A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted periods. Hence direct inhalation to the respiratory epithelium has been investigated extensively in the past decade, and seems to be an attractive approach to eradicate and hence overcome this widespread problem. Moreover, engineering inhalation formulations wherein the antibiotics are encapsulated within nanoscale carriers could serve to overcome many of the limitations faced by conventional antibiotics, like difficulty in treating intracellular pathogens such as mycobacteria spp. and salmonella spp., biofilmassociated pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, passage through the sputum associated with disorders like cystic fibrosis and chronic obstructive pulmonary disorder, systemic side effects following oral/parenteral delivery and inadequate concentrations of antibiotic at the site of infection leading to resistance. Encapsulation of antibiotics in nanocarriers may help in providing a protective environment to combat antibiotic degradation, confer controlled-release properties, hence reducing dosing frequency, and may increase uptake via specific and non-specific targeting modalities. Hence nanotechnology combined with direct administration to the airways using commercially available delivery devices, is a highly attractive formulation strategy to eradicate microorganisms from the lower respiratory tract, which might otherwise present opportunities for multi-drug resistance

A new era of pulmonary delivery of nano-antimicrobial therapeutics to treat chronic pulmonary infections

Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted period. Hence direct inhalation to the respiratory epithelium has been investigated extensively in the past decade, and seems to be an attractive approach to eradicate and hence overcome this widespread problem. Moreover, engineering inhalation formulations wherein the antibiotics are encapsulated within nanoscale carriers could serve to overcome many of the limitations faced by conventional antibiotics, like difficulty in treating intracellular pathogens such as mycobacteria spp. and salmonella spp., biofilm-associated pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, passage through the sputum associated with disorders like cystic fibrosis and chronic obstructive pulmonary disorder, systemic side effects following oral/parenteral delivery and inadequate concentrations of antibiotic at the site of infection leading to resistance. Encapsulation of antibiotics in nanocarriers may help in providing a protective environment to combat antibiotic degradation, confer controlled-release properties, hence reducing dosing frequency, and may increase uptake via specific and non-specific targeting modalities. Hence nanotechnology combined with direct administration to the airways using commercially available delivery devices, is a highly attractive formulation strategy to eradicate microorganisms from the lower respiratory tract, which might otherwise present opportunities for multi-drug resistance

What is the effect of riskshaw noise on its driver?

Objective: Occupational hearing loss is common in the industrialized world. Road noise is a major contributor to perceived environmental noise. The objective of this study was to assess hearing loss in rickshaw drivers due to rickshaw noise.Methods: Hearing loss in rickshaw drivers and taxi drivers of Karachi who were 50 years of age or younger was estimated, with a Smith Hearing Screening (SHS) questionnaire that was modified, translated into the national language, Urdu and field tested prior to administration.Results: Interviews for 91 rickshaw drivers and 94 taxi drivers were completed. All subjects were male; mean ages were 34 and 33 years for rickshaw and taxi drivers respectively. None of the rickshaws were fitted with silencers. Rickshaw drivers were about thrice as likely to be screened as hearing impaired by the SHS questionnaire (RR 2.9, 95% confidence interval 1.6, 5.0), twice as likely to report tinnitus (RR 2.2, 95% confidence interval, 1.1, 3.3) and two and a half times as likely to have difficulty in following telephonic conversations (RR 2.4, 95% confidence interval 1.2, 4.8).CONCLUSION: There is loss of hearing and tinnitus among rickshaw drivers that could be attributed to their trade. Use of silencers by rickshaw drivers could result in less hearing loss among rickshaw drivers and less noise in the environment for the other 11 million residents in the city

Study on the pulmonary delivery system of apigenin loaded albumin nanocarriers with antioxidant activity

Background: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury (ALI). Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations consist of nanoparticles (NPs) have several advantages over other administration routes therefore this study investigated the application of apigenin loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery. Methods: Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction. The influence of dispersibility enhancers(lactose monohydrate and L-leucine) on the in vitro aerosol deposition using a next generation impactor (NGI) was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using Franz cell apparatus. The antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH˙) free radical scavenging assay. Results: The encapsulation efficiency and the drug loading was measured to be 82.61 ± 4.56% and 7.51 ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray dried BSA-Api-NPs possessed good the aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose and fine particle fraction. The aerodynamic properties was enhanced by leucine and decreased by lactose, however, the dissolution was reversely affected. The DPPH˙ assay confirmed that the antioxidant activity of encapsulated Api was preserved. Conclusion: This study provides evidence to support that albumin nanoparticles 49 are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs is a novel delivery system against lung injury with potential antioxidant activity

Real Time Wireless Air Pollution Monitoring system

Air pollution has significant influence on the concentration of constituents in the atmosphere leading to effects like global warming and acid rains. To avoid such adverse imbalances in the nature, an air pollution monitoring system is utmost important. This paper attempts to develop an effective solution for pollution monitoring using wireless sensor networks (WSN) on a real time basis namely real time wireless air pollution monitoring system. Commercially available discrete gas sensors for sensing concentration of gases l ike CO 2 , NO 2, CO and O 2 are calibrated using appropriate calibration technologies. These pre - calibrated gas sensors are then integrated with the wireless sensor motes for field deployment at the campus and the Hyderabad city using multi hop data aggregatio n algorithm. A light weight middleware and a web interface to view the live pollution data in the form of numbers and charts from the test beds was developed and made available from anywhere on the internet. Other parameters like temperature and humidity w ere also sensed along with gas concentrations to enable data analysis through data fusion techniques. Experimentation carried out using the developed wireless air pollution monitoring system under different physical conditions show that the system collects reliable source of real time fine - grain pollution data

Dry powder pulmonary delivery of cationic PGA-co-PDL nanoparticles with surface adsorbed model protein.

Pulmonary delivery of macromolecules has been the focus of attention as an alternate route of delivery with benefits such as; large surface area, thin alveolar epithelium, rapid absorption and extensive vasculature. In this study, a model protein, bovine serum albumin (BSA) was adsorbed onto cationic PGA-co-PDL polymeric nanoparticles (NPs) prepared by a single emulsion solvent evaporation method using a cationic surfactant didodecyldimethylammonium bromide (DMAB) at 2% w/w (particle size: 128.64±06.01nm and zeta-potential: +42.32±02.70mV). The optimum cationic NPs were then surface adsorbed with BSA, NP:BSA (100:4) ratio yielded 10.01±1.19μg of BSA per mg of NPs. The BSA adsorbed NPs (5mg/ml) were then spray-dried in an aqueous suspension of L-leucine (7.5mg/ml, corresponding to a ratio of 1:1.5/NP:l-leu) using a Büchi-290 mini-spray dryer to produce nanocomposite microparticles (NCMPs) containing cationic NPs. The aerosol properties showed a fine particle fraction (FPF, dae<4.46μm) of 70.67±4.07% and mass median aerodynamic diameter (MMAD) of 2.80±0.21μm suggesting a deposition in the respiratory bronchiolar region of the lungs.The cell viability was 75.76±03.55% (A549 cell line) at 156.25μg/ml concentration after 24h exposure. SDS-PAGE and circular dichroism (CD) confirmed that the primary and secondary structure of the released BSA was maintained. Moreover, the released BSA showed 78.76±1.54% relative esterolytic activity compared to standard BSA

Synthesis, biological and in silico evaluation of pure nucleobase-containing spiro (Indane-Isoxazolidine) derivatives as potential inhibitors of MDM2-p53 interaction

Nucleobase-containing isoxazolidines spiro-bonded to an indane core have been synthesized in very good yields by regio- and diastereoselective 1, 3-dipolar cycloaddition starting from indanyl nitrones and N-vinylnucleobases by using environmentally benign microwave technology. The contemporary presence of various structural groups that are individually active scaffolds of different typology of drugs, has directed us to speculate that these compounds may act as inhibitors of MDM2-p53 interaction. Therefore, both computational calculations and antiproliferative screening against A549 human lung adenocarcinoma cells and human SH-SY5Y neuroblastoma cells were carried out to support this hypothesis

COVID-19 Vaccine Hesitancy among Pregnant Women Attending Antenatal Clinics in Pakistan: A Multicentric, Prospective, Survey-Based Study

This study aimed to assess the vaccination status and factors contributing to vaccine hesitancy among pregnant women in the largest province of Pakistan. A multicentric, prospective, survey-based study using an interviewer-administered tool was conducted among pregnant women attending antenatal clinics between 1 December 2021 through 30 January 2022 across seven hospitals in Pakistan. The healthcare professionals providing care at the participating hospitals administered the survey. Four hundred and five pregnant women fully consented and completed the study. The majority of the study participants (70.6%, n = 286) were aged between 25 and 34 and had a previous successful pregnancy history. More than half of the study participants (56.0%, n = 227) did not receive COVID-19 vaccination at the time of data collection despite their family members (93.9%, n = 372) had already received at least one dose of COVID-19 vaccine. Among those who received COVID-19 vaccination (n = 173), vaccine efficacy, protection for the foetus, and risk of COVID-19-associated hospitalisation were the main driving factors for vaccine hesitancy. The majority of the unvaccinated women (77.8%, n = 182) had no intention of receiving the vaccine. However, more than two-thirds (85.7%, n = 342) consulted the doctor about COVID-19 vaccines, and most were recommended to receive COVID-19 vaccines by the doctors (80.7%, n = 280). Women were significantly more likely to be vaccinated if they had employment (odds ratio [OR] 4.47, 95% confidence interval [CI]: 2.31–8.64) compared with their counterparts who were homemakers, consulted their doctors (OR 0.12, 95% CI: 0.04–0.35), and if they did not have pregnancy-related issues (OR 6.02, 95% CI: 2.36–15.33). In this study, vaccine hesitancy was prevalent, and vaccine uptake was low among pregnant women. Education and employment did impact COVID vaccination uptake, emphasising the need for more targeted efforts to enhance the trust in vaccines

Nonconcordance between Clinical and Head CT Findings: The Specter of Overdiagnosis

Background:. It is unclear whether history and physical examination findings can predict abnormalities on head computed tomography (CT) believed to indicate increased risk of lumbar-puncture- (LP-) induced brain herniation. The objectives of this study were to (1) identify head CT findings felt to be associated with increased risk of brain herniation and (2) to assess the ability of history and physical examination to predict those findings. Methods:. Using a modified Delphi survey technique, an expert panel defined CT abnormalities felt to predict increased risk of LP-induced brain herniation. Presence of such findings on CT was compared with history and physical examination (H&P) variables in 47 patients. Results:. No H&P variable predicted “high-risk” CT; combining H&P variables to improve sensitivity led to extremely low specificity and still failed to identify all patients with high-risk CT. Conclusions:. “High-risk” CT is not uncommon in patients with clinical characteristics known to predict an absence of actual risk from LP, and thus it may not be clinically relevant. “Overdiagnosis” will be increasingly problematic as technological advances identify increasingly subtle deviations from “normal.

Early stage morphology of quench condensed Ag, Pb and Pb/Ag hybrid films

Scanning Tunneling Microscopy (STM) has been used to study the morphology of Ag, Pb and Pb/Ag bilayer films fabricated by quench condensation of the elements onto cold (T=77K), inert and atomically flat Highly Oriented Pyrolytic Graphite (HOPG) substrates. All films are thinner than 10 nm and show a granular structure that is consistent with earlier studies of QC films. The average lateral diameter, $\bar {2r}$, of the Ag grains, however, depends on whether the Ag is deposited directly on HOPG ($\bar {2r}$ = 13 nm) or on a Pb film consisting of a single layer of Pb grains ($\bar {2r}$ = 26.8 nm). In addition, the critical thickness for electrical conduction ($d_{G}$) of Pb/Ag films on inert glass substrates is substantially larger than for pure Ag films. These results are evidence that the structure of the underlying substrate exerts an influence on the size of the grains in QC films. We propose a qualitative explanation for this previously unencountered phenomenon.Comment: 11 pages, 3 figures and one tabl