Immunotherapeutic targets in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most common types of cancer in the world and has a 5-year survival rate of ~20%. Immunotherapies have shown promising results leading to durable responses, however, they are only effective for a subset of patients. To determine the best therapeutic approach, a thorough and in-depth profiling of the tumour microenvironment (TME) is required. The TME is a complex network of cell types that form an interconnected network, promoting tumour cell initiation, growth and dissemination. The stroma, immune cells and endothelial cells that comprise the TME generate a plethora of cytotoxic or cytoprotective signalling pathways. In this review, we discuss immunotherapeutic targets in NSCLC tumours and how the TME may influence patients' response to immunotherapy.     

Imaging data in COVID-19 patients: focused on echocardiographic findings

To assess imaging data in COVID-19 patients and its association with clinical course and survival and 86 consecutive patients (52 males, 34 females, mean age?=?58.8 year) with documented COVID-19 infection were included. Seventy-eight patients (91%) were in severe stage of the disease. All patients underwent transthoracic echocardiography. Mean LVEF was 48.1% and mean estimated systolic pulmonary artery pressure (sPAP) was 27.9 mmHg. LV diastolic dysfunction was mildly abnormal in 49 patients (57.6%) and moderately abnormal in 7 cases (8.2%). Pericardial effusion was present in 5/86 (minimal in size in 3 cases and mild- moderate in 2). In 32/86 cases (37.2%), the severity of infection progressed from “severe” to “critical”. Eleven patients (12.8%) died. sPAP and computed tomography score were associated with disease progression (P value?=?0.002, 0.002 respectively). Tricuspid annular plane systolic excursion (TAPSE) was significantly higher in patients with no disease progression compared with those who deteriorated (P value?=?0.005). Pericardial effusion (minimal, mild or moderate) was detected more often in progressive disease (P?=?0.03). sPAP was significantly lower among survivors (P value?=?0.007). Echocardiographic findings (including systolic PAP, TAPSE and pericardial effusion), total CT score may have prognostic and therapeutic implication in COVID-19 patients.

     

Healthy ranges of serum alanine aminotransferase levels in Iranian blood donors

AIM: The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors. METHODS: A total of 1,939 blood donors were included. ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels. RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L, and for non-overweight men was 40 U/L. CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

Healthy ranges of serum alanine aminotransferase levels in Tranian blood donors

AIM:The healthy ranges for serum alanine aminotransferase (ALT) levels are less well studied. The aim of this study was to define the upper limit of normal (ULN) for serum ALT levels, and to assess factors associated with serum ALT activity in apparently healthy blood donors.METHODS: A total of 1 939 blood donors were included.ALT measurements were performed for all cases using the same laboratory method. Healthy ranges for ALT levels were computed from the population at the lowest risk for liver disease. Univariate and multivariate analyses were performed to evaluate associations between clinical factors and ALT levels.RESULTS: Serum ALT activity was independently associated with body mass index (BMI) and male gender, but not associated with age. Association of ALT with BMI was more prominent in males than in females. Upper limit of normal for non-overweight women (BMI of less than 25) was 34 U/L,and for non-overweight men was 40 U/L.CONCLUSION: Serum ALT is strongly associated with sex and BMI. The normal range of ALT should be defined for male and female separately.     

The effect of spraying different disinfectants on condensational silicone impressions; an in vitro study

Background:

Dentistry equipment are exposed to different types of pathogenic microorganisms. The aim of this study was to investigate the effect of spraying three different types of disinfectants on condensational silicones after 5 and 10 min.

Materials and Methods:

Totally, 66 circular samples of condensational silicone impression materials of 1 cm diameter and 2 mm thickness were contaminated by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans fungus. Except for control samples, all of them were disinfected with sodium hypochlorite (NaOCl) 0.525%, Deconex and Epimax by spraying method. Afterward, they kept in plastic bags with humid rolled cotton for 5 and 10 min. In order to isolate microbiotas, the samples were immersed in 2% trypsin for 1 h and diluted with normal saline in a portion of 1, 1/2, and 1/4. The trypsin suspensions were transferred to culture plates for incubation and colony-forming unit assay. The data were analyzed by Mann–Whitney test and SPSS software version 16 at a significant level of 0.05.

Results:

There was a meaningful difference between disinfection effects of Epimax-Deconex for all mentioned microorganisms after 5 min (P = 0.034), and between disinfection effects of NaOCl 0.525%-Epimax for S. aureus (P = 0.043) and P. aeruginosa (P = 0.046) after 5 min. Furthermore, there was a meaningful difference between disinfection effects of Epimax-Deconex (P = 0.034) and NaOCl 0.525%-Epimax (P = 0.034) for P. aeruginosa after 10 min.

Conclusion:

Condensational silicone can be effectively disinfected by spraying tested three disinfecting agents. More specifically, Deconex showed the best results compared to the other agents.Key Words: Condensational silicone, disinfection, impression materials, spray     

Genetics and immunodysfunction underlying Behçet’s disease and immunomodulant treatment approaches

Behçet’s disease (BD) is a chronic autoimmune condition primarily prevalent in populations along the Mediterranean Sea. The exact etiology of BD has not been fully explained yet, but the disease occurrence is associated with a genetic factor, human leukocyte antigen (HLA)-B51 antigen. Among the various immunodysfunctions that are found in BD, patients are increased neutrophil motility and superoxide production, as well as elevated production of tumor necrosis factor (TNF)-α and decreased production of interleukin (IL)-10. Elevated levels of inflammatory cytokines like IL-1 and IL-17 in BD have been found associated with aberrant expression of microRNA. Gene polymorphisms in BD patients have been observed in molecules involved in responses to pathogens that can ultimately modulate the host antimicrobial response. Moreover, several single nucleotide polymorphisms (SNPs) have been reported in genes encoding chemokines and adhesion molecules; many of these changes manifest as increases in vascular inflammation and vascular damage. Lastly, genetic and epigenetic changes have been suggested as involved in the pathogenesis of BD. Modifications in DNA methylation have been found in BD patient monocytes and lymphocytes, leading to adverse function of these cells. This review presents a comprehensive compilation of the literature with regard to the immunodysfunction underlying BD, as well as of the genetics, newly described clinical specifications and novel treatment strategies using immunomodulants based on the current understanding of BD.     

Microextraction technique based on ionic liquid for preconcentration and determination of palladium in food additive,sea water,tea and biological samples

Modified cold-induced aggregation microextraction (M-CIAME) is a fast and simple method for extraction and preconcentration of metal ions from samples with high salt content. Furthermore, this technique is much safer in comparison with the organic solvent extraction. The extraction of palladium (Pd) was performed in the presence of Michler thioketone (TMK) as the complexing agent. In this method, sodium hexafluorophosphate (NaPF₆) was added to the sample solution containing small amounts of 1-hexyl-3-methylimidazolium tetrafluoroborate [Hmim][BF₄]. Afterwards, the solution was placed in the ice bath and a cloudy solution was formed. After centrifuging, the extraction phase was settled. Under the optimum conditions, the limit of detection (LOD) was 0.2 ng mL⁻¹. The relative standard deviation (RSD) was 1.7% for 40 ng mL⁻¹ of palladium (n = 5).     

Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients

Background

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection.

Methods

A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control.

Results

TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values.

Conclusions

TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.