Case Presentation: We present a case of a 29-year-old lady who sustained severe burn injuries after a gas explosion at home. She was admitted to the United Arab Emirates (UAE) National Burns Unit and required several episodes of surgical debridement. She developed S. paucimobilis bloodstream infection whilst being treated with Piperacillin-tazobactam. She was subsequently treated with Meropenem for a total of 7 days after removing the source of infection, an infected central line. The S. paucimobilis isolate showed intermediate resistance to Piperacillin-tazobactam.

Conclusion: Numerous case reports indicate high morbidity in patients with life-threatening S. paucimobilis infections, immunocompromised patients, and patients with underlying medical comorbidity; however, this is the first reported case from the UAE.

Case Presentation: A 4-month-old baby girl was admitted to a district hospital because of diarrhea and fever. WBC count, urinalysis, urine cultures, and stool cultures were normal. She was treated with intravenous cefuroxime for 5 days. She was discharged on oral cefprozil for 5 days. After the end of therapy, she was admitted again to the same hospital with fever, diarrhea, vomits, and irritability. Cerebrospinal fluid examination revealed pleocytosis, while S. enterica was isolated. Empirical therapy with ceftriaxone, amikacin, and dexamethasone was started. Because of intracranial hypertension signs, she was transferred to the pediatric intensive care unit of our tertiary hospital. Therapy continued with intravenous ceftriaxone. Brain MRI revealed subarachnoid space dilatation. Increased head circumference and pulsating bregmatic fontanel led to a new cerebral MRI, in which ventricular dilatation and extraparenchymal subdural collection were noted. Ceftriaxone was changed to cefotaxime and ciprofloxacin was added. She remained clinically well; her brain MRI, a week later, showed marked improvement, and the course of intravenous antibiotics for 5 weeks was completed. Her baseline immunodeficiency screening tests were normal and repeat MRI two months post-treatment cessation did not reveal the previous abnormalities.

Conclusion: Invasive Salmonella diseases, such as meningitis, are very uncommon in industrial countries nowadays, and the optimal management is yet not well established. Late onset of complications from Salmonella meningitis warrants more thorough neurodevelopmental follow-ups.

Objective: This article aims to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of GABHS pharyngitis.

Methods: A search was conducted in December 2022 in PubMed Clinical Queries using the key term “group A β-hemolytic streptococcal pharyngitis”. This review covers mainly literature published in the previous ten years.

Results: Children with GABHS pharyngitis typically present with an abrupt onset of fever, intense pain in the throat, pain on swallowing, an inflamed pharynx, enlarged and erythematous tonsils, a red and swollen uvula, enlarged tender anterior cervical lymph nodes. As clinical manifestations may not be specific, even experienced clinicians may have difficulties diagnosing GABHS pharyngitis solely based on epidemiologic or clinical grounds alone. Patients suspected of having GABHS pharyngitis should be confirmed by microbiologic testing (e.g., culture, rapid antigen detection test, molecular point-of-care test) of a throat swab specimen prior to the initiation of antimicrobial therapy. Microbiologic testing is generally unnecessary in patients with pharyngitis whose clinical and epidemiologic findings do not suggest GABHS. Clinical score systems such as the Centor score and McIssac score have been developed to help clinicians decide which patients should undergo diagnostic testing and reduce the unnecessary use of antimicrobials. Antimicrobial therapy should be initiated without delay once the diagnosis is confirmed. Oral penicillin V and amoxicillin remain the drugs of choice. For patients who have a non-anaphylactic allergy to penicillin, oral cephalosporin is an acceptable alternative. For patients with a history of immediate, anaphylactic-type hypersensitivity to penicillin, oral clindamycin, clarithromycin, and azithromycin are acceptable alternatives.

Conclusion: Early diagnosis and antimicrobial treatment are recommended to prevent suppurative complications (e.g., cervical lymphadenitis, peritonsillar abscess) and non-suppurative complications (particularly rheumatic fever) as well as to reduce the severity of symptoms, to shorten the duration of the illness and to reduce disease transmission.

Objective: This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases.

Methods: A comprehensive collection of evidence and insights was obtained from scientific journals and books from physical libraries and electronic platforms like Google Scholar and PubMed. The time frame selected was from year 1992 to July 2023.

Results: The review delves into diosmetin's impact on cellular signaling pathways and its potential in various diseases. Due to its ability to modulate signaling pathways and reduce oxidative stress, it can be suggested as a potential versatile therapeutic agent for mitigating oxidative stressassociated pathogenesis.

Conclusion: The amalgamation of the review underscores diosmetin's promising role as a multifaceted therapeutic agent, highlighting its potential for drug development and clinical applications.

Objectives: The aim of this article is to provide an updated narrative review on the similarities and differences between SARS-CoV-2 and influenza encephalitis.

Methods: A PubMed search was performed with the function “Clinical Queries” using the key terms “SARS-CoV-2” OR “Influenza” AND “Encephalitis”. The search strategy included metaanalyses, clinical trials, randomized controlled trials, reviews and observational studies. The search was restricted to the English literature and pediatric population. This article compares similarities and contrasts between SARS-CoV-2 and influenza-associated encephalitis.

Results: Encephalitis is an uncommon manifestation of both influenza and SARS-CoV-2. Both viruses are associated with fever and respiratory symptoms. However, SARS-CoV-2 patients may only have mild symptoms or be asymptomatic as silent carriers, rendering the disease spread difficult to control. Influenza patients usually have more severe symptomatology and are often bed bound for several days limiting its spread. Influenza is associated with seasonal and annual outbreaks, whereas SARS-CoV-2 has become endemic. Complications of encephalitis are rare in both viral infections but, when present, may carry serious morbidity and mortality. Many long-term sequelae of COVID- 19 infections (long COVID-19) have been described but not with influenza infections. Mortality associated with encephalitis appears higher with influenza than with SARS-CoV-2. Prophylaxis by immunization is available for both influenza and SARS-CoV-2. Specific efficacious antivirals are also available with oseltamivir for influenza and nirmatrelvir/ritonavir for SARS-CoV-2. Steroids are indicated with more severe SARS-CoV-2 but their role is not distinct in influenza disease.

Conclusion: Encephalitis is a rare complication of influenza and SARS-CoV-2 infections. Both carry significant morbidity and mortality. Efficacious vaccines for prophylaxis and antivirals for treatment are available for both viruses.

Methods: In this study, we focused on the expression of recombinant PurA from SEZ ATCC 35246. We evaluated the immunoreactivity of this recombinant protein using convalescent minipig sera. Additionally, we conducted experiments in mice to assess its immunogenic properties.

Results: Our findings revealed that the recombinant PurA triggered a substantial antibody response in mice, resulting in an 80% protection rate against SEZ infection. Notably, mice immunized with PurA exhibited significantly reduced bacterial colonization in all organs compared to the PBS control group. Furthermore, the levels of IL-6, IL-8, IL-1β, and TNF-α in mouse serum were significantly elevated in the PurA-immunized group compared to the control group. Hyperimmune sera targeting PurA effectively eliminated SEZ in bactericidal tests. Remarkably, antibodies against PurA demonstrated a significant inhibitory effect on developing SEZ biofilm.

Conclusion: Immunization with PurA elicited robust humoral and cellular immune responses in mice. These promising results suggest the potential utility of PurA in developing SEZ vaccine immunogens, providing a valuable avenue for further research into SEZ infection prevention and control.

Objective: To understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach.

Methodology: Several scientific database repositories were searched using different keywords: “Phytochemicals,” “Alkaloids,” “Polyphenols,” “Flavonoids,” “Lectins,” “Glycosides,” “Tannins,” “Terpenoids,” “Sterols,” “Immunomodulators,” and “Human Immune System” without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma.

Results: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS.

Conclusion: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259 indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

Poor patient compliance and adherence are major issues with the conventional line of therapy. This burden may be more significant in resource-constrained settings, necessitating the creation of simple formulations that are both geriatric and child-friendly. An extensive literature survey has been conducted in this study using databases of Google Scholar, PubMed, and Research Gate, with a focus on specific research works on oro-dispersible films, tablets, and wafer technology loaded with anti-tuberculosis drugs from 2022 to 2010.

Mouth dissolving formulation technology is a very novel approach in the arena of tuberculosis therapy. This may pave the way for future researchers to develop different mouth dissolving formulations to treat both pulmonary and extra-tuberculosis. This review paper has summarized all the formulation approaches alongside the present state of the art in tuberculosis therapy using mouth dissolving formulations.

Methods: The data were extracted from the official database of hospital NIs records. For each patient, the reported infections were abbreviated as: UTI-SUTI, VAE-PVAP, BSI-LCBI, SSIDIP and so on. For continuous variables, mean ± standard deviation, and for categorical variables, frequency was used.

Results: The study population was 5542 patients, comprised of males (n = 3282) and females (n = 2260). With a minimum of 15 and a maximum of 99, the mean age in 5313 patients was 58.5 ± 19.1 years old. The highest reported NIs (n = 77%) were associated with the ages between 30- 80 years old. Sites of NIs in 93% were as: VAE-PVAP- VAE-IVAC; 31%, UTI-SUTI; 30%, SSI-DIP; 19%, BSI-LCBI; 13%, and other individual infection (7%) with the main pathogens associated with Acinetobacter baumannii, Klebsiella pneumonia, Candida and Staphylococcus spp. Antibiotic susceptibilty testing showed the most sensitivity of isolates against Vancomycin (62%), Gentamicin (59%), Ampicillin (44%), Amikacin (35%) and Co-trimoxazol (32%).

Conclusion: As most NIs are avoidable, for commissioning an efficient surveillance system, further study of pathogens in relation to evidence-based antibiotic-therapy and advanced infection control program is suggested to be valuable.

Methodology: A systematic literature search was conducted on the PubMed database to identify peerreviewed publications pertaining to the epidemiology of Haemophilus influenzae meningitis, both before and after the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines. The search query employed a combination of relevant keywords, including \"invasive,\" \"Haemophilus,\" \"influenzae,\" \"meningitis,\" and specific serotype b (Hib). Additionally, terms related to epidemiology, burden, risk factors, impact, Hib vaccine, Hib conjugate vaccine, combination vaccine, vaccine production, efficacy, immunisation coverage, surveillance, review, clinical aspects, outcomes, and various age groups (adults and children) were incorporated.

Result: The search encompassed articles published till now. Subsequently, relevant research papers concerning Haemophilus influenzae meningitis were subjected to a comprehensive review and analysis.

Conclusion: The Hib conjugate vaccination has shown to be extremely effective when administered to the entire population. However, changes to the immunisation protocol appear to be required in order to effectively manage invasive Hib illness.

Case Presentation: A healthy 18-year-old female presented with intractable hiccups and rapidly progressing paraparesis. MRI demonstrated T2 edema extending from the medulla to the conus, consistent with longitudinally extensive transverse myelitis. Serum and CSF Aquaporin-4 IgG (AQP4) were both positive with high titers. In conjunction with antiviral therapy, immunomodulatory treatment was initiated using pulse methylprednisolone, plasmapheresis and Rituximab. A month and a half after admission, the patient was fully ambulatory with no residual symptoms. On her rheumatology follow-up visit, West Nile Virus-specific IgM in CSF was found to be positive from the patient’s initial presentation.

Conclusion: We propose that West Nile Virus may have been the autoimmune trigger to the patient’s development of NMOSD, highlighting the importance of evaluating viral triggers in autoimmune diseases.

Objective: This study aimed to analyze the electronic parameters, chemical stability, kinetic stability, and binding modes of the compounds.

Methods: Density functional theory (DFT) and molecular electrostatic potential (MESP) calculations were computed using Jaguar with a basis set of 6-31G**++ (B3LYP) in the gas phase. MD simulation was performed for the 100 ns using Desmond available in Maestro to determine the stability and obtain an insight into the molecular mechanism of E. coli ParE docked complexes.

Results: From the DFT calculations, the energy gap ΔE -7.58 and -7.75 eV between the HOMO and LUMO of both the compounds P1 (4-(2-(2-(2-chloroacetamido)phenoxy)acetamido)-3-nitrobenzoic acid) and P2 (4-(2-(benzo[d]thiazol-2-ylthio)acetamido)-3-nitrobenzoic acid) explained the chemical and kinetic stability of the system. MD results demonstrated the minimum fluctuations and conformational stability of the protein structures.

Conclusion: The P1 and P2 compounds were chemically and kinetically stable. Furthermore, MD results demonstrated the stability and inhibitory action of the ligands dependent on hydrophobic, ionic and water bridges than that of hydrogen-bonding interactions.

Objective: This review aims to pay attention to recent development, particularly made in the past two decades and published in this field, and pay particular attention to promising DHFR inhibitors. Hence, an attempt has been made in this article to highlight the structure of dihydrofolate reductase, the mechanism of action of DHFR inhibitors, most recently reported DHFR inhibitors, diverse pharmacological applications of DHFR inhibitors, reported in silico study data and recent patents based on DHFR inhibitors to comprehensively portray the current scenery for researchers interested in designing novel DHFR inhibitors.

Conclusion: A critical review of recent studies revealed that most novel DHFR inhibitor compounds either synthetically or naturally derived are characterized by the presence of heterocyclic moieties in their structure. Non-classical antifolates like trimethoprim, pyrimethamine, and proguanil are considered excellent templates to design novel DHFR inhibitors, and most of them have substituted 2,4-diamino pyrimidine motifs. Targeting DHFR has massive potential to be investigated for newer therapeutic possibilities to treat various diseases of clinical importance.

Material and Methods: COHb level measurement was made using a signal capture CO-pulse oximeter (Masimo's SET Rainbow, Masimo's Co, USA) at the first admission of the patients. Then, COHb levels were confirmed by arterial blood gas(ABG) analysis. The patients were divided into two groups as mild and moderate-severe, according to their Glasgow coma scores (GCS) [Mild (14–15); Moderate (9–13) or Severe (3–8)]. The control group was composed of 16 healthy and non-smoking volunteers.

Results: The serum S100B protein and MMP-9 values at 0 hr of admission in the hospital and 3hr of treatment were not significantly different in the patient group as compared to the control group. Tau protein levels were significantly higher in the patient group at 0 and 3 hours (p> 0.05) as compared to healthy person.

Conclusion: There was no relationship between CO poisoning and MMP-9 and S100B protein levels. NSE and Tau protein were significantly higher in the patient group than the control group. Tau protein may be more useful marker as compared to neuron-specific enolase.

Case Presentation: Here, we report an unusual adenovirus meningoencephalitis with a co-infection of neurocysticercosis in an immunocompetent adult patient. An 18-year-old healthy female student was admitted with fever and headache for 11 days and progressive altered behaviour for 5 days, followed by altered sensorium for 3 days. This variable and unusual presentation of adenoviral infection involving CNS provoked diagnostic difficulties, but with the help of advanced diagnostics, especially molecular, exact aetiology was detected. Even with the neurocysticercosis infection in this patient, the outcome was not adversely affected.

Conclusion: This unusual co-infection with a successful outcome is the first case of this type in literature.

Aim: Determination of molecular patterns, relative synonymous codon usage, codon preference, codon bias, codon pair bias, and rare codons so that genetic manipulation of autophagy genes may be done to curb viral infection.

Methods: Using various software, algorithms, and statistical analysis, insights into codon patterns were obtained. A total of 41 autophagy genes were envisaged as they are involved in virus infection.

Results: The A/T and G/C ending codons are preferred by different genes. AAA-GAA and CAG-CTG codon pairs are the most abundant codon pairs. CGA, TCG, CCG, and GCG are rarely used codons.

Conclusion: The information generated in the present study helps manipulate the gene expression level of virus infection-associated autophagy genes through gene modification tools like CRISPR. Codon deoptimization for reducing while codon pair optimization for enhancing is efficacious for HO-1 gene expression.

Case Presentation: In this case report we describe a case of intracranial infection of T. marneffei in a 42-year-old AIDS patient. Contrast enhanced MRI showed the left occipital lobe mass with ring enhancement, MRS showed elevated AAs and Lip waves in the mass. Surgical resection of the occipital lobe confirmed the lesion to be T. marneffei infection and possibly with tuberculosis after a pathological examination. Patients with intracranial ring enhancing space-occupying lesions on MRI should be considered for intracranial T. marneffei infection. Intracranial T. marneffei infection is relatively rarely reported and recently studied.

Conclusion: The MRI, in this case, suggests that ring enhancement mass and elevated AAs and Lip waves are helpful in the diagnosis of T. marneffei infection.

Methods: In silico virtual screening approach was executed to evaluate the binding affinity of several natural flavonoids to the MRSA β-lactamase active site. After that, the stability of interactions between top inhibitors and the residues incorporated inside the β-lactamase was examined by molecular dynamics (MD) simulation. Moreover, the most connected amino acid within the catalytic domain of the enzyme was determined.

Results: Rutin, isoquercitrin, nicotiflorin, quercetin-3-rhamnoside, vicenin-2, quercitrin, and orientin demonstrated a salient binding affinity with the β-lactamase active site (ΔG _binding < −10 kcal/mol). Interestingly, the inhibition constant value (Ki) for rutin was estimated at the picomolar scale. The docked poses of these compounds were demonstrated to be stable. Moreover, Gln237 was revealed to be the most crucial residue involved in ligand binding.

Conclusion: Rutin, isoquercitrin, nicotiflorin, quercetin-3-rhamnoside, vicenin-2, quercitrin, and orientin may be potent inhibitors of β-lactamase and may be helpful for the treatment of several invasive infections caused by MRSA strains. However, experimental studies are needed in the future to validate our findings.

Objective: The objective of this study was to determine the antibiotic resistance patterns and frequency of multidrug resistance (MDR) phenotype in E. coli isolated from patients in two major hospitals in Sari, north Iran.

Methods: In this descriptive-analytical study, a total of 13322 clinical specimens were collected from patients. All the specimens were evaluated to determine the presence of E. coli strains using conventional biochemical tests and API kit. Susceptibility testing against twelve antibiotics was determined using the disk-diffusion method. Results were interpreted in accordance with the Clinical and Laboratory Standard Institute (CLSI) protocol.

Results: Out of 13322 studied samples, 964 (7.23%) E. coli strains were identified. In two hospitals, high resistance to ampicillin and cefalexin was presented in 621 (64.4%) and 402 (41.7%) isolates, respectively. The highest antibiotic resistance was observed in the burn unit, the burn intensive care unit (ICU) and the burn restoration section, while all the strains (eight) that were isolated from the neonatal-ICU, were sensitive to all the tested antibiotics except cefalexin, nitrofurantoin, nalidixic acid, and ampicillin. Also, strains isolated from urine, wound, stool, and blood samples were resistant to all tested antibiotics.

Conclusion: Increased resistance to different antibiotics in burn hospitals has created increasing concern. Very high resistance to some antibiotics indicates that these drugs are misused in therapeutic centers and highlights that infection control measures should be arranged in the ICUs of our hospitals.

Case Presentation: Here, a 55-year-old lady was referred with a history of diffuse headache and intermittent fever for two months, projectile vomiting, and altered mental status for five days. Nonpruritic maculopapular rashes and diffuse desquamation of the skin were noted. She had no significant previous medical history. Based on clinical findings and investigations, she was diagnosed with ICL having disseminated cryptococcosis. Unfortunately, the patient did not undergo specific treatment as she was recognized late, and unfortunately, she died.

Conclusion: It is of paramount importance to recognize the clinical entity as early as possible to start appropriate treatment, which may positively impact the outcome. Therefore, the clinician must be aware of disseminated cryptococcosis associated with non-HIV states.

Objective: This study aimed to determine the characteristics of the 67 kDa pilus protein, including its capacity as hemagglutinin and adhesin and its amino acid sequence (AA).

Methods: The LCMS/MS method is used to determine the AA sequence of the 67 kDa pilus protein. The AA structure was analyzed through BLASTP by matching it with the sequence of the protein data bank of S. pneumoniae (taxid: 1313). The ProtParam tool from ExPASY was used to calculate various physical and chemical parameters of the protein, while for evaluating its immunogenicity, the VaxiJen V2.0 online server was used.

Results: The results of this study indicate that the 67 kD a pilus protein, is an anti-hemagglutinin protein and has a role as an adhesin protein. Adhesion tests show the action between protein concentration and the number of bacteria attached to enterocyte cells. LCMS/MS test results obtained by BLASTP showed that the 67 kDa pilus protein had three AA sequences (ITYMSPDFAAPTLAGLDDATK, AEFVEVTK, and LVVSTQTALA), which had similarities with the A backbone chain of S. pneumoniae pilus. The physicochemical test showed that the protein is hydrophilic and nonpolar, while the antigenicity test showed that the protein is antigenic.

Conclusion: Based on these characteristics, it can be concluded that the 67 kDa S. pneumoniae pilus protein can be used as a vaccine candidate for pneumococcus.]]> https://www.benthamscience.comarticle/124933Background: Infection caused by multidrug-resistant K. pneumoniae is regarded as a severe public health concern worldwide, with most countries reporting an increase in fatality rates over time. Efflux pumps are significant determinants of acquired and/or intrinsic resistance in K. pneumoniae.

Objectives: Our aim is to explore efflux-mediated resistance mechanisms in K. pneumoniae by using quantitative real-time PCR in order to evaluate the expression of efflux pump genes (acrA, acrB, oqxA, and oqxB) and pump regulators (marA, soxS, and rarA).

Methods: Efflux pump inhibitor CCCP reduced MIC values of ciprofloxacin by 2 to 64-fold in 43/46 (93%) of MDR-K. pneumoniae isolates.

Results: Compared to the control strain (untreated one), our results demonstrated that acrA, acrB, oqxA, oqxB, marA, soxS, and rarA were overexpressed in 29 (63%), 24 (52%), 29 (63%), 24 (52%), 17 (37%), 16 (35%), and 16 (35%) of K. pneumoniae isolates, respectively. Additionally, a positive correlation was established between the expressions of acrAB and marA (r = 0.50, r = 0.45, respectively) and oqxAB and rarA (r = 0.462912, r = 0.519354, respectively).

Conclusion: Ciprofloxacin resistance was caused by overexpression of the efflux pump genes acrAB and oqxAB, as well as the transcriptional regulators marA, soxS, and rarA in clinical isolates of K. pneumonia.

Objectives: This review aims to provide an overview of the role of cannabinoids in various diseases like metabolic disorders, infectious diseases, and psychological disorders.

Methods: Various e-resources like Pubmed, Science Direct, and Google Scholar were thoroughly searched and read to make an informative, comprehensive manuscript. Here we tried to summarize the therapeutic aspect of Cannabis sativa and its bioactive compound cannabinoids with respect to various diseases.

Results: This review highlights the various constituents which are present in Cannabis sativa, the endocannabinoid system, and the role of cannabinoids in various diseases.

Conclusion: Recent research on Cannabis has suggested its role in neurodegenerative diseases, inflammation, sleep disorders, pediatric diseases, and their analgesic nature. Therefore, the authors majorly focus on the therapeutic aspect of Cannabis sativa in various diseases. The focus is also on the endocannabinoid system (ECS) and its role in fighting or preventing bacterial, parasitic, fungal, and viral infections.

Objective: Therefore, this study was conducted to evaluate the antifungal activity of AgNPs on Candida albicans, Candida dubliniensis, and Candida guilliermondii.

Methodology: Antifungal activity of AgNPs on Candida albicans, Candida dubliniensis, and Candida guilliermondii was assessed by agar and macrodilution diffusion methods in an in-vitro investigation. Structural changes were investigated by scanning electron microscope (SEM). Then, the obtained data were evaluated by SPSS statistical software.

Results: Based on the results, the mean diameter of growth inhibition halos by AgNPs was equal to 20, 20.2, and 40.7mm for Candida albicans, Candida dubliniensis, and Candida guilliermondii, respectively. The minimum inhibitory concentrations (MIC) equal 62.50, 31.25, and 15.62 mg/ml for Candida albicans, Candida dubliniensis, and Candida guilliermondii, respectively. The minimum fungicidal concentrations (MFC) were equal to 125, 62.50, and 31.25 mg/ml for Candida albicans, Candida dubliniensis, and Candida guilliermondii, respectively.

Conclusion: Our results revealed that AgNPs inhibit the growth of Candida albicans, Candida dubliniensis, and Candida guilliermondii. SEM observations also showed that NPs disrupted cell membrane/wall. Changes in yeast levels from smooth to uneven were also observed.

Objective: In this study, we investigated the microbial epidemiology and resistance pattern of enterococcal bacteremia.

Methods: This study was a cross-sectional study that investigated all cases of positive blood cultures with Enterococcus spp. at a tertiary referral colligates hospital in Tehran in 2018.

Results: Enterococcus spp. was isolated from blood cultures of a total of 73 patients. Most of the patients were male i.e: 42 (57.7%). The mean age of the patients was 58.8 (±18.8) years. Hospital- acquired infection was the most prevalent type of infection involving enterococcal bacteremia (80.8%) compared with community-acquired (6.7%) and the health care-associated one (12.3%). Renal failure and cancer were the most underlying disease in E. faecalis and E. faecium, respectively. Mortality for Vancomycin-resistant enterococci (VRE) was approximately two times more than the sensitive ones. Between the dead/alive groups, the following items were significantly different (P.Value<0.05): Vancomycin resistance for enterococcus isolated, immunodeficiency as an underlying disease, Mechanical ventilation, hospitalization period, and the empiric regimen.

Conclusion: Increased antibiotic-resistant strains, especially Vancomycin-resistant enterococci (VRE), pose a serious threat to the general public, especially hospitalized patients, causing an increase in mortality. Surveillance of microorganisms and antimicrobial resistance is a crucial part of an efficient health care system.

Case Presentation: This case report describes an immunocompetent patient who had a right total hip arthroplasty (THA) complicated with Coccidioidomycosis. This patient is the 9th reported case of Coccidioidomycosis, causing a PJI and only the second case to be reported in a THA. Once progressed, it can be difficult to treat, often reoccurring and requiring repeat surgical and prolonged therapy.

Conclusion: This study discusses the clinical presentation in this patient and reviews the literature on the currently published cases.

Methods: S. cristaefolium powder (50 mesh) was extracted with three different solvents, including hexane, ethyl acetate, and methanol. S. cristaefolium powder residue was dried prior to serial re-extraction using different solvents. Three serial extracts were obtained and named as 1-stage extract, 2-stage extract, and 3-stage extract. Besides, a single-step extract (i.e., extraction using only methanol) was produced to be compared with three serial extracts in antibacterial activity tests (against E. coli and S. aureus). The three serial extracts were detected for their antibacterial compounds using GC-MS, LC-HRMS, and FT-IR.

Results: The 3-stage extract exhibited the highest extraction yield. On S. aureus, the inhibition zone in all extracts was not significantly different. On E.coli, the highest inhibition zone (5.42±0.14 mm) was of the 3-stage extract; indeed, it was higher than both antibiotic and a single- step extract. Antibacterial compounds, such as phenol, 9-Tricosene(Z)-, palmitic acid, and oleamide, were present in all extracts. Other antibacterial compound types, both the 1-stage and 2-stage extracts, contained 7 types, whilst the 3-stage extract contained the most types (11 types). Particularly, hexyl cinnamic aldehyde, betaine and several cinnamic aldehyde groups were detected only in the 3-stage extract comprising the dominant area. The carboxylic acid groups were detected in all extracts to confirm the fatty acid structure.

Conclusion: The serial extraction technique could produce the 3-stage extract which exhibited the strongest antibacterial activity and contained the richest antibacterial compounds.

Methods: We had screened Google Scholar database with the keywords nCoV, corona virus in India, effect of SARS-CoV-2 in India, 2019-nCoV, treatment pattern in India for nCoV and therapy used to treat nCoV in India. In the final review, we had included a total of 49 articles.

Results: As a result we had found that the Indian Council of Medical Research and NIH have given a standard guideline of Hydroxychloroquine and other antiviral drugs for nCoV, and also there are various researches going on related to nCoV treatment like, chemicals from natural products, herbs and spices commonly used in India, combination therapy of lopinavir and ritonavir, ultra-violet radiation therapy, molecular dynamic (MD) simulations of molecules for vaccine preparation, Convalescent plasma transfusion (CPT) therapy and many more.

Conclusions: New drugs and therapy are in the premature stage for this hazardous pandemic. We need more time to gain the detailed knowledge of the life cycle of the nCoV, which can speed up the drug/vaccine development process against nCoV.

Methods: To explore the genomic epidemiology of S. aureus, in-silico Multi Locus Sequence Typing (MLST) was carried out for 355 complete genomes. Diversity within the species was investigated through pan-genome analysis and a subtractive genomic approach was employed for the identification of the core immunogenic targets.

Results: Epidemiological study identified 62 different sequence types (STs) of S. aureus distributed worldwide, in which ST-8, ST-5, ST-398, ST-239, and ST-30 were the most dominant STs comprising more than 50% of the isolates. The pan-genome of S. aureus is still open with 7,199 genes and there is a major contribution (80%) of MRSA strains in the S. aureus species pangenome. The core genome (2,025 genes) of S. aureus is almost stable (comprising 72% of S. aureus genome size), while accessory and unique genes (28% of S. aureus genome size) are gradually increasing. Screening of 2,025 core genes identified putative vaccine candidates. The best scoring and dominant B-cell and T-cell epitopes were predicted out of the selected potential vaccine candidate proteins with the help of a multi-step screening procedure.

Conclusion: We believe that the current study will provide insight into the genetic epidemiology and diversity of S. aureus, and the predicted epitopes against the pathogen can be tested further for their immunological responses within the host and may provide both humoral and cellular immunity against the disease.]]> https://www.benthamscience.comarticle/116641 https://www.benthamscience.comarticle/120278 https://www.benthamscience.comarticle/120673 https://www.benthamscience.comarticle/118048Background: Infections caused by drug-resistant microorganisms have been increasing worldwide, thereby being one of the major causes of morbidity in the 21st century. Klebsiella pneumoniae is one such bacteria causing lung inflammation, lung injury and death. The emergence of hyper-virulent and drug-resistant species, such as ESBL and CRKP, has made this microbe a serious and urgent threat. The pace of emergence of these species is outgrowing the development of novel drug and vaccine candidates, thereby shifting the research focus towards the drug repurposing approach.

Objective: The study aimed at Homology Modeling of Thymidylate Synthase, verification of modeled structure, Molecular Docking and Molecular Dynamic Simulation of the docked complex, and finally, in vitro analysis of 5-FU activity against Klebsiella pneumonia.

Methods: The 3D structure of Thymidylate Synthase was predicted using the Swiss model server and validated by in silico approaches. The protein-protein interactions were determined using the STRING database. Molecular Docking has been carried out and MD simulations of 5-FU with the predicted structure of thymidylate synthase have been conducted. Finally, in vitro antimicrobial drug sensitivity assay has been carried out at different concentrations.

Results: Hydrogen bond was observed in Molecular Docking, protein-ligand complex remained stable during simulation, while 5-FU showed antimicrobial activity against Klebsiella pneumonia during the in vitro study.

Conclusion: Both in silico as well as in vitro analysis have indicated that 5-FU can potentially be developed as an antimicrobial agent towards Klebsiella pneumonia.

Discussion: The degree of effectiveness of any vaccine largely depends on the choice of appropriate adjuvant. Along with the optimum biocompatibility, an ideal adjuvant must be biodegradable, economical and easy to manufacture. To date, various organic and inorganic substances have been used as an adjuvant to augment the effectiveness of the vaccine. Immunological adjuvants are essential for strong and long-term effects against various pathogens. However, a very limited number of licensed adjuvants are available for the formulation of a successful vaccine. This leads to a challenging situation in medical science.

Conclusion: The present review concisely summarizes the mechanism of action of various bioactive organic and inorganic immunological adjuvants, their limitations and future perspectives for their appropriate modification. Current trends of anticancer therapies using immunological adjuvants have also been highlighted in this review.

Methods: A literature search was performed through PubMed and Scopus to summarize the extrapulmonary manifestations of SARS-CoV-2 infection in children since the beginning of the pandemic. Peer-reviewed papers in English were retrieved using the following keywords and combinations: ‘pediatric,’ ‘child,’ ‘infant,’ ‘neonate,’ ‘novel coronavirus,’ ‘SARS-CoV-2,’ ‘COVID 19’ and ‘gastrointestinal,’ ‘renal,’ ‘cardiac,’ ‘dermatologic’ or ‘ophthalmologic’. We included published case series and case reports providing clinical symptoms and signs in SARS-CoV2 pediatric patients.

Results: Although fever and symptoms of upper respiratory infection are the most frequently presented, a variety of other atypical presentations has also been reported. The clinical spectrum includes dermatological, ophthalmological, neurological, cardiovascular, renal, reproductive, and gastrointestinal presentations. In addition, a rare multi-inflammatory syndrome associated with SARS-- CoV-2 infection has been reported in children, often leading to shock and requiring inotropic support and mechanical ventilation.

Conclusion: Clinicians need to be aware of the wider range of extrapulmonary atypical manifestations of SARS-CoV-2 infection in children, so that appropriate testing, treatment, and public health measures can be implemented rapidly.

Objective: The purpose of this work was to carry out a comprehensive review of naphthoquinones and their derivatives obtained from both natural and synthetic sources, also, to analyze their biological activity against Leishmania spp. (Leishmaniasis), Trypanosoma cruzi (Chagas disease), Plasmodium falciparum (Malaria), Toxoplasma gondii (Toxoplasmosis), and Toxocara canis (Toxocariasis). All of these agents are responsible for relevant diseases worldwide.

Results: Natural naphthoquinones, such as plumbagin, diospyrin, burmanin, lapachol, lawsone and psychorubrin, show an antiprotozoal activity similar or enhanced antiprotozoal activity to reference drugs. Some naphthoquinones obtained by synthesis or semi-synthesis showed better biological activity or less toxic effects than natural compounds.

Conclusion: In this review, natural and synthetic naphthoquinones showed antiparasitic activity, in most cases, with improved results than current drugs currently used in clinical trials. A modification of their structure with different functional groups can enhance their biological effects, improve solubility, and reduce undesirable side effects. Therefore, naphthoquinones are important molecules in the development of new chemotherapeutic agents against parasitic diseases.

The multidrug resistance (MDR) and antibiotics losing efficacy, esp. in methicillin resistance Staphylococcus aureus (MRSA) urge for novel antimicrobial agents. The MRSA strains are resistant to the entire class of β-lactam antibiotics and limit effective treatment, leading to still spread of staphylococcal infections. MRSA also exhibits resistance to cephalosporins, macrolides, fluoroquinolones, aminoglycosides, and glycopeptides (teicoplanine and vancomycin), leading to resistant strains-glycopeptide resistant strain (GRSA) and glycopeptide intermediate (GISA) S. aureus. In this review, chemical constituents responsible for the anti-MRSA activity of tea are explored.

Objective: The aim of this study was to present repurposed drugs, and potential candidates, that can serve as anticancer medications intended to target resistant cancer cells, i.e. CSCs.

Methods: Research publications, FDA filings, and patents have been reviewed for repurposed drugs or drug combinations that can act to improve cancer treatment and care.

Results: Drugs that act against CSCs include ones approved for treatment of diabetes (metformin & thiazolidinediones), parasitic diseases (chloroquine, niclosamide, mebendazole & pyrvinium), psychotic disorders (thioridazine, clomipramine & phenothiazines), alcoholism (disulfiram), lipid disorder (statins), inflammatory diseases (tranilast, auranofin, acetaminophen & celecoxib), antibiotics (azithromycin), and other disorders. Current research findings advocate the existence of beneficial effects by combining these repurposed drugs, and also through their complementary use with conventional cancer therapies.

Conclusion: Repurposing FDA-approved medications towards cancer care, by targeting the resistant CSCs, will allow for a quicker, cheaper development and approval process. A larger drug library available to physicians will allow for increased efficacy during both first-line and recurrent cancer treatments.

Curcumin, a redox-active natural product, for centuries, has been used in Asian traditional medicine for the treatment of various diseases. It is known for possessing multiple biological and pharmacological activities. Curcumin has been investigated extensively over the years for its anti-inflammatory, anticancer, antiparasitic, antiviral and antibacterial activities, and no toxicity is associated with the compound. Despite its potency and good safety profile, curcumin is still in clinical trials for the treatment of diseases, such as tuberculosis, acquired immunodeficiency syndrome (AIDS), Crohn’s disease, colorectal cancer, and multiple myeloma, among many others, as it is yet to be qualified as a therapeutic agent. This review summarizes events over the last decade, especially regarding the discovery of curcumin, an update of its synthesis, its pathogen specific mechanisms of action, and the pharmacological effects of its derivatives, combinations and formulations as potential antibacterial, antifungal, antiparasitic and antiviral agents for the treatment of various infectious diseases.

Methods: The antimicrobial analysis of the extracts of leaves, roots and stems of C. borivilianum is based on the agar well diffusion method and Minimum Inhibitory Concentration (MIC). The phytochemical screening and characterization of saponin on the basis of structural and antimicrobial activity present in C. borivilianum were analyzed by different spectrophotometric methods such as HPLC, UV-visible, IR, NMR, LC-ESI-MS and pharmacophore modeling.

Results: The results revealed that the methanolic leaf, stem and root extracts have inhibitory potential against the growth of K. pneumonia, B. subtilis, M. tuberculosis, E coli and S. aureus in case of bacteria and C. albicans, A. fumigatus and Tricoderma in case of fungus. The MIC values of leaf, stem and root extracts were found in the range of 1 mg/ml to 0.125 mg/ml. Moreover, the purified saponins indicated MIC in the range of 0.5 mg/ml to 0.0625 mg/ml against the selected microbial pathogens. Saponins act as one of the major phytocomponents present in C. borivilianum. The antimicrobial and structural analysis of purified saponins of C. borivilianum was also performed using different spectral analysis methods.

Conclusion: The anti-microbial results showed that the extract from the leaf and stems had higher anti-pathogenic activity as compared to the roots. The MIC results showed that the purified saponin also possessed the anti-microbial activity and oleanolic acid content, as detected by spectral analysis the fundamental structure of the extracted saponin.

Exclusion Criteria: Patients are seen in A/E and ambulatory care who did not stay overnight and those who received antimicrobials for perioperative or medical prophylaxis were excluded.

Statistical Analysis: Statistical Analysis was done using excel program descriptive statistics were used to describe the baseline demographic data and clinical characteristics. Categorical variables are presented as counts and percentages, whereas continuous variables are presented as mean.

Results: A total of 666 patients’ medical records were reviewed during January 2020 to April 2020. Respiratory tract infections were the most common diagnosis encountered (456/666), representing 68.5% in total. A total of 994 courses of antimicrobials were prescribed during the study period. Antimicrobial was considered 'appropriate' in 70.3% (979/1393), and ‘not indicated' in 19.7% (273/1393) of cases. In the remaining 10% of cases (141/1393), antimicrobial was indicated but required antimicrobial stewardship team (A.M.S) intervention. The compliance to accept antimicrobial stewardship team recommendations and change therapy accordingly in our study was only 32.6% (133/412)

Conclusion: In this study, the prevalence of inappropriate antimicrobial prescribing is comparable to that found in other studies worldwide. However, the compliance with AMS recommendations is much lower than described in the literature.]]> https://www.benthamscience.comarticle/109590 https://www.benthamscience.comarticle/110315Introduction: The increase in contagious diseases like nosocomial infections, urinary tract infections, and meningitis has led to the emergence of antimicrobial resistance urgently needs new antimicrobial medication with new modes of action. Some of the antibiotics present in the market have been obtained from terrestrial plants, or extracted semisynthetically from materials which can be fermented.

Methods: Marine microorganisms account for approximately 80% of sea biomass. They are essential for the survival and well-being of aquatic habitats due to their indispensable contribution to biogeochemical cycles and biological processes. In marine ecosystems, microorganisms live as microbial communities in seawater, where symbiotic relationships are formed, and their ecological functions are fulfilled.

Results: Marine microorganisms remain the largest, most diverse and most exciting source of structurally and functionally complex antimicrobial agents. They are extremely involved in their structure and functions. Enormous biological wealth lies in marine habitats. These microorganisms are potential sources of novel antimicrobial compounds to combat the most infectious diseases like nosocomial infections, and urinary tract infections.

Conclusion: This study deals with biologically active antimicrobial compounds taken from marine microorganism source, which was reported between the years 2005 and 2019. This review highlights their chemical groups, their bioactivities and sources. Marine microorganism exploitation techniques have also been reported by the authors.

Objective: Development and validation of RP-UFLC (using ion-pairing reagent) method for accurate estimation of ceftriaxone in rat serum and CSF.

Methods: Method validation is done according to the ICH Guidelines (Q2) for the estimation of ceftriaxone in rat serum and its CSF (cerebrospinal fluid) by the RP-UFLC method. The blood was collected from the rat tail vein and CSF was collected carefully from cisterna magna of the rats by a 23G syringe. The mobile phase was used in a ratio of 70:30%v/v of phosphate buffer with ion-pairing reagent and acetonitrile with a pH of 8.0

Results: Limit of detection and limit of quantification of ceftriaxone in rat serum was 1.08 μg/ml and 3.84 μg/ml, respectively. Similarly, the limit of detection and limit of quantification of ceftriaxone in CSF of rats was 0.94 μg/ml and 2.84 μg/ml, respectively. In both cases, the R² value was more than 0.99 and showed 99% accuracy.

Conclusion: The experimental results suggest that the new RP-UFLC method developed and validated can be effectively used to assess ceftriaxone in preclinical studies in rats.]]> https://www.benthamscience.comarticle/105915 Methods: A systematic literature search was carried out to identify papers published by Iranian authors in the Web of Science, PubMed, Scopus, Embase and Google Scholar electronic databases from January 2000 to December 2018. Then, eight publications that met our inclusion criteria were selected for data extraction and analysis by Comprehensive Meta-Analysis software.

Objective: Due to the high similarity among genera and species of pathogens, it is sometimes difficult for microbiologists to differentiate between them. Their automatic classification using deeplearning models can help in gaining reliable and accurate outcomes.

Methods: Deep-learning models, namely; AlexNet, GoogleNet, ResNet101, and InceptionV3 are used with numerous variations including training model from scratch, fine-tuning without pre-trained weights, fine-tuning along with freezing weights of initial layers, fine-tuning along with adjusting weights of all layers and augmenting the dataset by random translation and reflection. Moreover, as the dataset is small, fine-tuning and data augmentation strategies are applied to avoid overfitting and produce a generalized model. A merged feature vector is produced using two best-performing models and accuracy is calculated by xgboost algorithm on the feature vector by applying cross-validation.

Results: Fine-tuned models where augmentation is applied produces the best results. Out of these, two-best-performing deep models i.e. (ResNet101, and InceptionV3) selected for feature fusion, produced a similar validation accuracy of 95.83 with a loss of 0.0213 and 0.1066, and testing accuracy of 97.92 and 93.75, respectively. The proposed model used xgboost to attain a classification accuracy of 98.17% by using 35-folds cross-validation.

Conclusion: The automatic classification using these models can help experts in the correct identification of pathogens. Consequently, they can help in controlling epidemics and thereby minimizing the socio-economic impact on the community.

Methods: Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child- Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess the severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serum-ascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid.

Results: Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis, fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development.

Conclusion: Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.

- Screening of new chemical classes of synthetic antimycotic compounds.

- Screening of natural compounds.

- Identification of new unique molecular targets in the fungal cell.

- Development of new compositions and dosage forms with effective delivery vehicles.

The methods of informatics, bioinformatics, genomics and proteomics were extensively investigated for the development of new antimycotics. These techniques were employed in finding and identification of new molecular proteins in a fungal cell; in the determination of the selectivity of drugprotein interactions, evaluation of drug-drug interactions and synergism of drugs; determination of the structure-activity relationship (SAR) studies; determination of the molecular design of the most active, selective and safer drugs for the humans, animals and plants. In medical applications, the methods of information analysis and pharmacogenomics allow taking into account the individual phenotype of the patient, the level of expression of the targets of antifungal drugs when choosing antifungal agents and their dosage. This review article incorporates some of the most significant studies covering the basic structures and approaches for the synthesis of antifungal drugs and the directions for their further development.]]> https://www.benthamscience.comarticle/106009Background: Escherichia coli especially its multiresistant strains as the common foodborne pathogens cause bloodstream infections, nosocomial pneumonia, infections of the skin and soft tissues. Therefore, the search for new effective biologically active compounds has been rapidly increasing in recent few decades. In this paper, we describe Quantitative Structure-Activity Relationships (QSAR) studies, molecular docking and in vitro antibacterial activity evaluation of a series of imidazolium-based Ionic Liquids (ILs) against E. coli spp.

Methods: M2D fragment-based, classification and regression QSAR models were created using machine learning methods and types of descriptors via the OCHEM server. Biological testing of a series of synthesized imidazolium ILs with predicted activity was performed by the disc diffusion method. The most typical structures of symmetric and asymmetric ILs with high anti-E. coli activity (1e, 1h) were docked into the active site of Enoyl-Acyl Carrier Protein Reductase (ENR) in E. coli.

Results: Symmetric imidazolium ILs with C8 alkyl chain length demonstrated the highest antibacterial activity in comparison to the high antibacterial potential of asymmetric ILs with C12 alkyl chain length against drug-sensitive and drug-resistant E. coli strains including hemolytic E. coli. It should be noted that symmetric ILs with C6 or C9 alkyl chain length have a slightly lower activity against certain E. coli strains. The key role in the binding of compounds (1e, 1h) in the E. coli ENR active site is associated with the NAD molecule and the amino acid residue Tyr146.

Conclusion: The highly active symmetric and asymmetric imidazolium ILs can be considered as promising drug-candidates effective against E. coli spp. pathogens including multidrug-resistant strains.

Case Presentation: A 30-year-old Sudanese male patient presented to our hospital with a complaint of fever associated with confusion for three days. He had signs of meningeal irritation in the form of neck stiffness, positive Kernig’s, and Lesage’s sign. The computerized tomography of the brain was normal. The CSF analysis showed a clear colorless sample with normal tension, decreased glucose, and slightly increased CSF protein level. We reviewed his occupational history; the patient was a farmer with regular contact with cattle and camels. The patient had positive Brucella antibodies for both B. Abortus and B. melitensis with a high titer (1/640). As described in various patents, we administered triple therapy for brucellosis for two weeks. A marked improvement in the conscious level was observed, and the patient was back to normal within a few days post-treatment.

Conclusion: We encouraged physicians to consider the diagnosis of neurobrucellosis with any neurologic sign without a known cause. Our case highlights the importance of occupational history in clinical medicine.