Respiratory Loss Research Articles

The effect of pre-exercise alkalosis on lactate/pH regulation and mitochondrial respiration following sprint-interval exercise in humans.

Purpose: The purpose of this study was to evaluate the effect of pre-exercise alkalosis, induced via ingestion of sodium bicarbonate, on changes to lactate/pH regulatory proteins and mitochondrial function induced by a sprint-interval exercise session in humans. Methods: On two occasions separated by 1week, eight active men performed a 3 × 30-s all-out cycling test, interspersed with 20min of recovery, following either placebo (PLA) or sodium bicarbonate (BIC) ingestion. Results: Blood bicarbonate and pH were elevated at all time points after ingestion in BIC vs PLA (p < 0.05). The protein content of monocarboxylate transporter 1 (MCT1) and basigin (CD147), at 6h and 24h post-exercise, and sodium/hydrogen exchanger 1 (NHE1) 24h post-exercise, were significantly greater in BIC compared to PLA (p < 0.05), whereas monocarboxylate transporter 4 (MCT4), sodium/bicarbonate cotransporter (NBC), and carbonic anhydrase isoform II (CAII) content was unchanged. These increases in protein content in BIC vs. PLA after acute sprint-interval exercise may be associated with altered physiological responses to exercise, such as the higher blood pH and bicarbonate concentration values, and lower exercise-induced oxidative stress observed during recovery (p < 0.05). Additionally, mitochondrial respiration decreased after 24h of recovery in the BIC condition only, with no changes in oxidative protein content in either condition. Conclusion: These data demonstrate that metabolic alkalosis induces post-exercise increases in several lactate/pH regulatory proteins, and reveal an unexpected role for acidosis in mitigating the loss of mitochondrial respiration caused by exercise in the short term.

Effect of Leaf Crinkle Virus infection on Nodulation, Productivity and Yield of Black Gram Vigna mungo

In the present study, effect of Urd bean leaf crinkle virus (ULCV) infection on the nodulation, productivity and yield of black gram (Vigna mungo) was investigated. Virus infection was shown to reduce the number, size and weight of nodules in both the cultivars of black gram viz., T-9 and IPU 94-1. Primary productivity was also adversely affected due to virus infection. Gross and net production rates decreased whereas respiratory loss increased in infected leaves. Virus infection also reduced the grain yield which ranged from 6.81 to 66 percent over healthy plants when inoculated at different growth stages. Decrease in the number of pods per plant and 100 grain weight was recorded. Early inoculated plants showed higher yield loss than the mid and late inoculated ones.

Multiscale responses and recovery of soils to wildfire in a sagebrush steppe ecosystem

Ecological theory predicts a pulse disturbance results in loss of soil organic carbon and short-term respiration losses that exceed recovery of productivity in many ecosystems. However, fundamental uncertainties remain in our understanding of ecosystem recovery where spatiotemporal variation in structure and function are not adequately represented in conceptual models. Here we show that wildfire in sagebrush shrublands results in multiscale responses that vary with ecosystem properties, landscape position, and their interactions. Consistent with ecological theory, soil pH increased and soil organic carbon (SOC) decreased following fire. In contrast, SOC responses were slope aspect and shrub-microsite dependent, with a larger proportional decrease under previous shrubs on north-facing aspects compared to south-facing ones. In addition, respiratory losses from burned aspects were not significantly different than losses from unburned aspects. We also documented the novel formation of soil inorganic carbon (SIC) with wildfire that differed significantly with aspect and microsite scale. Whereas pH and SIC recovered within 37 months post-fire, SOC stocks remained reduced, especially on north-facing aspects. Spatially, SIC formation was paired with reduced respiration losses, presumably lower partial pressure of carbon dioxide (pCO2), and increased calcium availability, consistent with geochemical models of carbonate formation. Our findings highlight the formation of SIC after fire as a novel short-term sink of carbon in non-forested shrubland ecosystems. Resiliency in sagebrush shrublands may be more complex and integrated across ecosystem to landscape scales than predicted based on current theory.

Natural product preferentially targets redox and metabolic adaptations and aberrantly active STAT3 to inhibit breast tumor growth in vivo

Dysregulated gene expression programs and redox and metabolic adaptations allow cancer cells to survive under high oxidative burden. These mechanisms also represent therapeutic vulnerabilities. Using triple-negative breast cancer (TNBC) as a model, we show that compared to normal human breast epithelial cells, the TNBC cells, MDA-MB-231 and MDA-MB-468 that harbor constitutively active STAT3 also express higher glucose-6-phosphate dehydrogenase (G6PD), thioredoxin reductase (TrxR)1, NADPH, and GSH levels for survival. Present studies discover that the natural product, R001, targets these adaptation mechanisms. Treatment of TNBC cells with R001 inhibited constitutively active STAT3, STAT3-regulated gene expression, and the functions of G6PD and TrxR1. Consequently, in the TNBC, but not normal cells, R001 suppressed GSH levels, but raised NADPH levels, reflective of a loss of mitochondrial respiration and which led to reactive oxygen species (ROS) induction, all of which led to loss of viable cells and inhibition of anchorage-dependent and independent growth. R001 treatment further led to early pyroptosis and late DNA damage, cell cycle arrest, and apoptosis only in the TNBC cells. Oral administration of 5 mg/kg R001 inhibited MDA-MB-468 xenografts growth in mice, with reduced pY705-STAT3, G6PD, TrxR1, and GSH levels. R001 serves as a therapeutic entity that targets the vulnerabilities of TNBC cells to inhibit tumor growth in vivo.

Respiratory loss during late-growing season determines the net carbon dioxide sink in northern permafrost regions.

Warming of northern high latitude regions (NHL, > 50 °N) has increased both photosynthesis and respiration which results in considerable uncertainty regarding the net carbon dioxide (CO2) balance of NHL ecosystems. Using estimates constrained from atmospheric observations from 1980 to 2017, we find that the increasing trends of net CO2 uptake in the early-growing season are of similar magnitude across the tree cover gradient in the NHL. However, the trend of respiratory CO2 loss during late-growing season increases significantly with increasing tree cover, offsetting a larger fraction of photosynthetic CO2 uptake, and thus resulting in a slower rate of increasing annual net CO2 uptake in areas with higher tree cover, especially in central and southern boreal forest regions. The magnitude of this seasonal compensation effect explains the difference in net CO2 uptake trends along the NHL vegetation- permafrost gradient. Such seasonal compensation dynamics are not captured by dynamic global vegetation models, which simulate weaker respiration control on carbon exchange during the late-growing season, and thus calls into question projections of increasing net CO2 uptake as high latitude ecosystems respond to warming climate conditions.

Do larger plants produce more and better seeds and seedlings? Testing the hypothesis in a globose cactus, Wigginsia sessiliflora

In iteroparous plants, an increase in allocation to reproduction is expected with increasing plant size. The aim of this study was to analyze how plant diameter is related to total produced seed mass, seed number, mean seed mass, percentage and mean germination time (MGT), and seedling size and shape in Wigginsia sessiliflora (Hook.) D.M. Porter (Cactaceae), a slow-growing globose species from central Argentina. Plant diameter was measured in a population of 185 individuals, and fruits were collected. We counted all seeds to obtain seed number, and weighed them to get seed mass and total seed mass. Seeds were germinated and data of germination percentage and MGT were collected. We also measured the size (height and width) and shape of seedlings (height/width relationship). Fifty-four percent of the plants did not produce fruits. Plant diameter was unimodally related to fruit number, total seed mass, and seed number, i.e., intermediate-sized plants presented the highest values. Height and shape of seedlings were positively related to plant diameter. Surprisingly, plant diameter was related in a unimodal way to reproductive outputs. As plants grow, surface–volume ratio decreases, meaning that respiratory losses would be higher than the increase in photosynthetic capacity; therefore, fewer resources may be available for reproduction.

Identification and prioritization of key health hazards to workers in roadway construction

Abstract Although various rating systems have been developed to promote sustainable development in roadway construction, sustainability evaluation from the perspective of safeguarding workers’ health is currently lacking. Three approaches were used in the study to identify and prioritize key health hazards to workers in roadway construction, including bibliometric analysis, questionnaire survey and analytic hierarchy process (AHP). Bibliometric analysis indicates that submicron particles and polycyclic aromatic compounds are the primary concerns of researchers, and ergonomics also attracts some attention. A questionnaire survey was conducted among construction workers in China. The results suggest that the most frequently encountered occupational disorders by roadway construction workers are musculoskeletal disorders, heat stroke, respiratory health issues and hearing loss, and the most commonly encountered hazards are noise, dust, asphalt fumes, heat stress and some adverse working conditions. Perceptions on associations between the health hazards and disorders were obtained. Although there are some discrepancies between the AHP scores provided by two groups of professionals in China, the commonly agreed top occupational hazards include dust, asphalt fumes, noise, high-/low-temperature stresses and chronic injuries. The findings may be incorporated into rating systems for roadway construction to encourage the industry to adopt better practices for the well-being of workers.

Anatomopathological and immunohistochemical characterization of a case of granulomatous meningoencephalitis in a bovine with systemic tuberculosis / Caracterização anatomopatológica e imuno-histoquímica de um caso de meningite granulomatosa em bovino com tuberculose sistêmica

A two-year-old male bovine of Aberdeen Angus breed with anorexia, weight loss, and apathy was reported for necropsy, being diagnosed with systemic tuberculosis and tuberculoid meningitis lesions. Bovine tuberculosis was observed and confirmed through the necropsy of granulomatous lesions, mainly in the lungs and regional lymph nodes; specific staining for alcohol-acid resistant bacilli and immunohistochemistry were also performed. It should be noted that bovine tuberculosis is a zoonotic disease, with mandatory notification, caused by Mycobacterium bovis. In most cases, it has nonspecific clinical symptoms, such as respiratory signs, weight loss, and lymphadenopathy. In rare cases, alterations in the central nervous system occur. Therefore, this study aimed to report a case of granulomatous meningitis in a bovine with systemic tuberculosis through the characterization of its anatomicopathological and immunohistochemical aspects.

Loss of mitochondrial ATPase ATAD3A contributes to nonalcoholic fatty liver disease through accumulation of lipids and damaged mitochondria

Mitochondrial ATPase ATAD3A is essential for cholesterol transport, mitochondrial structure, and cell survival. However, the relationship between ATAD3A and nonalcoholic fatty liver disease (NAFLD) is largely unknown. In this study, we found that ATAD3A was upregulated in the progression of NAFLD in livers from rats with diet-induced nonalcoholic steatohepatitis and in human livers from patients diagnosed with NAFLD. We used CRISPR-Cas9 to delete ATAD3A in Huh7 human hepatocellular carcinoma cells and used RNAi to silence ATAD3A expression in human hepatocytes isolated from humanized liver-chimeric mice to assess the influence of ATAD3A deletion on liver cells with free cholesterol (FC) overload induced by treatment with cholesterol plus 58035, an inhibitor of acetyl-CoA acetyltransferase. Our results showed that ATAD3A KO exacerbated FC accumulation under FC overload in Huh7 cells and also that triglyceride levels were significantly increased in ATAD3A KO Huh7 cells following inhibition of lipolysis mediated by upregulation of lipid droplet-binding protein perilipin-2. Moreover, loss of ATAD3A upregulated autophagosome-associated light chain 3-II protein and p62 in Huh7 cells and fresh human hepatocytes through blockage of autophagosome degradation. Finally, we show the mitophagy mediator, PTEN-induced kinase 1, was downregulated in ATAD3A KO Huh7 cells, suggesting that ATAD3A KO inhibits mitophagy. These results also showed that loss of ATAD3A impaired mitochondrial basal respiration and ATP production in Huh7 cells under FC overload, accompanied by downregulation of mitochondrial ATP synthase. Taken together, we conclude that loss of ATAD3A promotes the progression of NAFLD through the accumulation of FC, triglyceride, and damaged mitochondria in hepatocytes.

Loss of ATAD3A contributes to NAFLD through the accumulation of lipids and damaged mitochondria

Mitochondrial ATPase ATAD3A is essential for cholesterol transport, mitochondrial structure, and cell survival. However, the relationship between ATAD3A and non‐alcoholic fatty liver disease (NAFLD) is largely unknown. In this study, we found that ATAD3A was upregulated in the progression of NAFLD in livers from rats with diet‐induced non‐alcoholic steatohepatitis (NASH) and in human livers with NAFLD. CRISPR‐Cas9 was used to delete ATAD3A function in Huh7 human hepatocellular carcinoma cells to assess the influence of ATAD3A deletion on liver cells with free cholesterol (FC) overload induced by treatment with cholesterol plus 58035, an inhibitor for acetyl‐CoA acetyltransferase, the enzyme converting FC to cholesterol ester. The results showed that ATAD3A KO exacerbated FC accumulation under FC overload in Huh7 cells. Triglyceride (TG) levels were also significantly increased in ATAD3A KO Huh7 cells under FC overload and control conditions via inhibited lipolysis mediated by upregulation of perilipin 2. Moreover, loss of ATAD3A downregulated mitophagy‐associated PTEN‐induced kinase 1 expression in Huh7 cells under FC overload and control conditions, suggesting that ATAD3A KO blocks mitophagy. Consistently, mitochondrial mass was increased in ATAD3A KO cells under FC overload as indicated by mitochondrial protein translocase of outer mitochondrial membrane 20 (TOM20). The results also showed that loss of ATAD3A impaired mitochondrial basal respiration and ATP production in Huh7 cells under FC overload, accompanied by downregulation of mitochondrial ATP synthase. In conclusion, loss of ATAD3A promotes the progression of NAFLD through the accumulation of FC, TG, and damaged mitochondria in hepatocytes.

Progress in Amyotrophic Lateral Sclerosis Gene Discovery: Reflecting on Classic Approaches and Leveraging Emerging Technologies.

Amyotrophic lateral sclerosis (ALS) is the most prominent motor neuron disease in humans. Its etiology consists of progressive motor neuron degeneration resulting in a rapid decline in motor function starting in the limbs or bulbar muscles and eventually fatally impairing central organs most typically resulting in loss of respiration. Pathogenic variants in 4 main genes, SOD1, TARDBP, FUS, and C9orf72, have been well characterized as causative for more than a decade now. However, these only account for a small fraction of all ALS cases. In this review, we highlight many additional variants that appear to be causative or confer increased risk for ALS, and we reflect on the technologies that have led to these discoveries. Next, we call attention to new challenges and opportunities for ALS and suggest next steps to increase our understanding of ALS genetics. Finally, we conclude with a synopsis of gene therapy paradigms and how increased understanding of ALS genetics can lead us to developing effective treatments. Ultimately, a consolidated update of the field can provide a launching point for researchers and clinicians to improve our search for ALS-related genes, defining pathogenic mechanisms, form diagnostics, and develop therapies.

Novel Control Strategy for Membrane Biofouling by Surface Loading of Aerobically and Anaerobically Applicable Photocatalytic Optical Fibers Based on a Z-Scheme Heterostructure Zr-MOFs/rGO/Ag3PO4 Photocatalyst.

The high replacement cost of modified membranes in antibiofouling application is inevitable. Here, surface-loaded photocatalytic optical fibers (POFs) were developed as antibiofouling strategies to replace membrane modification. To prepare aerobically and anaerobically applicable POFs, novel visible light-driven zirconium-based metal-organic framework/reduced graphene oxide/Ag3PO4 (Zr-MOFs/rGO/Ag3PO4) Z-scheme heterojunctions were constructed and coated on optical fibers. After loading the POFs on the membrane surface, the antibiofouling capability of the POFs was demonstrated during membrane filtration of bacteria and foulants under visible light irradiation. The disinfection efficiencies of the POFs against Escherichia coli and Staphylococcus aureus reached 95.7 and 92.4%, respectively, by aerobic treatment and 90.3 and 85.5%, respectively, by anaerobic treatment. For the inactivated bacteria, cell membrane and membrane-associated functions were destroyed, accompanied by antioxidant enzyme decomposition, loss of cell respiration and adenosine triphosphate (ATP) synthesis capacity, and leakage and oxidation of protein, lipid, potassium, DNA, and RNA. During membrane filtration of model foulants and membrane bioreactor sludge, the POFs significantly alleviated the membrane flux decline by foulant disintegration. By qualitative and quantitative detection and quenching tests of reactive species, aerobically generated •O2- and •OH and anaerobically generated •OH from POFs played dominant roles in the antibiofouling process. This work provides unique insights into membrane fouling control based on environmentally friendly and efficient photocatalytic technology.

Carbon balance in grapevines (Vitis viniferaL.): effect of environment, cultivar and phenology on carbon gain, losses and allocation

Background and Aims Measuring the carbon assimilation and respiration during vine phenology can provide an understanding of the dynamics of carbon fluxes from different organs and their relationship. Most field studies to date do not consider the respiratory losses of different plant organs and their variability under environmental, genetic and phenological changes. The aim of this study was to investigate the effect of genotype and water regime on carbon assimilation, respiration and allocation during vine phenology. Methods and Results Field trials were carried out during 2013 and 2014 to study the effect of genotype and water status on carbon assimilation, respiratory losses from leaves, shoots, fruits and roots during the vine phenological cycle, and on biomass production. Carbon respiration varied during plant phenology and represented a significant proportion of the total vine carbon assimilation. The integrated carbon respiratory loss in leaves, fruits and roots was greater in irrigated vines than in non-irrigated vines. Tempranillo recorded the highest carbon assimilation, leaf and stem respiration, as well as the highest above-ground biomass. Garnacha showed a higher root respiration loss and allocated more biomass to the permanent organs. Accumulation of above-ground biomass was influenced by plant carbon budgets during the growing season. Conclusions Vine phenology, cultivar and plant water status affected carbon assimilation, carbon loss and carbon allocation. Non-irrigated vines had a higher respiratory carbon loss in respect to the total carbon assimilation by photosynthesis. Above- and below-ground carbon fluxes were coupled during vine phenology. Significance of the Study The present work illustrates the importance of respiratory processes on the carbon balance and the relationship among different carbon balance components during vine phenology.

Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis.

Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1000-fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX expression rescued this phenotype. These studies show that NAD+ regeneration represents a major role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.

Hemolytic uremic syndrome following COVID-19; a case report

High incidence of thromboembolic diseases in patients with coronavirus disease 2019 (COVID-19) have been reported that can affect several organs ranging from cutaneous thrombosis to pulmonary embolism, stroke, coronary thrombosis or kidney infarction. There are two proposed mechanisms for these phenomena, disseminated intravascular coagulation (DIC) and endotheliopathy. We report a case of 11-year-old girl presented to the emergency department with generalized tonic colonic seizure with upward gaze which was repeated in emergency room. Respiratory distress and loss of consciousness happened which led to her intubation. Due to increased serum creatinine levels and impaired consciousness which was associated with thrombocytopenia and hemolysis, she underwent plasmapheresis three times by the diagnosis of hemolytic uremic syndrome. Additionally, antihypertensive therapy was conducted. The patient’s condition improved and was discharged with good circumstances. Two weeks later the patient returned with thromboembolism that happened in the distal part of her left hand which underwent fasciotomy and thrombectomy.

PERK is a critical metabolic hub for immunosuppressive function in macrophages.

Chronic inflammation triggers compensatory immunosuppression to stop inflammation and minimize tissue damage. Studies have demonstrated that endoplasmic reticulum (ER) stress augments the suppressive phenotypes of immune cells; however, the molecular mechanisms underpinning this process and how it links to the metabolic reprogramming of immunosuppressive macrophages remain elusive. In the present study, we report that the helper T cell 2 cytokine interleukin-4 and the tumor microenvironment increase the activity of a protein kinase RNA-like ER kinase (PERK)-signaling cascade in macrophages and promote immunosuppressive M2 activation and proliferation. Loss of PERK signaling impeded mitochondrial respiration and lipid oxidation critical for M2 macrophages. PERK activation mediated the upregulation of phosphoserine aminotransferase 1 (PSAT1) and serine biosynthesis via the downstream transcription factor ATF-4. Increased serine biosynthesis resulted in enhanced mitochondrial function and α-ketoglutarate production required for JMJD3-dependent epigenetic modification. Inhibition of PERK suppressed macrophage immunosuppressive activity and could enhance the efficacy of immune checkpoint programmed cell death protein 1 inhibition in melanoma. Our findings delineate a previously undescribed connection between PERK signaling and PSAT1-mediated serine metabolism critical for promoting immunosuppressive function in M2 macrophages.

Mitochondrial energy metabolism regulates the nutrient import activity and endocytosis of APC transporters.

Nutrient import by APC-type transporters is predicted to have a high energy demand because it depends on the plasma membrane proton gradient established by the ATP-driven proton pump Pma1. We show that Pma1 is indeed a major energy consumer and its activity is tightly linked to the cellular ATP levels. The low Pma1 activity caused by acute loss of respiration resulted in a dramatic drop in cytoplasmic pH, which triggered the downregulation of the major proton importers, the APC transporters. This regulatory system is likely the reason for the observed rapid endocytosis of APC transporters during many environmental stresses. Furthermore, we show the importance of respiration in providing ATP to maintain a strong proton gradient for efficient nutrient uptake.

Unique characteristics of ecosystem CO2 exchange in Sundarban mangrove forest and their relationship with environmental factors

Sundarban mangroves, known to be the largest single block of tidal halophytic mangrove forest globally, covers a significant portion of the world's mangroves and contributes substantially to the global mangrove carbon budget. Nevertheless, there is still a lack of long-term continuous monitoring of CO2 fluxes over this crucial ecosystem and their dynamics in response to climatic variations. This study presents the carbon balance and seasonal dynamics of this oldest and undisturbed mangrove ecosystem using quasi-continuous eddy covariance measurements from April 2012 to March 2016. These tidal forests are found to be net C sink with a mean net primary production (NEP) of 276 g C m−2 yr−1 (±35; ±1 Standard deviation amongst the four years). The NEP is partitioned into gross primary production (GPP) and ecosystem respiration indicate gross sequestration of 1581 (±152) g C m−2 yr−1 with a respiratory loss of 1305 (±184) g C m−2 yr−1. We have observed that inter- and intra-annual variations in CO2 fluxes are primarily controlled by environmental factors such as temperature, vapour pressure deficit (VPD), rainfall and photosynthetic active radiation. At the study site, the photosynthetic activity and light use efficiency decreased with an increase in temperature and VPD. Though minimal seasonal fluctuations in CO2 fluxes were observed, a strong linkage has been observed between C fluxes and satellite-derived enhanced vegetation index (MODIS EVI) during the study period. Further, the carbon assimilation rates were found to be higher under diffused sky than normal conditions due to the increased photosynthetic activity by penetration of diffused radiation within the mangrove canopies. Additionally, ecosystem productivity during the study period was higher during the wet periods than dry periods. Our findings show that ecosystem productivity rates are strongly related to temperature, vapour pressure deficit, rainfall, and radiation, implying that global warming could have a significant impact on these environmental factors and other underlying parameters (such as salinity, tidal inundation patterns etc.) and potentially reduce the C sequestration potential of these tropical mangroves of India.

THE LOSS OF SMELL (ANOSMIA) IN COVID 19 PATIENTS-TO WHAT EXTENT IT HELPS IN THE DIAGNOSIS OF COVID 19 AND FACTORS INFLUENCING ITS RECOVERY-A CLINICAL STUDY

Objectives: COVID-19 outbreak is a major pandemic affecting many people worldwide, including India. The main clinical features of this disease are cough, fever, and myalgia, and in some cases, breathing difficulty. There are many non-specific symptoms also. Loss of smell (Anosmia) is one of the non-specific clinical features in many patients. The main objective of this study is to diagnose COVID-19 disease in patients presenting with loss of smell, which helps in early isolation of the patient and prevents the spread of infection to others before the diagnosis of COVID-19 is confirmed by RTPCR, which may take 2–3 days. Another objective of this study is to know the factors that influence recovery from anosmia. Methods: Data was collected from 105 patients who attended Outpatient Department/COVID Ward in GITAM Institute of Medical Sciences and Research, Rushikonda, Visakhapatnam, from April 2020 to August 2020. The follow-up study for factors influencing the recovery of anosmia was performed in 100 patients who tested positive for COVID-19 disease with loss of smell as a presenting feature. Results: Male, to female ratio of patients with upper respiratory infection and loss of smell was 64:36. Out of 105 patients, 27 were tested positive for COVID19. Thus, the prevalence of anosmia in COVID 19 patients was 28.35%. In the follow-up study, out of 100 patients, 34 patients showed complete recovery in 2 weeks, and 42 patients showed partial recovery in 2 weeks and complete recovery in 4 weeks, and 24 patients showed only partial or no recovery within 1 month from the onset of anosmia. Conclusions: The presence of anosmia can be considered as a non-specific clinical feature in COVID-19, and early identification and isolation of the patient will help in decreasing the spread of disease to other people before the COVID-19 diagnosis is confirmed. It also suggests that recovery from loss of smell is better in middle-aged and female patients. The recovery has been delayed in patients with comorbidities and older people.

Proton motive force underpins respiration-mediated potentiation of aminoglycoside lethality in pathogenic Escherichia coli

It is well known that loss of aerobic respiration in Gram-negative bacteria can diminish the efficacy of a variety of bactericidal antibiotics, which has lead to subsequent demonstrations that the formation of reactive oxygen species (ROS) and the proton motive force (PMF) can both play a role in antibiotic toxicity. The susceptibility of Gram-negative bacteria to aminoglycoside antibiotics, particularly gentamicin, has previously been linked to both the production of ROS and the rate of antibiotic uptake that is mediated by the PMF, although the relative contributions of ROS and PMF to aminoglycoside toxicity has remained poorly understood. Herein, gentamicin was shown to elicit a very modest increase in ROS levels in an aerobically grown Escherichia coli clinical isolate. The well-characterised uncoupler 2,4-dinitrophenol (DNP) was used to disrupt the PMF, which resulted in a significant decrease in gentamicin lethality towards E. coli. DNP did not significantly alter respiratory oxygen consumption, supporting the hypothesis that this uncoupler does not increase ROS production via elevated respiratory oxidase activity. These observations support the hypothesis that maintenance of PMF rather than induction of ROS production underpins the mechanism for how the respiratory chain potentiates the toxicity of aminoglycosides. This was further supported by the demonstration that the uncoupler DNP elicits a dramatic decrease in gentamicin lethality under anaerobic conditions. Together, these data strongly suggest that maintenance of the PMF is the dominant mechanism for the respiratory chain in potentiating the toxic effects of aminoglycosides.