Cell interaction with three-dimensional sharp-tip nanotopography

Cells in their native microenvironment interact with three-dimensional (3D) nanofeatures. Despite many reports on the effects of substrate nanotopography on cells, the independent effect of 3D parameters has not been investigated. Recent advances in nanofabrication for precise control of nanostructure pattern, periodicity, shape, and height enabled this systematic study of cell interactions with 3D nanotopographies. Two distinct nanopatterns (posts and grates) with varying three-dimensionalities (50-600 nm in nanostructure height) were created, while maintaining the pattern periodicity (230 nm in pitch) and tip shape (needle- or blade-like sharp tips). Human foreskin fibroblasts exhibited significantly smaller cell size and lower proliferation on needle-like nanoposts, and enhanced elongation with alignment on blade-like nanogrates. These phenomena became more pronounced as the nanotopographical three-dimensionality (structural height) increased. The nanopost and nanograte architectures provided the distinct contact guidance for both filopodia extension and the formation of adhesion molecules complex, which was believed to lead to the unique cell behaviors observed.     

The clinical spectrum of postpartum thyroid disease

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed post-partum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.      

Review article: Identifying occupational violence patient risk factors and risk assessment tools in the emergency department: A scoping review

Occupational violence (OV) is a daily risk for ED staff. It contributes to staff stress, sick leave, turn‐over and burn‐out, and limits the capacity of staff to provide unimpeded quality care to patients and their families. Many factors contribute to incidents of OV; however, early detection of such risk factors could pre‐empt incidences of OV during ED episodes of care. A five‐stage methodological framework for scoping reviews was used to identify, summarise and synthesise OV risk factors from five key databases. A validated tool was used to appraise the quality of included studies. Independent evaluation by the reviewers was used throughout. Patient factors were extracted and described from 24 methodologically and geographically diverse papers. Methodological quality for these studies varied from moderate to high. A total of 34 OV risk factors were identified. Although there was variation in, and differences between, staff‐perceived and objective (documented) OV risk factors, patient risk factors can be categorised into three main groups: clinical presentation, behaviours and past history. Five existing ED OV risk assessment tools were identified, with limited supporting evidence for each. The results support the development of a reliable and validated OV risk assessment tool to be initiated at triage.     

Solitary fibrous tumour of the cheek: An unusual presentation of a rare soft tissue tumour

This case report discusses the unusual presentation and ultrasound features of a solitary fibrous tumour of the face. Solitary fibrous tumour is an uncommon form of soft tissue tumour which, although seen predominantly within the lung pleura, can occur throughout the body in sites such as the peritoneum, mediastinum and head and neck. Ultrasound is an excellent imaging modality in the assessment of soft tissue masses in the head and neck. The ultrasound features demonstrated by this example of solitary fibrous tumour are reviewed. This report also highlights that ultrasound alone is ultimately limited in reaching a definitive diagnosis. The roles of other investigations such as ultrasound-guided biopsy and cross-sectional imaging are discussed.     

The repopulation potential of fetal liver hematopoietic stem cells in mice exceeds that of their liver adult bone marrow counterparts

Varying, limiting numbers of unseparated or purified cells (Ly-5.1), either from 14.5-day-old fetal liver (FL) or from adult bone marrow (BM) were coinjected with 10(5) unseparated BM cells (Ly-5.2) into lethally irradiated adult C57B1/6 recipients (Ly-5.2). The kinetics of donor cell repopulation of the lymphoid and myeloid compartments by Ly- 5.1+ donor hematopoietic stem cells (ie, competitive repopulation units [CRU]) were monitored at various time points after the transplantation by Ly-5 analysis of the peripheral white blood cells (WBC). Recipients that had received on average less than 2 adult BM or FL CRU did not show a significant difference in the level of donor-reconstitution when analyzed 4 weeks after the transplantation, However, at 8 and 16 weeks, the FL recipients showed a significantly higher percentage of donor- derived nucleated peripheral blood cells than did the recipients of adult BM cells. Analysis of individual mice showed that approximately 80% of the recipients of FL CRU showed an increase in mature WBC output between 4 and 8 weeks after transplantation, whereas this occurred in less than 40% in the recipients of adult BM cells. In addition to this effect on mature cell output, the cellularity of the reconstituted BM was significantly higher in recipients of FL CRU than in recipients of adult BM CRU, even at 7 to 9 months after transplantation, which is consistent with an increased clonal expansion of FL CRU. When marrow cells from primary recipients of FL CRU were injected into secondary recipients, a significantly higher percentage of these mice showed donor-reconstitution of their lymphoid and myeloid compartments (P < .01) and to a greater extent (P < .008) as compared with mice that had received marrow cells from primary recipients of similar numbers of adult BM CRU. Taken together, these results show that individual FL CRU exhibit a greater proliferative activity in vivo than similar cells from adult BM that is accompanied by a greater production of daughter CRU.     

Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder.     

The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and primary sclerosing cholangitis

Background  

In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) fatigue is a major clinical problem. Abnormal amino acid (AA) patterns have been implicated in the development of fatigue in several non-hepatological conditions but for PBC and PSC no data are available. This study aimed to identify abnormalities in AA patterns and to define their relation with fatigue.     

Fibrinolytic properties of a human endothelial hybrid cell line (Ea.hy 926)

The fibrinolytic characteristics of the endothelial hybrid cell line EA.hy 926, established by fusing a human umbilical vein endothelial cell with a human carcinoma cell line, were studied. The hybrid cell line produced large amounts of tissue-type plasminogen activator (t- PA), plasminogen activator inhibitor type 1, and a small amount of urokinase. All plasminogen activator present in conditioned medium was complexed with inhibitor because the cells secreted plasminogen activator inhibitor in excess over plasminogen activator and no activator activity was detectable in conditioned media by direct activity assays. t-PA activator activity was, however, demonstrable in conditioned media after treatment with sodium dodecyl sulfate, in agreement with t-PA antigen determinations. Increased plasminogen activator inhibitor activity could be induced by incubating the cells in the presence of endotoxin or microtubule inhibitors, whereas increased t-PA activity could be induced by microtubule inhibitors. Interleukin-1 had no effect. The fibrinolytic characteristics of the hybrid cell line were stable for at least 30 passages. The perpetual human hybrid cell line EA.hy 926 therefore may be a useful tool for the study of fibrinolysis in cultured endothelial cells.