Multiple primary malignant tumors involving the large bowel

We reviewed 5680 autopsy protocols in order to determine the frequency of Multiple Primary Malignant Tumors (MPMT) in different organs. The large bowel was the organ most frequently involved, making up to 32 per cent of all MPMT cases. Of 26 patients with colorectal MPMT, six were multicentric in the large bowel, and 20 were associated with extracolonic malignancies. The tissues harboring primary malignancies were, in order of decreasing frequency, liver, lung, and female and male reproductive organs. We compared the exact location of large bowel cancers in patients with and without a prior cholecystectomy; there was no statistically significant difference between the two groups, especially for right-sided colonic carcinoma in women.     

Proximal 1q21 duplication: A syndrome or a susceptibility locus?

Proximal 1q21 microduplication is an incomplete penetrance and variable expressivity syndrome. This study reports 28 new cases and summarizes data on phenotype, gender, and parental origin. Data on isolated proximal 1q21.1 microduplications (g. chr1:145,394,956–145,762,959 GRCh37/hg19) was retrieved in postnatal and prenatal “clinical cases” group, and prenatal “control group.” The “clinical cases” cases included cases where chromosomal microarray (CMA) was performed due to congenital anomalies, autism spectrum disorder, seizures, and developmental delay/intellectual disability. The “control group” cases consisted of fetal CMA performed upon parental request despite normal nuchal translucency and anatomical second trimester fetal scans. We analyzed a local database of 27,990 cases and another cohort of 80,000 cases (including both indicated and non-indicated cases) for population frequency analysis. A total of 62 heterozygous cases were found, including 28 index cases and 34 family members. Among the index cases, 13 (9 males, 4 females) were identified in the “clinical cases” group, of which 10 had developmental abnormalities. Parental origin was tested in 9/13 cases, and all were found to be maternally inherited. In the “control group,” which comprised non-affected cases, of 15 cases (10 males, 5 females), only 5/11 were maternally inherited. Four cases with clinical follow-up showed no reported neurodevelopmental abnormalities. No de-novo cases were detected, and the population frequency in both cohorts was 1:1000. Proximal 1q21.1 microduplication is a recurrent copy number variant, associated with neurodevelopmental abnormalities. It has a greater impact on males inheriting it from their mothers than females from their fathers.     

Autocrine VEGF‐A/KDR loop protects epithelial ovarian carcinoma cells from anoikis

Epithelial ovarian carcinoma (EOC) patients are usually diagnosed at an advanced stage, characterized by interperitoneal carcinomatosis and production of large volumes of ascites. Vascular endothelial growth factor‐A (VEGF‐A) and its main signaling receptor VEGFR2 (KDR) are coexpressed in primary ovarian tumors, ascitic cells and metastases, suggesting the existence of an autocrine VEGF‐A/KDR loop in EOC cells. In the present study, we examined this possibility and explored the role of this autocrine loop in protecting EOC cells from apoptosis under anchorage free growth conditions (anoikis). We found that 3 different EOC cell lines (Caov3, OVCAR3, SKOV3) express both VEGF‐A and its receptors, including KDR. In these cells, KDR is constitutively phosphorylated and is detected both in the cell plasma membrane and in the nucleus. Treating EOC cells with specific internal inhibitors of KDR kinase activity or a VEGF‐A neutralizing antibody abolished KDR autophosphorylation and resulted in significant increase in apoptosis when cells were grown in single‐cell, anchorage‐free conditions. By contrast, these blocking reagents had no effect on cell viability when EOC cells were grown in adhesive monolayers. In summary, our results indicate that an autocrine VEGF‐A/KDR loop exists in EOC cells and that it plays a role in protecting the cells from anoikis. Our results imply that treating EOC patients with VEGF blocking agents may potentially reduce peritoneal dissemination by decreasing vascular permeability as well as inducing apoptosis of shed ovarian cancer cells in ascites. © 2008 Wiley‐Liss, Inc.     

Asymmetric misfit nanotubes: Chemical affinity outwits the entropy at high-temperature solid-state reactions

Asymmetric two-dimensional (2D) structures (often named Janus), like SeMoS and their nanotubes, have tremendous scope in material chemistry, nanophotonics, and nanoelectronics due to a lack of inversion symmetry and time-reversal symmetry. The synthesis of these structures is fundamentally difficult owing to the entropy-driven randomized distribution of chalcogens. Indeed, no Janus nanotubes were experimentally prepared, so far. Serendipitously, a family of asymmetric misfit layer superstructures (tubes and flakes), including LaX-TaX₂ (where X = S/Se), were synthesized by high-temperature chemical vapor transport reaction in which the Se binds exclusively to the Ta atoms and La binds to S atoms rather than the anticipated random distribution. With increasing Se concentration, the LaS-TaX₂ misfit structure gradually transformed into a new LaS-TaSe₂-TaSe₂ superstructure. No misfit structures were found for x_Se = 1. These counterintuitive results shed light on the chemical selectivity and stability of misfit compounds and 2D alloys, in general. The lack of inversion symmetry in these asymmetric compounds induces very large local electrical dipoles. The loss of inversion and time-reversal symmetries in the chiral nanotubes offers intriguing physical observations and applications.

High-temperature, solid-state multielement reactions are often dominated by large entropy and diffusion, with the chemical affinity playing lesser importance. In particular, the reaction of S and Se with transition metals at elevated temperatures is expected to yield a random distribution of the chalcogen in the anion lattice sites (e.g., in transition metal chalcogenide alloys, in which S and Se tend to occupy the lattice indiscriminately) (1). However, the selective occupation of chalcogen in a particular lattice or plane has fundamental interest due to the structural symmetry breaking. Recently, a simple asymmetric (Janus) two-dimensional (2D) structure of SeMoS/SeWS was fabricated by combining a series of complex chemical and physical processes (2, 3). These strategies cannot be applied to get one-dimensional (1D) structures, such as multiwall asymmetric nanotubes. Nonetheless, the asymmetric distribution of chalcogen on different crystallographic planes or selectivity toward different lattice sites in these structures can bring about a new physics. Despite the large interest in such Janus nanotubes (4–7), attempts to synthesize 1D nanotubes with an asymmetric structure failed so far. One such platform to study the asymmetric distribution of S and Se is superlattices of misfit layered compounds (MLC) and nanotubes thereof (8, 9). MLCs are nonstoichiometric compounds with the general formula (MX)_1+y(TX₂)_n (M = Pb, Sn, Bi, rare-earth [Ln], T= Ta, Nb, Cr, Ti and X = S, Se and 1+y =2a_T/a_O) (10–12). The MLC structure is built from the periodically repeated LaX (O) and TaX₂ (T) units (Fig. 1A) and is commonly designated as MX-TX₂ or (O-T) superstructure (SI Appendix, T1.1). The nonstoichiometry arises due to the incommensurate a-axes (Fig. 1B) of the alternating rocksalt LaX and orthohexagonal TaX₂ subunits. Furthermore, combining two independent forces, i.e., the relaxation of the misfit lattice (incommensurate a lattice vector) (13, 14), and healing of the dangling bonds in the rim atoms (15, 16), various MLC nanotubes were produced in recent years (SI Appendix, T1.2).Open in a separate windowFig. 1.Structure of MLCs, distribution of S/Se in La (S,Se)-Ta(S,Se)₂, asymmetric nanotubes, and chemical maps. (A) Schematic drawing of the LaS-TaS₂ MLC lattice along the c-direction (O and T represent orthorhombic and trigonal prismatic coordination of La and Ta, respectively). (B) MLC viewed in a-b plane exhibiting the incommensurate a and commensurate b axes. The unit cell of rocksalt (LaS), hexagonal (TaS₂), and orthohexagonal lattice are marked by black, green, and dotted pink rectangles, respectively. (C–E) Schematic models of the mixed (S,Se) MLC and their nanotubes. (C) S and Se distribute randomly in the lattice; (D) Se binds to La, while S binds to the Ta; and (E) opposite binding (La-S and Ta-Se). (F) SEM images of flakes and nanotubes of both x_Se = 0.2 and 0.8. (Scale bar, 1 μm.) Note that the nanotubes are abundant in x_Se = 0.2 and are much less so in x_Se = 0.8 (SI Appendix). The corresponding SEM-EDS chemical maps of individual nanotubes from the x_Se = 0.2 (up) and 0.8 (down) are shown. (Scale bars, 1 and 3 μm, respectively.)If both S and Se were used for the synthesis, instead of pure S, MLC alloys containing both elements would be expected to form (Fig. 1 C–E). In fact, one would expect a random distribution of chalcogen atoms in the (O-T) superlattice (as shown in Fig. 1C; SI Appendix, T1.3). Surprisingly, an asymmetric distribution with the Se atoms binding exclusively to Ta and La atoms to S in both nanotubes and flakes were found at elevated temperatures (Fig. 1E). Such selectivity induces a very large dipole moment and could have a remarkable influence on the physical behavior of these nanomaterials due to the breaking of inversion and time-reversal symmetries (17). MLC nanotubes of the form Ln(S,Se)-Ta(S,Se)₂ with Ln = rare-earth and Se/S concentration ratio of 1:1 were among the few quaternary MLC nanotubes studied before (18). Though the signature of asymmetric distribution was observed in those cases, the lack of advanced analytical tools and the unique 1:1 Se/S composition did not allow for exquisite control of the chemical selectivity and elucidating the stability limits of these asymmetric MLC. Here, we report a family of asymmetric misfit LaS-Ta(S,Se)₂ nanotubes with varying Se concentration (x_Se) from 0 to 1 (0 ≤ x_Se ≤ 1; SI Appendix, T2.1). The preferential binding of Se and S implies that under increasing selenium content, the periodic (O-T) LaS-Ta(S,Se)₂ structure gradually becomes unstable and transforms into a periodic (O-T-T) structure of LaS-TaSe₂-TaSe₂, at x_Se = 0.8. Ultimately, the MLC lattice at pure Se content became unstable, decomposing into the binary counterparts. Since LaSe is more covalent than its sulfur counterpart (10, 19), the charge transfer in this case would be much less favorable compared to the respective sulfide, making the MLC unstable. Some general conclusions regarding the chemical reactivity and stability of MLC compounds and nanotubes thereof as well as their physical behavior will be drawn from this study.     

Medical iPad use in the cardiac catheterization and echo laboratories

The present study aims to describe a dedicated cardiac imaging application on a tablet and to assess the accuracy and reproducibility of this novel application for measurement on angiography and echocardiography data sets. Tablet devices have recently been used in radiological image interpretation and enable transfer of images. It allows the clinician to look up clinical information, search the Internet and communicate with colleagues and family. The study group consisted of 30 patients who had both echocardiographic and angiographic examinations. For each patient, a few measurements (i.e. length, area and angle) were performed using the iPad, and compared to the McKesson workstation, which is routinely used in the hospital. In order to show the equivalence between these two methods, a linear regression was fitted and the distribution of differences between measurements was examined. In addition, the variability of the measurements was compared between two different reviewers (inter-observer test) and between the measurements of the same reviewer at two different time settings (intra-observer test) by calculating the intraclass correlation coefficient (ICC). In all comparisons, the linear regression showed high correlation coefficient (r > 0.9), and the distribution of differences was around zero, implying that the two methods lead to equivalent results. The absolute mean difference between the two different observers demonstrated high agreement between the two observers’ repeated measurements. The same conclusions can be deduced from the same observer’s repeated measurements. The ICC indicates the resemblance between the two sets, and could be considered almost perfect (ICC > 0.968 for all cases). The newly developed cardiology iPad application offers the opportunity to accurately present the cardiac procedure in a visual, clear and professional manner.     

Adolescents’ risk-taking behavior is driven by tolerance to ambiguity

Adolescents engage in a wide range of risky behaviors that their older peers shun, and at an enormous cost. Despite being older, stronger, and healthier than children, adolescents face twice the risk of mortality and morbidity faced by their younger peers. Are adolescents really risk-seekers or does some richer underlying preference drive their love of the uncertain? To answer that question, we used standard experimental economic methods to assess the attitudes of 65 individuals ranging in age from 12 to 50 toward risk and ambiguity. Perhaps surprisingly, we found that adolescents were, if anything, more averse to clearly stated risks than their older peers. What distinguished adolescents was their willingness to accept ambiguous conditions—situations in which the likelihood of winning and losing is unknown. Though adults find ambiguous monetary lotteries undesirable, adolescents find them tolerable. This finding suggests that the higher level of risk-taking observed among adolescents may reflect a higher tolerance for the unknown. Biologically, such a tolerance may make sense, because it would allow young organisms to take better advantage of learning opportunities; it also suggests that policies that seek to inform adolescents of the risks, costs, and benefits of unexperienced dangerous behaviors may be effective and, when appropriate, could be used to complement policies that limit their experiences.     

Crohn��s Disease: A Surgeon��s Perspective

Crohn’s disease (CD) is known for wide anatomic distribution, different presentations, life-threatening complications, and multiple modalities of management. Its multiple implications are still unaddressed. Since all the patients do not show a good response to medical modalities of treatment, a significant percentage of these patients are referred to the surgeon for the palliation of complications or for the ultimate curative treatment. Since most surgeons come across such patients only rarely, it is sometimes difficult for them to choose the appropriate procedure at the time of need. Moreover, the various surgical modalities available for the different presentations and complications of the disease have not been adequately discussed. The aim of this review is to offer insight and a detailed account of the management of CD from a surgical perspective. This review offers an overview of the various surgical options available, their utility in context, and an approach to various scenarios of complicated CD.     

Cognitive and Verbal Abilities of 24- to 36-month-old Siblings of Children with Autism

The cognitive and language skills of 30 siblings of children with autism (SIBS-A) and 30 siblings of typically developing children (SIBS-TD) were compared. Non-significant group differences emerged for cognition at both ages. At 24 months, significantly more SIBS-A demonstrated language scores one or two standard deviations below the mean compared to SIBS-TD. At 36 months, the groups differed significantly in receptive language, and more SIBS-A displayed receptive and expressive difficulties compared to SIBS-TD. Six SIBS-A (including one diagnosed with autism) revealed language scores more than two standard deviations below the mean at both ages, a pattern not seen in the SIBS-TD. Results are discussed in reference to language difficulties in autism spectrum disorders and the genetic liability for autism.