Next generation imidazothiazole and imidazooxazole derivatives as potential drugs against brain-eating amoebae.

Managing primary amoebic meningoencephalitis, induced by Naegleria fowleri poses a complex medical challenge. There is currently no specific anti-amoebic drug that has proven effectiveness against N. fowleri infection. Ongoing research endeavours are dedicated to uncovering innovative treatment strategies, including the utilization of drugs and immune modulators targeting Naegleria infection. In this study, we explored the potential of imidazo[2,1-b]thiazole and imidazooxazole derivatives that incorporate sulfonate and sulfamate groups as agents with anti-amoebic properties against N. fowleri. We assessed several synthesized compounds (1f, 1m, 1q, 1s, and 1t) for their efficacy in eliminating amoebae, their impact on cytotoxicity, and their influence on the damage caused to human cerebral microvascular endothelial (HBEC-5i) cells when exposed to the N. fowleri (ATCC 30174) strain. The outcomes revealed that, among the five compounds under examination, 1m, 1q, and 1t demonstrated notable anti-parasitic effects against N. fowleri (P ≤ 0.05). Compound 1t exhibited the highest anti-parasitic activity, reducing N. fowleri population by 80%. Additionally, three compounds, 1m, 1q, and 1t, significantly mitigated the damage inflicted on host cells by N. fowleri. However, the results of cytotoxicity analysis indicated that while 1m and 1q had minimal cytotoxic effects on endothelial cells, compound 1t caused moderate cytotoxicity (34%). Consequently, we conclude that imidazo[2,1-b]thiazole and imidazooxazole derivatives containing sulfonate and sulfamate groups exhibit a marked capacity to eliminate amoebae viability while causing limited toxicity to human cells. In aggregate, these findings hold promise that could potentially evolve into novel therapeutic options for treating N. fowleri infection.

Anti-amoebic activity of a series of benzofuran/benzothiophene derivatives against Acanthamoeba castellanii belonging to the T4 genotype.

AIMS: To determine the anti-amoebic activity of benzofuran/benzothiophene-possessing compounds against Acanthamoeba castellanii of the T4 genotype. METHOD AND RESULTS: A series of benzofuran/benzothiophene-possessing compounds were tested for their anti-amoebic activities, in particular, to block encystation and excystation processes in amoebae. Cytotoxicity of the compounds were evaluated using lactate dehydrogenase (LDH) assays. The amoebicidal assay results revealed significant anti-amoebic effects against A. castellanii. Compounds 1p and 1e showed the highest amoebicidal activity, eliminating 68% and 64% of the amoebae, respectively. These compounds remarkably repressed both the encystation and excystation processes in A. castellanii. Furthermore, the selected compounds presented minimal cytotoxic properties against human cells, as well as considerably abridged amoeba-mediated cytopathogenicity when compared to the amoebae alone. CONCLUSIONS: Our findings show that benzofuran/benzothiophene derivatives depict potent anti-amoebic activities; thus these compounds should be used as promising and novel agents in the rationale development of therapeutic strategies against Acanthamoeba infections.

Detection of HPV16 viral load in L2 gene as a related predictor of cervical cancer among women in Dhi-Qar province by qRT-PCR.

BACKGROUND: The most common infection among young women that increases the risk of developing cervical cancer (CC) is human papillomavirus (HPV). In this study, we are going to assess whether HPV16 DNA concentration helps indicate cervical cancer progression ,As well as for age groups and their relationship to cervical cancer. METHODS: Present study included 93 adult females suffering from cervical cancer during the period from 2017 to 2020. Molecular detection of HPV was done using amplification of the L2 gene (minor capsid protein). RESULTS: Present results showed that 60 (65%) of the patients from 93 cervical cancer cases were infected by HPV16 while only 5 (8%) of healthy patients from the control group were positive for HPV16. So, the current study revealed high HPV16 load in cervical cancer ranged from 1.09 × 102 IU/ml to 5.07 × 103 IU/ml with a mean ± SD of viral load was 1043.25 ± 8.50 IU/ml while in healthy individuals very low viral load ranging from 88 IU/ml to 101 IU/ml and mean ± SD of viral load was 91.25 ± 2.90 IU/ml was reported. CONCLUSION: HPV16 viral load is significantly associated with cervical carcinoma among women in Dhi-Qar Province.

Potential anti-amoebic activity of sulfonate- and sulfamate-containing carboxamide derivatives against pathogenic Acanthamoeba castellanii belonging to the genotype T4.

Acanthamoeba are ubiquitously distributed in the environment and can cause infection of the central nervous system as well a sight-threatening eye infection. Herein, the potential anti-amoebic activity of a series of sulfonate/sulfamate derivatives against pathogenic A. castellanii was evaluated. These compounds were tested using several assays namely amoebicidal, adhesion, excystation, cytotoxic, and cytopathogenicity. Amoebicidal assays revealed that the selected compounds reduced amoebae viability significantly (P < 0.05), and exhibited IC50 values at two-digit micromolar concentrations. Sulfamate derivatives 1j & 1k inhibited 50% of amoebae at 30.65 µM and 27.21 µM, respectively. The tested compounds blocked amoebae binding to host cells as well as inhibited amoebae excystation. Notably, the selected derivatives exhibited minimal human cell cytotoxicity but reduced parasite-mediated host cell damage. Overall, our study showed that sulfamate derivatives 1j & 1k have anti-amoebic potential and offer a promising avenue in the development of potential anti-amoebic drug candidates.

Risk Awareness and Demographic Characteristics Associated With the Use of Sexual Enhancement Supplements Among University Staff: A Cross-Sectional Study in the United Arab Emirates.

Sexual enhancement supplements (SESs) that have illegal additions of pharmaceuticals or analogues pose a significant health risk, particularly with long-term usage. When supplements are adulterated with phosphodiesterase type 5 (PDE-5) inhibitors, dosages can vary widely and there may be an increase in adverse effects and drug-drug interactions which cannot be avoided. Consequently, there is a need to evaluate the public risk awareness toward SES and the associated adverse events as well as explore significant factors associated with knowledge and risk awareness. A cross-sectional community-based study was conducted among University male students and staff at Ajman University, United Arab Emirates (UAE), using a self-administered survey via a web-based electronic link to explore key issues. A total of 1,101 male subjects participated in the study and completed the questionnaire. Four hundred and thirty-three(39.3%) (95% confidence interval [CI]: 33.2-44.5) participants reported using SES products. Of these, 137 (31.6%) [95% CI: 28.6-37.2] experienced adverse effects from SES product use. SES use was more prevalent among participants aged 60 to 69 years (odds ratio [OR]: 2.94; 95% CI: 1.63-5.28), diabetic patients (OR: 2.61; 95% CI: 1.75-3.90), hypertension patients (OR: 2.12; 95% CI: 1.45-3.1), and those overweight or obese (OR: 1.84; 95% CI: 1.44-2.35). This study indicates that SES is a popular practice among the UAE university staff and students. However, there is a need to implement risk awareness programs to raise public awareness regarding SES use and safety. Regulatory bodies are encouraged to provide additional advice on the proper use and possible risks of consuming SES.

Alpha to Omicron (Variants of Concern): Mutation Journey, Vaccines, and Therapy.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initially emerged in December 2019 and has subsequently expanded globally, leading to the ongoing pandemic. The extensive spread of various SARS-CoV-2 variants possesses a serious public health threat. An extensive literature search along with deep analysis was performed to describe and evaluate the characteristics of SARS-CoV-2 variants of concern in relation to the effectiveness of the current vaccines and therapeutics. The obtained results showed that several significant mutations have evolved during the COVID-19 pandemic. The developed variants and their various structural mutations can compromise the effectiveness of several vaccines, escape the neutralizing antibodies, and limit the efficiency of available therapeutics. Furthermore, deep analysis of the available data enables the prediction of the future impact of virus mutations on the ongoing pandemic along with the selection of appropriate vaccines and therapeutics.

Knowledge, Practices, and Risk Perception Associated with Foodborne Illnesses among Females Living in Dubai, United Arab Emirates.

Foodborne illnesses are a widespread and growing public health concern worldwide. The aim of this study was to investigate the knowledge, practices, and risk perception pertaining to food safety among females living in Dubai, United Arab Emirates (UAE). A questionnaire-based cross-sectional study was undertaken consisting of 827 female participants between January to April 2020. The study showed that the overall food safety risk perception was below satisfactory (53.3%). The highest score was seen in the "recognition of foodborne illnesses" aspect (76.7%). The participants were aware of "personal hygiene and cleaning" (61.7%), "cross-contamination prevention" (62.5%), "food purchasing" (60.0%), and "storage of frozen foods" (55.6%). The participants had a low level of knowledge pertaining to "food cooking" (26.0%) and "risk of microbiological infection" (13.3%). There was a statistically significant (p ≤ 0.05) association between knowledge and practices of respondents with employment status, age, and educational levels. In conclusion, the female respondents might act as vehicles for the spread of foodborne illnesses. To reduce this risk, providing food safety awareness programs to this portion of the population is paramount.

Nanovesicles containing curcumin hold promise in the development of new formulations of anti-Acanthamoebic agents.

In this study, curcumin-nanoformulations were tested for anti-Acanthamoebic properties. Curcumin-loaded nanovesicles were synthesized, followed by characterization with Fourier transform infrared spectroscopy, ultraviolet-visible spectrophotometry, and atomic force microscopy. Using amoebicidal assay, the effects of curcumin-nanoformulations were investigated against A. castellanii belonging to the T4 genotype. To determine the effects of curcumin-nanoformulations on host cells, cytotoxicity assays were performed using human keratinocyte cells (HaCat). The results revealed that nanovesicles formulation of curcumin enhanced the anti-Acanthamoebic effects of curcumin as compared with curcumin alone. The viability decreased with increasing concentration of curcumin and/or lipid-based carrier (Noisome) (FCBR18) in a dose-dependent manner. Curcumin and curcumin-loaded nanovesicles exhibited minimal cytotoxic effects against human cells in all tested concentrations. Both concentrations of FCBR18 proved effective in inhibiting amoebae excystation. In contrast, curcumin alone showed insignificant effects against amoebae excystation. Taken together, these findings clearly showed that curcumin-loaded nanovesicles show enhanced anti-Acanthamoebic efficacy without harming human cells, and these nanotherapeutics may hold promise in the development of new formulations of anti-Acanthamoebic agents.

Evaluation of nanoparticles with 5-fluorouracil and chloroquine on Acanthamoeba castellanii activity.

Acanthamoeba is opportunistic pathogens that cause vision-threatening Acanthamoeba keratitis (AK). Previous studies proposed the use of chloroquine (CQ) and 5-fluorouracil (5FU) as anti-Acanthamoeba agents. The objective of this study was to determine the benefit of using 5FU and CQ nanoparticles (NP) formulations against A. castellanii that belonging to the T4 genotype and evaluate their anti-Acanthamoebic characteristic. Triplicate batches of 5FU nanoparticles (5FU-NP) were synthesized by using a modified nanoprecipitation method, while CQ nanoparticles (CQ-NP) synthesized using a modified double emulsion method. The synthesized nanoparticles were subjected to biological assays to investigate their amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects against A. castellanii, as well as cell cytotoxicity. Cytotoxicity assays were performed using human keratinocyte cells (HaCaT) to determine the effect of CQ and 5FU nanoformulations on host cells. 5FU-NP with a concentration of 60 µM showed significant inhibition to amoeba binding into human cell lines and remarkable prevention mainly during the encystation stage. Moreover, 5FU-NP resulted in less cytotoxicity and pathogenicity when compared with the free 5FU. On the other hand, CQ and CQ-NP, at the same concentration, showed poor inhibition to amoeba binding into human cells and insignificant prevention to encystation stage. Moderate human cells damage was resulted following their treatment with CQ and CQ-NP. In conclusion, 5FU may have the potential as an antiamoebic agent against Acanthamoeba spp. preferably as a nanoformulation to enhance its activity and reduce its cytoxicity.

Evaluation of IL-17 and IL-35 in patients with giardiasis in Thi-Qar province, Iraq.

Giardia lamblia, Entamoeba histolytica, Cryptosporidium, and Blastocystis are some parasites primarily responsible for human infections. Giardia lamblia, also known as Giardia intestinalis or Giardia duodenalis, is a common pathogenic protozoan found in the human duodenum and jejunum that causes giardiasis. This study collected stool and blood samples from patients with diarrhea aged less than 1 month to 15 years, from September 2020 to December 2020, in Thi-Qar province. Our study aimed to reveal the diagnosis of Giardia lamblia using direct microscopy examination and detect some immunological parameters such as IL-17 and IL-35 in patients infected with giardiasis.

Imidazothiazole Derivatives Exhibited Potent Effects against Brain-Eating Amoebae.

Naegleria fowleri (N. fowleri) is a free-living, unicellular, opportunistic protist responsible for the fatal central nervous system infection, primary amoebic meningoencephalitis (PAM). Given the increase in temperatures due to global warming and climate change, it is estimated that the cases of PAM are on the rise. However, there is a current lack of awareness and effective drugs, meaning there is an urgent need to develop new therapeutic drugs. In this study, the target compounds were synthesized and tested for their anti-amoebic properties against N. fowleri. Most compounds exhibited significant amoebicidal effects against N. fowleri; for example, 1h, 1j, and 1q reduced N. fowleri's viability to 15.14%, 17.45% and 28.78%, respectively. Furthermore, the majority of the compounds showed reductions in amoeba-mediated host death. Of interest are the compounds 1f, 1k, and 1v, as they were capable of reducing the amoeba-mediated host cell death to 52.3%, 51%, and 56.9% from 100%, respectively. Additionally, these compounds exhibit amoebicidal properties as well; they were found to decrease N. fowleri's viability to 26.41%, 27.39%, and 24.13% from 100%, respectively. Moreover, the MIC50 values for 1e, 1f, and 1h were determined to be 48.45 µM, 60.87 µM, and 50.96 µM, respectively. Additionally, the majority of compounds were found to exhibit limited cytotoxicity, except for 1l, 1o, 1p, 1m, 1c, 1b, 1zb, 1z, 1y, and 1x, which exhibited negligible toxicity. It is anticipated that these compounds may be developed further as effective treatments against these devastating infections due to brain-eating amoebae.

Antiamoebic Activity of Imidazothiazole Derivatives against Opportunistic Pathogen Acanthamoeba castellanii.

We examined the antiamoebic effect of several imidazothiazole derivatives on Acanthamoeba castellanii of the T4 genotype. Trypan blue exclusion assays and haemocytometer counting were used to determine the reduction in A. castellanii trophozoite proliferation, in response to treatment with these compounds. To determine the effects of these compounds on host cells, lactate dehydrogenase assay was performed using HeLa cell lines. Amoebicidal assays revealed that the tested compounds at concentrations of 50 µM significantly inhibited amoebae trophozoites compared to controls. Compounds 1m and 1zb showed the highest amoebicidal effects eradicating 70% and 67% of A. castellanii, respectively. The compounds blocked both the encystation and excystation process in A. castellanii. Compounds 1m and 1zb blocked 61% and 55%, respectively, of amoeba binding to human cells. Moreover, the compounds showed minimal cytotoxic effects against host cells and considerably reduced amoeba-mediated host cell death. Overall, our study revealed that compounds 1m and 1zb have excellent antiamoebic potential, and should be considered in the development of curative antiamoebic medications in future studies. Further work is critical to determine the translational value of these findings.

Socio-demographic correlate of knowledge and practice toward COVID-19 among people living in Mosul-Iraq: A cross-sectional study.

Since the World Health Organization (WHO) announced that the coronavirus disease (COVID-19) is a worldwide pandemic, many countries' authorities, including the Iraqi authorities, started responding and taking action to control the spread of the pandemic. The public's knowledge and practices play an important role in curbing the spreading of the virus by following the health guidelines. This study aimed to assess the socio-demographic correlate of knowledge and practices of Iraqi living in Mosul-Iraq towards COVID-19 during its rapid rise. A cross-sectional online survey of 909 participants was conducted among a sample of the Mosul-Iraq population between 20th June to 1st July 2020. The survey included three parts: 1) socio-demographic characteristics, 2) participants' knowledge, 3) participants' practices. T-test, ANOVA, chi-square, and binary logistic regression were used. A p-value less than 0.05 (p < 0.05) was considered statistically significant. The results showed a knowledge and practice mean score of (12.91±1.67) and (21.56± 2.92) with cumulative knowledge and practice of 86% and 76% respectively towards COVID-19. Socio-demographic characteristics such as age, marital status, gender, level of education and employment were statistically related with a higher mean score of knowledge and practice towards the virus as P<0.05. We concluded that the majority of the respondents demonstrate a high level of knowledge and practices towards COVID-19 except for respondents with socio-demographic characteristics such as those who were younger, male respondents, those with lower education and those unemployed as such campaigns that will increase the knowledge and encourage adequate preventive practice towards COVID-19 should be targeted towards this group.

Side effects and perceptions following Sinopharm COVID-19 vaccination.

OBJECTIVES: Vaccines are one of the best interventions developed for eradicating COVID-19. This study aimed to provide evidence on Sinopharm COVID-19 vaccine side effects. METHODS: A cross-sectional survey study was conducted between January and April 2021 to collect data on the effects of the COVID-19 vaccine among individuals in the United Arab Emirates. Demographic data, vaccination and the response of people unwilling to take the COVID-19 vaccine were reported. RESULTS: Side effects post first vaccine dose of normal injection site pain, fatigue and headache were more common in participants aged ≤49 years versus >49 years, while pain at the vaccination site, fatigue, lethargy, headache and tenderness were the most common side effects post second dose in both groups. All side effects for both doses were more prevalent among participants aged ≤49 years. Side effects were more common in females compared with males for both doses. The most common reason for being unwilling to take the COVID-19 vaccine was that vaccines are not effective. CONCLUSION: Post-vaccination side effects for the first and second doses were mild and predictable, and there were no hospitalization cases; this data will help reduce vaccine hesitancy.

COVID-19 health awareness among the United Arab Emirates population.

In response to the global COVID-19 epidemic, the United Arab Emirates (UAE) government is taking precautionary action to mitigate the spread of the virus. The aim of this study was to evaluate the knowledge and practices toward COVID-19 among the general public in the UAE during the current outbreak. A cross-sectional online survey of 1356 respondents in the UAE was conducted during the epidemic outbreak between 9th to 24th June-2020. The questionnaire consisted of three sections: Socio-demographic, knowledge, practices. Independent-samples t-test, one-way analysis of variance (ANOVA), chi-square and binary logistic regression was used. A p-value of (p < 0.05) was considered statistically significant. The total correct score of knowledge and practice questions was high 85% and 90%, respectively. Male's sex, other marital status, and illiterate/primary educational levels had a lower level of knowledge and practices than others. Participants aged 18-29 had little higher knowledge than other ages but had a lower level in practices, people who live in Abu Dhabi had better knowledge and practices than other emirates, employed people had a lower level of knowledge but higher in practices. Binary logistic regression analysis presented that females, 18-29 years, and married participants significantly associated with a higher score of knowledge, while female, over 30 years old, the martial status of singles, college-level and higher, unemployed, were significantly associated with high mean practices score. This study provided a full screening of the knowledge and practices among a sample of residents in The UAE toward COVID-19, continuing to implement the health education programs pursued by the UAE is highly important to maintain the appropriate level of awareness among the public.

Knowledge, attitude, perception, and preventative practices towards COVID-19 in sub-Saharan Africa: A scoping review.

BACKGROUND: Knowledge, attitudes, perception, and preventative practices regarding coronavirus- 2019 (COVID-19) are crucial in its prevention and control. Several studies have noted that the majority of people in sub-Saharan African are noncompliant with proposed health and safety measures recommended by the World Health Organization (WHO) and respective country health departments. In most sub-Saharan African countries, noncompliance is attributable to ignorance and misinformation, thereby raising questions about people's knowledge, attitudes, perception, and practices towards COVID-19 in these settings. This situation is particularly of concern for governments and public health experts. Thus, this scoping review is aimed at mapping evidence on the knowledge, attitudes, perceptions, and preventive practices (KAP) towards COVID-19 in sub-Saharan Africa (SSA). METHODS: Systematic searches of relevant articles were performed using databases such as the EBSCOhost, PubMed, Science Direct, Google Scholar, the WHO library and grey literature. Arksey and O'Malley's framework guided the study. The risk of bias for included primary studies was assessed using the Mixed Method Appraisal Tool (MMAT). NVIVO version 10 was used to analyse the data and a thematic content analysis was used to present the review's narrative account. RESULTS: A total of 3037 eligible studies were identified after the database search. Only 28 studies met the inclusion criteria after full article screening and were included for data extraction. Studies included populations from the following SSA countries: Ethiopia, Nigeria, Cameroon, Uganda, Rwanda, Ghana, Democratic Republic of Congo, Sudan, and Sierra Leone. All the included studies showed evidence of knowledge related to COVID-19. Eleven studies showed that participants had a positive attitude towards COVID-19, and fifteen studies showed that participants had good practices towards COVID-19. CONCLUSIONS: Most of the participants had adequate knowledge related to COVID-19. Despite adequate knowledge, the attitude was not always positive, thereby necessitating further education to convey the importance of forming a positive attitude and continuous preventive practice towards reducing contraction and transmission of COVID-19.

Mapping Evidence of Impacts of COVID-19 Outbreak on Sexual and Reproductive Health: A Scoping Review.

INTRODUCTION: The emergence of the coronavirus disease 2019 (COVID-19) pandemic has rapidly transformed the pre-existing worldwide sexual and reproductive health environment. The provision and supply of contraceptives, and a wide variety of sexual health, new-born, and maternal health services have been seriously affected. Thus, this scoping review mapped the available evidence on the impacts of the COVID-19 outbreak on sexual and reproductive health. METHODS: Arksey and O'Malley's methodological framework guided this scoping review. A search was conducted from the following databases: Embase, PubMed, CINAHL, Scopus, WOS, and AJOL. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) chart and PRISMA extension for scoping reviews (PRISMA-ScR) checklist were used to document the review process. The McMaster critical review checklist was used to determine the quality of the included studies. Thematic analyses were conducted using NVivo version 12. RESULTS: Three studies showed evidence on the impact of COVID-19 and family planning services, six studies reported on maternal and child services and eleven studies reported on sexual health (sexual behavior). Limited access to family planning use, reduction in multiple sexual partnership, decreased transactional sex, and maternal and child services disruption were some impacts reported in the included studies. CONCLUSION: This study has demonstrated the impacts of COVID-19 on family planning access, multiple sexual partnership, transactional sex, and disruption of maternal and child health services. Interventions that will consider the immediate availability of and access to all sexual and reproductive health services should be prioritized.

Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms.

Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.