Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.     

Some Insights into MIMO Mutual Information: The High SNR Case

We consider mutual information of multiple-input multiple-output (MIMO) wireless channels with complex isotropic Gaussian input in the case where the receiver has perfect channel, knowledge. For arbitrary fading statistics, a mutual information lower bound is decomposed in a sum of three terms involving: a) average SNR; b) channel fading; and c) a term characterizing the "effective rank", or eigenvalue dispersion, of the channel matrix. The decomposition suggests that spatial multiplexing efficiency of a MIMO channel can be characterized by the so-called ellipticity statistic. Distribution functions, means and variances of the random terms in the decomposition for the case of Rayleigh fading are also derived     

46,XX/69,XXX diploid-triploid mixoploidy with hypothyroidism and precocious puberty

We report a 20 month old female patient with diploid-triploid mixoploidy (46,XX/69,XXX) syndrome with hypothyroidism and precocious puberty. The triploid cell line was only expressed in the fibroblast culture and comprised the majority (95%) of the cells. Chromosome analysis of the fetal blood sample and peripheral blood sample were normal. The patient shows typical features of full triploidy (growth and severe mental retardation, cranial and facial dysmorphism, complete syndactyly of fingers 3/4, partial syndactyly of toes 2/3) and facial but no body asymmetry. At the age of 5 months central hypothyroidism and precocious puberty were diagnosed. Thin pigmented streaks were visible on the wrists and legs of the patient at the age of 16 months. This is the first patient reported so far with 46,XX/69,XXX mixoploidy suffering from hypothyroidism and precocious puberty.     

Heart transplantation in Finland 1985-1995

BACKGROUND: Clearance of large molecules from the interstitial space is an important function of lymphatics and is affected by local pathologic changes. OBJECTIVE: To determine if the clearance rate of interstitially injected albumin is correlated to tumour characteristics and outcome in women with invasive breast cancer. METHOD: In a consecutive series of women coming to biopsy for suspected breast cancer, technetium-tagged albumin was injected into the tissue adjacent to the palpable mass. The isotope disappearance rate was measured over two hours. Also assessed were the maximum vessel density (MVD-using Factor VIII polyclonal antisera), the proliferation rate (using Ki-67 antisera), node status, tumour size, histologic and nuclear grade, mitotic rate, and p53 and c-erbB-2 oncoproteins. All patients were followed until relapse and for a minimum of 10 years. RESULTS: In multivariate analysis, an association between relapse-free survival and isotope clearance rate was suggested (p = 0.024). The best outcome was seen in patients with the least isotope clearance. Node status, size, histologic and nuclear grade, and mitotic rate correlated with survival. MVD did not correlate with survival and was inversely related to the isotope clearance rate. Tumour proliferation rate, and the c-erbB-2 and p53 oncoproteins did not relate to outcome. CONCLUSION: The role of lymphatics in breast cancer is difficult to study. Measurement of interstitial clearance may be a useful technique and could be a prognostic factor.     

Macrophage activation results in bone resorption

Monocytes or macrophages from important accessory cells in the regulation of bone metabolism and destruction. Cells of the mononuclear phagocyte lineage form the precursor cells of the osteoclasts. Soluble products produced by activated macrophages regulate progenitor cell proliferation, recruitment, differentiation, and activity of osteoblasts and osteoclasts. After osteoclasts are removed from the resorption site, macrophages process bone surfaces and create a cement line before osteoblasts enter to form new bone. Although osteolysis associated with normal bone remodeling is seen as an osteoclast driven process, it may be that in chronic inflammation macrophage activation and vascular derangements lead to low pH, local bone demineralization (acid attack), and H+ mediated stimulation of the primary afferent nociceptive nerve fibers (bone pain). Osteoclasts are not able to attach to demineralized bone or to osteoid surfaces. However, if macrophages degrade the demineralized organic bone matrix, chemotactic factors and attachment sites for osteoclasts are produced. In such a scenario, the osteoclast-osteoblast mediated activation, resorption, and formation cycle would be secondarily activated. Such events may play a role in the most common orthopaedic problem related to macrophage activation, aseptic loosening of orthopaedic joint implants, which is secondary to a chronic foreign body reaction and to micromovement.     

Atlantoaxial instability complicating radiation therapy for recurrent nasopharyngeal carcinoma. A case report

STUDY DESIGN: A case report of a patient in whom atlantoaxial instability developed secondary to repeat radiation therapy for recurrent nasopharyngeal carcinoma. OBJECTIVES: To illustrate a dramatic and previously unreported complication of local radiation to the posterior nasopharynx. SUMMARY OF BACKGROUND DATA: Nasopharyngeal carcinoma is an unusual tumor that usually is managed with local, external-beam radiation. It is not thought to involve the cervical spine directly, although local invasion of the skull base is common. METHODS: A review of the medical records and radiographs of the only patient known to develop this complication of radiation used to manage nasopharyngeal carcinoma. RESULTS: Atlantoaxial instability developed in a patient as a result of repeat radiation for a locally recurrent tumor. The instability was associated with intrusion of the anterior arch of C1 into the posterior nasopharynx and was managed successfully with a posterior stabilization using transarticular screws and supplemental wiring. CONCLUSIONS: Patients who have undergone local irradiation for nasopharyngeal carcinoma may be at risk for developing atlantoaxial instability.     

Expression and Roles of Individual HIF Prolyl 4-Hydroxylase Isoenzymes in the Regulation of the Hypoxia Response Pathway along the Murine Gastrointestinal Epithelium

The HIF prolyl 4-hydroxylases (HIF-P4H) control hypoxia-inducible factor (HIF), a powerful mechanism regulating cellular adaptation to decreased oxygenation. The gastrointestinal epithelium subsists in “physiological hypoxia” and should therefore have an especially well-designed control over this adaptation. Thus, we assessed the absolute mRNA expression levels of the HIF pathway components, Hif1a, HIF2a, Hif-p4h-1, 2 and 3 and factor inhibiting HIF (Fih1) in murine jejunum, caecum and colon epithelium using droplet digital PCR. We found a higher expression of all these genes towards the distal end of the gastrointestinal tract. We detected mRNA for Hif-p4h-1, 2 and 3 in all parts of the gastrointestinal tract. Hif-p4h-2 had significantly higher expression levels compared to Hif-p4h-1 and 3 in colon and caecum epithelium. To test the roles each HIF-P4H isoform plays in the gut epithelium, we measured the gene expression of classical HIF target genes in Hif-p4h-1^−/−, Hif-p4h-2 hypomorph and Hif-p4h-3^−/− mice. Only Hif-p4h-2 hypomorphism led to an upregulation of HIF target genes, confirming a predominant role of HIF-P4H-2. However, the abundance of Hif-p4h-1 and 3 expression in the gastrointestinal epithelium implies that these isoforms may have specific functions as well. Thus, the development of selective inhibitors might be useful for diverging therapeutic needs.     

Modification of phenol–formaldehyde resol resins by lignin,starch, and urea

Lignin‐based chemicals, starch, and urea were used as modifiers for phenol–formaldehyde resol resins. The effects of the addition stage of the modifiers used in the synthesis of the resins and the type of modification reagent on the structures of the resins and their molar masses and reactivities were investigated. The modifications with corn starch and lignin promoted condensation; this was verified by increased molar masses and high ratios of methylene bridges to the sum of free ortho and para aromatic groups with respect to the corresponding reference resin without a modification reagent. The later the modifier was added to the resin condensation mixture, the more methylene bridges were formed with respect to the amounts of free ortho and para aromatic groups. In addition, when urea or wheat starch was added in the later condensation stage, the final condensation also reached high stages. The modifications with lignosulfonate and starch, as well as the early addition of urea, enhanced p–p′ bridge structures. The lowest condensation stage and, therefore, the highest reactivity were found when wheat starch was added with the starting reagents. The curing heat of the wheat‐starch‐modified resins decreased according to the deferred addition point of starch. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 582–588, 2003     

Additive manufacturing in the spare parts supply chain

As additive manufacturing (AM) evolves to become a common method of producing final parts, further study of this computer integrated technology is necessary. The purpose of this research is to evaluate the potential impact of additive manufacturing improvements on the configuration of spare parts supply chains. This goal has been accomplished through scenario modeling of a real-life spare parts supply chain in the aeronautics industry. The spare parts supply chain of the F-18 Super Hornet fighter jet was selected as the case study because the air-cooling ducts of the environmental control system are produced using AM technology. In total, four scenarios are investigated that vary the supply chain configurations and additive manufacturing machine specifications. The reference scenario is based on the spare parts supplier's current practice and the possible future decentralization of production and likely improvements in AM technology. Total operating cost, including downtime cost, is used to compare the scenarios. We found that using current AM technology, centralized production is clearly the preferable supply chain configuration in the case example. However, distributed spare parts production becomes practical as AM machines become less capital intensive, more autonomous and offer shorter production cycles. This investigation provides guidance for the development of additive manufacturing machines and their possible deployment in spare parts supply chains. This study contributes to the emerging literature on AM deployment in supply chains with a real-world case setting and scenario model illustrating the cost trade-offs and critical requirements for technology development.     

Safety Considerations during Different Stages of a Project Life Cycle in the Manufacturing Industry

At sites with multiple employers, efficient safety management is essential to ensure safety for both customers and providers. However, implementing effective safety management is challenging, particularly for companies that provide services. Provider companies encounter difficulties managing the safety of service projects for many reasons, including the variety of customers and changes in work environment. Proper preparation and integration of safety into the different project life cycle stages improves safety, but the topic has not received much attention to date. This article discusses the integration of safety considerations into service projects. Material was collected from Finnish manufacturing companies via interviews and a questionnaire. The results show that systematic methods for developing and producing services have not been adopted in the provider companies, but these are often implemented as a result of practical experience. On the other hand, providers and customers both believed that safety is taken into account during different stages of a given service project—safety issues were to some extent taken into account during the tendering and contract stages of a project, and preventive safety measures were commonly implemented during the delivery of services. However, safety performance often was not evaluated after completion of work. For this reason, companies may not have an accurate estimation of each other's safety performance in these types of multi‐employer situations. The results of this study can be used in provider organizations to help systematize safety considerations during service projects and to focus efforts on the most essential points of service project safety management.