Strawberry Consumption, Cardiometabolic Risk Factors, and Vascular Function: A Randomized Controlled Trial in Adults with Moderate Hypercholesterolemia.

BACKGROUND: Certain fruits, such as strawberries, may impart cardiometabolic benefits due to their phytochemical content. OBJECTIVES: Study aims were to assess the effects of strawberry intake on cardiometabolic risk factors and vascular endothelial function in adults with moderate hypercholesterolemia. METHODS: This study was a randomized, controlled, double-blinded, 2-arm, 2-period (4-wk/period) crossover trial. Adults (n = 34; male/female 1:1; mean ± SEM age, 53 ± 1 y; BMI, 31 ± 1 kg/m2;  LDL cholesterol, 133 ± 3 mg/dL) were randomly allocated to 1 of 2 study sequences in a 1:1 ratio. Participants drank study beverages twice daily containing freeze-dried strawberry powder (2 × 25 g) or energy-, volume-matched control powder for 4 wk separated by a 4-wk washout. The primary outcome variable was the difference in fasting LDL cholesterol after 4-wk interventions. Secondary outcomes were metabolic markers, inflammation, quantitative (poly)phenolic metabolomics, flow-mediated dilation (FMD), and blood pressure (BP), with the latter (FMD, BP) also assessed acutely at 1 h and 2 h after a 50-g bolus strawberry or control beverage. Mixed-model analysis of repeated measures via PROC MIXED, PC-SAS was performed on primary and secondary outcome variables. RESULTS: LDL cholesterol did not differ after the 4-wk interventions (P > 0.05), nor did fasting total cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, FMD, or BP (all P > 0.05). Significant intervention-by-hour interaction for FMD (P = 0.03) and BP (P = 0.05) revealed increased FMD at 1 h after strawberry compared with control by 1.5 ± 0.38% (P = 0.0008) and attenuated systolic BP at 2 h by 3.1 ± 0.99 mmHg (P = 0.02). Select phenolic metabolites increased significantly (P < 0.05) in blood following strawberry consumption while others decreased, including 3-(4-methoxyphenyl)propanoic acid-3-O-glucuronide, which was significantly correlated with increased FMD (P < 0.05). CONCLUSION: Strawberries may improve vascular health, independent of other metabolic changes. The effect may be related to changes in microbial-derived phenolic metabolites after strawberry consumption influencing endothelial function. Data support inclusion of strawberries in a heart-healthy diet in adults with moderate hypercholesterolemia.This trial was registered at clinicaltrials.gov as NCT02612090.

C4d in Native Glomerular Diseases.

Complement activation occurs in many glomerular diseases, the exact pathway(s) of activation has been studied in detail in some diseases but not in all. C4d is generated by the activation of classical and lectin pathways, and its presence can point to the activation of either of these pathways. This review aims to summarize the available data with regard to the deposition of glomerular C4d in native kidney biopsies in different glomerular pathologies that may be useful for future research into the role of complement activation in glomerular diseases. While there is more information on C4d in certain diseases (e.g., Immunoglobulin A (IgA) nephropathy), there is scant data in other diseases (such as focal segmental glomerulosclerosis).

Contribution of Berry Polyphenols to the Human Metabolome.

Diets rich in berries provide health benefits, however, the contribution of berry phytochemicals to the human metabolome is largely unknown. The present study aimed to establish the impact of berry phytochemicals on the human metabolome. A "systematic review strategy" was utilized to characterize the phytochemical composition of the berries most commonly consumed in the USA; (poly)phenols, primarily anthocyanins, comprised the majority of reported plant secondary metabolites. A reference standard library and tandem mass spectrometry (MS/MS) quantitative metabolomics methodology were developed and applied to serum/plasma samples from a blueberry and a strawberry intervention, revealing a diversity of benzoic, cinnamic, phenylacetic, 3-(phenyl)propanoic and hippuric acids, and benzyldehydes. 3-Phenylpropanoic, 2-hydroxybenzoic, and hippuric acid were highly abundant (mean > 1 µM). Few metabolites at concentrations above 100 nM changed significantly in either intervention. Significant intervention effects (P < 0.05) were observed for plasma/serum 2-hydroxybenzoic acid and hippuric acid in the blueberry intervention, and for 3-methoxyphenylacetic acid and 4-hydroxyphenylacetic acid in the strawberry intervention. However, significant within-group effects for change from baseline were prevalent, suggesting that high inter-individual variability precluded significant treatment effects. Berry consumption in general appears to cause a fluctuation in the pools of small molecule metabolites already present at baseline, rather than the appearance of unique berry-derived metabolites, which likely reflects the ubiquitous nature of (poly)phenols in the background diet.

Bioprospection of actinobacteria derived from freshwater sediments for their potential to produce antimicrobial compounds.

BACKGROUND: Actinobacteria from freshwater habitats have been explored less than from other habitats in the search for compounds of pharmaceutical value. This study highlighted the abundance of actinobacteria from freshwater sediments of two rivers and one lake, and the isolates were studied for their ability to produce antimicrobial bioactive compounds. RESULTS: 16S rRNA gene sequencing led to the identification of 84 actinobacterial isolates separated into a common genus (Streptomyces) and eight rare genera (Nocardiopsis, Saccharopolyspora, Rhodococcus, Prauserella, Amycolatopsis, Promicromonospora, Kocuria and Micrococcus). All strains that showed significant inhibition potentials were found against Gram-positive, Gram-negative and yeast pathogens. Further, three biosynthetic genes, polyketide synthases type II (PKS II), nonribosomal peptide synthetases (NRPS) and aminodeoxyisochorismate synthase (phzE), were detected in 38, 71 and 29% of the strains, respectively. Six isolates based on their antimicrobial potentials were selected for the detection and quantification of standard antibiotics using ultra performance liquid chromatography (UPLC-ESI-MS/MS) and volatile organic compounds (VOCs) using gas chromatography mass spectrometry (GC/MS). Four antibiotics (fluconazole, trimethoprim, ketoconazole and rifampicin) and 35 VOCs were quantified and determined from the methanolic crude extract of six selected Streptomyces strains. CONCLUSION: Infectious diseases still remain one of the leading causes of death globally and bacterial infections caused millions of deaths annually. Culturable actinobacteria associated with freshwater lake and river sediments has the prospects for the production of bioactive secondary metabolites.

Correction to: Bioprospection of actinobacteria derived from freshwater sediments for their potential to produce antimicrobial compounds.

Upon publication of this article [1], it was brought to our attention that Figs. 3, 4 and 5 are incorrectly presented in the original version of the article. The figures were inadvertently swapped in the original submission and published. Figure 3 should be treated as Fig. 5; Fig. 4 should be 3 and Fig. 5 should be Fig. 4.

Analysis of phytochemical variations in dioecious Tinospora cordifolia stems using HPLC/QTOF MS/MS and UPLC/QqQLIT -MS/MS.

INTRODUCTION: The stem of dioecious Tinospora cordifolia (Menispermaceae) is a commonly used traditional Ayurvedic medicine in India having several therapeutic properties. OBJECTIVE: To develop and validate LC-MS methods for the identification and simultaneous quantitation of various secondary metabolites and to study metabolomic variations in the stem of male and female plants. METHODS: Ethanolic extract of stems were analysed by HPLC/ESI-QTOF-MS/MS for rapid screening of bioactive phytochemicals. High resolution MS and MS/MS in positive ESI mode were used for structural investigation of secondary metabolites. An UPLC/ESI-QqQ(LIT) -MS/MS method in MRM mode was developed and validated for the simultaneous quantitation of five bioactive alkaloids. RESULTS: Identification and characterisation of 36 metabolites including alkaloids, sesquiterpenes and phytoecdysteroids were performed using LC-MS and MS/MS techniques. The bioactive alkaloids such as jatrorrhizine, magnoflorine, isocorydine, palmatine and tetrahydropalmatine were successfully quantified in male and female plants. The mean abundances of magnoflorine jatrorrhizine, and oblongine were significantly (P < 0.05) higher in male plants while mean abundances of tetrahydropalmatine, norcoclaurine, and reticuline were significantly (P < 0.05) higher in female plants. CONCLUSIONS: Phytochemicals in the stem of male and female Tinospora cordifolia showed significant qualitative and quantitative variations. LC-MS and MS/MS methods can be used to differentiate between male and female plants based on their chemical profiles and quantities of the marker bioactive alkaloids. This chemical composition difference was also evident during vegetative stage when there were no male and female flowers.

Quality control assessment of polyherbal formulation based on a quantitative determination multimarker approach by ultra high performance liquid chromatography with tandem mass spectrometry using polarity switching combined with multivariate analysis.

An ultra high performance liquid chromatography with electrospray ionization tandem mass spectrometry method has been developed and validated for the simultaneous quantification of 28 major bioactive compounds in Mentat tablet, a complex Indian herbal medicine used in the treatment of neurological disorder and improvement of mental health. Multiple-reaction monitoring scanning was employed for quantification in positive and negative ion switching mode. The analysis was accomplished on Waters ACQUITY UPLC BEH C18 column with linear gradient elution of water/formic acid (0.1%) and acetonitrile/formic acid (0.1%) at a flow rate of 0.3 mL/min. The proposed method was validated with acceptable linearity (r2 , 0.9984-0.9999), precision (RSD, 0.22-2.11%), stability (RSD, 0.16-1.78%), and recovery (RSD ≤ 3.74%), under optimum conditions. The limits of quantitation ranged from 0.28 to 3.88 ng/mL. The method was successfully applied for simultaneous determination of 28 compounds in 20 batches of Mentat tablet. Hierarchical cluster analysis and principal component analysis were performed to evaluate the similarity and variation of the 20 samples based on the characteristics of 28 bioactive compounds. Results indicated that this method is rapid, sensitive, and reliable to show the quality of the Mentat tablet's composition, hence may be used for quality control of polyherbal formulations having similar markers/raw herbs.

Simultaneous quantitative determination of multiple bioactive markers in Ocimum sanctum obtained from different locations and its marketed herbal formulations using UPLC-ESI-MS/MS combined with principal component analysis.

INTRODUCTION: Ocimum sanctum L., with phenolic acids, flavonoids, propenyl phenols and terpenoids as active pharmacological constituents, is a popular medicinal herb and is present as an ingredient in many herbal formulations. Therefore, development of a reliable analytical method for simultaneous determination of the pharmacologically active constituents of O. sanctum is of high importance. OBJECTIVE: To develop and validate a new, rapid, sensitive and selective UPLC-ESI/MS/MS method for simultaneous determination of 23 bioactive markers including phenolic acids, flavonoids, propenyl phenol and terpenoid in the leaf extract and marketed herbal formulations of O. sanctum. METHODS: An UPLC-ESI/MS/MS method using negative electrospray ionisation (ESI) in multiple-reaction-monitoring (MRM) mode was used for simultaneous determination. Chromatographic separation was achieved on an Acquity UPLC BEH C18 -column using a gradient elution with 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Principal component analysis (PCA) was applied to correlate and discriminate eight geographical collections of O. sanctum based on quantitative data of the analytes. RESULTS: The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate, with overall recovery in the range 95.09-104.84% (RSD ≤ 1.85%), precise (RSD ≤ 1.98%) and linear (r(2) ≥ 0.9971) over the concentration range of 0.5-1000 ng/mL. Ursolic acid was found to be the most abundant marker in all the samples investigated, except for the marketed tablet. CONCLUSION: The method established is simple, rapid and sensitive, hence it can be reliably utilised for the quality control of O. sanctum and derived herbal formulations.

Direct renin inhibitor induced renal failure.

Aliskiren, a direct renin inhibitor, is a novel antihypertensive agent with placebo-like tolerability. The patient developed acute renal failure after addition of aliskiren to combination of diuretic, angiotensin-converting enzyme inhibitor and aldosterone antagonist. This case highlights the point that acute renal failure can occur as an adverse effect of aliskiren. Because there is no conclusive evidence about the safety of aliskiren when used in combination with multiple drugs that inhibit renin angiotensin aldosterone system, caution should be exercised while initiating this drug in patients already on combination of diuretic, angiotensin-converting enzyme inhibitor and aldosterone antagonist.

Relationship between heart rate variability and pulse wave velocity and their association with patient outcomes in chronic kidney disease.

BACKGROUND: Arterial stiffness and low heart rate variability (HRV) have each been associated with increased cardiovascular risk in a variety of patient populations. We explored the relationship between HRV and pulse wave velocity (PWV measure of arterial stiffness) in patients with chronic kidney disease (CKD prior to ESRD) along with examining their association with the outcomes of cardiovascular disease (CVD), death, and progression to end stage renal disease (ESRD). METHODS: The RRI-CKD Study is a 4-center prospective cohort study of CKD stages 3 - 5 (n = 834). A subset underwent both HRV testing by 24-hour Holter and carotid-femoral PWV (n = 240). Multiple linear regression was used to assess predictors of PWV and Cox regression to investigate the association of HRV and PWV with time to first CVD event or death and ESRD. RESULTS: Although several HRV measures were inversely correlated with PWV, this association was attenuated after adjustment for age and/or diabetes and no longer significant after adjustment for C-reactive protein. Low HRV and high PWV were individually associated with increased risk of the composite endpoint of CVD/death in multivariable analysis. The risk of the composite of CVD/death was highest for patients with both low HRV and high PWV. CONCLUSION: Age, diabetes, and inflammation together explained the inverse association between HRV and PWV. Inflammation may play a role in the pathogenesis of both low HRV and high PWV. The combination of low HRV and high PWV showed the strongest association with a composite CVD outcome. Mechanisms underlying abnormalities in PWV and HRV, and the role of these measures as intermediate outcomes in future trials in CKD patients, merit further study.

Development and validation of an ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry method for the simultaneous determination of selected flavonoids in Ginkgo biloba.

A rapid and sensitive ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry method was developed and validated for the simultaneous determination of 13 flavonoids in leaf, stem, and fruit extracts of male and female trees of Ginkgo biloba to investigate gender- and age-related variations of flavonoids content. Chromatographic separation was accomplished on an Acquity UPLC BEH C18 column (50 mm × 2.1 mm id, 1.7 µm) in 5 min. Quantitation was performed using negative electrospray ionization mass spectrometry in multiple reaction monitoring mode. The calibration curves of all analytes showed a good linear relationship (r(2) ≥ 0.9977) over the concentration range of 1-1000 ng/mL. The precision evaluated by an intra- and interday study showed RSD ≤ 1.98% and good accuracy with overall recovery in the range from 97.90 to 101.09% (RSD ≤ 1.67%) for all analytes. The method sensitivity expressed as the limit of quantitation was typically 0.25-3.57 ng/mL. The results showed that the total content of 13 flavonoids was higher in the leaf extract of an old male Ginkgo tree compared to young female Ginkgo trees.

Chronic and postprandial effect of blueberries on cognitive function, alertness, and mood in participants with metabolic syndrome - results from a six-month, double-blind, randomized controlled trial.

BACKGROUND: Anthocyanin and blueberry intakes positively associated with cognitive function in population-based studies and cognitive benefits in randomized controlled trials of adults with self-perceived or clinical cognitive dysfunction. To date, adults with metabolic syndrome (MetS) but without cognitive dysfunction are understudied. OBJECTIVES: Cognitive function, mood, alertness, and sleep quality were assessed as secondary end points in MetS participants, postprandially (>24 h) and following 6-mo blueberry intake. METHODS: A double-blind, randomized controlled trial was conducted, assessing the primary effect of consuming freeze-dried blueberry powder, compared against an isocaloric placebo, on cardiometabolic health >6 mo and a 24 h postprandial period (at baseline). In this secondary analysis of the main study, data from those completing mood, alertness, cognition, and sleep assessments are presented (i.e., n = 115 in the 6 mo study, n = 33 in the postprandial study), using the following: 1) Bond-Lader self-rated scores, 2) electronic cognitive battery (i.e., testing attention, working memory, episodic memory, speed of memory retrieval, executive function, and picture recognition), and 3) the Leeds Sleep Evaluation Questionnaire. Urinary and serum anthocyanin metabolites were quantified, and apolipoprotein E genotype status was determined. RESULTS: Postprandial self-rated calmness significantly improved after 1 cup of blueberries (P = 0.01; q = 0.04; with an 11.6% improvement compared with baseline between 0 and 24 h for the 1 cup group), but all other mood, sleep, and cognitive function parameters were unaffected after postprandial and 6-mo blueberries. Across the ½ and 1 cup groups, microbial metabolites of anthocyanins and chlorogenic acid (i.e., hydroxycinnamic acids, benzoic acids, phenylalanine derivatives, and hippuric acids) and catechin were associated with favorable chronic and postprandial memory, attention, executive function, and calmness. CONCLUSIONS: Although self-rated calmness improved postprandially, and significant cognition-metabolite associations were identified, our data did not support strong cognitive, mood, alertness, or sleep quality improvements in MetS participants after blueberry intervention. This trial was registered at clinicaltrials.gov as NCT02035592.

Dronedarone-induced digoxin toxicity: new drug, new interactions.

Dronedarone is a relatively new antiarrhythmic drug approved for paroxysmal or persistent atrial fibrillation. Dronedarone can inhibit P-glycoprotein-mediated digoxin clearance and increase steady-state digoxin level 2.5 times. It is important to closely monitor plasma digoxin levels or administer a lower loading dose of digoxin in patients taking dronedarone concomitantly. We report a case of digoxin toxicity in a patient taking concomitant dronedarone as a result of interaction between digoxin and dronedarone.

Predictors of heart rate variability and its prognostic significance in chronic kidney disease.

BACKGROUND: Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney disease (CKD). METHODS: HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3-5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD). RESULTS: A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker. CONCLUSIONS: This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study.

Disseminated tuberculosis secondary to adalimumab.

A 62-year-old woman with rheumatoid arthritis presented with fever (T-103.9°F). Vital signs and physical examination were normal. She was taking adalimumab, methotrexate, and prednisone for the past 9 months. Blood and urine cultures, human immunodeficiency virus, rapid plasma reagin, purified protein derivative, and cerebrospinal fluid test findings were negative. Computed tomography showed scattered 0.2-cm nodules in the lungs and innumerable subcentimeter lesions in the liver and spleen. Broad-spectrum antibiotics were started empirically. Liver biopsy findings revealed necrotizing granulomas and were negative for acid fast bacilli and fungi on staining. As the patient was persistently febrile despite antibiotics, the antibiotics were discontinued, and an antituberculous regimen including INH, ethambutol, and pyrazinamide was initiated empirically on day 40 of hospitalization. Fourteen days after liver biopsy, acid-fast bacilli grew in the tissue culture. Disseminated tuberculosis (TB) was diagnosed. Fever subsided after 1 week of anti-TB treatment. Antitumor necrosis factor alpha therapy in rheumatoid arthritis increases the risk of TB 5-fold. This is mostly as a result of reactivation of latent TB and commonly presents as disseminated TB. It usually occurs in the early stage of treatment. In our patient, the screening test results for TB before initiation of Adalimumab could have been falsely negative due to immunosuppression secondary to steroids. Our case emphasizes that current screening tests can miss latent TB especially in immunosuppressed patients. As it is difficult to diagnose TB with polymerase chain reaction and culture, histopathology should be sought early. Patients on antitumor necrosis factor alpha therapy presenting with fever of unknown origin should be considered for empirical anti-TB treatment regardless of microbiological and tissue diagnosis.

Complete heart block following a blow on the chest by a soccer ball: a rare manifestation of commotio cordis.

Commotio cordis is a rare type of blunt cardiac injury in which low impact chest trauma causes sudden cardiac arrest, usually occurs from being struck by a projectile during sports. The most common arrhythmia during commotio cordis is ventricular fibrillation, although complete heart block and an idioventricular rhythm have also been reported. We describe a case of a young patient who presented with a persistent third-degree atrioventricular block and a left bundle branch block, following blunt chest trauma, as a result of blow by soccer ball and subsequently needed a permanent pacemaker.

Blueberry anthocyanin intake attenuates the postprandial cardiometabolic effect of an energy-dense food challenge: Results from a double blind, randomized controlled trial in metabolic syndrome participants.

BACKGROUND & AIMS: Whilst the cardioprotective effects of blueberry intake have been shown in prospective studies and short-term randomized controlled trials (RCTs), it is unknown whether anthocyanin-rich blueberries can attenuate the postprandial, cardiometabolic dysfunction which follows energy-dense food intakes; especially in at-risk populations. We therefore examined whether adding blueberries to a high-fat/high-sugar meal affected the postprandial cardiometabolic response over 24 h. METHODS: A parallel, double-blind RCT (n = 45; age 63.4 ± 7.4 years; 64% male; BMI 31.4 ± 3.1 kg/m2) was conducted in participants with metabolic syndrome. After baseline assessments, an energy-dense drink (969 Kcals, 64.5 g fat, 84.5 g carbohydrate, 17.9 g protein) was consumed with either 26 g (freeze-dried) blueberries (equivalent to 1 cup/150 g fresh blueberries) or 26 g isocaloric matched placebo. Repeat blood samples (30, 60, 90, 120, 180, 360 min and 24 h), a 24 h urine collection and vascular measures (at 3, 6, and 24 h) were performed. Insulin and glucose, lipoprotein levels, endothelial function (flow mediated dilatation (FMD)), aortic and systemic arterial stiffness (pulse wave velocity (PWV), Augmentation Index (AIx) respectively), blood pressure (BP), and anthocyanin metabolism (serum and 24 h urine) were assessed. RESULTS: Blueberries favorably affected postprandial (0-24 h) concentrations of glucose (p < 0.001), insulin (p < 0.01), total cholesterol (p = 0.04), HDL-C, large HDL particles (L-HDL-P) (both p < 0.01), extra-large HDL particles (XL-HDL-P; p = 0.04) and Apo-A1 (p = 0.01), but not LDL-C, TG, or Apo-B. After a transient higher peak glucose concentration at 1 h after blueberry intake ([8.2 mmol/L, 95%CI: 7.7, 8.8] vs placebo [6.9 mmol/L, 95%CI: 6.4, 7.4]; p = 0.001), blueberries significantly attenuated 3 h glucose ([4.3 mmol/L, 95%CI: 3.8, 4.8] vs placebo [5.1 mmol/L, 95%CI: 4.6, 5.6]; p = 0.03) and insulin concentrations (blueberry: [23.4 pmol/L, 95%CI: 15.4, 31.3] vs placebo [52.9 pmol/L, 95%CI: 41.0, 64.8]; p = 0.0001). Blueberries also improved HDL-C ([1.12 mmol/L, 95%CI: 1.06, 1.19] vs placebo [1.08 mmol/L, 95%CI: 1.02, 1.14]; p = 0.04) at 90 min and XL-HDLP levels ([0.38 × 10-6, 95%CI: 0.35, 0.42] vs placebo [0.35 × 10-6, 95%CI: 0.32, 0.39]; p = 0.02) at 3 h. Likewise, significant improvements were observed 6 h after blueberries for HDL-C ([1.17 mmol/L, 95%CI: 1.11, 1.24] vs placebo [1.10 mmol/L, 95%CI: 1.03, 1.16]; p < 0.001), Apo-A1 ([1.37 mmol/L, 95%CI: 1.32, 1.41] vs placebo [1.31 mmol/L, 95%CI: 1.27, 1.35]; p = 0.003), L-HDLP ([0.70 × 10-6, 95%CI: 0.60, 0.81] vs placebo [0.59 × 10-6, 95%CI: 0.50, 0.68]; p = 0.003) and XL-HDLP ([0.44 × 10-6, 95%CI: 0.40, 0.48] vs placebo [0.40 × 10-6, 95%CI: 0.36, 0.44]; p < 0.001). Similarly, total cholesterol levels were significantly lower 24 h after blueberries ([4.9 mmol/L, 95%CI: 4.6, 5.1] vs placebo [5.0 mmol/L, 95%CI: 4.8, 5.3]; p = 0.04). Conversely, no effects were observed for FMD, PWV, AIx and BP. As anticipated, total anthocyanin-derived phenolic acid metabolite concentrations significantly increased in the 24 h after blueberry intake; especially hippuric acid (6-7-fold serum increase, 10-fold urinary increase). In exploratory analysis, a range of serum/urine metabolites were associated with favorable changes in total cholesterol, HDL-C, XL-HDLP and Apo-A1 (R = 0.43 to 0.50). CONCLUSIONS: For the first time, in an at-risk population, we show that single-exposure to the equivalent of 1 cup blueberries (provided as freeze-dried powder) attenuates the deleterious postprandial effects of consuming an energy-dense high-fat/high-sugar meal over 24 h; reducing insulinaemia and glucose levels, lowering cholesterol, and improving HDL-C, fractions of HDL-P and Apo-A1. Consequently, intake of anthocyanin-rich blueberries may reduce the acute cardiometabolic burden of energy-dense meals. CLINICAL TRIAL REGISTRY: NCT02035592 at www.clinicaltrials.gov.

Minimal change disease and COVID-19 vaccination: Four cases and review of literature.

There have been multiple reports of the development of de novo or relapse of glomerular diseases after SARS-CoV-2 vaccination. While most of them have occurred with the mRNA vaccines (Pfizer/BioNTech and Moderna/NIAID), there also have been reports associated with the vector vaccines (AstraZeneca/ChAdOx1-S) vaccine and the inactivated vaccines. Minimal change disease (MCD) is one of the more common glomerular diseases noted to have been associated with the COVID-19 vaccination. We report here 4 more cases of MCD occurring in association with the COVID-19 vaccine, 3 were de novo cases, and 1 case had a relapse of MCD. We also review all the 41 cases described thus far in the literature and review potential common pathways activated by the vaccination that play a role in the pathogenesis of MCD.

Electrocardiographic changes in Takotsubo cardiomyopathy.

INTRODUCTION: Takotsubo cardiomyopathy (TC) is a unique transient nonischemic cardiomyopathy that mimics acute myocardial infarction (MI). The aim of our study was to evaluate electrocardiographic changes in patients with TC, including the frequency of ST elevation and other abnormalities. METHODS: Eleven patients were retrospectively identified from echocardiography database. All patients underwent coronary angiography and fulfilled the Mayo criteria for diagnosis of TC during the period November 2005 to September 2010. Standard 12-lead electrocardiograms recorded daily during the first week of hospitalization, after onset of symptoms were analyzed. RESULTS: Eight of 11 patients were found to have ST elevation, of which two patients had ST depression in reciprocal leads. No patient had ST elevation in lead V1, most likely reason being that wall-motion abnormalities in TC rarely extend to the region faced by lead V1. Pathological Q waves were found in five patients, of which two patients had transient Q waves, suggesting less myocardial damage. All 11 patients had T-wave inversion; eight of these patients had diffuse symmetric T-wave inversion, extending beyond the perfusion territory of any single coronary artery. QTc interval prolongation was found in 10 patients. All patients had left ventricular ejection fraction between 25% and 35% on presentation, which could not be predicted by the extent of electrocardiogram (ECG) changes. CONCLUSION: ECG changes in TC are distinctive and differ from those typically seen in acute anterior MI. The ECG abnormalities described may be important clues for the clinician to suspect diagnosis of TC in the right clinical setting.

Acute glomerulonephritis in a hematopoietic blood stem cell donor.

Use of granulocyte colony-stimulating factor (G-CSF) has been associated with side effects including reports of acute glomerulonephritis (GN), almost all of which have been immune complex associated. There is one prior report of pauci-immune GN in a child, but was negative for ANCA (anti-neutrophilic cytoplasmic antibodies). We describe the first case of ANCA-positive pauci-immune GN exacerbated by the use of G-CSF for peripheral blood stem cell (PBSC) donation in a patient with no prior history of vasculitis. Given the use of G-CSF in PBSC donation and neutropenias associated with various conditions, it is important that both the nephrologist and the hematologist are aware of the renal risks associated with its use.