Immunolocalization of IL-1beta and IL-6 in optic nerves of patients with AIDS.

PURPOSE. Immunohistochemical procedures were employed to test the hypothesis that cytokines such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are involved in AIDS-related optic neuropathy and to determine the primary cell types involved. METHODS. Fixed sections of six human HIV-1 infected optic nerves were immunostained for the presence of IL-1beta and IL-6, using horseradish peroxidase and diaminobenzidine as markers. RESULTS. IL-1beta and IL-6 were found in astrocytes, macrophages, microglia, and endothelial cells. The great majority of astrocytes demonstrated strong immunoreactivity. CONCLUSION. Our findings support the premise that IL-1beta and IL-6 are significant pro-inflammatory mediators in AIDS-related optic neuropathy. This finding supports the theory that HIV infection stimulates the release of IL-1beta and IL-6 in astrocytes, macrophages, and endothelial cells in the optic nerve which ultimately leads to demyelination, astrogliosis, and neuronal destruction.     

Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis

The composition of tumor-targeted T cell infiltrates is a major prognostic factor in colorectal cancer (CRC) outcome; however, the functional role of these populations in prolonging patient survival remains unclear. Here, we evaluated 190 patients with CRC for the presence of functionally active tumor-infiltrating lymphocytes (TILs), the tumor specificity of these TILs, and the correlation between patient TILs and long-term survival. Using intracytoplasmic cytokine staining in conjunction with HLA multimers loaded with tumor peptide and antigen-specific cytokine secretion assays, we determined that TNF-α expression delineates a population of tumor antigen–specific (TA-specific) cytotoxic T lymphocytes (CTLs) present within tumors from patients with CRC. Upregulation of TNF-α expression in TILs strongly correlated with an increase in the total amount of intratumoral TNF-α, which is indicative of tumor-specific CTL activity. Moreover, a retrospective multivariate analysis of 102 patients with CRC, which had multiple immune parameters evaluated, revealed that increased TNF-α concentration was an independent prognostic factor. Together, these results indicate that the prognostic impact of T cell infiltrates for CRC maybe largely based on subpopulations of active TA-specific T cells within the tumor, suggesting causal implication for these cells in patient survival. Additionally, these results support the use of intratumoral TNF-α, which is indicative of T cell function, as a prognostic parameter for CRC.     

A surface-enhanced Raman scattering-based approach for rapid and highly sensitive quantitative analysis of 3-carboxy-4-methyl-5-propyl-2-furanpropionate and indole-3-acetic acid in saline,human serum and uremic serum of patients with chronic kidney disease

3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) and indole-3-acetic acid (IAA) are critical protein-bound uremic toxins that occur during chronic kidney disease (CKD). This study offers the first reported instance of surface-enhanced Raman scattering (SERS) coupled with an Au nanoparticle substrate for the simple quantification of CMPF and IAA in human serum samples. The detection limits of the CMPF and IAA analysis were estimated to be 0.04 nM (S/N = 3) and 0.05 μM (S/N = 3), respectively. The results demonstrate that the SERS technique is fast-acting and highly sensitive when it comes to the simultaneous and individual quantitative detection of CMPF and IAA in biological samples. We believe that this analytical tool could serve as a very useful method for practical applications during the analysis of CMPF and IAA in the serum and urine of patients at all stages of CKD and of healthy volunteers as well as in various reservoirs.

Rapid and highly sensitive quantitative analysis of 3-carboxy-4-methyl-5-propyl-2-furanpropionate and indole-3-acetic acid in uremic serum of patients with chronic kidney disease.     

Accelerated Blood Clearance of PEGylated PLGA Nanoparticles Following Repeated Injections: Effects of Polymer Dose, PEG Coating, and Encapsulated Anticancer Drug

Purpose

To investigate accelerated blood clearance (ABC) induction upon repeated injections of PLGA-PEG nanoparticles as a commonly used polymeric drug carrier.

Methods

Etoposide-loaded PLGA-PEG NPs were developed and administered as the test dose to rats pre-injected with various NP treatments at certain time intervals. Pharmacokinetic parameters of etoposide and production of anti-PEG IgM antibody were evaluated.

Results

A notable ABC effect was induced by a wide range of polymer doses (0.1 to 20 mg) of empty NPs, accompanied by IgM secretion. However, a further increase in polymer dose resulted not only in the abrogation of the observed ABC induction but also in distinctly a higher value for AUC of the NPs relative to the control. The data from the PEG-negative group verified the fundamental role of PEG for ABC induction. The first injection of etoposide-containing PEGylated nanoparticles (a cell cycle phase-specific drug) produced a strong ABC phenomenon. Three sequential administrations of etoposide-loaded NPs abolished ABC, although a high level of IgM was still detected, which suggests saturation with insignificant poisoning of immune cells.

Conclusion

The presented results demonstrate the importance of clinical evaluations for PLGA-PEG nanocarriers that consider the administration schedule in multiple drug delivery, particularly in cancer chemotherapy.     

Growth factor receptor expression in orbital lymphangioma: possible therapeutic implications

OBJECTIVE: To examine the expression of molecules targeted by imatinib mesylate (STI571;Gleevec) and epidermal growth factor receptor (EGFR) inhibitors in orbital lymphangiomas. DESIGN: Retrospective observational case series. PARTICIPANTS: Six patients with orbital lymphangioma treated at four institutions between March 2000 and December 2002. METHODS: Tissue specimens and medical records from six patients were collected. Immunohistochemical analysis was performed using antibodies against c-kit and platelet-derived growth factor receptor (PDGFR) alpha and beta and EGFR tyrosine kinase.     

Caesarean or normal vaginal delivery: overview of physicians’ self-preference and suggestion to patients

Purpose  Caesarean delivery in the absence of any medical indications has become a major issue of concern among the women’s health professionals. The patients’ choice of caesarean is influenced by several factors predominating by their physicians’ suggestion. Our objective was to examine factors that may affect the physicians’ responses to patients consulting the mode of delivery. Methods  Questionnaires were posted to 1,000 female obstetricians and gynaecologists practicing in Tehran in winter 2007. Questionnaires included demographic information of physicians and their history of pregnancy and delivery. Finally, they were asked their preferred mode of delivery and the mode they suggest when being consulted by parturient. Results  From 1,000 physicians, 785 cases (78.5%) responded to the survey. The rate of responses in favour of suggesting normal vaginal delivery, Caesarean Section and painless vaginal delivery was 60.8, 25.6 and 13.6%, respectively. There was a correlation between the suggested and the preferred mode of delivery, it means that the physicians mostly suggested their self-preferred mode of delivery to their patients. Conclusions  Physicians normally suggest to their patients as the safe mode of delivery what they prefer for themselves. This preference and subsequent suggestion is influenced by different factors including their age, marital status, and previous modes of delivery. As conclusion, it is inferred that informing a physician to choose the right mode of delivery for herself leads to better suggestions to the patients.     

Architecture of a multi-channel and easy-to-make microfluidic paper-based colorimetric device (μPCD) towards selective and sensitive recognition of uric acid by AuNPs: an innovative portable tool for the rapid and low-cost identification of clinically relevant biomolecules

Uric acid (UA) is the end product of purine metabolism. Uric acid is usually excreted in the urine, but its abnormal increase and toxic amount can lead to diseases such as gout, hyperuricemia, Lesch–Nyhan syndrome, and cardiovascular disease. On the other hand, UA reduction can lead to neurodegenerative diseases such as sarcoma, glioblastoma, Hodgkin, and etc. Therefore, rapid identification of UA is of great importance. In this work, a simple, portable, inexpensive, and fast microfluidic paper-based colorimetric sensor based on the color change in the presence of UA by using AuNPs was developed. The results can be easily identified with naked eye and further confirmed by UV-vis spectrophotometry. In this method, iron pattern and fiberglass paper were used to construct diagnostic areas and hydrophilic microfluidic channels. We greatly reduced the preparation time of this pattern using a magnet (about three minutes). In this work, four types of nanoparticles with different lower limit of quantification (LLOQ) were used. Linear range of 10⁻⁶ to 10⁻³ M and LLOQ of 10⁻⁶ M were obtained for the determination of uric acid using AuNPs–CysA as optical probe. Also, by AuNPs as optical probe a linear range of 10⁻⁴ to 10⁻² M and the obtained LLOQ was 10⁻⁴ M. Finally, by AuNFs as optical probe linear range from 10⁻⁶ to 10⁻² M and 5 × 10⁻⁵ to 10⁻² M along with LLOQ of 10⁻⁶ and 5 × 10⁻⁵ M, respectively. The designed system successfully studied in human urine samples.

A portable microfluidic paper-based colorimetric sensor based on various type of gold nanoparticle (AuNPs) for the monitoring of UA was developed.     

Prevalence and determinant factors of anemia in children aged 6–12 months after starting an iron supplement in the east of Iran

ObjectiveAnemia in infants is a common problem, with regular iron supplementation the suggested policy for prevention and control of anemia. The aim of this study was to determine the prevalence and the determining factors of anemia as well as the benefits of regular iron supplementation in 6- to 12-month-old children.Design/setting/subjectsIn this cross-sectional study, 897 children aged from 6 to 12 months cared for at the Tabas Health Centers, affiliated with Birjand University of Medical Sciences, South Khorasan, Iran, were enrolled in the study. Demographic and anthropometric data as well as the level of hemoglobin were collected through interviews and laboratory tests, respectively. Data analysis was performed using SPSS-22 and stata-13. Chi², polychromic PCA, and logistic regression were used. The statistical significance level was 0.05.ResultThe prevalence of anemia, according to the WHO criterion for hemoglobin, was 36.8% (95% CI, 33.6–40.0). Its prevalence showed a decreasing trend as age and duration of iron supplement increased. Each 1-month increase in infant age was associated with a decreased risk of anemia [OR = 0.88 (95% CI, 0.80–0.98)]. Anemia was not significantly different between genders. Individuals in the highest category for parity (≥3) were at a 2.3-fold greater risk of anemia compared with the lowest category [OR = 2.35 (95% CI, 1.43–3.84)]. In contrast, individuals in the highest category for maternal age (>35 years) had a 62% lower risk of anemia compared with the reference category (<25 years) [OR = 0.38 (95% CI, 0.20–0.72)].ConclusionImplementation of an iron supplementation plan in Iran has decreased anemia among 6- to 12-month-old children.     

Experts’ perspectives on the application of public-private partnership policy in prevention of road traffic injuries

Purpose: Successful application experiences on public-private partnership (PPP) in different countries, suggest that PPP could be an option in road traffic injury (RTI) prevention. The present study aims at investigating the applicability of PPP policy in RTI prevention in Iran based on the experts’ perspectives. Methods: This is a qualitative study with grounded theory approach which has been conducted in Tabriz University of Medical Sciences, Iran in 2018. The participants were 22 experts in the field of RTIs selected using purposive sampling method. Data were collected by semi-structured interviews and analyzed with content-analysis method. Results: The results were classified under 5 main themes (applicability, scopes and services, challenges, advantages, and strategies) for applying PPP policy and 37 sub-themes. Due to the prevalence of RTIs, the present challenges in public sector, existence of qualified private sector, and successful experiences in other areas, there are opportunities for private sector partnership in prevention of RTIs. Private sector could participate in different scopes and services regarding RTI prevention, including road construction and maintenance, maintenance and provision of vehicles safety and public education. The main challenges including legislation issues, ambiguities in collaboration, political and organizational unsustainability, government''s financial hardship and lack of experienced experts in the field of RTI. However, there are significant advantages including high efficiency in program implementation, covering the weaknesses of public sector, effective and efficient management on application of PPP in RTI prevention. The strategies include identifying and prioritizing the assignable activities, identifying the qualified private sector, developing PPP policies and legal frameworks, creating a common language between public and private parties, trying to meet the expectations of the private sector by public sector, developing a comprehensive and sound contract, and cultivating public culture to accept private sector in the field of RTI prevention. Conclusion: This study sought to determine whether PPP could be used as strategy to reduce the burden of RTIs in Iran. But it requires a lot of preliminary studies to provide the context and conditions for applying this policy