Mechanism and antibacterial synergies of poly(Dabco-BBAC) nanoparticles against multi-drug resistant Pseudomonas aeruginosa isolates from human burns.

Multi-drug resistant bacteria are a major problem in the treatment of infectious diseases, such as pneumonia, meningitis, or even coronavirus disease 2019 (COVID-19). Cationic nanopolymers are a new type of antimicrobial agent with high efficiency. We synthesized and characterized cationic polymer based on 1,4-diazabicyclo [2.2.2] octane (DABCO) and Bis (bromoacetyl)cystamine (BBAC), named poly (DABCO-BBAC) nanoparticles(NPs), and produced 150 nm diameter NPs. The antibacterial activity of poly (DABCO-BBAC) against eight multi drug resistant (MDR) Pseudomonas aeruginosa isolates from human burns, its possible synergistic effect with gentamicin, and the mechanism of action were examined. Poly(DABCO-BBAC) could effectively inhibit and kill bacterial strains at a very low concentration calculated by minimum inhibitory concentration (MIC) assay. Nevertheless, its synergism index with gentamicin showed an indifferent effect. Moreover, transmission electron microscopy and lipid peroxidation assays showed that poly (DABCO-BBAC) distorted and damaged the bacterial cell wall. These results suggest that the poly (DABCO-BBAC) could be an effective antibacterial agent for MDR clinical pathogens.

Quantitative measurement of CA 15-3 cancer biomarker using an electrochemical aptasensor based on the electrodeposition of Au thin film on cauliflower-like rGO-MoS2 nanocomposite.

The present research was conducted to design and construct an electrochemical aptasensor for evaluating carbohydrate antigen 15-3 (CA15-3) as a biomarker for breast cancer. The aptasensor has been fabricated by a gold thin film (AuTF) electrodeposited on a cauliflower-like reduced graphene oxide-molybdenum sulfide nanocomposite (rGO-MoS2). The modified electrode's surface was used to immobilize the thiolated aptamer, which was subsequently treated with CA 15-3 antigen. The aptasensor fabrication process was assessed using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). This research also applied EIS to the quantitative measurement of CA 15-3 antigen by the proposed aptasensor. The interfacial charge transfer resistance (Rct) alteration before and after incubation of CA 15-3 by the immobilized aptamer was considered a signal for the quantitative measurement of CA 15-3. A linear concentration ranging from 5.0 to 200.0 U mL-1 with a detection limit of 3.0 × 10-1 U mL-1 was obtained for CA 15-3 using the EIS method. This designed aptasensor indicates satisfactory repeatability and stability, good selectivity, and high sensitivity. Moreover, clinical samples were assayed by the prepared aptasensor and compared with the ELISA method, yielding acceptable results. The recovery and relative standard deviation (RSD) of CA 15-3 in human serum samples were in the range 95.0 to 107.0% and 3.5 to 7.5%, respectively.

Saponin and fluorine-modified polycation as a versatile gene delivery system.

Despite the development of many novel carriers for the delivery of various types of genetic material, the lack of a delivery system with high efficiency and low cytotoxicity is a major bottleneck. Herein, low molecular weight polyethylenimine (PEI1.8k) was functionalized with saponin residues using phenylboronic acid (PBA) as an ATP-responsive cross-linker, and a fluorinated side chain to construct PEI-PBA-SAP-F polycation as a highly efficient delivery vector. This vehicle could transfect small plasmid DNA (∼3 kb) with outstanding efficiency into various cells, including HEK 293T, NIH3T3, A549, PC12, MCF7 and HT-29, as well as robust transfection of a large plasmid (∼9 kb) into HEK 293T cells. The carrier indicated good transfection efficacy even at high concentration of serum and low doses of plasmid. The use of green fluorescent protein (GFP) knock-out analysis demonstrated transfection of different types of CRISPR/Cas9 complexes (Cas9/sgRNA ribonucleoproteins RNP, plasmid encoding Cas9 plus sgRNA targeting GFP, Cas9 expression plasmid plusin vitro-prepared sgRNA). In summary, we report an effective PEI-PBA-SAP-F gene carrier with the appropriate lipophilic/cationic balance for biomedical applications.

A Blockchain-Based Spatial Crowdsourcing System for Spatial Information Collection Using a Reward Distribution.

Due to the increasing relevance of spatial information in different aspects of location-based services, various methods are used to collect this information. The use of crowdsourcing due to plurality and distribution is a remarkable strategy for collecting information, especially spatial information. Crowdsourcing can have a substantial effect on increasing the accuracy of data. However, many centralized crowdsourcing systems lack security and transparency due to a trusted party's existence. With the emergence of blockchain technology, there has been an increase in security, transparency, and traceability in spatial crowdsourcing systems. In this paper, we propose a blockchain-based spatial crowdsourcing system in which workers confirm or reject the accuracy of tasks. Tasks are reports submitted by requesters to the system; a report comprises type and location. To our best knowledge, the proposed system is the first system that all participants receive rewards. This system considers spatial and non-spatial reward factors to encourage users' participation in collecting accurate spatial information. Privacy preservation and security of spatial information are considered in the system. We also evaluated the system efficiency. According to the experiment results, using the proposed system, information accuracy increased by 40%, and the minimum time for reviewing reports by facilities reduced by 30%. Moreover, we compared the proposed system with the current centralized and distributed crowdsourcing systems. This comparison shows that, although our proposed system omits the user's history to preserve privacy, it considers a consensus-based approach to guarantee submitted reports' accuracy. The proposed system also has a reward mechanism to encourage more participation.

An Investigation of the Pathology Report of Bladder Cancer Patients with Radical Cystectomy in Southern Iran, 2013-2018: A Cross-Sectional Study.

Background: The oncological outcomes of bladder cancer are directly associated with disease pathology and surgical technique. Therefore, we investigated the pathologic factors of radical cystectomy (RC) specimens. Methods: In this retrospective study, 365 patients who underwent RC between March 2013 to March 2018 in hospitals affiliated to Shiraz University were enrolled. The patients' clinicopathological parameters, such as tumor type, tumor grade, carcinoma in situ, lymph node (LN) involvement, lymphovascular invasion (LVI), perineural invasion (PNI), and age, were recorded from their pathology reports. For comparison of variables, an independent t test was used. P < 0.05 was regarded as significant. The statistical software SPSS version 22 was used to examine the data. Results: The participants' mean age was 64.52 ± 11.54 years, and 320 (87.7%) patients were men and 45 (12.3%) were women. The mean dissected LN was 9.69 ± 8.70 nodes and 1.06 ±3.49 of the dissected LNs were involved by tumor. PNI and perivesical invasion were presented in 148 (40.5%) and 96 (26.3%) patients, respectively. Ureteral, urethral, and prostate involvements were seen in 23 (6.3%), 50 (13.7%), and 66 (18.1%) patients. Most patients had pathologic tumor stage 2 (36.4%). Factors such as LVI, PNI, perivesical invasion, and prostate involvement, were strongly correlated with positive LN (P ≤ 0.05). Conclusion: The examination of the RC specimen is critical for patient care, outcome, and justification of adjuvant therapy. Factors such as LVI, perineural invasion, perivesical invasion, and prostate involvement were strongly correlated with positive LN.

An Interoperable Architecture for the Internet of COVID-19 Things (IoCT) Using Open Geospatial Standards-Case Study: Workplace Reopening.

To safely protect workplaces and the workforce during and after the COVID-19 pandemic, a scalable integrated sensing solution is required in order to offer real-time situational awareness and early warnings for decision-makers. However, an information-based solution for industry reopening is ineffective when the necessary operational information is locked up in disparate real-time data silos. There is a lot of ongoing effort to combat the COVID-19 pandemic using different combinations of low-cost, location-based contact tracing, and sensing technologies. These ad hoc Internet of Things (IoT) solutions for COVID-19 were developed using different data models and protocols without an interoperable way to interconnect these heterogeneous systems and exchange data on people and place interactions. This research aims to design and develop an interoperable Internet of COVID-19 Things (IoCT) architecture that is able to exchange, aggregate, and reuse disparate IoT sensor data sources in order for informed decisions to be made after understanding the real-time risks in workplaces based on person-to-place interactions. The IoCT architecture is based on the Sensor Web paradigm that connects various Things, Sensors, and Datastreams with an indoor geospatial data model. This paper presents a study of what, to the best of our knowledge, is the first real-world integrated implementation of the Open Geospatial Consortium (OGC) Sensor Web Enablement (SWE) and IndoorGML standards to calculate the risk of COVID-19 online using a workplace reopening case study. The proposed IoCT offers a new open standard-based information model, architecture, methodologies, and software tools that enable the interoperability of disparate COVID-19 monitoring systems with finer spatial-temporal granularity. A workplace cleaning use case was developed in order to demonstrate the capabilities of this proposed IoCT architecture. The implemented IoCT architecture included proximity-based contact tracing, people density sensors, a COVID-19 risky behavior monitoring system, and the contextual building geospatial data.

Comparison between novel star-like redox-sensitive amphiphilic block copolymer and its linear counterpart copolymer as nanocarriers for doxorubicin.

Linear and star-like redox-sensitive amphiphilic block copolymers have been studied as anticancer drug delivery systems. However, few reports directly compared the properties of those two structures especially when they are used as nanocarriers for antitumor drugs. To address this, a novel star-like copolymer and its linear counterpart were synthesized with a hydrophobic/redox-responsive/hydrophilic structure. The overall molecular weight of the star-shaped copolymer was nearly equal to that of the linear counterpart. The star-like micelles exhibit size of 90 nm, which was smaller than that of linear copolymers (151.6 nm) and critical micelle concentration of 1 mg/L, which was lower than that of the linear micelles (8.9 mg/L). The disassembly behaviors and the redox-sensitivity of the nanoparticles to reductive stimuli of glutathione was evaluated from the changes of the micellar size and morphology. Furthermore, doxorubicin was physically loaded into the hydrophobic part of the copolymers. The drug-loading capacities in the star-like and linear micelles were 15.94 and 7.53 wt%, respectively. Drug release studies carried out at two different glutathione concentrations. A cytotoxicity study of the micelles was performed by MTT assay. The prepared star copolymer showed no significant toxicity against HDF cells while enhanced cytotoxicity of the DOX-loaded micelles against MCF-7 cells was observed. Therefore, developing sucrose-PCL-SS-PEG copolymer reported in this paper as an effective reduction-responsive carrier with excellent properties and cell biocompatibility is promising for the efficient intracellular delivery of hydrophobic chemotherapeutic drugs. This work also indicates that modification of the nanocarrier structure is a potential strategy for optimizing drug delivery.

Context-aware personal navigation using embedded sensor fusion in smartphones.

Context-awareness is an interesting topic in mobile navigation scenarios where the context of the application is highly dynamic. Using context-aware computing, navigation services consider the situation of user, not only in the design process, but in real time while the device is in use. The basic idea is that mobile navigation services can provide different services based on different contexts-where contexts are related to the user's activity and the device placement. Context-aware systems are concerned with the following challenges which are addressed in this paper: context acquisition, context understanding, and context-aware application adaptation. The proposed approach in this paper is using low-cost sensors in a multi-level fusion scheme to improve the accuracy and robustness of context-aware navigation system. The experimental results demonstrate the capabilities of the context-aware Personal Navigation Systems (PNS) for outdoor personal navigation using a smartphone.

Nucleic acid-responsive smart systems for controlled cargo delivery.

Stimulus-responsive delivery systems allow controlled, highly regulated, and efficient delivery of various cargos while minimizing side effects. Owing to the unique properties of nucleic acids, including the ability to adopt complex structures by base pairing, their easy synthesis, high specificity, shape memory, and configurability, they have been employed in autonomous molecular motors, logic circuits, reconfigurable nanoplatforms, and catalytic amplifiers. Moreover, the development of nucleic acid (NA)-responsive intelligent delivery vehicles is a rapidly growing field. These vehicles have attracted much attention in recent years due to their programmable, controllable, and reversible properties. In this work, we review several types of NA-responsive controlled delivery vehicles based on locks and keys, including DNA/RNA-responsive, aptamer-responsive, and CRISPR-responsive, and summarize their advantages and limitations.

Application of Uterus Manipulator in Total Abdominal Hysterectomy for Benign Diseases.

Objective: Pelvic access is a challenging matter in abdominal hysterectomy especially in obese patients and presence of pelvic adhesions. Uterus manipulators (UM) have been used in a number of studies on laparoscopic approach to improve surgical performance. This study aimed to assess the impact of UM application on the operation time and blood loss in total abdominal hysterectomy (TAH) for benign diseases. Materials and methods: Forty-one patients aged 34 to 56 years were enrolled for abdominal hysterectomy - 20 as the case group (hysterectomy with UM application) and 21 as the control group (conventional hysterectomy). In the case group, UM was used after uterus artery ligation during TAH. The control group underwent traditional TAH. Results: The mean operation time was significantly less in TAH with UM compared to traditional TAH (90.23 ± 10.54 minutes vs. 140.5 ± 16.61 minutes; p-value<0.001). The mean decline between preoperative and 12-hour postoperative hemoglobin was 0.74 ± 0.23 mg/dL in the TAH with UM group and 1.65± 1.02 mg/dL in the traditional TAH group (p-value<0.001). Also, no difference was detected in intra- and post-operative complications. Conclusion: The current study showed that, using UM is beneficial in total abdominal hysterectomy by decreasing the operative time and blood loss.

Fetal Outcomes and Prognostic Factors After Radiofrequency Ablation for the Selective Reduction in Complicated Monochorionic Multiple Pregnancies.

RATIONALE AND OBJECTIVES: Monochorionic pregnancies are responsible for some severe complications, and selective reduction of a single fetus can improve pregnancy outcomes. This study evaluated the fetal outcomes and procedure-related prognostic factors after radiofrequency ablation (RFA) in complicated monochorionic multiple pregnancies. MATERIALS AND METHODS: This prospective cross-sectional study was conducted in an academic center from June 2020 to January 2022. The participants were 70 women with monochorionic multiple pregnancies who were candidates for selective fetal reduction by RFA. All participants' demographic data, RFA-related information, and pregnancy outcomes were evaluated and reported. RESULTS: The RFA procedure was successful in all participants. The most frequent RFA indications were twin-to-twin transfusion syndrome following selective intrauterine growth restriction. The mean gestational age at birth was 33.60 ± 5.62 weeks. Also, 11 (15.7%) of the cases had preterm delivery up to 30 days after RFA. The total pregnancy loss rate was 12 (17.14%), and the total fetal survival rate after RFA was 82.85%. The mean time of the RFA procedure was 130.8 ± 83.3 seconds. The procedure was conducted easily in 31 (44.2%) cases. Although the meantime of RFA procedure was longer in the not-easy group, the difference in surgery time was not significant (P = .296). There was no significant relationship (P = .623) between RFA indications and the gestational age of the remained fetus at delivery. The RFA needle was passed through the placenta in 18 (25.7%) cases. The mean gestational age at the delivery time was significantly lower in this group compared to their counterparts' gestational ages without needle placental passage (P = .030). Also, there was no significant correlation between gestational age at pregnancy termination and RFA cycles (P = .219). CONCLUSION: RFA is a relatively safe and minimally invasive procedure for the selective reduction of complicated monochorionic fetuses. Although mortality, premature membrane rupture, and preterm delivery are the potential risk factors for the remaining co-twin. According to this study, gestational age at the time of the procedure and passing the needle through the placenta can affect the outcome. Other procedure-related factors like easy- or hard-access procedures, and the number of RFA cycles are not significantly associated with gestational age at birth.

Radiofrequency Ablation and Intrauterine Transfusion in a Delayed Diagnosed Acardiac Twin Pregnancy.

Twin reversed arterial perfusion (TRAP) sequence or acardiac twin is a rare and severe complication of monochorionic multiple pregnancies. Acardiac twin accounts for 10% of all TRAP sequences, which is the most morphologically developed acardius. We present an undiagnosed TRAP sequence case up to 24 weeks of gestation who underwent successful amnioreduction, radiofrequency ablation (RFA), and intrauterine transfusion (IUT). During follow-up, hydrops of surviving co-twin disappeared, and fetal heart function improved. Finally, a healthy girl weighing 2400 g was born at 36 weeks of gestation. To our knowledge, this is the first reported acardiac twin pregnancy, which requires IUT, in addition to RFA, due to late diagnosis. Therefore, this case report presents successful management options for TRAP sequence cases diagnosed late in pregnancy.

Effect of intra-ovarian platelet rich plasma in women with poor ovarian response.

Background: Poor ovarian responder (POR) women, whose ovarian response to gonadotropin stimulation has decreased, are at higher risk of unsuccessful in-vitro fertilization (IVF). Therefore, this study designed to evaluate the effect of intra-ovarian platelet rich plasma (PRP) on POR women. Methods: This single-arm trial research was done on 20 POR women referred to the IVF Unit, university-based hospital, Tehran, Iran between October 2020 and September 2021. For all participants, autologous PRP was injected into each ovary by transvaginal ultrasound guidance under spinal anesthesia between days 12 and 14 of the menstrual cycle. After 12 weeks of PRP injection, embryo transfers were carried out following our routine IVF department protocol. The study outcomes were the number of mature oocytes, and pregnancy rates. Results: The average age of the participants was 41.80±1.82 yr. The average infertility duration was 9.70±1.89 yrs., with 80% primary infertility type. After PRP injection, follicle-stimulating hormone levels dropped about 1% (P=0.499), anti-Mullerian hormone levels were on average 4.5% higher (P=0.356), and estradiol levels raised by 1.2% (P=0.681). The average number of oocytes and their quality increased after PRP injection, while these changes were not significant (p-value>0.05). Chemical pregnancy was detected in 3 (15%) women and clinical pregnancy was detected only in one person. Conclusion: This study revealed that PRP injection into ovaries of POR women is safe and had a tendency to improve ovarian reserve markers and serum levels of AMH, estradiol, number and quality of oocytes.

Importance of pre-operative COVID-19 screening test in elective surgeries.

Background and Objectives: Since the COVID-19 pandemic initiation, more than 28 million elective surgeries were postponed with a cancellation rate of 72.3%. However, studies suggested that the patient treatment should be conducted within 12 weeks of diagnosis because delay in treatment might have had adverse impacts on patients' health status, prognosis, and pathologic stage. Hence, the current study aimed to assess the importance of a pre-operative COVID-19 screening test for the patients were candidates for elective surgery. Materials and Methods: This cross-sectional study was conducted on 141 patients who were candidates for any type of elective surgeries or cesarean section at a tertiary university-based hospital, between June 2020, and September 2020. Results: The mean age of participants was 41.38 ± 11.66 years. Of them, 91.5% were women and 8.5% were men. The COVID-19 polymerase chain reaction (PCR) screening tests were positive in 12 (8.5%) patients. From whose PCR tests were positive, only five people (less than half) had symptoms of COVID-19 such as fever (three patients), a distinctive smell (two patients), and cough (one patient). Suspected exposure to COVID-19 was reported in four of them. Conclusion: In this study, we found that more than half of PCR positive COVID-19 patients were asymptomatic. Therefore, to have a safe hospital environment, and improve patient health outcomes, the COVID-19 screening test should be applied before any interventions.

Smart Strategies for Precise Delivery of CRISPR/Cas9 in Genome Editing.

The emergence of CRISPR/Cas technology has enabled scientists to precisely edit genomic DNA sequences. This approach can be used to modulate gene expression for the treatment of genetic disorders and incurable diseases such as cancer. This potent genome-editing tool is based on a single guide RNA (sgRNA) strand that recognizes the targeted DNA, plus a Cas nuclease protein for binding and processing the target. CRISPR/Cas has great potential for editing many genes in different types of cells and organisms both in vitro and in vivo. Despite these remarkable advances, the risk of off-target effects has hindered the translation of CRISPR/Cas technology into clinical applications. To overcome this hurdle, researchers have devised gene regulatory systems that can be controlled in a spatiotemporal manner, by designing special sgRNA, Cas, and CRISPR/Cas delivery vehicles that are responsive to different stimuli, such as temperature, light, magnetic fields, ultrasound (US), pH, redox, and enzymatic activity. These systems can even respond to dual or multiple stimuli simultaneously, thereby providing superior spatial and temporal control over CRISPR/Cas gene editing. Herein, we summarize the latest advances on smart sgRNA, Cas, and CRISPR/Cas nanocarriers, categorized according to their stimulus type (physical, chemical, or biological).

Dual Redox/pH-Sensitive Micelles Self-Assembled From Star-Like Amphiphilic Copolymers Based On Sucrose For Controlled Doxorubicin Delivery.

Novel dual redox/pH-sensitive star-like amphiphilic sucrose-oligo(butyl fumarate) (thioglycolic acid conjugate)-SS-poly(ethylene glycol) (Suc-OBF(TGA)-SS-PEG) copolymers and their self-assembled micelles were prepared and utilized for intracellular doxorubicin delivery. Importance of changing the hydrophobic chain length on micelles properties was investigated. Results showed that the micelles with longer hydrophobic chain exhibited smaller size and were more stable in aqueous solution. The redox and pH sensitivity of the micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic light scattering and the change of micellar morphology observed by scanning electron microscope. The micelles display a decent doxorubicin loading capacity. In vitro release studies showed that only 14.3% doxorubicin was released from doxorubicin-loaded micelles under physiological conditions in 30 h. The release of doxorubicin was accelerated at pH 5.5 or in the presence of 10 mM glutathione at pH 7.4 (46.9% and 76.9% of doxorubicin was released, respectively, in 30 h). The doxorubicin release was further expedited under pH 5.5 and 10 mM GSH conditions (91.4%). Suc-OBF(TGA)-SS-PEG micelles displayed no cytotoxicity toward HDF cells. MTT assays indicated that doxorubicin-loaded micelles had good cytotoxicity against MCF-7 cells. This work suggested that star-like amphiphilic Suc-OBF(TGA)-SS-PEG copolymer micelles may provide a promising platform for delivering doxorubicin and other hydrophobic anticancer drugs.