REVIEW | doi:10.20944/preprints202302.0122.v1
Subject: Medicine And Pharmacology, Oncology And Oncogenics Keywords: Osteosarcoma; Tumorigenesis; Metastasis; Immune Evasion; Chemoresistance; Mutation
Online: 7 February 2023 (06:12:43 CET)
There has been no significant efficacy in treatment for osteosarcoma (OS) metastasis after nearly four decades of trials. This motivates us to elucidate OS therapies according to their four bidirectional mutation stages. To refresh the OS therapy status quo, the historical developments and clinical advancements are briefly described. However, the main issue of metastasis remains unresolved, accounting for 90% of pulmonary metastasis deaths. Thus, this metastasis problem is related to immune evasion and chemoresistance that are being induced after long-term treatment by the use of immunotherapy for tumorigenesis. Therefore, it is rationale to discuss the relationship cycles of mutation stages including tumorigenesis, metastasis, immune evasion, and chemoresistance. Even though many combinational and targeted therapies have been developed to intensify these mutation treatments, successful clinical translations with higher cure rates are still rare. Through this review, an in-depth understanding of the bidirectional relationship between the four OS mutation stages and their respective therapies is provided. Herein, we summarise the medicines used to treat tumorigenesis, including COLGALT2 inhibitors, Tra2B, and AGAP1, miR-148a and miR-21-5p EVs, and the lncRNA LIFR-AS1. Following the medicines used to treat metastasis are AXL, miR-135a-5p, mRNA BCL6, TGFβ1, Tim-3, SOCS5, CASC15, KLF3-AS1, PDCD4, ATG5, and Rab22a-NeoF1. Then the medicines used to treat immune evasion are N-cadherin, anti-IL-9, USP12 inhibitor, IgG-4+ B-cells, LAP inhibitor, anti-Wnt2 mAb, anti-αvβ8 integrin, HK2-mediated IκBα, IDO inhibitor with NO, and TGF-βRII with anti-IgG1. Finally, the medicines used to treat chemoresistance are DHFR, FPGS, HSP-90AA1, XCT-790, ATKI, and IGF1. As a result, this contribution is expected to serve as a reference and guide for scientists and clinicians.
REVIEW | doi:10.20944/preprints202101.0502.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Superstition; Scientific knowledge; Conflict; Traditional healers
Online: 25 January 2021 (14:11:54 CET)
Superstition is a belief that is not based on scientific knowledge. Traditional healers usually use superstition in their practices to manage human health problems and diseases; such practices create a conflict with the medical profession and its evidence-based practices. Medical professionals confirm that this kind of practice is not safe to human health as it is done by untrained people (e.g., tradition healers) utilizing unsterilized instruments within unhygienic environments. Most of the cases eventually develop a variety of complications, which are sometimes fatal. Female genital mutilation, uvulectomy, oral mutilation (tooth bud extraction to cure “Ibyinyo”), and eyebrow incisions are examples of the many different types of superstitious practices which occur commonly in different parts of the world. We described how these traditional practices of superstition have been and continue to be performed in various parts of the world, their complications on oral and general health, and the ways such practices hinder modern medical practices. This paper aims to increase the awareness of these superstition-driven traditional and potentially harmful practices by promoting the importance of evidence-based medical practices.
REVIEW | doi:10.20944/preprints202201.0241.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: Diabetes Mellitus; Vascular Dementia; Alzheimer’s Disease; Inflammation; Atherosclerosis; Mitochondrial dysfunction; Cognitive dysfunction
Online: 17 January 2022 (15:46:10 CET)
Type 2 Diabetes Mellitus is being increasingly associated with dysfunction of cognition. Dementia, including vascular dementia and Alzheimer’s disease, is being recognized as comorbidities of this metabolic disorder. The progressive hallmarks of this cognitive dysfunction include mild impairment of cognition and cognitive decline. Dementia and mild impairment of cognition appear in older patients primarily. Studies on risk factors, neuropathology, and brain imaging have provided important suggestions for mechanisms that lie behind the development of dementia. It is a significant challenge to understand the disease processes related to diabetes which affect the brain and lead to dementia development. The connection between Diabetes Mellitus and dysfunction of cognition has been observed in many human and animal studies that have noted mechanisms related to Diabetes Mellitus are possibly responsible for aggravating cognitive dysfunction. This article attempts to narrate the possible association between type 2 diabetes and Dementia, reviewing studies that have noted this association in vascular dementia and Alzheimer’s disease and helping to explain the potential mechanisms behind the disease process. The Google search for ‘Diabetes Mellitus and Dementia’ was carried out. Also, the search was done using ‘Diabetes Mellitus,’ ‘Vascular Dementia,’ ‘Alzheimer’s Disease.’ The literature search was done from Google Scholar, Pubmed, Embase, ScienceDirect, and MEDLINE. Keeping in mind the increasing rate of Diabetes Mellitus, it is important to establish the type 2 diabetes effect on the brain and diseases of neurodegeneration. This narrative review aims to build awareness regarding different types of dementia and their relationship with diabetes.
ARTICLE | doi:10.20944/preprints202203.0108.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: intestinal parasitic; contagions; diseases; pediatric patients; Metropolitan City of Bangladesh; cryptosporidiosis
Online: 7 March 2022 (15:51:25 CET)
Background: Gastrointestinal parasitic infections are one of the global health concerns in developing countries like Bangladesh. Among them, Cryptosporidium spp. plays an essential role in causing diarrhea, malnutrition, and poor cognitive function, especially in children. The study was conducted to identify the frequency of cryptosporidium cases and other parasitic agents. Methods: A Cross-sectional observational study was conducted among 219 hospitalized children with diarrhea. The conventional microscopic technique was applied for parasitic detection. A particular staining procedure was performed to identify oocysts of Cryptosporidium spp. And PCR was conducted to determine the SSU rRNA and gp60 gene of Cryptosporidium. Results: Cyst of Giardia, ova of Ascaris lumbricoides (AL), Trichuris trichiura (TT), AL, and TT were identified in 2.3%, 1.4%, 0.5%, and 0.9% samples by wet mount preparation. The distribution of Cryptosporidium spp. was 1.4% and 4.1%, which was detected by the staining method and nested PCR. Factors independently associated with Cryptosporidium infection are unsafe water, lack of regular hand washing, and insufficiency of exclusive breastfeeding. Conclusions: This is the first report to detect the frequency of Cryptosporidium and other intestinal parasites and associated factors in Chattogram city of Bangladesh.
ARTICLE | doi:10.20944/preprints202104.0534.v1
Subject: Biology And Life Sciences, Virology Keywords: COVID-19, SARS-CoV-2, Serological test, Sensitivity, Specificity, Serosurveillance.
Online: 20 April 2021 (11:36:09 CEST)
Background: Flow-through dot-blot assay (FT-DBA) for SARS-CoV-2 specific IgG detection will provide a reliable and affordable immunoassay for the rapid serosurveillance against COVID-19. Method: SARS-CoV-2 antigens were immobilized on nitrocellulose membrane to capture IgG immunoglobulins, which were then detected with AuNP anti-human IgG. A total of 181 samples were characterized with in-house and commercial immunoassay. The positive panel consisted of RT-PCR positive samples from patients with both <14 days and >14 days from the onset of symptoms, while the negative panel contained samples collected either from the pre-pandemic era dengue patients from healthy donors during the pandemic period. Results: In-house ELISA selected a total of 79 true seropositive and 100 seronegative samples. The sensitivity of samples with <14 days using FT-DBA was 94.7% which increased to 100% for samples >14 days. The overall detection sensitivity and specificity were 98.8% and 98%, respectively, whereas the overall PPV and NPV were 97.6% and 99%. Moreover, comparative analysis between ELISA and FT-DBA revealed clinical agreement of Cohen’s Kappa value of 0.944. Conclusion: The assay can confirm past SARS-CoV-2 infection with high accuracy within 2 minutes compared to ELISA. It can help track SARS-CoV-2 disease progression, population screening, and vaccination response.
ARTICLE | doi:10.20944/preprints202203.0235.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Antimicrobial; Prescribing; Drug Resistance; Knowledge; Perception; Medical Students; Malaysia
Online: 16 March 2022 (14:44:53 CET)
Background: Worldwide, microbes are becoming more dangerous by acquiring virulent skills to adapt and develop antimicrobial resistance (AMR). This is a concern as this increases morbidity, mortality, and costs. Consequently, physicians need to be trained inappropriate prescribing, starting with medical students. Objective: Evaluate medical students' confidence in antimicrobial agent prescribing and drug resistance Methods: Cross-sectional study assessing medical students' knowledge, perception, and confidence in prescribing antimicrobial agents and drug resistance in a Malaysian University. A universal sampling method was used. Results: Most respondents believe that educational input regarding overall prescribing was sufficient. Regarding the principle of appropriate and accurate prescriptions, female medical students had less knowledge [Odds Ratio (OR)=0.51; 95% Confidence Interval (CI) 0.25-0.99; p=0.050]. Year-IV and Year-V students had more excellent knowledge than Year-III students regarding confidence in antibiotic prescribing. Year-V students also showed appreciably higher confidence in the broad principles of prescribing, including infectious diseases, compared to those in other years. Conclusion: Overall, medical students, gain more excellent knowledge and confidence regarding prescribing, including antimicrobials, as their academic careers progress.
ARTICLE | doi:10.20944/preprints202201.0225.v2
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Misdiagnosis; Random Amplification of Polymorphic DNA; 16S rRNA Sequencing; Loop-Mediated Isothermal Amplification; Antibiotic Resistance
Online: 19 January 2022 (11:39:41 CET)
Abstract Successful treatment against infectious agents depends on rapid and accurate detection of the causative organisms. Misdiagnosis can hamper such success while leading to improper advising of antibiotics. In Bangladesh, the majority of the diagnostic centers detect and identify pathogens through culture and biochemical test-based methods and suggest antibiotics based solely on the results of disk-diffusion methods. This pilot study tried to validate the identity of the isolates characterized by diagnostic facilities near Dhaka. One hundred and twenty pre-characterized clinical isolates were analyzed biochemically and genotypically. Random Amplification of Polymorphic DNA-PCR, rcsA, and phoA genes-based PCR, and Loop-Mediated Isothermal Amplification (LAMP)-based identification of Klebsiella pneumoniae and Escherichia coli, respectively, followed by 16S rRNA sequencing confirmed misidentification of some clinical pathogens of other genera as Klebsiella spp. and E. coli. According to the antibiotic susceptibility testing guidelines, antibiotic choice, sensitivity pattern, and breakpoint measurement are different for each group of organisms. The lack of adherence to proper standards results in misdiagnosis and may facilitate the development of antibiotic resistance. The pilot study observers misidentification of clinical pathogens identified by the diagnostic centers. Well-characterized rapid molecular techniques like LAMP are suggested in clinical diagnosis to avoid misdiagnosis and subsequently circumvent antibiotic resistance development.
ARTICLE | doi:10.20944/preprints202204.0096.v1
Subject: Public Health And Healthcare, Nursing Keywords: Health; Policy; Knowledge; Perception; Medical Students; Malaysia
Online: 11 April 2022 (11:07:12 CEST)
Background: Health policy is a set of comprehensive principles and legislations that guide how healthcare should be effectively delivered in the community. Medical schools should prepare students to undertake managerial responsibilities by incorporating health policy in the curriculum to deal with the intricacies of healthcare systems and their clinical roles in their future professional careers. Objective: To examine medical students' perception at a Public University in Malaysia regarding teaching health policy and their participation in health policy roles. Material and Methods: A cross-sectional study using universal sampling was carried out among the medical students using a paper-based questionnaire to collect the data. Results: Most respondents opined their willingness to learn health policy (80.9%) and that teaching health policy (83.6%) should be compulsory for medical students. The respondents thought health policy should be introduced earlier in Year 1 or 2. The student scores on their knowledge regarding health policy and year of study were significantly associated with their involvement in the health policy roles in both the simple and multiple logistic regression. Both statistical tests reported higher participation in health policy roles with the higher year of study, though only Year 4 and 5 were significant in the simple logistic regression and only Year 5 in the multiple logistic regression compared to Year 1. On the other hand, age and type of admission show significant results only in the simple logistic regression, while the race was only significant at the multivariate level. Conclusion: This study demonstrated that most respondents showed their willingness to learn health policy, participate in the health policy programs, and recommend that health policy be considered an essential topic in the medical curriculum, which should be taught right from the first year of medical school. We recommend encouraging students’ participation in health policy activities.