Effects of dietary minerals on acid-base balance and eggshell quality in chickens

Three experiments were conducted in hens to determine the effects of high levels of dietary phosphorus (P, 1-1.5%), chloride (Cl, 0.8%) or both on acid-base balance and eggshell quality and to consider whether any adverse effects on eggshell quality can be attributed to alteration of blood acid-base balance. Eggshell quality and values for a blood indicator of acid-base balance were reduced by high levels of dietary P or Cl in all of the experiments. Eggshell quality and values for the blood acid-base indicator were further reduced by high dietary levels of the combination of minerals. The adverse effects associated with high levels of the combination were greater than the sum of adverse effects associated with high levels of each mineral. The effects of P and Cl on plasma levels of these minerals were inconsistent and varied among experiments. The use of pair-fed controls revealed that the adverse effects of combined P and Cl on eggshell quality and acid-base balance were independent of their effects on feed and calcium intake. Calcium excretion was increased by consumption of the high P, high Cl diet. The information obtained from these experiments suggests that the adverse effects of high levels of dietary P and/or Cl on eggshell quality may be due, at least in part, to increased Ca excretion. This, in turn, may be mediated by acidemia resulting from the dietary manipulations, although the present data were insufficient to provide a direct link between acidemia and Ca excretion.     

Mechanisms of immunotherapeutic intervention by anti-CD154 (CD40L) antibody in high-risk corneal transplantation.

This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts.     

MUC4 expression increases progressively in pancreatic intraepithelial neoplasia

Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma. We documented the pattern of expression of MUC4 in PanINs by studying a series of 71 PanIN lesions immunohistochemically using a new monoclonal antibody to MUC4. Five (17%) of 30 PanIN-1 lesions, 10 (36%) of 28 PanIN-2 lesions, 11 (85%) of 13 PanIN-3 lesions, and 25 (89%) of 28 invasive adenocarcinomas labeled with the MUC4 antibody used in the study. In addition, afew nonneoplastic lesions labeled with the MUC4 antibody, including reactive ducts in chronic pancreatitis, atrophic ducts filled with inspissated secretions, and ducts showing squamous metaplasia. Our data help establish the patterns of MUC4 expression in neoplastic precursors in the pancreas and add further support to the progression model for pancreatic adenocarcinoma.     

Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically

Sarcomas can be divided into those with specific translocations displaying monotonous cytomorphology, and those with complex karyotypes and marked cellular pleomorphism. Telomeres contain terminal DNA sequence repeats that maintain chromosomal stability. Telomeres shorten with cell division and may become dysfunctional leading to chromosomal instability. Using a fluorescence in situ hybridization/immunofluorescence method to assess telomere lengths in archival tissues we analyzed these two types of sarcomas using paraffin-embedded primary tumor specimens. Tissues from nine sarcomas with characteristic translocations (two synovial sarcomas, two alveolar rhabdomyosarcomas, two desmoplastic round cell tumors, and one each of infantile fibrosarcoma, myxoid liposarcoma, cellular congenital mesoblastic nephroma) and nine without (four malignant fibrous histiocytomas, two leiomyosarcomas, one pleomorphic rhabdomyosarcoma, one dedifferentiated chondrosarcoma, and one malignant peripheral nerve sheath tumor) were analyzed. In all (nine of nine) cases with specific translocations, which generally have few karyotypic abnormalities, telomere lengths were similar to or reduced compared to surrounding nonneoplastic tissues. In contrast, telomeres in cases lacking specific translocations, which generally contain complex karyotypes, were often found to be dramatically lengthened and heterogeneous. In addition to markedly elongated telomeres, seven of nine (78%) complex cases exhibited large brightly stained regions corresponding to a specific type of promyelocytic leukemia nuclear body found in immortalized cells that maintain telomeres in a telomerase-independent manner [alternative lengthening of telomeres (ALT) pathway]. This phenotype is unlike that of epithelial neoplasms that typically display complex karyotypes with abnormally short telomeres maintained by the enzyme telomerase. The discovery of heterogeneous telomere lengths and evidence of the ALT pathway in the majority of sarcomas with complex karyotypes supports the existence of a telomere maintenance pathway incapable of full karyotypic stabilization in pleomorphic sarcomas. These findings provide additional molecular-genetic evidence supporting the dichotomous grouping of sarcomas into those with characteristic signature translocations without extensive additional karyotypic abnormalities, and those without such signature translocations that typically display very complex karyotypes, and point to telomere dysfunction as a plausible contributor to the chromosomal aberrations found in complex sarcomas.     

The V599E BRAF mutation is uncommon in biliary tract cancers.

Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation--V599E--accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study.     

Portfolio Theory and Cost-Effectiveness Analysis: A Further Discussion

OBJECTIVES: Portfolio theory has been suggested as a means to improve the risk-return characteristics of investments in health-care programs through diversification when costs and effects are uncertain. This approach is based on the assumption that the investment proportions are not subject to uncertainty and that the budget can be invested in toto in health-care programs. METHODS: In the present paper we develop an algorithm that accounts for the fact that investment proportions in health-care programs may be uncertain (due to the uncertainty associated with costs) and limited (due to the size of the programs). The initial budget allocation across programs may therefore be revised at the end of the investment period to cover the extra costs of some programs with the leftover budget of other programs in the portfolio. RESULTS: Once the total budget is equivalent to or exceeds the expected costs of the programs in the portfolio, the initial budget allocation policy does not impact the risk-return characteristics of the combined portfolio, i.e., there is no benefit from diversification anymore. CONCLUSION: The applicability of portfolio methods to improve the risk-return characteristics of investments in health care is limited to situations where the available budget is much smaller than the expected costs of the programs to be funded.     

Review of Plasmonic Nanocomposite Metamaterial Absorber

Plasmonic metamaterials are artificial materials typically composed of noble metals in which the features of photonics and electronics are linked by coupling photons to conduction electrons of metal (known as surface _lasmon). These rationally designed structures have spurred interest noticeably since they demonstrate some fascinating properties which are unattainable with naturally occurring materials. Complete absorption of light is one of the recent exotic properties of plasmonic metamaterials which has broadened its application area considerably. This is realized by designing a medium whose impedance matches that of free space while being opaque. If such a medium is filled with some lossy medium, the resulting structure can absorb light totally in a sharp or broad frequency range. Although several types of metamaterials perfect absorber have been demonstrated so far, in the current paper we overview (and focus on) perfect absorbers based on nanocomposites where the total thickness is a few tens of nanometer and the absorption band is broad, tunable and insensitive to the angle of incidence. The nanocomposites consist of metal nanoparticles embedded in a dielectric matrix with a high filling factor close to the percolation threshold. The filling factor can be tailored by the vapor phase co-deposition of the metallic and dielectric components. In addition, novel wet chemical approaches are discussed which are bio-inspired or involve synthesis within levitating Leidenfrost drops, for instance. Moreover, theoretical considerations, optical properties, and potential application of perfect absorbers will be presented.     

Combined effects of auditory and visual cues on the perception of vection

Vection is the illusion of self-motion in the absence of real physical movement. The aim of the present study was to analyze how multisensory inputs (visual and auditory) contribute to the perception of vection. Participants were seated in a stationary position in front of a large, curved projection display and were exposed to a virtual scene that constantly rotated around the yaw-axis, simulating a 360° rotation. The virtual scene contained either only visual, only auditory, or a combination of visual and auditory cues. Additionally, simulated rotation speed (90°/s vs. 60°/s) and the number of sound sources (1 vs. 3) were varied for all three stimulus conditions. All participants were exposed to every condition in a randomized order. Data specific to vection latency, vection strength, the severity of motion sickness (MS), and postural steadiness were collected. Results revealed reduced vection onset latencies and increased vection strength when auditory cues were added to the visual stimuli, whereas MS and postural steadiness were not affected by the presence of auditory cues. Half of the participants reported experiencing auditorily induced vection, although the sensation was rather weak and less robust than visually induced vection. Results demonstrate that the combination of visual and auditory cues can enhance the sensation of vection.