Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)‐derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson’s disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder‐ and xenogeneic‐free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock‐in lines (LMX1A‐eGFP and PITX3‐eGFP) for in‐depth in vitro and in vivo tracking. Across multiple embryonic and induced hPSC lines, this “next generation” protocol consistently increases both the yield and proportion of vmDA neural progenitors (OTX2/FOXA2/LMX1A) and neurons (FOXA2/TH/PITX3) that display classical vmDA metabolic and electrophysiological properties. We identify the mechanism underlying these improvements and demonstrate clinical applicability with the first report of scalability and cryopreservation of bona fide vmDA progenitors at a time amenable to transplantation. Finally, transplantation of xeno‐free vmDA progenitors from LMX1A‐ and PITX3‐eGFP reporter lines into Parkinsonian rodents demonstrates improved engraftment outcomes and restoration of motor deficits. These findings provide important and necessary advancements for the translation of hPSC‐derived neurons into the clinic. Stem Cells Translational Medicine 2017;6:937–948
Coronavirus disease-19 (COVID-19) is a highly contagious infection that mainly affects the respiratory system of patients. To date, more than 10 million people have been affected by this virus, and Saudi Arabia has also reported over 210 million cases. At present, there is no established treatment for COVID-19. Vaccination is one of the ways to defeat the pandemic. Recent reports have indicated rare but serious adverse events after vaccination, causing an anxious response from the general public worldwide. Therefore, this study was aimed at evaluating the knowledge, attitude, and perception of the COVID-19 vaccine among the Saudi population. This study is a cross-sectional, web-based online survey conducted using a snowball sampling technique. A self-administered questionnaire prepared in Arabic and English was used to collect feedback from the general population on their knowledge, attitudes, and perceptions about the COVID-19 vaccine. Participants (n = 2022) from different regions of the country replied to the questions. The responses to the questions were recorded on a spreadsheet and analyzed using the SPSS software. Statistical analysis was performed using one-way ANOVA and non-parametric tests to draw conclusions about the results. Multivariate stepwise regression analysis was performed to determine the association between the knowledge, attitude, and perception scores and the demographic variables. p < 0.05 was used to indicate the significance of the data. The data from the study indicated that most of the participants were males (81%), between 18 and 59 years of age (85.9%), Saudi nationals (98.3%), and possessed graduation or above as a qualification (62.9%). The results suggest that a major portion of respondents have satisfactory knowledge (76%), a positive attitude (72.4%), and perception (71.3%) towards the use of COVID-19 vaccines. Their responses can be categorized as between ‘good’ and ‘fair’. However, 30–40% of respondents lacked information about COVID-19 vaccination availability for under 18-year-olds as well as for pregnant women, in addition to the lack of knowledge about the serious unreported adverse reactions and long-term protection offered by the vaccine against coronavirus. The correlation analysis between the variables (p > 0.05) indicated that the response to the KAP domains has no direct relationship. The survey results suggest that most of the Saudi population has sound knowledge and a positive attitude and perception. Since the COVID-19 vaccines have been approved for use in pregnancy and above 12-year-old children by health authorities, the lack of information shown by a significant percentage of participants requires strategies to update this information. Awareness programs targeting all sections of the population must be continued to provide all the updates, including vaccinations for pregnant women and children.
Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.
Detailed description of malaria in low transmission areas is crucial for elimination. The current study aimed to provide a comprehensive description for malaria transmission in Jazan, a low transmission district, southwestern Saudi Arabia. Patients at a tertiary care hospital were recruited in our study between August 2016 and September 2018. Malaria diagnosis was performed through a species-specific nested polymerase chain reaction (nested PCR), microscopy and Paramax-3 TM rapid detection test (RDT). Malaria was detected in 30 patients by the PCR, with point prevalence of 10.9%. Of these malaria infections, 80% was imported, 26.6% was asymptomatic and 23.3% was sub-microscopic. Malaria was reported throughout the year, with February/March and September/October peaks. Infection was significantly more in males than in females (P = 0.01). Likewise, infections were detected more in febrile than in non-febrile patients (P = 0.01). Adult aged 15-24 years, fever and travel were identified as high-risk factors. Malaria was primarily attributed to Plasmodium falciparum mono-infections, followed by P. vivax mono-infections and lastly to falciparum/vivax mixed infections accounting 76.6%, 16.6%, and 6.6% of PCR-confirmed malaria cases, respectively. The nested PCR was superior to the smear microscopy (sensitivity 76.6%; specificity 100%) and the RDT (sensitivity 83.3%, specificity 94.2%). The overall percent agreement between microscopy and the RDT was 92.7% (kappa= 0.63). High proportion of imported malaria including sub-microscopic and sub-patent cases were described. We suggest that incorporation of molecular tool into the conventional malaria diagnosis is beneficial in Jazan district.
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