Deciphering the Mechanisms and Biotechnological Implications of Nanoparticle Synthesis Through Microbial Consortia.

Nanomaterial synthesis is a growing study area because of its extensive range of uses. Nanoparticles' high surface-to-volume ratio and rapid interaction with various particles make them appealing for diverse applications. Traditional physical and chemical methods for creating metal nanoparticles are becoming outdated because they involve complex manufacturing processes, high energy consumption, and the formation of harmful by-products that pose major dangers to human health and the environment. Therefore, there is an increasing need to find alternative, cost-effective, dependable, biocompatible, and environmentally acceptable ways of producing nanoparticles. The process of synthesizing nanoparticles using microbes has become highly intriguing because of their ability to create nanoparticles of varying sizes, shapes, and compositions, each with unique physicochemical properties. Microbes are commonly used in nanoparticle production because they are easy to work with, can use low-cost materials, such as agricultural waste, are cheap to scale up, and can adsorb and reduce metal ions into nanoparticles through metabolic activities. Biogenic synthesis of nanoparticles provides a clean, nontoxic, ecologically friendly, and sustainable method using renewable ingredients for reducing metals and stabilizing nanoparticles. Nanomaterials produced by bacteria can serve as an effective pollution control method due to their many functional groups that can effectively target contaminants for efficient bioremediation, aiding in environmental cleanup. At the end of the paper, we will discuss the obstacles that hinder the use of biosynthesized nanoparticles and microbial-based nanoparticles. The paper aims to explore the sustainability of microorganisms in the burgeoning field of green nanotechnology.

Approaches to the management of haemoptysis in young people with cystic fibrosis.

Haemoptysis occurs in up to 25 % of young people with Cystic fibrosis (CF) [1]. We undertook a literature review and described the management approach to haemoptysis in CF between 2010 and 2020 at an Australian tertiary paediatric centre, The Children's Hospital Westmead, Sydney, New South Wales, using a retrospective review of the medical records which identified 67 episodes. Sixty episodes met inclusion criteria, including 31 patients. Using the US CF Foundation guidelines, episodes were classified as scant (53.3 %), moderate (38.3 %) or massive (8.3 %). Fifty-two percent of patients were female, mean age at presentation was 15.4 years (SD+/- 2.4) and 58 % were homozygous for the Fdel508 genotype. Twelve episodes (9 patients) required bronchial artery embolization (BAE). BAE was used in all cases of massive haemoptysis 5/5 (100 %), 6/23 (22 %) episodes of moderate and 1/32 (3 %) episode of scant haemoptysis as an elective procedure for recurrent haemoptysis. Our literature review and institutional experience highlights the need for up-to-date management guidelines in the management of haemoptysis in Cystic Fibrosis. Based on our experience, we provide a proposed algorithm to help guide the management of haemoptysis in CF.

Update in management of paediatric primary spontaneous pneumothorax.

Paediatric spontaneous pneumothorax (PSP) management continues to lack paediatric-specific guideline recommendations. There have been increasing reports of paediatric retrospective case studies supplemented by important well designed RCT (predominantly) adult studies. Taken together, these suggest that conservative management may have an increasing role to play in the management of PSP and that aspiration may have limited utility as a first line intervention. Our local experience, as part of a multicentre retrospective analysis and subsequent audit of management since, corroborates recent published data: it highlights an increasing trend towards conservative management in spontaneous pneumothorax with similar rates of recurrence, compared to intervention, and low use of aspiration with similarly low success rates. We have therefore updated our local practice guidelines and share these with readers. Specifically, we have removed aspiration in the management of primary spontaneous pneumothorax and reserved intervention for children who are clinically unstable or show evidence of increasing air leak irrespective of pneumothorax size. Whilst the success of this change in clinical practice will need to be reviewed in the next 5-10 years, the overall low incidence of the condition, demands a multicentre, and probably multinational, collaborative approach to allow the best chance of obtaining definitive evidence to guide clinical paediatric management.

Transition to adult care in cystic fibrosis: The challenges and the structure.

In developed countries, it is projected that there will be a 70% increase in the number of adults living with Cystic Fibrosis (CF) between 2010 and 2025. This shift in demographics highlights the importance of high-quality transition programmes with developmentally appropriate integrated health care services as the individual moves through adolescence to adulthood. Adolescents living with CF face additional and unique challenges that may have long-term impacts on their health, quality of life and life-expectancy. CF specific issues around socially challenging symptoms, body image, reproductive health and treatment burden differentiate people with CF from their peers and require clinicians to identify and address these issues during the transition process. This review provides an overview of the health, developmental and psychosocial challenges faced by individuals with CF, their guardians and health care teams considering the fundamental components and tools that are required to build a transition programme that can be tailored to suit individual CF clinics.

Glibenclamide treatment in a Cantú syndrome patient with a pathogenic ABCC9 gain-of-function variant: Initial experience.

Cantú syndrome (CS), characterized by hypertrichosis, distinctive facial features, and complex cardiovascular abnormalities, is caused by pathogenic variants in ABCC9 and KCNJ8 genes. These genes encode gain-of-function mutations in the regulatory (SUR2) and pore-forming (Kir6.1) subunits of KATP channels, respectively, suggesting that channel-blocking sulfonylureas could be a viable therapy. Here we report a neonate with CS, carrying a heterozygous ABCC9 variant (c.3347G>A, p.Arg1116His), born prematurely at 32 weeks gestation. Initial echocardiogram revealed a large patent ductus arteriosus (PDA), and high pulmonary pressures with enlarged right ventricle. He initially received surfactant and continuous positive airway pressure ventilation and was invasively ventilated for 4 weeks, until PDA ligation. After surgery, he still had ongoing bilevel positive airway pressure (BiPAP) requirement, but was subsequently weaned to nocturnal BiPAP. He was treated for pulmonary hypertension with Sildenafil, but failed to make further clinical improvement. A therapeutic glibenclamide trial was commenced in week 11 (initial dose of 0.05 mg-1 kg-1 day-1 in two divided doses). After 1 week of treatment, he began to tolerate time off BiPAP when awake, and edema improved. Glibenclamide was well tolerated, and the dose was slowly increased to 0.15 mg-1 kg-1 day-1 over the next 12 weeks. Mild transient hypoglycemia was observed, but there was no cardiovascular dysfunction. Confirmation of therapeutic benefit will require studies of more CS patients but, based on this limited experience, consideration should be given to glibenclamide as CS therapy, although problems associated with prematurity, and complications of hypoglycemia, might limit outcome in critically ill neonates with CS.

Disease caused by non-tuberculous mycobacteria in children with cystic fibrosis.

Non-tuberculous mycobacterial (NTM) (especially M. abscessus complex) infections pose a considerable challenge in the management of lung disease in patients with cystic fibrosis (CF). The apparent increase in prevalence is likely multifactorial. Emergent evidence of patient-to-patient transmission and isolation of highly resistant strains is a concern for all CF centers around the world. Treatment is often long and burdensome with multiple agents. Treatment side effects are frequent and can cause significant morbidity. Although consensus guidelines provide some direction, many units are faced with the challenges of: finding drug combinations for highly resistant strains; dealing with interruptions of treatment; discussing additional facilitating procedures in the form of gastrostomy and long-term vascular access devices; as well as supporting families emotionally and psychologically through the process.

Respiratory manifestations and management in children with Common Variable Immunodeficiency.

Common variable immunodeficiency is an antibody deficiency that usually presents in childhood with recurrent sino-pulmonary infections. Diagnostic delay is frequent and thus respiratory morbidity is common, ranging from recurrent suppurative bronchitis to bronchiectasis. Immunoglobulin replacement therapy is the mainstay of treatment, whilst prophylactic antibiotic therapy and muco-ciliary clearance are additional treatment options. This review examines the diagnosis and management of respiratory issues in children with CVID.

Discovery of 1H-pyrazolo[3,4-b]pyridines as potent dual orexin receptor antagonists (DORAs).

Compound rac-1 was identified by high throughput screening. Here we report SAR studies and MedChem optimization towards the highly potent dual orexin receptor antagonists (S)-2 and (S)-3. Furthermore, strategies to overcome the suboptimal physicochemical properties are highlighted and the pharmacokinetic profiles of representative compounds is presented.

Exercise-induced respiratory symptoms not due to asthma.

This manuscript describes two interesting patients who had exercise-induced symptoms that unmasked an alternative underlying diagnosis. The first is an 8-year-old boy who was treated for asthma all his life but really had exercise-induced stridor (labelled as wheeze) causing significant exercise limitation, which was due to a double aortic arch with the right arch compressing the trachea. The second case describes the diagnosis of vocal cord dysfunction in a 13-year-old anxious high achiever. He also initially had exercise-induced symptoms treated as exercise-induced wheeze but again had a stridor due to vocal cord dysfunction. Both these cases demonstrate the importance of detailed history including during exercise, which can unmask alternative diagnosis. Another important message is that if there is no response to bronchodilator treatment with absence of typical signs and symptoms of asthma, alternative diagnosis should be considered.

Effect of general anesthesia on pulmonary function and clinical status on children with cystic fibrosis.

INTRODUCTION: Children with cystic fibrosis (CF) receive general anesthesia (GA) for a variety of different procedures. Historical studies assessing risk of GA report a high risk of morbidity. There is a paucity of data evaluating the risk of currently available anesthetic agents. The aim of this study was to assess the effect of GA on clinical status and lung function on children with CF. METHODS: Children with CF aged 8-18 years admitted for IV antibiotic treatment for a pulmonary exacerbation were invited to participate. Spirometry, forced oscillation technique (FOT), and CF clinical score (CFCS) were measured pre-GA, at 24 and 48 h post-GA. The nature and duration of the GA were recorded. RESULTS: Twenty two patients were recruited of which 19 patients (mean age 11.4 years, range 8-18 years, 12 male) required GA. Typically, either propofol or sevoflurane was used as induction agent and maintenance of anesthesia was with sevoflurane. A laryngeal mask was used in most cases. FEV1 mean (±SD) pre-GA was 75.1% (±23.46) which decreased at 24 h to 74.8 (±23.0) and at 48 h to 74.3 (±20.5). FOT resistance and reactance decreased at 24 and 48 h from baseline. Changes in spirometry and CFCS were not statistically significant. Two adverse events were observed in this cohort. CONCLUSION: The results suggest that children with mild to moderate CF lung disease do not experience significant deterioration in central or peripheral airway function following GA. The low rate of complications suggests an improved level of safety for children with CF with modern anesthesia compared with historical published data.

Factors influencing treatment response of pulmonary exacerbation in children with cystic fibrosis.

BACKGROUND: Pulmonary exacerbations in cystic fibrosis (CF) significantly impact morbidity and mortality. This study aimed to assess treatment response rates and identify contributing factors towards treatment response. METHODS: In this single-center, retrospective, longitudinal study spanning four years, we analyzed all pulmonary exacerbation admissions. We compared lung function at baseline, admission, end of treatment, and 6-week follow-up. Treatment response was defined as ≥95% recovery of baseline FEV1%. RESULTS: There were 78 children who required a total of 184 admissions. The mean duration of treatment was 14.9±2.9 days. FEV1% returned to 95% of baseline in 59% following treatment. The magnitude of the decline in lung function on admission in children who did not respond to treatment was 21.7±15.2% while the decline in children who responded to treatment was 8.3±9.4%, P<0.001. Children who experienced a decline in FEV1% greater than 40% exhibited an 80% reduced likelihood of returning to their baseline values (OR -0.8, 95% CI -0.988; -0.612). Similarly, those with FEV1% reductions in the ranges of 30-39% (OR -0.63, 95% CI -0.821; -0.439), 20-29% (OR -0.52, 95% CI -0.657; -0.383), and 10-19% (OR -0.239, 95% CI -0.33; -0.148) showed progressively lower odds of returning to baseline. Fourty-eight children required readmission within 7.7±5.4 months, children who responded to treatment had a longer time taken to readmission (8.9±6.4 months) versus children who did not respond to treatment (6.4±3.5 months), (OR: -0.20, 95% CI -0.355; -0.048). CONCLUSIONS: A greater decline in lung function on admission and readmission within 6 months of the initial admission predicts non-response to treatment. This highlights the importance of re-evaluating follow-up strategies following discharge.

The changing epidemiology of pulmonary infection in children and adolescents with cystic fibrosis: an 18-year experience.

The impact of evolving treatment regimens, airway clearance strategies, and antibiotic combinations on the incidence and prevalence of respiratory infection in cystic fibrosis (CF) in children and adolescents remains unclear. The incidence, prevalence, and prescription trends from 2002 to 2019 with 18,339 airway samples were analysed. Staphylococcus aureus [- 3.86% (95% CI - 5.28-2.43)] showed the largest annual decline in incidence, followed by Haemophilus influenzae [- 3.46% (95% CI - 4.95-1.96)] and Pseudomonas aeruginosa [- 2.80%95% CI (- 4.26-1.34)]. Non-tuberculous mycobacteria and Burkholderia cepacia showed a non-significant increase in incidence. A similar pattern of change in prevalence was observed. No change in trend was observed in infants < 2 years of age. The mean age of the first isolation of S. aureus (p < 0.001), P. aeruginosa (p < 0.001), H. influenza (p < 0.001), Serratia marcescens (p = 0.006) and Aspergillus fumigatus (p = 0.02) have increased. Nebulised amikacin (+ 3.09 ± 2.24 prescription/year, p = 0.003) and colistin (+ 1.95 ± 0.3 prescriptions/year, p = 0.032) were increasingly prescribed, while tobramycin (- 8.46 ± 4.7 prescriptions/year, p < 0.001) showed a decrease in prescription. Dornase alfa and hypertonic saline nebulisation prescription increased by 16.74 ± 4.1 prescriptions/year and 24 ± 4.6 prescriptions/year (p < 0.001). There is a shift in CF among respiratory pathogens and prescriptions which reflects the evolution of cystic fibrosis treatment strategies over time.

Microbial Fuel Cell-Based Biosensors and Applications.

The sustainable development of human society in today's high-tech world depends on some form of eco-friendly energy source because existing technologies cannot keep up with the rapid population expansion and the vast amounts of wastewater that result from human activity. A green technology called a microbial fuel cell (MFC) focuses on using biodegradable trash as a substrate to harness the power of bacteria to produce bioenergy. Production of bioenergy and wastewater treatment are the two main uses of MFC. MFCs have also been used in biosensors, water desalination, polluted soil remediation, and the manufacture of chemicals like methane and formate. MFC-based biosensors have gained a lot of attention in the last few decades due to their straightforward operating principle and long-term viability, with a wide range of applications including bioenergy production, treatment of industrial and domestic wastewater, biological oxygen demand, toxicity detection, microbial activity detection, and air quality monitoring, etc. This review focuses on several MFC types and their functions, including the detection of microbial activity.

Recent advances and challenges in the utilization of nanomaterials in transesterification for biodiesel production.

Due to diminishing fossil fuel supplies and rising energy needs, there has been an ever-increasing demand for renewable energy sources. The available renewable energy resources, such as solar, wind, hydropower, and biofuels, provide a new way of supplying the world's energy needs. Biofuels stand out among them because they are sustainable and have the potential to bring the idea of a global bioeconomy to life. As a result of their production of biofuels like biomethane, biohydrogen, and biodiesel, atmospheric CO2 is being fixed, eventually lowering the world's carbon footprint. Current developments in the production of bioenergy have concentrated on producing biodiesel among other biofuels. Biodiesel is being produced from a variety of feedstocks using a number of processes, including transesterification, micro-emulsion, direct mixing, and pyrolysis. The most popular method among these is transesterification, which makes use of a variety of catalysts. As a result of the development of nanotechnology, nanocatalysts with desirable properties, such as increased catalytic activity, increased surface area, and superior thermal stability, have been made and modified. In this review, various nanocatalyst types and manufacturing processes are examined in relation to transesterification. It explores how crucial nanocatalysts are in boosting biodiesel production, highlights potential barriers, and makes recommendations for their widespread use in the future.

Respiratory problems in children with Down syndrome.

Down syndrome is associated with a significant health burden, which is particularly apparent in young children who will frequently present with cardiac and respiratory problems. Respiratory presentations include problems related to structural abnormalities of the airways and lungs, glue ears, recurrent lower respiratory tract infections and obstructive sleep apnoea. These conditions are readily identifiable and able to be treated. An awareness of the breadth of respiratory problems and a plan to monitor patients with Down syndrome for their development has the potential to improve outcomes.

Biologically Derived Gold Nanoparticles and Their Applications.

Nanotechnology is a rapidly evolving discipline as it has a wide variety of applications in several fields. They have been synthesized in a variety of ways. Traditional processes such as chemical and physical synthesis have limits, whether in the form of chemical contamination during synthesis operations or in subsequent applications and usage of more energy. Over the last decade, research has focused on establishing easy, nontoxic, clean, cost-effective, and environmentally friendly techniques for nanoparticle production. To achieve this goal, biological synthesis was created to close this gap. Biosynthesis of nanoparticles is a one-step process, and it is ecofriendly in nature. The metabolic activities of biological agents convert dissolved metal ions into nanometals. For biosynthesis of metal nanoparticles, various biological agents like plants, fungus, and bacteria are utilized. In this review paper, the aim is to provide a summary of contemporary research on the biosynthesis of gold nanoparticles and their applications in various domains have been discussed.

Integrating Human Waste with Microbial Fuel Cells to Elevate the Production of Bioelectricity.

Due to the continuous depletion of natural resources currently used for electricity generation, it is imperative to develop alternative energy sources. Human waste is nowadays being explored as an efficient source to produce bio-energy. Human waste is renewable and can be used as a source for an uninterrupted energy supply in bioelectricity or biofuel. Annually, human waste such as urine is produced in trillions of liters globally. Hence, utilizing the waste to produce bioenergy is bio-economically suitable and ecologically balanced. Microbial fuel cells (MFCs) play a crucial role in providing an effective mode of bioelectricity production by implementing the role of transducers. MFCs convert organic matter into energy using bio-electro-oxidation of material to produce electricity. Over the years, MFCs have been explored prominently in various fields to find a backup for providing bioenergy and biofuel. MFCs involve the role of exoelectrogens which work as transducers to convert the material into electricity by catalyzing redox reactions. This review paper demonstrates how human waste is useful for producing electricity and how this innovation would be beneficial in the long term, considering the current scenario of increasing demand for the supply of products and shortages of natural resources used to produce biofuel and bioelectricity.

Use of biomass-derived biochar in wastewater treatment and power production: A promising solution for a sustainable environment.

Over the past few years, we are witnessing the advent of a revolutionary bioengineering technology in biochar production and its application in waste treatment and an important component in power generation devices. Biochar is a solid product, highly rich in carbon, whose adsorption properties are ideal for wastewater decontamination. Due to its high specific surface area to volume ratio, it can be utilized for many environmental applications. It has diverse applications in various fields. This review focuses on its various applications in wastewater treatment to remove various pollutants such as heavy metals, dyes, organic compounds, and pesticides. This review also highlights several energy-based applications in batteries, supercapacitors, and microbial fuel cells. It described information about the different feedstock materials to produce LB-derived biochar, the various conditions for the production process, i.e., pyrolysis and the modification methods of biochar for improving properties required for wastewater treatment. The present review helps the readers understand the importance of biochar in wastewater treatment and its application in power generation in terms of batteries, supercapacitors, microbial fuel cells, applications in fuel production, pollutant and dye removal, particularly the latest development on using LB-derived biochar. This review also highlights the economic and environmental sustainability along with the commercialization of biochar plants. It also describes various pyrolytic reactors utilized for biochar production.

Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action.

Mutations in MEK1/2 have been described as a resistance mechanism to BRAF/MEK inhibitor treatment. We report the discovery of a novel ATP-competitive MEK1/2 inhibitor with efficacy in wildtype (WT) and mutant MEK12 models. Starting from a HTS hit, we obtained selective, cellularly active compounds that showed equipotent inhibition of WT MEK1/2 and a panel of MEK1/2 mutant cell lines. Using a structure-based approach, the optimization addressed the liabilities by systematic analysis of molecular matched pairs (MMPs) and ligand conformation. Addition of only three heavy atoms to early tool compound 6 removed Cyp3A4 liabilities and increased the cellular potency by 100-fold, while reducing log P by 5 units. Profiling of MAP855, compound 30, in pharmacokinetic-pharmacodynamic and efficacy studies in BRAF-mutant models showed comparable efficacy to clinical MEK1/2 inhibitors. Compound 30 is a novel highly potent and selective MEK1/2 kinase inhibitor with equipotent inhibition of WT and mutant MEK1/2, whose drug-like properties allow further investigation in the mutant MEK setting upon BRAF/MEK therapy.