A historical literature review on the role of posterior axillary boost field in the axillary lymph node coverage and development of lymphedema following regional nodal irradiation in breast cancer

To elucidate whether (1) a posterior axillary boost (PAB) field is an optimal method to target axillary lymph nodes (LNs); and (2) the addition of a PAB increases the incidence of lymphedema, a systematic review was undertaken. A literature search was performed in the PubMed database. A total of 16 studies were evaluated. There were no randomized studies. Seven articles have investigated dosimetric aspects of a PAB. The remaining 9 articles have determined the effect of a PAB field on the risk of lymphedema. Only 2 of 9 articles have prospectively reported the impact of a PAB on the risk of lymphedema development. There are conflicting reports on the necessity of a PAB. The PAB field provides a good coverage of level I/II axillary LNs because these nodes are usually at a greater depth. The main concern regarding a PAB is that it produces a hot spot in the anterior region of the axilla. Planning studies optimized a traditional PAB field. Prospective studies and the vast majority of retrospective studies have reported the use of a PAB field does not result in increasing the risk of lymphedema development over supraclavicular-only field. The controversies in the incidence of lymphedema suggest that field design may be more important than field arrangement. A key factor regarding the use of a PAB is the depth of axillary LNs. The PAB field should not be used unless there is an absolute indication for its application. Clinicians should weigh lymphedema risk in individual patients against the limited benefit of a PAB, in particular after axillary dissection. The testing of the inclusion of upper arm lymphatics in the regional LN irradiation target volume, and universal methodology measuring lymphedema are all areas for possible future studies.     

Discovery and characterization of a novel humanized anti-IL-15 antibody and its relevance for the treatment of refractory celiac disease and eosinophilic esophagitis

Interleukin-15 (IL-15) is a critical regulator of immune responses, especially at mucosal interfaces within the gastro-intestinal tract. Here, we describe the discovery and characterization of a humanized antibody to IL-15. Data from its epitope and mode of action, cell biology and primate pharmacology, as well as translational studies in human samples and in vivo proof-of-concept experiments in mouse models demonstrate the therapeutic potential of this new antibody targeting IL-15 for refractory celiac disease and eosinophilic esophagitis.     

A new species of frog-eyed gecko,genus Teratoscincus Strauch, 1863 (Squamata: Sphaerodactylidae), from southeastern Iran

Herein we describe a new species of Teratoscincus Strauch, 1863 from remote desert areas of the Sistan and Baluchistan Province in southeastern Iran. Based on morphological characters, this species, Teratoscincus sistanense sp. n., has a close relationship with T. microlepis and is distinct from all other members of its genus by the number of small scales around the midbody. We provide information about the ecology, biology and conservation of this new species. A comparison with the other three Iranian species of Teratoscincus and an updated key to this genus in Iran are presented.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:77F54322-6CCA-46F1-A74B-B8A75E1F1F8D     

Comparative fate of organohalogen contaminants in two top carnivores in Greenland: captive sledge dogs and wild polar bears

The limited knowledge and/or the inability to control physiological condition parameters that influence the fate of organohalogen contaminants (OHCs) has been the foremost confounding aspect in monitoring programs and health risk assessments of wild top predators in the Arctic such as the polar bear (Ursus maritimus). In the present comparative study, we used a potential surrogate Canoidea species for the East Greenland polar bear, the captive sledge dog (Canis familiaris), to investigate some factors that may influence the bioaccumulation and biotransformation of major chlorinated and brominated OHCs in adipose tissue and blood (plasma) of control (fed commercial pork fat) and exposed (fed West Greenland minke whale (Balaenoptera acutorostrata) blubber) adult female sledge dogs. Furthermore, we compared the patterns and concentrations of OHCs and their known or suggested hydroxylated (OH) metabolites (e.g., OH-PCBs) in sledge dogs with those in adipose tissue and blood (plasma) of East Greenland adult female polar bears, and blubber of their main prey species, the ringed seal (Pusa hispida). The two-year feeding regime conducted with sledge dogs led to marked differences in overall adipose tissue (and plasma) OHC residue accumulation between the control and exposed groups. Characteristic prey-to-predator OHC bioaccumulation dynamics for major PCB and PBDE congeners (patterns and concentrations) and biotransformation capacity with respect to PCB metabolite formation and OH-PCB retention distinguished, to some extent, captive sledge dogs and wild polar bears. Based on the present findings, we conclude that the use of surrogate species in toxicological investigations for species in the Canoidea family should be done with great caution, although they remain essential in the context of contaminants research with sensitive arctic top carnivore species such as the polar bear.     

Proteomic analysis of peanut seed storage proteins and genetic variation in a potential peanut allergen

Peanut allergy is one of the most severe food allergies. One effort to alleviate this problem is to identify peanut germplasm with lower levels of allergens which could be used in conventional breeding to produce a less allergenic peanut cultivar. In this study, we identified one peanut line, GT-C9, lacking several seed proteins, which were identified as Ara h 3 isoforms by peptide sequencing and named iso-Ara h 3. Total seed proteins were analyzed by one-dimensional (SDS-PAGE) and two-dimensional gel electrophoreses (2-D PAGE). The total protein extracts were also tested for levels of protein-bound end products or adducts such as advanced glycation end products (AGE) and N-(carboxymethyl) lysine (CML), and IgE binding. Peanut genotypes of GT-C9 and GT-C20 exhibited significantly lower levels of AGE adducts and of IgE binding. This potential peanut allergen iso-Ara h 3 was confirmed by peptide sequences and Western blot analysis using specific anti-Ara h 1, Ara h 2, and Ara h 3 antibodies. A full-length sequence of iso-ara h 3 (GenBank number DQ855115) was obtained. The deduced amino acid sequence iso-Ara h 3 (ABI17154) has the first three of four IgE-binding epitopes of Ara h 3. Anti-Ara h 3 antibodies reacted with two groups of protein peptides, one with strong reactions and another with weak reactions. These peptide spots with weak reaction on 2-D PAGE to anti-Ara h 3 antibodies are subunits or isoallergens of this potential peanut allergen iso-Ara h 3. A recent study suggested that Ara h 3 basic subunits may be more significant allergenicity than the acidic subunits.     

A novel type of membranes based on cholesteryl phosphate

Mixtures of the rigid amphiphile disodium cholesteryl phosphate (DCP) with the non-phosphorylated diacyl amphiphile dimyristoylglycerol (DMG) give self-organized systems in a wide range of pH, as demonstrated by differential microcalorimetry. These systems can be closed bilayer vesicles, as shown by optical microscopy (Nomarski and confocal). Neither DMG nor DCP, taken alone, give vesicles in these conditions but 10% DMG is enough to lead to the formation of vesicles from pH 5.8 to 9.3. These novel self-organized systems are akin to the classical eucaryotic ones, built on a phosphorylated diacylglycerol and free cholesterol (or analogues), the only difference being the site of the phosphate head-group.     

Peptide selected by phage display increases survival of SH-SY5Y neurons comparable to brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) is a well-known neuroprotectant and a potent therapeutic candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we designed and developed BDNF-mimicking small peptides as an alternative to circumvent these problems. A phage-displayed peptide library was screened using BDNF receptor (neurotrophic tyrosine kinase receptor type2 [NTRK2]) and evaluated by ELISA. The peptide sequences showed similarity to loop2 of BDNF, they were recognized as discontinuous epitopes though. Interestingly, in silico molecular docking showed strong interactions between the peptide three-dimensional models and the surface residues of the NTRK2 protein at the IgC2 domain. A consensus peptide sequence was then synthesized to generate a mimetic construct (named as RNYK). The affinity binding and function of this construct was confirmed by testing against the native structure of NTRK2 in SH-SY5Y cells in vitro using flow-cytometry and MTT assays, respectively. RNYK at 5 ng/mL prevented neuronal degeneration of all- trans-retinoic acid-treated SH-SY5Y with equal efficacy to or even better than BDNF at 50 ng/mL.     

Preparation of liposomal doxorubicin-graphene nanosheet and evaluation of its in vitro anti-cancer effects

In recent years there has been much interest in development of multifunctional drug delivery systems. In this work, liposomes that contain doxorubicin (Dox), a potent anticancer drug, and graphene nanosheets (GNS) were prepared. The GNSs have excellent optical properties, such as photoluminescence which enables tracking of the liposomes, high absorption in ultra violet region of electromagnetic spectrum which can be exploited in photodynamic and photothermal therapy, and low toxicity to mammalian cells. Nanoliposomes were prepared using the thin film hydration method. Dox and GNSs were loaded to the liposomes during the hydration of the lipid film. Liposomes were characterized and the profile of in vitro drug release, cellular uptake, and cytotoxicity of the prepared liposomes on MCF-7 cells were determined. Despite the earlier reports, the liposomes have kept their spherical structures in the presence of GNSs. The cytotoxicity of liposomal Dox and GNSs were shown to be higher than the free forms of them. Novel nanoliposomes that contain GNSs have provided a multi-functional system with the potential of tracking, photodynamic and photothermal therapy. Further improvements of this versatile nanosystem would be promising for treatment of cancer.     

Methyltetrahydrofolate vs Folic Acid Supplementation in Idiopathic Recurrent Miscarriage with Respect to Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms: A Randomized Controlled Trial

Purpose

To determine whether 5-methylenetetrahydrofolate (MTHF) is more effective than folic acid supplementation in treatment of recurrent abortion in different MTHFR gene C677T and A1298C polymorphisms.

Methods

A randomized, double blind, placebo-controlled trial conducted April 2011-September 2014 in recurrent abortion clinics in Tehran, Iran. The participants were women with three or more idiopathic recurrent abortion, aged 20 to 45 years. Two hundred and twenty eligible women who consented to participate were randomly assigned to receive either folic acid or 5-MTHF according to the stratified blocked randomization by age and the number of previous abortions. Participants took daily 1 mg 5-methylentetrahydrofolate or 1 mg folic acid from at least 8 weeks before conception to the 20^th week of the pregnancy. The primary outcome was ongoing pregnancy rate at 20^th week of pregnancy, and the secondary outcomes were serum folate and homocysteine at the baseline, after 8 weeks, and at the gestational age of 4, 8, 12, and 20 weeks, MTHFR gene C677T and A1298C polymorphisms.

Results

There was no significant difference in abortion rate between two groups. Serum folate increased significantly in both groups over time; these changes were significantly higher in the group receiving 5-MTHF than the group receiving folic acid (value = 2.39, p<00.1) and the result was the same by considering the time (value = 1.24, p<0.01). Plasma tHcys decreased significantly in both groups over time; however these changes were not significantly different between the groups (value = 0.01, p = 0.47).

Conclusion

The results do not support any beneficial effect of 5-MTHF vs. folate supplementation in women with recurrent abortion with any MTHFR C677T and/or A1298C polymorphism.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01976676","term_id":"NCT01976676"}}NCT01976676     

Growth kinetics and Pho84 phosphate transporter activity of <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> under phosphate-limited conditions

The effect of phosphate (P _i ) concentration on the growth behavior of Saccharomyces cerevisiae strain CEN.PK113-5D in phosphate-limited batch and chemostat cultures was studied. The range of dilution rates used in the present study was 0.08–0.45 h⁻¹. The batch growth of yeast cells followed Monod relationship, but growth of the cells in phosphate-limited chemostat showed change in growth kinetics with increasing dilution rates. The difference in growth kinetics of the yeast cells in phosphate-limited chemostat for dilution rates below and above approximately 0.2 h⁻¹ has been discussed in terms of the batch growth kinetic data and the change in the metabolic activity of the yeast cells. Immunological detection of a C-terminally myc epitope-tagged Pho84 fusion protein indicated derepressive expression of the Pho84 high-affinity P _i transporter in the entire range of dilution rates employed in this study. Phosphate transport activity mediated by Pho84 transporter was highest at very low dilution rates, i.e. 0.08–0.1 h⁻¹, corresponding to conditions in which the amount of synthesized Pho84 was at its maximum.