Clinical relevance of molecular testing methods in the diagnosis and guidance of therapy in patients with staphylococcal empyema: a systematic review and meta-analysis

BackgroundEfficient detection tools for determining staphylococcal pleural infection are critical for its eradication. The objective of this meta-analysis was to assess the diagnostic utility of nucleic acid amplification tests (NAAT) in suspected empyema cases to identify staphylococcal strains and avoid unnecessary empiric methicillin-resistant Staphylococcus aureus (MRSA) therapy.MethodsFrom inception to July 24, 2021, relevant records were retrieved from PubMed, Embase, Scopus, Web of Science, and the Cochrane Library. The quality of studies was determined using the QUADAS-2 tool. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and hierarchical summary receiver operating characteristic (HSROC) curve for NAAT’s diagnostic performance were evaluated using an HSROC model.ResultsEight studies comprising 424 samples evaluated NAAT accuracy for Staphylococcus aureus (SA) identification, while four studies comprising 317 samples evaluated methicillin-resistant Staphylococcus aureus (MRSA) identification. The pooled NAAT summary estimates for detection of both SA (sensitivity: 0.35 (95% CI 0.19–0.55), specificity: 0.95 (95% CI 0.92–0.97), PLR: 7.92 (95% CI 4.98–12.59), NLR: 0.44 (95% CI 0.14–1.46), and DOR: 24.0 (95% CI 6.59–87.61) ) and MRSA (sensitivity: 0.45 (95% CI 0.15–0.78), specificity: 0.93 (95% CI 0.89–0.95), PLR: 10.06 (95% CI 1.49–67.69), NLR: 0.69 (95% CI 0.41–1.15), and DOR: 27.18 (95% CI 2.97–248.6) ) were comparable. The I2 statistical scores for MRSA and SA identification sensitivity were 13.7% and 74.9%, respectively, indicating mild to substantial heterogeneity. PCR was frequently used among NAA tests, and its diagnostic accuracy coincided well with the overall summary estimates. A meta-regression and subgroup analysis of country, setting, study design, patient selection, and sample condition could not explain the heterogeneity (meta-regression P = 0.66, P = 0.46, P = 0.98, P = 0.68, and P = 0.79, respectively) in diagnostic effectiveness.ConclusionsOur study suggested that the diagnostic accuracy of NAA tests is currently inadequate to substitute culture as a principal screening test. NAAT could be used in conjunction with microbiological culture due to the advantage of faster results and in situations where culture tests are not doable

ERpred: a web server for the prediction of subtype-specific estrogen receptor antagonists

Estrogen receptors alpha and beta (ERα and ERβ) are responsible for breast cancer metastasis through their involvement of clinical outcomes. Estradiol and hormone replacement therapy targets both ERs, but this often leads to an increased risk of breast and endometrial cancers as well as thromboembolism. A major challenge is posed for the development of compounds possessing ER subtype specificity. Herein, we present a large-scale classification structure-activity relationship (CSAR) study of inhibitors from the ChEMBL database which consisted of an initial set of 11,618 compounds for ERα and 7,810 compounds for ERβ. The IC50 was selected as the bioactivity unit for further investigation and after the data curation process, this led to a final data set of 1,593 and 1,281 compounds for ERα and ERβ, respectively. We employed the random forest (RF) algorithm for model building and of the 12 fingerprint types, models built using the PubChem fingerprint was the most robust (Ac of 94.65% and 92.25% and Matthews correlation coefficient (MCC) of 89% and 76% for ERα and ERβ, respectively) and therefore selected for feature interpretation. Results indicated the importance of features pertaining to aromatic rings, nitrogen-containing functional groups and aliphatic hydrocarbons. Finally, the model was deployed as the publicly available web server called ERpred at http://codes.bio/erpred where users can submit SMILES notation as the input query for prediction of the bioactivity against ERα and ERβ

Tackling the Antibiotic Resistance Caused by Class A β-Lactamases through the Use of β-Lactamase Inhibitory Protein

β-Lactams are the most widely used and effective antibiotics for the treatment of infectious diseases. Unfortunately, bacteria have developed several mechanisms to combat these therapeutic agents. One of the major resistance mechanisms involves the production of β-lactamase that hydrolyzes the β-lactam ring thereby inactivating the drug. To overcome this threat, the small molecule β-lactamase inhibitors (e.g., clavulanic acid, sulbactam and tazobactam) have been used in combination with β-lactams for treatment. However, the bacterial resistance to this kind of combination therapy has evolved recently. Therefore, multiple attempts have been made to discover and develop novel broad-spectrum β-lactamase inhibitors that sufficiently work against β-lactamase producing bacteria. β-lactamase inhibitory proteins (BLIPs) (e.g., BLIP, BLIP-I and BLIP-II) are potential inhibitors that have been found from soil bacterium Streptomyces spp. BLIPs bind and inhibit a wide range of class A β-lactamases from a diverse set of Gram-positive and Gram-negative bacteria, including TEM-1, PC1, SME-1, SHV-1 and KPC-2. To the best of our knowledge, this article represents the first systematic review on β-lactamase inhibitors with a particular focus on BLIPs and their inherent properties that favorably position them as a source of biologically-inspired drugs to combat antimicrobial resistance. Furthermore, an extensive compilation of binding data from β-lactamase–BLIP interaction studies is presented herein. Such information help to provide key insights into the origin of interaction that may be useful for rationally guiding future drug design efforts

Characterization of the Secretome of Pathogenic Candida glabrata and Their Effectiveness against Systemic Candidiasis in BALB/c Mice for Vaccine Development

Infections by non-albicans Candida species have increased drastically in the past few decades. Candida glabrata is one of the most common opportunistic fungal pathogens in immunocompromised individuals, owing to its capability to attach to various human cell types and medical devices and being intrinsically weakly susceptible to azoles. Immunotherapy, including the development of antifungal vaccines, has been recognized as an alternative approach for preventing and treating fungal infections. Secretory proteins play a crucial role in establishing host–pathogen interactions and are also responsible for eliciting an immune response in the host during candidiasis. Therefore, fungal secretomes can provide promising protein candidates for antifungal vaccine development. This study attempts to uncover the presence of immunodominant antigenic proteins in the C. glabrata secretome and delineate their role in various biological processes and their potency in the development of antifungal vaccines. LC–MS/MS results uncovered that C. glabrata secretome consisted of 583 proteins, among which 33 were identified as antigenic proteins. The protection ability of secretory proteins against hematogenously disseminated infection caused by C. glabrata was evaluated in BALB/c mice. After immunization and booster doses, all the animals were challenged with a lethal dose of C. glabrata. All the mice showing signs of distress were sacrificed post-infection, and target organs were collected, followed by histopathology and C. glabrata (CFU/mg) estimation. Our results showed a lower fungal burden in target organs and increased survival in immunized mice compared to the infection control group, thus revealing the immunogenic property of secreted proteins. Thus, identified secretome proteins of C. glabrata have the potential to act as antigenic proteins, which can serve as potential candidates for the development of antifungal vaccines. This study also emphasizes the importance of a mass-spectrometry approach to identifying the antigenic proteins in C. glabrata secretome

Characterization of Defensin-like Protein 1 for Its Anti-Biofilm and Anti-Virulence Properties for the Development of Novel Antifungal Drug against Candida auris

Candida auris has emerged as a pan-resistant pathogenic yeast among immunocompromised patients worldwide. As this pathogen is involved in biofilm-associated infections with serious medical manifestations due to the collective expression of pathogenic attributes and factors associated with drug resistance, successful treatment becomes a major concern. In the present study, we investigated the candidicidal activity of a plant defensin peptide named defensin-like protein 1 (D-lp1) against twenty-five clinical strains of C. auris. Furthermore, following the standard protocols, the D-lp1 was analyzed for its anti-biofilm and anti-virulence properties. The impact of these peptides on membrane integrity was also evaluated. For cytotoxicity determination, a hemolytic assay was conducted using horse blood. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values ranged from 0.047–0.78 mg/mL and 0.095–1.56 mg/mL, respectively. D-lp1 at sub-inhibitory concentrations potentially abrogated both biofilm formation and 24-h mature biofilms. Similarly, the peptide severely impacted virulence attributes in the clinical strain of C. auris. For the insight mechanism, D-lp1 displayed a strong impact on the cell membrane integrity of the test pathogen. It is important to note that D-lp1 at sub-inhibitory concentrations displayed minimal hemolytic activity against horse blood cells. Therefore, it is highly useful to correlate the anti-Candida property of D-lp1 along with anti-biofilm and anti-virulent properties against C. auris, with the aim of discovering an alternative strategy for combating serious biofilm-associated infections caused by C. auris

Stability Analysis of Chaotic Grey-Wolf Optimized Grid-Tied PV-Hybrid Storage System during Dynamic Conditions

This paper presents the stability improvement of the three-phase four-wire (3P-4W) grid-tied PV-hybrid energy storage system (HESS) using chaotic grew wolf optimization (CGWO) for DC bus voltage (Vdc) and AC bus voltage (Vpcc) control. The CGWO tuned fractional order proportional–integral (FOPI) controllers reduce the Vdc and Vpcc variations during diverse, dynamic conditions, i.e., sudden irradiation variations, deep voltage sag/swell, etc. The DC bus is responsible for the current injection/extraction control, maximum PV power extraction, bi-directional power flow, dc second-harmonics component elimination, and active power balance. At the point of common coupling (PCC), the AC bus is accountable for bi-directional power flow and active and reactive power control. The two-level voltage source converter (VSC) is controlled by a novel variable step-size incremental least mean square (VSS-ILMS) in zero voltage regulation (ZVR) mode. Due to its varying step size, VSC control is less prone to noise signals offers better stability, improved convergence rate, dc offset rejection, and tracking speed during dynamics, i.e., large oscillations. A battery and ultracapacitor are coupled to the DC link by buck-boost converters in the HESS. To regulate power transit between the DC bus and the grid, the HESS current control technique is designed to shift frequently from charging to discharging stage and vice versa. The novelty of the PV-HESS system lies in CGWO tuned VSS-ILMS control of VSC, which effectively and efficiently filter out the active fundamental constituents of load current and eliminate dc offset from VSC output. The HESS control maintains the DC bus voltage profile by absorbing and delivering energy (during dynamic conditions) rather than curtailing it. The presented system is simulated in a MATLAB/SIMULINK environment. The simulation results in graphical and numerical forms verify the stable and satisfactory operation of the proposed system as per IEEE519 standard

Stability Analysis of Chaotic Grey-Wolf Optimized Grid-Tied PV-Hybrid Storage System during Dynamic Conditions

This paper presents the stability improvement of the three-phase four-wire (3P-4W) grid-tied PV-hybrid energy storage system (HESS) using chaotic grew wolf optimization (CGWO) for DC bus voltage (Vdc) and AC bus voltage (Vpcc) control. The CGWO tuned fractional order proportional–integral (FOPI) controllers reduce the Vdc and Vpcc variations during diverse, dynamic conditions, i.e., sudden irradiation variations, deep voltage sag/swell, etc. The DC bus is responsible for the current injection/extraction control, maximum PV power extraction, bi-directional power flow, dc second-harmonics component elimination, and active power balance. At the point of common coupling (PCC), the AC bus is accountable for bi-directional power flow and active and reactive power control. The two-level voltage source converter (VSC) is controlled by a novel variable step-size incremental least mean square (VSS-ILMS) in zero voltage regulation (ZVR) mode. Due to its varying step size, VSC control is less prone to noise signals offers better stability, improved convergence rate, dc offset rejection, and tracking speed during dynamics, i.e., large oscillations. A battery and ultracapacitor are coupled to the DC link by buck-boost converters in the HESS. To regulate power transit between the DC bus and the grid, the HESS current control technique is designed to shift frequently from charging to discharging stage and vice versa. The novelty of the PV-HESS system lies in CGWO tuned VSS-ILMS control of VSC, which effectively and efficiently filter out the active fundamental constituents of load current and eliminate dc offset from VSC output. The HESS control maintains the DC bus voltage profile by absorbing and delivering energy (during dynamic conditions) rather than curtailing it. The presented system is simulated in a MATLAB/SIMULINK environment. The simulation results in graphical and numerical forms verify the stable and satisfactory operation of the proposed system as per IEEE519 standard

Multi-Objective Grasshopper Optimization Based MPPT and VSC Control of Grid-Tied PV-Battery System

This article presents the control of a three-phase three-wire (3P-3W) dual-stage grid-tied PV-battery storage system using a multi-objective grass-hopper optimization (MOGHO) algorithm. The voltage source converter (VSC) control of the presented system is implemented with adaptive kernel width sixth-order maximum correntropy criteria (AKWSOMCC) and maximum power point tracking (MPPT) control is accomplished using the variable step-size incremental conductance (VSS-InC) technique. The proposed VSC control offers lower mean square error and better accuracy, convergence rate and speed as compared to peer adaptive algorithms, i.e., least mean square (LMS), least mean fourth (LMF), maximum correntropy criteria (MCC), etc. The adaptive Gaussian kernel width is a function of the error signal, which changes to accommodate and filter Gaussian and non-Gaussian noise signals in each iteration. The VSS-InC based MPPT is provided with a MOGHO based modulation factor for better and faster tracking of the maximum power point during changing solar irradiation. Similarly, an optimized gain conventional PI controller regulates the DC bus to improve the power quality, and DC link stability during dynamic conditions. The optimized DC-link generates an accurate loss component of current, which further improves the VSC capability of fundamental load current component extraction. The VSC is designed to perform multi-functional operations, i.e., harmonics elimination, reactive power compensation, load balancing and power balancing at point of common coupling during diverse dynamic conditions. The MOSHO based VSS-InC, and DC bus performance is compared to particle swarm optimization (PSO) and genetic algorithm (GA). The proposed system operates satisfactorily as per IEEE519 standards in the MATLAB simulation environment

<i>Beta vulgaris </i>Assisted Fabrication of Novel Ag-Cu Bimetallic Nanoparticles for Growth Inhibition and Virulence in <i>Candida albicans</i>

Beta vulgaris extract contains water-soluble red pigment betanin and is used as a food colorant. In this study, the biogenic Ag-Cu bimetallic nanoparticles were synthesized and characterized by different spectroscopic and microscopic techniques, including UV–Visible, FTIR, TEM. SEM-EDX, XRD, and TGA. Further, Ag-Cu bimetallic nanoparticles capped with Beta vulgaris biomolecules were evaluated for their antifungal activity against Candida albicans via targeting its major virulence factors, including adherence, yeast to hyphae transition, extracellular enzyme secretion, biofilm formation, and the expression of genes related to these pathogenic traits by using standard methods. C. albicans is an opportunistic human fungal pathogen that causes significant morbidity and mortality, mainly in immunocompromised patients. The current antifungal therapy is limited with various shortcomings such as host toxicity and developing multidrug resistance. Therefore, the development of novel antifungal agents is urgently required. Furthermore, NPs were screened for cell viability and cytotoxicity effect. Antifungal susceptibility testing showed potent antifungal activity of the Ag-Cu bimetallic NPs with a significant inhibitory effect on adherence, yeast to hyphae transition, extracellular enzymes secretion, and formation of biofilms in C. albicans at sub-inhibitory and inhibitory concentrations. The RT-qPCR results at an MIC value of the NPs exhibited a varying degree of downregulation in expression levels of virulence genes. Results also revealed the dose-dependent effect of NPs on cellular viability (up to 100%) using MUSE cell analyzer. Moreover, the low cytotoxicity effect of bimetallic NPs has been observed using haemolytic assay. The overall results indicated that the newly synthesized Ag-Cu bimetallic NPs capped with Beta vulgaris are proven to possess a potent anticandidal activity, by affecting the vital pathogenic factors of C. albicans

A Silver Nanoparticles-Based Selective and Sensitive Colorimetric Assay for Ciprofloxacin in Biological, Environmental, and Commercial Samples

The wide-spread usage of ciprofloxacin (CIP) resulted in its presence in different parts of the ecosystem. Thus, a simple, reliable, on-spot detection method for CIP is required in environmental context. Herein, a colorimetric assay is developed for the detection of CIP based on the branched polyethyleneimine (PEI) conjugated silver nanoparticles (PEI-AgNPs). AgNPs are prepared using PEI as stabilizing agent following a simple one-pot two-phase procedure. The prepared PEI-AgNPs are subsequently used for an efficient and selective detection of CIP. The characteristic yellow colour of PEI-AgNPs changed to colourless when CIP was added which was further confirmed by quenching in the intensity of the SPR (surface plasmon resonance) band (hypochromic shift). The proposed method is efficient for the quantitation of CIP in a linear dynamic range (LDR) of 0.1–200 µM with a limit of detection (LOD) of 0.038 µM, and limit of quantification (LOQ) of 0.12 µM. The developed method is selective, efficient, and sensitive to CIP in the presence of numerous interfering species and in real biological, environmental, and commercial pharmaceutical samples. Excellent performance of the proposed method compared to UV-Vis spectroscopy and UPLC in environmental, biological, and commercial pharmaceutical samples is demonstrated