The role of exosomes and miRNAs in drug‐resistance of cancer cells

Chemotherapy, one of the principal approaches for cancer patients, plays a crucial role in controlling tumor progression. Clinically, tumors reveal a satisfactory response following the first exposure to the chemotherapeutic drugs in treatment. However, most tumors sooner or later become resistant to even chemically unrelated anticancer agents after repeated treatment. The reduced drug accumulation in tumor cells is considered one of the significant mechanisms by decreasing drug permeability and/or increasing active efflux (pumping out) of the drugs across the cell membrane. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated, including drug efflux, which is mediated by extracellular vesicles (EVs). Exosomes, a subset of EVs with a size range of 40–150 nm and a lipid bilayer membrane, can be released by all cell types. They mediate specific cell‐to‐cell interactions and activate signaling pathways in cells they either fuse with or interact with, including cancer cells. Exosomal RNAs are heterogeneous in size but enriched in small RNAs, such as miRNAs. In the primary tumor microenvironment, cancer‐secreted exosomes and miRNAs can be internalized by other cell types. MiRNAs loaded in these exosomes might be transferred to recipient niche cells to exert genome‐wide regulation of gene expression. How exosomal miRNAs contribute to the development of drug resistance in the context of the tumor microenvironment has not been fully described. In this review, we will highlight recent studies regarding EV‐mediated microRNA delivery in formatting drug resistance. We also suggest the use of EVs as an advancing method in antiresistance treatment.     

Association of KCNJ11 and ABCC8 single-nucleotide polymorphisms with type 2 diabetes mellitus in a Kinh Vietnamese population

Type 2 diabetes mellitus (T2DM) is a genetically influenced disease, but few studies have been performed to investigate the genetic basis of T2DM in Vietnamese subjects. Thus, the potential associations of KCNJ11 and ABCC8 single nucleotide polymorphisms (SNPs) with T2DM were investigated in a Kinh Vietnamese population. A cross-sectional study consisting of 404 subjects including 202 T2DM cases and 202 non-T2DM controls was designed to examine the potential associations of 4 KCNJ11 and ABCC8 SNPs (rs5219, rs2285676, rs1799859, and rs757110) with T2DM. Genotypes were identified based on restriction fragment length polymorphism and tetra-primer amplification refractory mutation system polymerase chain reaction. After statistically adjusting for age, sex, and BMI, rs5219 was found to be associated with an increased risk of T2DM under 2 inheritance models: codominant (OR = 2.15, 95% confidence intervals [CI] = 1.09–4.22) and recessive (OR = 2.08, 95%CI = 1.09–3.94). On the other hand, rs2285676, rs1799859, and rs757110 were not associated with an increased risk of T2DM. Haplotype analysis elucidated a strong linkage disequilibrium between the 3 SNPs, rs5219, rs2285676, and rs757110. The haplotype rs5219(A)/rs2285676(T)/rs757110(G) was associated with an increased risk of T2DM (OR = 1.42, 95%CI = 1.01–1.99). The results show that rs5219 is a lead candidate SNP associated with an increased risk of developing T2DM in the Kinh Vietnamese population. Further functional characterization is needed to uncover the mechanism underlying the potential genotype-phenotype associations.     

Ultra-low detection limit chemoresistive NO2 gas sensor using single transferred MoS2 flake: an advanced nanofabrication

In this work, a method of fabricating a NO₂ nano-sensor working at room temperature with a low detectable concentration limit is proposed. A 2D-MoS₂ flake is isolated by transferring a single MoS₂ flake to SiO₂/Si substrate, followed by applying an advanced e-beam lithography (EBL) to form a metal contact with Au/Cr electrodes. The resulting chemoresistive nano-sensor using a single MoS₂ flake was applied to detect a very low concentration of NO₂ at the part-per-billion (ppb) level. This result is obtained due to the ability to create microscopic nano-sized MoS₂ gaps using e-beam lithography (300 nm–400 nm). Experimental results also show that the sensor can capture changes in concentration and send the information out extremely quickly. The response and recovery time of the sensor also reached the lowest point of 50 and 75 ms, outperforming other sensors with a similar concentration working range.

In this work, a method of fabricating a NO₂ nano-sensor working at room temperature with a low detectable concentration limit is proposed.     

The value of quantitative magnetic resonance imaging signal intensity in distinguishing between spinal meningiomas and schwannomas

Background: Prior studies have suggested a number of the subjective visual characteristics that help distinguish between spinal meningiomas and schwannomas on magnetic resonance imaging and computed tomography; however, objective quantification of the signal intensity can be useful information. This study assessed whether quantitative magnetic resonance imaging (MRI) signal intensity (SI) measurements could distinguish intradural-extramedullary schwannomas from meningiomas.Methods: From July 2019 to September 2021, 54 patients with intradural-extramedullary tumors (37 meningiomas and 17 schwannomas) underwent surgery, and tumors were verified pathologically. Defined regions of interest were used to quantify SI values on T1- (T1W) and T2-weighted images (T2W). Receiver operating characteristic curve analysis was used to obtain cutoff values and calculate the area under the curve (AUC), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV).Results: Both Maximum (T2_max) and mean (T2_mean) T2W SI values demonstrated outstanding (AUC: 0.91) abilities to differentiate meningiomas from schwannomas with Se, Sp, PPV, and NPV values of 94.6%, 70.6%, 87.5%, and 85.7%, respectively, for T2_max and 81.1%, 88.2%, 93.8%, and 68.2% for T2_mean. The maximum SI value on contrast-enhanced T1W (T1CE_max) and the T2W tumor: fat SI ratio (rTF) demonstrated acceptable abilities (AUC: 0.73 and 0.79, respectively) to differentiate meningiomas from schwannomas with Se, Sp, PPV, and NPV values of 94.6%, 70.6%, 87.5%, and 85.7%, respectively, for T1CE_max and 81.1%, 88.2%, 93.8%, and 68.2% for rTF.Conclusions: Quantitative SI values (T2_max, T2_mean, T2_min, T1CE_max, rTF) can be used to differentiate intradural-extramedullary schwannomas from meningiomas.     

Emerging Infections Program—State Health Department Perspective

The Emerging Infections Program (EIP) is a collaboration between the Centers for Disease Control and Prevention and 10 state health departments working with academic partners to conduct active population-based surveillance and special studies for several emerging infectious disease issues determined to need special attention. The Centers for Disease Control and Prevention funds the 10 EIP sites through cooperative agreements. Our objective was to highlight 1) what being an EIP site has meant for participating health departments and associated academic centers, including accomplishments and challenges, and 2) the synergy between the state and federal levels that has resulted from the collaborative relationship. Sharing these experiences should provide constructive insight to other public health programs and other countries contemplating a collaborative federal–local approach to collective public health challenges.     

When Is a Maze Procedure a Maze Procedure?

The initial surgical attempts to treat atrial fibrillation (AF) were isolation procedures designed to confine the arrhythmia to a specific area of the heart for relief of symptoms. The first surgical attempt to ablate AF was unsuccessful but was quickly followed by the Maze-I procedure on September 25, 1987. Because of several adverse sequelae of the Maze-I procedure, it was sequentially modified to the Maze-II and then Maze-III procedures. The Maze-IV procedure was introduced some 10 years later; these are the only 4 procedures that adhere to the concept of a maze pattern of lesions to ablate AF and leave both atria capable of being activated during normal sinus rhythm. The term maze procedure has become generic for virtually any operation designed to treat AF, but procedures that do not adhere to the concept of creating lesions of conduction block in the pattern of a maze are not maze procedures. These include, among others, the Wolf Mini-Maze, the Left-Sided Maze, and the 5-Box Maze, none of which are truly based on the maze-pattern concept. The cardinal feature of maze procedures that is necessary for both effectiveness and comparability to classical maze procedures includes lines of conduction block that preclude macro-reentry anywhere in either atrium while leaving both atria capable of activation by a sinus-generated impulse. Components essential to achieving this include appropriate lesions in both atria, the absence of gaps that allow electrical activity to bypass an intended line of block, and the absence of alternate pathways by which impulses can reach the intended maze exit.     

Dietary Assessment on a Mobile Phone Using Image Processing and Pattern Recognition Techniques: Algorithm Design and System Prototyping

Dietary assessment, while traditionally based on pen-and-paper, is rapidly moving towards automatic approaches. This study describes an Australian automatic food record method and its prototype for dietary assessment via the use of a mobile phone and techniques of image processing and pattern recognition. Common visual features including scale invariant feature transformation (SIFT), local binary patterns (LBP), and colour are used for describing food images. The popular bag-of-words (BoW) model is employed for recognizing the images taken by a mobile phone for dietary assessment. Technical details are provided together with discussions on the issues and future work.     

The pharmacokinetics of artemisinin after administration of two different suppositories to healthy Vietnamese subjects

Eight healthy Vietnamese male subjects received 400 mg artemisinin formulated into fatty suppositories (FS), and six different subjects received 500 mg of artemisinin formulated in polyethylene glycol suppositories (PEGS). Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection; concentration versus time curves were analyzed with nonparametric methods. No statistically significant differences were found between the two formulations. The maximum concentration (Cmax) was 100 +/- 102 microg/L (mean +/- SD, range = 24-330) microg/L (FS), the pharmacokinetic lag time (Tlag) was 1.3 +/- 1.0 hr (range = 0-3) (FS), and the time of the maximum concentration (Tmax) was 7.1 +/- 2.1 hr (range = 3-10) hr (FS). Because artemisinin is not available for intravenous dosage, absolute bioavailability cannot be assessed. However, compared with a previous study on oral artemisinin in healthy Vietnamese subjects, bioavailability relative to oral administration was estimated to be approximately 30%. We conclude that therapeutic blood concentrations of artemisinin can be reached after rectal dosage. The dose after rectal administration should probably be higher than after oral administration; doubling or tripling the oral dose might be necessary, which would imply a rectal dose of at least 20 mg/kg of body weight given twice a day.     

The genetic and antigenic diversity of avian influenza viruses isolated from domestic ducks, muscovy ducks, and chickens in northern and southern Vietnam, 2010–2012

To estimate the prevalence of avian influenza virus infection in Vietnam, surveillance was conducted in domestic and wild birds from households, live-bird markets, slaughtering sites, and bird sanctuaries in Vietnam between October 2010 and October 2012. Of the 4,550 samples collected, 226 influenza A virus isolates were obtained from domestic ducks, muscovy ducks, and chickens. Of these, 25 and 22 H5N1 highly pathogenic avian influenza viruses (HPAIVs) were isolated from apparently healthy domestic ducks in live-bird markets and slaughtering sites in northern and southern Vietnam, respectively. The HA genes of H5 viruses isolated from birds in northern Vietnam phylogenetically belonged to the genetic clade 2.3.2.1 and those in southern Vietnam belonged to the genetic clade 1.1. In addition, 39 H3, 12 H4, 1 H5, 93 H6, 2 H7, 18 H9, 3 H10, and 11 H11 viruses were isolated. Phylogenetic and antigenic analyses of the H6 and H9 viruses revealed that they were closely related to the isolates obtained from domestic poultry in China. Phylogenetic analyses of internal gene segments of these isolates revealed that these viruses were circulating in both domestic and wild birds in Asia and reassortment events had occurred frequently. Therefore, it will be important to continue the surveillance and strict controls over the movement and trade of poultry and poultry products in order to eradicate H5N1 HPAIV from Asia.