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1.
Iranian Journal of Basic Medical Sciences ; 25(9):1110-1116, 2022.
Article in English | Academic Search Complete | ID: covidwho-2040585

ABSTRACT

Objective(s): The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), giving rise to the coronavirus disease 2019 (COVID-19), has become a danger to wellbeing worldwide. Thus, finding efficient and safe vaccines for COVID-19 is of great importance. As a basic step amid contamination, SARS-CoV-2 employs the receptor-binding domain (RBD) of the spike protein to lock in with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells. SARS-CoV-2 receptor-binding domain (RBD) is the main human antibody target for developing vaccines and virus inhibitors, as well as neutralizing antibodies. A bacterial procedure was developed for the expression and purification of the SARS-CoV-2 spike protein receptor-binding domain. Materials and Methods: In this research study, RBD was expressed by Escherichia coli and purified with Ni-NTA chromatography. Then it was affirmed by the western blot test. The immunogenicity and protective efficacy of RBD recombinant protein were assessed on BALB/c mice. Additionally, RBD recombinant protein was tested by ELISA utilizing sera of COVID-19 healing patients contaminated with SARS-CoV-2 wild type and Delta variation. Results: Indirect ELISA was able to detect the protein RBD in serum of the immunized mouse expressed in E. coli. The inactive SARS-CoV2 was detected by antibodies within the serum of immunized mice. Serum antibodies from individuals recovered from Covid19 reacted to the expressed protein. Conclusion: Our findings showed that RBD is of great importance in vaccine design and it can be used to develop recombinant vaccines through induction of antibodies against RBD. [ FROM AUTHOR] Copyright of Iranian Journal of Basic Medical Sciences is the property of Mashhad University of Medical Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
Photochem Photobiol ; 2022.
Article in English | PubMed | ID: covidwho-2038178

ABSTRACT

Germicidal ultraviolet (UV) devices have been widely used for pathogen disinfection in water, air, and on food and surfaces. Emerging UV technologies, like the krypton chloride (KrCl*) excimer emitting at 222 nm, are rapidly gaining popularity due to their minimal adverse health effects compared to conventional UV lamps emitting at 254 nm, opening opportunities for UV disinfection in occupied public spaces. In this study, inactivation of seven bacteria and five viruses, including waterborne, foodborne, and respiratory pathogens, was determined in a thin-film aqueous solution using a filtered KrCl* excimer emitting primarily at 222 nm. Our results show that the KrCl* excimer can effectively inactivate all tested bacteria and viruses, with most microorganisms achieving more than 4-log (99.99%) reduction with a UV dose of 10 mJ/cm(2) . Compared to conventional UV lamps, KrCl* excimer exhibited better disinfection performance for viruses but was less effective for bacteria. The relationships between UV sensitivities at 222 nm and 254 nm for bacteria and viruses were evaluated using regression analysis, resulting in factors that could be used to estimate the KrCl* excimer disinfection performance from well-documented UV kinetics using conventional 254 nm UV lamps. This study provides fundamental information for pathogen disinfection when employing KrCl* excimers.

3.
Medical News of North Caucasus ; 17(2):202-204, 2022.
Article in English | EMBASE | ID: covidwho-2033430

ABSTRACT

The study determined the etiological structure and sensitivity to antibacterial agents of pathogens of uncomplicated and complicated forms of pneumonia in children treated in a multidisciplinary hospital. According to the study, that timely bacteriological diagnosis in the treatment of pneumonia in childhood with an adequate selection of effective antibacterial agents helps reduce hospitalizations and the development of complicated forms of pneumonia.

4.
HemaSphere ; 6:1985-1987, 2022.
Article in English | EMBASE | ID: covidwho-2032163

ABSTRACT

Background: Ibrutinib (IBR) is an oral covalent Bruton tyrosine kinase inhibitor (BTKi), licensed for treatment of relapsed or refractory mantle cell lymphoma (MCL). Under NHS interim Covid-19 agreements in England, IBR with or without rituximab (R) was approved for the frontline treatment for MCL patients (pts) as a safer alternative to conventional immunochemotherapy. Although recent phase 2 studies have reported high response rates in low-risk patients for this combination in the frontline setting, randomised phase 3 and real-world data are currently lacking. Aims: To describe the real-world response rates (overall response rate (ORR), complete response (CR) rate) and toxicity profile of IBR +/-R in adult patients with previously untreated MCL. Methods: Following institutional approval, adults commencing IBR +/-R for untreated MCL under interim Covid-19 arrangements were prospectively identified by contributing centres. Hospital records were interrogated for demographic, pathology, response, toxicity and survival data. ORR/CR were assessed per local investigator according to the Lugano criteria using CT and/or PET-CT. Results: Data were available for 66 pts (72.7% male, median age 71 years, range 41-89). Baseline demographic and clinical features are summarised in Table 1. 23/66 pts (34.8%) had high-risk disease (defined as presence of TP53 mutation/deletion, blastoid or pleomorphic variant MCL, or Ki67%/MiB-1 ≥30%). IBR starting dose was 560mg in 56/62 pts (90%) and was given with R in 22/64 pts (34%). At a median follow up of 8.7 months (m) (range 0-18.6), pts had received a median of 7 cycles of IBR. 19/60 pts (32%) required a dose reduction or delay in IBR treatment. New atrial fibrillation and grade ≥3 any-cause toxicity occurred in 3/59 pts (5.8%) and 8/57 (14.0%) respectively. For the whole population and high-risk pts only, ORR was 74.4% and 64.7% respectively (p=0.2379), with a median time to response of 3.8m, coinciding with the first response assessment scan. Seven pts (16.7%), of whom 2 had highrisk disease, attained CR at a median of 6.0m. ORR for pts receiving vs not receiving R were 84.2% and 66.7% respectively (p=0.1904). IBR was discontinued in 20/61 pts (32.8%) at a median time to discontinuation of 4.1m, due to progressive disease (PD, 19.7%), toxicity (4.9%), death (3.3%;1 pt each of Covid-19 and E. coli infection), pt choice (3.3%) and other unspecified reasons (1.6%). 15/66 pts (22.7%) overall and 7/23 (30.4%) with high-risk disease progressed on IBR at a median time to PD of 4.0m. No pts underwent autologous stem cell transplantation consolidation during the study period. 12/57 pts (21.1%) received second line treatment (R-chemotherapy n=7, Nordic MCL protocol n=2, VR-CAP n=2, pirtobrutinib n=1). Response to second line treatment was CR in 4/11 pts, PD in 7/11. Of the 2 Nordic-treated patients, 1 had CR after cycle 2 and 1 PD. Fourteen pts (21.2%) died during the follow up period, due to MCL (n=11), Covid-19 (n=2) and congestive cardiac failure (n=1). Overall survival was lower for patients with high-risk disease (HR 0.55, p=0.038). Image: Summary/Conclusion: In this real-world UK cohort of pts receiving first-line IBR +/-R for MCL, including older and high-risk pts, we report high ORR rates in a similar range to the phase II Geltamo IMCL-2015 study of combination IBR-R in an exclusively low-risk population. Documented CR rates were lower, possibly reflecting a low usage of rituximab in the Covid-19 pandemic as well as CT assessment of response. Treatment was generally well tolerated, with low rates of toxicityrelated treatment discontinuation. The study is ongoing.

5.
HemaSphere ; 6:3524-3525, 2022.
Article in English | EMBASE | ID: covidwho-2032095

ABSTRACT

Background: Infections contribute to an early mortality risk of 15 percent in newly diagnosed multiple myeloma(NDMM) cases. There is a limited literature on the type of infections in fully vaccinated NDMM patients. Aims: To study epidemiology, clinical profile and predictors of infection in NDMM who are immunised against pneumococci and influenza. Methods: NDMM patients were prospectively studied for 6 months for the pattern of infections . All patients were vaccinated with pneumococcal and Influenza vaccine at diagnosis. PJP prophylaxis and fluconazole prophylaxis was given for patients receiving high dose steroids while acyclovir was given to all. Infections were classified as microbiologically defined, clinically defined and fever of unknown focus according to definitions published by the International Immunocompromised Host Society. Severity of infections were graded according to the NCI CTCAE Ver5. Results: Forty-eight NDMM patients with a median age 55 years comprising of 26 males and 22 females were enrolled. Renal involvement was noted in 42% of enrolled patients and two third of them required renal replacement therapy. ISSIII and R-ISS III were 70.8 % and 62.5 % respectively. 85% had poor performance status(ECOG ≥2) at baseline. RVD was the most common regimen (37%)used. 6 patients received daratumumab based regimen. Treatment response of atleast VGPR was seen in 97 % of NDMM patients. A total of 19 episodes of infections were observed during 6 months. All episodes of infections were reported in the first 45 of myeloma diagnosis(Median 6 days;Range 0-45). Ten of these episodes of infection were diagnosed during the initial evaluation for myeloma defining events. Microbiological diagnosis was possible in 63 %. Commonest infectious agent was COVID 19(n=8) followed by Gram negative bacteria (n=5) viz E.coli and Klebsiella pneumoniae . None of the eight patients who developed COVID 19 infection had received COVID vaccine as they antedated the operationalisation of national guidelines for immunisation. Respiratory and the urinary tract were the most common focus of infection. All critically ill COVID patients succumbed to progressive respiratory failure and all patients with mild and moderate COVID illness recovered uneventfully. Early mortality in our cohort of forty eight patients was twenty percent(n=10). Three fourths of infections in our cohort were Grade≥3 severity. A total of seven deaths were attributable to infectious diseases in this cohort of NDMM patients. Imune paresis was seen in eighty four percent of patients at diagnosis. On follow up at 6 months;immune paresis had persisted in only thirty seven percent. Regression analysis of variables with odds of infection is shown in Table 1 Baseline BMI<18.5 kg/m2;albumin<3g/dl and ISS or R-ISS stage ≥ 2 was found to be have statistically significant odds of predicting infection risk in the cohort of patients. The choice of myeloma regimen, presence of high risk cytogenetics and response to therapy did not correlate with increased odds of infection in our cohort. Summary/Conclusion: Conclusion In this prospective study of NDMM patients vaccinated against pneumococci and influenza at baseline;infection attributable early mortality was 14.5 %. Advanced stage of presentation, hypoalbuminemia and baseline BMI < 18.5 kg/m2 correlated with increased odds of infection. COVID vaccination and COVID appropriate behavioural practices may mitigate COVID related outcomes including deaths in myeloma patients.

6.
Annals of Medicine and Surgery ; 81, 2022.
Article in English | EMBASE | ID: covidwho-2031099
7.
Gut Microbes ; 14(1):2117503, 2022.
Article in English | MEDLINE | ID: covidwho-2028942

ABSTRACT

The origins of preexisting SARS-CoV-2 cross-reactive antibodies and their potential impacts on vaccine efficacy have not been fully clarified. In this study, we demonstrated that S2 was the prevailing target of the preexisting S protein cross-reactive antibodies in both healthy human and SPF mice. A dominant antibody epitope was identified on the connector domain of S2 (1147-SFKEELDKYFKNHT-1160, P144), which could be recognized by preexisting antibodies in both human and mouse. Through metagenomic sequencing and fecal bacteria transplant, we demonstrated that the generation of S2 cross-reactive antibodies was associated with commensal gut bacteria. Furthermore, six P144 reactive monoclonal antibodies were isolated from naive SPF mice and were proven to cross-react with commensal gut bacteria collected from both human and mouse. A variety of cross-reactive microbial proteins were identified using LC-MS, of which E. coli derived HSP60 and HSP70 proteins were confirmed to be able to bind to one of the isolated monoclonal antibodies. Mice with high levels of preexisting S2 cross-reactive antibodies mounted higher S protein specific binding antibodies, especially against S2, after being immunized with a SARS-CoV-2 S DNA vaccine. Similarly, we found that levels of preexisting S2 and P144-specific antibodies correlated positively with RBD binding antibody titers after two doses of inactivated SARS-CoV-2 vaccination in human. Collectively, our study revealed an alternative origin of preexisting S2-targeted antibodies and disclosed a previously neglected aspect of the impact of gut microbiota on host anti-SARS-CoV-2 immunity.

8.
Wiener Tierarztliche Monatsschrift ; 109(Artikel 11), 2022.
Article in English | CAB Abstracts | ID: covidwho-2025202

ABSTRACT

We have evaluated the diagnostic performance of immunochromatographic point-of-care tests (POCT) for the detection of rotavirus, coronavirus, Escherichia (E.) coli F5, Cryptosporidium (C.) parvum, Clostridium (Cl.) perfringens and Giardia (G.) intestinalis in fresh and thawed faecal samples from calves aged up to six months with diarrhoea. We performed POCTs to detect rotavirus, coronavirus, E. coli F5, C. parvum, Cl. perfringens and G. intestinalis on fresh samples in a field study and re-evaluated the performance for C. parvum, Cl. perfringens and G. intestinalis using thawed samples. We calculated the performance based on the results of the reference methods, which were RT-qPCR for the detection of rota- and coronavirus and bacteriological culturing and PCR to detect E. coli F5 and Cl. perfringens a and ss2 toxins. C. parvum was detected by phase-contrast microscopy and G. intestinalis by immunofluorescence microscopy. We collected 177 faecal samples from diarrhoeic calves. We found good performance for the POCT targeting rotavirus (sensitivity (SE)=92.9%;specificity (SP)=95.6%) and C. parvum (SE=63.3%;SP=96.2%). For E. coli F5, the number of true positive samples (n=1) was too low to evaluate the performance. The POCT to detect coronavirus gave a poor performance (SE=3.3%;SP=96.6%) and the POCT to detect Cl. perfringens a moderate performance (SE=52.8%;SP=78.2%). G. intestinalis POCT showed a higher sensitivity to immunofluorescence microscopy in thawed than in fresh faecal samples (SE=43.9% versus SE=29.2%). There are substantial differences in diagnostic performance between the commercially available immunochromatographic POCTs. Still, POCT can make a valuable contribution to the diagnosis and prevention of calf diarrhoea.

9.
Wiener Tierarztliche Monatsschrift ; 109(Artikel 9), 2022.
Article in German | CAB Abstracts | ID: covidwho-2025201

ABSTRACT

Introduction: Neonatal calf diarrhoea is a multifactorial disease that sometimes leads to high economic losses. It can be fatal due to dehydration and acidosis and has been one of the main causes of calf mortality. Material and methods: This retrospective study considered calves of a maximum of 35 days of age and with a diagnosed infection with rotavirus and/or bovine coronavirus. We examined the clinical records of 156 calves that were referred to the University Clinic for Ruminants in Vienna. Results Calves that had been treated with antibiotics before admission to the Clinic had a higher risk of staying longer, suggesting either that these calves had a more serious illness or that antibiotic treatment was not indicated and so therapeutic success was not achieved. Twenty-three calves died or were euthanized at the Clinic. At the time of admission, they were younger than the surviving calves and they had a lower inner body temperature and a lower base excess at the first examination. The four most common pathogens in faecal samples were rotavirus, bovine coronavirus, Cryptosporidium parvum and Escherichia coli, which were detected in 67.1%, 53.9%, 48.1% and 94.1% of the faecal samples examined. The most common co-infection was rotavirus with Cryptosporidium parvum (17 faecal samples). We inspected the four most common pathogens in more detail. There were significant correlations between bovine coronavirus and season, with the risk of suffering from bovine coronavirus 1.6 times higher in winter than in other seasons. There was also a correlation between Cryptosporidium parvum and general behaviour: the risk of being infected with Cryptosporidium parvum was 2.6 times higher in calves that were moderately to severely depressed at the first examination. There was a correlation between co-infections and mortality, with calves with a co-infection at three times higher risk of dying than calves with a mono-infection.

10.
Methods Protoc ; 5(4)2022 Jul 22.
Article in English | MEDLINE | ID: covidwho-2023950

ABSTRACT

With the plethora of commercially available UV-C devices exhibiting different intensity and lifespans, it is critical to consumer safety that companies verify and clearly communicate the efficacy of their devices as per the intended use. The purpose of this study was to define a low-cost protocol for investigating the antimicrobial efficacy of commercial UV devices for industry use. The tested devices included: a wall-mounted unit (Device A), a troffer unit (Device B), and an induction lamp unit (Device C). The devices were installed within an enclosed tower to prevent the transmission of UV-C radiation outside of the testing area. The procedure details determining the devices' antimicrobial efficacy using plastic coupons inoculated with Escherichia coli or Staphylococcus aureus. The protocol includes suggested time-distance treatments according to the potential application of each device type and reports the results as log CFU/mL reduction or percent reduction.

11.
International Journal of Molecular Sciences ; 23(17):9884, 2022.
Article in English | ProQuest Central | ID: covidwho-2023750

ABSTRACT

The rapid and decentralized detection of bacteria from biomedical, environmental, and food samples has the capacity to improve the conventional protocols and to change a predictable outcome. Identifying new markers and analysis methods represents an attractive strategy for the indirect but simpler and safer detection of pathogens that could replace existing methods. Enterobactin (Ent), a siderophore produced by Escherichia coli or other Gram-negative bacteria, was studied on different electrode materials to reveal its electrochemical fingerprint—very useful information towards the detection of the bacteria based on this analyte. The molecule was successfully identified in culture media samples and a future goal is the development of a rapid antibiogram. The presence of Ent was also assessed in wastewater and treated water samples collected from the municipal sewage treatment plant, groundwater, and tap water. Moreover, a custom configuration printed on a medical glove was employed to detect the target in the presence of another bacterial marker, namely pyocyanin (PyoC), that being a metabolite specific of another pathogen bacterium, namely Pseudomonas aeruginosa. Such new mobile and wearable platforms offer considerable promise for rapid low-cost on-site screening of bacterial contamination.

12.
International Journal of Molecular Sciences ; 23(16):9175-N.PAG, 2022.
Article in English | Academic Search Complete | ID: covidwho-2023737

ABSTRACT

Antimicrobial resistance is a public health burden with worldwide impacts and was recently identified as one of the major causes of death in 2019. Fosfomycin is an antibiotic commonly used to treat urinary tract infections, and resistance to it in Enterobacteriaceae is mainly due to the metalloenzyme FosA3 encoded by the fosA3 gene. In this work, we adapted a CRISPR-Cas9 system named pRE-FOSA3 to restore the sensitivity of a fosA3+  Escherichia coli strain. The fosA3+  E. coli strain was generated by transforming synthetic fosA3 into a nonpathogenic E. coli TOP10. To mediate the fosA3 disruption, two guide RNAs (gRNAs) were selected that used conserved regions within the fosA3 sequence of more than 700 fosA3+  E. coli isolates, and the resensitization plasmid pRE-FOSA3 was assembled by cloning the gRNA into pCas9. gRNA_195 exhibited 100% efficiency in resensitizing the bacteria to fosfomycin. Additionally, the edited strain lost the ampicillin resistance encoded in the same plasmid containing the synthetic fosA3 gene, despite not being the CRISPR-Cas9 target, indicating plasmid clearance. The in vitro analysis presented here points to a path that can be explored to assist the development of effective alternative methods of treatment against fosA3+ bacteria. [ FROM AUTHOR] Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

13.
Chemosensors ; 10(8):299, 2022.
Article in English | ProQuest Central | ID: covidwho-2023203

ABSTRACT

The rapid and selective detection of bacterial contaminations and bacterial infections in a non-laboratory setting using advanced sensing materials holds the promise to enable robust point-of-care tests and rapid diagnostics for applications in the medical field as well as food safety. Among the various possible analytes, bacterial enzymes have been targeted successfully in various sensing formats. In this current work, we focus on the systematic investigation of the role of surface area on the sensitivity in micro- and nanostructured autonomously reporting sensing hydrogel materials for the detection of bacterial enzymes. The colorimetric sensing materials for the detection of β-glucuronidase (ß-GUS) from Escherichia coli (E. coli) were fabricated by template replication of crosslinked pullulan acetoacetate (PUAA) and by electrospinning chitosan/polyethylene oxide nanofibers (CS/PEO NFs), both equipped with the chromogenic substrate 5-bromo-4-chloro-3-indolyl-β-D-glucuronide. The investigation of the dependence of the initial reaction rates on surface area unveiled a linear relationship of rate and thereby time to observe a signal for a given concentration of bacterial enzyme. This knowledge was exploited in nanoscale sensing materials made of CS/PEO NFs with diameters of 295 ± 100 nm. Compared to bulk hydrogel slabs, the rate of hydrolysis was significantly enhanced in NFs when exposed to bacteria suspension cultures and thus ensuring a rapid detection of living E. coli that produces the enzyme β-GUS. The findings afford generalized design principles for the improvement of known and novel sensing materials towards rapid detection of bacteria by nanostructuring in medical and food related settings.

14.
Journal of Basic and Clinical Pharmacy ; 11(3):1-1, 2020.
Article in English | CAB Abstracts | ID: covidwho-2012258

ABSTRACT

This study provides a simple, widely available deterrence medication to minimize COVID-19 infection using by tea and coffee infusions. By mixing white with an equal amount of water, add a small amount of tea/coffee infusion. Dull brownish albumen-tannin complex, a soft precipitate is formed and sinks to the bottom. The infusion should reach the furthest points in the respiratory tract so that a maximum number of viral particles are trapped. It is necessary to hold the infusion rolling about for a little while, 20 seconds in the mouth before swallowing. Gargling with the infusion is better. Tannins in tea or coffee infusions will form complexes with the 4-5 types of viral surface proteins [spikes], rendering them ineffective. Protein-tannin astringent complexation is a fundamental chemical reaction and is bound to act, unlike specific antimetabolites or enzyme-mediated actions of antibiotics. In fact, tannins react to some extent with the cell lining of the mucous membranes of the mouth and stomach. Tannins also chelate iron [Fe] and other metal ions required for many of the metabolic reactions of micro-organisms [viruses?], depriving them of these nutrients and further retarding their propagation. Two gargles per day, 12 hours apart, are recommended to disable the virus and eventually kill it. The procedure disables free viruses before tissue invasion. Therefore, the earlier the gargle commences, the better. Suspected contacts should preferably have three daily eight-hourly gargles. Astringent activity is an added activity of tea and coffee, demonstrated in this study [using E. coli and Salmonella] to that of immune boosting action generally spoken about.

15.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 1515-1516, 2021.
Article in English | Scopus | ID: covidwho-2012143

ABSTRACT

The result readouts of loop-mediated isothermal amplification (LAMP) still remain challenging because current techniques require bulky equipment and could not give clear visualization. In this study, we developed a paper device to integrate LAMP and a novel strategy for power-free and naked-eye readout of result relied on polydopamine aggregation. The introduced paper device was used to detect DNA extracted from Escherichia coli O157:H7 (E. coli O157:H7), Enterococcus faecium (E. faecium), and SARS-CoV-2 plasmid. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

16.
25th International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2021 ; : 803-804, 2021.
Article in English | Scopus | ID: covidwho-2010849

ABSTRACT

When it comes to preventive medicine and human safety, biosensing of infectious diseases is crucial. This necessity has become more obvious in the current pandemic scenario. In this context, we proposed a sensible, rapid, one-step and cost-effective immunosensing platform to determine analytes associated to infectious diseases such as gastrointestinal diseases, bacterial vaginosis and COVID-19. The biosensing system exhibits different analytical behavior and optimal time of determination for each analyte tested (E. coli, sialidase and COVID-19 antibodies). Thereby, this technology was proven useful with different matrixes (cauliflower, vaginal swab and human serum) to demonstrate its potential in real applications, proving to be highly sensible, efficient, rapid and cost effective. © 2021 MicroTAS 2021 - 25th International Conference on Miniaturized Systems for Chemistry and Life Sciences. All rights reserved.

17.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009868

ABSTRACT

Extracellular vesicles (EVs) are membrane-bound particles released by cells in various (patho)physiological conditions. EVs can transfer effector molecules and elicit potent responses in recipient cells, making them attractive therapeutic agents and drug delivery platforms. In contrast to their tremendous potential, only a few EV-based therapies and drug delivery have been approved for clinical use, which is largely attributed to limited therapeutic loading technologies and efficiency. As EV cargo has major influence on their functionality, understanding and translating the biology underlying the packaging and transferring of biomolecule cargos (e.g. miRNAs, pathogen antigens, small molecule drugs) into EVs is key in harnessing their therapeutic potential. In this review, through recent insights into EVs’ content packaging, we discuss different mechanisms utilized by EVs during cargo packaging, and how one might therapeutically exploit this process. Apart from the well-characterized EVs like exosomes and microvesicles, we also cover the less-studied and other EV subtypes like apoptotic bodies, large oncosomes, bacterial outer membrane vesicles, and migrasomes to highlight therapeutically-diverse opportunities of EV armoury.

18.
Frontiers in Immunology ; 13, 2022.
Article in English | EMBASE | ID: covidwho-2009862

ABSTRACT

Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are still not clear due to the biological complexity of multicellular and multiorgan interactions upon microbial infections. In this review, we show the infection leading to neurodegeneration mediated by multiorgan interconnections and neuroinflammation. Firstly, we highlight three inter-organ communications as possible routes from infection sites to the brain: nose-brain axis, lung-brain axis, and gut-brain axis. Next, we described the biological crosstalk between microglia and astrocytes upon pathogenic infection. Finally, our study indicates how neuroinflammation is a critical player in pathogen-mediated neurodegeneration. Taken together, we envision that antibiotics targeting neuro-pathogens could be a potential therapeutic strategy for neurodegeneration.

19.
Female Pelvic Medicine and Reconstructive Surgery ; 28(6):S33-S34, 2022.
Article in English | EMBASE | ID: covidwho-2008694

ABSTRACT

Introduction: Postmenopausal women with recurrent urinary tract infections (RUTI) are repeatedly exposed to antibiotics and therefore at risk for colonization by multi-drug resistant organisms. Methenamine hippurate (MH) is FDAapproved for the prevention of RUTI;however, the mechanism of action of MH or, more specifically, the role of MH in the alteration of the urobiome is not known. Since preliminary data has shown that MH may be effective against some bacteria (e.g., Escherichia coli), but not others (e.g., Enterococcus faecalis), we hypothesize that resident bladder microbiota will be altered by administration of MH. Objective: Our objective is to determine the longitudinal effect of MH on the urobiome of postmenopausal women with RUTI. Methods: A longitudinal study with a convenient sample of 10 postmenopausal women with a clinical history of RUTI was conducted (Figure 1). UDI6 questionnaires, voided urine, catheterized urine, and peri-urethral swabs were obtained at baseline and three months after daily MH use. Expanded quantitative urine culture (EQUC) was performed on these specimens. In addition, during the 3-month timeframe, four self-collection windows were completed (windows A-D): (A) prior to initiating MH (baseline urobiome), (B) one week after starting MH, (C) two weeks before the 3-month follow-up, and (D) one week before the 3-month follow-up. Voided urine and peri-urethral swabs were collected daily for one week during windows A-D to determine how the urobiome changed. Sequencing of samples from these collection windows is pending. Results: Ten participants enrolled;however, three participants were not able to complete the study due to allergic reaction, improper handling of samples, and COVID infection. Six participants have completed the study;microbiological studies for one participant are still in process. There were no episodes of acute cystitis for any participant during the length of the study. UDI6 results suggested a trend towards a decrease in frequency, leakage with urgency, and abdominal pain;however, none of these were statistically significant (Table 1). Of the six remaining participants, the average baseline urine pH was 5.8 ± 0.8. For the completed participants, an initial microbiological comparison of EQUC results at baseline and 3-month visits show differences in sample diversity. Specifically, the number of species detected (richness) in catheterized urine increased for all but one participant (Figures 2A and 2B) though there was little or no changes in overall diversity (Shannon Index, Figure 2B) or evenness (Pielou's Index, Figure 2C) for any sample type. Exposure to MH did not result in the loss of uropathogenic species present in catheterized urine at baseline;instead, additional uropathogenic and commensal microbiota were detected at the 3-month visit. Conclusions: UDI6 trended towards symptom improvement in frequency, urge incontinence, and pain, consistent with RUTI prevention and symptoms control. Microbiological results suggest that MH increases the richness of the bladder urobiome. This consistent trend suggests MH may reduce RUTI events by altering the urobiome community richness instead of eliminating uropathogenic microbiota from the bladder. Further studies are needed to understand the interaction between MH and a host that is susceptible to uropathogen overgrowth (Table Presented).

20.
Kesmas-National Public Health Journal ; 17(1):44-48, 2022.
Article in English | Web of Science | ID: covidwho-2006650

ABSTRACT

Urinary tract infections (UTIs) are a significant issue in women of all ages, but they are especially common during pregnancy. Co-infection of the Coronavirus Disease 2019 (COVID-19) with UTIs in pregnant females is a hot topic today, as it may be linked to various conditions. Furthermore, understanding the types of bacteria that cause UTIs and related antimicrobial resistance may aid the clinician in selecting the appropriate empirical treatment. This study aimed to isolate and characterize causative agents of UTIs and determine antimicrobial treatment sensitivity patterns among pregnant women diagnosed with the COVID-19 admitted to Teaching Hospital X in Iraq. Antimicrobial drug resistance testing was performed on 42 mid-stream urine samples that had been prepared for culture. Escherichia coli (18/42.85%), Klebsiella pneumoniae (9/21.45%), Streptococcus galactica (7/16.66%), and Proteus mirabilis (4/9.52%) were the bacteria isolated and diagnosed from pregnant women. The infections Pseudomonas aeruginosa and Staphylococcus aureus were the least common (2/4.7). In conclusion, the isolated uro-pathogens showed high resistance to Gentamicin, Cefuroxime, Ceftriaxone and sensitive to Ampicillin and Nitrofurantoin. The common cause of UTIs among pregnant women infected with the COVID-19 was discovered to be Escherichia coli. Before recommending therapy, culture and sensitivity testing of isolates from urine tests should be conducted on a regular basis.

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