Experimental study and sensitivity analysis of force behavior in cortical bone milling.

Bone milling force is a key factor to be controlled during the orthopedic surgery. Cutting force has significant influence on the breaking of the tools or causing bone cracks. The cutting force depends on machining parameters, cutting tools and the cortical bone tissue. In this paper, rotational speed, feed rate, cutting depth, tool diameter and the osteon orientation are considered as input parameters. For statistical modeling and experimental study, the response surface method was used. Moreover, using the Sobol statistical sensitivity analysis method the effect of each input parameter on the process force is investigated both qualitatively and quantitatively. Results revealed that bone milling force decreases with increasing rotational speed while it increases with feed rate due to an increase in the thickness of the deformed chip as well as an escalation of friction. Moreover, increasing cutting depth due to increased thickness of the deformed chip, increases friction and thus increases cutting force. Additionally, as the diameter of the blade increases, the cutting force increases. Finally, in the perpendicular direction to the osteon, less force is applied to the bone tissue than that of parallel to osteon. Based on Sobol sensitivity analysis, cutting depth (51.4%), feed rate (21.9%), tool rotational speed (19%), milling direction (4.8%) and tool diameter (1.9%) are the most effective respectively. Response optimization was also presented using Derringer algorithm, which provided a minimum cutting force of 3.76 N, when tool diameter of 4 mm, rotational speed of 3000 rpm and feed rate of 100 mm/min and cutting depth of 1 mm were selected in milling perpendicular to the osteon orientation. This research can be used to optimize milling parameters in order to assist robotic surgery and orthopedic tool design.

Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis

Introduction and objectives: Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes. Patients and methods: This case-control study consisted of 20 AR patients and 20 healthy subjects. The serum level of total immunoglobulin E (IgE) was measured using the electro-chemiluminescence (ECL) technology. The percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry. The amounts of IL-4 in CD4+ T cells culture supernatant was also measured by the enzyme-linked immunosorbent assay (ELISA). Results: OX40L expression on B lymphocytes of patients was significantly higher than the control group (44.32 ± 19.21% vs. 2.79 ± 2.48% respectively, p < 0.001). In AR patients, OX40L expression correlated positively with the levels of serum total IgE and IL-4 produced by CD4+ T lymphocytes (p < 0.01 - p < 0.05) respectively. Conclusions: Collectively, the findings of this work suggest that there is a relationship between the OX40L expression level on B lymphocytes and allergic markers such as IgE and IL-4 in patients with allergic rhinitis

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Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis.

INTRODUCTION AND OBJECTIVES: Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes. PATIENTS AND METHODS: This case-control study consisted of 20 AR patients and 20 healthy subjects. The serum level of total immunoglobulin E (IgE) was measured using the electro-chemiluminescence (ECL) technology. The percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry. The amounts of IL-4 in CD4+ T cells culture supernatant was also measured by the enzyme-linked immunosorbent assay (ELISA). RESULTS: OX40L expression on B lymphocytes of patients was significantly higher than the control group (44.32±19.21% vs. 2.79±2.48% respectively, p<0.001). In AR patients, OX40L expression correlated positively with the levels of serum total IgE and IL-4 produced by CD4+ T lymphocytes (p<0.01 - p<0.05) respectively. CONCLUSIONS: Collectively, the findings of this work suggest that there is a relationship between the OX40L expression level on B lymphocytes and allergic markers such as IgE and IL-4 in patients with allergic rhinitis.

Association analysis of -416 G>C polymorphism of T-cell immunoglobulin and mucin domain-1 gene with asthma in Iran.

TIM (T-cell immunoglobulin (Ig) and mucin domain)-1, one of the members of TIM family, expresses on Th2 cells and promotes the production of Th2 signature cytokines. This can increase a series of responses in these cells which could be one of the causes of asthma or asthma-related phenotypes. The aim of this study was to investigate whether a TIM-1 promoter single nucleotide polymorphism (SNP), -416 G>C, is associated with asthma in Iranian population. In this case-control study, existence of the -416 G>C polymorphism was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in 300 patients with asthma (97 atopic, 203 nonatopic) and 309 healthy volunteers. Additionally, the relationship between these polymorphism genotypes and total serum IgE levels in this Iranian population was evaluated. We discovered a significant association between the -416 G>C polymorphism and atopic asthma susceptibility in the population, but this SNP showed no connection with nonatopic asthma (P < 0.05). However, our results showed significant relation between this polymorphism and serum IgE level (P < 0.05). Our results suggest that -416 G>C polymorphism in TIM-1 gene could be a predisposing factor for atopic asthma in Iranian population, and CC genotype of this SNP can be associated with increased level of IgE in patients with asthma in the same population.

Membranous Nectin-4 expression is a risk factor for distant relapse of T1-T2, N0 luminal-A early breast cancer.

Nectins are Ca(2+)-independent immunoglobulin-like cell adhesion molecules that compose a family of four members that regulate several cellular activities such as movement, proliferation, survival, differentiation, polarization, and the entry of viruses. Nectin-4 has recently emerged as a metastatis-associated protein in several cancers. Here, we have evaluated the association between the expression of Nectin-4 and the clinical outcome of patients with node-negative, T1/T2 breast cancers.The study group consisted of 197 patients presenting with primary unilateral breast carcinoma (T1/T2), with no evidence of nodal involvement and distant metastases. Nectin-4 protein expression was assessed by immunohistochemistry on tissue microarrays, and the results correlated with the clinical data using Kaplan-Meier curves and multivariate Cox regression analysis. Thirty-four out of 197 tumors (17.3%) exhibited Nectin-4 expression on cell membrane (m-Nectin-4) and 122 out of the 163m-Nectin-4 negative tumors (74.8%) showed high cytoplasmic expression of Nectin-4 (c-Nectin-4(High)). At Kaplan-Meier analysis, m-Nectin-4 positivity was significantly associated with a lower disease-free survival (DFS) and distant relapse-free survival (DRFS) rate in patients with a luminal-A phenotype (P=0.030 and P=0.002, respectively). Multivariate analysis showed that in luminal-A tumors m-Nectin-4 positivity is an independent prognostic factor for DFS (P=0.018) and DRFS (P=0.004), but not for local relapse-free survival (LRFS). On the other hand, c-Nectin-4(High) was significantly associated with higher rates of DFS and LRFS, but not DRFS, in the whole population (P=0.008 and P=0.004, respectively) and in patients with luminal-A tumors (P=0.022 and P=0.018, respectively). In patients with luminal-A tumors, multivariate analysis showed that the prognostic value of c-Nectin-4(Low/Negative) is limited to DFS (P=0.012) and LRFS (P=0.022). We suggest that Nectin-4 represents a prognostic factor and a therapeutic target in luminal-A early stage breast cancer.

Dual targeting of ErbB-2/ErbB-3 results in enhanced antitumor activity in preclinical models of pancreatic cancer.

ErbB-3 and its ligand NRG-1ß are key players in driving oncogenic signaling and resistance to therapy through the activation of the PI3K/Akt pathway. We have recently reported that EV20, a humanized anti-ErbB3 antibody, possesses a marked antitumor activity in a variety of human tumor models, including pancreatic cancer (PC). Here, we report that despite epidermal growth factor receptor overexpression, PC cells are more sensitive to NRG-1ß than EGF in terms of Akt activation and cell proliferation. Using stable ErbB-3-knocked down cells and EV20 in combination with trastuzumab, we showed that dual targeting of ErbB-2 and ErbB-3 was necessary to completely abrogate ErbB-3 signaling and to impair cell proliferation. Similarly, enhanced therapeutic efficacy of the antibody combination was seen in xenografts originating from K-Ras-mutated HPAF-II and SW1990 cells, without increasing the toxicity. These results indicate that dual targeting of ErbB-2 and ErbB-3 could represent a new therapeutic approach in PC.Oncogenesis (2014) 3, e117; doi:10.1038/oncsis.2014.31; published online 18 August 2014.

Metal-dielectric metamaterials for guided wave silicon photonics.

The aim of the present paper is to investigate the potential of metallic metamaterials for building optical functions in guided wave optics at 1.5 µm. A significant part of this work is focused on the optimization of the refractive index variation associated with localized plasmon resonances. The minimization of metal related losses is specifically addressed as well as the engineering of the resonance frequency of the localized plasmons. Our numerical modeling results show that a periodic chain of gold cut wires placed on the top of a 100 nm silicon waveguide makes it possible to achieve a significant index variation in the vicinity of the metamaterial resonance and serve as building blocks for implementing optical functions. The considered solutions are compatible with current nano-fabrication technologies.

Efficient control of a 3D optical mode using a thin sheet of transformation optical medium.

We report on a mode adapter that transitions light between two SOI waveguides having different widths. The device has been designed using a two-dimensional embedded coordinate transformation and consists of a thin sheet of a controlled anisotropic material directly placed on top of the Si slab. We demonstrate that this layer effectively controls the flow of energy propagating in the Si slab by performing three-dimensional full-wave simulations. The proposed geometry can be implemented with planar optical metamaterials for various applications in guided optics.

Interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms in patients with periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial disease and immunologic and genetic factors have an important role in its pathogenesis. Mutation in the promoter regions of the interleukin-4 and interferon-gamma genes has been reported to modify the protein expression. The objective of this study was to evaluate the possible role of interleukin-4 (C-590T) and interferon-gamma (G5644A) polymorphisms in the susceptibility to periodontitis. MATERIAL AND METHODS: In this case-control study, 53 patients (36 women and 17 men), comprising 27 patients with aggressive periodontitis and 26 patients with chronic periodontitis, and 56 healthy volunteers, were enrolled. DNA was isolated from all subjects, and the polymerase chain reaction-sequence specific primer method was used to study the interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms. RESULTS: Our results showed no significant difference in the allele and genotype frequencies of interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms between patients with periodontal disease and controls. CONCLUSION: The results suggest that the interleukin-4 (C-590T) and interferon-gamma (G5644A) gene polymorphisms may not be associated with the susceptibility of Iranian individuals to periodontitis.

Pre-marriage prevention of thalassaemia: report of a 100,000 case experience in Isfahan.

BACKGROUND: Iran like other middle east countries has a large number of major thalassaemics. Due to religious restrictions on abortion, the routine prevention of the birth of thalassaemic children by this means is not possible. The aim of this study is to describe an alternative means to prevent the birth of thalassaemic children. METHODS: From January 1993 to January 1996, 10,000 people preparing for marriage were screened for the thalassaemia trait, using CBC and HbA2 level measurement. High risk couples were referred for further consultation regarding the disease and the means of its prevention. The proposed actions of the couples regarding thalassaemia prevention were evaluated immediately after consultation and then re-evaluated three months later. RESULT: After the project had been running for three years the average of high risk couple initially deciding not to marry was 90% and no new cases of thalassemia were detected in the children of the screened population. CONCLUSION: Where both members of the couple were trait-positive their preferred choice was not to marry, rather than to marry and use other or no methods of preventing a thalassemia affected child being born to them. Cultural and religious ideas can affect such decisions and in some Islamic countries the establishment and use of a genetic counselling centre can help prevent most of new thalassaemia cases.

A randomized, placebo-controlled trial of a two-week regimen of aminosidine (paromomycin) ointment for treatment of cutaneous leishmaniasis in Iran.

The effect of a two-week regimen of topical aminosidine was investigated in a randomized, double-blind, placebo-controlled trial of 251 selected Iranian patients with zoonotic cutaneous leishmaniasis. Patients underwent clinical and parasitologic assessment before and 15 (end of therapy), 45, and 105 days after starting the treatment. Aminosidine ointment was safe and well-tolerated, and produced significant reductions in the prevalence of parasitologically positive smears on days 15 and 105 (but not day 45) after treatment compared with placebo. However, there was no clear clinical benefit at any stage after treatment. We conclude that this twice a day two-week regimen of aminosidine was inadequate to accelerate the recovery of most cases of cutaneous leishmaniasis. However, the ointment did show some clear evidence of parasitologic efficacy and should now be studied in longer or more frequent regimens in an effort to prevent parasitologic relapse and thus promote clinical improvement.