Case report: The management of advanced oral cancer in a Jehovah's Witness using the Ultracision Harmonic Scalpel

We present the first case of a head and neck oncological procedure accomplished in a Jehovah's Witness using the Ultracision Harmonic Scalpel (Ethicon, Cincinnati, OH). Jehovah's Witnesses present a serious challenge to the head and neck cancer surgeon due to their refusal to accept transfusion of any blood products. However, our experience reinforces the view that surgical management of head and neck cancer is possible in these patients. We show the Harmonic Scalpel, an ultrasonic tissue dissector, to be a useful surgical tool in obviating the need for blood transfusion. Preoperative optimisation, intra-operative surgical and anaesthetic techniques are also fully discussed

A deletion of FGFR2 creating a chimeric IIIb/IIIc exon in a child with Apert syndrome

<p>Abstract</p> <p>Background</p> <p>Signalling by fibroblast growth factor receptor type 2 (FGFR2) normally involves a tissue-specific alternative splice choice between two exons (IIIb and IIIc), which generates two receptor isoforms (FGFR2b and FGFR2c respectively) with differing repertoires of FGF-binding specificity. Here we describe a unique chimeric IIIb/c exon in a patient with Apert syndrome, generated by a non-allelic homologous recombination event.</p> <p>Case Presentation</p> <p>We present a child with Apert syndrome in whom routine genetic testing had excluded the <it>FGFR2 </it>missense mutations commonly associated with this disorder. The patient was found to harbour a heterozygous 1372 bp deletion between <it>FGFR2 </it>exons IIIb and IIIc, apparently originating from recombination between 13 bp of identical DNA sequence present in both exons. The rearrangement was not present in the unaffected parents.</p> <p>Conclusions</p> <p>Based on the known pathogenesis of Apert syndrome, the chimeric FGFR2 protein is predicted to act in a dominant gain-of-function manner. This is likely to result from its expression in mesenchymal tissues, where retention of most of the residues essential for FGFR2b binding activity would result in autocrine activation. This report adds to the repertoire of rare cases of Apert syndrome for which a pathogenesis based on atypical <it>FGFR2 </it>rearrangements can be demonstrated.</p

Adjuvant breast cancer chemotherapy during late-trimester pregnancy: not quite a standard of care

<p>Abstract</p> <p>Background</p> <p>Diagnosis of breast cancer during pregnancy was formerly considered an indication for abortion. The pendulum has since swung to the other extreme, with most reviews now rejecting termination while endorsing immediate anthracycline-based therapy for any pregnant patient beyond the first trimester. To assess the evidence for this radical change in thinking, a review of relevant studies in the fields of breast cancer chemotherapy, pregnancy, and drug safety was conducted.</p> <p>Discussion</p> <p>Accumulating evidence for the short-term safety of anthracycline-based chemotherapy during late-trimester pregnancy represents a clear advance over the traditional norm of therapeutic abortion. Nonetheless, the emerging orthodoxy favoring routine chemotherapy during gestation should continue to be questioned on several grounds: (1) the assumed difference in maternal survival accruing from chemotherapy administered earlier – i.e., during pregnancy, rather than after delivery – has not been quantified; (2) the added survival benefit of adjuvant cytotoxic therapy prescribed within the hormone-rich milieu of pregnancy remains presumptive, particularly for ER-positive disease; (3) the maternal survival benefit associated with modified adjuvant regimens (e.g., weekly schedules, omission of taxanes, etc.) has not been proven equivalent to standard (e.g., post-delivery) regimens; and (4) the long-term transplacental and transgenerational hazards of late-trimester chemotherapy are unknown.</p> <p>Summary</p> <p>Although an incrementally increased risk of cancer-specific mortality is impossible to exclude, mothers who place a high priority on the lifelong well-being of their progeny may be informed that deferring optimal chemotherapy until after delivery is still an option to consider, especially in ER-positive, node-negative and/or last-trimester disease.</p

Medium/Long wavelength sensitive opsin diversity in Pitheciidae

New World primates feature a complex colour vision system. Most species have polymorphic colour vision where males have a dichromatic colour perception and females can be either ichromatic or trichromatic. The adaptive value of high allelic diversity of opsins, a light sensitive protein, found in primates’ eyes remains unknown. Studies revealing the allelic diversity are important as they shed light on our understanding of the adaptive value of differences in the colouration of species and their ecologies. Here we investigate the allelic types found in Pitheciidae, an understudied New World primate family, revealing the diversity of medium/long wavelength sensitive opsins both in cryptic and conspicuous species of this primate family. We found five alleles in Cacajao, six in Callicebinae (i.e. Plecturocebus, Cheracebus, and Callicebus), four in Chiropotes, and three in Pithecia, some of them reported for the first time. Both cryptic and conspicuous species in this group presented high allelic diversity

Thin Film Magnesium Boride Superconductor with Very High Critical Current Density and Enhanced Irreversibility Field

The discovery of superconductivity at 39 K in magnesium diboride offers the possibility of a new class of low-cost, high-performance superconducting materials for magnets and electronic applications. With twice the critical temperature of Nb_3Sn and four times that of Nb-Ti alloy, MgB_2 has the potential to reach much higher fields and current densities than either of these technological superconductors. A vital prerequisite, strongly linked current flow, has already been demonstrated even at this early stage. One possible drawback is the observation that the field at which superconductivity is destroyed is modest. Further, the field which limits the range of practical applications, the irreversibility field H*(T), is ~7 T at liquid helium temperature (4.2 K), significantly lower than ~10 T for Nb-Ti and ~20 T for Nb_3Sn. Here we show that MgB_2 thin films can exhibit a much steeper temperature dependence of H*(T) than is observed in bulk materials, yielding H*(4.2 K) above 14 T. In addition, very high critical current densities at 4.2 K, 1 MA/cm_2 at 1 T and 10_5 A/cm_2 at 10 T, are possible. These data demonstrate that MgB_2 has credible potential for high-field superconducting applications.Comment: 4 pages pdf, submitted to Nature 3/20/0

Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms

Background:Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart.Methods:Goto-Kakizaki (GK) rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin) or vehicle (n=10, each). After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays.Results:Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36), alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells.Conclusions:Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36) promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actionsThis work was supported by national funding from Ministerio de Educación y Ciencia (SAF2009-08367), Comunidad de Madrid (CCG10-UAM/ BIO-5289), and a unrestricted grant from by Merck/MS

Surface functionalisation of nanodiamonds for human neural stem cell adhesion and proliferation.

Biological systems interact with nanostructured materials on a sub-cellular level. These interactions may govern cell behaviour and the precise control of a nanomaterial's structure and surface chemistry allow for a high degree of tunability to be achieved. Cells are surrounded by an extra-cellular matrix with nano-topographical properties. Diamond based materials, and specifically nanostructured diamond has attracted much attention due to its extreme electrical and mechanical properties, chemical inertness and biocompatibility. Here the interaction of nanodiamond monolayers with human Neural Stem Cells (hNSCs) has been investigated. The effect of altering surface functionalisation of nanodiamonds on hNSC adhesion and proliferation has shown that confluent cellular attachment occurs on oxygen terminated nanodiamonds (O-NDs), but not on hydrogen terminated nanodiamonds (H-NDs). Analysis of H and O-NDs by Atomic Force Microscopy, contact angle measurements and protein adsorption suggests that differences in topography, wettability, surface charge and protein adsorption of these surfaces may underlie the difference in cellular adhesion of hNSCs reported here