Caring for Critically Ill Patients : Clinicians’ Empathy Promotes Job Satisfaction and Does Not Predict Moral Distress

Background: Several studies have highlighted the benefits of empathy in healthcare settings. A correlation between clinicians' empathy and patients' adherence and satisfaction, as well as the ability for the clinician to accurately assess family members' needs, has been found. However, empathy is often seen by clinicians as a risk factor for their wellbeing. This study aims to assess whether the level of empathy of clinicians working in critical care settings may expose them to moral distress, poor job satisfaction, and intention to quit their job. Methods: Italian clinicians who attended the 2016 "Smart Meeting Anesthesia Resuscitation in Intensive Care" completed the Empathy Quotient questionnaire, the Moral Distress Scale-Revised, and two questions assessing job satisfaction and intention to quit the job. Multiple linear and logistic regressions were performed to determine if clinicians' empathy influences moral distress, job satisfaction, and intention to quit. Age, gender, and profession were used as control variables. Results: Out of 927 questionnaires distributed, 216 were returned (23% response rate) and 210 were used in the analyses. Respondents were 56% physicians, 24% nurses, and 20% residents. Over half of the clinicians (58%) were female. Empathy resulted the only significant predictor of job satisfaction (\u3b2 = 0.193; p < 0.05). None of the variables included in the model predicted moral distress. Conclusion: Empathy determined neither moral distress nor intention to quit. Findings suggest that empathy is not a risk factor for critical care clinicians in developing moral distress and the intention to quit their job. On the contrary, empathy was found to enhance clinicians' job satisfaction

Topical administration of a doxorubicin-specific monoclonal antibody prevents drug-induced mouth apoptosis in mice

One of the most severe side effects of anti-tumour chemotherapy is mucositis due to drug toxicity for rapidly dividing cells. We show here that anti-DXR monoclonal antibodies can prevent DXR-induced damage. Indeed, apoptosis, confined to the proliferative compartment of the basal mucosa, observed in the tongue of DXR-treated mice was completely inhibited by topical application of the anti-DXR antibodies. © 2001 Cancer Research Campaign http://www.bjcancer.co

Lubricating effect of sialomucin and hyaluronan on pleural mesothelium

Coefficient of kinetic friction (m) between rabbit visceral and parietal pleura, sliding in vitro at physiological velocities and load, increases markedly after blotting mesothelial surface with filter paper; this increase is only partially reduced by wetting blotted mesothelium with Ringer solution. Given that mesothelial surface is covered by a thick coat with sialomucin and hyaluronan, we tested whether addition of sialomucin or hyaluronan solution after blotting lowers m more than Ringer alone. Actually, these macromolecules lowered m more than Ringer, so that m was no longer significantly higher than its preblotting value. Moreover, Ringer addition, after washout of macromolecule solution, increased m, in line with their dilution. These findings indicate that mesothelial blotting removes part of these molecules from the coat covering mesothelial surface, and their relevance for pleural lubrication. Transmission electron micrographs of pleural specimens after mesothelial blotting showed that microvilli were partially or largely removed from mesothelium, consistent with a substantial loss of macromolecules normally entrapped among them

Expression of Toll-like receptors 4 and 7 in the embryonic and adult pancreas, liver and adrenal gland of the mouse

The role of Toll protein in development and immunity is very well understood in Drosophila melanogaster (Anderson et al.,1985). Conversely, the contribution of Tolllike receptors (TLRs) in mammalian development is just beginning to be revealed. In this study, we evaluated the expression of TLR4 and TLR7 by immunohistochemistry on paraffin-embedded tissue in the adrenal gland, liver and pancreas of mouse embryos from stages E12, E14 and E16 and in the adult organs. Results show that TLR4 and TLR7 start to be detectable during embryonic development already at the first stage examined (E12). This expression follows the maturation of the organs and is still present in the adult with a different distribution pattern. Before this study no data in the literature were present on TLR4 and 7 expression in mammalian splanchnic organs development and in the adult no localization studies were available for TLR7. A possible interpretation of the results suggests that, besides their immunitary function, TLRs might be involved in a shared mechanism that regulates proliferation and differentiation both in embryonic organs and adult organs (Sato et al., 2009). These results also suggest that the contribution of TLRs in the context of carcinogenesis should be investigated not only in relation to chronic inflammation and tissue damage but also in relation to their contribution to the process of organogenesis

Expression of TLR7 in the murine eye during the embryonic period and in the adult animal

In the present study, we evaluated Toll-like receptor 7 (TLR7) expression at different stages of the murine eye development and in the adult organ. In mammals, TLRs are best known for their immunitary function, however data from the literature are demonstrating that in analogy to their Drosophila homologue Toll, they also participate in developmental mechanisms (Okun, Griffioen and Mattson 2011, Shechter et al. 2008). Immunohistochemistry for TLR7 and double immunofluorescence for TLR7/PCNA were performed on E12, E14 and E16 formalin-fixed paraffin-embedded mouse heads and on eyes enucleated from 3 months adult mice Results of experiments indicate that TLR7 expression is present in different compartments of the mouse eye (cornea, pigmented epithelium, neural retina, and lens) during gestation both in proliferating and differentiating cells and that such expression persists also in the adult organ. These observations indicate that besides being involved in protective mechanisms in the adult eye, TLR7 is also likely involved in the morphogenetic processes of this complex organ to which cells and tissues of different embryological origin contribute

Desmocollin 1 and desmoglein 1 expression in human epidermis and keratinizing oral mucosa: a comparative immunohistochemical and molecular study

Epidermis and keratinizing oral mucosa (KOM) are effective barriers against a wide spectrum of insults. The optimal form of protection provided by each epithelium is determined also by the molecular composition of desmosomes. Up to now, the expression of the "skin type" desmosomal cadherins, i.e. desmocollin 1 (Dsc1) and desmoglein 1 (Dsg1), was correlated with the morphological features of keratinocyte terminal differentiation in epidermis, but not in KOM. The aim of the present study was to investigate Dsc1 and Dsg1 expression in adult human KOM compared to epidermis. Biopsies of epidermis and KOM were obtained from young healthy adults (n=6) and simultaneously processed for immunofluorescence analysis, post-embedding immunogold electron microscopy (immunogold EM), and RT-PCR analysis. For molecular biology analysis, as a negative control, we considered human fibroblasts. By immunofluorescence and immunogold EM, Dsc1 labeling was not detected in any suprabasal layer of KOM, but it was present in the upper spinous/granular layers of epidermis. Immunofluorescence and transmission electron microscopy analysis showed that (i) Dsg1 expression was evident in the spinous, granular, and horny layer of the oral epithelium and (ii) Dsg1 immunoreactivity was always lower in desmosomes between oral keratinocytes than in all epidermal junctions. RT-PCR analysis confirmed that in KOM Dsc1 gene expression was undetectable. On the whole, these observations suggest a weakened adhesion in KOM, allowing oral keratinocytes to undergo a faster transition throughout the living layers of the epithelium. The intrinsic and specific regulation of the molecular composition of desmosomes can contribute in defining a specific keratinocyte phenotype in KOM and in epidermis

Activation of TLR‐4 to produce tumour necrosis factor‐α in neuropathic pain caused by paclitaxel

BackgroundNeuropathic pain is a common complication of treatment with the anti‐neoplastic drug paclitaxel. Animal studies suggest neuroinflammation and transient receptor potential channels TRPA1 and TRPV4 are involved in the pathogenesis of pain in this condition. However, how neuroinflammation and TRPA1 and TRPV4 are linked to cause pain in paclitaxel‐treated animals is not known.MethodsPaclitaxel‐induced pain was modelled by IP injection of paclitaxel (16 mg/kg) once a week for 5 weeks. The role of toll‐like receptor 4 (TLR‐4) in tumour necrosis factor‐α (TNF‐α) production and the effect of TNF‐α on the expression of TRPA1 and TRPV4 were evaluated in vitro and in vivo. TNF‐α signalling in dorsal root ganglion (DRG) was blocked by expressing soluble TNF receptor I (TNFsR) from a herpes simplex virus (HSV)‐based vector (vTNFsR).ResultsPaclitaxel treatment increased the expression and release of TNF‐α in satellite glial cells and increased the expression of TRPA1 and TRPV4 in DRG neurons in animals. In vitro, paclitaxel enhanced the expression and release of TNF‐α in enriched primary satellite glial cells, an effect that was blocked by an inhibitor of TLR‐4. Direct application of TNF‐α to primary DRG neurons in culture up‐regulated the expression of TRPA1 and TRPV4. In vivo, vector‐mediated TNFsR release from DRG neurons reduced paclitaxel‐induced up‐regulation of TRPA1 and TRPV4 expression and prevented paclitaxel‐induced pain.ConclusionThese results suggest that paclitaxel activation of TLR‐4 to cause release of TNF‐α from satellite glial cells increases the expression of TRPA1 and TRPV4 in DRG neurons to cause neuropathic pain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112183/1/ejp613.pd

PDGFR\u3b2 and FGFR2 mediate endothelial cell differentiation capability of triple negative breast carcinoma cells

Triple negative breast cancer (TNBC) is a very aggressive subgroup of breast carcinoma, still lacking specific markers for an effective targeted therapy and with a poorer prognosis compared to other breast cancer subtypes. In this study we investigated the possibility that TNBC cells contribute to the establishment of tumor vascular network by the process known as vasculogenic mimicry, through endothelial cell differentiation. Vascular-like functional properties of breast cancer cell lines were investigated in vitro by tube formation assay and in vivo by confocal microscopy, immunofluorescence or immunohistochemistry on frozen tumor sections. TNBCs express endothelial markers and acquire the ability to form vascular-like channels in vitro and in vivo, both in xenograft models and in human specimens, generating blood lacunae surrounded by tumor cells. Notably this feature is significantly associated with reduced disease free survival. The impairment of the main pathways involved in vessel formation, by treatment with inhibitors (i.e. Sunitinib and Bevacizumab) or by siRNA-mediating silencing, allowed the identification of PDGFR\u3b2 and FGFR2 as relevant players in this phenomenon. Inhibition of these tyrosine kinase receptors negatively affects vascular lacunae formation and significantly inhibits TNBC growth in vivo. In summary, we demonstrated that TNBCs have the ability to form vascular-like channels in vitro and to generate blood lacunae lined by tumor cells in vivo. Moreover, this feature is associated with poor outcome, probably contributing to the aggressiveness of this breast cancer subgroup. Finally, PDGFR\u3b2 and FGFR2-mediated pathways, identified as relevant in mediating this characteristic, potentially represent valid targets for a specific therapy of this breast cancer subgroup

The Role of TLR4 in the Paclitaxel Effects on Neuronal Growth In Vitro

Paclitaxel (Pac) is an antitumor agent that is widely used for treatment of solid cancers. While being effective as a chemotherapeutic agent, Pac in high doses is neurotoxic, specifically targeting sensory innervations. In view of these toxic effects associated with conventional chemotherapy, decreasing the dose of Pac has been recently suggested as an alternative approach, which might limit neurotoxicity and immunosuppression. However, it remains unclear if low doses of Pac retain its neurotoxic properties or might exhibit unusual effects on neuronal cells. The goal of this study was to analyze the concentration-dependent effect of Pac on isolated and cultured DRG neuronal cells from wild-type and TLR4 knockout mice. Three different morphological parameters were analyzed: the number of neurons which developed neurites, the number of neurites per cell and the total length of neurites per cell. Our data demonstrate that low concentrations of Pac (0.1 nM and 0.5 nM) do not influence the neuronal growth in cultures in both wild type and TLR4 knockout mice. Higher concentrations of Pac (1-100 nM) had a significant effect on DRG neurons from wild type mice, affecting the number of neurons which developed neurites, number of neurites per cell, and the length of neurites. In DRG from TLR4 knockout mice high concentrations of Pac showed a similar effect on the number of neurons which developed neurites and the length of neurites. At the same time, the number of neurites per cell, indicating the process of growth cone initiation, was not affected by high concentrations of Pac. Thus, our data showed that Pac in high concentrations has a significant damaging effect on axonal growth and that this effect is partially mediated through TLR4 pathways. Low doses of Pac are devoid of neuronal toxicity and thus can be safely used in a chemomodulation mode. © 2013 Ustinova et al

c-Myc expression in human anagen hair follicles

The hair follicle represents a very attractive organ system for studying the precise balance between cell proliferation, growth, differentiation, and death of cells, because it periodically and regularly regenerates, retaining its morphogenetic signals throughout its life. One of the most intriguing oncogenes which is able to induce both cell growth and apoptosis, depending upon the environmental conditions, is c-Myc. The aim of the present study was to investigate its presence and localization in human hair follicles by immunohistochemistry and immunofluorescence. Our observations demonstrated the consistent presence of two clusters of c-Myc-expressing cells in anagen follicles, located in two annular regions of the inner root sheath, at the border between cells characterized by putative trichohyalin granules and cells which are keratinized. The lower group belongs to Henle's layer, while the upper group belongs to Huxley's layer. c-Myc oncoprotein seems to favour apoptosis/differentiation and may be a marker for terminal differentiation of trichocytes, at least in the inner root sheath. Our findings agree with the interpretation that the complex morphology of the hair follicle reflects its complex function; the extrusion of a highly organized multicellular structure, the hair shaft, driven by another highly organized multicellular structure, the inner root sheath