Effectiveness of telephone-based screening and triage during COVID-19 outbreak in the promoted primary healthcare system: a case study in Ardabil province,Iran

Journal of Public Health - Screening services for early detection of patients is one of the important capabilities of the health system with a proper referral system. In the crisis of respiratory...     

Acoustic characterization of a miniature matrix transducer for pediatric 3D transesophageal echocardiography

This paper presents the design, fabrication and characterization of a miniature PZT-on-CMOS matrix transducer for real-time pediatric 3-dimensional (3D) transesophageal echocardiography (TEE). This 3D TEE probe consists of a 32?×?32 array of PZT elements integrated on top of an Application Specific Integrated Circuit (ASIC). We propose a partitioned transmit/receive array architecture wherein the 8?×?8 transmitter elements, located at the centre of the array, are directly wired out and the remaining receive elements are grouped into 96 sub-arrays of 3?×?3 elements. The echoes received by these sub-groups are locally processed by micro-beamformer circuits in the ASIC that allow pre-steering up to ±37°. The PZT-on-CMOS matrix transducer has been characterized acoustically and has a centre frequency of 5.8 MHz, -6 dB bandwidth of 67%, a transmit efficiency of 6 kPa/V at 30 mm, and a receive dynamic range of 85 dB with minimum and maximum detectable pressures of 5 Pa and 84 kPa respectively. The properties are very suitable for a miniature pediatric real-time 3D TEE probe.     

Evaluating the effects of single and combined chelators therapies on spatial learning and memory impairments in chronic manganese poisoning

Manganese (Mn) is considered an essential metal; nevertheless, exposure to high levels of Mn may cause neurotoxic effects. In the present study, we examined the effect of Mn on spatial learning and memory impairment and ability of three known chelators deferasirox (DFX), deferiprone (L1) and desferrioxamine (DFO) as single and combined therapies in removing Mn from the body and their effect on spatial learning and memory in rats poisoned with manganese. Male Wistar rats divided to 19 groups (5 rats per group). Two doses of manganese chloride (30 and 60?mg/kg/b.w. in drinking water) were administrated for 90 days. Then chelators were given for 14 days. Results showed that exposure to Mn (high and low doses) significantly impaired the spatial learning and memory compared to control group (p?<?0.01). Chelation therapy improved it in chelator agents groups compared to vehicle group (p?<?0.001). Chelator agents with removing Mn from brain can improve MWM performance. Results indicated that combined therapies were more efficient compared to single therapies.     

Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles

Background

Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system.

Methods

The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed.

Results

The particle size of NPs ranged from 170 to 190 nm and increased about 20–30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased further after HSA conjugation. The HSA conjugation in prepared NPs was proved by Fourier transform infrared (FT-IR) spectroscopy, faster degradation of HSA in Differential scanning calorimetry (DSC) characterization, and other evidences such as the increasing in size and the decreasing in zeta potential. The PTX released in a biphasic mode for all colloidal suspensions. A sustained release profile for approximately 33 days was detected after a burst effect of the loaded drug. The in vitro cytotoxicity evaluation also indicated that the HSA NPs are more cytotoxic than plain NPs.

Conclusions

HSA decoration of PLGA NPs may be a suitable method for longer blood circulation of NPs.     

CD44‐Targeted Docetaxel Conjugate for Cancer Cells and Cancer Stem‐Like Cells: A Novel Hyaluronic Acid‐Based Drug Delivery System

A CD44‐targeted macromolecular conjugate of docetaxel was prepared via a pH‐sensitive linkage to hyaluronic acid and was characterized using NMR, gel permeation chromatography, and differential scanning calorimetry. The conjugated species were further evaluated in terms of drug release, cytotoxicity, cellular uptake, cell cycle inhibition, and subacute toxicity in mice. Cellular microscopic studies revealed that CD44‐expressing cells including MCF‐7 cancer stem cells and MDA‐MB‐231 metastatic breast cancer cells had internalized the conjugates via a selective receptor‐mediated mechanism, leading to cell cycle arrest in the G2/M phase. Hyaluronic acid–docetaxel conjugates showed specific toxicity only in CD44‐expressing cells in vitro, along with a decreased risk of neutropenia and dose‐dependent mortality in vivo. Hyaluronic acid–drug conjugates represent a promising and efficient platform for solubilization of sparingly soluble molecules as well as active and selective targeted delivery to cancer cells and cancer stem cells.     

Expression of glycodelin protein and mRNA in human ductal breast cancer carcinoma in situ, invasive ductal carcinomas, their lymph node and distant metastases, and ductal carcinomas with recurrence

Glycodelin, previously known as PP14, has been localized in endometrial, ovarian and cervical carcinoma cells. Recently, glycodelin was demonstrated to be expressed in cancerous human breast tissue. In this study, paraffin-embedded slides of carcinoma in situ, invasive carcinomas without metastases, invasive carcinomas with corresponding lymph node metastases, invasive carcinomas with corresponding recurrence and invasive carcinomas with corresponding distant metastases were investigated for glycodelin protein and mRNA expression. Protein expression was found in all cases of carcinoma in situ, in invasive carcinoma without lymph node metastases in 90% of cases, in breast cancer with lymph node metastases in 50% of cases, in breast cancer with recurrence in 38% of cases and in breast cancer with distant metastases in 40% of cases. Results were confirmed by in situ hybridization showing reduced glycodelin expression as lymph node metastasis progressed, compared to carcinoma in situ. Glycodelin mRNA expression is not further reduced in carcinomas with distant metastasis and recurrence compared to carcinoma in situ. Results demonstrate that invasive breast carcinomas without metastases are more likely to express glycodelin. In contrast, cases of breast cancer with metastatic infiltration and recurrence show weak expression of glycodelin. On the basis of these results, we speculate that glycodelin could be used as a prognostic marker for breast cancer.     

Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3

Adenosine is a regulatory molecule with widespread physiological effects in almost every cells and acts as a potent regulator of cell growth. Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via caspase activation and Bcl-2/Bax pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the OVCAR-3 human ovarian cancer cells. MTT viability, BrdU and cell counting assays were used to study the cell proliferation effect of adenosine in presence of adenosine deaminase inhibitor and the nucleoside transporter inhibitor. Cell cycle analysis, propidium iodide and annexin V staining, caspase-3 activity assay, cyclinD1, Cdk4, Bcl-2 and Bax protein expressions were assessed to detect apoptosis. Adenosine significantly inhibited cell proliferation in a concentration-dependent manner in OVCAR-3 cell line. Adenosine induced cell cycle arrest in G0/G1 phase via Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by Annexin V-FITC staining and increased sub-G1 population. Moreover, down-regulation of Bcl-2 protein expression, up-regulation of Bax protein expression and activation of caspase-3 were observed in response to adenosine treatment. The results of this study suggest that extracellular adenosine induced G1 cell cycle arrest and apoptosis in ovarian cancer cells via cyclinD1/ Cdk4 and Bcl-2/Bax pathways and caspase-3 activation. These data might suggest that adenosine could be used as an agent for the treatment of ovarian cancer.