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Dose escalation of Stereotactic Body Radiotherapy (SBRT) for locally advanced unresectable pancreatic cancer patients with CyberKnife: protocol of a phase I study
No full textAbstract
Background
Dose escalation of SBRT for locally advanced pancreatic cancer patients had been reported in several studies in one or three fractions, and phase I protocol was developed to investigate the maximum tolerated dose with CyberKnife for locally advanced unresectable pancreatic cancer patients in five fractions.
Methods
The study is designed as a mono-center phase I study. The primary endpoint is to determine the maximum tolerated dose by frequency of III/IV GI (gastrointestinal) toxicity. Adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Doses of 7\ua0Gy, 7.5\ua0Gy, 8\ua0Gy, 8.5\ua0Gy, 9\ua0Gy, 9.5Gy x 5 respectively would be delivered while meeting with normal tissue constraints. A minimum of three patients will be included for each dosage level. And an interval is 4\ua0weeks from the first patient treatment to the next patient treatment at each dose level. The maximal tolerated dose will be defined as the dose for which at least two patients in three, or at least three patients in nine, will present with a limiting toxicity.
Discussion
Since the dose and fractions of SBRT treatment for locally advanced pancreatic cancer patients are still unknown, we propose to conduct a Phase I study determining the maximum tolerated dose of CyberKnife SBRT for the treatment of locally advanced pancreatic tumor based on a 5 fractions treatment regimen. This trial protocol has been approved by the Ethics committee of Changhai hospital. The ethics number is 2016-030-01.
Trial registration
Clinical trials number: NCT02716207 .
Date of registration: 20 March 2016
Synthesis, spectroscopic, dielectric, molecular docking and DFT studies of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one: an anticancer agent
No full textAbstract
Background
Coumarin (2 H -chromen-2-one) and its derivatives have a wide range of biological and pharmaceutical activities. They possess antitumor, anti-HIV, anticoagulant, antimicrobial, antioxidant, and anti-inflammatory activities. Synthesis and isolation of coumarins from different species have attracted the attention of medicinal chemists. Herein, we report the synthesis, molecular structure, dielectric, anticancer activity and docking studies with the potential target protein tankyrase.
Results
Molecular structure of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2 H -chromen-2-one (MBDC) is derived from quantum chemical calculations and compared with the experimental results. Intramolecular interactions, stabilization energies, and charge delocalization are calculated by NBO analysis. NLO property and dielectric quantities have also been determined. It indicates the formation of a hydrogen bonding between \u2013OH group of alcohol and C=O of coumarin. The relaxation time increases with the increase of bond length confirming the degree of cooperation and depends upon the shape and size of the molecules. The molecule under study has shown good anticancer activity against MCF-7 and HT-29 cell lines. Molecular docking studies indicate that the MBDC binds with protein.
Conclusions
In this study, the compound (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2 H -chromen-2-one was synthesized and characterized by spectroscopic studies. The computed and experimental results of NMR study are tabulated. The dielectric relaxation studies show the existence of molecular interactions between MBDC and alcohol. Theoretical results of MBDC molecules provide the way to predict various binding sites through molecular modeling and these results also support that the chromen substitution is more active in the entire molecule. Molecular docking study shows that MBDC binds well in the active site of tankyrase and interact with the amino acid residues. These results are compared with the anti cancer drug molecule warfarin derivative. The results suggest that both molecules have comparable interactions and better docking scores. The results of the antiproliferative activity of MBDC and Warfarin derivative against MCF-7 breast cancer and HT-29 colon cancer cell lines at different concentrations exhibited significant cytotoxicity. The estimated half maximal inhibitory concentration (IC 50) value for MBDC and Warfarin derivative was 15.6 and 31.2\ua0\u3bcg/ml, respectively. This enhanced cytotoxicity of MBDC in MCF-7 breast cancer and HT-29 colon cancer cell lines may be due to their efficient targeted binding and ..
Prevalence and factors associated with overweight and obesity among private kindergarten school children in Bahirdar Town, Northwest Ethiopia: cross-sectional study
No full textAbstract
Background
In Sub-Saharan Africa, most nutrition efforts have concentrated on under-nutrition in children. However, national surveys rarely report the high prevalence of overweight and obesity among children. Likewise, in Ethiopia there is growing recognition of the emergence of a \u201cdouble-burden\u201d of malnutrition, with under and over nutrition occurring simultaneously among children, especially allied with improvements in socio-economic conditions. Hence, the study aimed to assess the prevalence and factors associated with overweight and obesity among private kindergarten school children aged 3\u20136\ua0years in Bahirdar town, Northwest Ethiopia.
Methods
A school-based cross sectional study was conducted in Bahirdar Town, northwest Ethiopia from August to September, 2015. Anthropometric measurements such as weight and height were taken from 462 private Kindergarten preschool children aged 3\u20136\ua0years; socio-economic and demographic factors and feeding practices were collected by interviewing the, mothers or caregivers of the children. The z-score values for BMI-for-age of children were generated using Emergency Nutrition Assessment (ENA) for Standardized Monitoring and Assessment of Relief Transitions (SMART) 2011. Binary logistic regression model was used to identify factors associated with overweight and obesity in children. Odds ratio with 95% confidence interval (CI) was calculated to show the strength of association.
Results
The overall prevalence of overweight and obesity was 6.9% [95% CI 2.4, 11.4]. The prevalence of overweight and obesity were 4.1 and 2.8%, respectively. The odds of overweight and obesity was higher among children with high dietary diversity score (DDS) [AOR\ua0=\ua05.12, 95% CI 1.42, 18.47], family size of less than five [AOR\ua0=\ua04.76, 95% CI 1.84, 12.31] and a family having a private car [AOR\ua0=\ua03.43, 95% CI 1.02, 11.49].
Conclusions
The prevalence of overweight and obesity among private kindergarten preschool children in the study area was high. Interventions on improving feeding practice and doing physical activities are important for the control of overweight and obesity among children in urban settings
treeman: an R package for efficient and intuitive manipulation of phylogenetic trees
No full textAbstract
Background
Phylogenetic trees are hierarchical structures used for representing the inter-relationships between biological entities. They are the most common tool for representing evolution and are essential to a range of fields across the life sciences. The manipulation of phylogenetic trees\u2014in terms of adding or removing tips\u2014is often performed by researchers not just for reasons of management but also for performing simulations in order to understand the processes of evolution. Despite this, the most common programming language among biologists, R , has few class structures well suited to these tasks.
Results
We present an R package that contains a new class, called TreeMan , for representing the phylogenetic tree. This class has a list structure allowing phylogenetic trees to be manipulated more efficiently. Computational running times are reduced because of the ready ability to vectorise and parallelise methods. Development is also improved due to fewer lines of code being required for performing manipulation processes.
Conclusions
We present three use cases\u2014pinning missing taxa to a supertree, simulating evolution with a tree-growth model and detecting significant phylogenetic turnover\u2014that demonstrate the new package\u2019s speed and simplicity
Thigh pyomyositis caused by group A streptococcus in an immunocompetent adult without any cause
No full textAbstract
Background
Pyomyositis is typically caused by Staphylococcus aureus , and is rare in temperate climates, although its prevalence has been recently increasing. This infection often involves the thigh, and is associated with immunodeficiency.
Case presentation
We report the case of a healthy 20-year-old Japanese woman who experienced a fever and continuous pain for several days. She was admitted to our hospital and was diagnosed with pyomyositis after we discovered an abscess between the muscles of her dorsal distal left thigh using computed tomography. This is a rare case of thigh pyomyositis, as it was caused by group A streptococcus and occurred in an immunocompetent adult from a temperate climate.
Conclusions
Our review of the literature revealed that group A streptococcus pyomyositis typically occurs in temperate climates, among young adults without any underlying disease, and is associated with a poorer prognosis, compared to general pyomyositis. We suggest that pyomyositis should be considered when immunocompetent adults present with apparently idiopathic inflammatory muscle lesions
Radiotherapy in the management of gist: state of the art and new potential scenarios
No full textAbstract
Background
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The main treatment for localized gastrointestinal stromal tumors is surgical resection. Unresectable or advanced GIST are poorly responsive to conventional cytotoxic chemotherapy but the introduction of tyrosine kinase inhibitors (TKIs) marked a revolutionary step in the treatment of these patients, radically improving prognosis and clinical benefit. Historically GIST has been considered radiation-resistant, and the role of radiotherapy in the management of patients with GIST is currently restricted to symptomatic palliation in current treatment guidelines.
Case presentation
Here we report two patients affected by metastatic GIST, treated with radiotherapy and radiosurgery in combination with TKIs, achieving an unexpected objective response in the first case and a significant clinical benefit associated with a local tumor control of several months in the second case.
Conclusions
These and other successful experiences that are progressively accumulating, open up new scenarios of use of radiation therapy in various settings of treatment. GIST is not universally radioresistant and radiotherapy, especially if combined with molecularly targeted therapy, can improve the outcomes for patients diagnosed with GIST
A fission yeast cell-based system for multidrug resistant HIV-1 proteases
No full textAbstract
Background
HIV-1 protease (PR) is an essential enzyme for viral production. Thus, PR inhibitors (PIs) are the most effective class of anti-HIV drugs. However, the main challenge to the successful use of PI drugs in patient treatment is the emergence of multidrug resistant PRs (
mdr
PRs). This study aimed to develop a fission yeast cell-based system for rapid testing of new PIs that combat
mdr
PRs.
Results
Three
mdr
PRs were isolated from HIV-infected patients that carried seven (
M7
PR), ten (
M10
PR) and eleven (
M11
PR) PR gene mutations, respectively. They were cloned and expressed in fission yeast under an inducible promoter to allow the measurement of PR-specific proteolysis and drug resistance. The results showed that all three
mdr
PRs maintained their abilities to proteolyze HIV viral substrates (MA\u2193CA and p6) and to confer drug resistance. Production of these proteins in the fission yeast caused cell growth inhibition, oxidative stress and altered mitochondrial morphologies that led to cell death. Five investigational PIs were used to test the utility of the established yeast system with an FDA-approved PI drug Darunavir (DRV) as control. All six compounds suppressed the wildtype PR (
wt
PR) and the
M7
PR-mediated activities. However, none of them were able to suppress the
M10
PR or the
M11
PR.
Conclusions
The three clinically isolated
mdr
PRs maintained their viral proteolytic activities and drug resistance in the fission yeast. Furthermore, those viral
mdr
PR activities were coupled with the induction of growth inhibition and cell death, which could be used to test the PI activities. Indeed, the five investigational PIs and DRV suppressed the
wt
PR in fission yeast as they did in mammalian cells. Significantly, two of the high level
mdr
PRs (
M10
PR and
M11
PR) were ..
Parallel implementation of color-based particle filter for object tracking in embedded systems
No full textAbstract
Recently, embedded systems have become popular because of the rising demand for portable, low-power devices. A common task for these devices is object tracking, which is an essential part of various applications. Until now, object tracking in video sequences remains a challenging problem because of the visual properties of objects and their surrounding environments. Among the common approaches, particle filter has been proven effective in dealing with difficulties in object tracking. In this research, we develop a particle filter based object tracking method using color distributions of video frames as features, and deploy it in an embedded system. Because particle filter is a high-complexity algorithm, we utilize computing power of embedded systems by implementing a parallel version of the algorithm. The experimental results show that parallelization can enhance the performance of particle filter when deployed in embedded systems
Comparing effects: a reanalysis of two studies on season of birth bias in anorexia nervosa
No full textAbstract
Background
Outcomes from studies on season of birth bias in eating disorders have been inconsistent. This inconsistency has been explained by differences in methodologies resulting in different types of effect sizes. The aim of the current study was to facilitate comparison by using the same methodology on samples from two studies with differing conclusions.
Methods
The statistical analyses used in each study were applied to the samples from the other study and the resulting effect sizes, Cram\uear\u2019s\ua0V and odds ratio (OR), were compared and discussed.
Results
For both studies, the Cram\uear\u2019s\ua0Vs ranged between 0.03 and 0.08 and the OR ranged between 0.85 and 1.31. According to common conventions, Cram\uear\u2019s Vs below 0.10 and ORs below 1.44 are considered small.
Conclusion
As a marker of one or more potential risk factors, the observed effects are considered to be small. When reanalysed allowing for direct comparisons, studies with contrasting conclusions converge towards an absence of support for a season of birth bias for patients with AN
Monitoring the accumulated water soluble airborne compounds deposited on surfaces of showcases and walls in museums, archives and historical buildings
No full textAbstract
Background
Cultural heritage objects are subject to the deposition of a multitude of airborne pollutants even when kept inside museums, archives, historical buildings or showcases. Some of the pollutants are quickly deposited onto any available surface, including the interior walls and CH objects themselves. This might make the compounds seem absent from analyses of indoor air samples.
Context and purpose of the study
A new method of detecting water soluble pollutants without taking samples from the interior walls or from the CH objects themselves has been developed. The method involves sampling the pollutants accumulated on a surface near the CH object, e.g. a nearby wall or an interior glass surface of a showcase. The samples were obtained by gently flushing the surface with deionised water to collect the ions readily removed from the surface. The method was tested on a variety of surfaces.
Results and main findings
The flushed water were analysed with IC (Ion Chromatography) and ICP-MS (Inductively Coupled Plasma Mass Spectrometry) and included ions of Al, As, Ba, Ca, CH
3
COOH, Cl, Co, (COOH)
2
, Cr, Cu, F, Fe, K, Mg, Mn, Na, NH
4
, Ni, Pb, S, Sb, Si, Sn, Sr, Ti and Zn, and the ions NO
3
\u2212
, PO
4
3\u2212
, and SO
4
2\u2212
. The resulting concentrations were converted to \ub5Eq, providing the ionic balance and the relative amounts of the ions and elements present. Ionic balance was observed on smooth and inert surfaces, but in some cases the chemistry of the wall contributed to the flush water. Solid samples of some of the surfaces have been analysed by XRF to clarify these more complex situations.
Conclusions
Clear results appear from smooth or well defined surfaces, whereas more complex situations arise when the underlying surface itself contributes to the flush water. The method is working very well and is easy and cheap to implement by curators and conservators, who can the send the flush water to specialized laboratories.
..