Diamond-Like Carbon: A Surface for Extreme, High-Wear Environments.

In this study, we present an in-depth characterization of a diamond-like carbon (DLC) film, using a range of techniques to understand the structure and chemistry of the film both in the interior and particularly at the DLC/air surface and DLC/liquid interface. The DLC film is found to be a combination of sp2 and sp3 carbon, with significant oxygen present at the surface. The oxygen seems to be present as OH groups, making the DLC somewhat hydrophilic. Quartz-Crystal Microbalance (QCM) isotherms and complementary neutron reflectivity data indicate significant adsorption of a model additive, bis(2-ethylhexyl) sulfosuccinate sodium salt (AOT) surfactant, onto the DLC from water solutions and indicate the adsorbed film is a bilayer. This initial study of the structure and composition of a model surfactant is intended to give a clearer insight into how DLC and additives function as antiwear systems.

A Novel Study on the Role of Pressure on Surface Adsorption from Solutions.

In this work, we present experimental data on the behavior of model additives adsorbed at the solid/liquid interface as a function of pressure. We report that some additives adsorbed from non-aqueous solvents exhibit rather little variation with pressure, while others exhibit more significant changes. We also display the important pressure dependence of added water. This pressure dependence is relevant, indeed central to many commercially important situations where the adsorption of molecular species to the solid/liquid interface under high pressure is key, such as wind turbines, and this work should help in understanding how protective, anti-wear, or friction-reducing agents can persist (or not) under these extreme conditions. With a very significant gap in the fundamental understanding of the role of pressure on adsorption from solution phases, this important fundamental study provides a methodology to investigate the pressure dependence of these academically and commercially important systems. In the best case, one may even be able to predict which additives will lead to more adsorption under pressure and avoid those that may desorb.

Corrosion inhibitor distribution on abrasive-blasted steels.

HYPOTHESIS: Abrasive-blasted steel surfaces exhibit a complex, multi-substrate environment. Adsorption to contaminant substrates can reduce the amount of available corrosion inhibitor and decrease its efficiency. Knowledge of where inhibitors preferentially adsorb is required. EXPERIMENTS: The quantitative extent and strength of adsorption of the representative corrosion inhibitor benzotriazole (BTAH) from toluene to particular substrates is given, including corrections for solution self-association, and complemented by X-ray photoelectron spectroscopy (XPS), sum-frequency generation spectroscopy (SFG), and quartz crystal microbalance (QCM) measurements. FINDINGS: All substrates show adsorbed BTAH layers. Based on the adsorption strength, preferential adsorption is found to be in the order steel > iron oxide > calcium carbonate and garnet > silica - this is relevant when there is limited BTAH. However, with ample BTAH, the amounts adsorbed in the plateau regions of the isotherm are more relevant and the order is calcium carbonate and silica > iron oxide > garnet > steel. Although the contaminant substrates deplete the BTAH concentration, the steel should still have a complete monolayer of BTAH inhibitor. This work is part of a larger initiative developing novel methods of corrosion inhibitor delivery via the blasting process, to prevent corrosion between blasting and repainting.

Deep androgen receptor suppression in prostate cancer exploits sexually dimorphic renal expression for systemic glucocorticoid exposure.

BACKGROUND: Enzalutamide and apalutamide are potent next-generation androgen receptor (AR) antagonists used in metastatic and non-metastatic prostate cancer. Metabolic, hormonal and immunologic effects of deep AR suppression are unknown. We hypothesized that enzalutamide and apalutamide suppress 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD2), which normally converts cortisol to cortisone, leading to elevated cortisol concentrations, increased ratio of active to inactive glucocorticoids and possibly suboptimal response to immunotherapy. On-treatment glucocorticoid changes might serve as an indicator of active glucocorticoid exposure and resultant adverse consequences. PATIENTS AND METHODS: Human kidney tissues were stained for AR and 11ß-HSD2 expression. Patients in three trials [neoadjuvant apalutamide plus leuprolide, enzalutamide ± PROSTVAC (recombinant poxvirus prostate-specific antigen vaccine) for metastatic castration-resistant prostate cancer (CRPC) and enzalutamide ± PROSTVAC for non-metastatic castration-sensitive prostate cancer] were analyzed for cortisol and its metabolites using liquid chromatography-mass spectrometry (LC-MS/MS). Progression-free survival was determined in the metastatic CRPC study of enzalutamide ± PROSTVAC for those with glucocorticoid changes above and below the median. RESULTS: Concurrent AR and 11ß-HSD2 expression occurs only in the kidneys of men. A statistically significant rise in cortisol concentration, cortisol/cortisone ratio and tetrahydrocortisol/tetrahydrocortisone ratio with AR antagonist treatment occurred uniformly across all three trials. In the trial of enzalutamide ± PROSTVAC for metastatic CRPC, high cortisol/cortisone ratio in the enzalutamide arm was associated with significantly improved progression-free survival. However, in the enzalutamide + PROSTVAC arm, the opposite trend was observed. CONCLUSION: Enzalutamide and apalutamide treatment toggles renal 11ß-HSD2 and significantly increases indicators of and exposure to biologically active glucocorticoids, which is associated with clinical outcomes.

Infectious etiology of chronic diarrhea in patients with primary immunodeficiency diseases.

Summary: Background.Primary immunodeficiency diseases (PIDs) are life-threatening disorders, which manifest commonly with gastrointestinal (GI) signs, mainly as chronic diarrhea. Objective. To investigate and compare infectious etiology of chronic diarrhea in different PIDs. Patients and methods. Assessing clinical features, obtaining immunological profiles, as well as characterizing infectious etiology of diarrhea were performed in 38 PID patients with chronic diarrhea. Stool samples and/or biopsy specimens were checked using culture, microscopic examination, RT-PCR, and PCR, as appropriate. The patients were diagnosed to have common variable immunodeficiency (CVID), severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and hyper-IgM (HIgM) syndrome. Results. In 32 patients we identified 41 infectious agents including 16 parasitic (39.0%, the most common Giardia lamblia), 11 bacterial (26.8%, the most common salmonella spp), 8 viral (19.5%, the most frequent group A rotavirus), and 6 fungal organisms (14.7%, the most common Candida albicans). From 6 of the patients, no infectious agent was isolated. In CVID bacteria and parasites, in SCID bacteria and viruses, in XLA parasites, and in individuals with HIgM syndrome parasites were the leading causes of chronic diarrhea. Infection with giardia and cryptosporidium were more frequent in XLA and HIgM, respectively. Conclusion. The current study suggests considering both usual and unusual pathogens in laboratory investigation and in the empiric treatment of chronic diarrhea. Opportunistic pathogens should be taken into account when no other pathogen is identified, especially in patients on long-term treatment or prophylaxis with antifungals/antibiotics and in those from geographical locations that favor pathogenicity of these organisms.

Biosensing by Learning: Cancer Detection as Iterative optimization.

We propose a novel cancer detection procedure (CDP) based on an iterative optimization method. The global minimum of a tumor-induced biological cost function indicates the tumor location, the domain of the cost function is the tissue region at high risk of malignancy, and the time-variant guess input is a swarm of externally controllable and trackable nanorobots for tumor sensing. We consider the spatial distrib-ution of fibrin as the cost function; the fibrin is formed during the coagulation cascade activated by tumor-targeted signalling modules (nanoparticles) and recruits clot-targeted receiving modules (nanorobots) towards the site of disease. Subsequently, the CDP can be interpreted from the iterative optimization perspective: the guess input (i.e., a swarm of nanorobots) is continuously updated according to the gradient of the cost function in order to find the optimum (i.e., cancer) by moving through the domain (i.e., tissue under screening). Along this line of thought, we consider the gradient descent (GD) iterative method, and propose the GD-inspired CDP, which takes into account the realistic in vivo propagation scenario of nanorobots. Finally, we present numerical examples to demonstrate the features of the GD-inspired CDP.

Canine visceral leishmaniosis: the relationship of blood serum thyroid hormones, lipids, and lipoproteins with clinical status.

The objective of the present study was to investigate the role of thyroid hormones and lipid profile in development and outcome of canine visceral leishmaniosis (CVL). We therefore studied the relationships between blood serum thyroid hormones [total T4, free T4, total T3, and free T3], lipids, and lipoproteins [total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [with no clinical signs (NCS; n = 15), and with clinical signs (CS; n = 16)] were assessed and compared with a group of healthy control dogs (n = 15). A significant decrease in serum total T4 (p < 0.05) concentration in the CS group was observed when compared to the NCS and control groups. The dogs in CS group revealed a significant decrease (p < 0.05) in free T4 concentration in comparison to the control group. The CS group presented a significant decrease in HDL-C (p < 0.01) concentrations, when compared to NCS and control groups. The observed findings in the present study suggested that thyroid hormone and lipoprotein alterations may have a role in susceptibility of dogs with Leishmania infection.

C-terminal BRE overexpression in 11q23-rearranged and t(8;16) acute myeloid leukemia is caused by intragenic transcription initiation.

Overexpression of the BRE (brain and reproductive organ-expressed) gene defines a distinct pediatric and adult acute myeloid leukemia (AML) subgroup. Here we identify a promoter enriched for active chromatin marks in BRE intron 4 causing strong biallelic expression of a previously unknown C-terminal BRE transcript. This transcript starts with BRE intron 4 sequences spliced to exon 5 and downstream sequences, and if translated might code for an N terminally truncated BRE protein. Remarkably, the new BRE transcript was highly expressed in over 50% of 11q23/KMT2A (lysine methyl transferase 2A)-rearranged and t(8;16)/KAT6A-CREBBP cases, while it was virtually absent from other AML subsets and normal tissues. In gene reporter assays, the leukemia-specific fusion protein KMT2A-MLLT3 transactivated the intragenic BRE promoter. Further epigenome analyses revealed 97 additional intragenic promoter marks frequently bound by KMT2A in AML with C-terminal BRE expression. The corresponding genes may be part of a context-dependent KMT2A-MLLT3-driven oncogenic program, because they were higher expressed in this AML subtype compared with other groups. C-terminal BRE might be an important contributor to this program because in a case with relapsed AML, we observed an ins(11;2) fusing CHORDC1 to BRE at the region where intragenic transcription starts in KMT2A-rearranged and KAT6A-CREBBP AML.

Multiple model predictive control for optimal drug administration of mixed immunotherapy and chemotherapy of tumours.

BACKGROUND: Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. METHODS: The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. RESULTS: Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. CONCLUSION: It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth.

A Randomized Controlled Clinical Trial Investigating the Effect of Synbiotic Administration on Markers of Insulin Metabolism and Lipid Profiles in Overweight Type 2 Diabetic Patients with Coronary Heart Disease.

Objective: The current study was performed to evaluate the effects of synbiotic administration on metabolic profiles in overweight diabetic patients with coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was done among 60 diabetic patients with CHD. Participants were randomly divided into 2 groups: group A (n=30) received synbiotic supplements containing 3 probiotic bacteria spices Lactobacillus acidophilus 2×109, Lactobacillus casei 2×109, Bifidobacterium bifidum 2×109 CFU/g plus 800 mg inulin and group B (n=30) received placebo for 12 weeks. Fasting blood samples were taken at baseline and after 12-week intervention to determine metabolic profiles. Results: After 12 weeks of intervention, patients who consumed synbiotic capsule had significantly decreased fasting plasma glucose (- 19.6±74.6 vs.+19.2±66.9 mg/dL, P=0.03), serum insulin concentrations (- 0.7±5.1 vs.+3.3±6.3 µIU/mL, P=0.01), the homeostasis model of assessment-estimated b cell function (- 3.4±19.5 vs.+11.5±21.0, P=0.006) and increased the quantitative insulin sensitivity check index (+ 0.002±0.01 vs.-0.01±0.02, P=0.03) compared with the placebo. In addition, changes in HLDL-cholesterol levels (+ 1.8±5.7 vs.-2.2±6.0 mg/dL, P=0.01) in supplemented patients were significantly different from those of patients in the placebo group. Conclusion: Synbiotic supplementation for 12 weeks among diabetic patients with CHD had beneficial effects on markers of insulin metabolism and HDL-cholesterol levels.

Autoimmune Hemolytic Anemia preceding the Diagnosis of Primary Central Nervous System Lymphoma.

In this study, a 2.5-year-old boy suffering from a febrile seizure with normal laboratory tests and a history of immune hemolytic anemia was examined. Brain MRI demonstrated some tumors in the frontal, parietal, and occipital lobe that corroborated the pathology results of primary central nervous system lymphoma for the patient. The patient was treated with high-dose of Methotrexate. Our result suggested regular and careful monitoring of patients with autoimmune hemolytic anemia in order to control the manifestations of concomitant disease such as lymphoma that may develop later.

Pupil dilation with intra-cameral lidocaine versus topical midriatics during phacoemulsification.

PURPOSE: To evaluate pupil dilation with intra-cameral injection of preservative-free lidocaine 1% (ICL) versus topical eye midriatics during phacoemulsification. METHODS: This case-control study included 40 patients with similar bilateral senile cataract scheduled for phacoemulsification and intraocular lens (IOL) implantation. patient's first eye received topical midriatic eye drops as control group and next eye operated by intra cameral preservative free lidocaine 1% without any preoperative or intraoperative midriatics. We did not add epinephrine to the irrigating solution in either group. The first eyes received 3 drops of cyclopentolate 1% and tropicamide 1% each 5 minutes, with first dose 60 minutes before surgery. The horizontal pupil diameter was measured before and after pupil dilation using the same caliper with operation microscope total surgical time was recorded in both groups. RESULTS: Patients included 20 male and 20 female with mean age of 72 and 70.9 years old .4 patients were diabetic and 11 cases had pseudo-exfoliation. Pupil diameter increased in both case and control groups significantly (P value<0.0) but the difference between mean increase in pupil size wasn't significantly different. Mean increase in pupil size was significantly greater in patients without pseudo-exfoliation (4.10 mm vs 3.85 mm, independent t test, P<0.05). There was no significant difference between diabetic and non- diabetic patients regarding of pre- and post-injection diameter of the pupil. CONCLUSION: Intra-cameral preservative-free lidocaine 1% supply adequate midriasis during cataract surgery by itself.

Association between helicobacter pylori infection and primary open angle glaucoma.

AIM: to compare the prevalence of Pylori infection in patients with primary open angle glaucoma (POAG) and control group with cataract. METHODS: This is a prospective case-control study. The participants were organized in two groups. First group (case) consisted of 35 patients with POAG and second group consisted of 35 age matched participants with cataract whose optic disk could be evaluated. Serum levels of anti H. pylori IgG antibody were evaluated with the method of ELISA. RESULTS: The seroprevalence of Pylori infection was 89.1 % (33 of 37) in patients with POAG and 59.5 % (25 of 42) in the control group. The difference was significant (P=0.008). The odds ratio for association between Pylori and POAG was 5.69 and the range of 95% confidence interval was from 1.58 to 20.50. CONCLUSION: This study suggests that Helicobacter Pylori infection might be associated with primary open angle glaucoma. 

Androgen metabolism in prostate cancer: from molecular mechanisms to clinical consequences.

Despite our most vigorous efforts, prostate cancer remains the second leading cause of cancer death in men. Understanding the intricacies of androgen metabolism is vital to finding therapeutic targets, particularly with progression of advanced prostate cancer after initial hormone therapy, where adrenal precursors are involved. Such is the case with castration-resistant prostate cancer, where adrenal androgens, for example, dehydroepiandrosterone, are a source for intratumoural synthesis of dihydrotestosterone. As prostate cancer progresses, androgen metabolism changes due to altered expression of steroidogenic enzymes and mutations in the components of the steroidogenic machinery. These alterations sustain disease and allow progression; mechanistically, they may also enable development of hormone therapy resistance. With the development of the newer agents, abiraterone acetate and enzalutamide, efforts have been made to better define the basis for response and resistance. This work can be carried out in cell lines, animal models, as well as with ex vivo analysis of tissues obtained from patients. Efforts to further elucidate the finer details of the steroidogenic pathway are necessary to move toward a curative paradigm for patients with localised disease at high risk for recurrence.

The role of DAB2IP in androgen receptor activation during prostate cancer progression.

Altered androgen-receptor (AR) expression and/or constitutively active AR are commonly associated with prostate cancer (PCa) progression. Targeting AR remains a focal point for designing new strategy of PCa therapy. Here, we have shown that DAB2IP, a novel tumor suppressor in PCa, can inhibit AR-mediated cell growth and gene activation in PCa cells via distinct mechanisms. DAB2IP inhibits the genomic pathway by preventing AR nuclear translocation or phosphorylation and suppresses the non-genomic pathway via its unique functional domain to inactivate c-Src. Also, DAB2IP is capable of suppressing AR activation in an androgen-independent manner. In addition, DAB2IP can inhibit several AR splice variants showing constitutive activity in PCa cells. In DAB2IP(-/-) mice, the prostate gland exhibits hyperplastic epithelia, in which AR becomes more active. Consistently, DAB2IP expression inversely correlates with AR activation status particularly in recurrent or metastatic PCa patients. Taken together, DAB2IP is a unique intrinsic AR modulator in normal cells, and likely can be further developed into a therapeutic agent for PCa.

Celiac disease and multiple sclerosis in the northwest of Iran.

OBJECTIVE: To compare the frequency of celiac disease (CD) in patients with multiple sclerosis (MS) and healthy controls using tissue transglutaminase IgA antibodies (anti-tTGA) as a screening tool. BACKGROUND: CD and MS are immune-mediated diseases, and it has been hypothesized that the genetic similarities between these conditions can predispose individuals to suffer from both. Data regarding this association are limited, particularly in Eastern countries. METHODS: One hundred clinically defined MS patients were randomly selected from Tabriz, northwest of Iran. The control group consisted of 121 age- and gender-matched healthy individuals. All subjects were screened with anti-tTGA. Total IgA was obtained for investigation of IgA deficiency. RESULTS: The mean age of MS patients (32 male and 68 female) was 33.06±8.79 years; the mean age of controls was 32.98±9.62 years. The mean expanded disability scale score (EDSS) for MS patients was 3.86±1.91. Approximately 78.5 % of MS patients suffered from a remitting relapsing type of MS. All subjects (MS patients and controls) were negative for anti-tTGA. IgA deficiency was demonstrated in 14 % of MS patients and 11 % of controls (p>0.1). No IgA-deficient subjects consented to undergo a duodenal mucosa biopsy. CONCLUSION: The present study failed to demonstrate a positive relationship between MS and CD. Therefore, we conclude that there is no basis for recommending the routine screening of MS sufferers for celiac disease (Ref. 23).

Role of frozen sections in the evaluation of moderate to severe dysplasia during uterine cervix conization.

BACKGROUND: The utility of frozen section examination (FSE) of cone specimens in evaluation of the resection margin status and in ruling out invasion in patients with high grade cervical intraepithelial neoplasia requires evaluation. METHODS: Twenty patients with high grade cervical intraepithelial neoplasia who underwent conization biopsy and frozen section examination were studied in a prospective trial from March 2008 through September 2009. The results with permanent paraffin sections were compared with those of FSE. RESULTS: Among the twenty cases, 15 (75%) had the same results in frozen and permanent sections of cone biopsy specimens. Among the other 5 patients, 2 had high grade cervical intraepithelial neoplasia in frozen sections and 2 showed a lower grade while only one case was found in which the FSE result was CIN3 while the permanent section showed invasive carcinoma which was of clinical importance and considered as significant. Paired sample t-testing showed no significant difference in the results of the two groups of frozen and permanent sections (P=0.716, CI=95%). CONCLUSION: Frozen section evaluation of cervical cone biopsy specimens in patients with a diagnosis of CIN 3 is accurate, efficient and cost-effective. Because of the great importance of missing even one case, further research is highly recommended on this controversial subject.

Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia.

AIMS: To determine whether there is an association between Type 2 diabetes mellitus and schizophrenia, independent of medication. METHODS: In this cross-sectional study we performed an oral glucose tolerance test on 38 non-obese white Caucasians who fulfilled the criteria for first-episode drug-naïve schizophrenia, 38 control subjects (matched for age, gender, smoking status, alcohol intake and ethnicity) and 44 first-degree relatives of the patients. RESULTS: The frequency of impaired glucose tolerance (IGT), defined by World Health Organization criteria, was 10.5% (n = 4) in patients with schizophrenia, 18.2% (n = 8) in unaffected relatives and 0.0% in healthy control subjects (chi(2) = 4.22, d.f. = 2, P < 0.05). CONCLUSIONS: The high point prevalence of IGT in never-treated patients and relatives supports either shared environmental or genetic predisposition to IGT. Both patients and their relatives present an ideal cost-effective opportunity to screen for Type 2 diabetes mellitus, as they are both easily identifiable.