Farina, Della Puppa Alessandro, Denaro Luca, Vittorina Zagonel
Backgroundglioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results. We performed a systematic review and a meta-analysis to clarify and evaluate their effectiveness in glioblastoma patients.Patients and methodswe searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases.Resultsfourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) were identified including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056). Bevacizumab did not improve overall survival. Twelve trials (4113 patients) were analyzed for progression-free survival. Among antiangiogenic drugs, only bevacizumab demonstrated an improvement of progression-free survival (HR=0.63, p<0.001), both alone (HR=0.60, p=0.003) or in combination to chemotherapy (HR=0.63; p<0.001), both as first-line treatment (HR=0.70, p<0.001) or in recurrent disease (HR=0.52, p<0.001).Conclusionsantiangiogenic drugs did not improve overall survival in glioblastoma patients, either as first or second-line treatment, and either as single agent or in combination with chemotherapy. Among antiangiogenic drugs, only bevacizumab improved progression-free survival regardless of treatment line, both as single agent or in combination with chemotherapy



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Health risk assessment of cadmium pollution emergency for urban populations in Foshan City, China

Abstract

With rapid socioeconomic development, water pollution emergency has become increasingly common and could potentially harm the environment and human health, especially heavy metal pollution. In this paper, we investigate the Cd pollution emergency that occurred in the Pearl River network, China, in 2005, and we build a migration and transformation model for heavy metals to simulate the spatiotemporal distribution of Cd concentrations under various scenarios of Cd pollution emergency in Foshan City. Moreover, human health hazard and carcinogenic risk for local residents of Foshan City were evaluated. The primary conclusions were as follows: (1) the number of carcinogen-affected people per year under scenario 1 reached 254.41 when the frequency was 0.1 year/time; specifically, the number of people with cancer per year in the area of the Datang, Lubao, and Nanbian waterworks was 189.36 accounting for 74% of the total number per year; (2) at the frequency of 5 years/time, the Lubao waterwork is the only one in extremely high- or high-risk grade, while besides it, the risk grade in the Datang, Nanbian, Xinan, Shitang, and Jianlibao waterworks is in the extremely high or high grade when the frequency is 0.1 year/time; (3) when Cd pollution accidents with the same level occurs again, Cd concentration decreases to a low level in the water only if the migration distance of Cd is at least 40–50 km. Based on the health risk assessment of Cd pollution, this study gives the recommendation that the distance should keep above 50 km in tidal river network of the Pearl River Delta between those factories existing the possibility of heavy metal pollution and the drinking water source. Only then can the public protect themselves from hazardous effects of higher levels of heavy metal.

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Impact of aeration disturbances on endogenous phosphorus fractions and their algae growth potential from malodorous river sediment

Abstract

The present work assessed the impact of aeration disturbances on sediment-bound phosphorus fractions and their algae growth potential from a typical malodorous river. Phosphorus was sequentially extracted by a modified version of Hedley fractionation method. It was found that the mean contents of TP was 1476.1 ± 60.3 mg/kg, consisting mainly of dilute HCl-extractable P (52.6%) and NaOH-P (19.2%). The algae growth potential tests demonstrated that algae growth had varied P-level requirements for different P speciation and NaOH-P promoted algae growth remarkably and its promoting effect was positively related to its concentration. Additionally, intermittent overlying water aeration modes were recommended, and run 1 (7.0 mg/L, 12 h) was deemed as the optimized aerated mode in terms of its relatively low ecological risk and high P retention. It was noted that NaOH-P was most affected by aeration disturbance and exhibited marked increase with the elevated dissolved oxygen (DO) level whether for intermittent overlying water or sediment aeration. This research helps to gain improved understanding of the ecological risk on sediment P, and NaOH-P is recognized as one ecologically important P fraction in the sediments considering its relatively high proportion and bioavailability.

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“To make a molehill out of a mountain”: An ERP-study on cognitive reappraisal of negative pictures in children with and without ADHD

Publication date: Available online 30 January 2017
Source:Clinical Neurophysiology
Author(s): Valerie Van Cauwenberge, Rachida El Kaddouri, Karel Hoppenbrouwers, Jan R. Wiersema
ObjectiveWe investigated cognitive reappraisal in children with ADHD by means of the late positive potential (LPP) and self-report ratings. We expected diminished LPP modulation following reappraisal and lower self-report scores in children with ADHD.MethodsEighteen children with ADHD and 24 typically developing (TD) children (8-12 years) performed a cognitive reappraisal task, while EEG was recorded, and filled out a questionnaire on cognitive reappraisal.ResultsDespite the lack of main reappraisal effects on LPP, LPP were less positively modulated during reappraisal in ADHD compared to TD children.ConclusionsChildren with ADHD reported less use of reappraisal and could be distinguished from TD children based on LLP modulation. However the lack of main effects of reappraisal on LPP in both groups hinders clear interpretation of this finding and questions the suitability of LPP modulation within the current paradigm as a neural index of reappraisal in children 8-12 years old, and warrants further research on the inter-individual variability and sensitivity of LPP modulation as a neural index of emotion regulation in children.SignificanceThis is the first study investigating the LPP during cognitive reappraisal in children with ADHD.



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Impact of volume-conducted potential in interpretation of cortico-cortical evoked potential: detailed analysis of high-resolution electrocorticography using two mathematical approaches

Publication date: Available online 30 January 2017
Source:Clinical Neurophysiology
Author(s): Seijiro Shimada, Naoto Kunii, Kensuke Kawai, Takeshi Matsuo, Yohei Ishishita, Kenji Ibayashi, Nobuhito Saito
ObjectiveCortico-cortical evoked potential (CCEP) has been utilized to evaluate connectivity between cortices. However, previous reports have rarely referred to the impact of volume-conducted potential (VCP) which must be a confounding factor of large potential around the stimulation site. To address this issue, we challenged the null hypothesis that VCP accounts for the majority of the recorded potential, particularly around the stimulation site.MethodsCCEP was recorded with high-density intracranial electrodes in 8 patients with intractable epilepsy. First, we performed regression analysis for describing the relationship between the distance and potential of each electrode. Second, we performed principal component analysis (PCA) to reveal the temporal features of recorded waveforms.ResultsThe regression curve, declining by the inverse square of the distance, fitted tightly to the plots (R²: 0.878 to 0.991) with outliers. PCA suggested the responses around the stimulation site had the same temporal features. We also observed the continuous declination over the anatomical gap and the phase reversal phenomena around the stimulation site.ConclusionsThese results were consistent with the null hypothesis.SignificanceThis study highlighted the risk of misinterpreting CCEP mapping, and proposed mathematical removal of VCP, which could lead to more reliable mapping based on CCEP.



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Magnetoencephalography with temporal spread imaging to visualize propagation of epileptic activity

Publication date: Available online 30 January 2017
Source:Clinical Neurophysiology
Author(s): Sumiya Shibata, Masao Matsuhashi, Takeharu Kunieda, Yukihiro Yamao, Rika Inano, Takayuki Kikuchi, Hisaji Imamura, Shigetoshi Takaya, Riki Matsumoto, Akio Ikeda, Ryosuke Takahashi, Tatsuya Mima, Hidenao Fukuyama, Nobuhiro Mikuni, Susumu Miyamoto
ObjectiveWe describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG).MethodsA three-dimensional grid of voxels covering the brain is created. The array-gain minimum-variance spatial filter is applied to an interictal spike to estimate the magnitude of the source and the time (Ta) when the magnitude exceeds a predefined threshold at each voxel. This calculation is performed through all spikes. Each voxel has the mean Ta (<Ta>) and spike number (Nsp), which is the number of spikes whose source exceeds the threshold. Then, a random resampling method is used to determine the cutoff value of Nsp for the statistically reproducible pattern of the activity. Finally, all the voxels where the source exceeds the threshold reproducibly shown on the MRI with a color scale representing <Ta>.ResultsFour patients with intractable mesial temporal lobe epilepsy (MTLE) were analyzed. In three patients, the common pattern of the overlap between the propagation and the hypometabolism shown by fluorodeoxyglucose-positron emission tomography (FDG-PET) was identified.ConclusionsTSI can visualize statistically reproducible patterns of the temporal and spatial spread of epileptic activity.SignificanceTSI can assess the statistical significance of the spatiotemporal pattern based on its reproducibility.



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Prescription drug monitoring programs, nonmedical use of prescription drugs, and heroin use: Evidence from the National Survey of Drug Use and Health

Publication date: June 2017
Source:Addictive Behaviors, Volume 69
Author(s): Mir M. Ali, William N. Dowd, Timothy Classen, Ryan Mutter, Scott P. Novak
In the United States, nonmedical prescription opioid use is a major public health concern. Various policy initiatives have been undertaken to tackle this crisis, including state prescription drug monitoring programs (PDMPs). This study uses the 2004–2014 National Survey of Drug Use and Health (NSDUH) and exploits state-level variation in the timing of PDMP implementation and PDMP characteristics to investigate whether PDMPs are associated with a reduction in prescription opioid misuse or whether they have the unintended consequence of increasing heroin use. In addition, the study examines the impact of PDMPs on the availability of opioids from various sources. The study finds no effect of PDMP status on various measures of nonmedical prescription opioid use (abuse, dependence, and initiation), but finds evidence of a reduction in the number of days of opioid misuse in the past year. The study also finds that implementation of PDMP was not associated with an increase in heroin use or initiation, but was associated with an increase in number of days of heroin use in the past year. Findings also suggest that PDMPs were associated with a significant decline in doctor shopping among individuals without increasing reliance on illegal sources (e.g., drug dealers, stealing, etc.) or social sources (friends or relatives) as a means of obtaining opioids. The President's FY2017 budget proposed the allocation of $1.1 billion in an effort to reduce prescription drug misuse, and highlighted the use of PDMPs as a policy tool. This study documents evidence that PDMPs might be having measurable impact.



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National Election Results: The Potential Impact on the ACC, Its Members, and Our Patients

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Correction

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Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials

AbstractBackground

Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy.

Objectives

The safety of alirocumab was evaluated in patients with at least 2 consecutive LDL-C values <25 or <15 mg/dl in the ODYSSEY program, with follow-up as long as 104 weeks.

Methods

Pooled data from 14 trials were analyzed (double-blind treatment 8 to 104 weeks; n = 3,340 alirocumab, n = 1,894 control [placebo or ezetimibe]; representing 4,029 [alirocumab] and 2,114 [control] double-blind patient-years' exposure).

Results

In alirocumab-treated patients, 839 (25.1%) achieved 2 consecutive LDL-C values <25 mg/dl, and 314 (9.4%) achieved <15 mg/dl. Baseline LDL-C was lower (mean 100.3 vs. 134.3 mg/dl) in patients with LDL-C <25 versus ≥25 mg/dl. Similar rates of adverse events occurred in patients achieving LDL-C <25 and <15 mg/dl (72.7% and 71.7%, respectively), compared with 76.6% in those who did not achieve LDL-C <25 mg/dl. Neurological and neurocognitive events were similar among the 3 groups. In a propensity score analysis, the rate of cataracts was higher in patients with LDL-C <25 mg/dl (2.6%) versus ≥25 mg/dl (0.8%; hazard ratio: 3.40; 95% confidence interval: 1.58 to 7.35). However, no difference in cataract incidence was observed between pooled alirocumab and control groups.

Conclusions

LDL-C levels <25 or <15 mg/dl on alirocumab were not associated with an increase in overall treatment-emergent adverse event rates or neurocognitive events, although cataract incidence appeared to be increased in the group achieving LDL-C levels <25 mg/dl. (Pooled analyses of already reported trials; NCT01288443, NCT01288469, NCT01266876, NCT01812707, NCT01507831, NCT01617655, NCT01623115, NCT01709500, NCT01644175, NCT01644188, NCT01730040, NCT01730053, NCT01644474, and NCT01709513)

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Reply: Percutaneous Revascularization of Left Main Disease: Could the Angiographic Follow-Up Improve the Survival?

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Low-Density Lipoprotein Cholesterol and the On-Target Effects of Therapy: How Low Is Too Low?

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Mode of Death in Heart Failure With Preserved Ejection Fraction

Abstract

Little is known about specific modes of death in patients with heart failure with preserved ejection fraction (HFpEF). Herein, the authors critically appraise the current state of data and offer potential future directions. They conducted a systematic review of 1,608 published HFpEF papers from January 1, 1985, to December 31, 2015, which yielded 8 randomized clinical trials and 24 epidemiological studies with mode-of-death data. Noncardiovascular modes of death represent an important competing risk in HFpEF. Although sudden death accounted for ~25% to 30% of deaths in trials, its definition is nonspecific; it is unclear what proportion represents arrhythmic deaths. Moving forward, reporting and definitions of modes of death must be standardized and tailored to the HFpEF population. Broad-scale systematic autopsies and long-term rhythm monitoring may clarify the underlying pathology and mechanisms driving mortal events. There is an unmet need for a longitudinal multicenter, global registry of patients with HFpEF to map its natural history.

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Outcomes of Intensive Blood Pressure Lowering in Older Hypertensive Patients

AbstractBackground

The 2014 Eighth Joint National Committee panel recommended a therapeutic target of systolic blood pressure (BP) <150 mm Hg in patients ≥60 years of age, a departure from prior recommendation of <140 mm Hg.

Objectives

This study assessed the efficacy and safety of intensive BP-lowering strategies in older (age ≥65 years) hypertensive patients.

Methods

The MEDLINE, Scopus, EMBASE, and Cochrane databases were searched for all relevant randomized controlled trials from 1965 through July 1, 2016. Cardiovascular (major adverse cardiovascular events [MACE], cardiovascular mortality, stroke, myocardial infarction, and heart failure), and safety (serious adverse events and renal failure) were evaluated. Random and fixed effects analysis were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs).

Results

We identified 4 high-quality trials involving 10,857 older hypertensive patients with a mean follow-up of 3.1 years. Intensive BP lowering was associated with a 29% reduction in MACE (RR: 0.71; 95% CI: 0.60 to 0.84), 33% in cardiovascular mortality (RR: 0.67; 95% CI: 0.45 to 0.98), and 37% in heart failure (RR: 0.63; 95% CI: 0.43 to 0.99) compared with standard BP lowering. Rates of myocardial infarction and stroke did not differ between the 2 groups. There was no significant difference in the incidence of serious adverse events (RR: 1.02; 95% CI: 0.94 to 1.09) or renal failure (RR: 1.81; 95% CI: 0.86 to 3.80) between the 2 groups. The fixed effects model yielded largely similar results, except for an increase in the risk of renal failure (RR: 2.03; 95% CI: 1.30 to 3.18) with intensive BP-lowering therapy.

Conclusions

In older hypertensive patients, intensive BP control (systolic BP <140 mm Hg) decreased MACE, including cardiovascular mortality and heart failure. Data on adverse events were limited, but suggested an increased risk of renal failure. When considering intensive BP control, clinicians should carefully weigh benefits against potential risks.

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Development of a Right Ventricular Outflow Tract Gradient During Upright Exercise: A Hemodynamic Observation

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Searching for the Optimal Blood Pressure Range in the Elderly: Are We There Yet?

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Reply: Medication Adherence and Cardiovascular Outcomes

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Isolated Subepicardial Right Ventricular Outflow Tract Scar in Athletes With Ventricular Tachycardia

AbstractBackground

High-level endurance training has been associated with right ventricular pathological remodeling and ventricular tachycardia (VT). Although overlap with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been suggested, the arrhythmogenic substrate for VTs in athletes is unknown.

Objectives

The goal of this study was to evaluate whether electroanatomic scar patterns related to sustained VT can distinguish exercise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathies.

Methods

In 57 consecutive patients (mean age 48 ± 16 years; 83% male) undergoing catheter ablation for scar-related right ventricular VT, 2 distinct scar distributions were identified: 1) scars involving the subtricuspid right ventricle in 46 patients (group A); and 2) scars restricted to the anterior subepicardial right ventricular outflow tract in 11 patients (group B).

Results

Definite ARVC or post-inflammatory cardiomyopathy was diagnosed in 40 (87%) of 46 group A patients but was not diagnosed in any patients in group B. All group B patients underwent intensive endurance training for a median of 15 h/week (interquartile range [IQR]: 10 to 20 h/week) for a median of 13 years (IQR: 10 to 18 years). The cycle lengths of scar-related VTs were significantly faster in group B patients (257 ± 34 ms vs. 328 ± 72 ms in group A; p = 0.003). Catheter ablation resulted in complete procedural success in 10 (91%) of 11 group B patients compared with 26 (57%) of 46 group A patients (p = 0.034). During a median follow-up of 27 months (IQR: 6 to 62 months), 50% of group A patients but none of the group B patients had a VT recurrence.

Conclusions

This study describes a novel clinical entity of an isolated subepicardial right ventricular outflow tract scar serving as a substrate for fast VT in high-level endurance athletes that can be successfully treated by ablation. This scar pattern may allow distinguishing exercise-induced arrhythmogenic remodeling from ARVC and post-inflammatory cardiomyopathy.

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Instructions For Authors

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Scar-Related Right Ventricular Tachycardias in Athletes: Too Much of a Good Thing?

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ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016 Appropriate Use Criteria for Coronary Revascularization in Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, and the Society of Thor

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Transcaval Access and Closure for Transcatheter Aortic Valve Replacement: A Prospective Investigation

AbstractBackground

Transcaval access may enable fully percutaneous transcatheter aortic valve replacement (TAVR) without the hazards and discomfort of transthoracic (transapical or transaortic) access.

Objectives

The authors performed a prospective, independently adjudicated, multicenter, single-arm trial of transcaval access for TAVR in patients who were ineligible for femoral artery access and had high or prohibitive risk of complications from transthoracic access.

Methods

A total of 100 patients underwent attempted percutaneous transcaval access to the abdominal aorta by electrifying a caval guidewire and advancing it into a pre-positioned aortic snare. After exchanging for a rigid guidewire, conventional TAVR was performed through transcaval introducer sheaths. Transcaval access ports were closed with nitinol cardiac occluders. A core laboratory analyzed pre-discharge and 30-day abdominal computed tomograms. The Society of Thoracic Surgeons predicted risk of mortality was 9.6 ± 6.3%.

Results

Transcaval access was successful in 99 of 100 patients. Device success (access and closure with a nitinol cardiac occluder without death or emergency surgical rescue) occurred 98 of 99 patients; 1 subject had closure with a covered stent. Inpatient survival was 96%, and 30-day survival was 92%. Second Valve Academic Research Consortium (VARC-2) life-threatening bleeding and modified VARC-2 major vascular complications possibly related to transcaval access were 7% and 13%, respectively. Median length of stay was 4 days (range 2 to 6 days). There were no vascular complications after discharge.

Conclusions

Transcaval access enabled TAVR in patients who were not good candidates for transthoracic access. Bleeding and vascular complications, using permeable nitinol cardiac occluders to close the access ports, were common but acceptable in this high-risk cohort. Transcaval access should be investigated in patients who are eligible for transthoracic access. Purpose-built closure devices are in development that may simplify the procedure and reduce bleeding. (Transcaval Access for Transcatheter Aortic Valve Replacement in People With No Good Options for Aortic Access; NCT02280824)

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Cardiac Outcomes With Pregnancy After Cardiotoxic Therapy for Childhood Cancer

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The Caval-Aortic Access for Performing TAVR: Pushing the Limits of Alternative Access for Nontransfemoral Candidates

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Percutaneous Revascularization of Left Main Disease: Could the Angiographic Follow-Up Improve the Survival?

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Randomized Comparison of Allogeneic Versus Autologous Mesenchymal Stem Cells for Nonischemic Dilated Cardiomyopathy: POSEIDON-DCM Trial

AbstractBackground

Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM).

Objectives

The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM.

Methods

Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers.

Results

There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05).

Conclusions

These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)

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Medication Adherence and Cardiovascular Outcomes

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Pars plana vitrectomy with 360° versus localized laser retinopexy in the management of retinal detachment with undetected breaks intraoperatively: a retrospective, comparative, interventional study

Abstract

The purpose of this study is to compare the efficacy of intraoperative 360° and localized laser retinopexy in 23-gauge pars plana vitrectomy (PPV) for rhegmatogenous retinal detachments (RRD) with undetected retinal breaks intraoperatively. This is a retrospective, comparative, interventional study. Medical records of 48 consecutive eyes with RRD of intraoperative undetected retinal breaks were reviewed. Nineteen patients (group I) received 360° laser retinopexy in PPV, while the remaining 29 patients (group II) underwent localized laser retinopexy. In group I, a triple row of confluent medium-white laser burns were placed posterior to the ora serrata. Anatomical and visual outcomes of the two groups were compared. The mean follow-up period was 13.46 ± 3.02 months. No significant difference was identified in baseline characteristics. A single-operation reattachment rate of 89.47% was achieved in group I, which was significantly higher than that of group II (55.17%, p = 0.01), and this trend was not weakened after adjustment for the confounding factor (odds ratio 0.15, p = 0.03). Moreover, greater improvement of postoperative best-corrected visual acuity was observed in group I. Significant complications sufficient to require further operation included proliferative vitreoretinopathy in 2 (4.17%) eyes and epiretinal membrane in 4 (8.33%) eyes. Three hundred sixty-degree laser retinopexy was associated with better anatomic and visual outcomes in RRD patients with unseen breaks intraoperatively, when compared with localized laser retinopexy in PPV.

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Photobiostimulation reverses allodynia and peripheral nerve damage in streptozotocin-induced type 1 diabetes

Abstract

For better evaluation of the efficacy of low-level laser therapy in treating painful diabetic neuropathy and in protecting nerve fiber damage, we conducted a study with type 1 diabetic rats induced by streptozotocin. It is well known that diabetic peripheral neuropathy is the leading cause of pain in those individuals who suffer from diabetes. Despite the efficacy of insulin in controlling glucose level in blood, there is no effective treatment to prevent or reverse neuropathic damage for total pain relief.Male Wistar rats were divided into saline, vehicle, and treatment groups. A single intraperitoneal (i.p.) injection of streptozotocin (STZ) (85 mg/kg) was administered for the induction of diabetes. The von Frey filaments were used to assess nociceptive thresholds (allodynia). Behavioral measurements were accessed 14, 28, 48, and 56 days after STZ administration. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 45 mWpk, beam spot size at target 0.13 cm², a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6,23 J/cm².The application of four sessions of low-level laser therapy was sufficient to reverse allodynia and protect peripheral nerve damage in diabetic rats.The results of this study indicate that low-level laser therapy is feasible to treat painful diabetic condition in rats using this protocol. Although its efficacy in reversing painful stimuli and protecting nerve fibers from damage was demonstrated, this treatment protocol must be further evaluated in biochemical levels to confirm its biological effects.

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Improving Drug-Like Properties of Insulin and GLP-1 via Molecule Design and Formulation and Improving Diabetes Management with Device & Drug Delivery

Publication date: Available online 30 January 2017
Source:Advanced Drug Delivery Reviews
Author(s): Sergei Pechenov, Himanshu Bhattacharjee, Daniel Yin, Sachin Mittal, Anand Subramony
There is an increased incidence of diabetes worldwide. The discovery of insulin revolutionized the management of diabetes, the revelation of glucagon-like peptide -1 (GLP-1) and introduction of GLP-1 mimetics to clinical practice was another breakthrough. Continued translational research resulted in better understanding of diabetes, which, in combination with cutting-edge biology, chemistry, and pharmaceutical tools, have allowed for the development of safer, more effective and convenient insulins and GLP-1s. Advances in self-administration of insulin and GLP-1 therapies with use of drug-device combination products have improved the outcomes of diabetes management and quality of life for diabetic patients. The synergies of insulin and GLP-1 actions have led to development of devices that can deliver both molecules simultaneously. New chimeric GLP-1-incretins and insulin-GLP-1-incretin molecules are also being developed. The objective of this review is to summarize molecular designs to improve the drug-like properties of insulin and GLP-1 and to highlight the continued advancement of drug-device combinations to improve diabetes management.

Graphical abstract

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Commentary on “Cranial Nerve Injury After Carotid Endarterectomy: Incidence, Risk Factors, and Time Trends”

Publication date: Available online 30 January 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): G.J. de Borst




http://ift.tt/2kk8DqS

Effectiveness of antiangiogenic drugs in glioblastoma patients: a systematic review and meta-analysis of randomized clinical trials

Publication date: Available online 30 January 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Giuseppe Lombardi, Ardi Pambuku, Luisa Bellu, Miriam Farina, Della Puppa Alessandro, Denaro Luca, Vittorina Zagonel
Backgroundglioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results. We performed a systematic review and a meta-analysis to clarify and evaluate their effectiveness in glioblastoma patients.Patients and methodswe searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from January 2006 to January 2016 in MEDLINE, WEB of SCIENCE, ASCO, ESMO and SNO databases.Resultsfourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) were identified including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056). Bevacizumab did not improve overall survival. Twelve trials (4113 patients) were analyzed for progression-free survival. Among antiangiogenic drugs, only bevacizumab demonstrated an improvement of progression-free survival (HR=0.63, p<0.001), both alone (HR=0.60, p=0.003) or in combination to chemotherapy (HR=0.63; p<0.001), both as first-line treatment (HR=0.70, p<0.001) or in recurrent disease (HR=0.52, p<0.001).Conclusionsantiangiogenic drugs did not improve overall survival in glioblastoma patients, either as first or second-line treatment, and either as single agent or in combination with chemotherapy. Among antiangiogenic drugs, only bevacizumab improved progression-free survival regardless of treatment line, both as single agent or in combination with chemotherapy



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Implementation of a New UPMC Gamma Knife Radiosurgery Quality Assurance Registry

Object: In this report, we discuss the development of a new, comprehensive, Health Insurance Portability and Accountability Act-compliant electronic quality assurance (QA) registry for Gamma Knife (GK) radiosurgery patients. This registry can be used to query outcomes, link with current hospital electronic medical records, and share data with future corporate or national professional society registries under development. Methods: A clinical task force comprising physicians and regulatory, legal, and information technology (IT) experts was created to define the nomenclature, regulatory requirements, hosting site, and required capabilities of the proposed system. A team of physicians and IT experts defined the clinical parameters and designed the query functions for the registry. Results: The UPMC GK Registry was established as a QA registry exempt from Institutional Review Board oversight. In order to facilitate subsequent query functions (analytics), data entry was created for 3 main categories: brain tumors, vascular malformations, and functional disorders. A Microsoft SQL-based database infrastructure was employed. Conclusions: We developed a new UPMC GK QA registry and successfully migrated our previous data on 13,000 patients into the registry. This simplified and user-friendly registry offers clinicians the opportunity to participate in national registries and to contribute to multicenter evidence-based outcome analyses.
Stereotact Funct Neurosurg 2017;95:49-59

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High tumor-infiltrating FoxP3+ T cells predict poor survival in estrogen receptor-positive breast cancer: a meta-analysis

Publication date: Available online 30 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Qian Feng, Qingping Yang, Linquan Wu, xiaojin Huang, Rongshou Wu, Shanshan Rao, Wenjun Liao, Yong Huang, Enliang Li
AimsTumor-infiltrating FoxP3⁺ T cells and FoxP3⁺ tumor cells have been reported in breast cancer (BC), which impaired immunity and promoted tumors progression. However, their prognostic value for survival in patients with breast BC remains controversial.MethodsA meta-analysis was performed. Original data included the hazard ratios (HR) of overall survival (OS), relapse-free survival and odds ratio (OR) in BC patients. We pooled HR/OR with 95% confidence intervals (CI) to estimate the hazard.ResultsThe overall survival of high tumor-infiltrating FoxP3⁺ T cells patients was lower than low tumor-infiltrating FoxP3⁺ T cells patients with estrogen receptor (ER)-positive (HR 0.86, 95% CI 0.77-0.96; P=0.009) but not ER-negative (HR 1.09, 95% CI 0.82-1.45; P=0.569) BC. And FoxP3⁺ tumor cells were not associated with the overall survival and recurrences of BC patients (P>0.05). In addition, a significant association was revealed between high tumor-infiltrating FoxP3⁺ T cells and grade (Ⅰ+Ⅱ/Ⅲ: OR 0.31, 95% CI 0.17-0.56; P<0.001), ER status (present: OR 2.39, 95% CI 1.51-3.76; P<0.001), HER2 status (present: OR 0.53, 95% CI 0.36-0.78; P=0.001), PR status (present: OR 1.88, 95% CI 1.31-2.71; P<0.001). And a significant association was revealed between positive FoxP3⁺ tumor cells and Nodal status (present: OR 0.48, 95% CI 0.23-0.97; P=0.04), grade (Ⅰ+Ⅱ/Ⅲ: OR 0.44, 95% CI 0.22-0.85; P=0.01), PR status (present: OR 2.37, 95% CI 1.54-3.36; P<0.001).ConclusionsHigh tumor-infiltrating FoxP3⁺ T cells were associated with a poorer prognosis for ER-positive BC, but not for ER-negative BC.



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Efficacy of Oral Moisturizing Jelly on Oral Health and Nutrition in Post-radiotherapy Head and Neck Cancer Patients

Conditions:   Cancer of Head Neck;   Radiation-Induced Xerostomia;   Dry Mouth
Interventions:   Dietary Supplement: Oral moisturizing jelly;   Other: Artificial saliva
Sponsors:   Dental Innovation Foundation Under Royal Patronage;   Mahidol University;   Srinakharinwirot University;   Ministry of Health, Thailand
Not yet recruiting - verified January 2017

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The Safety and Efficacy Test of Nutri-PEITC Jelly in Head and Neck Cancer Patients

Conditions:   Head and Neck Neoplasms;   Quality of Life;   Nutrition Related Cancer
Interventions:   Dietary Supplement: Nutri-jelly with PEITC;   Dietary Supplement: Nutri-jelly
Sponsors:   Dental Innovation Foundation Under Royal Patronage;   Mahidol University;   Srinakharinwirot University;   Ministry of Health, Thailand
Recruiting - verified January 2017

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Physiotherapy After Anterior Cervical Spine Surgery

Conditions:   Cervical Disc Disease;   Radiculopathy, Cervical
Interventions:   Other: Prescribed Physical Activity;   Other: Exercises with Internet support
Sponsor:   Linkoeping University
Not yet recruiting - verified January 2017

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Tocilizumab Promotes Regulatory T-cell Alleviation in STAT3 Gain-of-function−associated Multi-organ Autoimmune Syndrome

Publication date: Available online 30 January 2017
Source:Clinical Therapeutics
Author(s): Tawfik Khoury, Vered Molho-Pessach, Yuval Ramot, Abu Rmeileh Ayman, Orly Elpeleg, Neville Berkman, Abraham Zlotogorski, Yaron Ilan
PurposeSignal transducer and activator of transcription 3 is a member of a family of proteins involved in the regulation of inflammation, differentiation, proliferation, and survival of cells. Here we describe a 38-year-old male who has experienced gastrointestinal, dermatologic, pulmonary, and malignant manifestations.MethodsWhole-exome sequencing, validated by Sanger sequencing, was performed after extensive investigations.FindingsWhole-exome sequencing revealed a heterozygous missense mutation in the signal transducer and activator of transcription 3 gene, c.1261G>A (p.G421R). Fluorescence-activated cell sorting analysis of peripheral T lymphocytes revealed low levels of CD4⁺CD25⁺FoxP3 and CD8⁺CD25⁺FoxP3 regulatory T cells. After treatment with 2 cycles of tocilizumab, an interleukin-6 receptor antibody, a significant increase in the level of regulatory T cells was observed, accompanied by clinical improvement.ImplicationsThis case sheds light on the emerging role of signal transducer and activator of transcription 3 gain-of-function mutation in the pathogenesis of autoimmune diseases, and further addresses the therapeutic role of interleukin-6 blocker treatment in this syndrome.



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Rapid assessment methodology in NORM measurements from building materials of Uzbekistan

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): A.A. Safarov, A.N. Safarov, A.N. Azimov, I.G. Darby
Utilizing low cost NaI(Tl) scintillation detector systems we present methodology for the rapid screening of building material samples and the determination of their Radium Equivalent Activity (Raeq). Materials from Uzbekistan as a representative developing country have been measured and a correction coefficient for Radium activity is deduced. The use of the correction coefficient offers the possibility to decrease analysis times thus enabling the express measurement of a large quantity of samples. The reduction in time, cost and the use of inexpensive equipment can democratize the practice of screening NORM in building materials in the international community.



http://ift.tt/2kM7jdB

Radon in harvested rainwater at the household level, Palestine

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Issam A. Al-Khatib, Hamzeh Al Zabadi, Ghassan Saffarini
The main objective of this study was to assess Radon concentration in the harvested rainwater (HRW) at the household level in Yatta area, Palestine. HRW is mainly used for drinking as it is the major source of water for domestic uses due to water scarcity. Ninety HRW samples from the household cisterns were collected from six localities (a town and five villages) and Radon concentrations were measured. The samples were randomly collected from different households to represent the Yatta area. Fifteen samples were collected from each locality at the same day. RAD7 device was used for analysis and each sample was measured in duplicate. Radon concentrations ranged from 0.037 to 0.26 Bq/L with a mean ± standard deviation of 0.14 ± 0.06 Bq/L. The estimated annual effective radiation doses for babies, children and adults were all far below the maximum limit of 5 mSvy⁻¹ set by the National Council on Radiation Protection and Measurements.



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90Sr determination in water samples using Čerenkov radiation

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Nataša Todorović, Ivana Stojković, Jovana Nikolov, Branislava Tenjović
A procedure for the determination of ⁹⁰Sr in environmental water samples using Čerenkov radiation and low–level liquid scintillation counter Quantulus 1220 was applied and optimized. Low diffusion polyethylene vials, high performance glass counting vials and low potassium borosilicate glass vilas of 20 ml volume (all from PerkinElmer) were used in order to examine their potential effect on counting process. The derived efficiencies were 45.86(9)%, and a minimum detectable activity of 0.32 Bq l⁻¹ in a 20 ml polyethylene vial (20 ml water sample) has been achieved during 300 min of measurement. Environmental water samples might be colored and this will lead to color quenching, which one of the most important problems that affect Čerenkov is counting (Mosqueda et al., 2005). The sample channel ratio (SCR) method has been applied to correct this effect. The analytical procedures and measurement techniques were tested by participating in the IAEA-TEL-2015-03 world-wide proficiency test on determination of ⁹⁰Sr in water sample.



http://ift.tt/2kxwFwk

The re-evaluation of the 234mPa's 1001.03 keV gamma emission absolute intensity for the precise assessment of 238U

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Y.Y. Ebaid, A.E.M. Khater
In this study the commonly used f-value for the 1001.03 keV (0.835 ± 0.004%) energy transition of the ^234mPa was re-evaluated due to an obvious consistent overestimation of the ²³⁸U activity concentration. Different calibration protocols, samples' matrices and geometries, and gamma-ray spectrometers were exploited in order to assure the accuracy of the derived data. An average positive relative bias of about 24% from the currently used f-value was estimating leading to newly adopted f-value of 1.037 ± 0.052%. This newly suggested f-value will lead to an improvement in the accurate assessment process of the ²³⁸U using gamma-ray spectrometry in both environmental and nuclear safeguard fields.



http://ift.tt/2jL293T

Soil erosion control, plant diversity, and arthropod communities under heterogeneous cover crops in an olive orchard

Abstract

A 3-year experiment compared in an olive orchard the effect of different cover crops' composition on runoff, water erosion, diversity of annual plants, and arthropod communities which could provide an alternative to conventional management based on tillage (CT). The cover crops evaluated were a seeded homogeneous grass (GC), a seeded mix of ten different species (MC_seeded), and a non-seeded cover by vegetation naturally present at the farm after 20 years of mowing (MC_natural). The results suggest that heterogeneous cover crops can provide a viable alternative to homogeneous ones in olives, providing similar benefits in reducing runoff and soil losses compared to management based on bare soil. The reduction in soil loss was particularly large: 46.7 in CT to 6.5 and 7.9 t ha⁻¹ year⁻¹ in GC and MC_seeded, respectively. The heterogeneous cover crops resulted in greater diversity of plant species and a modification of the arthropod communities with an increased number of predators for pests. The reduction of the cost of implanting heterogeneous cover crops, improvement of the seeding techniques, and selection of species included in the mixes require additional research to promote the use of this practice which can deliver enhanced environmental benefits.

http://ift.tt/2jKDkFc

Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with 177 Lu-D OTATATE

Abstract

Purpose

Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs.

Methods

From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6–8 weeks), according to kidney and bone marrow parameters.

Results

Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered.

Conclusion

Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting.

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Erratum to: The need of standardization and of large clinical studies in an emerging indication of [18 F]FDG PET: the autoimmune encephalitis

http://ift.tt/2kKwRLW

Asymmetric relapse of an HIV-associated Kaposi sarcoma

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Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks

Abstract

During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although [¹⁸F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression.

http://ift.tt/2kKt0yy

Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success

Abstract

Purpose

Increased articular ^99mTc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy.

Methods

Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples.

Results

Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022).

Conclusions

Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.

http://ift.tt/2kLYbW8

The need of standardization and of large clinical studies in an emerging indication of [ 18 F]FDG PET: the autoimmune encephalitis

http://ift.tt/2kKBgyF

A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism (Niccolini and Politis, 2016)

http://ift.tt/2kLTAU3

**-Postprandial pancreatic [ 11 C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release

Abstract

Purpose

[S-methyl-¹¹C]-L-methionine ([¹¹C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [¹¹C]MET uptake.

Methods

Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [¹¹C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated.

Results

The uptake of [¹¹C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC₃₀ correlated with the SUVmax increment between 15 and 30 minutes (R² = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [¹¹C]MET. Total integrated SUVmax correlated with insulin AUC₆₀ (R² = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC₆₀ and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of ¹¹C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R² = 0.78, p < 0.0001).

Conclusion

Postprandial [¹¹C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.

http://ift.tt/2kKG2wf

A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism

http://ift.tt/2kM4mJI

Erratum to: Role of PET/CT in malignant pediatric lymphoma

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William C. Klingesmith III: The Mathematics and Biology of the Biodistribution of Radiopharmaceuticals: A Clinical Perspective

http://ift.tt/2kLQdN0

Computed-tomography-guided anatomic standardization for quantitative assessment of dopamine transporter SPECT

Abstract

Purpose

For the quantitative assessment of dopamine transporter (DAT) using [¹²³I]FP-CIT single-photon emission computed tomography (SPECT) (DaTscan), anatomic standardization is preferable for achieving objective and user-independent quantification of striatal binding using a volume-of-interest (VOI) template. However, low accumulation of DAT in Parkinson's disease (PD) would lead to a deformation error when using a DaTscan-specific template without any structural information. To avoid this deformation error, we applied computed tomography (CT) data obtained using SPECT/CT equipment to anatomic standardization.

Methods

We retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images.

Results

The SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups.

Conclusion

CT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.

http://ift.tt/2kKAEcc

“la synoviorthèse” can more than synovitis!

http://ift.tt/2kM4clW

FDG-PET imaging to detect and characterize infectious disorders; an unavoidable path for the foreseeable future

http://ift.tt/2kKAgKK

Intraindividual tumor heterogeneity in NET – Further insight by C-X-C motif chemokine receptor 4-directed imaging

http://ift.tt/2kM0rwx

Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

Abstract

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future.

http://ift.tt/2kKvUmP

Intra-lesional spatial correlation of static and dynamic FET-PET parameters with MRI-based cerebral blood volume in patients with untreated glioma

Abstract

Purpose

¹⁸F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV.

Methods

Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined.

Results

While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average.

Conclusions

Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.

http://ift.tt/2kM4rNL

Influence of blood-brain barrier permeability on O-(2- 18 F-fluoroethyl)-L-tyrosine uptake in rat gliomas

Abstract

Purpose

O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on ¹⁸F-FET uptake in two rat glioma models and one human xenograft model.

Methods

F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent ¹⁸F-FET PET followed by autoradiography. Time activity curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of ¹⁸F-FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of-Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD fluorescence. The membrane gaps of blood vessel endothelial tight junctions were measured using electron microscopy to visualize ultrastructural BBB alterations in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way ANOVAs.

Results

In Dex treated animals EBD extravasation was significantly reduced in 9L (P < 0.001) and U87 (P = 0.008) models and showed a trend in F98 models (P = 0.053). In contrast, no significant differences of ¹⁸F-FET uptake were observed between Dex treated animals and control group except a decrease of the TBR in the 9L tumor model in PET (P < 0.01). Ultrastructural evaluation of tumor blood vessel endothelia revealed significant reduction of the cleft diameter between endothelial cells after Dex treatment in F98 model (P = 0.010).

Conclusion

Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of ¹⁸F-FET uptake were noted in this experimental study. Thus, ¹⁸F-FET uptake in gliomas appears to be widely independent of the permeability of the BBB.

http://ift.tt/2kKABNy

The prognostic and predictive value of sstr 2 -immunohistochemistry and sstr 2 -targeted imaging in neuroendocrine tumors

Abstract

Purpose

Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr₂) in neuroendocrine tumors (NETs).

Methods

We established a tissue microarray and imaging database from NET patients that received sstr₂-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr₂-imaging and sstr₂-immunohistochemistry.

Results

We included a total of 279 patients. In these patients, sstr₂-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 – 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr₂-expression on immunohistochemistry correlated with tumor uptake on sstr₂-imaging (n = 170, p < 0.001); however, sstr₂-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 – 56 %, p = 0.025). Sstr₂-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93).

Conclusions

Our results suggest sstr₂ as an independent prognostic marker in NETs. Sstr₂-immunohistochemistry correlates with sstr₂-imaging; however, sstr₂-imaging is more accurate for determining the individual prognosis.

http://ift.tt/2kLYeRS

Ordered titanium templates functionalized by gold films for biosensing applications – Towards non-enzymatic glucose detection

Publication date: 1 May 2017
Source:Talanta, Volume 166
Author(s): Katarzyna Grochowska, Mariusz Szkoda, Jakub Karczewski, Gerard Śliwiński, Katarzyna Siuzdak
Recently, metal nanostructures evoke much interest due to application potential in highly sensitive detectors in biochemistry and medical diagnostics. In this work we report on preparation and characteristics of thin (1–100nm) Au films deposited onto highly ordered structured titanium templates for SERS (Surface Enhanced Raman Spectroscopy) and electrochemical sensing. The Ti templates are formed by selective removal of TiO2 nanotubes out of as-anodized titanium substrate. The surface of the obtained material reproduce precisely the bottom layer of the nanotubes and consists of a uniformly distributed dimples with diameter of ~100nm. For all structures covered with Au films the measured average SERS signal is markedly higher than the one observed for bare Ti templates. This is due to strong electromagnetic field in the vicinity of the film grains. Moreover, such nanostructured gold surface exhibits also attractive electrochemical and electrocatalytic properties, which should be attributed to enhancement of the electron transfer at the Au-Ti interface formed without any linker molecules. It is shown that prepared material can be used as an enzyme-free sensor for glucose detection in air-saturated neutral media especially in case of low sugar concentrations present in human body liquids, such as saliva, sweat and interstitial fluid.

Graphical abstract

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Role of two-sided crosstalk between NO and H2S on improvement of mineral homeostasis and antioxidative defense in Sesamum indicum under lead stress

Publication date: May 2017
Source:Ecotoxicology and Environmental Safety, Volume 139
Author(s): Rayhaneh Amooaghaie, Faezeh zangene-madar, Shekoofeh Enteshari
H2S and NO are two important gasotransmitters that modulate stress responses in plants. There are the contradictory data on crosstalk between NO and H2S in the studies. Hence, in the present study, the role of interplay between NO and H2S was assessed on the Pb tolerance of Sesamum indicum using pharmacological and biochemical approaches. Results revealed that Pb stress reduced the plant growth and the content of photosynthetic pigments and Fv/Fm ratio, increased the lipid peroxidation and the H2O2 content, elevated the endogenous contents of nitric oxide (NO), H2S and enhanced the activities of antioxidant enzymes (except APX). Additionally, concentrations of most mineral ions (K, P, Mg, Fe, Mn and Zn) in both shoots and roots decreased. Pb accumulation in roots was more than it in shoots. Both sodium hydrosulfide (NaHS as a donor of H2S) and sodium nitroprusside (SNP as an NO donor) improved the plant growth, the chlorophyll and carotenoid contents and PSII efficiency, reduced oxidative damage, increased the activities of antioxidant enzymes and reduced the proline content in Pb-stressed plants. Furthermore, both NaHS and SNP significantly restricted the uptake and translocation of Pb, thereby minimizing antagonistic effects of Pb on essential mineral contents in sesame plants. NaHS increased the NO generation and many NaHS-induced responses were completely reversed by cPTIO, as the specific NO scavenger. Applying SNP also enhanced H2S release levels in roots of Pb-stressed plants and only some NO-driven effects were partially weakened by hypotuarine (HT), as the scavenger of H2S.These findings proposed for the first time that two-sided interplay between H2S and NO might confer an increased tolerance to Pb stress via activating the antioxidant systems, reducing the uptake and translocation of Pb, and harmonizing the balance of mineral nutrient.



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Ginkgo biloba exocarp extracts induces apoptosis in Lewis lung cancer cells involving MAPK signaling pathways

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Chenjie Cao, Ya Su, Dongdong Han, Yanqi Gao, Menghua Zhang, Huasheng Chen, Aihua Xu
Ethnopharmacological relevanceA fruit of Ginkgo biloba L. is known as Ginkgo nuts. It is an edible traditional Chinese medicine, and could be used for the treatment of cancer thousands of years ago in China. The extracts prepared from the exocarp of Ginkgo biloba (Ginkgo biloba exocarp extracts, GBEE) has the effects of anti-cancer, immune promotion, anti-aging and etc.Aim of studyTo study the effects of GBEE inducing apoptosis in Lewis lung cancer (LLC) cells and the role of Mitogen-activated protein kinase(MAPK) signaling pathways in it.Materials and methodsThe LLC solid tumor model was established in C57BL/6J mice. The tumor-bearing mice were randomly divided into 5 groups. A normal control group without tumor cells was established additionally. There were 10 mice in each group, and they were dosed 24h after inoculation. The GBEE (50, 100, 200mg/kg b.w.) groups were dosed by intragastric gavage (i.g.). The mice in positive control group were intraperitoneal (i.p.) injected with cyclophosphamide (CPA) at a dose of 20mg/kg (b.w.). The model control group and the normal control group were both given normal saline (NS) by i.g.. All the groups were dosed at a volume of 0.1mL/10g (b.w.), once a day for 18d. The day after the last administration, the transplanted tumors was stripped and weighed, and the inhibition rate was calculated. In vitro experiments, MTT method was applied to detect the effects of GBEE on LLC cells and primary cultured mouse lung cells. Annexin V-FITC/PI method was used to detect the apoptosis rate of LLC cells. Rhodamine 123 method was used to detect the Mitochondrial transmembrane potential (MTP). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the levels of Fas mRNA. Western Blot was used to detect the expression of Bax, Bcl-2, Cyt C, cleaved Caspase-3 and MAPK proteins in the corresponding parts of LLC cells.ResultsGBEE (50–200mg/kg) inhibited the growth of LLC transplanted tumors with a dose-effect relationship. GBEE (5–160µg/mL) inhibited the proliferation of LLC cells in vitro with the half maximal inhibitory concentration (IC50) value of 162.43µg/mL, while it had no significant inhibitory effects on the primary cultured mouse lung cells. After GBEE (10, 20 and 40µg/mL) acted on the LLC cells, the apoptosis rate was increased and the MTP was decreased. The ratio of Bax/Bcl-2 was increased in the cells. Meanwhile, it also promoted the translocation of Bax/Bcl-2 in mitochondrial membrane and the release of Cyt C from mitochondria to cytosol. In addition, it up-regulated the cleaved-Caspase-3 protein expression. The mRNA levels of Fas and the protein levels of Fas, FasL and p-p38 in the cells were both increased. The levels of p-ERK1/2 and p-JNK1/2 protein were down-regulated but the p38, ERK1/2 and JNK1/2 were not significantly changed.ConclusionsGBEE induces apoptosis in LLC cells via mitochondrial-mediated intrinsic pathway and death receptor-mediated extrinsic pathway, which may be closely relevant to the regulation of MAPK signaling pathways.

Graphical abstract

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Noni (Morinda citrifolia L.) fruit juice reverses age-related decline in neural-immune interactions in the spleens of old F344 rats

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Uday P. Pratap, Lalgi Hima, Hannah P. Priyanka, Srinivasan ThyagaRajan
Ethnopharmacological relevanceVarious parts of the tropical plant, Morinda citrifolia L. (Noni), have been widely used in traditional medicine in South and Southeast Asia for several centuries. The therapeutic effects of the noni are believed to be mediated through several phytochemicals such as anthraquinones, iridoid, fatty acid glycosides, alcohols, etc.Aim of the studyThe aim of the study is to investigate the effects of Morinda citrifolia fruit juice (noni fruit juice; NFJ) on neural-immune interactions through the involvement of intracellular signaling pathways both in vitro and in vivo in the splenic lymphocytes of young and old male F344 rats.Material and methodsIn the in vitro study, splenocytes from young and old F344 rats were isolated and treated with 0.0001–1% concentrations of NFJ for a period of 24h, while in the in vivo study, old F344 rats were orally administered (5ml/kg body weight) with NFJ (5%, 10% and 20%) twice daily for 60 days. After the treatment period, concanavalin A (Con A)-induced lymphocyte proliferation, cytokines (IL-2, IFN-γ, IL-6, and TNF-α) production, expression of tyrosine hydroxylase (p-TH), nerve growth factor (NGF), m-TOR, IκB-α, p-NF-κB (p50 and p65), p-ERK, p-Akt, p-CREB and lipid peroxidation, protein carbonyl formation, nitric oxide (NO) production were examined in the splenocytes.ResultsIn vitro NFJ incubation of splenic lymphocytes increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and expression of p-ERK, p-Akt, and p-CREB in young and old rats. In vivo treatment of old rats with NFJ increased lymphoproliferation, IL-2 and IFN-γ production, the expression of p-TH, NGF, and NO production, and suppressed IL-6 production, lipid peroxidation, protein carbonyl formation, and the expression of IκB-α and p-NF-κB (p50) in the splenocytes.ConclusionTaken together, these results suggest that Morinda citrifolia fruit juice enhanced neural-immune interactions and cell survival pathways while inhibiting inflammatory processes that may be useful in the treatment of age-associated diseases.

Graphical abstract

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Anti-inflammatory and toxicological evaluation of essential oil from Piper glabratum leaves

Publication date: 23 February 2017
Source:Journal of Ethnopharmacology, Volume 198
Author(s): Lidiane Schultz Branquinho, Joyce Alencar Santos, Claudia Andrea Lima Cardoso, Jonas da Silva Mota, Ubirajara Lanza Junior, Cândida Aparecida Leite Kassuya, Arielle Cristina Arena
Ethnopharmacological relevanceAlthough some of the species of the genus Piper exhibit interesting biological properties, studies on Piper glabratum Kunth are very limited.Aim of the studyThis study investigated the anti-inflammatory activity and the toxicological profile of the essential oil from P. glabratum leaves (OEPG) in mice.Materials and MethodsThe acute toxicity of OEPG was evaluated by oral administration to female mice as single doses of 500, 1000, 2000 or 5000mg/kg/body weight. In the subacute toxicity test, the females received 500 or 1000mg/kg/body weight of OEPG for 28 days. The anti-inflammatory potential of OEPG was evaluated using four models including pleurisy, edema, mechanical hyperalgesia and cold allodynia models in mouse paws.ResultsNo clinical signs of toxicity were observed in animals after acute treatment, which suggested that the LD50 is greater than 5000mg/kg. The subacute exposure to OEPG produced no significant changes in the hematological or biochemical parameters. Similarly, the histology of the organs and the estrus cycle displayed no marked alterations. OEPG exhibited anti-inflammatory activity as indicated by inhibition of the leukocyte migration (100, 300, 700mg/kg) and the protein extravasation into the pleural exudates (700mg/kg). After intraplantar injection of carrageenan, it was observed that the 700mg/kg dose of OEPG reduced edema formation and decreased the sensitivity to mechanical stimulation and cold.ConclusionsThese results demonstrate the anti-inflammatory potential of the essential oil of P. glabratum leaves in the absence of toxicity in female mice.

Graphical abstract

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The neurocognitive basis of borrowed context information

Publication date: Available online 30 January 2017
Source:Cortex
Author(s): Meagan O'Neill, Rachel A. Diana
Falsely remembered items can be accompanied by episodic context retrieval. This finding is difficult to explain because there is no episode that binds the remembered item to the experimenter-controlled context features. The current study examines the neural correlates of false context retrieval when the context features can be traced to encoding episodes of semantically-similar items. Our neuroimaging results support a "dissociated source" mechanism for context borrowing in false memory. We found that parahippocampal cortex (PHc) activation, thought to indicate context retrieval, was greater during trials that involved context borrowing (an incorrect, but plausible source decision) than during baseline correct context retrieval. In contrast, hippocampal activation, thought to indicate retrieval of an episodic binding, was stronger during correct source retrieval than during context borrowing. Vivid context retrieval during false recollection experiences was also indicated by increased activation in visual perceptual regions for context borrowing as compared to other incorrect source judgments. The pattern of findings suggests that context borrowing can arise when unusually strong activation of a semantically-related item's contextual features drives relatively weak retrieval of the associated episodic binding with failure to confirm the item information within that binding. This dissociated source retrieval mechanism suggests that context-driven episodic retrieval does not necessarily lead to retrieval of specific item details. That is, source information can be retrieved in the absence of item memory.



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Exploiting microRNAs As Cancer Therapeutics

Abstract

miRNAs are a well-studied class of non-coding RNAs, predominantly functioning to down-regulate gene expression from messenger RNA (mRNA) in a targeted manner by binding to complementary sequence on the target mRNA. Many miRNAs have been linked to the development of hallmarks of cancer. miRNAs represent valuable therapeutic targets to exploit in the search for novel cancer treatments, due to their ubiquitous expression and their ability to tightly regulate the gene expression of a whole host of genes and pathways in a single hit. The miRNA system may be harnessed for therapeutic use either through replacement of tumour suppressive miRNAs lost in cancer, or through inhibition of oncogenic miRNAs overexpressed in cancer. There is a large body of work investigating optimal systemic and localised delivery strategies, and while miRNA therapeutics show promise, it is clear that further developments to delivery strategies may be required to allow safe translation of miRNAs to the clinic. The information gleaned from miRNA signatures as biomarkers is already proving invaluable in the fight to better understand and treat individual tumours, and there is great promise to the applications of these small, but mighty molecules in the future of cancer therapeutics.

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Topical diphencyprone for Kaposi sarcoma

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Hyaluronic acid filler combined with antioxidants for infraorbital rejuvenation: Report of two cases

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Efficacy and safety of topical calcipotriol in management of alopecia areata: A pilot study

Abstract

Reports have highlighted serum vitamin D deficiency and reduced 1,25-dihydroxyvitamin D(3) receptors(VDR) expression on hair follicles of alopecia areata(AA) patients. Very few studies have demonstrated efficacy of topical calcipotriol (vitamin D analogue) in AA. We intended to study the efficacy of calcipotriol lotion 0.005% in AA and correlate its outcome with serum vitamin D levels. We conducted a prospective study, in which 22 patients with AA were treated with calcipotriol lotion 0.005% twice daily for 3 months. Clinico-epidemiological parameters including severity of AA and SALT score were calculated at baseline and at 12 weeks. Hair regrowth was assessed monthly at 4, 8, 12 weeks. Serum vitamin D levels were measured at baseline. After 12 weeks of treatment, hair regrowth was observed in 13 (59.1%) patients. Mean period for onset of disease stabilization and hair regrowth was 4 weeks and 4.21± 2.13 weeks, respectively. Among these 13 patients, SALT₅₀ and SALT₁₀₀ was observed in 6(46.2%) and 2(9%) patients, respectively. Response to treatment was better in patients with lower vitamin D levels (p < .009). Topical calcipotriol can be an alternative treatment in AA and it could prove to be more useful in patients who are vitamin D deficient.

http://ift.tt/2kipmeF

Tranexamic acid in treatment of melasma: A comprehensive review of clinical studies

Abstract

Melasma is a human melanogenesis dysfunction that results in localized, chronic acquired hyperpigmentation of the skin. It has a significant impact on appearance, causing psychosocial and emotional distress, and reducing the quality of life of the affected patients. Tranexamic acid (TA) is a plasmin inhibitor used to prevent abnormal fibrinolysis to reduce blood loss and exerts its effect by reversibly blocking lysine binding sites on plasminogen molecules, thus inhibiting plasminogen activator (PA) from converting plasminogen to plasmin. As plasminogen also exists in human epidermal basal cells and cultured human keratinocyte are known to produce PA, there is basic rationale that TA will affect keratinocyte function and interaction. A thorough literature review indicates that while TA is used through various route of administration including oral, topical, and intradermal injection and as adjutant therapy with laser to treat melasma, its efficacy is not established adequately. Further studies are needed to clarify the role of TA in treatment of melasma.

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Efficacy of topical tofacitinib, a Janus kinase inhibitor, in the treatment of plaque psoriasis

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Anti-HCV for porphyria cutanea tarda

http://ift.tt/2kiD4y7

Use of topical sirolimus in the management of multiple familial trichoepitheliomas

Abstract

The management of trichoepitheliomas is challenging, especially in children. This challenge is exemplified in patients with multiple trichoepitheliomas who present with progression of lesion count and size despite treatment with current strategies, including CO₂ laser and surgery. We present the novel use of topical 1% sirolimus cream in two siblings with multiple facial trichoepitheliomas; one was treated with a combination of CO₂ laser ablation and topical sirolimus, and the other was treated with topical sirolimus alone. Both siblings had a reduction in the growth of new lesions with no reported side effects. This is the first report demonstrating that topical sirolimus, either in combination with CO₂ laser or alone, can be a promising treatment for trichoepitheliomas.

http://ift.tt/2juaWUn

An MR-compatible gyroscope-based arm movement tracking system

Publication date: Available online 29 January 2017
Source:Journal of Neuroscience Methods
Author(s): S.Iman Shirinbayan, Jochem W. Rieger
BackgroundFunctional magnetic resonance imaging is well suited to link neural population activation with movement parameters of complex natural arm movements. However, currently existing MR-compatible arm tracking devices are not constructed to measure arm joint movement parameters of unrestricted movements. Therefore, to date most research focuses on simple arm movements or includes very little knowledge about the actual movement kinematics.New methodWe developed a low cost gyroscope-based arm movement tracking system (GAMTS) that features MR-compatibility. The system consists of dual-axis analogue gyroscopes that measure rotations of upper and lower arm joints. After MR artifact reduction, the rotation angles of the individual arm joints are calculated and used to animate a realistic arm model that is implemented in the OpenSim platform. The OpenSim platform can then provide the kinematics of any point on the arm model.ResultsIn order to demonstrate the capabilities of the system, we first assessed the quality of reconstructed wrist movements in a low-noise environment where typical MR-related problems are absent and finally, we validated the reconstruction in the MR environment.Comparison with existing methodsThe system provides the kinematics of the whole arm when natural unrestricted arm movements are performed inside the MR-scanner.ConclusionThe GAMTS is reliably capable of reconstructing the kinematics of trajectories and the reconstruction error is small in comparison with the movement induced variation of speed, displacement, and rotation. Moreover, the system can be used to probe brain areas for their correlation with movement kinematics.



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The Plastic Surgery Compass: Navigating the Reconstructive Ladder in the Personalized Health Care Era

Summary: The reconstructive ladder and the reconstructive elevator have withstood the test of time as didactic tools for resident education. Over time, many alternative models have been suggested to incorporate the technological advances in plastic surgery, but none of them have focused on the patient. Changes in practice and the trend toward personalized health care demand a 360-degree evaluation and solution of surgical problems incorporating patient-specific characteristics. We, therefore, suggest the concept of the plastic surgery compass to navigate the ladder.

http://ift.tt/2e2nno9

Metallurgical-based prediction of stress-temperature induced rapid heating and cooling phase transformations for high speed machining Ti-6Al-4V alloy

Publication date: 5 April 2017
Source:Materials & Design, Volume 119
Author(s): Qingqing Wang, Zhanqiang Liu, Dong Yang, Aziz Ul Hassan Mohsan
Local phase transformations of materials during mechanical machining influence the variation of surface integrity directly. The aim of this work is to investigate the relationship between cutting parameters and phase transformations during high speed machining (HSM) of Ti-6Al-4V. Rapid heating and cooling phase transformation models are firstly proposed based on phase transformation dynamics. Then, the proposed models are implemented into the Ti-6Al-4V cutting simulation model as a user subroutine of Abaqus/Explicit. The simulated results indicate that, in the chip formation process, β phase volume fraction increases from 8% to 90% in the serrated chips and the machined surface at the cutting speed range of 50–600m/min. In the rapid cooling process, the ratio of the transformed α" phase is about 4%. Finally, comparisons of the simulated results and high speed cutting experiments indicate that the developed models can precisely predict the phase transformations during HSM Ti-6Al-4V. The results help to get deeper insights into understanding the phase transformation mechanisms during HSM o Ti-6Al-4V. The research can also provide an instruction for optimizing the cutting parameters to control the surface integrity in machining of Ti-6Al-4V.

Graphical abstract

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The effects of hydroporation on melasma with anti-aging cocktail

Summary

Background

Jet-M is a device for epidermal peeling and is used to deliver substances by spraying air and microdroplets. Previously, a case was treated with a mixed solution of copper-GHK, oligo-hyaluronic acid, Rhodiola extract, tranexamic acid, and β-glucan. The results showed significant improvement of aged skin.

Aims

This study was conducted to evaluate the effects of hydroporation on melasma with the formulation in a small group of volunteers.

Methods

Clinical effects were evaluated by both subjective and objective methods including melanin index (MI) and erythema index (EI) measurement.

Results

Clinically, pigmentation and erythema were relieved and also both MI and EI decreased. Histopathologic observation revealed that type IV collagen and procollagen were increased in the upper dermis. Furthermore, the number of p63-positive cells is increased along the basement membrane. These results all suggest that hydroporation with GHR formulation induced anti-aging effects by reconstruction of extracellular matrix.

Conclusion

These findings suggest that the treatment may have depigmenting effects and erythema decreasing effects by enhancing the microenvironment of the skin.

http://ift.tt/2jIcVHS

Acne RA-1,2, a novel UV-selective face cream for patients with acne: Efficacy and tolerability results of a randomized, placebo-controlled clinical study

Summary

Background

General skincare measures such as the use of moisturisers and products containing adequate photoprotection are important components of acne patients' management to complement the pharmacological regimen. Acne RA-1,2 is a novel dermato-cosmetic product which contains selective photofilters and active ingredients against the multifactorial pathophysiology of acne.

Objectives

To evaluate the tolerability of Acne RA-1,2 and its effect on the clinical signs of acne.

Methods

This double-blind, placebo-controlled study randomized 40 adult patients with 10-25 comedones per half face to once-daily application of Acne RA-1,2 or placebo for 8 weeks. Evaluations after 4 and 8 weeks included the number of comedones, transepidermal water loss (TEWL), sebum production, and tolerability.

Results

In the Acne RA-1,2 group, there was a significant 35% decrease in the mean number of comedones from 26 at baseline to 17 at Week 8 (P<.001), a 7% significant reduction in TEWL (9.32 to 8.66 g/h/m²; P<.001), and a 24% significant reduction in sebum production (154.8 to 117.6 μg/cm²; P<.001). The reductions in TEWL and sebum production were significantly greater than those in the placebo group at Weeks 4 and 8 (P<0.05). There were no adverse events.

Conclusions

Acne RA-1,2 was well tolerated and effective at reducing comedones and sebum production and improving epidermal barrier function. These results suggest that Acne RA-1,2 is useful against acne-prone facial skin, particularly as it targets sebum production, which topical pharmacological acne therapies do not address.

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Glassy dynamics in polymers

Publication date: Available online 29 January 2017
Source:Materials Today
Author(s): David Bradley




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The recent structure-based coarse graining of polymer melts using PRISM theory does not give thermodynamic consistency

Publication date: 24 February 2017
Source:Polymer, Volume 111
Author(s): Qiang Wang, Delian Yang
The full thermodynamic consistency claimed by Guenza and co-workers in their recent papers (J. McCarty et al., Macromolecules 45 (2012) 8482; A. J. Clark et al., Phys. Rev. Lett. 109 (2012) 168301; and A. J. Clark et al., J. Chem. Phys. 139 (2013) 124906), where they performed structure-based coarse graining of homopolymer melts using the polymer reference interaction site model theory, directly contradicts the well-established and widely cited finding by several research groups. In this Communication, we clearly showed that (1) the full thermodynamic consistency claimed by Guenza and co-workers is simply due to the (incorrect) approximations used in their analytical derivation, (2) none of their criticisms on our work (D. Yang, Q. Wang, J. Chem. Phys. 142 (2015) 054905) given in their Comment (A. J. Clark et al., J. Chem. Phys. 143 (2015) 067101) is valid, and (3) the simulation-free coarse-graining strategy presented in our work is crucially different from the coarse-graining approach in their recent papers.

Graphical abstract

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Hybrid peptides in the landscape of drug discovery

Publication date: Available online 29 January 2017
Source:Peptides
Author(s): Daniel Fourmy




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Evaluation of cognitive performance in professional divers by means of event-related potentials and neuropsychology

Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Mehmet Ergen, Atilla Uslu, Ozlem Caglar, Sukriye Akca-Kalem, Maide Cimsit, Hakan Gurvit
ObjectiveWe investigated whether professional air diving with no decompression illness causes any long-term changes in cognitive functions.MethodsThe all-male participants consisted of 18 healthy control (HC) volunteers and 32 divers. Divers were divided into two subgroups as moderate exposure group, Divers-I (DI) and extensive exposure group, Divers-II (DII). Participants were administered a comprehensive neuropsychological battery and event-related potentials (ERPs) were recorded while they performed auditory oddball task and visual continuous performance test (CPT).ResultsP3 waves in oddball and CPT were significantly attenuated and peak latencies were prolonged in both diver groups compared with HC. Amplitude decrements in CPT P3 were graded with respect to level of diving exposure. Neuropsychologically, DII group displayed significantly poorer performance than HC and DI groups in measures of visuo-constructional and visual long-term memory tests. DI group performed better than HC group in some measures of planning ability.ConclusionsMost of the changes in neurophysiological measures and poorer neuropsychological performance were found in DII group, and this might be interpreted as a red flag for the reflection of the slowly progressing deleterious effects of silent bubbles in brain function.SignificanceThis study reports impairments in certain neuropsychological measures and apparent neurophysiological markers pointing to slow cognitive decline referring to long-term effects of diving.



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Corticokinematic coherence as a new marker for somatosensory afference in newborns

Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Eero Smeds, Sampsa Vanhatalo, Harri Piitulainen, Mathieu Bourguignon, Veikko Jousmäki, Riitta Hari
ObjectiveSomatosensory evoked potentials have high prognostic value in neonatal intensive care, but their recording from infants is challenging. Here, we studied the possibility to elicit cortical responses in newborns by simple passive hand movements.MethodsWe examined 13 newborns (postnatal age 1–46 days) during clinically indicated 19-channel electroencephalography (EEG) recordings in the neonatal intensive care unit; EEG indications included birth asphyxia and suspected epileptic seizures. The experimenter moved the infant's wrist or fingers at 1 or 2 Hz for 5–10 min, separately on both sides. We measured movement kinematics with an accelerometer attached to the infant's hand, and computed coherence between the EEG and acceleration signals (corticokinematic coherence, CKC).ResultsStatistically significant CKC (amplitude 0.020–0.511) with characteristic scalp topography was observed in all infants at twice the movement frequency. CKC was contralaterally dominant on the central scalp (median laterality index 0.53 for right-hand and –0.63 for left-hand movements).ConclusionsPassive movements elicit cortical responses that can be readily observed in clinical EEG recordings from newborns in the intensive care environment.SignificanceCKC is a novel, noninvasive marker for the somatosensory system. Its robustness and practical ease make it attractive for bedside assessment of neurologically compromised newborns.



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Sharpening a classic scalpel to face the growth of Alzheimer’s dementia

Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Tarek K. Rajji




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Status Epilepticus after Cardiac Arrest: Some Strides

Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): G. Bryan Young




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Peripheral nerve ultrasonography in patients with transthyretin amyloidosis

Publication date: Available online 29 January 2017
Source:Clinical Neurophysiology
Author(s): Simon Podnar, Stayko Sarafov, Ivailo Tournev, Gregor Omejec, Janez Zidar
ObjectiveTo systematically study peripheral nerve morphology in patients with transthyretin (TTR) amyloidosis and TTR gene mutation carriers using high-resolution ultrasonography (US).MethodsIn this prospective cross-sectional study we took a structured history, performed neurological examination, and measured peripheral nerve cross-sectional areas (CSAs) bilaterally at 28 standard locations using US. Demographic and US findings were compared to controls.ResultsPeripheral nerve CSAs were significantly larger in 33 patients with familial amyloid polyneuropathy (FAP) compared to 50 controls, most dramatically at the common entrapment sites (median nerve at the wrist, ulnar nerve at the elbow), and in the proximal nerve segments (median nerve in the upper arm, sciatic nerve in the thigh). Findings in 21 asymptomatic TTR gene mutation carriers were less marked compared to controls, with CSAs being larger only in the median nerve in the upper arm. Nerve CSAs correlated with abnormalities on nerve conduction studies.ConclusionUsing US, we confirmed previous pathohistological and imaging reports in FAP of the most pronounced peripheral nerve thickening in the proximal limb segments.SignificanceSimilar to US findings in diabetic and vasculitic neuropathies these predominantly proximal locations of nerve thickening may be attributed to ischaemic nerve damage caused by poor perfusion in the watershed zones along proximal limb segments.



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