HPMC-Zein Film-forming Gel Loaded with 5-Fluorouracil Coupled with CO2 Laser Dermabrasion for Managing Stable Vitiligo.

Vitiligo is a significant dermatological challenge affecting 0.5 to 2% of the global population. Despite the various existing medical approaches, current vitiligo treatments are far from ideal. The present study aimed to prepare and evaluate a film-forming gel of 5 fluorouracil (5FU) using different ratios of hydroxypropyl methylcellulose (HPMC) and Zein for treating vitiligo. The prepared film-forming gels were fully characterized in terms of morphology, Fourier-transform infrared spectroscopy, drug content, pH, drying time, in-vitro drug release, and clinical investigation. A 32-full factorial design was used to study the impact of varying concentrations of HPMC (X1) and Zein (X2) on the percentage of 5FU released (Y1) from the prepared film-forming gels. Scanning electron microscopy (SEM) revealed a cross-linked network structure between polymers. An increase in HPMC concentration (2-4%) correlated with higher 5FU release, whereas increased Zein concentration (1-2%) resulted in reduced 5FU release. Furthermore, patients treated with 5FU film-forming gel after dermabrasion with fractional CO2 (FCO2) laser exhibited a significant decrease in JAK3 gene expression and higher effectiveness than those treated with FCO2 laser alone. Our results suggest that the film-forming gel of 5FU is promising as an effective formulation for treating vitiligo.

Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats.

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV-Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis. The optimal formulation (F2) exhibited the smallest particle size (41.77 ±â€¯6.8 nm), reasonable PDI (0.59 ±â€¯0.17), high %EE (94.43 ±â€¯0.25 %), a moderate zeta potential (-8.44 ±â€¯1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin's antibacterial efficacy, lowering minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

MicroRNA signatures in the pathogenesis and therapy of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a persistent inflammatory illness of the gastrointestinal tract (GIT) triggered by an inappropriate immune response to environmental stimuli in genetically predisposed persons. Unfortunately, IBD patients' quality of life is negatively impacted by the symptoms associated with the disease. The exact etiology of IBD pathogenesis is not fully understood, but the emerging research indicated that the microRNA (miRNA) plays an important role. miRNAs have been documented to possess a significant role in regulating pro- and anti-inflammatory pathways, in addition to their roles in several physiological processes, including cell growth, proliferation, and apoptosis. Variations in the miRNA profiles might be a helpful prognostic indicator and a valuable tool in the differential diagnosis of IBD. Most interestingly, these miRNAs have a promising therapeutic target in several pre-clinical animal studies and phase 2 clinical studies to alleviate inflammation and improve patient's quality of life. This comprehensive review discusses the current knowledge about the significant physiological role of different miRNAs in the health of the intestinal immune system and addresses the role of the most relevant differentially expressed miRNAs in IBD, identify their potential targets, and emphasize their diagnostic and therapeutic potential for future research.

Quorum Sensing Inhibitors: An Alternative Strategy to Win the Battle against Multidrug-Resistant (MDR) Bacteria.

Antibiotic resistance is a major problem and a major global health concern. In total, there are 16 million deaths yearly from infectious diseases, and at least 65% of infectious diseases are caused by microbial communities that proliferate through the formation of biofilms. Antibiotic overuse has resulted in the evolution of multidrug-resistant (MDR) microbial strains. As a result, there is now much more interest in non-antibiotic therapies for bacterial infections. Among these revolutionary, non-traditional medications is quorum sensing inhibitors (QSIs). Bacterial cell-to-cell communication is known as quorum sensing (QS), and it is mediated by tiny diffusible signaling molecules known as autoinducers (AIs). QS is dependent on the density of the bacterial population. QS is used by Gram-negative and Gram-positive bacteria to control a wide range of processes; in both scenarios, QS entails the synthesis, identification, and reaction to signaling chemicals, also known as auto-inducers. Since the usual processes regulated by QS are the expression of virulence factors and the creation of biofilms, QS is being investigated as an alternative solution to antibiotic resistance. Consequently, the use of QS-inhibiting agents, such as QSIs and quorum quenching (QQ) enzymes, to interfere with QS seems like a good strategy to prevent bacterial infections. This review sheds light on QS inhibition strategy and mechanisms and discusses how using this approach can aid in winning the battle against resistant bacteria.

Neutrophils and monocyte toll like receptors 2 and 4 expression in preterm versus term delivery.

Pregnancy results in an increase in immune cells, especially monocytes, which enhances the innate immune system. The increase of inflammatory cytokines in pregnant women's amniotic fluid, can cause uterine contraction, is linked to preterm labor. These inflammatory responses are controlled by Toll-like receptors (TLRs), which are largely expressed on neutrophils and monocytes. This study aimed to determine the role of neutrophils and monocyte subsets, as well as their expression of TLR-2 and TLR-4 in women with preterm and full-term delivery. The study involved a total of 74 women, comprising of 29 preterm labor, 25 full-term labor, and 20 non-pregnant women. The distribution of three monocyte subsets, namely (CD14++CD16-), (CD14+CD16+), and (CD14-/dim CD16++) was measured. Also, the expression of TLR2 and TLR4 in monocytes and neutrophils was analyzed using flow cytometry. Non-classical monocytes and intermediate monocytes were significantly higher in the preterm group than the control and full-term groups (p=0.041, p=0.043, and p=0.004, p= 0.049, respectively). Women in the preterm group showed significantly TLR2 expression on nonclassical monocytes compared to the control and full-term groups (p=0.002, and p=0.010, respectively). Also, preterm group expression of TLR4 was significantly higher in classical monocytes and nonclassical monocytes in comparison to the control group (p=0.019, and p≤0.0001, respectively). Besides, TLR4 expression was significantly up regulated in the preterm group compared to full-term in non-classical monocyte subset (p < 0.0001). Moreover, the expression of TLR-4 in neutrophils from the preterm group was statistically higher than expression from the full-term labor and control groups (p < .0001 for both). Such findings highlight the important role of monocyte subsets and neutrophils in activating the innate immune system and initiating strong pro-inflammatory responses that induce preterm labor. Additionally, TLR4 and TLR2 expressions on non-classical monocytes may be used as a marker to assess the probability of preterm labor.

Knowledge, Attitude, and Practice (KAP) Study of Egyptian physicians towards HIV infection: a multicentre study.

INTRODUCTION: In Egypt, there is a paucity of new data regarding awareness of HIV/AIDS among physicians. This study aimed to assess the level of awareness, attitude, practice, and knowledge of a sample of Egyptian physicians regarding HIV regarding natural history, epidemiology, and virology, method of transmission, clinical manifestations, diagnosis, prevention, and management. METHODOLOGY: Sixty-eight Egyptian physicians were enrolled in an observational analytic multicenter cross-sectional KAP study in Egyptian tertiary health care facilities covering different localities, including New Valley University, Assiut University, South Valley University, Helwan University, Alexandria University, Aswan University, and Al-Azhar University. RESULTS: The attitude of physicians towards the privacy of persons living with HIV, was the one with the highest percentage 85.3%. On the other hand, respondents think that only 25% of physicians do not stigmatize HIV patients. Moreover, only 25% of the study group do not stigmatize persons living with HIV. The highest proportion of favorable practice was 39.7% and the lowest was 17.6%. With regard to their knowledge about HIV, the lowest proportion of correct answers to a question was 4.4%, and the highest proportion was 92.6%. Most of the enrolled physicians were found to have a moderate knowledge score, 49/68 (72%). There was a significant difference between different specialties regarding knowledge scores. CONCLUSIONS: There are some knowledge gaps among a sample of Egyptian physicians with regard to HIV/AIDS. In addition, Egyptian physicians may have a moderate degree of undesirable attitude and practice toward HIV/AIDS.

A Mutual Nexus Between Epilepsy and α-Synuclein: A Puzzle Pathway.

Alpha-synuclein (α-Syn) is a specific neuronal protein that regulates neurotransmitter release and trafficking of synaptic vesicles. Exosome-associated α-Syn which is specific to the central nervous system (CNS) is involved in the pathogenesis of epilepsy. Therefore, this review aimed to elucidate the possible link between α-Syn and epilepsy, and how it affects the pathophysiology of epilepsy. A neurodegenerative protein such as α-Syn is implicated in the pathogenesis of epilepsy. Evidence from preclinical and clinical studies revealed that upregulation of α-Syn induces progressive neuronal dysfunctions through induction of oxidative stress, neuroinflammation, and inhibition of autophagy in a vicious cycle with subsequent development of severe epilepsy. In addition, accumulation of α-Syn in epilepsy could be secondary to the different cellular alterations including oxidative stress, neuroinflammation, reduction of brain-derived neurotrophic factor (BDNF) and progranulin (PGN), and failure of the autophagy pathway. However, the mechanism of α-Syn-induced-epileptogenesis is not well elucidated. Therefore, α-Syn could be a secondary consequence of epilepsy. Preclinical and clinical studies are warranted to confirm this causal relationship.

Cholera rages in Africa and the Middle East: A narrative review on challenges and solutions.

Background and Aim: Cholera is a life-threatening infectious disease that is still one of the most common acute watery diarrheal diseases in the world today. Acute diarrhea and severe dehydration brought on by cholera can cause hypovolemic shock, which can be fatal in minutes. Without competent clinical therapy, the rate of case fatality surpasses 50%. The purpose of this review was to highlight cholera challenges in Africa and the Middle East and explain the reasons for why this region is currently a fertile environment for cholera. We investigated cholera serology, epidemiology, and the geographical distribution of cholera in Africa and the Middle East in 2022 and 2023. We reviewed detection methods, such as rapid diagnostic tests (RDTs), and treatments, such as antibiotics and phage therapy. Finally, this review explored oral cholera vaccines (OCVs), and the vaccine shortage crisis. Methods: We carried out a systematic search in multiple databases, including PubMed, Web of Science, Google Scholar, Scopus, MEDLINE, and Embase, for studies on cholera using the following keywords: ((Cholera) OR (Vibrio cholera) and (Coronavirus) OR (COVID-19) OR (SARS-CoV2) OR (The Middle East) OR (Africa)). Results and Conclusions: Cholera outbreaks have increased dramatically, mainly in Africa and many Middle Eastern countries. The COVID-19 pandemic has reduced the attention devoted to cholera and disrupted diagnosis and treatment services, as well as vaccination initiatives. Most of the cholera cases in Africa and the Middle East were reported in Malawi and Syria, respectively, in 2022. RDTs are effective in the early detection of cholera epidemics, especially with limited advanced resources, which is the case in much of Africa. By offering both direct and indirect protection, expanding the use of OCV will significantly reduce the burden of current cholera outbreaks in Africa and the Middle East.

Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review.

Background: Diabetes has evolved into a worldwide public health issue. One of the most serious complications of diabetes is diabetic foot ulcer (DFU), which frequently creates a significant financial strain on patients and lowers their quality of life. Up until now, there has been no curative therapy for DFU, only symptomatic relief or an interruption in the disease's progression. Recent studies have focused attention on mesenchymal stem cells (MSCs), which provide innovative and potential treatment candidates for several illnesses as they can differentiate into various cell types. They are mostly extracted from the placenta, adipose tissue, umbilical cord (UC), and bone marrow (BM). Regardless of their origin, they show comparable features and small deviations. Our goal is to investigate MSCs' therapeutic effects, application obstacles, and patient benefit strategies for DFU therapy. Methodology: A comprehensive search was conducted using specific keywords relating to DFU, MSCs, and connected topics in the databases of Medline, Scopus, Web of Science, and PubMed. The main focus of the selection criteria was on English-language literature that explored the relationship between DFU, MSCs, and related factors. Results and Discussion: Numerous studies are being conducted and have demonstrated that MSCs can induce re-epithelialization and angiogenesis, decrease inflammation, contribute to immunological modulation, and subsequently promote DFU healing, making them a promising approach to treating DFU. This review article provides a general snapshot of DFU (including clinical presentation, risk factors and etiopathogenesis, and conventional treatment) and discusses the clinical progress of MSCs in the management of DFU, taking into consideration the side effects and challenges during the application of MSCs and how to overcome these challenges to achieve maximum benefits. Conclusion: The incorporation of MSCs in the management of DFU highlights their potential as a feasible therapeutic strategy. Establishing a comprehensive understanding of the complex relationship between DFU pathophysiology, MSC therapies, and related obstacles is essential for optimizing therapy outcomes and maximizing patient benefits.

Characterization of antibiotic and disinfectant susceptibility in biofilm-forming Acinetobacter baumannii: A focus on environmental isolates.

The clinical role of Acinetobacter baumannii has been highlighted in numerous infectious syndromes with a high mortality rate, due to the high prevalence of multidrug-resistant (MDR) isolates. The treatment and eradication of this pathogen is hindered by biofilm-formation, providing protection from noxious environmental factors and antimicrobials. The aim of this study was to assess the antibiotic susceptibility, antiseptic susceptibility and biofilm-forming capacity using phenotypic methods in environmental A. baumannii isolates. One hundred and fourteen (n = 114) isolates were collected, originating from various environmental sources and geographical regions. Antimicrobial susceptibility testing was carried out using the disk diffusion method, while antiseptic susceptibility was performed using the agar dilution method. Determination of biofilm-forming capacity was carried out using a microtiter-plate based method. Resistance in environmental A. baumannii isolates were highest for ciprofloxacin (64.03%, n = 73), levofloxacin (62.18%, n = 71) and trimethoprim-sulfamethoxazole (61.40%, n = 70), while lowest for colistin (1.75%, n = 2). Efflux pump overexpression was seen in 48.25% of isolates (n = 55), 49.12% (n = 56) were classified as MDR. 6.14% (n = 7), 9.65% (n = 11), 24.65% (n = 28) and 59.65% (n = 68) of isolates were non-biofilm producers, weak, medium, and strong biofilm producers, respectively. No significant differences were observed between non-MDR vs. MDR isolates regarding their distribution of biofilm-producers (P = 0.655). The MIC ranges for the tested antiseptics were as follows: benzalkonium chloride 16-128 µg mL-1, chlorhexidine digluconate 4-128 µg mL-1, formaldehyde 64-256 µg mL-1 and triclosan 2-16 µg mL-1, respectively. The conscientious use of antiseptics, together with periodic surveillance, is essential to curb the spread of these bacteria, and to maintain current infection prevention capabilities.

Sequencing analysis and efficient biodiesel production by lipase from Pseudomonas aeruginosa.

BACKGROUND: Recently, lipase processing for biodiesel production has shown a global increase as it is considered a potential alternative clean-fuel source. The current study's objective is to investigate of lipolytic activity of lipase produced from different strains of Pseudomonas aeruginosa (P. aeruginosa) in biodiesel production using edible plant oils. The goal is to develop an efficient and cost-effective method for producing inexpensive and environmentally friendly biodiesel. METHODS AND RESULTS: Four P. aeruginosa isolates were obtained from different environmental sources (soil), phenotypically identified, and it was confirmed by the PCR detection of the 16SrRNA gene. The isolated P. aeruginosa strains were screened for lipase production, and the recovered lipase was purified. Besides, the lipase (lip) gene was detected by PCR, and the purified PCR products were sequenced and analyzed. The production of biofuel was conducted using gas chromatography among tested oils. It was found that castor oil was the best one that enhances lipase production in-vitro.

Meat and meat products as potential sources of emerging MDR Bacillus cereus: groEL gene sequencing, toxigenic and antimicrobial resistance.

BACKGROUND: Bacillus cereus is implicated in severe foodborne infection in humans. This study intended to assess the occurrence, groEL gene sequencing, biofilm production, and resistance profiles of emerged multidrug resistant (MDR) B. cereus in meat and meat product samples. Moreover, this work highlights the virulence and toxigenic genes (hblABCD complex, nheABC complex, cytK, ces, and pc-plc) and antimicrobial resistance genes (bla1, tetA, bla2, tetB, and ermA). METHODS: Consequently, 200 samples (sausage, minced meat, luncheon, beef meat, and liver; n = 40 for each) were indiscriminately collected from commercial supermarkets in Port Said Province, Egypt, from March to May 2021. Subsequently, food samples were bacteriologically examined. The obtained isolates were tested for groEL gene sequence analysis, antibiotic susceptibility, biofilm production, and PCR screening of toxigenic and resistance genes. RESULTS: The overall prevalence of B. cereus among the inspected food samples was 21%, where the highest predominance was detected in minced meat (42.5%), followed by beef meat (30%). The phylogenetic analysis of the groEL gene exposed that the examined B. cereus strain disclosed a notable genetic identity with other strains from the USA and China. Moreover, the obtained B. cereus strains revealed ß-hemolytic activity, and 88.1% of the recovered strains tested positive for biofilm production. PCR evidenced that the obtained B. cereus strains usually inherited the nhe complex genes (nheA and nheC: 100%, and nheB: 83.3%), followed by cytK (76.2%), hbl complex (hblC and hblD: 59.5%, hblB: 16.6%, and hblA: 11.9%), ces (54.7%), and pc-plc (30.9%) virulence genes. Likewise, 42.9% of the examined B. cereus strains were MDR to six antimicrobial classes and encoded bla1, bla2, ermA, and tetA genes. CONCLUSION: In summary, this study highlights the presence of MDR B. cereus in meat and meat products, posing a significant public health risk. The contamination by B. cereus is common in minced meat and beef meat. The molecular assay is a reliable fundamental tool for screening emerging MDR B. cereus strains in meat and meat products.

Knowledge, attitude, and practice (KAP) study of Egyptian physicians towards HIV infection: a multicentre study

Introduction: In Egypt, there is a paucity of new data regarding awareness of HIV/AIDS among physicians. This study aimed to assess the level of awareness, attitude, practice, and knowledge of a sample of Egyptian physicians regarding HIV regarding natural history, epidemiology, and virology, method of transmission, clinical manifestations, diagnosis, prevention, and management.Methodology: Sixty-eight Egyptian physicians were enrolled in an observational analytic multicenter cross-sectional KAP study in Egyptian tertiary health care facilities covering different localities, including New Valley University, Assiut University, South Valley University, Helwan University, Alexandria University, Aswan University, and Al-Azhar University.Results: The attitude of physicians towards the privacy of persons living with HIV, was the one with the highest percentage 85.3%. On the other hand, respondents think that only 25% of physicians do not stigmatize HIV patients. Moreover, only 25% of the study group do not stigmatize persons living with HIV. The highest proportion of favorable practice was 39.7% and the lowest was 17.6%. With regard to their knowledge about HIV, the lowest proportion of correct answers to a question was 4.4%, and the highest proportion was 92.6%. Most of the enrolled physicians were found to have a moderate knowledge score, 49/68 (72%). There was a significant difference between different specialties regarding knowledge scores.Conclusions: There are some knowledge gaps among a sample of Egyptian physicians with regard to HIV/AIDS. In addition, Egyptian physicians may have a moderate degree of undesirable attitude and practice toward HIV/AIDS

The secrets of environmental Pseudomonas aeruginosa in slaughterhouses: Antibiogram profile, virulence, and antibiotic resistance genes.

Environmental pollution is a serious problem that can cause sicknesses, fatality, and biological contaminants such as bacteria, which can trigger allergic reactions and infectious illnesses. There is also evidence that environmental pollutants can have an impact on the gut microbiome and contribute to the development of various mental health and metabolic disorders. This study aimed to study the antibiotic resistance and virulence potential of environmental Pseudomonas aeruginosa (P. aeruginosa) isolates in slaughterhouses. A total of 100 samples were collected from different slaughterhouse tools. The samples were identified by cultural and biochemical tests and confirmed by the VITEK 2 system. P. aeruginosa isolates were further confirmed by CHROMagar™ Pseudomonas and genetically by rpsL gene analysis. Molecular screening of virulence genes (fimH, papC, lasB, rhlI, lasI, csgA, toxA, and hly) and antibiotic resistance genes (blaCTX-M, blaAmpC, blaSHV, blaNDM, IMP-1, aac(6')-Ib-, ant(4')IIb, mexY, TEM, tetA, and qnrB) by PCR and testing the antibiotic sensitivity, biofilm formation, and production of pigments, and hemolysin were carried out in all isolated strains. A total of 62 isolates were identified as P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant and most of them have multiple resistant genes. blaCTX-M gene was detected in all strains; 23 (37.1%) strains have the ability for biofilm formation, 33 strains had virulence genes, and 26 isolates from them have more than one virulence genes. There should be probably 60 (96.8%) P. aeruginosa strains that produce pyocyanin pigment. Slaughterhouse tools are sources for multidrug-resistant and virulent pathogenic microorganisms which are a serious health problem. Low-hygienic slaughterhouses could be a reservoir for resistance and virulence genes which could then be transferred to other pathogens.

Resistance profiles, virulence and antimicrobial resistance genes of XDR S. Enteritidis and S. Typhimurium.

Avian salmonellosis is concomitant with high financial crises in the poultry industry as well as food-borne illness in man. The present study is designed to investigate the emergence of Salmonella Enteritidis and Salmonella Typhimurium in diseased broilers, resistance profiles, and monitoring virulence and antibiotic resistance genes. Consequently, 450 samples (cloacal swabs, liver, and spleen) were collected from 150 diseased birds from different farms in Giza Governorate, Egypt. Subsequently, the bacteriological examination was done. Afterward, the obtained Salmonella isolates were tested for serogrouping, antibiogram, PCR monitoring of virulence (invA, stn, hilA, and pefA), and antimicrobial resistance genes (blaTEM, blaCTX-M, blaNDM, ermA, sul1, tetA, and aadA1). The total prevalence of Salmonella in the examined diseased broilers was 9.3%, and the highest prevalence was noticed in cloacal swabs. Among the recovered Salmonella isolates (n = 35), 20 serovars were recognized as S. Enteritidis and 15 serovars were identified as S. Typhimurium. Almost 60% of the retrieved S. Enteritidis serovars were extensively drug-resistant (XDR) to seven antimicrobial classes and inherited sul1, blaTEM, tetA, blaCTX-M, ereA, and aadA1 genes. Likewise, 25% of the recovered S. Enteritidis serovars were multidrug-resistant (MDR) to six classes and have sul1, blaTEM, tetA, blaCTX-M, and ereA resistance genes. Also, 66.7% of the retrieved S. Typhimurium serovars were XDR to seven classes and have sul1, blaTEM, tetA, blaCTX-M, ereA, and aadA1 genes. Succinctly, this report underlined the reemergence of XDR S. Typhimurium and S. Enteritidis in broiler chickens. Meropenem and norfloxacin exposed a hopeful antimicrobial activity toward the re-emerging XDR S. Typhimurium and S. Enteritidis in broilers. Moreover, the recurrence of these XDR Salmonella strains poses a potential public health threat.

Phage Therapy, a Salvage Treatment for Multidrug-Resistant Bacteria Causing Infective Endocarditis.

Infective endocarditis (IE) is defined as an infection of the endocardium, or inner surface of the heart, most frequently affecting the heart valves or implanted cardiac devices. Despite its rarity, it has a high rate of morbidity and mortality. IE generally occurs when bacteria, fungi, or other germs from another part of the body, such as the mouth, spread through the bloodstream and attach to damaged areas in the heart. The epidemiology of IE has changed as a consequence of aging and the usage of implantable cardiac devices and heart valves. The right therapeutic routes must be assessed to lower complication and fatality rates, so this requires early clinical suspicion and a fast diagnosis. It is urgently necessary to create new and efficient medicines to combat multidrug-resistant bacterial (MDR) infections because of the increasing threat of antibiotic resistance on a worldwide scale. MDR bacteria that cause IE can be treated using phages rather than antibiotics to combat MDR bacterial strains. This review will illustrate how phage therapy began and how it is considered a powerful potential candidate for the treatment of MDR bacteria that cause IE. Furthermore, it gives a brief about all reported clinical trials that demonstrated the promising effect of phage therapy in combating resistant bacterial strains that cause IE and how it will become a hope in future medicine.

Global genomic epidemiology of chromosomally mediated non-enzymatic carbapenem resistance in Acinetobacter baumannii: on the way to predict and modify resistance.

Introduction: Although carbapenemases are frequently reported in resistant A. baumannii clinical isolates, other chromosomally mediated elements of resistance that are considered essential are frequently underestimated. Having a wide substrate range, multidrug efflux pumps frequently underlie antibiotic treatment failure. Recognizing and exploiting variations in multidrug efflux pumps and penicillin-binding proteins (PBPs) is an essential approach in new antibiotic drug discovery and engineering to meet the growing challenge of multidrug-resistant Gram-negative bacteria. Methods: A total of 980 whole genome sequences of A. baumannii were analyzed. Nucleotide sequences for the genes studied were queried against a custom database of FASTA sequences using the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) system. The correlation between different variants and carbapenem Minimum Inhibitory Concentrations (MICs) was studied. PROVEAN and I-Mutant predictor suites were used to predict the effect of the studied amino acid substitutions on protein function and protein stability. Both PsiPred and FUpred were used for domain and secondary structure prediction. Phylogenetic reconstruction was performed using SANS serif and then visualized using iTOL and Phandango. Results: Exhibiting the highest detection rate, AdeB codes for an important efflux-pump structural protein. T48V, T584I, and P660Q were important variants identified in the AdeB-predicted multidrug efflux transporter pore domains. These can act as probable targets for designing new efflux-pump inhibitors. Each of AdeC Q239L and AdeS D167N can also act as probable targets for restoring carbapenem susceptibility. Membrane proteins appear to have lower predictive potential than efflux pump-related changes. OprB and OprD changes show a greater effect than OmpA, OmpW, Omp33, and CarO changes on carbapenem susceptibility. Functional and statistical evidence make the variants T636A and S382N at PBP1a good markers for imipenem susceptibility and potential important drug targets that can modify imipenem resistance. In addition, PBP3_370, PBP1a_T636A, and PBP1a_S382N may act as potential drug targets that can be exploited to counteract imipenem resistance. Conclusion: The study presents a comprehensive epidemiologic and statistical analysis of potential membrane proteins and efflux-pump variants related to carbapenem susceptibility in A. baumannii, shedding light on their clinical utility as diagnostic markers and treatment modification targets for more focused studies of candidate elements.

Gallibacterium anatis infection in poultry: a comprehensive review.

Gallibacterium anatis (G. anatis), a member of the Pasteurellaceae family, normally inhabits the upper respiratory and lower genital tracts of poultry. However, under certain circumstances of immunosuppression, co-infection (especially with Escherichia coli or Mycoplasma), or various stressors, G. anatis caused respiratory, reproductive, and systemic diseases. Infection with G. anatis has emerged in different countries worldwide. The bacterium affects mainly chickens; however, other species of domestic and wild birds may get infected. Horizontal, vertical, and venereal routes of G. anatis infection have been reported. The pathogenicity of G. anatis is principally related to the presence of some essential virulence factors such as Gallibacterium toxin A, fimbriae, haemagglutinin, outer membrane vesicles, capsule, biofilms, and protease. The clinical picture of G. anatis infection is mainly represented as tracheitis, oophoritis, salpingitis, and peritonitis, while other lesions may be noted in cases of concomitant infection. Control of such infection depends mainly on applying biosecurity measures and vaccination. The antimicrobial sensitivity test is necessary for the correct treatment of G. anatis. However, the development of multiple drug resistance is common. This review article sheds light on G. anatis regarding history, susceptibility, dissemination, virulence factors, pathogenesis, clinical picture, diagnosis, and control measures.

Pangenome analysis of Corynebacterium striatum: insights into a neglected multidrug-resistant pathogen.

BACKGROUND: Over the past two decades, Corynebacterium striatum has been increasingly isolated from clinical cultures with most isolates showing increased antimicrobial resistance (AMR) to last resort agents. Advances in the field of pan genomics would facilitate the understanding of the clinical significance of such bacterial species previously thought to be among commensals paving the way for identifying new drug targets and control strategies. METHODS: We constructed a pan-genome using 310 genome sequences of C. striatum. Pan-genome analysis was performed using three tools including Roary, PIRATE, and PEPPAN. AMR genes and virulence factors have been studied in relation to core genome phylogeny. Genomic Islands (GIs), Integrons, and Prophage regions have been explored in detail. RESULTS: The pan-genome ranges between a total of 5253-5857 genes with 2070 - 1899 core gene clusters. Some antimicrobial resistance genes have been identified in the core genome portion, but most of them were located in the dispensable genome. In addition, some well-known virulence factors described in pathogenic Corynebacterium species were located in the dispensable genome. A total of 115 phage species have been identified with only 44 intact prophage regions. CONCLUSION: This study presents a detailed comparative pangenome report of C. striatum. The species show a very slowly growing pangenome with relatively high number of genes in the core genome contributing to lower genomic variation. Prophage elements carrying AMR and virulence elements appear to be infrequent in the species. GIs appear to offer a prominent role in mobilizing antibiotic resistance genes in the species and integrons occur at a frequency of 50% in the species. Control strategies should be directed against virulence and resistance determinants carried on the core genome and those frequently occurring in the accessory genome.

COVID-19 associated Mucormycosis among ICU patients: risk factors, control, and challenges.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is still difficult to be controlled. The spread of this virus and the emergence of new variants are considered a great challenge worldwide. Disturbance in infection control guidelines implementation, use of steroids, antibiotics, hospital crowdedness, and repeated use of oxygen masks during the management of critically ill COVID-19 patients lead to an increase in the rate of opportunistic infections. So, patients need to fight both the virus with its different variants and opportunistic pathogens including bacteria and fungi especially patients with diabetes mellitus, malignancy, or those who undergo hemodialysis and receive deferoxamine. During the pandemic, many cases of Mucormycosis associated with COVID-19 infection were observed in many countries. In this review, we discuss risk factors that increase the chance of infection by opportunistic pathogens, especially fungal pathogens, recent challenges, and control measures.