Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and involves the cornerstone metabolic pathways which take place in the microsomes within hepatocytes. APAP hepatotoxicity remains a global issue; in the United States, in particular, it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases. The pathophysiology, disease course and management of acute liver failure secondary to APAP toxicity remain to be precisely elucidated, and adverse patient outcomes with increased morbidity and mortality continue to occur. Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients. Future research focus in this field may benefit from shifting towards obtaining antidotal knowledge at the molecular level, with focus on the underlying molecular signaling pathways.

Interleukin-6 (IL-6) is a pleiotropic cytokine which plays an important role in a number of cellular processes including proliferation, survival, differentiation, migration and invasion. IL-6 mediates its downstream effects by activating a number of signaling cascades including JAK/STAT, PI3K/AKT and MAPK pathways. In addition to its effects on tumor cells, IL-6 also regulates tumor progression and tumor metastasis by modulating tumor angiogenesis and tumor lymphangiogenesis. A number of studies have shown that IL-6 levels are markedly upregulated in cancer patients. We and others have shown that high IL-6 expression independently predicts tumor recurrence, tumor metastasis and poor survival in head and neck cancer patients. Therefore targeting IL-6 signaling is a potential therapeutic strategy for the treatment of head and neck squamous cell carcinoma (HNSCC). In this review, we discuss the current understanding of the role of IL-6 in HNSCC progression and potential therapeutic strategies to target IL-6 signaling for the treatment of head and neck cancer patients.

Ocular manifestations are present in many connective tissue diseases which are characterized by an immune system that is directed against self. In this paper, we review the ocular findings in various connective tissue diseases and systemic vasculitides and highlight gender differences in each disease. In rheumatoid arthritis, we find that dry eyes affect women nine times more than men. The other extra-articular manifestations of rheumatoid arthritis affect women three times more commonly than men. Systemic lupus erythematosus can involve all ocular structures and women are nine times more affected than men. Systemic sclerosis is a rare disease but, again, it is more common in women with a female to male ratio of 8 : 1. Polymyositis and dermatomyositis also affect women more commonly than men but no gender differences have been found in the incidence or disease course in the systemic vasculitides associated with antineutrophil cytoplasmic antibody such as granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis). Finally, Behcet's disease is more common in males, and male gender is a risk factor for Behcet's disease. There is a slight female preponderance in sarcoidosis with female gender carrying a worse prognosis in the outcome of ocular disease.

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This article reviews the scientific and engineering principles and practices involved in the mathematical modeling of flow and heat transfer phenomena in industrial-scale glass melting, delivery, and forming processes. The approach taken is to highlight the characteristic features of flow and heat transfer in each of the three processes, summarize the relevant transport and constitutive equations and boundary conditions, and illustrate practical applications of mathematical models. The article also describes modeling approaches used for auxiliary processes and phenomena associated with melting, delivery, and forming operations. Thus, modeling of batch melting, electric heating of glass melt, convection due to bubbling, combustion, turbulence, and viscoelasticity are discussed. Unlike melting and delivery processes, which share many similarities across the various glass industry segments, forming tends to be segment specific. So, the article focuses on one forming process (container) and, through it, emphasizes the key technical attributes of forming models. A selection of results is provided to bring out modeling capabilities and limitations. The article also provides a historical perspective on the development of advanced mathematical models and their industrial applications. Finally, key areas needing research and development are identified to further enhance the practical utility of mathematical models for the glassmaking processes.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in individuals over the age of 50 years. Choroidal neovascularization (CNV) is the hallmark of 'wet' or 'exudative' AMD, and is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. Since the approval of ranibizumab in 2006, VEGF inhibitors have rapidly altered the treatment and standard of care for wet AMD. Ranibizumab, bevacizumab, and aflibercept are now the most widely used anti-VEGF agents for the treatment of wet AMD. This chapter discusses the pharmacologic properties, pharmacokinetics, safety, and efficacy of these medications, as well as revisits landmark clinical trials that establish these drugs as gold standards in care. While these medications have greatly and positively altered the way we treat AMD, there are still many economic and therapeutic limitations with our current therapy regimens. There continue to be advancements and innovations in exploring alternative and new treatment modalities, as well as combining existing treatment options to improve efficacy, and reduce cost and patient burden.

We hypothesized that IL-12 would enhance the anti-tumor activity of the anti-HER1 antibody cetuximab against squamous cell carcinomas of the head and neck (SCCHN) by activating the FcR effector mechanisms of NK cells. All cell lines showed high expression of HER1 by flow cytometry and immunoblot analysis. NK cell lysis of cetuximab-coated SCCHN cell lines was markedly enhanced by 12 hr pre-treatment of NK cells with IL-12 (p=0.005 vs. cetuximab). Similar levels of lysis were noted for both HPV-positive and HPV-negative cell lines. Other NK cell-activating factors such as IL-2, IL-15 and IL-21 also enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). The stimulus of IL-12 and cetuximab-coated tumor cells induced synergistic production of nanogram levels of interferon-gamma (IFN-γ; >6-fold increase over controls) (p<0.001). A similar effect was seen for NK cell production of the chemokines MIP-1α, RANTES and IL-8. Phosphorylation of ERK (critical for FcR functions) was enhanced in NK cells costimulated with cetuximab and IL-12 compared to controls. Cytokine stimulation of NK cells in the presence of cetuximab-coated SCCHN cells leads to enhanced NK cell-mediated ADCC and cytokine secretion independent of tumor cell HPV-status. Cytokine administration could be a useful adjuvant in the cetuximab treatment of HER1-positive head and neck cancer.

Background: Electroconvulsive therapy (ECT) is shown to be effective in many psychiatric illnesses, but its distorted projection by the Pakistani media and its unregulated use by many physicians across the country have adversely affected its acceptability. Given this situation we aimed to assess the awareness and perceptions regarding ECT as a treatment modality among the psychiatric patients.