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1.
Infect Dis Ther ; 13(1): 221-236, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38236515

ABSTRACT

INTRODUCTION: Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients' health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3. METHODS: This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8 weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial's blinded phase only. RESULTS: Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week 8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week 8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p < 0.05) and mental domain (16.2 [6.0], p < 0.01) scores vs. placebo from baseline to week 8. CONCLUSION: Compared to placebo, RBL demonstrated a significantly higher treatment success in preventing further rCDI and enhanced HRQL among patients at first recurrence, establishing RBL as an effective treatment to prevent further recurrences in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03244644.

2.
RSC Adv ; 13(47): 32940-32971, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-38025849

ABSTRACT

Epoxides derived from waste biomass are a promising avenue for the production of bio-based polymers, including polyamides, polyesters, polyurethanes, and polycarbonates. This review article explores recent efforts to develop both catalytic and non-catalytic processes for the epoxidation of terpene, employing a variety of oxidizing agents and techniques for process intensification. Experimental investigations into the epoxidation of limonene have shown that these methods can be extended to other terpenes. To optimize the epoxidation of bio-based terpene, there is a need to develop continuous processes that address limitations in mass and heat transfer. This review discusses flow chemistry and innovative reactor designs as part of a multi-scale approach aimed at industrial transformation. These methods facilitate continuous processing, improve mixing, and either eliminate or reduce the need for solvents by enhancing heat transfer capabilities. Overall, the objective of this review is to contribute to the development of commercially viable processes for producing bio-based epoxides from waste biomass.

4.
Open Forum Infect Dis ; 10(8): ofad383, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37564743

ABSTRACT

Background: Recurrence of Clostridioides difficile infection (rCDI) is common, prolonging disease morbidity and leading to poor quality of life. We evaluated disease-specific health-related quality of life (HRQL) in patients with rCDI treated with fecal microbiota, live-jslm (REBYOTA [RBL]; Rebiotix) versus placebo. Methods: This was a secondary analysis of a randomized, double-blind, placebo-controlled phase 3 study (PUNCH CD3). The disease-specific Clostridioides difficile Quality of Life Survey (Cdiff32) was administered at baseline and at weeks 1, 4, and 8. Changes in Cdiff32 total and domain (physical, mental, social) scores from baseline to week 8 were compared between RBL and placebo and for responders and nonresponders. Results: Findings were analyzed in a total of 185 patients (RBL, n = 128 [69.2%]; placebo, n = 57 [30.8%]) with available Cdiff32 data. Patients from both arms showed significant improvements in Cdiff32 scores relative to baseline across all outcomes and at all time points (all P < .001); RBL-treated patients showed significantly greater improvements in mental domain than those receiving placebo. In adjusted analyses, RBL-treated patients showed greater improvements than placebo in total score and physical and mental domains (all P < .05). Similar improvement in mental domain was observed among responders, while nonresponders showed numerical improvements with RBL but not placebo. Conclusions: In a phase 3 double-blinded clinical trial, RBL-treated patients reported more substantial and sustained disease-specific HRQL improvements than placebo-treated patients. Clinical Trials Registration: ClinicalTrials.gov NCT03244644 (https://clinicaltrials.gov/ct2/show/NCT03244644).

5.
Comput Methods Programs Biomed ; 241: 107780, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37651816

ABSTRACT

BACKGROUND AND OBJECTIVE: Quantitative measures extracted from ventricular fibrillation (VF) waveform reflect the metabolic state of the myocardium and are associated with survival outcome. The quality of delivered chest compressions during cardiopulmonary resuscitation are also linked with survival. The aim of this research is to explore the viability and effectiveness of a thoracic impedance (TI) based chest compression (CC) guidance system to control CC depth within individual subjects and influence VF waveform properties. METHODS: This porcine investigation includes an analysis of two protocols. CC were delivered in 2 min episodes at a constant rate of 110 CC min-1. Subject-specific CC depth was controlled using a TI-thresholding system where CC were performed according to the amplitude (ZRMS, 0.125 to 1.250 Ω) of a band-passed TI signal (ZCC). Protocol A was a retrospective analysis of a 12-porcine study to characterise the response of two VF waveform metrics: amplitude spectrum area (AMSA) and mean slope (MS), to varying CC quality. Protocol B was a prospective 12-porcine study to determine if changes in VF waveform metrics, due to CC quality, were associated with defibrillation outcome. RESULTS: Protocol A: A directly proportional relationship was observed between ZRMS and CC depth applied within each subject (r = 0.90; p <0.001). A positive relationship was observed between ZRMS and both AMSA (p <0.001) and MS (p <0.001), where greater TI thresholds were associated with greater waveform metrics. PROTOCOL B: MS was associated with return of circulation following defibrillation (odds ratio = 2.657; p = 0.043). CONCLUSION: TI-thresholding was an effective way to control CC depth within-subjects. Compressions applied according to higher TI thresholds evoked an increase in AMSA and MS. The response in MS due to deeper CC resulted in a greater incidence of ROSC compared to shallow chest compressions.


Subject(s)
Amsacrine , Ventricular Fibrillation , Swine , Animals , Ventricular Fibrillation/therapy , Electric Impedance , Prospective Studies , Retrospective Studies
6.
RSC Adv ; 13(33): 22717-22743, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37502825

ABSTRACT

Anthropogenic carbon dioxide (CO2) emissions contribute significantly to global warming and deplete fossil carbon resources, prompting a shift to bio-based raw materials. The two main technologies for reducing CO2 emissions are capturing and either storing or utilizing it. However, while capture and storage have high reduction potential, they lack economic feasibility. Conversely, by utilizing the CO2 captured from streams and air to produce valuable products, it can become an asset and curb greenhouse gas effects. CO2 is a challenging C1-building block due to its high kinetic inertness and thermodynamic stability, requiring high temperature and pressure conditions and a reactive catalytic system. Nonetheless, cyclic carbonate production by reacting epoxides and CO2 is a promising green and sustainable chemistry reaction, with enormous potential applications as an electrolyte in lithium-ion batteries, a green solvent, and a monomer in polycarbonate production. This review focuses on the most recent developments in the synthesis of cyclic carbonates from glycerol and bio-based epoxides, as well as efficient methods for chemically transforming CO2 using flow chemistry and novel reactor designs.

7.
J Hypertens ; 41(9): 1389-1400, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37272080

ABSTRACT

BACKGROUND: NOX4 activation has been implicated to have vasoprotective and blood pressure (BP)-lowering effects. Molecular mechanisms underlying this are unclear, but NOX4-induced regulation of the redox-sensitive Ca 2+ channel TRPM2 and effects on endothelial nitric oxide synthase (eNOS)-nitric oxide signalling may be important. METHOD: Wild-type and LinA3, renin-expressing hypertensive mice, were crossed with NOX4 knockout mice. Vascular function was measured by myography. Generation of superoxide (O 2- ) and hydrogen peroxide (H 2 O 2 ) were assessed by lucigenin and amplex red, respectively, and Ca 2+ influx by Cal-520 fluorescence in rat aortic endothelial cells (RAEC). RESULTS: BP was increased in NOX4KO, LinA3 and LinA3/NOX4KO mice. This was associated with endothelial dysfunction and vascular remodelling, with exaggerated effects in NOX4KO groups. The TRPM2 activator, ADPR, improved vascular relaxation in LinA3/NOX4KO mice, an effect recapitulated by H 2 O 2 . Inhibition of PARP and TRPM2 with olaparib and 2-APB, respectively, recapitulated endothelial dysfunction in NOX4KO. In endothelial cells, Ang II increased H 2 O 2 generation and Ca 2+ influx, effects reduced by TRPM2 siRNA, TRPM2 inhibitors (8-br-cADPR, 2-APB), olaparib and GKT137831 (NOX4 inhibitor). Ang II-induced eNOS activation was blocked by NOX4 and TRPM2 siRNA, GKT137831, PEG-catalase and 8-br-cADPR. CONCLUSION: Our findings indicate that NOX4-induced H 2 O 2 production activates PARP/TRPM2, Ca 2+ influx, eNOS activation and nitric oxide release in endothelial cells. NOX4 deficiency impairs Ca 2+ homeostasis leading to endothelial dysfunction, an effect exacerbated in hypertension. We define a novel pathway linking endothelial NOX4/H 2 O 2 to eNOS/nitric oxide through PARP/TRPM2/Ca 2+ . This vasoprotective pathway is perturbed when NOX4 is downregulated and may have significance in conditions associated with endothelial dysfunction, including hypertension.


Subject(s)
Hypertension , TRPM Cation Channels , Animals , Mice , Rats , Calcium/metabolism , Endothelial Cells/metabolism , Hydrogen Peroxide/pharmacology , Hypertension/metabolism , Nitric Oxide/metabolism , Poly(ADP-ribose) Polymerase Inhibitors , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism
8.
Therap Adv Gastroenterol ; 16: 17562848231174277, 2023.
Article in English | MEDLINE | ID: mdl-37333464

ABSTRACT

Background: Microbiota-based treatments reduce the incidence of recurrent Clostridioides difficile infections (rCDIs), but prospectively collected safety data needed to broaden patient access and protect public health have been limited. Objectives: We provide cumulative safety data from five prospective clinical trials evaluating fecal microbiota, live-jslm (RBL) - the first microbiota-based live biotherapeutic product approved by the US Food and Drug Administration - for preventing rCDI in adults. Design: Integrated safety analysis includes three phase II trials (PUNCH CD, PUNCH CD2, PUNCH Open-Label) and two phase III trials (PUNCH CD3, PUNCH CD3-OLS) of RBL. Methods: Trial participants were at least 18 years of age with documented rCDI who completed standard-of-care antibiotic therapy before treatment with RBL. Assigned study treatment regimen was one or two doses of RBL (or placebo) administered rectally, depending on the trial design. In four of the five trials, participants with CDI recurrence within 8 weeks after RBL or placebo administration were eligible for treatment with open-label RBL. Treatment-emergent adverse events (TEAEs) were recorded for at least 6 months following last study treatment; in PUNCH CD2 and PUNCH Open-Label trials, TEAEs and serious TEAEs were collected through 12 and 24 months, respectively. Results: Among the five trials, 978 participants received at least one dose of RBL (assigned treatment or after recurrence) and 83 participants received placebo only. TEAEs were reported in 60.2% of Placebo Only participants and 66.4% of RBL Only participants. Only abdominal pain, nausea, and flatulence were significantly higher in the RBL Only group compared with the Placebo Only group. Most TEAEs were mild or moderate in severity and were most frequently related to preexisting conditions. There were no reported infections for which the causative pathogen was traced to RBL. Potentially life-threatening TEAEs were infrequent (3.0% of participants). Conclusion: Across five clinical trials, RBL was well tolerated in adults with rCDI. In aggregate, these data consistently demonstrated the safety of RBL.

9.
Open Forum Infect Dis ; 10(5): ofad171, 2023 May.
Article in English | MEDLINE | ID: mdl-37256213

ABSTRACT

Background: Fecal microbiota, live-jslm (RBL; REBYOTA™), the first microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults, has been evaluated in 5 prospective clinical trials. A retrospective analysis considered the safety and efficacy of RBL administered under US Food and Drug Administration enforcement discretion to patients with rCDI and broad eligibility criteria mimicking real-world practice. Methods: We retrospectively identified adults with rCDI treated with RBL under enforcement discretion between November 1, 2015, and September 30, 2019, across 5 study sites. CDI diagnosis was based on site-specific practice. The primary safety set (PSS) included all patients who were naïve to previous RBL treatment and had continuously comprehensive medical records for 6 months following treatment. Results: The primary treatment cohort had 94 patients; the PSS included 64 patients with common comorbidities receiving diverse chronic therapeutics. Most treatment-emergent adverse events were mild to moderate in severity and comparable between comorbidity subgroups and the overall population. There were no serious adverse events related to RBL or the administration procedure. In the PSS, 82.8% of RBL-treated patients responded at 8 weeks, of whom 88.7% had sustained response through 6 months. The number of RBL doses administered had no marked effect on outcome. Conclusions: Together with prospective clinical trial outcomes, these findings support the efficacy and safety of RBL to prevent rCDI, with diagnostics and comorbidities representative of real-world clinical practice.

10.
Heliyon ; 9(3): e14237, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36950658

ABSTRACT

In this research, a dielectric barrier discharge (DBD) reactor is used to study the cracking of the toluene into C1-C6 hydrocarbons. The combined effect of parameters such as temperature (20-400 °C) and plasma power (10-40 W) was investigated to evaluate the DBD reactor performance. The main gaseous products from the decomposition of toluene include lower hydrocarbon (C1-C6). The cracking of toluene increases with power at all temperatures (20-400 °C). On the otherhand, it decreases from 92.8 to 73.1% at 10 W, 97.2 to 80.5% at 20, 97.5 to 86.5% at 30 W, and 98.4 to 93.7% at 40 W with raising the temperature from 20 to 400 °C. Nonetheless, as the temperature and plasma input power increase, the methane yield increases. At 40 W, the maximum methane yield was 5.1%. At 10 and 20 W, the selectivity to C2 increases as the temperature rises up to 400 °C. At 30 and 40 W, it began to drop after 300 °C due to the formation of methane and the yield of methane increases significantly beyond this temperature.

11.
Resuscitation ; 185: 109738, 2023 04.
Article in English | MEDLINE | ID: mdl-36806652

ABSTRACT

BACKGROUND: Quality of chest compressions (CC) during cardiopulmonary resuscitation (CPR) often do not meet guideline recommendations for rate and depth. This may be due to the fatiguing nature of physically compressing a patient's chest, meaning that CPR quality reduces over time. OBJECTIVE: This analysis investigates the effect of CPR duration on the performance of continuous CCs delivered by firefighters equipped with CPR feedback devices. METHODS: Data were collected from a first responder group which used CPR feedback and automatic external defibrillator devices when attending out-of-hospital cardiac arrest events. Depth and rate of CC were analysed for 134 patients. Mean CC depth and rate were calculated every 5 s during two-minute episodes of CPR. Regression models were created to evaluate the relationship between applied CC depth and rate as a function of time. RESULTS: Mean (SD) CC depth during the investigation was 48 (9) mm. An inverse relationship was observed between CC depth and CPR duration, where CC depth decreased by 3.39 mm, over two-minutes of CPR (p < 0.001). Mean (SD) CC rate was 112.06 (5.87) compressions per minute. No significant relationship was observed between CC rate and CPR duration (p = 0.077). Mean depth was within guideline range for 33.58% of patient events, while guideline rate was observed in 92.54% of cases. CONCLUSIONS: A reduction in CC depth was observed during two-minutes of continuous CCs while CC rate was not affected. One third of patients received a mean CC depth within guideline range (50 to 60 mm).


Subject(s)
Cardiopulmonary Resuscitation , Firefighters , Out-of-Hospital Cardiac Arrest , Humans , Out-of-Hospital Cardiac Arrest/therapy , Defibrillators , Time Factors
12.
Open Forum Infect Dis ; 10(1): ofac703, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36686631

ABSTRACT

Background: Advanced age and underlying comorbidities are associated with greater rates of recurrence in patients with Clostridioides difficile infection (CDI). Reducing the likelihood of recurrence through treatment with an antimicrobial followed by a microbiota replacement therapy can decrease the burden of this infection and improve patient outcomes. We report the efficacy and safety of RBX2660, a microbiota-based live biotherapeutic, in older adults with recurrent CDI, grouped by comorbidities. Methods: In this post hoc subgroup analysis of the PUNCH CD3 trial, we assessed outcomes in older adults (age ≥65 years) grouped by Charlson Comorbidity Index severity scores at screening (moderate [3-4] and severe [≥5]) and by the presence of underlying cardiac, renal, or gastrointestinal disorders. Results: RBX2660 treatment success rates in older adults with comorbidities were consistent across subgroups and similar to those in the total RBX2660-treated population. A greater percentage of RBX2660-treated older adults remained free of CDI recurrence through 8 weeks following treatment compared with placebo-treated participants in all but 2 subgroups assessed. Across all subgroups, most treatment-emergent adverse events (TEAEs) were mild or moderate in severity and related to a preexisting condition. None of the serious or life-threatening TEAEs that occurred were related to RBX2660 or its administration. Occurrence of TEAEs did not cluster in any subgroup. Conclusions: RBX2660 is efficacious and safe in older adults with recurrent CDI and underlying comorbidities.

13.
Sci Total Environ ; 862: 160702, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36481155

ABSTRACT

The purpose of this study was to examine the application of the mathematical model of drift flux to the experimental results of the effect of cationic trimethyl-ammonium bromide (CTAB)-aided continuous foam flotation harvesting on the lipid content in Chlorella vulgaris microalgae. An experiment was conducted to determine the effect of the operating conditions on the enrichment factor (EF) and percentage recovery efficiency (%RE), where the flow rates at the inlet and bottom outlet remained constant. Data for the binary system (without algae) and ternary system (with algae) in an equal-area foam column show that the EF decreases linearly with increasing initial CTAB concentrations ranging from 30 to 75 mg/L for three levels of the studied air volumetric flow rate range (1-3) L/min. The percentage harvesting efficiency increased with increasing initial CTAB concentration and air volumetric flow rate to 96 % in the binary systems and 94 % in the ternary systems. However, in the foam column with the riser used in the three systems, a lower volume of liquid foam in the upward outlet stream resulted in a lower RE% than that of the column without the riser. The objective function of EF for the system with algae increased when the initial CTAB concentration was increased from 30 to 45 mg/L in the foam column with a riser for all air flow rates, and after 45 mg/L, a sudden drop in the microalgae EF was observed. In the comparison between the foam column with and without the riser for the system with algae, the optimum EF was 145 for the design of the column with the riser and 139 for the column without the riser.


Subject(s)
Chlorella vulgaris , Microalgae , Cetrimonium , Biofuels , Fresh Water , Biomass
14.
Otol Neurotol ; 44(2): e95-e102, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36477093

ABSTRACT

OBJECTIVE: To clarify whether the reported lack of racial and ethnic diversity among Menière's disease (MD) patients is representative of selection bias or disease susceptibility. STUDY DESIGN: Retrospective medical record review and population-level analyses. SETTING: Tertiary referral center. PATIENTS: Cohort of 1091 patients diagnosed with MD by the tertiary otology service. MAIN OUTCOME MEASURE: Demographic and population-level characteristics (age, sex, race, insurance status, ZIP code, median income, education level) compared with local, regional, health system, and otolaryngology clinic demographics. RESULTS: Patients seen for MD were significantly older than those seen throughout the otolaryngology clinic (median, 65.0 versus 58.8 yr) or health system (65.0 versus 50.8 yr). A majority of patients with MD were of White race (92%), compared with 2.7% Black race and 0.5% Asian. Using population-level data, median income and having medical insurance were significantly correlated with care for MD. A disproportionate rate of care for MD was seen in ZIP codes outside urban areas as compared with other otologic and otolaryngologic conditions seen in the same clinic. CONCLUSION: Patients with MD are of older age, more likely to be of White race, and disproportionately from rural locales. The demographic profile of patients diagnosed with MD by tertiary otology is better explained by differential susceptibility to MD than by selection bias.


Subject(s)
Meniere Disease , Humans , Meniere Disease/epidemiology , Retrospective Studies , Selection Bias , Asian , Demography
15.
PLoS Genet ; 18(11): e1010485, 2022 11.
Article in English | MEDLINE | ID: mdl-36350851

ABSTRACT

Telomerase activity is the principal telomere maintenance mechanism in human cancers, however 15% of cancers utilise a recombination-based mechanism referred to as alternative lengthening of telomeres (ALT) that leads to long and heterogenous telomere length distributions. Loss-of-function mutations in the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) gene are frequently found in ALT cancers. Here, we demonstrate that the loss of ATRX, coupled with telomere dysfunction during crisis, is sufficient to initiate activation of the ALT pathway and that it confers replicative immortality in human fibroblasts. Additionally, loss of ATRX combined with a telomere-driven crisis in HCT116 epithelial cancer cells led to the initiation of an ALT-like pathway. In these cells, a rapid and precise telomeric elongation and the induction of C-circles was observed; however, this process was transient and the telomeres ultimately continued to erode such that the cells either died or the escape from crisis was associated with telomerase activation. In both of these instances, telomere sequencing revealed that all alleles, irrespective of whether they were elongated, were enriched in variant repeat types, that appeared to be cell-line specific. Thus, our data show that the loss of ATRX combined with telomere dysfunction during crisis induces the ALT pathway in fibroblasts and enables a transient activation of ALT in epithelial cells.


Subject(s)
Neoplasms , Telomerase , alpha-Thalassemia , Humans , Telomerase/genetics , Telomerase/metabolism , Telomere Homeostasis/genetics , X-linked Nuclear Protein/genetics , alpha-Thalassemia/genetics , Telomere/genetics , Telomere/metabolism
16.
Sci Rep ; 12(1): 14575, 2022 08 26.
Article in English | MEDLINE | ID: mdl-36028561

ABSTRACT

Public access automated external defibrillators (AEDs) represent emergency medical devices that may be used by untrained lay-persons in a life-critical event. As such their usability must be confirmed through simulation testing. In 2020 the novel coronavirus caused a global pandemic. In order to reduce the spread of the virus, many restrictions such as social distancing and travel bans were enforced. Usability testing of AEDs is typically conducted in-person, but due to these restrictions, other usability solutions must be investigated. Two studies were conducted, each with 18 participants: (1) an in-person usability study of an AED conducted in an office space, and (2) a synchronous remote usability study of the same AED conducted using video conferencing software. Key metrics associated with AED use, such as time to turn on, time to place pads and time to deliver a shock, were assessed in both studies. There was no difference in time taken to turn the AED on in the in-person study compared to the remote study, but the time to place electrode pads and to deliver a shock were significantly lower in the in-person study than in the remote study. Overall, the results of this study indicate that remote user testing of public access defibrillators may be appropriate in formative usability studies for determining understanding of the user interface.


Subject(s)
COVID-19 , Cardiopulmonary Resuscitation , Defibrillators/classification , Out-of-Hospital Cardiac Arrest/therapy , Physical Distancing , Cardiopulmonary Resuscitation/methods , Cardiopulmonary Resuscitation/standards , Defibrillators/standards , Defibrillators/statistics & numerical data , Humans , Pandemics , Time Factors , User-Centered Design , User-Computer Interface
17.
Commun Biol ; 5(1): 746, 2022 07 26.
Article in English | MEDLINE | ID: mdl-35882956

ABSTRACT

Hyperaldosteronism causes cardiovascular disease as well as hypomagnesemia. Mechanisms are ill-defined but dysregulation of TRPM7, a Mg2+-permeable channel/α-kinase, may be important. We examined the role of TRPM7 in aldosterone-dependent cardiovascular and renal injury by studying aldosterone-salt treated TRPM7-deficient (TRPM7+/Δkinase) mice. Plasma/tissue [Mg2+] and TRPM7 phosphorylation were reduced in vehicle-treated TRPM7+/Δkinase mice, effects recapitulated in aldosterone-salt-treated wild-type mice. Aldosterone-salt treatment exaggerated vascular dysfunction and amplified cardiovascular and renal fibrosis, with associated increased blood pressure in TRPM7+/Δkinase mice. Tissue expression of Mg2+-regulated phosphatases (PPM1A, PTEN) was downregulated and phosphorylation of Smad3, ERK1/2, and Stat1 was upregulated in aldosterone-salt TRPM7-deficient mice. Aldosterone-induced phosphorylation of pro-fibrotic signaling was increased in TRPM7+/Δkinase fibroblasts, effects ameliorated by Mg2+ supplementation. TRPM7 deficiency amplifies aldosterone-salt-induced cardiovascular remodeling and damage. We identify TRPM7 downregulation and associated hypomagnesemia as putative molecular mechanisms underlying deleterious cardiovascular and renal effects of hyperaldosteronism.


Subject(s)
Hyperaldosteronism , TRPM Cation Channels , Aldosterone/pharmacology , Animals , Fibrosis , Hyperaldosteronism/genetics , Hyperaldosteronism/metabolism , Kidney/metabolism , Magnesium/metabolism , Mice , Protein Phosphatase 2C/metabolism , Sodium Chloride , TRPM Cation Channels/deficiency , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism
18.
RSC Adv ; 12(23): 14385-14396, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35733914

ABSTRACT

The oxidative desulfurization (ODS) of dibenzothiophene in diesel fuel cut using a homogeneous liquid catalytic system in a novel reactor is presented. Hydrogen peroxide was the oxidizing agent and acetic acid was the liquid catalyst. The oxidation process was conducted in a meso-oscillatory baffled reactor ("mesoOBR") under mild operating conditions: atmospheric pressure, and 60 to 80 °C. The reactor was operated over a range of residence times (1-3 min), and frequencies and amplitudes of oscillation, leading to oscillatory Reynolds numbers in the range 64-383, and net flow Reynolds numbers in the range 5 to 16. The results showed that dibenzothiophene (DBT) removal in the OBR was significantly higher than in conventional processes under the same conditions (pressure of 1 atm and temperature near room temperature). The maximum DBT conversion was 94%, which was achieved in 3 min at 4 Hz and 6 mm amplitude. A significant improvement in the removal efficiency of DBT was achieved in OBR within only 3 minutes compared to previous studies, which required at least a half-hour reaction time to achieve the same or less removal efficiency. A reaction kinetic model was developed using the optimum experimental results achieved in the OBR. The apparent reaction order was 1, with significantly low apparent activation energies (24.7-29.0 kJ mol-1).

19.
RSC Adv ; 12(27): 17454-17465, 2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35765421

ABSTRACT

This work reports the first known synthesis of α-pinane carbonate from an α-pinene derivative. Pinane carbonate is potentially useful as a monomer for poly(pinane carbonate), which would be a sustainable bio-based polymer. α-Pinene is a major waste product from the pulp and paper industries and the most naturally abundant monoterpene in turpentine oil. α-Pinene is routinely converted to pinene oxide and pinanediol, but no study has yet demonstrated the conversion of pinanediol into α-pinane carbonate. Here, α-pinane carbonate was synthesised via carboxylation of α-pinanediol with dimethyl carbonate under base catalysis using triazabicyclodecene guanidine (TBD). 81.1 ± 2.8% α-pinane carbonate yield was achieved at 98.7% purity. The produced α-pinane carbonate was a white crystalline solid with a melting point of 86 °C. It was characterised using FTIR, NMR, GCMS and a quadrupole time-of-flight (QTOF) mass spectrometer. The FTIR exhibited a C[double bond, length as m-dash]O peak at 1794 cm-1 confirming the presence of a cyclic carbonate. GCMS showed that the α-pinane carbonate fragments with loss of CO2, forming pinene epoxide. Base hydrolysis of the α-pinane carbonate using NaOH/ethanol/water regenerated the pinanediol with formations of Na2CO3.

20.
RSC Adv ; 12(18): 10997-11007, 2022 Apr 07.
Article in English | MEDLINE | ID: mdl-35425072

ABSTRACT

In this work, a non-thermal plasma dielectric barrier discharge (DBD) was used to remove methanol from ambient air. The effects of carrier gases (N2, dry and humidified air), power (2-10 W), inlet concentration (260-350 ppm), and residence time (1.2-3.3 s) were investigated to evaluate the performance of the plasma DBD reactor in terms of removal efficiency, product selectivity and reduction of unwanted by-products at ambient temperature and atmospheric pressure. It was found that the conversion of methanol increased with power and residence time regardless of the carrier gas used. However, the removal efficiency decreased with the increasing concentration of CH3OH. Almost complete removal of methanol (96.7%) was achieved at 10 W and a residence time of 3.3 s in dry air. The removal efficiency of methanol followed a sequence of dry air > humidified air > N2 carrier gas. This was due to the action of the O radical in dry air, which dominates the decomposition process of the plasma system. The introduction of water vapour into the DBD system decreased the removal efficiency but had a number of significant advantages: increased CO2 selectivity and yield of H2, it significantly reduced the formation of O3, CO and higher hydrocarbons. These influences are probably due to the presence of potent OH radicals, and the conversion pathways for the various effects are proposed. It is important to note that no solid residue was formed in the DBD reactor in any carrier gas. Overall, this research indicates that methanol can be almost completely removed with the correct operating parameters (96.7% removal; 10 W; 3.3 s) and shows that humidification of the gas stream is beneficial.

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