Chronic Pulmonary Aspergillosis: Clinical Presentation and Management.

Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of Aspergillus organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on Aspergillus immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of Aspergillus adaptation in the lung environment, the contribution of non-fumigatus Aspergillus species, and the role of new antifungal agents, immunotherapy, and combination therapy.

Definitions matter: Heterogeneity of COVID-19 disease severity criteria and incomplete reporting compromise meta-analysis.

Therapeutic efficacy in COVID-19 is dependent upon disease severity (treatment effect heterogeneity). Unfortunately, definitions of severity vary widely. This compromises the meta-analysis of randomised controlled trials (RCTs) and the therapeutic guidelines derived from them. The World Health Organisation 'living' guidelines for the treatment of COVID-19 are based on a network meta-analysis (NMA) of published RCTs. We reviewed the 81 studies included in the WHO COVID-19 living NMA and compared their severity classifications with the severity classifications employed by the international COVID-NMA initiative. The two were concordant in only 35% (24/68) of trials. Of the RCTs evaluated, 69% (55/77) were considered by the WHO group to include patients with a range of severities (12 mild-moderate; 3 mild-severe; 18 mild-critical; 5 moderate-severe; 8 moderate-critical; 10 severe-critical), but the distribution of disease severities within these groups usually could not be determined, and data on the duration of illness and/or oxygen saturation values were often missing. Where severity classifications were clear there was substantial overlap in mortality across trials in different severity strata. This imprecision in severity assessment compromises the validity of some therapeutic recommendations; notably extrapolation of "lack of therapeutic benefit" shown in hospitalised severely ill patients on respiratory support to ambulant mildly ill patients is not warranted. Both harmonised unambiguous definitions of severity and individual patient data (IPD) meta-analyses are needed to guide and improve therapeutic recommendations in COVID-19. Achieving this goal will require improved coordination of the main stakeholders developing treatment guidelines and medicine regulatory agencies. Open science, including prompt data sharing, should become the standard to allow IPD meta-analyses.

Graphene-based nano composites and their applications. A review.

The purpose of the current review article is to present a comprehensive understanding regarding pros and cons of graphene related nanocomposites and to find ways in order to improve the performance of nanocomposites with new designs. Nanomaterials including GR are employed in industrial applications such as supercapacitors, biosensors, solar cells, and corrosion studies. The present article has been prepared in three main categories. In the first part, graphene types have been presented, as pristine graphene, graphene oxide and reduced graphene oxide. In the second part, nanocomposites with many graphene, inorganic and polymeric materials such as polymer/GR, activated carbon/GR, metal oxide/GR, metal/graphene and carbon fibre/GR have been investigated in more detail. In the third part, the focus in on the industrial applications of GR nanocomposite, including super capacitors, biosensors, solar cells, and corrosion protection studies.

Progress in utilisation of graphene for electrochemical biosensors.

This review discusses recent graphene (GR) electrochemical biosensor for accurate detection of biomolecules, including glucose, hydrogen peroxide, dopamine, ascorbic acid, uric acid, nicotinamide adenine dinucleotide, DNA, metals and immunosensor through effective immobilization of enzymes, including glucose oxidase, horseradish peroxidase, and haemoglobin. GR-based biosensors exhibited remarkable performance with high sensitivities, wide linear detection ranges, low detection limits, and long-term stabilities. Future challenges for the field include miniaturising biosensors and simplifying mass production are discussed.

Synthesis and utilisation of graphene for fabrication of electrochemical sensors.

This review summarises the most recent contributions in the fabrication of graphene-based electrochemical biosensors in recent years. It discusses the synthesis and application of graphene to the fabrication of graphene-based electrochemical sensors, its analytical performance and future prospects. An increasing number of reviews and publications involving graphene sensors have been reported ever since the first design of graphene electrochemical biosensor. The large surface area and good electrical conductivity of graphene allow it to act as an "electron wire" between the redox centres of an enzyme or protein and an electrode's surface, which make it a very excellent material for the design of electrochemical biosensors. Graphene promotes the different rapid electron transfers that facilitate accurate and selective detection of cytochrome-c, ß-nicotinamide adenine dinucleotide, haemoglobin, biomolecules such as glucose, cholesterol, ascorbic acid, uric acid, dopamine and hydrogen peroxide.

Vapour phase polymerisation of conducting and non-conducting polymers: a review.

Vapour phase polymerisation (VPP) is a well established technique in which the monomer is introduced to an oxidant-coated substrate in vapour form. Polymerisation then takes place at the oxidant vapour interface. VPP is a technique that could be used to immobilise materials to the modified electrode surface. This review article concentrates on the VPP of conducting polymers such as Polypyrrole (PPy) polythiophen (PT) and polyaniline (PANi). VPP of conducting polymers and other non-conducting polymers have extensively been investigated. This review article is divided into three main parts as given in Table of contents related to the VPP process of some important conducting polymers such as PPy, PT, PANi and Poly(3,4-ethylenedioxythiophene). A total of 181 references are cited in this review article and it attempts to look into VPP from inception of the method till present day.

Polypyrrole based amperometric and potentiometric phosphate biosensors: a comparative study B.

The preparation of two electrochemical (potentiometric and amperometric) phosphate biosensors is described and compared. Purine nucleoside phosphorylase (PNP) and xanthine oxidase (XOD) were co-immobilized via entrapment into polypyrrole (PPy) films by galvanostatic polymerization. Polypyrrole entrapment was achieved with 0.5M pyrrole by using a polymerization time of 200 s and a mole ratio of 1:8 (6.2U/mL XOD: 49.6 U/mL PNP) in amperometric phosphate biosensor. Potentiometric bi-layer biosensor PPy-NO(3)/BSA-GLA-PNP-XOD is made of an inner electropolymerized PPy-NO(3) layer and an outer layer of PNP and XOD cross-linked with a mixture of bovine serum albumen (BSA) and gultaraldehyde (GLA).The optimum conditions for potentiometric bi-layer biosensor include a polymerization time of 300 s for the inner layer at an applied current density of 0.25 mA cm(-2), a drying time of 30 min for the outer layer, pH 7, and 0.025MTris-HCl. Sensitive amperometric measurements obtained from PPy-PNP-XOD-Fe(CN)(6)(4-) biosensors were compared with those of potentiometric measurements obtained from PPy-NO(3)/BSA/GLA-PNP-XOD bi-layer biosensor. A minimum detectable concentration of 20.0 µM phosphates and a linear concentration range of 20-200 µM were achieved with potentiometric PPy-NO(3)/BSA/GLA-PNP-XOD biosensor. In comparison, a minimum detectable concentration of 10 µM and a linear concentration range of 0.1-1 mM were achieved with amperometric biosensor. The presence of uric and ascorbic acids had the least effect on the performance of the PPy-PNP-XOD-Fe(CN)(6)(4-) amperometric and PPy-NO(3)/BSA/GLA-PNP-XOD potentiometric bi-biosensors, therefore, they will not have any effect on phosphate measurement in both biosensors at levels normally present in water. PPy-NO(3)/BSA-GLA-PNP-XOD potentiometric biosensor was used to analyse phosphate in real samples.

Progress and recent advances in fabrication and utilization of hypoxanthine biosensors for meat and fish quality assessment: a review.

This review provides an update on the research conducted on the fabrication and utilization of hypoxanthine (Hx) biosensors published over the past four decades. In particular, the review focuses on progress made in the development and use of Hx biosensors for the assessment of fish and meat quality which has dominated research in this area. The various fish and meat freshness indexes that have been proposed over this period are highlighted. Furthermore, recent developments and future advances in the use of screen-printed electrodes and nanomaterials for achieving improved performances for the reliable determination of Hx in fish and meat are discussed.

Mediated xanthine oxidase potentiometric biosensors for hypoxanthine based on ferrocene carboxylic acid modified electrode.

A potentiometric enzyme electrode for detection of hypoxanthine (Hx) in fish meat is described. The sensor was developed by entrapment of xanthine oxidase (XOD) and ferrocene carboxylic acid (Fc) into polypyrrole (PPy) film during galvanostatic polymerisation film formation. The responses for Hx were obtained in 0-05 M phosphate buffer (pH 7.1) at 0.0 mV vs Ag/AgCl (3M KCl). The optimum condition for the formation of PPy-XOD-Fc film include 0.4M PPy, 6.2U/mL XOD, 40 mM Fc, polymerisation time of 200 s and applied current density of 0-5 mA cm(-2). The sensor provides a linear response to Hx in concentration range of 5-20 µM, (r=0.998) and was successfully used for determination of Hx in fish.

Fabrication of a bilayer potentiometric phosphate biosensor by cross-link immobilization with bovine serum albumin and glutaraldehyde.

Chemical cross-linking of purine nucleoside phosphorylase (PNP) and xanthine oxidase (XOD) with glutaraldehyde (GLA) and bovine serum albumin (BSA) has been used to fabricate a stable and reliable bilayer potentiometric phosphate biosensor. The bilayer arrangement consists of an inner BSA-GLA layer and an outer BSA-GLA-PNP-XOD layer. The inclusion of the inner BSA-GLA layer improves the adhesion of the outer BSA-GLA-PNP-XOD layer and ensures stability of the phosphate biosensor. Established optimum conditions for immobilization of the enzymes in the outer layer and for reliable potentiometric measurement were 4.5% v/v GLA, 6.8% w/v BSA, XOD:PNP mole ratio of 1:8, and a film drying time of 30 min. As little as 20 µM of phosphate can be detected with the BSA-GLA/BSA-GLA-XOD-PNP bilayer biosensor with a linear concentration range between 40 and 120 µM. The biosensor was very stable for 21 days, achieving a good reproducibility with a rsd of only 5.7% and, even after more than a month, the change in the initial potential value was only 10%.