Recent Advances in the Detection of Food Toxins Using Mass Spectrometry.

Edibles are the only source of nutrients and energy for humans. However, ingredients of edibles have undergone many physicochemical changes during preparation and storage. Aging, hydrolysis, oxidation, and rancidity are some of the major changes that not only change the native flavor, texture, and taste of food but also destroy the nutritive value and jeopardize public health. The major reasons for the production of harmful metabolites, chemicals, and toxins are poor processing, inappropriate storage, and microbial spoilage, which are lethal to consumers. In addition, the emergence of new pollutants has intensified the need for advanced and rapid food analysis techniques to detect such toxins. The issue with the detection of toxins in food samples is the nonvolatile nature and absence of detectable chromophores; hence, normal conventional techniques need additional derivatization. Mass spectrometry (MS) offers high sensitivity, selectivity, and capability to handle complex mixtures, making it an ideal analytical technique for the identification and quantification of food toxins. Recent technological advancements, such as high-resolution MS and tandem mass spectrometry (MS/MS), have significantly improved sensitivity, enabling the detection of food toxins at ultralow levels. Moreover, the emergence of ambient ionization techniques has facilitated rapid in situ analysis of samples with lower time and resources. Despite numerous advantages, the widespread adoption of MS in routine food safety monitoring faces certain challenges such as instrument cost, complexity, data analysis, and standardization of methods. Nevertheless, the continuous advancements in MS-technology and its integration with complementary techniques hold promising prospects for revolutionizing food safety monitoring. This review discusses the application of MS in detecting various food toxins including mycotoxins, marine biotoxins, and plant-derived toxins. It also explores the implementation of untargeted approaches, such as metabolomics and proteomics, for the discovery of novel and emerging food toxins, enhancing our understanding of potential hazards in the food supply chain.

Stimuli-responsive magnetic materials: impact of spin and electronic modulation.

Addressing molecular bistability as a function of external stimuli, especially in spin-crossover (SCO) and metal-to-metal electron transfer (MMET) systems, has seen a surge of interest in the field of molecule-based magnetic materials due to their enormous potential in various technological applications such as molecular spintronics, memory and electronic devices, switches, sensors, and many more. The fine-tuning of molecular components allow the design and synthesis of materials with tailored properties for these vast applications. In this Feature Article, we discuss a part of our research work into this broad topic, pertaining to the recent discoveries in the field of switchable molecular magnetic materials based on SCO and MMET systems, along with some historical background of the area and related accomplishments made in recent years.

Dietary antioxidants and vascular calcification: From pharmacological mechanisms to challenges.

Vascular calcification (VC), an actively regulated process, has been recognized as an independent and strong predictor of cardiovascular disease (CVD) and mortality worldwide. Diet has been shown to have a major role in the progression of VC. Oxidative stress (OS), a common pro-calcification factor, is closely related to VC, and evidence strongly suggests that dietary antioxidants directly prevent VC. Herein, we provided an overview of OS and its key role in VC and underlined the mechanisms of harmful effects of OS on VC. Furthermore, we introduced dietary antioxidants, and discussed about surrounding the challenges of dietary antioxidants in VC management. This review will benefit future research about the effects of dietary antioxidants on cardiovascular health.

An observational study on the timing of intubation and outcome in COVID-19 ARDS patients who were treated with high flow nasal oxygen prior to invasive mechanical ventilation: A time series analysis (InOutHFNO trial).

Background and Aims: Prolonged high flow nasal oxygen (HFNO) application might delay intubation and increase mortality in acute hypoxemic respiratory failure (AHRF) patients. Intubation in coronavirus disease 2019 (COVID-19) AHRF (CAHRF) patients 24 to 48 hours after HFNO initiation has been associated with increased mortality in previous studies. This cut-off period is variable in previous studies. A time series analysis could reflect more robust data on outcome in relation to HFNO duration before intubation in CAHRF. Methods: A retrospective study was conducted at 30-bedded ICU of a tertiary care teaching hospital from July 2020 to August 2021. The study cohort comprised 116 patients who required HFNO and were subsequently intubated following HFNO failure. A time series analysis of patient outcomes on each day of HFNO application prior to invasive mechanical ventilation (IMV) was done. Results: ICU and hospital mortality was 67.2%. Beyond day 4 of HFNO application, there was a trend towards increased risk-adjusted ICU and hospital mortality for each day delay in intubation of CAHRF patients on HFNO [OR 2.718; 95% CI 0.957-7.721; P 0.061]. This trend was maintained till day 8 of HFNO application, after which there was 100% mortality. Taking day four as a cut-off in the timeline of HFNO application, we have observed an absolute mortality benefit of 15% with early intubation despite a higher APACHE-IV score than the late intubation group. Conclusion: IMV beyond the 4th day of HFNO initiation in CAHRF patients increases mortality.

An Observational Study on Patients With COVID-19 Infection Admitted to the Intensive Care Unit With Respect to Their Vaccination Status.

Background SARS-CoV-2 (COVID-19) created unprecedented recurrent waves of pandemic globally. Apart from COVID-19-appropriate behavior, vaccinating the population was proposed to be the most effective measure to control these outbreaks. However, the outcomes of vaccinated patients admitted to the intensive care unit (ICU) and their comparison with unvaccinated counterparts, especially in developing countries, have not been extensively studied. Materials and methods Our study examined consecutive patients with positive RT-PCR for COVID-19 admitted to the ICU from August 1, 2021, to July 31, 2022. Prior vaccination status and its relation to demographics, disease severity, mortality, and length of stay were analyzed. Results Among 436 patients admitted to the ICU, 76 (15.4%) were unvaccinated and 369 (84.6%) were vaccinated against COVID-19. Vaccinated patients were significantly older and hypertensive, and had comparatively less severity of illness than unvaccinated patients. Crude ICU and hospital mortality were significantly lower among vaccinated patients than unvaccinated patients (15.2% versus 25.4% and 16% versus 22.3%, respectively; P<0.05). Furthermore, risk-adjusted multivariate analysis demonstrated a strong but statistically nonsignificant inverse association between vaccination status and ICU mortality (odds ratio (OR)=0.540, 95% confidence interval (CI)=0.290-1.006, P=0.052). Conclusion In severe COVID-19-infected patients who required admission to the ICU, the majority were vaccinated. However, the severity of illness and hospital mortality was significantly lower among vaccinated patients with breakthrough infections.

Impact of Counteranion on Reversible Spin-State Switching in a Series of Cobalt(II) Complexes Containing a Redox-Active Ethylenedioxythiophene-Based Terpyridine Ligand.

The self-assembly of a redox-active ethylenedioxythiophene (EDOT)-terpyridine-based tridentate ligand and cobalt(II) unit with different counteranions has led to a series of new cobalt(II) complexes [Co(L)2](X)2 (X = BF4 (1), ClO4 (2), and BPh4 (3)) (L = 4'-(3,4-ethylenedioxythiophene)-2,2':6',2″-terpyridine). The impact of various counteranions on stabilization and spin-state switching of the cobalt(II) center was explored through detailed magneto-structural investigation using variable temperature single-crystal X-ray diffraction, magnetic, spectroscopic, electrochemical, and spectroelectrochemical studies. All three complexes 1-3 consisted of an isostructural dicationic distorted octahedral CoN6 coordination environment offered by the two L ligands in a bis-meridional fashion and BF4-, ClO4-, and BPh4- as a counteranion, respectively. Complex 2 with ClO4- counteranion showed a reversible, gradual, and nearly complete spin-state switching between low-spin (LS) (S = 1/2) and high-spin (HS) (S = 3/2) states, while an incomplete spin-state switching behavior was observed for complexes 1 (BF4-) and 3 (BPh4-) in the measured temperature range of 350-2 K. The non-covalent cation-anion interactions played a significant role in stabilizing the spin-state in 1-3. Additionally, complexes 1-3 also exhibited interesting redox-stimuli-based reversible paramagnetic HS cobalt(II) (S = 3/2) to diamagnetic LS cobalt(III) (S = 0) conversion, offering an alternate way to switch the magnetic properties.

Magnesium and Zinc Intake Ratio Mediates the Increase of Coronary Artery Calcification through Upregulating Interleukin 6.

The relation between dietary minerals and coronary artery calcification (CAC) has been emphasized. However, the effects of multiple dietary minerals on CAC progression remain unclear. This study Investiagetes the effect of combined dietary mineral intake on the progression of CAC. We analyzed a population-based cohort with 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores were measured at baseline and subsequent follow-up examinations by Multi-detector computed tomography (MDCT) scans with Agatston scores. Then, the progression of CAC was defined through increased CAC scores in the follow-up from the baseline exam. The results revealed that the dietary intake of individual minerals did not show significant differences across CAC progression vs non progression groups. However, participants with CAC progression had an increased Magnesium (Mg):Zinc (Zn) ratio (P < 0.05). This effect was significant in logistic regression after adjusting for multiple established risk factors of CAC progression (OR 1.050; 95% CI 1.003, 1.099; P = 0.038). The increased risk of CAC associated with Mg/Zn was mediated through an increase level of IL-6, which increased with association to the Mg: Zn ratio. In conclusion, the dietary of Mg: Zn ratio, rather than individual mineral intake is associated with increased risk of CAC progression, which is mediated by pro-calcific IL-6. Therefore, the consideration of dietary intake of Zn and Mg together would play a cardio protective role among CAC patients.

DMAP Catalyzed Domino Rauhut-Currier Cyclization Reaction between Alkylidene Pyrazolones and Nitro-olefins: Access to Tetrahydropyrano[2,3-c]pyrazoles.

Herein, we employ unsaturated pyrazolones in the Rauhut-Currier reaction for the first time. A domino Rauhut-Currier cyclization reaction has been developed between unsaturated pyrazolones and nitro-olefins. The trisubstituted tetrahydropyrano[2,3-c]pyrazoles were obtained in moderate to high yields with excellent diastereoselectivities. A few applications including a synthesis of disubstituted tetrahydropyrano[2,3-c]pyrazole have been demonstrated. A preliminary catalytic asymmetric version of this process was also studied with chiral DMAP catalysts.

A Comparative Study on the Outcomes of Mechanically Ventilated COVID-19 vs Non-COVID-19 Patients with Acute Hypoxemic Respiratory Failure.

BACKGROUND: Due to the coronavirus disease-2019 (COVID-19) pandemic, there has been a surge of patients requiring mechanical ventilation over a short period of time. The morbidity and mortality outcome in these patients have been variably reported in the published literature. Comparative analyses of ventilated COVID-19 and non-COVID-19 patients during the same time period have been lacking. MATERIALS AND METHODS: Prospective data for each mechanically ventilated patient was collected from both COVID-19 and non-COVID ICU for a period of 8 months. Their demographic details and disease severity scores were included. Risk-adjusted outcomes across two groups were analyzed using multivariable regression methods. RESULTS: Crude ICU and hospital mortality were similar in COVID-19- and non-COVID-19 ventilated groups (43.8 vs 40% and 43.8 vs 41.1%, respectively; p >0.05). After risk adjustment for the severity of illness by APACHE IV, no significant differences were observed in ICU mortality (OR 1.498; 95% CI 0.669-3.327; p =0.328) and hospital mortality (OR 1.574; 95% CI 0.707-3.504; p =0.267). However, mechanically ventilated COVID-19 patients had increased ICU stay (OR 6.261; 95% CI 3.778-8.744; p <0.001) as well as prolonged ventilatory support (OR 4.358; 95% CI 2.910-7.424; p <0.001) when compared to non-COVID-19 patients. CONCLUSION: In mechanically ventilated patients, no significant differences in terms of mortality were noted between COVID-19 and non-COVID-19 patients. Mechanically ventilated COVID-19 patients had longer ICU stay and more number of days on ventilation. HOW TO CITE THIS ARTICLE: Todi S, Ghosh S. A Comparative Study on the Outcomes of Mechanically Ventilated COVID-19 vs Non-COVID-19 Patients with Acute Hypoxemic Respiratory Failure. Indian J Crit Care Med 2021;25(12):1377-1381.

Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis.

PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it. METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam. RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression. CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.

Role of gut microbiota-derived metabolites on vascular calcification in CKD.

The interaction between gut microbiota and the host has gained widespread concern. Gut microbiota not only provides nutrients from the ingested food but also generates bioactive metabolites and signalling molecules to impact host physiology, especially in chronic kidney disease (CKD). The development of CKD, accompanied by changed diet and medication, alters the gut flora and causes the effect in distant organs, leading to clinical complications. Vascular calcification (VC) is an actively regulated process and a high prevalence of VC in CKD has also been linked to an imbalance in gut microbiota and altered metabolites. In this review, we focused on gut microbiota-derived metabolites involved in VC in CKD and explained how these metabolites influence the calcification process. Correcting the imbalance of gut microbiota and regulating microbiota-derived metabolites by dietary modification and probiotics are new targets for the improvement of the gut-kidney axis, which indicate innovative treatment options of VC in CKD.

Warfarin Accelerates Aortic Calcification by Upregulating Senescence-Associated Secretory Phenotype Maker Expression.

Warfarin, a vitamin K antagonist (VKA), is known to promote arterial calcification (AC). In the present study, we conducted a case-cohort study within the Multi-Ethnic Study of Atherosclerosis (MESA); 6655 participants were included. From MESA data, we found that AC was related to both age and vitamin K; furthermore, the score of AC increased with SASP marker including interlukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) rising. Next, a total of 79 warfarin users in our center developed significantly more calcified coronary plaques as compared to non-VKA users. We investigated the role of warfarin in phosphate-induced AC in different ages by in vitro experimental study. Furthermore, dose-time-response of warfarin was positively correlated with AC score distribution and plasma levels of the SASP maker IL-6 among patients < 65 years, but not among patients ≥ 65 years. In addition, in vitro research suggested that warfarin treatment tended to deteriorate calcification in young VSMC at the early stage of calcification. Our results suggested that aging and warfarin-treatment were independently related to increased AC. Younger patients were more sensitive to warfarin-related AC than older patients, which was possibly due to accumulated warfarin-induced cellular senescence.

Diabetes and calcification: The potential role of anti-diabetic drugs on vascular calcification regression.

Vascular calcification (VC) has been well-established as an independent and strong predictor of cardiovascular diseases (CVD) as well as major cardiac adverse events (MACE). VC is associated with increased mortality in patients with CVD. Pathologically, VC is now believed to be a multi-directional active process ultimately resulting in ectopic calcium deposition in vascular beds. On the other hand, prevalence of diabetes mellitus (DM) is gradually increasing thus making the current population more prone to future CVD. Although the mechanisms involved in development and progression of VC in DM patients are not fully understood, a series of evidences demonstrated positive association between DM and VC. It has been highlighted that different cellular pathways are involved in this process. These intermediates such as tumor necrosis factor alpha (TNF-α), various interleukins (ILs) and different cell-signaling pathways are over-expressed in DM patients leading to development of VC. Thus, considering the burden and significance of VC it is of great importance to find a therapeutic approach to prevent or minimize the development of VC in DM patients. Over the past few years various anti diabetic drugs (ADDs) have been introduced and many of them showed desired glucose control. But no study demonstrated the effects of these medications on regression of VC. In this review, we will briefly discuss the current understanding on DM and VC and how commonly used ADDs modulate the development or progression of VC.