Persistent bacteremia predicts poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections receiving appropriate therapy.

PURPOSE: Identifying persistent bacteremia early in patients with neutropenia may improve outcome. This study evaluated the role of follow-up blood cultures (FUBC) positivity in predicting outcomes among patients with neutropenia and carbapenem-resistant gram-negative bloodstream infections (CRGNBSI). METHODS: This retrospective cohort study conducted between December 2017 and April 2022 included patients more than 15 years old with neutropenia and CRGNBSI, who survived for ≥ 48 h, receiving appropriate antibiotic therapy and had FUBCs. Patients with polymicrobial bacteremia within 30 days were excluded. The primary outcome was 30 day mortality. Persistent bacteremia, septic shock, recovery from neutropenia, prolonged or profound neutropenia, requirement of intensive care and dialysis, and initiation of appropriate empirical therapy were also studied. RESULTS: In our study cohort of 155 patients, the 30 day mortality rate was 47.7%. Persistent bacteremia was common in our patient cohort (43.8%). Carbapenem resistant isolates identified in the study were K.pneumoniae (80%), E.coli (12.26%), P.aeruginosa (5.16%), A.baumanii (1.94%) and E.cloacae (0.65%). The median time for sending a FUBC was 2 days (IQR, 1-3 days). Patients with persistent bacteremia had higher mortality than those without (56.76% versus 32.1%; p < 0.001). Appropriate initial empirical therapy was given to 70.9%. Recovery from neutropenia occurred in 57.4% while 25.8% had prolonged or profound neutropenia. Sixty-nine percent (107/155) had septic shock and needed intensive care; 12.2% of patients required dialysis. Non-recovery from neutropenia (aHR, 4.28; 95% CI 2.53-7.23), presence of septic shock (aHR, 4.42; 95%CI 1.47-13.28), requirement of intensive care (aHR,3.12;95%CI 1.23-7.93), and persistent bacteremia (aHR,1.74; 95%CI 1.05-2.89) significantly predicted poor outcomes in multivariable analysis. CONCLUSION: FUBC showing persistent bacteremia predicted poor outcomes among neutropenic patients with carbapenem-resistant gram-negative bloodstream infections (CRGNBSI) and should be routinely reported.

Rare Mesenchymal Tumors of the Pelvis: Imaging and Pathologic Correlation.

Most pelvic tumors originate from the organs. Less commonly, tumors can arise from the various anatomic pelvic compartments and are comprised of mesenchymal tissue: muscles, connective tissue, vessels, lymphatics, and fat. Among some of the rarer entities are benign tumors (eg, angiomyxoma, cellular angiofibroma, and desmoid fibromatosis), malignant tumors (eg, sarcoma), and tumors that can manifest as benign or malignant (eg, solitary fibrous tumor or nerve sheath tumor). Because these tumors are uncommon and often manifest with nonspecific clinical features, imaging (usually MRI) is an initial step in the evaluation. Radiologists interpreting these images are asked to help narrow the differential diagnosis and assess the likelihood of malignancy for treatment planning. Thus, the MRI report should include the imaging features that would indicate the underlying tissue histology for pathologic diagnosis as well as a description of the anatomic extent and pattern of growth. The authors describe multiple locally aggressive benign and malignant mesenchymal tumors and highlight characteristic clinical and imaging features that enable the radiologist to narrow the differential diagnosis. The anatomic spaces of the pelvis are reviewed with illustrations to aid the radiologist in describing these tumors, which often span multiple pelvic compartments. Tumor appearance at T2-weighted, diffusion-weighted, and postcontrast MRI is summarized and illustrated with correlation at CT or fluorodeoxyglucose PET/CT, when available. MRI features that correspond to specific types of tissue (eg, myxoid, fibrous, or vascular) are highlighted and correlated with images from pathologic evaluation. Online supplemental material is available for this article. ©RSNA, 2021.

A study on seroconversion following first & second doses of ChAdOx1 nCoV-19 vaccine in Central Kerala.

Background & objectives: Vaccination against COVID-19 induces spike protein-binding IgG antibodies, a robust correlate of protection against COVID-19. This study was undertaken to assess the humoral response after completion of both the doses of ChAdOx1 nCoV vaccine in healthcare workers (HCWs) at a tertiary care health centre in India. Methods: A cross-sectional COVID-19 vaccine-induced antibody study was conducted among HCWs. IgG antibodies against spike protein were measured at least 28 days after the first dose and the second dose of vaccination in both SARS CoV-2 naïve and recovered HCWs. Mean and median antibody titre following each dose of vaccine and its association with age, gender, co-morbidities and factors such as exercise, stress and sleep deprivation were also explored. Results: Among the 200 vaccine recipients, 91.5 per cent showed seroconversion after the first dose and 99.5 per cent after the second dose. The mean titre after the second dose was significantly higher when compared to the first dose (12.68±4.17 vs. 9.83±6.3, P=0.001). More than half (54%) had high antibody titre ≥12 S/Co (Signal/cut-off). Previous COVID-19 infection was the single most important factor influencing antibody production, where the mean titre just after a single dose [mean-17.81±5.94, median-20.5 (interquartile range [IQR]-3.7)] surpassed the titre after the second dose in SARS CoV-2 naïve individuals [mean-12.29±4.00, median-12.8 (IQR-3.7), P=0.001]. Furthermore, 28 per cent of vaccinees showed a reduction in titre after the second dose. The mean fall in titre was 2.25±1.40 and was more pronounced in males, the younger age group and those with previous COVID-19 infection. Interpretation & conclusions: ChAdOx1 nCov-19 vaccine after two doses elicited an excellent immune response. However, greater immunogenicity after the first dose was seen among those with previous COVID-19 infection, even surpassing the titre achieved by the second dose of vaccine in SARS CoV-2 naïve recipients. A fall in antibody titre after the second dose is a matter of concern and requires further studies.

Novel Spray Dried Algae-Rosemary Particles Attenuate Pollution-Induced Skin Damage.

The present study investigated the effect of spray-dried algae-rosemary particles against pollution-induced damage using ex-vivo human biopsies exposed to diesel engine exhaust (DEE). For this, the complexation of hydroalcoholic rosemary extract with Chlorella (RCH) and Spirulina (RSP) protein powders was conducted. The process efficiency and concentration of rosmarinic acid (RA), carnosic acid (CA), and carnosol (CR) phenolic compounds of both products were compared. The RSP spray-dried production was more efficient, and RSP particles presented higher CR and CA and similar RA concentrations. Therefore, spray-dried RSP particles were prioritized for the preparation of a gel formulation that was investigated for its ability to mitigate pollution-induced skin oxinflammatory responses. Taken altogether, our ex-vivo data clearly demonstrated the ability of RSP gel to prevent an oxinflammatory phenomenon in cutaneous tissue by decreasing the levels of 4-hydroxynonenal protein adducts (4HNE-PA) and active matrix metalloproteinase-9 (MMP-9) as well as by limiting the loss of filaggrin induced by DEE exposure. Our results suggest that the topical application of spirulina-rosemary gel is a good approach to prevent pollution-induced skin aging/damage.

In vitro mineral nutrition of Curcuma longa L. affects production of volatile compounds in rhizomes after transfer to the greenhouse.

BACKGROUND: Turmeric is a rich source of bioactive compounds useful in both medicine and cuisine. Mineral concentrations effects (PO43-, Ca2+, Mg2+, and KNO3) were tested during in vitro rhizome development on the ex vitro content of volatile constituents in rhizomes after 6 months in the greenhouse. A response surface method (D-optimal criteria) was repeated in both high and low-input fertilizer treatments. Control plants were grown on Murashige and Skoog (MS) medium, acclimatized in the greenhouse and grown in the field. The volatile constituents were investigated by GC-MS. RESULTS: The total content of volatiles was affected by fertilizer treatments, and in vitro treatment with Ca2+ and KNO3; but PO43- and Mg2+ had no significant effect. The content was higher in the high-input fertilizer treatments (49.7 ± 9 mg/g DM) with 4 mM Ca2+, 60 mM KNO3 and 5 mM NH4+, than the low-input fertilizer (26.6 ± 9 mg/g DM), and the MS control (15.28 ± 2.7 mg/g DM; 3 mM Ca2+, 20 mM K+, 39 mM NO3-, 20 mM NH4+, 1.25 mM PO43-, and 1.5 mM Mg2+). The interaction of Ca2+ with KNO3 affected curcumenol isomer I and II, germacrone, isocurcumenol, and ß-elemenone content. Increasing in vitro phosphate concentration to 6.25 mM increased ex vitro neocurdione and methenolone contents. CONCLUSION: These results show that minerals in the in vitro bioreactor medium during rhizome development affected biosynthesis of turmeric volatile components after transfer to the greenhouse six months later. The multi-factor design identified 1) nutrient regulation of specific components within unique phytochemical profile for Curcuma longa L. clone 35-1 and 2) the varied phytochemical profiles were maintained with integrity during the greenhouse growth in high fertility conditions.

Correction to: In vitro mineral nutrition of Curcuma longa L. affects production of volatile compounds in rhizomes after transfer to the greenhouse.

Following publication of the original article [1], the author reported a formatting error and an error in the figure caption. The original article has been corrected. The details of the errors are as follows.

Influence of Ingesting a Flavonoid-Rich Supplement on the Metabolome and Concentration of Urine Phenolics in Overweight/Obese Women.

This study evaluated the effect of ingesting a flavonoid-rich supplement (329 mg/d) on total urine phenolics and shifts in plasma metabolites in overweight/obese female adults using untargeted metabolomics procedures. Participants (N = 103, 18-65 y, BMI ≥ 25 kg/m2) were randomized to flavonoid (F) or placebo (P) groups for 12 weeks with blood and 24 h urine samples collected prestudy and after 4 and 12 weeks in a parallel design. Supplements were prepared as chewable tablets and included vitamin C, wild bilberry fruit extract, green tea leaf extract, quercetin, caffeine, and omega 3 fatty acids. At 4 weeks, urine total phenolics increased 24% in F versus P with similar changes at 12 weeks (interaction effect, P = 0.041). Groups did not differ in markers of inflammation (IL-6, MCP-1, CRP) or oxidative stress (oxLDL, FRAP). Metabolomics data indicated shifts in 63 biochemicals in F versus P with 70% from the lipid and xenobiotics superpathways. The largest fold changes in F were measured for three gut-derived phenolics including 3-methoxycatechol sulfate, 3-(3-hydroxyphenyl)propanoic acid sulfate, and 1,2,3-benzenetriol sulfate (interaction effects, p ≤ 0.050). This randomized clinical trial of overweight/obese women showed that 12 weeks ingestion of a mixed flavonoid nutrient supplement was associated with a corresponding increase in urine total phenolics and gut-derived phenolic metabolites.

Mycobacterium riyadhense in Saudi Arabia.

We explored in detail the nationwide existence of Mycobacterium riyadhense in Saudi Arabia. In 18 months, 12 new cases of M. riyadhense infection were observed, predominantly among Saudi nationals, as a cause of pulmonary disease. M. riyadhense may be emerging as a more common pathogen in Saudi Arabia.

One-step isolation of carnosic acid and carnosol from rosemary by centrifugal partition chromatography.

Carnosic acid and carnosol are the main bioactive components responsible for the significant antioxidant activity of Rosmarinus officinalis. Nevertheless, they are known for their instability in solutions. Separation of both compounds from crude rosemary extract was successfully achieved by one-step centrifugal partition chromatography without any degradation. A two-phase solvent system, hexane/ethyl acetate/methanol/water (3:2:3:2 v/v) was run on a preparative scale applying the elution-extrusion technique in descending mode. A 900 mg quantity of the crude extract containing 39.7% carnosic acid and 12.3% carnosol was loaded onto a 500 mL column, rotating at 1800 rpm. Carnosic acid and carnosol were obtained at purities of 96.1 ± 1% and 94.4 ± 0.9%, with recoveries of 94.3 ± 4.4% and 94.8 ± 2.3%, respectively. The compounds were identified by mass spectrometry, tandem mass spectrometry, and comparison with authentic standards.

Metabolic Effects of Berries with Structurally Diverse Anthocyanins.

Overconsumption of energy dense foods and sedentary lifestyle are considered as major causes of obesity-associated insulin resistance and abnormal glucose metabolism. Results from both cohort studies and randomized trials suggested that anthocyanins from berries may lower metabolic risks, however these reports are equivocal. The present study was designed to examine effects of six berries with structurally diverse anthocyanin profiles (normalized to 400 µg/g total anthocyanin content) on development of metabolic risk factors in the C57BL/6 mouse model of polygenic obesity. Diets supplemented with blackberry (mono-glycosylated cyanidins), black raspberry (acylated mono-glycosylated cyanidins), blackcurrant (mono- and di-glycosylated cyanidins and delphinidins), maqui berry (di-glycosylated delphinidins), Concord grape (acylated mono-glycosylated delphinidins and petunidins), and blueberry (mono-glycosylated delphinidins, malvidins, and petunidins) showed a prominent discrepancy between biological activities of delphinidin/malvidin-versus cyanidin-type anthocyanins that could be explained by differences in their structure and metabolism in the gut. Consumption of berries also resulted in a strong shift in the gastrointestinal bacterial communities towards obligate anaerobes that correlated with decrease in the gastrointestinal luminal oxygen and oxidative stress. Further work is needed to understand mechanisms that lead to nearly anoxic conditions in the gut lumens, including the relative contributions of host, diet and/or microbial oxidative activity, and their implication to human health.

Novel strategies for capturing health-protective mango phytochemicals in shelf stable food matrices.

Cost-effective methods for concentration and stabilization of otherwise perishable mango fruit phytoactives into shelf stable high protein ingredients were developed to combat stunting (malnutrition) in rural Africa. Mango juices complexed with sunflower oil and protein-rich legume flours yielded carotenoid-enriched oils and pelleted polyphenol-enriched flour matrices. Carotenoids from juices were concentrated 9-10 times in the fortified sunflower oil. Protein-rich soy and peanut flours captured 2.2-3.2 mg/g polyphenols from the juices. Alternatively, mango juice was sorbed and co-dried with flours, which stably bound the polyphenols, carotenoids, and natural sugars in soy or peanut protein-rich matrices. The concentration of provitamin A carotenoids was almost doubled and total polyphenols were enriched 4-5 times higher in the matrices compared to fresh pureed juice. Both strategies require minimal instrumentation, are compatible with rural village dietary practices; and capture the benefits of otherwise perishable seasonal resources by complexing healthful proteins together with phytoactive compounds.

Cytotoxic effects of ellagitannins isolated from walnuts in human cancer cells.

Walnuts contain many bioactive components that may slow cancer growth. A previous report showed that a diet supplemented with walnuts decreased the tumor size formed by MDA-MB-231 human cancer cells injected into nude mice. However, the mechanism of action was never determined. We characterized the effects of a methanol extract prepared from walnuts on human MDA-MB-231, MCF7, and HeLa cells. The extract was cytotoxic to all cancer cells. We identified compounds from the methanol extract that induced this cytotoxicity. The predominant compounds were Tellimagrandin I and Tellimagrandin II, members of the ellagitannin family. We also show a walnut extract decreases the intracellular pH, depolarizes the mitochondrial membrane with release of cytochrome c and phosphatidylserine flipping. The antimitogenic effects of walnut extract were associated with a twofold reduction of mitochondria respiration. These results suggest impairment of mitochondrial function and apoptosis as relevant mechanism of anticancer effects of the walnut extract.

Phlorotannins from Alaskan seaweed inhibit carbolytic enzyme activity.

Global incidence of type 2 diabetes has escalated over the past few decades, necessitating a continued search for natural sources of enzyme inhibitors to offset postprandial hyperglycemia. The objective of this study was to evaluate coastal Alaskan seaweed inhibition of α-glucosidase and α-amylase, two carbolytic enzymes involved in serum glucose regulation. Of the six species initially screened, the brown seaweeds Fucus distichus and Alaria marginata possessed the strongest inhibitory effects. F. distichus fractions were potent mixed-mode inhibitors of α-glucosidase and α-amylase, with IC50 values of 0.89 and 13.9 µg/mL, respectively; significantly more efficacious than the pharmaceutical acarbose (IC50 of 112.0 and 137.8 µg/mL, respectively). The activity of F. distichus fractions was associated with phlorotannin oligomers. Normal-phase liquid chromatography-mass spectrometry (NPLC-MS) was employed to characterize individual oligomers. Accurate masses and fragmentation patterns confirmed the presence of fucophloroethol structures with degrees of polymerization from 3 to 18 monomer units. These findings suggest that coastal Alaskan seaweeds are sources of α-glucosidase and α-amylase inhibitory phlorotannins, and thus have potential to limit the release of sugar from carbohydrates and thus alleviate postprandial hyperglycemia.

Anthocyanin profiling of wild maqui berries (Aristotelia chilensis [Mol.] Stuntz) from different geographical regions in Chile.

BACKGROUND: Maqui (Aristotelia chilensis) is a Chilean species which produces small berries that are collected from the wild. Anthocyanins, because of their health benefits, are the major focus of interest in maqui fruit. For this study, we examined anthocyanin and phenolic content of maqui fruits from individuals that belonged to four geographical areas in Chile, and used DNA marker analysis to examine the genetic variability of maqui populations that had distinctly different fruit anthocyanin content. RESULTS: Twelve primers generated a total of 145 polymorphic inter simple sequence repeat-polymerase chain reaction (ISSR-PCR) bands. ISSR-PCR showed different banding patterns for the individuals evaluated, confirming that maqui populations belonged to different genotypes. Maqui fruit from four different geographical regions during two consecutive growing seasons showed high total anthocyanin (6.6-15.0 g cy-3-glu kg⁻¹ fresh weight (FW)) and phenolic (10.7-20.5 g GAE kg⁻¹ FW) contents and different anthocyanin profiles. CONCLUSION: Three maqui genotypes exhibited significantly higher anthocyanin content than the others, as measured by pH differential method and high-performance liquid chromatography-mass spectrometry. Significant genetic diversity was noted within each ecological population. ISSR-PCR analysis provided a fingerprinting approach applicable for differentiation of maqui genotypes.

Leishmanicidal activity of a daucane sesquiterpene isolated from Eryngium foetidum.

CONTEXT: Eryngium foetidum L. (Apiaceae) is a traditional herb that has been used for numerous medicinal applications, including as a treatment for parasitic infections, especially in the Neotropics from where it originates. OBJECTIVE: This study evaluates the in vitro leishmanicidal and cytotoxicity activities of isolated compounds based on a bioassay-guided fractionation approach. MATERIALS AND METHODS: Defatted aerial parts of E. foetidum were subjected to extraction with methanol followed by partitioning with n-hexane, ethyl acetate and 50% methanol. Then, the first two fractions were subsequently fractionated by column chromatography and HPLC. Compound identity was confirmed by mass spectrometry and NMR spectroscopy. Leishmania tarentolae (promastigotes) and L. donovani (amastigotes) were used as testing parasites. L6 rat myoblasts were used for cytotoxicity. All extracts and fractions were tested at 20 µg/mL. RESULTS: The initial methanol extract showed 20% growth inhibition of L. tarentolae. Then, the n-hexane and ethyl acetate fractions were also active showing approximately 40% growth inhibition. From these two fractions, the following compounds were isolated: lasidiol p-methoxybenzoate (1), a daucane sesquiterpene; and 4-hydroxy-1,1,5-trimethyl-2-formyl-cyclohexadien-(2,5)-[α-acetoxymethyl-cis-crotonate] (2), a terpene aldehyde ester derivative. Compound 1 inhibited the growth of both L. tarentolae and L. donovani with IC50 values of 14.33 and 7.84 µM, respectively; and showed no cytotoxicity (IC50 > 50 µM). Compound 2 was inactive in the L. tarentolae assay (IC50 > 50 µM). DISCUSSION AND CONCLUSION: This study presented the bioassay-guided fractionation with the leishmanicidal and cytotoxicity activities of two compounds isolated for the first time from an Eryngium species.

Bioactive capacity, sensory properties, and nutritional analysis of a shelf stable protein-rich functional ingredient with concentrated fruit and vegetable phytoactives.

Well-known health-protective phytochemicals from muscadine grape and kale were stably complexed with food grade protein (soy or hemp protein isolates) to create biofortified food ingredients for use in a variety of convenient, portable food formulations. The bioactive (anti-inflammatory) potential, sensory attributes and proximates of the prepared formulations were evaluated in this study. Anti-inflammatory properties of the protein-phytoactive ingredient particles were contributed by the polyphenolic content (muscadine-protein) or the combination of polyphenol, carotenoid, and glucosinolate content (kale-protein aggregates). Phytoactive compounds from the fortified matrices suppressed at least two biomarkers of inflammation; most notable with the expression of chronic pro-inflammatory genes IL-6 and Mcp1. Sensory analysis suggested both sweet and savory functional food applications for the biofortified ingredients. Proximate analyses determined that fortification of the soy protein isolate (SPI) with muscadine or kale bioactives resulted in elevated dietary fibers, total carbohydrates, and free sugars, but did not increase calories/100 g dry matrix compared to unfortified SPI. Overall protein content in the aggregate matrices was about 37% less (muscadine-SPI, kale-SPI and kale- HP50) or 17.6% less (muscadine-HP50) on a weight basis, likely due to solubility of some proteins during preparation and partial displacement of some protein mass by the fruit and vegetable phytoactive constituents.

Concentrating immunoprotective phytoactive compounds from fruits and vegetables into shelf-stable protein-rich ingredients.

Co-delivery of edible proteins with health-protective fruit (muscadine grape) and vegetable (kale) phytoactive compounds was accomplished in a biofortified ingredient for use in convenient, portable food formulations. Polyphenolics were concentrated (10-42 mg/g range) in dry muscadine-protein matrices. Kale-fortified protein matrices also captured polyphenolics (8 mg/g), carotenoids (69 µg/g) and glucosinolates (7 µmol/g). Neither total phenolics nor glucosinolates were significantly diminished even after long term (6 months) storage at 4, 20, or 37 °C, whereas carotenoids degraded over time, particularly at higher temperatures. Dry biofortified phytoactive-protein ingredients allowed delivery of immunoprotective compounds from fruits and vegetables in a stable, lightweight matrix.

Colloidal and interfacial properties of spray dried pulse protein-blueberry polyphenol particles in model dispersion systems.

The phytochemical composition and physicochemical attributes of polyphenol-enriched protein particle ingredients produced with pulse proteins (e.g. chickpea protein, pea protein, and a chickpea-pea protein blend) and polyphenols recovered from wild blueberry pomace were investigated for colloidal and interfacial properties. Anthocyanins were the major polyphenol fraction (27.74-36.47 mg C3G/g) of these polyphenol-rich particles (44.95-62.08 mg GAE/g). Dispersions of pea protein-polyphenol particles showed a superior phase stability before and after heat treatment compared to the chickpea pea protein-polyphenol system. This observation was independent of the added amount of NaCl in the dispersion. In general, at quasi equilibrium state, pulse protein-polyphenol particles and parental pulse protein ingredients showed similar oil-water interfacial tension. However, pea protein-polyphenol particles demonstrated a reduced diffusion-driven oil-water interfacial adsorption rate constant compared to the parental pea protein ingredient. Overall, the obtained results suggest application potential of pea protein-polyphenol particles as a functional food/beverage ingredient.

An automated ensemble approach using Harris Hawk optimization for visually evoked EEG signal classification.

Steady-state visually evoked potential is one of the active explorations in the brain-computer interface research. Electroencephalogram based brain computer interface studies have been widely applied to perceive solutions for real-world problems in the healthcare domain. The classification of externally bestowed visual stimuli of different frequencies on a human was experimented to identify the need of paralytic people. Although many classifiers are at the fingertip of machine learning technology, recent research has proven that ensemble learning is more efficacious than individual classifiers. Despite its efficiency, ensemble learning technology exhibits certain drawbacks like taking more time on selecting the optimal classifier subset. This research article utilizes the Harris Hawk Optimization algorithm to select the best classifier subset from the given set of classifiers. The objective of the research is to develop an efficient multi-classifier model for electroencephalogram signal classification. The proposed model utilizes the Boruta Feature Selection algorithm to select the prominent features for classification. Thus selected prominent features are fed into the multi-classifier subset which has been generated by the Harris Hawk Optimization algorithm. The results of the multi-classifier ensemble model are aggregated using Stacking, Bagging, Boosting, and Voting. The proposed model is evaluated against the acquired dataset and produces a promising accuracy of 96.1%, 98.7%, 91.91%, and 99.01% with the ensemble techniques respectively. The proposed model is also validated with other performance metrics such as sensitivity, specificity, and F1-Score. The experimental results show that the proposed model proves its supremacy in segregating the multi-class classification problem with high accuracy.