Search

Anaphylactic shock is a rare, but potentially lethal complication, combining life-threatening circulatory failure and massive fluid shifts. Treatment guidelines rely on adrenaline and volume expansion by intravenous fluids, but there is no solid evidence for the choice of one specific type of fluid over another. Our purpose was to compare the time to achieve target mean arterial pressure upon resuscitation using adrenaline alone versus adrenaline with different resuscitation fluids in an animal model and to compare the tissue oxygen pressures (PtiO2) with the various strategies. Twenty-five ovalbumin-sensitised Brown Norway rats were allocated to five groups after anaphylactic shock induction: vehicle (CON), adrenaline alone (AD), or adrenaline with isotonic saline (AD+IS), hydroxyethyl starch (AD+HES) or hypertonic saline (AD+HS). Time to reach a target mean arterial pressure value of 75 mmHg, cardiac output, skeletal muscle PtiO2, lactate/pyruvate ratio and cumulative doses of adrenaline were recorded. Non-treated rats died within 15 minutes. The target mean arterial pressure value was reached faster with AD+HES (median: 10 minutes, range: 7.5 to 12.5 minutes) and AD+IS (median: 17.5 minutes, range: 5 to 25 minutes) versus adrenaline alone (median: 25 minutes, range: 20-30 minutes). There were also reduced adrenaline requirements in these groups. The skeletal muscle PtiO2 was restored only in the AD+HES group. Although direct extrapolation to humans should be made with caution, our results support the combined use of adrenaline and volume expansion for resuscitation from anaphylactic shock. When used with adrenaline the most effective fluid was hydroxyethyl starch, whereas hypertonic saline was the least effective. [ABSTRACT FROM AUTHOR]

To analyze age-related interactions between obesity, its associated metabolic disorders, and macrocirculation, we studied large artery stiffness and fatty acid responsiveness in lean and obese Zucker rats, aged 25 (adult) and 80 weeks (very old). Systolic arterial pressure was higher in old obese than in old lean rats (178 ± 10 vs 134 ± 8 mmHg, respectively). Carotid elastic modulus-wall stress curves showed increased age-dependent arterial stiffening, which was greater in obese animals. Old obese exhibited endothelial dysfunction with increased systemic oxidative stress. Adult obese had elevated plasma free fatty acid levels (1,866 ± 177 vs 310 ± 34 [mu]g/[mu]L in lean animals). In old obese, linoleate and palmitate increased contractility to phenylephrine and reduced relaxation to acetylcholine. Thus, obesity at 25 weeks appears to trigger accelerated arterial aging observed at 80 weeks. The early increase in free fatty acids may be a key effector in the severe arterial stiffness of the aged obese Zucker model. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of blackcurrant (BC) on gut microbiota abundance and composition, inflammatory and immune responses, and their relationship with bone mass changes. The effects of BC on bone mineral density (BMD), gut microbiota, and blood inflammatory and immune biomarkers were evaluated using DXA, stool and fasting blood collected from a pilot three-arm, randomized, double-blind, placebo-controlled clinical trial. Fifty-one peri- and early postmenopausal women aged 45-60 years were randomly assigned into one of three treatment groups for 6 months: control, low BC (392 mg/day) and high BC (784 mg/day); and 40 women completed the trial. BC supplementation for 6 months effectively mitigated the loss of whole-body BMD (P<.05). Six-month changes (%) in peripheral IL-1β (P=.056) and RANKL (P=.052) for the high BC group were marginally significantly lower than the control group. Six-month changes in whole-body BMD were inversely correlated with changes in RANKL (P<.01). In proteome analysis, four plasma proteins showed increased expression in the high BC group: IGFBP4, tetranectin, fetuin-B, and vitamin K-dependent protein S. BC dose-dependently increased the relative abundance of Ruminococcus 2 (P<.05), one of six bacteria correlated with BMD changes in the high BC group (P<.05), suggesting it might be the key bacteria that drove bone protective effects. Daily BC consumption for 6 months mitigated bone loss in this population potentially through modulating the gut microbiota composition and suppressing osteoclastogenic cytokines. Larger-scale clinical trials on the potential benefits of BC and connection of Ruminococcus 2 with BMD maintenance in postmenopausal women are warranted. Trial Registration: NCT04431960, https://classic.clinicaltrials.gov/ct2/show/NCT04431960., Competing Interests: Declaration of competing interests The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The present study aimed to assess the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. We then examined their associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone metabolism., Methods: Fecal and blood samples from a pilot randomized controlled trial were collected and analyzed from 37 eligible peri- and early postmenopausal women aged 45-60 years who were randomized into one of three treatment groups consuming one placebo capsule (control), 392 mg BC (low BC) or 784 mg BC (high BC) daily for six months., Results: Significant differences were observed between groups at baseline in acetic, propionic, valeric, caproic and heptanoic acids ( p < 0.05). Isobutyric acid significantly decreased from baseline (0 months) to six months in the control group ( p < 0.05) and the high BC group had a significantly greater concentration than the control group at six months ( p < 0.05). Butyric acid was significantly greater in the high BC group than low BC at six months ( p < 0.05). Six-month changes in caproic and isobutyric acids showed weak correlations with changes in whole-body BMD (r = 0.3519, p < 0.05 and r = 0.3465, p < 0.05, respectively). Isovaleric and valeric acids displayed weak correlations with BALP (r = 0.3361, p < 0.05) and OPG (r = 0.3593, p < 0.05), respectively. Enterodiol was positively correlated with BALP (r = 0.6056, p < 0.01) while enterolactone was positively correlated with osteocalcin (r = 0.5902, p < 0.001) and negatively correlated with sclerostin (r = -0.3485, p < 0.05)., Conclusions: The results suggest that BC may be a potential dietary agent to reduce postmenopausal bone loss through modulating microbially-derived SCCAs and phytoestrogen metabolites.

The communication between the brain and digestive tract is critical for optimising nutrient preference and food intake, yet the underlying neural mechanisms remain poorly understood 1-7 . Here, we show that a gut-brain-gut circuit loop gates sugar ingestion in flies. We discovered that brain neurons regulating food ingestion, IN1 8 , receive excitatory input from enteric sensory neurons, which innervate the oesophagus and express the sugar receptor Gr43a . These enteric sensory neurons monitor the sugar content of food within the oesophagus during ingestion and send positive feedback signals to IN1s, stimulating the consumption of high-sugar foods. Connectome analyses reveal that IN1s form a core ingestion circuit. This interoceptive circuit receives synaptic input from enteric afferents and provides synaptic output to enteric motor neurons, which modulate the activity of muscles at the entry segments of the crop, a stomach-like food storage organ. While IN1s are persistently activated upon ingestion of sugar-rich foods, enteric motor neurons are continuously inhibited, causing the crop muscles to relax and enabling flies to consume large volumes of sugar. Our findings reveal a key interoceptive mechanism that underlies the rapid sensory monitoring and motor control of sugar ingestion within the digestive tract, optimising the diet of flies across varying metabolic states., Competing Interests: Competing interests The authors declare no competing interests.

Recent cell and animal studies suggest the potential of blackcurrants (BCs; Ribes nigrum ) as a dietary agent that may reduce the risk of cardiovascular disease (CVD) by improving dyslipidemia, oxidative stress, and inflammation. This study aimed to examine the effects of BC anthocyanin (ACN) extract supplementation on biomarkers of CVD risk in healthy adult women in menopause transition. The effects of BC ACN supplementation on body composition, fasting blood lipids and biomarkers of inflammation and oxidative stress were evaluated using anthropometric measures and blood samples collected from a pilot randomized controlled clinical trial in peri- and early postmenopausal women. Thirty-eight eligible peri- and early postmenopausal women aged 45-60 completed the entire trial, in which they were randomly assigned into one of three treatment groups: placebo (control group), 392 mg/day (low BC group), or 784 mg/day (high BC group) for six months. The significance of differences in outcomes was tested using repeated-measures ANOVA. Overall, following six-month BC consumption, significantly decreased triglyceride (TG) levels were observed between treatment groups ( p < 0.05) in a dose-dependent manner. Plasma interleukin-1β (IL-1β) was significantly reduced in a dose and time dependent manner ( p < 0.05). Significant decreases in thiobarbituric acid reactive substances (TBARS) levels were also observed between treatment groups ( p < 0.05) in a dose-dependent manner. Six-month change in oxidized LDL was inversely correlated with changes in catalase (CAT) and total antioxidant capacity (TAC) ( p < 0.05), while C-reactive protein (hs-CRP) change was positively correlated with changes in TG and IL-1β ( p < 0.01). Together, these findings suggest that daily BC consumption for six months effectively improved dyslipidemia, inflammation, and lipid peroxidation, thus potentially mitigating the risk of postmenopausal CVD development in study participants. Future studies with larger sample sizes and at-risk populations are warranted to confirm these findings.

The physiological, perceptual, and functional effects of dehydration may depend on how it is incurred (e.g., intense exercise releases endogenous water via glycogenolysis) but this basic notion has rarely been examined. We investigated the effects of active (exercise) heat- vs. passive heat-induced dehydration, and the kinetics of ad libitum rehydration following each method. Twelve fit participants (five females and seven males) completed four trials in randomised order: DEHydration to -3% change in body mass (∆BM) under passive or active heat stress, and EUHydration to prevent ∆BM under passive or active heat stress. In all trials, participants then sat in a temperate-controlled environment, ate a standard snack and had free access to water and sports drink during their two-hour recovery. During mild dehydration (≤2% ∆BM), active and passive heating caused comparable increases in plasma osmolality (P osm : ~4 mOsmol/kg, interaction: p = 0.138) and reductions in plasma volume (PV: ~10%, interaction: p = 0.718), but heat stress per se was the main driver of hypovolaemia. Thirst in DEHydration was comparably stimulated by active than passive heat stress ( p < 0.161) and shared the same relation to P osm (r ≥ 0.744) and ∆BM (r ≥ 0.882). Following heat exposures, at 3% gross ∆BM, PV reduction was approximately twice as large from passive versus active heating ( p = 0.003), whereas P osm perturbations were approximately twice as large from EUHydration versus DEHydration ( p < 0.001). Rehydrating ad libitum resulted in a similar net fluid balance between passive versus active heat stress and restored PV despite the incomplete replacement of ∆BM. In conclusion, dehydrating by 2% ∆BM via passive heat stress generally did not cause larger changes to PV or P osm than via active heat stress. The heat stressors themselves caused a greater reduction in PV than dehydration did, whereas ingesting water to maintain euhydration produced large reductions in P osm in recovery and therefore appears to be of more physiological significance.

Hydration is a particular concern for infants and young children due to their greater risk of dehydration. However, studies on their water intakes are scarce. The current survey aimed to analyse total water intake (TWI) in non-breastfed children aged 0·5-35 months compared with the adequate intake (AI) for the same age group set by the European Food Safety Authority and to examine the different contributors to TWI as well as beverage consumption patterns. Nationally representative data from the Nutri-Bébé cross-sectional survey were used to assess food, beverage and plain water consumption by age group over three non-consecutive days. With age, median TWI in 1035 children increased from 732 to 1010 ml/d, without differences between sexes, but with a great inter-individual variation, and the percentage of children who did not meet the AI increased from 10 to 88 %. Median weight-related TWI decreased from 136·6 to 69·0 ml/kg per d. Among infants, 90 % had a ratio of water:energy below the AI, similarly for about 75 % of toddlers. Milk and milk products were the main contributors to TWI, while the part of plain water increased gradually to be 25 % in the older toddlers, half of which was tap water. The beverage consumption pattern varied in types and timing, with little consumption of juices and sweetened beverages. Vegetables and fruits accounted for 20 % of TWI after the age of 6 months. These initial results, showing strong discrepancies between actual and recommended water intakes in young children, should help identify ways to increase children's water consumption.

Background and Aims: Beverages are an important aspect of diet, and their quality can possibly affect health. The Healthy Beverage Index (HBI) has been developed to take into account these effects. This study aimed to highlight the relationships between health and beverage quality by assessing the association of the HBI and its components with kidney and cardiometabolic (CM) outcomes in an initially healthy population-based familial cohort. Methods: This study included 1,271 participants from the STANISLAS cohort. The HBI, which includes 10 components of habitual beverage consumption, was calculated. Associations of the HBI and its components with estimated glomerular filtration rate (eGFR), albuminuria, hypertriglyceridemic waist (HTG waist), metabolic syndrome (MetS), carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass (LV mass) were analyzed using multivariable linear or logistic regression models. Results: The median HBI score was 89.7 (78.6-95) out of 100 points. While the overall HBI score was not significantly associated with any of the studied outcomes, individual HBI components were found differently associated with the outcomes. cfPWV and cIMT were lower in participants who did not meet the full-fat milk criteria ( p = 0.03 and 0.001, respectively). In men, higher cfPWV was observed for the "low Fat milk" ( p = 0.06) and "alcohol" ( p = 0.03) non-adherence criteria. Odds of HTG waist were higher with the non-adherence to sugar-sweetened beverages criteria ( p < 0.001). eGFR was marginally higher with non-adherence to the coffee/tea criteria ( p = 0.047). Conclusions: In this initially healthy population, HBI components were differently associated with kidney and cardiometabolic outcomes, despite a good overall HBI score. Our results highlight specific impacts of different beverage types and suggest that beverages could have an impact on kidney and cardiometabolic health., Competing Interests: SW reports a grant from the International Society of Nephrology, outside of the submitted work. PR received grants and personal fees from Vifor Fresenius Medical Care Renal Pharma, personal fees from Idorsia, personal fees from KBP, Sanofi, NovoNordisk, personal fees from Ablative Solutions, non-financial support from G3P, personal fees from Corvidia, grants, personal fees from Relypsa a Vifor company and Vifor, personal fees from CardioRenal, grants and personal fees from AstraZeneca, grants and personal fees from Bayer, grants and personal fees from CVRx, personal fees from Fresenius, grants and personal fees from Novartis, personal fees from Grunenthal, personal fees from Servier, personal fees from Stealth Peptides, and all outside the submitted work. NG reports personal fees outside of the submitted work from Novartis, Vifor and AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wagner, Merkling, Girerd, Bozec, Van den Berghe, Hoge, Guillaume, Kanbay, Cakir-Kiefer, Thornton, Boivin, Mercklé, Laville, Rossignol and Nazare.)

Optimal physiological function throughout life is assured by activation, inhibition and/or modulation of multiple gene cascades resulting in new protein synthesis (possible biomarker), increased or decreased production of existing proteins, and other regulatory activities that maintain the organism in a relative healthy state for survival. Changes in physiological health state demand further (rapid) production/activation/inhibition/modulation of proteins that should ensure continued physiological functions in the short term, but these changes may not necessarily be ideal for long term survival. Medications, or even way of life changes, may help to stabilise overall organism's survival but cannot necessarily repair or reverse changes in gene expression already endured nor return the organism to an initial optimal healthy state., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Women's fertility is characterized both quantitatively and qualitatively mainly by the pool of ovarian follicles. Monthly, gonadotropins cause an intense multiplication of granulosa cells surrounding the oocyte. This step of follicular development requires a high proliferation ability for these cells. Telomere length plays a crucial role in the mitotic index of human cells. Hence, disrupting telomere homeostasis could directly affect women's fertility. Strongly expressed in ovaries, telomerase is the most effective factor to limit telomeric attrition and preserve ovarian reserve. Considering these facts, two situations of infertility could be correlated with the length of telomeres and ovarian telomerase activity: PolyCystic Ovary Syndrome (PCOS), which is associated with a high density of small antral follicles, and Premature Ovarian Failure (POF), which is associated with a premature decrease in ovarian reserve. Several authors have studied this topic, expecting to find long telomeres and strong telomerase activity in PCOS and short telomeres and low telomerase activity in POF patients. Although the results of these studies are contradictory, telomere length and the ovarian telomerase impact in women's fertility disorders appear obvious. In this context, our research perspectives aimed to explore the stimulation of ovarian telomerase to limit the decrease in the follicular pool while avoiding an increase in cancer risk.

In the context of a continuously increased delay of motherhood and of an increase of the incidence of premature ovarian failure, it is of the greatest interest to dispose of a predictive marker of the duration of the fertility window. Unfortunately, current available markers of women's fertility (hormonal rates or echography count of small follicles) have a poor predictive value of premature ovarian failure. In the last ten years, some studies have suggested that telomere length may be correlated with premature ovarian failure, but the results of these studies are contradictory.In accordance with guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this systematic review of the literature selected studies evaluating telomere length or telomerase activity in granulosa cells and/or in leukocytes as a premature ovarian failure marker.Five publications (252 premature ovarian failure patients) were included in this review of experimental evidence. Two of them studied telomere length and/or telomerase activity in granulosa cells and 4 in leukocytes in women with premature ovarian failure. For each study, authors determined if there was a positive or a negative correlation between telomeric parameters and premature ovarian failure.3 studies (178 premature ovarian failure patients) found shorter telomere length in granulosa cells and/or leukocytes and/or lower telomerase activity in premature ovarian failure patients. 2 studies (74 premature ovarian failure patients) presented contradictory results about the correlation of leucocyte telomere length with premature ovarian failure.Shorter telomeres and diminished telomerase activity in granulosa cells appear to be associated with ovarian insufficiency. However, the number of studies and of subjects within are low and the methodology questionable. The confirmation of these results is essential with more subjects, better defined populations and more adapted methodology, in order to consider telomere length in granulosa cells and/or in leucocytes as an early and reliable marker for the decline of ovarian function.

Protein sufficiency is tightly controlled through different sensing and signaling processes that modulate and adapt protein and energy metabolism and feeding behavior to reach and maintain a well-balanced protein status. High-protein diets, often discussed in the context of body weight management, usually activate anorexigenic pathways, leading to higher satiety, decreased food and energy intake, and decreased body weight and adiposity. Diets marginally low in protein (3-8% energy) or marginally deficient in some indispensable amino acid more often activate orexigenic pathways, with higher appetite and a specific appetite for protein, a response that leads to an increase in protein intake to partially compensate for the deficit in protein and amino acid. Diets severely deficient in protein (2-3% energy as protein) usually depress food intake and induce lower weight and lower fat mass and lean tissues that characterize a status of protein deficiency. The control of protein sufficiency involves various peripheral and central signals, including modulation of both metabolic pathways at the periphery as well as central pathways of the control of food and protein intake, including a reward-driven specific sensitivity to the protein content of foods.

Salivary biomarkers may offer a noninvasive and easy sampling alternative in cardiovascular risk evaluation. The aim of the present study was to establish associations of salivary potassium, sodium, calcium, and phosphate levels with the cardiovascular phenotype determined by carotid ultrasound and carotid-femoral pulse wave velocity and to identify possible covariates for these associations. N = 241 samples of nonstimulated whole buccal saliva were obtained from subjects with ( n = 143; 59%) or without ( n = 98; 41%) hypertension. The potassium concentrations were 10-fold higher in saliva compared with plasma, whereas sodium concentrations exhibited the reverse relation between saliva and blood. There were no significant correlations between the levels of sodium, potassium, or calcium in saliva and plasma. All salivary electrolytes, except sodium, were significantly associated with age. In age-adjusted analyses, salivary potassium was significantly associated with carotid artery intima media thickness (cIMT) and carotid-femoral pulse wave velocity, and these associations were at the limit of significance in multivariate analyses including prevalent cardiovascular disease and risk factors. Body mass index was a significant confounder for salivary potassium. Salivary phosphate was significantly associated with cIMT in the multivariate analysis. Salivary potassium, calcium, and phosphate levels were significantly associated with heart rate in the univariate age-adjusted as well as in two different multivariate models, whereas no significant associations between sodium and heart rate were observed. In conclusion, the differential association of salivary electrolytes with cardiovascular phenotypes indicates that these electrolytes should be further studied for their predictive value as noninvasive biomarkers for cardiovascular risk evaluation.

Background: The metabolic syndrome (MetS) and aging are associated with modifications in blood coagulation factors, vascular inflammation, and increased risk of thrombosis. Objectives: Our aim was to determine concomitant changes in thrombin generation in the blood compartment and at the surface of vascular smooth muscle cells (VSMCs) and its interplay with adipokines, free fatty acids (FFA), and metalloproteinases (MMPs) in obese Zucker rats that share features of the human MetS. Methods: Obese and age-matched lean Zucker rats were compared at 25 and 80 weeks of age. Thrombin generation was assessed by calibrated automated thrombography (CAT). Results: Endogenous thrombin potential (ETP) was increased in obese rats independent of platelets and age. Clot half-lysis time was delayed with obesity and age. Interleukin (IL)-1β and IL-13 were increased with obesity and age respectively. Addition of exogenous fibrinogen, leptin, linoleic, or palmitic acid increased thrombin generation in plasma whereas adiponectin had an opposite effect. ETP was increased at the surface of VSMCs from obese rats and addition of exogenous palmitic acid further enhanced ETP values. Gelatinase activity was increased in aorta at both ages in obese rats and MMP-2 activity was increased in VSMCs from obese rats. Conclusions: Our study demonstrated in MetS an early prothrombotic phenotype of the blood compartment reinforced by procoagulant properties of dedifferentiated and inflammatory VSMCs. Mechanisms involved (1) increased fibrinogen and impaired fibrinolysis and (2) increased saturated fatty acids responsible for additive procoagulant effects. Whether specifically targeting this hypercoagulability using direct thrombin inhibitors would improve outcome in MetS is worth investigating.

Exercise-associated hyponatremia can be life-threatening. Excessive hypotonic fluid ingestion is the primary etiological factor but does not explain all variability. Possible effects of chronic sodium intake are unknown. The aim of this study was to determine whether dietary sodium affects plasma sodium concentration [Na + ] during exercise in the heat, when water intake nearly matches mass loss. Endurance-trained men (n = 9) participated in this crossover experiment. Each followed a low-sodium (lowNa) or high-sodium (highNa) diet for 9 days with 24-h fluid intakes and urine outputs measured before experimental trials (day 10). The trials were ≥2 week apart. Trials comprised 3 h (or if not possible to complete, to exhaustion) cycling (55% VO 2max ; 34 °C, 65% RH) with water intake approximating mass loss. Plasma [Na + ], hematocrit, sweat and urine [Na + ], heart rate, core temperature, and subjective perceptions were monitored. Urine [Na + ] was lower on lowNa 24 h prior to (31 ± 24, 76 ± 30 mmol/L, P = 0.027) and during trials (10 ± 10, 52 ± 32 mmol/L, P = 0.004). Body mass was lower on lowNa (79.6 ± 8.5, 80.5 ± 8.9, P = 0.03). Plasma [Na + ] was lower on lowNa before (137 ± 2, 140 ± 3, P = 0.007) and throughout exercise (P = 0.001). Sweat [Na + ] was unaffected by diet (54.5 ± 40, 54.5 ± 23 mmol/L, P = 0.99). Heart rate and core temperature were higher on lowNa (P ≤ 0.001). Despite decreased urinary sodium losses, plasma sodium was lower on lowNa, with decreased mass indicating (extracellular) water may have been less, explaining greater heart rate and core temperature. General population health recommendations to lower salt intake may not be appropriate for endurance athletes, particularly those training in the heat., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Atmospheric CO 2 concentrations increased significantly over the last century and continuing increases are expected to have significant effects on current ecosystems. This study evaluated the behavioural and physiological (hormone status, muscle structure) effects of prolonged CO 2 exposure in young female Wistar rats exposed at 700ppm of CO 2 during 6h a day for 15days. Prolonged CO 2 exposure, though not continuous, produced significant disturbances in behaviour with an increase in drinking, grooming and resting, and a reduction in rearing, jumping-play and locomotor activity. Furthermore, CO 2 exposure was accompanied by increased plasma levels of corticosterone, suggesting that prolonged exposure to CO 2 was stressful. The muscular structure can also be modified also when respiratory working conditions change. The expression of myosin heavy chain was significantly affected in the diaphragm and oral respiratory muscles: Masseter Superficialis and Anterior Digastric. Modified behaviour and hormonal changes both appear to be at the origin of the observed muscular adaptation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Significant efforts have been made to improve physician-to-physician communication and care coordination during transition of care in order to reduce adverse events and readmissions. As electronic health records (EHRs) become widely available, many hospitals have implemented physician collaboration and hand-off tools to automatically send admission notifications, discharge summaries, and pending laboratory results to a patient's primary care physician (PCP). However, the effectiveness of such tools depends on a fundamental question that remains unstudied: who is the patient's PCP? Missing or outdated PCP information may become the bottleneck to effective patient-centered care coordination regardless of existing efforts on promoting interoperability among healthcare providers. In this paper, we characterized patient-reported PCPs and experimented with an imputation algorithm that automatically infers a patient's primary provider based on patient-provider encounter data. We compared the imputation results with patient-reported PCPs and suggested practical uses of our findings.

This mini-review develops the hypothesis that increased hydration leads to body weight loss, mainly through a decrease in feeding, and a loss of fat, through increased lipolysis. The publications cited come from animal, mainly rodent, studies where manipulations of the central and/or the peripheral renin-angiotensin system lead to an increased drinking response and a decrease in body weight. This hypothesis derives from a broader association between chronic hypohydration (extracellular dehydration) and raised levels of the hormone angiotensin II (AngII) associated with many chronic diseases, such as obesity, diabetes, cancer, and cardiovascular disease. Proposed mechanisms to explain these effects involve an increase in metabolism due to hydration expanding cell volume. The results of these animal studies often can be applied to the humans. Human studies are consistent with this hypothesis for weight loss and for reducing the risk factors in the development of obesity and type 2 diabetes.

In the course of exposure to fluid deprivation and heated environment, mammals regulate their hydromineral balance and body temperature by a number of mechanisms including sweating, water and salt intakes. Here we challenged obese Zucker rats, known to have a predisposition to hypertension, with 0.9%NaCl alone or with 2%NaCl solution + water to drink under fluid deprivation and heated conditions. Food and fluid intakes, body weight, diuresis and natriuresis were measured daily throughout. Serum aldosterone levels and Na(+) concentration were also analyzed. Data showed that obese and lean rats presented similar baseline measurements of food, 0.9%NaCl and fluid intakes, diuresis and fluid balance; whereas hypertonic 2%NaCl consumption was almost absent. Before and during fluid deprivation animals increased isotonic but not hypertonic NaCl intake; the obese showed significant increases in diuresis and Na(+) excretion, whereas, total fluid intake was similar between groups. Heat increased isotonic NaCl intake and doubled natriuresis in obese which were wet on their fur and displayed a paradoxical increase of fluid gain. Fluid deprivation plus heat produced similar negative fluid balance in all groups. Body weight losses, food intake and diuresis reductions were amplified under the combined conditions. Animals exposed to 2%NaCl showed higher circulating levels of aldosterone and obese were lower than leans. In animals which drank 0.9%NaCl, obese showed higher serum levels of Na(+) than leans. We conclude that in spite of their higher sensitivity to high salt and heat obese Zucker rats can control hydromineral balance in response to fluid deprivation and heat by adjusting isotonic NaCl preference with sodium balance and circulating levels of aldosterone. This suggests a key hormonal role in the mechanisms underlying thermoregulation, body fluid homeostasis and sodium intake., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Variation in systemic hydration status, namely chronic systemic hypohydration or dehydration, can influence the development of several chronic non-ophthalmic diseases. Owing to the eye's high water content and unique system of fluid regulation, we hypothesized that hydration status may affect the eye in health and disease states. Therefore, we performed a systematic review of the current evidence implicating changes in hydration and their association with ocular physiology and morphological characteristics. We also reviewed relevant clinical correlations of changes in hydration and major common eye diseases. Our findings suggest that systemic hydration status broadly affects a variety of ocular pathophysiologic processes and disease states. For example, dehydration may be associated with development of dry eye syndrome, cataract, refractive changes and retinal vascular disease. On the other hand, excessive hydration is associated with some ocular diseases. Tear fluid osmolarity may be an effective marker of systemic hydration status. Recent studies implicate chronic renin-angiotensin-aldosterone system activation in the pathogenesis of diabetic retinopathy and glaucoma but also suggest its antagonism may be a useful therapeutic target. Our findings indicate that assessment of hydration status may be an important consideration in the management of patients with chronic eye diseases and undergoing eye surgery. Further research investigating the role of acute and chronic changes in hydration in individuals with and without ocular disease is warranted., (© 2015 Royal Australian and New Zealand College of Ophthalmologists.)

Background: In contrast to other types of shock, anaphylactic shock decreases cerebral blood flow more than would be expected from severe arterial hypotension, thus potentially affecting survival through brain ischaemia/hypoxia. We hypothesised that epinephrine (EPI) used as a first-line treatment of anaphylactic shock and arginine vasopressin (AVP) proposed in case of EPI refractoriness may have different effects on brain oxygenation., Objectives: To compare the effect of EPI and AVP on brain oxygenation under similar macro-haemodynamic target values in an anaphylactic shock model., Design: Prospective laboratory study., Setting: University laboratory., Animals: Male brown Norway rats (n = 27)., Interventions: Twenty-seven rats were sensitised with ovalbumin (OVA). Twenty rats had anaphylactic shock induced with OVA and were resuscitated with either 0.9% saline (OVA group), EPI (EPI group) or AVP (AVP group). Sensitised control rats received only 0.9% saline and no OVA (CON group)., Main Outcome Measures: Mean arterial pressure (MAP), carotid artery blood flow (CaBF), cerebral cortical blood flow (CBF) and hippocampal oxygen partial pressure (PtiO2) were recorded., Results: All rats in the OVA group died within 15 min. EPI and AVP restored comparable levels of MAP, carotid artery blood flow and CBF, and extended survival time. EPI was associated with biologically relevant and significantly (P < 0.05) higher PtiO2 values (nadir values at 20 min: 25.0 ± 2.2 mmHg) compared with the AVP group (14.9 ± 2.0 mmHg). The slopes of the correlations of MAP vs. PtiO2 and CBF were significantly steeper with AVP (more pressure dependence) compared with EPI. By the end of the experiment, hippocampal PtiO2 values between the EPI (24.1 ± 2.1 mmHg) and the AVP (20.8 ± 2.0 mmHg) groups were similar., Conclusion: At early, but not at late time points, resuscitation of anaphylactic shock with EPI or AVP to similar MAP and CBF endpoints resulted in hippocampal PtiO2 being significantly higher after EPI. In addition, the PtiO2 after EPI always remained above the threshold for brain hypoxia, whereas PtiO2 after AVP was below the hypoxic threshold most of the time. Because of this early brain hypoxia, AVP may not be the drug of first choice for resuscitation of anaphylactic shock.

Aldosterone and mineralocorticoid receptors are important regulators of inflammation. During this process, chemokines and extracellular matrix degradation by matrix metalloproteases, such as MMP-9, help leukocytes reaching swiftly and infiltrating the injured tissue, two processes essential for tissue repair. Leukocytes, such as neutrophils, are a rich source of MMP-9 and possess mineralocorticoid receptors (MR). The aim of our study was to investigate whether aldosterone was able to regulate proMMP-9, active MMP-9 and MMP-9/NGAL production in human neutrophils. Here we show that aldosterone increased MMP-9 mRNA in a dose- and time-dependent manner. This hormone up-regulated also dose-dependently proMMP-9 and active MMP-9 protein release as well as the MMP-9/NGAL protein complex. PI3K, p38 and ERK1/2 inhibition diminished these aldosterone-induced neutrophil productions. Furthermore, spironolactone, a MR antagonist, counteracted aldosterone-induced increases of proMMP-9, active MMP-9 and MMP-9/NGAL complex. These findings indicate that aldosterone could participate in tissue repair by modulating neutrophil activity and favoring extracellular matrix degradation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

As the field of medicine grows more complicated and doctors become more specialized in a particular field, the number of healthcare providers involved in healing an individual patient increases. This is particularly true of patients with multiple chronic conditions. Establishing effective communications among the care providers becomes critical to facilitate care coordination and more efficient resource use, which will ultimately result in health outcome improvement. The first step for care coordination is to understand who have been involved in a patient's care and their relationships with the patient. The widespread adoption of Electronic Health Records provides us an opportunity to explore solutions to well-coordinated care. This paper presents the concept of a patient's care team and demonstrates the feasibility of identifying relevant healthcare providers for an individual patient by leveraging electronic patient encounter data. Combined with network analysis techniques, we further visualize the care team structure with quantified strength of patient-provider relationships. Our work is foundational to the larger goal of patient-centered, coordinated care in the digital age of healthcare.

Growing participation in Healthcare Information Exchange (HIE) has created opportunities for the seamless integration of external data into an organization's own EHR and clinical workflows. The process of integrating external data has the potential to detect data integrity issues. Lack of critiquing external data before its incorporation can lead to data unfit for use in the clinical setting. HIE data adjudication, by detecting inconsistencies, physiological and temporal incompatibilities, data completeness and timeliness issues in HIE data, facilitates corrective actions and improves clinical data integrity.

Hydration pertains simplistically to body water volume. Functionally, however, hydration is one aspect of fluid regulation that is far more complex, as it involves the homeostatic regulation of total body fluid volume, composition and distribution. Deliberate or pathological alteration of these regulated factors can be disabling or fatal, whereas they are impacted by exercise and by all environmental stressors (e.g. heat, immersion, gravity) both acutely and chronically. For example, dehydration during exercising and environmental heat stress reduces water volume more than electrolyte content, causing hyperosmotic hypohydration. If exercise continues for many hours with access to food and water, composition returns to normal but extracellular volume increases well above baseline (if exercising upright and at low altitude). Repeating bouts of exercise or heat stress does likewise. Dehydration due to physical activity or environmental heat is a routine fluid-regulatory stress. How to gauge such dehydration and - more importantly-what to do about it, are contested heavily within sports medicine and nutrition. Drinking to limit changes in body mass is commonly advocated (to maintain ≤2% reduction), rather than relying on behavioural cues (mainly thirst) because the latter has been deemed too insensitive. This review, as part of the series on moving in extreme environments, critiques the validity, problems and merits of externally versus autonomously controlled fluid-regulatory behaviours, both acutely and chronically. Our contention is that externally advocated hydration policies (especially based on change in body mass with exercise in healthy individuals) have limited merit and are extrapolated and imposed too widely upon society, at the expense of autonomy. More research is warranted to examine whether ad libitum versus avid drinking is beneficial, detrimental or neither in: acute settings; adapting for obligatory dehydration (e.g. elite endurance competition in the heat), and; development of chronic diseases that are associated with an extreme lack of environmental stress.

The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the center of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the center of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Spontaneously hypertensive heart failure rats (SHHF) appear to constitute an original model for analyzing the evolution of the metabolic syndrome towards heart failure. This study aimed to characterize early cardiac dysfunction and remodeling in SHHF rats: (1) as compared with spontaneously hypertensive rats (SHR) and with a control group of Kyoto rats (WKY), and (2) by using the 3-dimensional quantitative analysis provided by acipimox-enhanced positron emission tomography (PET) with (18)F-fluorodesoxyglucose (FDG). Left ventricular (LV) ejection fraction (EF) and volume were quantified by automatic software on the FDG-PET images recorded in SHR (n = 20), SHHF (n = 18) and WKY-rats (n = 19) at ages 3 or 10 months old. Arterial blood pressure was determined by cardiac catheterization and cardiac fibrosis was quantified after sacrifice. Blood pressure was similarly elevated in SHR and SHHF rats (respective systolic blood pressures at 10-months: 199 ± 39 vs. 205 ± 2 mmHg), but SHHF rats had higher body mass than SHR rats (at 10-months, 630 ± 36 vs. 413 ± 27 g, p < 0.05) and higher blood levels of cholesterol and of triglycerides. At 3 months, cardiac parameters did not show significant differences between groups but at 10-months, SHHF and SHR rats exhibited an enhancement in myocardial mass and fibrosis associated with a clear decline in LV-EF (SHHF: 46 ± 6 %; SHR: 47 ± 5 %) as compared with WKY (56 ± 6 %, p < 0.01 for both comparisons). Cardiac remodeling of SHHF rats was clearly observable by FDG-PET from the age of 10-months, but in a similar way to that observed for SHR rats, suggesting a predominant role of hypertension.

Background: Severe hypotension resulting from anaphylactic shock may be refractory to epinephrine and impair cerebral oxygenation and metabolism contributing to anaphylactic shock morbidity and mortality. Refractoriness to epinephrine could be corrected by nitric oxide pathway inhibitors such as methylene blue., Objectives: To compare the systemic and regional (brain and skeletal muscle) effects of epinephrine and methylene blue given alone or in combination in a rat model of anaphylactic shock., Design: Prospective laboratory study., Setting: University laboratory., Subjects: Male Brown-Norway rats (n = 60)., Interventions: After sensitization and induction of anaphylactic shock by ovalbumin, animals received either vehicle (ovalbumin group) or a 3-mg/kg methylene blue bolus (methylene blue group) or epinephrine (epinephrine group) or both (methylene blue-epinephrine group). Sensitized control rats received only vehicle and no ovalbumin (control group)., Measurement and Main Results: Mean arterial pressure, cardiac output, cerebral blood flow, skeletal muscular oxygen partial pressure, cerebral oxygen partial pressure, skeletal muscular, and cerebral interstitial lactate/pyruvate ratio were measured. Cleaved caspase 3 and hypoxia-inducible factor-1α expression were analyzed in the cerebral cortex by Western blot. Without treatment, rats died rapidly within 15 mins from a decrease in cardiac output and mean arterial pressure, whereas treated rats survived until the end of the experiment. Methylene blue alone extended survival time but without significant improvement of hemodynamic variables and tissue perfusion and did not prevent neuronal injury. Epinephrine restored partially systemic hemodynamic variables and cerebral perfusion preventing glutamate-induced excitotoxicity. Compared with epinephrine alone, the methylene blue-epinephrine association avoided neuronal excitotoxicity and had an additive effect both on hemodynamic variables and for prevention of brain ischemia. Neither treatment could significantly restore cardiac output or prevent muscular compartment ischemia and microvascular leakage., Conclusions: Anaphylactic shock is associated with severe impairment of cerebral blood flow despite correction of arterial hypotension. Epinephrine must still be considered as the first-line vasoconstrictive agent to treat anaphylactic shock. The epinephrine-methylene blue association was the most effective treatment to prevent cerebral ischemia and could be used in anaphylactic shock refractory to epinephrine.

The effects of acute reduction in arterial blood pressure in severe anaphylactic shock (AS) on cerebral blood flow are of paramount importance to be investigated. We studied cerebral circulation and oxygenation in a model of severe AS and compared it with a pharmacologically induced arterial hypotension of similar magnitude. Anaphylactic shock was induced by 1 mg intravenous ovalbumin (OVA) in sensitized rats. Rats were randomized to three groups: (i) no resuscitation (OVA; n = 10) (ii) intravenous volume expansion (10 mL in 10 min after OVA injection) (OVA + VE; n = 10); (iii) control hypotension (100 μg of nicardipine followed by continuous infusion of 1 mg · 100 g · h intravenously; NICAR; n = 10). Mean arterial pressure (MAP), carotid blood flow (CBF), cardiac output, cerebral cortical blood flow (CCBF; estimated by laser Doppler technique), and cerebral tissue oxygen pressure (PtiO2) were recorded over the 15 min following AS induction in all three groups. Results are expressed as mean (SD). One minute after OVA or nicardipine injection, there was a rapid and significant 50% decrease in MAP from basal values. In the OVA group, AS severely altered systemic and cerebral hemodynamics in 5 min: 93% (SD, 4%) decrease in CBF, 66% (SD, 8%) in CCBF, and 44% (SD, 8%) in PtiO2; the decrease in CBF was significantly (P < 0.05) attenuated in the OVA + VE group; however, CCBF and PtiO2 were not statistically different in the OVA versus OVA + VE groups. On the contrary, nicardipine-induced hypotension had only a limited impact on CBF, cardiac output, CCBF, and PtiO2 for a similar MAP decrease. There was a linear relation between CCBF and blood pressure in the OVA (regression slope: 0.87 [SD, 0.06]; median r = 0.81) but not in the NICAR group (regression slope: 0.23 [SD, 0.32]; median r = 0.33). Anaphylactic shock resulted in severe impairment of cerebral blood flow and oxygenation, beyond what could be expected from the level of arterial hypotension.

Percutaneous left ventricular assist device (pLVAD) utilization is increasing as the potential applications expand. We report a case of high-risk balloon aortic valvuloplasty and percutaneous coronary intervention using the Impella 2.5 pLVAD in a patient with severely depressed left ventricular function as a bridge to heart transplantation.

Background: Pharmacokinetic data suggests that the intravenous form of n-acetylcysteine (NAC) may be more effective than the oral formulation in preventing contrast induced nephropathy (CIN). NAC owing to its anti-oxidant properties might be beneficial for patients with acute coronary syndromes (ACS) who are at increased risk for CIN. The aim of this prospective randomized, single-center, double-blind, placebo controlled trial (NCT00939913) was to assess the effect of high-dose intravenous NAC on CIN in ACS patients undergoing coronary angiography and/or percutaneous coronary intervention (PCI)., Methods: We randomized 398 ACS patients scheduled for diagnostic angiography ± PCI to an intravenous regimen of high-dose NAC (1,200 mg bolus followed by 200 mg/hr for 24 hr; n = 206) or placebo (n = 192). The primary end-point was incidence of CIN defined as an increase in serum creatinine concentration ≥ 25% above the baseline level within 72 hr of the administration of intravenous contrast., Results: There was no difference found for the primary end point with CIN in 16% of the NAC group and in 13% of the placebo group (p = 0.40). Change in serum cystatin-C, a sensitive marker for renal function, was 0.046 ± 0.204 in the NAC group and 0.002 ± 0.260 in the control group (p = 0.07)., Conclusion: In ACS patients undergoing angiography ± PCI, high-dose intravenous NAC failed to reduce the incidence of CIN., (Copyright © 2011 Wiley Periodicals, Inc.)