Severe respiratory failure develops in some infants with bronchiolitis because of a complex pathophysiologic process involving increased airways resistance, alveolar atelectasis, muscle fatigue, and ...hypoxemia due to mismatch between ventilation and perfusion. Nasal CPAP and high-flow nasal cannula (HFNC) oxygen may improve the work of breathing and oxygenation. Although the mechanisms behind these noninvasive modalities of respiratory support are not well understood, they may help infants by way of distending pressure and delivery of high concentrations of warmed and humidified oxygen. Observational studies of varying quality have suggested that CPAP and HFNC may confer direct physiologic benefits to infants with bronchiolitis and that their use has reduced the need for intubation. No trials to our knowledge, however, have compared CPAP with HFNC in bronchiolitis. Two randomized trials compared CPAP with oxygen delivered by low-flow nasal cannula or face mask and found some improvements in blood gas results and some physiologic parameters, but these trials were unable to demonstrate a reduction in the need for intubation. Two trials evaluated HFNC in bronchiolitis (one comparing it with headbox oxygen, the other with nebulized hypertonic saline), with the results not seeming to suggest important clinical or physiologic benefits. In this article, we review the pathophysiology of respiratory failure in bronchiolitis, discuss these trials in detail, and consider how future research studies may be designed to best evaluate CPAP and HFNC in bronchiolitis.
A biofilm is an aggregation of surface-associated microbial cells that is confined in an extracellular polymeric substance (EPS) matrix. Infections caused by microbes that form biofilms are linked to ...a variety of animals, including insects and humans. Antibiotics and other antimicrobials can be used to remove or eradicate biofilms in order to treat infections. However, due to biofilm resistance to antibiotics and antimicrobials, clinical observations and experimental research clearly demonstrates that antibiotic and antimicrobial therapies alone are frequently insufficient to completely eradicate biofilm infections. Therefore, it becomes crucial and urgent for clinicians to properly treat biofilm infections with currently available antimicrobials and analyze the results. Numerous biofilm-fighting strategies have been developed as a result of advancements in nanoparticle synthesis with an emphasis on metal oxide np. This review focuses on several therapeutic strategies that are currently being used and also those that could be developed in the future. These strategies aim to address important structural and functional aspects of microbial biofilms as well as biofilms' mechanisms for drug resistance, including the EPS matrix, quorum sensing (QS), and dormant cell targeting. The NPs have demonstrated significant efficacy against bacterial biofilms in a variety of bacterial species. To overcome resistance, treatments such as nanotechnology, quorum sensing, and photodynamic therapy could be used.
In spite of the widespread use of electronic cigarettes, also known as e-cigarettes, and the proposed adverse cardiac effects of nicotine, the detrimental effects of e-cigarettes on the heart are not ...well known. This study examines the detrimental effects of e-cigarettes with nicotine at doses that yield circulating nicotine and cotinine in the ranges similar to the levels found in habitual smokers, and a high fat diet (HFD) on cardiac structure and function in a commonly used model of diet-induced obesity (DIO). C57BL/6J mice on an HFD were exposed to e-cigarette in the presence (2.4% nicotine) or absence (0% nicotine) of nicotine and saline aerosol for 12 weeks. Echocardiographic data demonstrated a decrease in left ventricular (LV) fractional shortening, LV ejection fraction, and velocity of circumferential fiber shortening (VCF) in mice treated with e-cigarette (2.4% nicotine) compared to e-cigarette (0% nicotine) or saline exposed mice. Cardiomyocytes (CMs) of mice treated with e-cigarette (2.4% nicotine) exhibited LV abnormalities, including lipid accumulation (ventricular steatosis), myofibrillar derangement and destruction, and mitochondrial hypertrophy, as revealed by transmission electron microscopy. The detrimental effects of e-cigarettes (2.4% nicotine) on cardiac structure and function was accompanied by increased oxidative stress, plasma free fatty acid levels, CM apoptosis, and inactivation of AMP-activated protein kinase and activation of its downstream target, acetyl-CoA-carboxylase. Our results indicate profound adverse effects of e-cigarettes (2.4% nicotine) on the heart in obese mice and raise questions about the safety of the nicotine e-cigarettes use.
With an objective of mapping novel low soil P (Phosphorus) tolerance loci in the non-Pup1 type donor rice line, Wazuhophek, we screened a recombinant inbred line (RIL) mapping population consisting ...of 330 lines derived from the cross Wazuhophek x Improved Samba Mahsuri (which is highly sensitive to low soil P) in a plot with low soil P for tolerance associated traits. Molecular mapping with SSR markers revealed a total of 16 QTLs (seven major and nine minor QTLs), which are associated with low soil P tolerance related traits. Interestingly, a QTL hotspot, harbouring 10 out of 16 QTLs were identified on the short arm of chromosome 8 (flanked by the makers RM22554 and RM80005). Five major QTLs explaining phenotypic variance to an extent of 15.28%, 17.25%, 21.84%, 20.23%, and 18.50%, associated with the traits, plant height, shoot length, the number of productive tillers, panicle length and yield, respectively, were located in the hotspot. Two major QTLs located on chromosome 1, associated with the traits, total biomass and root to shoot ratio, explaining 15.44% and 15.44% phenotypic variance, respectively were also identified. Complex epistatic interactions were observed among the traits, grain yield per plant, days to 50% flowering, dry shoot weight, and P content of the seed. In-silico analysis of genomic regions flanking the major QTLs revealed the presence of key putative candidate genes, possibly associated with tolerance.
The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release-inhibitory fragment catestatin ...is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished catestatin might increase the risk for hypertension. We generated Chga and humanized mice through transgenic insertion of a human CHGA haplotype in order to probe CHGA and catestatin in vivo. Chga mice displayed extreme phenotypic changes, including: (a) decreased chromaffin granule size and number; (b) elevated BP; (c) loss of diurnal BP variation; (d) increased left ventricular mass and cavity dimensions; (e) decreased adrenal catecholamine, neuropeptide Y (Npy), and ATP contents; (f) increased catecholamine/ATP ratio in the chromaffin granule; and (g) increased plasma catecholamine and Npy levels. Rescue of elevated BP to normalcy was achieved by either exogenous catestatin replacement or humanization of Chga mice. Loss of the physiological "brake" catestatin in Chga mice coupled with dysregulation of transmitter storage and release may act in concert to alter autonomic control of the circulation in vivo, eventuating in hypertension.
Ship-borne observations of spectral aerosol optical depth (AOD) have been carried out over the entire Bay of Bengal (BoB) as part of the W-ICARB cruise campaign during the period 27 December 2008–30 ...January 2009. The results reveal a pronounced temporal and spatial variability in the optical characteristics of aerosols mainly due to anthropogenic emissions and their dispersion controlled by local meteorology. The highest aerosol amount, with mean AOD500>0.4, being even above 1.0 on specific days, is found close to the coastal regions in the western and northern parts of BoB. In these regions the Ångström exponent is also found to be high (~1.2–1.25) indicating transport of strong anthropogenic emissions from continental regions, while very high AOD500 (0.39±0.07) and α380–870 values (1.27±0.09) are found over the eastern BoB. Except from the large α380–870 values, an indication of strong fine-mode dominance is also observed from the AOD curvature, which is negative in the vast majority of the cases, suggesting dominance of an anthropogenic-pollution aerosol type. On the other hand, clean maritime conditions are rather rare over the region, while the aerosol types are further examined through a classification scheme based on the relationship between α and dα. It was found that even for the same α values the fine-mode dominance is larger for higher AODs showing the strong continental influence over the marine environment of BoB. Furthermore, there is also an evidence of aerosol-size growth under more turbid conditions indicative of coagulation and/or humidification over specific BoB regions. The results obtained using OPAC model show significant fraction of soot aerosols (~6 %–8 %) over the eastern and northwestern BoB, while coarse-mode sea salt particles are found to dominate in the southern parts of BoB.
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•Thioredoxin reductase is important for the survivability of the filarial parasites.•Inhibition of TrxR results into ROS mediated apoptosis.•TrxR mediated apoptosis follows the ...ASK-1/p38 signaling cascade.•TrxR is an important drug target to eradicate lymphatic filariasis.
Inhibition of an imperative antioxidant enzyme with subsequent death is a victorious and widely accepted strategy to combat various infectious diseases. Among different antioxidant enzymes, thioredoxin reductase (TrxR) is an exclusive one. Studies have revealed that direct inhibition of TrxR by different classes of chemical moieties promptly results in the death of an organism. Especially the structural as well as biochemical modifications of the enzyme upon inhibition project serious threat towards the subject organism. Herein, an attempt was made to inhibit TrxR of filarial species by administering Auranofin, 1 chloro 2,4 dinitrobenzene (CDNB), Curcumin, and a novel carbamo dithioperoxo(thioate) derivative (4a). Our study has revealed that inhibition of TrxR resulted in the induction of the classical CED pathway of apoptosis along with the intrinsic and extrinsic pathways of apoptosis (Caspase mediated) routed through the ASK-1/p38 axis. Druggability analysis of filarial TrxR for the selected compounds was performed in silico through molecular docking studies. Therefore, this study attempts to decipher the mechanism of apoptosis induction following TrxR inhibition. The safety of those four compounds in terms of dose and toxicity was taken under consideration. Thitherto, the mechanism of TrxR mediated initiation of cell death in filarial parasite has remained undercover, and therefore, it is a maiden report on the characterization of apoptosis induction upon TrxR inhibition which will eventually help in generating effective antifilarial drugs in the future.
Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time, which also gained increased transmissibility and spread ...in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we summarize the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, providing up-to-date insights for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.
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•Presence of Thioredoxin reductase (TrxR) has been documented in the bovine filarial nematode parasite Setaria cervi.•TrxR is distributed throughout the developmental stages of the ...parasite (oocyte, microfilariae (Mf), adult).•Box-Behnken design based Response Surface Methodology was used for optimizing the extraction of TrxR.•The developed optimization model provided reasonable degree of adequacy and reproducibility.
Exploration of novel drug targets has been the major thrust area in filarial research. In this regard, identification and characterization of oxidative enzymes that play pivotal role in the survival of filarial parasite inside host are of immense importance. In this study, we are reporting the presence of an important redox regulatory enzyme, thioredoxin reductase (TrxR) in the bovine filarial parasite Setaria cervi. TrxR was found to be exists throughout the developmental stages viz. oocyte, microfilaria and adult of the parasite. Since further studies on this enzyme require adequate quantity, influential extraction parameters were optimized statistically using response surface methodology (RSM) employing a seven factors based Box-Behnken design matrix. ANOVA analysis revealed the relative importance of each parameter and a regression equation was eventually developed that could predict the specific activity (SA) of TrxR. Finally the optimized extraction conditions predicted by RSM was 6.1ml of 61.86mM buffer, pH 6.0, with extraction temperature 39.96°C for 180min in addition to 450rpm agitation and 20μl/ml of protease inhibitor. Therefore this study is going to be the maiden report depicting the identity of TrxR in filarial parasite and the optimized extraction conditions for its isolation with better kinetic efficiency.
The present study focuses on analyzing the seasonal changes in aerosol characteristics using a classification scheme proposed by Gobbi et al. (2007). This scheme is based on the correlation between ...the Ångström exponent (α) in the 440–870 nm range and the difference in α values dα = α (440–675 − α(675–870) including the size of fine-mode particles (Rf) and the fine-mode fraction (η). The classification scheme can therefore provide information on the aerosol characteristics and their modification in transit. Spectral aerosol measurements using the Microtops-II sun photometer (MT-II) have systematically been conducted in Hyderabad, India during April 2009–March 2010 and analysed to study the seasonal effects. The results reveal a seasonal dependence, i.e. the presence of fine-mode aerosols under turbid atmospheres in winter and post-monsoon, a mixture of fine and coarse aerosol types in pre-monsoon and a significant influence of marine mixed with dust air masses during the monsoon season. The identification of the aerosol source type and the modification processes are discussed along with clustered air-mass trajectory analysis. Furthermore, we have also checked the consistency of this scheme with the findings arrived from the columnar size distributions (CSDs) computed by numerical inversion of spectral AOD using King's inversion algorithm and the scatter plot between AOD and spectral α. The comparison clearly demonstrates the usefulness of the classification scheme and highlights its advantages for the monitoring and study of seasonal variation of the aerosol types and the modification processes in the atmosphere.
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