DFNB40, a recessive form of sensorineural hearing loss, maps to chromosome 22q11.21-12.1

We report on a novel localization for a recessive form of deafness (DFNB), by linkage analysis in an Iranian consanguineous family. Affected individuals suffer from prelingual profound sensorineural hearing loss. Genome-wide analysis led to the characterization of a new locus, DFNB40, which maps to an approximately 9 Mb interval between markers D22S427 and D22S1144 at chromosome 22q11.21-12.1. Maximum lod score of 3.09 was obtained with D22S1174. Since the Bronx waltzer (bv) mouse mutant, characterized by waltzing behavior, deafness, and degeneration of cochlear inner hair cells, has been mapped to the syntenic region on murine chromosome 5, we suggest that DFNB40 and bv may result from orthologous gene defects.     

Human microvasculature-on-a chip: anti-neovasculogenic effect of nintedanib in vitro

Idiopathic pulmonary fibrosis is characterized by a progressive scarring and stiffening of the peripheral lung tissue that decreases lung function. Over the course of the disease, the lung microvasculature undergoes extensive remodeling. There is increased angiogenesis around fibrotic foci and an absence of microvessels within the foci. To elucidate how the anti-fibrotic drug nintedanib acts on vascular remodeling, we used an in vitro model of perfusable microvessels made with primary endothelial cells and primary lung fibroblasts in a microfluidic chip. The microvasculature model allowed us to study the impact of nintedanib on permeability, vascularized area, and cell–cell interactions. The anti-vasculogenic impact of nintedanib was visible at the minimal concentrations of 10 nM, showing a significant increase in vessel permeability. Furthermore, nintedanib decreased microvessel density, diameter, and influenced fibroblast organization around endothelial microvessels. These results show that nintedanib acts on the endothelial network formation and endothelial–perivascular interactions. Advanced in vitro microvasculature models may thus serve to pinpoint the mechanistic effect of anti-fibrotic drugs on the microvascular remodeling in 3D and refine findings from animal studies.     

Additive effects of flavour-caffeine and flavour-flavour pairings on liking for the smell and flavour of a novel drink

Previous research has established that caffeine consumption can reinforce changes in liking for caffeine-paired flavours, while pairing a novel flavour with a liked or dislike taste can also result in enduring changes in liking for the flavour. The present study examined how these two forms of flavour-learning interact. 72 habitual caffeine consumers who liked sweet tastes rated the odour and flavour of a novel tea drink before and after four training sessions where the flavour was paired with either 100 mg caffeine or placebo in one of three flavour contexts: added sweetness (aspartame), bitterness (quinine) or control. The liking for both the odour and flavour of the tea increased after pairing with caffeine regardless of flavour context, while pairing with bitterness reduced flavour liking regardless of the presence of caffeine. Pairing with quinine increased the rated bitterness of the tea odour, and reduced the rated sweetness of the tea flavour, post-training, independent of effects of caffeine. These data suggest that flavour-caffeine and flavour-flavour associations have additive effects on drink liking, while confirming that flavour-flavour associations can alter the immediate sensory experience of a flavour alone.     

Ablation of Breast Cancer Cells Using Trastuzumab‐Functionalized Multi‐Walled Carbon Nanotubes and Trastuzumab‐Diphtheria Toxin Conjugate

Trastuzumab (Herceptin^®) is a monoclonal antibody (mAb) for specific ablation of HER2‐overexpressing malignant breast cancer cells. Intensification of antiproliferative activity of trastuzumab through construction of immunotoxins and nano‐immunoconjugates is a promising approach for treatment of cancer. In this study, trastuzumab was directly conjugated to diphtheria toxin (DT). Also, conjugates of trastuzumab and multiwalled carbon nanotubes (MWCNT) were constructed by covalent immobilization of trastuzumab onto MWCNTs. Then, antiproliferative activity of the fusion constructs against HER2‐overexpressing SK‐BR‐3 and also HER2‐negative MCF‐7 cancer cell lines were examined. Cells treated with trastuzumab‐MWCNT conjugates were irradiated with near‐infrared (NIR) light. Efficient absorption of NIR radiation and its conversion to heat by MWCNTs can be resulted to thermal ablation of cancerous cells. Our results strongly showed that both trastuzumab‐MWCNT and trastuzumab‐DT conjugates were significantly efficient in the specific killing of SK‐BR‐3 cells. Targeting of MWCNTs to cancerous cells using trastuzumab followed by exposure of cells to NIR radiation was more efficient in repression of cell proliferation than treatment for cancer cells with trastuzumab‐DT. Our results also showed that conjugation linkers can significantly affect the cytotoxicity of MWCNT‐immunoconjugates. In conclusion, our data demonstrated that trastuzumab‐MWCNT is a promising nano‐immunoconjugate for killing of HER2‐overexpressing cancerous cells.     

Iranian migrants' discourses of health and the implications for using standardized health measures with minority groups

This paper explores the concept of health implied in the SF-36 within a group of Iranians in Australia. Qualitative data were collected from a sample of 21 people—10 females and 11 males. For the first time, the NUD*IST program was used to organize and manage the data in Persian (also known as Farsi), the language spoken by Iranians. Health was defined in terms of holistic, spiritual, social, physical/emotional aspects, and absence-of-disorder dimensions. Among these, physical, absence of disorder, holistic, and spiritual aspects of health were mentioned more frequently than other themes. The findings of the study raise concerns about the extent to which the SF-36 captures the diversity of the concept of health as expressed by the sample of Iranian migrants.