Grape skin phenolics as inhibitors of mammalian α-glucosidase and α-amylase – effect of food matrix and processing on efficacy

Inhibition of mammalian α-amylase and α-glucosidase was studied for white grape skin samples recovered from wineries and found to be higher than that of the drug acarbose

A Modular BAM Complex in the Outer Membrane of the α-Proteobacterium Caulobacter crescentus

Mitochondria are organelles derived from an intracellular α-proteobacterium. The biogenesis of mitochondria relies on the assembly of β-barrel proteins into the mitochondrial outer membrane, a process inherited from the bacterial ancestor. Caulobacter crescentus is an α-proteobacterium, and the BAM (β-barrel assembly machinery) complex was purified and characterized from this model organism. Like the mitochondrial sorting and assembly machinery complex, we find the BAM complex to be modular in nature. A ∼150 kDa core BAM complex containing BamA, BamB, BamD, and BamE associates with additional modules in the outer membrane. One of these modules, Pal, is a lipoprotein that provides a means for anchorage to the peptidoglycan layer of the cell wall. We suggest the modular design of the BAM complex facilitates access to substrates from the protein translocase in the inner membrane

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

<i style="mso-bidi-font-style:normal"><span style="font-size:15.0pt; mso-bidi-font-size:11.0pt;mso-bidi-font-family:"Times New Roman";color:black; font-weight:normal;mso-bidi-font-weight:bold" lang="EN-US">In vitro</span></i><span style="font-size:15.0pt;mso-bidi-font-size:11.0pt;mso-bidi-font-family: "Times New Roman";color:black;font-weight:normal;mso-bidi-font-weight:bold" lang="EN-US"> propagation of <i style="mso-bidi-font-style:normal">Rivina humilis</i> L. through proliferation of axillary shoots and shoot tips of mature plants </span>

481-485<span style="font-size:9.0pt; mso-bidi-font-size:11.0pt;mso-bidi-font-family:" times="" new="" roman";color:black;="" font-weight:normal;mso-bidi-font-weight:bold"="" lang="EN-US">In vitro <span style="font-size:9.0pt;mso-bidi-font-size:11.0pt;mso-bidi-font-family: " times="" new="" roman";color:black;font-weight:normal;mso-bidi-font-weight:bold"="" lang="EN-US">propagation of Rivina humilis L. was attempted through proliferation of axillary shoots and shoot tips obtained from mature plants. The shoot tips and nodal shoot segments exhibited 70 and 80% shoot initiation when cultured on Murashige and Skoog (MS) basal medium supplemented with 4.44 µM 6-benzylaminopurine (BAP)+2.85 µM indole-3-acetic acid (IAA) and 8.88 µM BAP+2.68 µM naphthalene acetic acid (NAA), respectively. Shoots (2 to 3) were obtained from both shoot tip and nodal explants on MS medium supplemented with BAP (2.22 µ<i style="mso-bidi-font-style: normal">M), IAA (2.85 µM) and silver nitrate (4 <span style="font-size:9.0pt;mso-bidi-font-size: 11.0pt;font-family:Symbol;mso-ascii-font-family:" times="" new="" roman";mso-hansi-font-family:="" "times="" roman";mso-bidi-font-family:"times="" roman";color:black;="" mso-char-type:symbol;mso-symbol-font-family:symbol;font-weight:normal;="" mso-bidi-font-weight:bold"="" lang="EN-US">mM<span style="font-size:9.0pt;mso-bidi-font-size:11.0pt;mso-bidi-font-family: " times="" new="" roman";color:black;font-weight:normal;mso-bidi-font-weight:bold"="" lang="EN-US"> AgNO3). Multiplication was maximum on MS medium supplemented with BAP (8.88 µM), IAA (2.85 µM) and AgNO3 (4 <span style="font-size:9.0pt;mso-bidi-font-size:11.0pt; font-family:Symbol;mso-ascii-font-family:" times="" new="" roman";mso-hansi-font-family:="" "times="" roman";mso-bidi-font-family:"times="" roman";color:black;="" mso-char-type:symbol;mso-symbol-font-family:symbol;font-weight:normal;="" mso-bidi-font-weight:bold"="" lang="EN-US">mM<span style="font-size:9.0pt;mso-bidi-font-size:11.0pt;mso-bidi-font-family: " times="" new="" roman";color:black;font-weight:normal;mso-bidi-font-weight:bold"="" lang="EN-US">) wherein 3-4 shoots per nodal explant were obtained. Microshoot elongation was achieved on MS medium containing BAP (2.22 µM) and gibberellic acid (2.89 µM GA3). Shoots (3-4 cm) exhibited 100% rooting within 4 wk in medium containing half MS with IAA (2.85-5.71 µM) or IBA (2.45-4.90 µM) alone or in combination with BAP (2.22 µM), resulting in simultaneous rooting and shoot growth. About 70% of micropropagated plants were established successfully in micropots and transferred to the field after 3 months. </span

Tuning Physical Properties of Tomato Puree by Fortification with Grape Skin Antioxidant Dietary Fiber

Grape skins recovered from winemaking by-products were investigated for use as sustainable, antioxidant fiber-rich ingredient for the innovation of low-energy dense tomato puree. Six tomato purees fortified with grape skin antioxidant fiber, with varying particle size distribution, and two control tomato purees were studied. Physical parameters of purees were analyzed upon mixing and either an intensive heat treatment or an optimized heat treatment designed to achieve six decimal reductions of a target microorganism (Alicyclobacillus acidoterrestris) as recommended for pasteurization of acidic fruit products. Mixing of grape skin antioxidant fiber with tomato purees led to a decrease in both surface-weighted mean diameter (Sauter mean diameter, d(3,2)) and volume-weighted mean diameter (d(4,3)) values and an increase in span. Changes in these descriptors were most significant in purees added with the smallest particle sizes. Thermal stabilization of purees slightly decreased the d(3,2) values further and increased d(4,3) values, suggesting concomitant occurrence of particle disaggregation and formation of flocs within the food matrix. Phenolic solubility was inversely correlated to d(3,2) values. Bostwick consistency, storage (G\u2032) and loss (G\u2033) moduli, and complex viscosity (\u3b7*) increased in the fortified purees. The \u3b7* values displayed a positive correlation with d(4,3) values. Variations in Hunter colorimetric parameters were within the acceptability threshold. Overall, the information obtained provides knowledge to assist development of fiber-rich, low-energy dense fruit purees

Modelling the stability of maltodextrin-encapsulated grape skin phenolics used as a new ingredient in apple puree

Highly soluble maltodextrin-encapsulated grape skin phenolics comprising anthocyanins and less hydrophilic flavonoids were added as an ingredient to apple puree. Upon formulation, heat treatments were applied to achieve 3-14 decimal reductions (D) of the target microorganism (Alicyclobacillus acidoterrestris). A storage study was performed at 15-35\ub0C for 1 month. Monomeric anthocyanins were retained at 100% after the 3 D treatment, while anthocyanin retention decreased to 72% with increasing heating intensity until 14 D. During storage, the concentration of monomeric anthocyanins decreased following first-order kinetics (k25 \ub0C = 34.4 d-1, activation energy = 51.0 kJ/mol). The flavanols were more stable than the monomeric anthocyanins. The hydroxycinnamic acid, dihydrochalcone and flavonol contents did not change. The fortified puree had a two-fold higher reducing capacity with respect to apple puree. Overall, this ingredient could meet the industrial demand for sustainable colouring agents and health promoting compounds