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1.
Front Endocrinol (Lausanne) ; 15: 1360989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38752172

RESUMO

Purpose: This feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy. Methods: Breath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS). Results: SESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis. Conclusion: This study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment.


Assuntos
Testes Respiratórios , Cetoacidose Diabética , Insulina , Humanos , Cetoacidose Diabética/metabolismo , Testes Respiratórios/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Insulina/metabolismo , Estudos de Viabilidade , Hidratação/métodos , Idoso , Biomarcadores/metabolismo , Biomarcadores/análise , Espectrometria de Massas por Ionização por Electrospray/métodos
2.
Vaccines (Basel) ; 12(5)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38793714

RESUMO

Tribal populations in India have health care challenges marked by limited access due to geographical distance, historical isolation, cultural differences, and low social stratification, and that result in weaker health indicators compared to the general population. During the pandemic, Tribal districts consistently reported lower COVID-19 vaccination coverage than non-Tribal districts. We assessed the MOMENTUM Routine Immunization Transformation and Equity (the project) strategy, which aimed to increase access to and uptake of COVID-19 vaccines among Tribal populations in Chhattisgarh and Jharkhand using the reach, effectiveness, adoption, implementation, and maintenance framework. We designed a qualitative explanatory case study and conducted 90 focus group discussions and in-depth interviews with Tribal populations, community-based nongovernmental organizations that worked with district health authorities to implement the interventions, and other stakeholders such as government and community groups. The active involvement of community leaders, targeted counseling, community gatherings, and door-to-door visits appeared to increase vaccine awareness and assuage concerns about its safety and efficacy. Key adaptations such as conducting evening vaccine awareness activities, holding vaccine sessions at flexible times and sites, and modifying messaging for booster doses appeared to encourage vaccine uptake among Tribal populations. While we used project resources to mitigate financial and supply constraints where they arose, sustaining long-term uptake of project interventions appears dependent on continued funding and ongoing political support.

3.
Vaccines (Basel) ; 11(12)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38140180

RESUMO

The COVID-19 pandemic posed substantial challenges to healthcare systems globally and severely disrupted essential health services, including routine immunization programs. In India, these disruptions were exacerbated due to the sudden emergence of the pandemic and lockdown measures, leading to mass migrations and a shortage of healthcare workers. Caregivers' concerns about routine immunization sessions further compounded the problem, resulting in a sharp increase in zero-dose children. This review paper examines India's strategies for conducting one of the world's largest COVID-19 vaccination programs while effectively restoring and perpetuating its Universal Immunization Program (UIP). The UIP played a pivotal role in sustaining immunization services during the pandemic, ultimately improving immunization coverage compared to pre-pandemic levels. India's accomplishments in this regard are highlighted through key performance indicators, the reach of immunization services, a reduction in zero-dose children, and antigen-wise coverage. The paper also discusses the successful integration of COVID-19 vaccination within the UIP framework, underscoring the significance of existing infrastructure, technology, and capacity building. India's dedication to concurrently managing routine immunization and COVID-19 vaccination showcases the adaptability and resilience of its healthcare system. India's journey serves as a global example of efficient mass immunization during challenging times, emphasizing the importance of political will, healthcare infrastructure investment, skilled healthcare workforces, and comprehensive vaccination programs. In a world grappling with the dual challenge of COVID-19 and routine immunization, India's experience provides a roadmap for strengthening healthcare systems and promoting public health as the critical agenda in challenging times.

4.
J Breath Res ; 18(1)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38029449

RESUMO

Secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) is an established technique in the field of breath analysis characterized by its short analysis time, as well as high levels of sensitivity and selectivity. Traditionally, SESI-HRMS has been used for real-time breath analysis, which requires subjects to be at the location of the analytical platform. Therefore, it limits the possibilities for an introduction of this methodology in day-to-day clinical practice. However, recent methodological developments have shown feasibility on the remote sampling of exhaled breath in Nalophan® bags prior to measurement using SESI-HRMS. To further explore the range of applications of this method, we conducted a proof-of-concept study to assess the impact of the storage time of exhaled breath in Nalophan® bags at different temperatures (room temperature and dry ice) on the relative intensities of the compounds. In addition, we performed a detailed study of the storage effect of 27 aldehydes related to oxidative stress. After 2 h of storage, the mean of intensity of allm/zsignals relative to the samples analyzed without prior storage remained above 80% at both room temperature and dry ice. For the 27 aldehydes, the mean relative intensity losses were lower than 20% at 24 h of storage, remaining practically stable since the first hour of storage following sample collection. Furthermore, the mean relative intensity of most aldehydes in samples stored at room temperature was higher than those stored in dry ice, which could be related to water vapor condensation issues. These findings indicate that the exhaled breath samples could be preserved for hours with a low percentage of mean relative intensity loss, thereby allowing more flexibility in the logistics of off-line SESI-HRMS studies.


Assuntos
Gelo-Seco , Polietilenotereftalatos , Humanos , Testes Respiratórios/métodos , Expiração , Aldeídos
5.
J Breath Res ; 17(4)2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37678210

RESUMO

Therapeutic drug monitoring (TDM) of medications with a narrow therapeutic window is a common clinical practice to minimize toxic effects and maximize clinical outcomes. Routine analyses rely on the quantification of systemic blood concentrations of drugs. Alternative matrices such as exhaled breath are appealing because of their inherent non-invasive nature. This is especially the case for pediatric patients. We have recently showcased the possibility of predicting systemic concentrations of valproic acid (VPA), an anti-seizure medication by real-time breath analysis in two real clinical settings. This approach, however, comes with the limitation of the patients having to physically exhale into the mass spectrometer. This restricts the possibility of sampling from patients not capable or available to exhale into the mass spectrometer located on the hospital premises. In this work, we developed an alternative method to overcome this limitation by collecting the breath samples in customized bags and subsequently analyzing them by secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS). A total ofn= 40 patients (mean ± SD, 11.5 ± 3.5 y.o.) diagnosed with epilepsy and taking VPA were included in this study. The patients underwent three measurements: (i) serum concentrations of total and free VPA, (ii) real-time breath analysis and (iii) off-line analysis of exhaled breath collected in bags. The agreement between the real-time and the off-line breath analysis methods was evaluated using Lin's concordance correlation coefficient (CCC). CCC was computed for ten mass spectral predictors of VPA concentrations. Lin's CCC was >0.6 for all VPA-associated features, except for two low-signal intensity isotopic peaks. Finally, free and total serum VPA concentrations were predicted by cross validating the off-line data set. Support vector machine algorithms provided the most accurate predictions with a root mean square error of cross validation of 29.0 ± 7.4 mg l-1and 3.9 ± 1.4 mg l-1for total and free VPA (mean ± SD), respectively. As a secondary analysis, we explored whether exhaled metabolites previously associated with side-effects and response to medication could be rendered by the off-line analysis method. We found that five features associated with side effects showed a CCC > 0.6, whereas none of the drug response-associated peaks reached this cut-off. We conclude that the clinically relevant free fraction of VPA can be predicted by this combination of off-line breath collection with rapid SESI-HRMS analysis. This opens new possibilities for breath based TDM in clinical settings.


Assuntos
Líquidos Corporais , Neoplasias da Mama , Humanos , Adolescente , Criança , Feminino , Ácido Valproico/uso terapêutico , Testes Respiratórios , Algoritmos
6.
Vaccines (Basel) ; 11(6)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37376411

RESUMO

Early in 2021, India embarked on the uphill journey of the COVID-19 vaccination of the largest population group in the world in a prioritized manner and in the shortest possible time. Considering the endless variety of geography and diverse socio-economic demographic, religious, and community contexts, there was a high likelihood of certain population subgroups with known vulnerabilities facing inequities, which were anticipated to be further accentuated by a digital divide. This necessitated devising solutions for such communities in a localized manner to aid the local government in breaking the service access and uptake barriers with an inclusive approach. To bridge this vital gap, the Momentum Routine Immunization Transformation and Equity project implemented a three-tiered collaboration, viz., government, non-governmental organizations (NGOs), and a wide range of vulnerable and at-risk communities, utilizing knowledge exchange and use of data. The project implemented localization strategies through the NGOs for community engagement in conjunction with government vaccination teams to universalize COVID-19 vaccination uptake up to the last mile. The collaboration resulted in reaching close to 50 million beneficiaries through messaging and facilitated the administration of more than 14 million vaccine doses, including 6.1 million doses for vulnerable and marginalized communities in 18 States and Union territories in India, along with suggesting implications for public health practice and research.

7.
Anal Chem ; 95(25): 9415-9421, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37311562

RESUMO

Dendritic cells (DCs) actively sample and present antigen to cells of the adaptive immune system and are thus vital for successful immune control and memory formation. Immune cell metabolism and function are tightly interlinked, and a better understanding of this interaction offers potential to develop immunomodulatory strategies. However, current approaches for assessing the immune cell metabolome are often limited by end-point measurements, may involve laborious sample preparation, and may lack unbiased, temporal resolution of the metabolome. In this study, we present a novel setup coupled to a secondary electrospray ionization-high resolution mass spectrometric (SESI-HRMS) platform allowing headspace analysis of immature and activated DCs in real-time with minimal sample preparation and intervention, with high technical reproducibility and potential for automation. Distinct metabolic signatures of DCs treated with different supernatants (SNs) of bacterial cultures were detected during real-time analyses over 6 h compared to their respective controls (SN only). Furthermore, the technique allowed for the detection of 13C-incorporation into volatile metabolites, opening the possibility for real-time tracing of metabolic pathways in DCs. Moreover, differences in the metabolic profile of naïve and activated DCs were discovered, and pathway-enrichment analysis revealed three significantly altered pathways, including the TCA cycle, α-linolenic acid metabolism, and valine, leucine, and isoleucine degradation.


Assuntos
Metabolômica , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização por Electrospray/métodos , Reprodutibilidade dos Testes , Metabolômica/métodos , Metaboloma , Células Dendríticas
8.
Cureus ; 15(2): e35404, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36851944

RESUMO

Background While immunization programs across the world have made considerable progress, children and communities continue to be beyond the reach of healthcare services. Globally, they are now referred to as zero-dose (ZD) children (those who have not received a single dose of diphtheria, pertussis, and tetanus-containing vaccine). Pre-COVID-19 pandemic analyses suggest that nearly 50% of vaccine-preventable deaths occur among ZD children. Two-thirds of these children live in extremely poor households suffering from multiple deprivations including lack of access to reproductive health services, water, and sanitation. Hence, ZD children have now been prioritized as a key cohort for identification and integration with the health systems as we build back from the pandemic. Methodology Extracting data from the last two National Family Health Survey (NFHS) rounds (NFHS 4, 2015-2016 and NFHS 5, 2019-2021), this study aims to ascertain the status of ZD children aged 12-23 months in India, the challenges, and the necessary action agenda going forward. Data were analyzed for equity determinants such as gender, place of residence, religion, birth order, caste, and mother's schooling. Key determinants included the change in ZD prevalence at the national, state, and district levels; variations across equity parameters and states with maximum improvements; and disparity across these indicators. A correlation analysis was also conducted to understand the nature of the association between ZD prevalence and critical maternal and child health indicators. Results The overall ZD prevalence between the two rounds was reduced by 4.1% (10.5-6.4%). A total of 26 states in the country reported a ZD prevalence of <10% in NFHS 5 compared to 18 in NFHS 4. In total, 324 districts reported a ZD prevalence of <5%, and 145 districts reported a prevalence of >10%. The equity parameters reflected a slow-footed reduction among ZD for girl children, across urban geographies, firstborn children, mothers with 12 or more years of schooling, and children in families with the highest wealth quintiles. A negative correlation accentuated between the two NFHS rounds was established between first-trimester registration, four or more antenatal visits, institutional deliveries, and ZD prevalence. Conclusions The findings point toward sustained improvement across key equity parameters, however, challenges do exist. Moreover, the impact of the pandemic on immunization programs across the globe and in India is bound to halt and reverse the progress and potentiate further inequities. It is thus imperative that continued and augmented efforts are continued to identify, integrate, and immunize ZD children, families, and communities.

9.
J Proteome Res ; 22(3): 990-995, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36812155

RESUMO

Real-time breath analysis using secondary electrospray ionization coupled with high-resolution mass spectrometry is a fast and noninvasive method to access the metabolic state of a person. However, it lacks the ability to unequivocally assign mass spectral features to compounds due to the absence of chromatographic separation. This can be overcomed by using exhaled breath condensate and conventional liquid chromatography-mass spectrometry (LC-MS) systems. In this study, to the best of our knowledge, we confirm for the first time the presence of six amino acids (GABA, Oxo-Pro, Asp, Gln, Glu, and Tyr) previously reported to be involved in response to and side effects from antiseizure medications in exhaled breath condensate and by extension in exhaled human breath. Raw data are publicly available at MetaboLights with the accession number MTBLS6760.


Assuntos
Aminoácidos , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Testes Respiratórios/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos
10.
J Public Health (Oxf) ; 45(2): 368-378, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35285932

RESUMO

BACKGROUND: Maternal health care financing is key to the smooth functioning of health systems in a country. In India, maternal health care still persists as a major public health issue. Adequate health insurance could transform the utilization of maternal health care services. Therefore, we aim to examine the health insurance policies that cover maternal health and their performance in India. METHODS: The unit-level data of social consumption on health by the National Sample Survey Organizations, conducted in India (2017-18), are used. Bivariate analysis, logistic regression and propensity scoring matching are applied. RESULTS: About 14.1% women are covered by health insurance support at the national level. Uninsured women are less likely to receive full antenatal care (ANC) services and institutional delivery. Socio-economic characteristics play a significant role in utilizing maternal health care benefits through health insurance support. CONCLUSIONS: Our study concludes that the health insurance coverage is the most significant contributor to the better utilization of full ANC and institutional delivery at the national level and hindrances in accessing them. There is a need for proactive and inclusive policy development by the Government of India to incentivize public financing through health insurance, which can shrink the challenges of public health burden and reduce the health risk.


Assuntos
Serviços de Saúde Materna , Saúde Materna , Feminino , Gravidez , Humanos , Masculino , Cuidado Pré-Natal , Seguro Saúde , Índia , Aceitação pelo Paciente de Cuidados de Saúde
11.
iScience ; 25(12): 105557, 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36479147

RESUMO

Exhaled breath contains valuable information at the molecular level and offers promising potential for precision medicine. However, few breath tests transition to routine clinical practice, partly because of the missing validation in multicenter trials. Therefore, we developed and applied an interoperability framework for standardized multicenter data acquisition and processing for breath analysis with secondary electrospray ionization-high resolution mass spectrometry. We aimed to determine the technical variability and metabolic coverage. Comparison of multicenter data revealed a technical variability of ∼20% and a core signature of the human exhaled metabolome consisting of ∼850 features, corresponding mainly to amino acid, xenobiotic, and carbohydrate metabolic pathways. In addition, we found high inter-subject variability for certain metabolic classes (e.g., amino acids and fatty acids), whereas other regions such as the TCA cycle were relatively stable across subjects. The interoperability framework and overview of metabolic coverage presented here will pave the way for future large-scale multicenter trials.

12.
Osong Public Health Res Perspect ; 13(5): 316-327, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36328236

RESUMO

The initial case of coronavirus disease 2019 (COVID-19) in India was reported on January 30, 2020, and subsequently, the number of COVID-19-infected patients surged during the first wave of April 2020 and the second wave in the same month of 2021. The government of India imposed a strict nationwide lockdown in April 2020 and extended it until May 2020. The second wave of COVID-19 in India overwhelmed the country's health facilities and exhausted its medical and paramedical workforce. This narrative review was conducted with the aim of summarizing the evidence drawn from policy documents of governmental and non-governmental organizations, as well as capturing India's COVID-19 vaccination efforts. The findings from this review cover the Indian government's vaccination initiatives, which ranged from steps taken to combat vaccine hesitancy to vaccination roadmaps, deployment plans, the use of digital health technology, vaccination monitoring, adverse effects, and innovative strategies such as Har Ghar Dastak and Jan Bhagidari Andolan (people's participation). These efforts collectively culminated in the successful administration of more than 1.8 billion doses of COVID-19 vaccines in India. This review also provides insights into other countries' responses to COVID-19 and guidance for future pandemics.

13.
iScience ; 25(10): 105080, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36157573

RESUMO

Early detection of pathogenic bacteria is needed for rapid diagnostics allowing adequate and timely treatment of infections. In this study, we show that secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) can be used as a diagnostic tool for rapid detection of bacterial infections as a supportive system for current state-of-the-art diagnostics. Volatile organic compounds (VOCs) produced by growing S. aureus or S. pneumoniae cultures on blood agar plates were detected within minutes and allowed for the distinction of these two bacteria on a species and even strain level within hours. Furthermore, we obtained a fingerprint of clinical patient samples within minutes of measurement and predominantly observed a separation of samples containing live bacteria compared to samples with no bacterial growth. Further development of this technique may reduce the time required for microbiological diagnosis and should help to improve patient's tailored treatment.

14.
Chimia (Aarau) ; 76(1-2): 127-132, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38069758

RESUMO

Real-time breath analysis by high-resolution mass spectrometry (HRMS) is a promising method to noninvasively retrieve relevant biochemical information. In this work, we conducted a head-to-head comparison of two ionization techniques: Secondary electrospray ionization (SESI) and plasma ionization (PI), for the analysis of exhaled breath. Two commercially available SESI and PI sources were coupled to the same HRMS device to analyze breath of two healthy individuals in a longitudinal study. We analyzed 58 breath specimens in both platforms, leading to 2,209 and 2,296 features detected by SESI-HRMS and by PI-HRMS, respectively. 60% of all the mass spectral features were detected in both platforms. However, remarkable differences were noted in terms of the signal-to-noise ratio (S/N), whereby the median (interquartile range, IQR) S/N ratio for SESI-HRMS was 115 (IQR = 408), whereas for PI-HRMS it was 5 (IQR = 5). Differences in the mass spectral profiles for the same samples make the inter-comparability of both techniques problematic. Overall, we conclude that both techniques are excellent for real-time breath analysis because of the very rich mass spectral fingerprints. However, further work is needed to fully understand the exact metabolic insights one can gather using each of these platforms.

15.
J Expo Sci Environ Epidemiol ; 32(2): 188-194, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34253834

RESUMO

BACKGROUND: Modeling of dose distribution of randomly moving population around a radioactive source is a complex problem. OBJECTIVE: The objective is to develop a model and solution techniques to estimate radiation absorbed dose to the population randomly moving around a radioactive source. METHODS: The problem is formulated using a second-order partial differential equation; different moments of the dose distribution function are defined related to physically realizable quantities, and solutions are obtained using standard moments methods. Alternatively, numerical simulations are performed to estimate the radiation doses using Monte Carlo approach for individual positions and random motions of the people around the source. RESULTS: A good agreement is found between average doses obtained from moments method and numerical simulations. A typical application of this model to different exposure conditions shows that the average dose is highly dependent on the population density. The study results show that average dose decreases with increase in the population density and movement area of random walker. SIGNIFICANCE: This mathematical model can be used as a rapid assessment tool by the emergency planners in resource optimization by providing quick estimates of likely exposures for triage and emergency response.


Assuntos
Modelos Teóricos , Humanos , Método de Monte Carlo , Doses de Radiação
16.
Anal Chem ; 93(47): 15579-15583, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34780695

RESUMO

Breath analysis by secondary electrospray ionization-high resolution mass spectrometry (SESI-HRMS) offers the possibility to measure comprehensive metabolic profiles. The technology is currently being deployed in several clinical settings in Switzerland and China. However, patients are required to exhale directly into the device located in a dedicated room. Consequently, clinical implementation in patients incapable of performing necessary exhalation maneuvers (e.g., infants) or immobile (e.g., too weak, elderly, or in intensive care) remains a challenge. The aim of this study was to develop a method to extend such breath analysis capabilities to this subpopulation of patients by collecting breath samples remotely (offline) and promptly (within 10 min) transfer them to SESI-HRMS for chemical analysis. We initially assessed the method in adults by comparing breath mass spectra collected offline with Nalophan bags against spectra of breath samples collected in real time. In total, 13 adults provided 176 pairs of real-time and offline measurements. Lin's concordance correlation coefficient (CCC) was used to estimate the agreement between offline and real-time analyses. Here, 1249 mass spectral features (55% of total detected) exhibited Lin's CCC > 0.6. Subsequently, the method was successfully deployed to analyze breath samples from infants (n = 16), obtaining as a result SESI-HRMS breath profiles. To demonstrate the clinical feasibility of the method, we measured in parallel other clinical variables: (i) lung function, which characterizes the breathing patterns, and (ii) nitric oxide, which is a surrogate marker of airway inflammation. As a showcase, we focused our analysis on the exhaled oxidative stress marker 4-hydroxynonenal and its association with nitric oxide and minute ventilation.


Assuntos
Testes Respiratórios , Expiração , Adulto , Idoso , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pulmão , Óxido Nítrico
17.
Chem Commun (Camb) ; 57(39): 4791-4794, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33982681

RESUMO

We report that influenza A virus infection induces changes in odor traits that could be captured by real-time high-resolution mass spectrometry in a living mouse model. The most striking changes in the volatile metabolites may be associated mostly to glyoxylate/dicarboxylate metabolism.


Assuntos
Infecções por Herpesviridae/diagnóstico , Compostos Orgânicos Voláteis/análise , Animais , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/virologia , Vírus da Influenza A/isolamento & purificação , Camundongos , Compostos Orgânicos Voláteis/metabolismo
18.
Commun Med (Lond) ; 1: 21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35602217

RESUMO

Background: Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of noninvasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient stratification by simultaneously monitoring drug-related and drug-modulated metabolites. Methods: This proof-of-principle observational study involved 93 breath measurements of 54 paediatric patients monitored over a period of 2.5 years, along with an adult's cohort of 37 patients measured in two different hospitals. Exhaled breath metabolome of epileptic patients was measured in real time using secondary electrospray ionisation-high-resolution mass spectrometry (SESI-HRMS). Results: We show that systemic ASM concentrations could be predicted by the breath test. Total and free valproic acid (VPA, an ASM) is predicted with concordance correlation coefficient (CCC) of 0.63 and 0.66, respectively. We also find (i) high between- and within-subject heterogeneity in VPA metabolism; (ii) several amino acid metabolic pathways are significantly enriched (p < 0.01) in patients suffering from side effects; (iii) tyrosine metabolism is significantly enriched (p < 0.001), with downregulated pathway compounds in non-responders. Conclusions: These results show that real-time breath analysis of epileptic patients provides reliable estimations of systemic drug concentrations along with risk estimates for drug response and side effects.

19.
Physiol Mol Biol Plants ; 26(10): 2019-2033, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33088046

RESUMO

Intracellular signaling is a critical determinant of the normal growth and development of plants. Signaling peptides, also known as peptide hormones, along with classical phytohormones, are the significant players of plant intracellular signaling. C-terminally encoded peptide (CEP), a 15-amino acid post-translationally peptide identified in Arabidopsis, plays a pivotal role in lateral root formation, nodulation, and act as long-distance root to shoot signaling molecule in N-starvation conditions. Expression of CEP gene members in Arabidopsis is perturbed by nitrogen starvation; however, not much is known regarding their role in other abiotic stress conditions. To gain a comprehensive insight into CEP biology, we identified CEP genes across diverse plant genera (Glycine max, Sorghum bicolor, Brassica rapa, Zea mays, and Oryza sativa) using bioinformatics tools. In silico promoter analysis revealed that CEP gene promoters show an abundance of abiotic stress-responsive elements suggesting a possible role of CEPs in abiotic stress signaling. Spatial and temporal expression patterns of CEP via RNA seq and microarray revealed that various CEP genes are transcriptionally regulated in response to abiotic stresses. Validation of rice CEP genes expression by qRT-PCR showed that OsCEP1, OsCEP8, OsCEP9, and OsCEP10 were highly upregulated in response to different abiotic stress conditions. Our findings suggest these CEP genes might be important mediators of the abiotic stress response and warrant further overexpression/knockout studies to delineate their precise role in abiotic stress response.

20.
Radiat Prot Dosimetry ; 190(2): 139-149, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32626895

RESUMO

Decommissioning of nuclear power plants is a multistage process involving complex operations like radiological characterization, decontamination and dismantling of plant equipment, demolition of structures, and processing and disposal of waste. Radioactive effluents released into the environment may result in exposure of population through various exposure pathways. The present study estimates the public dose due to atmospheric discharge of important radionuclides during proposed decommissioning activities of Indian Pressurized Heavy Water Reactors. This study shows that major dose contributing radionuclides are 60Co followed by 94Nb, 134Cs, 154Eu, 152Eu, 133Ba, 99Tc, 93Mo and 41Ca. It is found that infant dose is higher than adult dose and major fraction of total dose (~98%) is through ground shine and ingestion; other pathways such as inhalation and plume shine contribute only a small fraction. This study will be helpful in carrying out radiological impact assessment for decommissioning operations which is an important regulatory requirement.


Assuntos
Centrais Nucleares , Resíduos Radioativos , Radioisótopos de Cálcio , Radioisótopos de Césio/análise , Európio , Humanos , Reatores Nucleares , Alta do Paciente , Resíduos Radioativos/análise , Radioisótopos
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