Predicting the optimal geometry of microneedles and their array for dermal vaccination using a computational model

Microneedle arrays have been developed to deliver a range of biomolecules including vaccines into the skin. These microneedles have been designed with a wide range of geometries and arrangements within an array. However, little is known about the effect of the geometry on the potency of the induced immune response. The aim of this study was to develop a computational model to predict the optimal design of the microneedles and their arrangement within an array. The three-dimensional finite element model described the diffusion and kinetics in the skin following antigen delivery with a microneedle array. The results revealed an optimum distance between microneedles based on the number of activated antigen presenting cells, which was assumed to be related to the induced immune response. This optimum depends on the delivered dose. In addition, the microneedle length affects the number of cells that will be involved in either the epidermis or dermis. By contrast, the radius at the base of the microneedle and release rate only minimally influenced the number of cells that were activated. The model revealed the importance of various geometric parameters to enhance the induced immune response. The model can be developed further to determine the optimal design of an array by adjusting its various parameters to a specific situation.     

An electrophoretic karyotype of Aspergillus niger

Summary An electrophoretic karyotype of Aspergillus niger was obtained using contour-clamped homogeneous electric field (CHEF) gel electrophoresis. Chromosomesized DNA was separated into four bands. Seven of the eight linkage groups could be correlated with specific chromosomal bands. For this purpose DNA preparations from seven transformant strains of A. niger each carrying the heterologous amdS gene of Aspergillus nidulans on a different chromosome were analysed. Some of the assignments were confirmed with linkage groupspecific A. niger probes. The estimated sizes of the A. niger chromosome range from 3.5 to 6.6 Mb, based on gel migration relative to the chromosomes of Schizosaccharomyces pombe strains, Saccharomyces cerevisiae and A. nidulans. The total genome size of A. niger significantly exceeds that of A. nidulans and is estimated to be about 35.5–38.5 Mb. Electrophoretic karyotyping was used to allocate non-mutant rRNA genes and to estimate the number of plasmids integrated in a high copy number transformant.     

Monensin interferes with the determination of the mesodermal cell line in embryos of Patella vulgata

Summary In embryos of the equally cleaving marine gastropod Patella vulgata, the mesodermal stem cell is determined during the interval between the fifth and sixth cleavage by means of cellular interactions between one of the four vegetally located macromeres with the overlying animal micromeres. Shortly before and during this interaction phase an extracellular matrix (ECM) is present between the interacting cells. In this study the glycosylation-perturbing ionophore monensin was used to investigate the possible morphogenetic significance of the ECM. Incubation of 32-cell-stage Patella embryos in 10^–6 M monensin results in radialized embryos in which none of the four macromeres interacts with the overlying animal micromeres. None of the macromeres is determined, therefore, to form mesoderm in such embryos. Trochophore larvae reared from these embryos retain their radial symmetry, as is indicated by the presence of four shell glands and four blastopore- or stomodeum-like invaginations in these larvae. The monensin-treated embryos probably secrete abnormal ECM that does not provide the proper conditions for the blastomeres to stretch and interact with the micromeres. Changes in intracellular ionic concentrations may also be involved.     

Susceptibility of peritoneal macrophages to rat cytomegalovirus infection

Abstract Peritoneal macrophages from Lewis (Lew) and Brown Norway (BN) rats did not support rat cytomegalovirus (RCMV) replication. Intraperitoneal (i.p.) inoculation of virus into the rats resulted in a rapid clearance of virus from the peritoneal lavage fluid and an uptake of virus in the macrophages. The virus did not persist in the peritoneal macrophages of the rats.     

Zebra mussels and polystyrene

The growth of settled and metamorphosed larvae of the zebra mussel (Dreissena polymorpha) is clearly retarded when polystyrene plates are used as a substrate compared with the growth of those forms attached to PVC plates. Possibly, low molecular weight compounds are released into the aquatic environment by the polystyrene and these materials may have a strongly adverse effect upon the growth of young zebra mussels. There is no difference in colonization of young mussels between PVC and polystyrene plates if these plates are sufficiently overgrown with bacteria and algae.     

Psychometric evaluation of the Orofacial Pain Scale for Non‐Verbal Individuals as a screening tool for orofacial pain in people with dementia

Objective

The aim of this study was to describe the psychometric evaluation of the Orofacial Pain Scale for Non‐Verbal Individuals (OPS‐NVI) as a screening tool for orofacial pain in people with dementia.

Background

The OPS‐NVI has recently been developed and needs psychometric evaluation for clinical use in people with dementia. The pain self‐report is imperative as a reference standard and can be provided by people with mild‐to‐moderate cognitive impairment.

Methods

The presence of orofacial pain during rest, drinking, chewing and oral hygiene care was observed in people with mild cognitive impairment (MCI) and dementia using the OPS‐NVI. Participants who were considered to present a reliable self‐report were asked about pain presence, and in all participants, the oral health was examined by a dentist for the presence of potential painful conditions. After item‐reduction, inter‐rater reliability and criterion validity were determined.

Results

The presence of orofacial pain in this population was low (0%‐10%), resulting in an average Positive Agreement of 0%‐100%, an average Negative Agreement of 77%‐100%, a sensitivity of 0%‐100% and a specificity of 66%‐100% for the individual items of the OPS‐NVI. At the same time, the presence of oral problems, such as ulcers, tooth root remnants and caries was high (64.5%).

Conclusion

The orofacial pain presence in this MCI and dementia population was low, resulting in low scores for average Positive Agreement and sensitivity and high scores for average Negative Agreement and specificity. Therefore, the OPS‐NVI in its current form cannot be recommended as a screening tool for orofacial pain in people with MCI and dementia. However, the inter‐rater reliability and criterion validity of the individual items in this study provide more insight for the further adjustment of the OPS‐NVI for diagnostic use. Notably, oral health problems were frequently present, although no pain was reported or observed, indicating that oral health problems cannot be used as a new reference standard for orofacial pain, and a regular oral examination by care providers and oral hygiene care professionals remains indispensable.     

Een carrière als specialist ouderengeneeskunde; iets voor de huidige geneeskundestudent?

Background

Due to the rise of older patients with multi-morbidity, we need more elderly care physicians. However, not all available training slots for the elderly care medicine specialty have been fully utilized in recent years. To assess medical student interest in this specialty as well as potential causes for this interest we explored the interest of medical students in the profession of elderly care physician, as well their perception of this profession, both in the ‘old curriculum’ and in a ‘new curriculum’, where the new curriculum had a mandatory elderly care medicine clerkship and more competency-related learning.

Method

At VUmc 120 final year medical students were asked to complete a questionnaire in 2014 about professional preferences and professional characteristics. The same questionnaire had been presented five years earlier, in 2009, to 150 medical students at the end of their final year.

Results

The response rates were 100% and 85% respectively. Of the students in the new curriculum 16,7% considered a career in elderly care medicine. This percentage was 9,4% for students in the old curriculum (p?=?0,087). The characteristics of the profession that appealed most to the students, but were not considered applicable to elderly care medicine were: diagnostics skills, acute complaints, visible results. The professional characteristics that students found to be very much applicable to this specialty, but less attractive for their future profession were: psychosocial, chronic and terminal conditions.

Discussion

We observe a trend that students in the new curriculum are more interested in the profession of elderly care physician, even though this interest remains limited. We recommend that the basic medical training, both in the bachelor phase and in a mandatory elderly care medicine clerkship, focus more on demonstrating that the characteristics students find appealing in the medical profession are indeed present in this speciality. Also, the basic training should concentrate more on guidance and treatment of patients with chronic and terminal conditions.