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Fulltext Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae

Zowawi HM, Forde BM, Alfaresi M, Alzarouni A, Farahat Y, Chong TM, et al.

Sci Rep, 2015;5:15082.
PMID: 26478520 DOI: 10.1038/srep15082

Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-bla(OXA-181) mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics.
Status of vancomycin-resistant Enterococcus in species of wild birds: A systematic review and meta-analysis

Wada Y, Ibrahim AB, Umar YA, Afolabi HA, Wada M, Alissa M, et al.

J Infect Public Health, 2024 Apr 10;17(6):1023-1036.
PMID: 38657438 DOI: 10.1016/j.jiph.2024.04.004

Wild birds could be a reservoir of medically relevant microorganisms, particularly multidrug-resistant Enterococcus spp. Resistant bacteria's epidemiology and transmission between animals and humans has grown, and their zoonotic potential cannot be ignored. This is the first study to evaluate the status of vancomycin resistant enterococci (VRE) in various wild bird species using meta-analysis and a systematic review. In this study, the pooled prevalence was obtained by analyzing data from published articles on the occurrence of VRE in wild bird species. It's unclear how the antibiotic resistance gene transfer cycle affects wild birds. Google Scholar and PubMed were used to conduct the research. The data and study methodology was assessed and extracted by two reviewers independently, with a third reviewing the results. Heterogeneity between study and publication bias were analyzed using the random effect model. Thirty-eight studies were included in the meta-analysis. 382 out of the 4144 isolates tested, were VRE. The pooled prevalence of VRE among wild birds was estimated at 11.0% (95% CI; 6.9 -17.2%; I2 = 93.204%; P
Experimental drugs in randomized controlled trials for long-COVID: what's in the pipeline? A systematic and critical review

Yong SJ, Halim A, Halim M, Ming LC, Goh KW, Alfaresi M, et al.

Expert Opin Investig Drugs, 2023;32(7):655-667.
PMID: 37534972 DOI: 10.1080/13543784.2023.2242773

INTRODUCTION: Over three years have passed since the emergence of coronavirus disease 2019 (COVID-19), and yet the treatment for long-COVID, a post-COVID-19 syndrome, remains long overdue. Currently, there is no standardized treatment available for long-COVID, primarily due to the lack of funding for post-acute infection syndromes (PAIS). Nevertheless, the past few years have seen a renewed interest in long-COVID research, with billions of dollars allocated for this purpose. As a result, multiple randomized controlled trials (RCTs) have been funded in the quest to find an effective treatment for long-COVID.
AREAS COVERED: This systematic review identified and evaluated the potential of current drug treatments for long-COVID, examining both completed and ongoing RCTs.
EXPERT OPINION: We identified four completed and 22 ongoing RCTs, investigating 22 unique drugs. However, most drugs were deemed to not have high potential for treating long-COVID, according to three pre-specified domains, a testament to the ordeal of treating long-COVID. Given that long-COVID is highly multifaceted with several proposed subtypes, treatments likely need to be tailored accordingly. Currently, rintatolimod appears to have modest to high potential for treating the myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) subtype, LTY-100 and Treamid for pulmonary fibrosis subtype, and metformin for general long-COVID prevention.
Pooled rates and demographics of POTS following SARS-CoV-2 infection versus COVID-19 vaccination: Systematic review and meta-analysis

Yong SJ, Halim A, Liu S, Halim M, Alshehri AA, Alshahrani MA, et al.

Auton Neurosci, 2023 Dec;250:103132.
PMID: 38000119 DOI: 10.1016/j.autneu.2023.103132

PURPOSE: To address recent concerns of postural orthostatic tachycardia syndrome (POTS) occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination.
METHODS: We searched PubMed, Web of Science, and Scopus as of 1st June 2023. We performed a systematic review and meta-analysis of pooled POTS rate in SARS-CoV-2-infected and COVID-19-vaccinated groups from epidemiological studies, followed by subgroup analyses by characteristic. Meta-analysis of risk ratio was conducted to compare POTS rate in infected versus uninfected groups. Meta-analysis of demographics was also performed to compare cases of post-infection and post-vaccination POTS from case reports and series.
RESULTS: We estimated the pooled POTS rate of 107.75 (95 % CI: 9.73 to 273.52) and 3.94 (95 % CI: 0 to 16.39) cases per 10,000 (i.e., 1.08 % and 0.039 %) in infected and vaccinated individuals based on 5 and 2 studies, respectively. Meta-regression revealed age as a significant variable influencing 86.2 % variance of the pooled POTS rate in infected population (P
Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review

Low ZXB, Yong SJ, Alrasheed HA, Al-Subaie MF, Al Kaabi NA, Alfaresi M, et al.

Prog Neuropsychopharmacol Biol Psychiatry, 2025 Mar 20;137:111279.
PMID: 39909170 DOI: 10.1016/j.pnpbp.2025.111279

RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.
OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.
RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.
CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.