Nevin Manimala

Rev Clin Esp (Barc). 2023 Jul 21:S2254-8874(23)00092-9. doi: 10.1016/j.rceng.2023.07.006. Online ahead of print.

ABSTRACT

INTRODUCTION AND AIM: N-acetylcysteine has been proposed for the treatment of COVID-19 thanks to its mucolytic, antioxidant and anti-inflammatory effects. Our aim is to evaluate its effect on patients admitted with COVID-19 in mortality terms.

MATERIAL AND METHODS: Retrospective single-center cohort study. All patients admitted to our hospital for COVID-19 from March to April 2020 have been considered.

RESULTS: A total of 378 patients were included, being 196 (51.9%) men, with an average age of 73.3 ± 14.5 years. 52.6% (199) received treatment with N-Acetylcysteine. More than 70% presented coughs, fever, and/or dyspnea. The global hospital mortality was 26.7%. A multivariate analysis through logistic regression identified the age of patients [older than 80; OR: 8.4 (CI95%:3-23.4)], a moderate or severe radiologic affectation measured by the RALE score [OR:7.3 (CI95%:3.2-16.9)], the tobacco consumption [OR:2.8 (CI95%:1.3-6.1)] and previous arrhythmia [OR 2.8 (CI95%: 1.3-6.2)]as risk factor that were independently associated with mortality during the admission. The treatment with N-Acetylcysteine was identified as a protective factor [OR: 0.57 (CI95%: 0.31-0.99)]. Asthma also seems to have a certain protective factor although it was not statistically significant in our study [OR: 0.19 (CI95%: 0.03-1.06)].

CONCLUSIONS: Patients with COVID-19 treated with N-acetylcysteine have presented a lower mortality and a better evolution in this study. Future prospective studies or randomized clinical trials must confirm the impact of N-Acetylcysteine on COVID-19 patients.

PMID:37482215 | DOI:10.1016/j.rceng.2023.07.006

Chem Biol Interact. 2023 Jul 21:110641. doi: 10.1016/j.cbi.2023.110641. Online ahead of print.

ABSTRACT

Beneficial effects of a natural zeolite clinoptilolite in vivo on mammals, including humans, have been empirically observed and documented in literature. The positive biological activities have been associated to its detoxifying and antioxidative properties, and its immunostimulative and adsorption properties. Herein, we present the in vitro and in vivo study of clinoptilolite zeolite materials adsorption properties for d-glucose. In particular, we present data on the interaction of d-glucose on the tested zeolites’ surface obtained by scanning electron microscope (SEM) and Energy-dispersive X-ray spectroscopy (EDS) and quantification by ultra high-performance liquid chromatography (UHPLC). We also present results on the reduction of blood glucose levels in mice pre-treated with clinoptilolite in vivo upon feeding with d-glucose. In vivo results were in line with the in vitro adsorption and/or interaction properties of tested zeolite materials for d-glucose and were quantified by UHPLC as well (11.34% for TMAZ; 10.82% for PMA and 8.76% for PMAO2). In vivo experiments in mice showed that PMA zeolite reduces blood glucose levels upon 15 min for 13% (at p < 0.05) up to 19.11% upon 120 min (without statistical significance) in clinoptilolite pre-treated mice fed by addition of d-glucose. Due to lack of explicit mechanistic knowledge on zeolite clinoptilolite interactions or adsorption with sugars in vitro and in vivo, presented study provides novel insights into these aspects for researchers in the field. The presented data merit further investigations as the material clearly shows a potential in management of hyperglycemia, such as for example in obese people, people with diabetes and people with metabolic syndrome where it could help regulate blood glucose levels.

PMID:37482210 | DOI:10.1016/j.cbi.2023.110641

Clin Gastroenterol Hepatol. 2023 Jul 21:S1542-3565(23)00543-8. doi: 10.1016/j.cgh.2023.07.008. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabis (^Δ9THC), a non-selective cannabinoid receptor (CBR) agonist relieves nausea and pain. Cannabidiol (CBD), a CBR2 inverse agonist with central effects, also reduces gut sensation and inflammation.

AIMS: To compare effects of 4 weeks’ treatment with pharmaceutical CBD vs. placebo in patients with idiopathic (IG) or diabetic (DM) gastroparesis.

METHODS: We performed a randomized, double-blinded, placebo-controlled study of CBD b.i.d. (Epidiolex® escalated to 20mg/kg/day) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD). After 4 weeks’ treatment, we measured GES, gastric volumes, and Ensure® satiation test (1kcal/mL, 30mL/min) to assess volume to comfortable fullness (VTF) and maximum tolerance (MTV). Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using ANOVA including baseline measurements and BMI as covariates.

RESULTS: Among 44 patients (32 IG, 6 DM1, and 6 DM2), 5 patients did not tolerate full dose escalation; 3 withdrew before completing 4 weeks’ treatment (2 placebo, 1 CBD); 95% completed 4 weeks’ treatment and diaries. Compared to placebo, CBD reduced total GCSI score (P=0.008), inability to finish a normal-sized meal (P=0.029), number of vomiting episodes/24 hours (P=0.006), and overall symptom severity (P=0.034). Patients treated with CBD had higher VTF and MTV and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14), fatigue (8), headache (8), and nausea (7).

CONCLUSIONS: CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES.

PMID:37482172 | DOI:10.1016/j.cgh.2023.07.008

Int J Radiat Oncol Biol Phys. 2023 Jul 21:S0360-3016(23)07647-2. doi: 10.1016/j.ijrobp.2023.07.015. Online ahead of print.

ABSTRACT

BACKGROUND: Radiation necrosis (RN) secondary to stereotactic radiosurgery is a significant cause of morbidity. The optimal management of corticosteroid-refractory brain RN remains unclear.

OBJECTIVE: To summarise the literature specific to efficacy and toxicity of treatment paradigms for patients with symptomatic corticosteroid refractory RN. To provide consensus guidelines for grading and management of RN on behalf of the International Stereotactic Radiosurgery Society (ISRS).

METHODS: A systematic review of articles pertaining to treatment of RN with bevacizumab, laser interstitial thermal therapy (LITT), surgical resection, or hyperbaric oxygen therapy (HBOT) was performed. The primary composite outcome was clinical and/or radiological stability/ improvement (i.e., proportion of patients achieving improvement or stability with the given intervention). Proportions of patients achieving the primary outcome were pooled using random weighted-effects analysis, but not directly compared between interventions.

RESULTS: Twenty-one articles were included, of which only two were prospective studies. Thirteen reports were relevant for bevacizumab, 5 for LITT, 5 for surgical resection and 1 for HBOT. Weighted effects analysis revealed that bevacizumab had a pooled symptom improvement/stability rate of 86% (95% CI: 77-92%), pooled T2 imaging improvement/stability rate of 93% (95% CI: 87 -98%), and pooled T1-post contrast improvement/stability rate of 94% (95% CI: 87 – 98%). Subgroup analysis showed a statistically significant improvement favouring treatment with low-dose (below median, ≤7.5 mg/kg every 3 weeks) vs. high-dose bevacizumab with regards to symptom improvement/stability rate (P=0.02), but not for radiological T1 or T2 changes. The pooled T1-post contrast improvement/stability rate for LITT was 88% (95% CI 82 – 93%), and pooled symptom improvement/stability rate for surgery was 89% (95% CI 81 – 96%). Toxicity was inconsistently reported but was generally low for all treatment paradigms.

CONCLUSION: Corticosteroid-refractory RN that does not need urgent surgical intervention, with sufficient non-invasive diagnostic testing that favours RN, can be treated medically with bevacizumab in carefully selected patients as a strong recommendation. The role of LITT is evolving as a less invasive image-guided surgical modality, however, the overall evidence for each modality is of low quality. Prospective head-to-head comparisons are needed to evaluate the relative efficacy and toxicity profile amongst treatment approaches.

PMID:37482137 | DOI:10.1016/j.ijrobp.2023.07.015

Int J Radiat Oncol Biol Phys. 2023 Jul 21:S0360-3016(23)07649-6. doi: 10.1016/j.ijrobp.2023.07.017. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study is to report pulmonary function tests (PFTs), clinician-reported and patient-reported QoL outcomes on a cohort of NSCLC patients treated with SABR.

METHODS: 119 patients with NSCLC were treated with SABR in the prospective cohort SSBROC study of patients with T1-T2N0M0 NSCLC. PFTs and quality of life measures were obtained at baseline pre-treatment and 6 monthly. Here we report on the 6- to 18-month time points. ANCOVA methods adjusting for baseline analysed potential predictors on outcomes of PFT and patient-reported dyspnoea at 18 months.

RESULTS: The only statistically significant decline in PFTs was seen in FEV1 at 18 months post-SABR with a decline of -0.11L (p = 0.0087, 95% CI -0.18 to -0.02). Of potential predictors of decline, only a 1 unit increase in smoking pack years resulted in a -0.12 change in DLCO (p = 0.026, 95% CI -0.02 to -0.23) and a 0.003 decrease in FEV1 (p = 0.026, 95% CI -0.006 to -0.0004). For patient reported outcomes, statistically significant worsening in both QLQC30 and QLQLC13 dyspnoea scores occurred at the 18-month time point, but not earlier. No potential predictors of worsening dyspnoea were statistically significant. There was no statistically significant decline in clinician-reported outcomes or global QoL scores.

CONCLUSIONS: We found a statistically significant decline in FEV1 at 18 months post-treatment. Smoking pack years was a predictor for decline in DLCO and FEV1 at 18 months. Worsening of patient-reported dyspnoea scores was observed, consistent with the expected progression of lung co-morbid disease.

PMID:37482136 | DOI:10.1016/j.ijrobp.2023.07.017

Complement Ther Med. 2023 Jul 21:102966. doi: 10.1016/j.ctim.2023.102966. Online ahead of print.

ABSTRACT

BACKGROUND: Ayurveda interventions have been used for prophylaxis and care during the COVID-19 pandemic in India and have shown promising results in promoting early clinical recovery from COVID-19.

OBJECTIVE: To assess the efficacy and safety of Ashwagandha [Withania somnifera (L.) Dunal] tablet and Shunthi (Zingiber officinale Roscoe) capsule in mild and moderate COVID-19 compared to conventional standard care.

METHODS: A randomized controlled exploratory trial was conducted at a designated COVID-19 care center in India with 60 participants having mild or moderate COVID-19. Ashwagandha, two tablets (250mg each), and Shunthi, two capsules (500mg each) twice daily for 15 days, were given orally to the participants in the Ayurveda group (AG) and the control group (CG) received conventional standard care. The outcome measures included clinical recovery rate, the proportion of participants with negative RT-PCR assay for COVID-19 on day 7 and day 15, mean time to attain clinical recovery, change in pro-inflammatory markers, serum IgG for COVID-19, HRCT chest findings, disease progression and incidence of adverse events (AE).

RESULTS: A total of 60 participants were enrolled, and the data of 48 participants (AG = 25 and CG = 23) were considered for the statistical analysis. The mean time for clinical recovery was reduced by almost 50% in the AG (6.9 days) compared to CG (13.0 days) (p<0.001). The proportion of participants who attained viral clearance in AG was 76.0% compared to 60.8% in the CG (RR= 1.24, 95% CI: 0.841, 1.851, p-value = 0.270). Changes in the pro-inflammatory markers, serum IgG for COVID-19, and HRCT chest findings were comparable in both groups, and no AE or disease progression was reported.

CONCLUSIONS: The Ayurveda interventions, Ashwagandha and Shunthi, can effectively reduce the duration of clinical recovery and improve time for viral clearance in mild and moderate COVID-19 is safe and well-tolerated during the duration of the trial.

TRIAL REGISTRATION: Clinical Trial Registry of India – CTRI/2020/08/027224.

PMID:37482107 | DOI:10.1016/j.ctim.2023.102966

Cerebrovasc Dis. 2023 Jul 21. doi: 10.1159/000531861. Online ahead of print.

ABSTRACT

INTRODUCTION: Several observational studies have indicated that polyunsaturated fatty acids serum levels (PUFAs) are associated with vascular dementia (VaD), but their causal relationships remain elusive. Therefore, we attempted to evaluate the causal effect of PUFAs on VaD in a two-sample Mendelian randomization (MR) analysis by using summary statistics from aggregated genome-wide association studies.

METHODS: The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (MR-Egger regression, weighted median, penalized weighted median and MR pleiotropy residual sum and outlier methods) were also implemented to estimate the effects of potential violations of MR hypotheses.

RESULTS: No causality was found for PUFAs (OR, 1.14; 95% CI, .91-1.42; p = .25) on VaD in the IVW model. The results were consistent in sensitivity analyses. There was no notable horizontal pleiotropy or heterogeneity.

CONCLUSION: In this two-sample MR analysis, our findings did not support the assumption that PUFAs play causal role in the occurrence or development of VaD.

PMID:37482052 | DOI:10.1159/000531861

Water Res. 2023 Jul 13;243:120344. doi: 10.1016/j.watres.2023.120344. Online ahead of print.

ABSTRACT

Understanding response of bacterioplankton community responsible for maintaining ecological functions of aquatic ecosystems to environmental disturbance is an important subject. However, it remains largely unclear how bacterioplankton generalists and specialists respond to dredging disturbance. Illumina MiSeq sequencing and statistical analyses were used to evaluate landscape patterns, evolutionary potentials, environmental adaptability, and community assembly processes of generalists and specialists in response to dredging in eutrophic Lake Nanhu. The Proteobacteria and Actinobacteria dominated bacterioplankton communities of generalists and specialists, and abundances of Proteobacteria decreased and Actinobacteria increased after dredging. The generalists displayed higher phylogenetic distance, richness difference, speciation rate, extinction rate, and diversification rate as well as stronger environmental adaptation than that of specialists. In contrast, the specialists rather than generalists showed higher community diversity, taxonomic distance, and species replacement as well as closer phylogenetic clustering. Stochastic processes dominated community assemblies of generalists and specialists, and stochasticity exhibited a larger effect on community assembly of generalists rather than specialists. Our results emphasized that lake dredging could change landscape patterns of bacterioplankton generalists and specialists, whereas the short-term dredging conducted within one year was unable to reverse community difference between generalists and specialists. Our findings extend our understanding of how bacterioplankton generalists and specialists responding to dredging disturbance, and these findings might in turn call on long-term dredging for better ecological restoration of eutrophic lakes.

PMID:37482008 | DOI:10.1016/j.watres.2023.120344

Water Res. 2023 Jul 13;243:120352. doi: 10.1016/j.watres.2023.120352. Online ahead of print.

ABSTRACT

Thirty-two short term (∼7.5 h) abiotic experiments were conducted with new ductile iron and copper coupons exposed to various water qualities, including pH (7 or 9), dissolved inorganic carbon (DIC, 10 or 50 mg C L^-1) and phosphate (0 or 3 mg P L^-1) concentrations and 4 mg Cl₂ L^-1 free chlorine or monochloramine. To quantify oxidant reactivity with the new metal coupons, microelectrodes were used to obtain oxidant (free chlorine or monochloramine and dissolved oxygen (DO)) concentration and pH microprofiles from the bulk water to near the metal coupon surface. From the microprofiles, apparent surface reaction rate constants (k) were determined for each oxidant. An ANOVA analysis evaluated if the five variables (Material, Oxidant, Phosphate, DIC, and pH) significantly affected estimates of k, finding that the Material and Oxidant variables and their interaction were statistically significant (p<0.05), but the effect of variables of Phosphate, DIC, and pH on k values were not significant in this study. In general, both ductile iron and copper coupons showed significant surface reactivity towards free chlorine and monochloramine. For ductile iron, DO consumption was greater than for copper, which showed minimal DO reactivity, and DO was less reactive towards the copper surface than either free chlorine or monochloramine. Furthermore, pH microprofiles provided insight into the complexity that might exist near corroding metal surfaces where the bulk water pH may be substantially different from that measured near metal surfaces which is significant as pH is a controlling variable in terms of scale formation and metal solubility. This study represents an important first step towards using microelectrodes to (1) understand and provide direct measurement of oxidant microprofiles from the bulk water to the metal surface; (2) determine pipe wall reactivity using the directly measured concentrations profiles versus estimated pipe wall reactivity from bulk water measurements, and (3) understand how variables measured by bulk water samples (e.g., pH) may be drastically different from what is occurring at and near the metal surface. Together, these insights will assist in understanding disinfectant residual maintenance, corrosion, and metal release.

PMID:37482000 | DOI:10.1016/j.watres.2023.120352

Psychoneuroendocrinology. 2023 Jul 14;156:106334. doi: 10.1016/j.psyneuen.2023.106334. Online ahead of print.

ABSTRACT

BACKGROUND: A high prevalence of mental disorders following COVID-19 has been described. It is therefore essential to elucidate underlying biological mechanisms linking SARS-CoV-2 infection and mental health. The kynurenine and catecholamine metabolic pathways are modulated by inflammation and can affect systemic levels of serotonin and dopamine. Their activity may hence link physical disorders with mental health. We investigated factors that affect kynurenine and catecholamine pathway activity in SARS-CoV-2 infection and recovery.

METHODS: The cross-sectional SIMMUN (n = 165) and longitudinal INCOV cohort (n = 167, Su et al. 2022) were analyzed. Demographic and clinical characteristic, inflammatory markers, SARS-CoV-2 infection, symptoms of depression and anxiety (HADS), and mental stress (PSS-4) served as explanatory variables. Blood serotonin and markers of kynurenine (kynurenine/tryptophan ratio), and catecholamine pathway activity (dopamine 3-O-sulfate, phenylalanine/tyrosine ratio) were modeled by multi-parameter linear regression.

RESULTS: In the SIMMUN cohort, the inflammatory marker neopterin (β = 0.47 [95% CI: 0.34-0.61]), SARS-CoV-2-positivity (0.42 [0.16-0.68]), mental stress (0.18 [0.055-0.31]), and age (0.26 [0.12-0.39]) were positively associated with the kynurenine/tryptophan ratio. The phenylalanine/tyrosine ratio was lower in SARS-CoV-2-positive than uninfected participants (-0.38 [-0.68 to -0.08]). In the INCOV cohort, markers of inflammation were associated with lower serotonin (IL6: -0.22 [-0.38 to -0.053]) and dopamine 3-O-sulfate levels (interferon-gamma: -0.15 [-0.26 to -0.036]). Serotonin (0.76 [0.34-1.2]) and dopamine 3-O-sulfate levels (0.63 [0.28-0.99]) were higher during recovery than in acute SARS-CoV-2 infection.

CONCLUSION: SARS-CoV-2 infection, inflammation, age and mental stress are key independent predictors of kynurenine pathway activity, which may influence serotonin availability. The catecholamine pathway was also affected in SARS-CoV-2 infection. Altered activity of these pathways may contribute to impaired mental health following COVID-19.

PMID:37481962 | DOI:10.1016/j.psyneuen.2023.106334