Polymorphism of adhesion molecule CD31 is not a significant risk factor for graft-versus-host disease

Mismatch between bone marrow transplant (BMT) patient and donor for an amino acid polymorphism within the adhesion molecule CD31 has recently been reported to increase risk for the development of graft-versus-host disease (GVHD). We further examined this association in a larger series of 301 BMT patients (227 with grade III/IV GVHD and 74 with grade 0 GVHD) and their HLA-identical sibling donors. CD31 genotypes were determined by polymerase chain reaction and restriction endonuclease digestion. The role of mismatch at the CD31 locus in the development of GVHD was assessed by analyzing the extent of CD31 identity and CD31 compatibility among the grade 0 GVHD and grade III/IV GVHD sibling pairs. No significant association between CD31 mismatch and the development of severe GVHD was detected in our overall patient population. Sixty-three percent of grade III/IV GVHD sibling pairs and 69% of grade 0 GVHD sibling pairs had CD31 genotypes that were identical (P = .36, odds ratio = 1.30). In addition, neither the grade 0 GVHD group (P = .10) nor the grade III/IV GVHD group (P = .27) differed significantly from the expected probability of identity between sibling pairs. Mismatch at the CD31 polymorphism between recipients and donors showed no consistent association with the development of GVHD. Current evidence does not support the value of CD31 mismatch in the selection of BMT donors.     

Breast Cancer Chemoprevention among High‐risk Women and those with Ductal Carcinoma In Situ

Chemoprevention with the anti‐estrogens, tamoxifen, raloxifene, and aromatase inhibitors, reduce breast cancer incidence in high‐risk women; however, uptake has been poor (<5%) in the prevention setting. We assessed use of anti‐estrogens for breast cancer prevention, among high‐risk women seen at an academic breast center, to observe how uptake rates compare in this setting. We collected data on demographics, breast cancer risk factors, and health behaviors via self‐administered questionnaires and medical chart abstraction. Women eligible for chemoprevention with anti‐estrogens had a 5‐year predicted breast cancer risk according to the Gail model of ≥1.67%, history of lobular or ductal carcinoma in situ (LCIS/DCIS), and/or BRCA mutation. We dichotomized anti‐estrogen use as ever or never. Predictors of use were evaluated using multivariable log‐binomial regression. Of 412 high‐risk women enrolled, 316 (77%) were eligible for chemoprevention. Among eligible women, 55% were non‐Hispanic white, 29% Hispanic, 8% non‐Hispanic black, and 7% Asian. Women were grouped based upon their highest category of breast cancer risk (in descending order): BRCA mutation carriers (3%), DCIS (40%), LCIS (22%), and 5‐year Gail risk ≥1.67% (36%). Among those eligible for chemoprevention, 162 (51%) had ever initiated anti‐estrogen therapy (71% tamoxifen, 23% raloxifene, 5% aromatase inhibitor). Anti‐estrogen use was highest among women with DCIS (73%). In multivariable analysis, women with a 5‐year Gail risk ≥1.67% had approximately a 20% lower likelihood of anti‐estrogen use compared to women with DCIS (p = 0.01). In the primary prevention setting, excluding women diagnosed with DCIS, anti‐estrogen use was 37%. Multivariable analysis showed differences in uptake by education and potentially by race/ethnicity. Among high‐risk women seen at a breast center, anti‐estrogen use for chemoprevention was relatively high as compared to the published literature. Clinicians can support high‐risk women by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of chemoprevention.     

The effects and effectiveness of electromotive drug administration and chemohyperthermia for treating non-muscle invasive bladder cancer

Introduction

Preliminary studies show that device assisted intravesical therapies appear more effective than passive diffusion intravesical therapy for the treatment of non-muscle invasive bladder cancer (NMIBC) in specific settings, and phase III studies are now being conducted. Consequently, we have undertaken a non-systematic review with the objective of describing the scientific basis and mechanisms of action of electromotive drug administration (EMDA) and chemohyperthermia (CHT).

Methods

PubMed, ClinicalTrials.gov and the Cochrane Library were searched to source evidence for this non-systematic review. Randomised controlled trials, systematic reviews and meta-analyses were evaluated. Publications regarding the scientific basis and mechanisms of action of EMDA and CHT were identified, as well as clinical studies to date.

Results

EMDA takes advantage of three phenomena: iontophoresis, electro-osmosis and electroporation. It has been found to reduce recurrence rates in NMIBC patients and has been proposed as an addition or alternative to bacillus Calmette–Guérin (BCG) therapy in the treatment of high risk NMIBC. CHT improves the efficacy of mitomycin C by three mechanisms: tumour cell cytotoxicity, altered tumour blood flow and localised immune responses. Fewer studies have been conducted with CHT than with EMDA but they have demonstrated utility for increasing disease-free survival, especially in patients who have previously failed BCG therapy.

Conclusions

It is anticipated that EMDA and CHT will play important roles in the management of NMIBC in the future. Techniques of delivery should be standardised, and there is a need for more randomised controlled trials to evaluate the benefits of the treatments alongside quality of life and cost-effectiveness.     

Toxicity induced by nanoparticles

Nanoparticle research is currently an area of intense scientific interest due to a wide variety of potential applications. Human beings have been exposed to airborne nanosized particles throughout their evolutionary stages, and such exposures have increased dramatically over the last century. Nanoparticle can modify the physicochemical properties of the material as well as create the opportunity for increased uptake and interaction with biological tissues through inhalation, ingestion, and injection. This combination of effects can generate adverse biological effects in living cells. Nanoparticles have proved toxic to human once in the blood stream, nanoparticles, spleen, bone marrow and nervous system can be transported around the body and be taken up by organs tissue and cell cultures, resulting in increased oxidative stress, inflammatory cytokine production and cell death. Unlike larger particles, nanoparticles may be taken up by cell mitochondria and the cell nucleus studies demonstrate the potential for nanoparticles to cause DNA mutation and induce major structural damage to mitochondria, even resulting in cell death. Size is therefore a key factor in determining the potential toxicity of a particle. How these nanoparticles behave inside the body is still a major question that needs to be resolved. There is a responsibility to test and optimize these new nanomaterials early during the development process to eliminate or ameliorate identified toxic characteristics.     

Specific Retrograde Transduction of Spinal Motor Neurons Using Lentiviral Vectors Targeted to Presynaptic NMJ Receptors

To understand how receptors are involved in neuronal trafficking and to be able to utilize them for specific targeting via the peripheral route would be of great benefit. Here, we describe the generation of novel lentiviral vectors with tropism to motor neurons that were made by coexpressing onto the lentiviral surface a fusogenic glycoprotein (mutated sindbis G) and an antibody against a cell-surface receptor (Thy1.1, p75^NTR, or coxsackievirus and adenovirus receptor) on the presynaptic terminal of the neuromuscular junction. These vectors exhibit binding specificity and efficient transduction of receptor positive cell lines and primary motor neurons in vitro. Targeting of each of these receptors conferred to these vectors the capability of being transported retrogradely from the axonal tip, leading to transduction of motor neurons in vitro in compartmented microfluidic cultures. In vivo delivery of coxsackievirus and adenovirus receptor-targeted vectors in leg muscles of mice resulted in predicted patterns of motor neuron labeling in lumbar spinal cord. This opens up the clinical potential of these vectors for minimally invasive administration of central nervous system-targeted therapeutics in motor neuron diseases.     

A review of the use of beeswax in skincare

Background

Beeswax is a naturally occurring product secreted from worker bees that has varied uses in modern day. In skincare, its function ranges from its role as an occlusive, helping to create a semi-occlusive skin barrier that minimizes transepidermal water loss; as a humectant, locking in hydration; and an emollient to soften and soothe the skin. As a natural substance, its use has been shown to help alleviate symptoms associated with common cutaneous conditions like dermatitis, psoriasis, and overgrowth of normal skin flora.

Aims

In this narrative review, we aim to describe current uses of beeswax in skincare that has been published in the literature.

Materials and methods

A review of beeswax related publications was performed by searching the PubMed database studies.

Results

A total of five clinical studies were included with three studies on animals and two studies in humans.

Discussion

Several studies show the benefits of topical beeswax in supporting the skin barrier.

Conclusion

Beeswax can be a low-cost, natural ingredient for use in products. Further studies with topical beeswax are warranted.