A dataset of global variations in directional solar radiation exposure for ocular research using the libRadtran radiative transfer model.

The libRadtran radiative transfer model was used to calculate examples of the amount of spectral radiation (250-2500 nm) incident on the eye. Simulations were run for every hour of four individual days (representing spring, summer, autumn and winter) and at three latitudes (from southern Spain to central Finland), in order to demonstrate diurnal and seasonal variations in directional photon flux density due to solar angle. The dataset also includes outputs under strong and weak aerosol optical density, three bidirectional reflectance distribution functions (corresponding to a forested, urban and snowy ground surfaces), eight cardinal directions, and two tilt angles (either looking towards the horizon or 15° downward). All simulations were parametrized according to local meteorological conditions (elevation, pressure, temperature) and atmospheric condition on the simulated day (aerosol optical density, water column, O3 and NO2 concentrations), at 170 cm above the ground (representing the average human height). Example data are presented for a 17° field of view relevant to exposure of the macula (without correction for spectral transmission of ocular media). For each simulation, a file in ".csv" format is available containing the radiance at each wavelength. The simulations were performed in batches via R software, from a template input parameter file modified for each simulation from a summary input table. The R code and input files are also available. By describing the amount and wavelength composition of directional radiation incident on the eye, this dataset and future simulations will help parameterize research aimed at understanding and mitigating eye-related diseases.

Design of the Building Research in CRC prevention (BRIDGE-CRC) trial: a 6-month, parallel group Mediterranean diet and weight loss randomized controlled lifestyle intervention targeting the bile acid-gut microbiome axis to reduce colorectal cancer risk among African American/Black adults with obesity.

BACKGROUND: Among all racial/ethnic groups, people who identify as African American/Blacks have the second highest colorectal cancer (CRC) incidence in the USA. This disparity may exist because African American/Blacks, compared to other racial/ethnic groups, have a higher prevalence of risk factors for CRC, including obesity, low fiber consumption, and higher intakes of fat and animal protein. One unexplored, underlying mechanism of this relationship is the bile acid-gut microbiome axis. High saturated fat, low fiber diets, and obesity lead to increases in tumor promoting secondary bile acids. Diets high in fiber, such as a Mediterranean diet, and intentional weight loss may reduce CRC risk by modulating the bile acid-gut microbiome axis. The purpose of this study is to test the impact of a Mediterranean diet alone, weight loss alone, or both, compared to typical diet controls on the bile acid-gut microbiome axis and CRC risk factors among African American/Blacks with obesity. Because weight loss or a Mediterranean diet alone can reduce CRC risk, we hypothesize that weight loss plus a Mediterranean diet will reduce CRC risk the most. METHODS: This randomized controlled lifestyle intervention will randomize 192 African American/Blacks with obesity, aged 45-75 years to one of four arms: Mediterranean diet, weight loss, weight loss plus Mediterranean diet, or typical diet controls, for 6 months (48 per arm). Data will be collected at baseline, mid-study, and study end. Primary outcomes include total circulating and fecal bile acids, taurine-conjugated bile acids, and deoxycholic acid. Secondary outcomes include body weight, body composition, dietary change, physical activity, metabolic risk, circulating cytokines, gut microbial community structure and composition, fecal short-chain fatty acids, and expression levels of genes from exfoliated intestinal cells linked to carcinogenesis. DISCUSSION: This study will be the first randomized controlled trial to examine the effects of a Mediterranean diet, weight loss, or both on bile acid metabolism, the gut microbiome, and intestinal epithelial genes associated with carcinogenesis. This approach to CRC risk reduction may be especially important among African American/Blacks given their higher risk factor profile and increased CRC incidence. TRIAL REGISTRATION: ClinicalTrials.gov NCT04753359 . Registered on 15 February 2021.

Effect of Diets Varying in Iron and Saturated Fat on the Gut Microbiota and Intestinal Inflammation: A Crossover Feeding Study among Older Females with Obesity.

Obesity is considered an independent risk factor for colorectal cancer (CRC). Altered nutrient metabolism, particularly changes to digestion and intestinal absorption, may play an important role in the development of CRC. Iron can promote the formation of tissue-damaging and immune-modulating reactive oxygen species. We conducted a crossover, controlled feeding study to examine the effect of three, 3-week diets varying in iron and saturated fat content on the colonic milieu and systemic markers among older females with obesity. Anthropometrics, fasting venous blood and stool were collected before and after each diet. There was a minimum 3-week washout period between diets. Eighteen participants consumed the three diets (72% Black; mean age 60.4 years; mean body mass index 35.7 kg/m2). Results showed no effect of the diets on intestinal inflammation (fecal calprotectin) or circulating iron, inflammation, and metabolic markers. Pairwise comparisons revealed less community diversity between samples (beta diversity, calculated from 16S rRNA amplicon sequences) among participants when consuming a diet low in iron and high in saturated fat vs. when consuming a diet high in iron and saturated fat. More studies are needed to investigate if dietary iron represents a salient target for CRC prevention among individuals with obesity.

The basis and design for time-restricted eating compared with daily calorie restriction for weight loss and colorectal cancer risk reduction trial (TRE-CRC trial).

OBJECTIVE: Approximately 42% of American adults are living with obesity, increasing their risk of colorectal cancer (CRC). Efficacious approaches to prevent and treat obesity may reduce CRC incidence. Daily calorie restriction (Cal-R) is the most common approach to treating obesity, yet clinically meaningful weight loss is elusive owing to waning adherence. Time-restricted eating (TRE) consists of consuming foods within a specified time frame, creating a natural calorie deficit. TRE in animals shows cancer protective effects. In humans, TRE is safe and acceptable among adults with obesity, producing ~3% to 5% weight loss and reductions in oxidative stress and insulin resistance. However, TRE has not been tested rigorously for CRC preventive effects. METHODS: The authors describe a 12-month randomized controlled trial of 8-hour TRE (ad libitum 12 PM-8 PM), Cal-R (25% restriction daily), or Control among 255 adults at increased risk for CRC and with obesity. RESULTS: Effects on the following will be examined: 1) body weight, body composition, and adherence; 2) circulating metabolic, inflammation, and oxidative stress biomarkers; 3) colonic mucosal gene expression profiles and tissue microenvironment; and 4) maintenance of benefits on body weight/composition and CRC risk markers. CONCLUSIONS: This study will examine efficacious lifestyle strategies to treat obesity and reduce CRC risk among individuals with obesity.

Quantitative action spectroscopy reveals ARPE19 sensitivity to ultraviolet radiation at 350 nm and 380 nm.

The role of ultraviolet radiation (UVR) exposure in the aetiology of retinal degeneration has been debated for decades with epidemiological evidence failing to find a clear consensus for or against it playing a role. A key reason for this is a lack of foundational research into the response of living retinal tissue to UVR in regard to modern ageing-specific parameters of tissue function. We therefore explored the response of cultured retinal pigmented epithelium (RPE), the loss of which heralds advanced visual decline, to specific wavelengths of UVR across the UV-B and UV-A bands found in natural sunlight. Using a bespoke in vitro UVR exposure apparatus coupled with bandpass filters we exposed the immortalised RPE cell line, ARPE-19, to 10 nm bands of UVR between 290 and 405 nm. Physical cell dynamics were assessed during exposure in cells cultured upon specialist electrode culture plates which allow for continuous, non-invasive electrostatic interrogation of key cell parameters during exposure such as monolayer coverage and tight-junction integrity. UVR exposures were also utilised to quantify wavelength-specific effects using a rapid cell viability assay and a phenotypic profiling assay which was leveraged to simultaneously quantify intracellular reactive oxygen species (ROS), nuclear morphology, mitochondrial stress, epithelial integrity and cell viability as part of a phenotypic profiling approach to quantifying the effects of UVR. Electrical impedance assessment revealed unforeseen detrimental effects of UV-A, beginning at 350 nm, alongside previously demonstrated UV-B impacts. Cell viability analysis also highlighted increased effects at 350 nm as well as 380 nm. Effects at 350 nm were further substantiated by high content image analysis which highlighted increased mitochondrial dysfunction and oxidative stress. We conclude that ARPE-19 cells exhibit a previously uncharacterised sensitivity to UV-A radiation, specifically at 350 nm and somewhat less at 380 nm. If upheld in vivo, such sensitivity will have impacts upon geoepidemiological risk scoring of macular sensitivity.

Prepregnancy Obesity Does Not Impact Placental Iron Trafficking.

BACKGROUND: Iron is critical for fetal development. Neonates of obese women may be at risk for poor iron status at birth as a result of maternal inflammation-driven overexpression of hepcidin. OBJECTIVES: The objective of this study was to determine differences in placental transfer of oral iron (57Fe) and expression of placental transferrin receptor 1 (TFR1) and ferroportin (FPN) mRNA and protein and their association with maternal and neonatal iron-related parameters, including maternal hepcidin, among women with and without prepregnancy (PP) obesity. METHODS: 57Fe ingested during the third trimester of pregnancy was recovered in venous umbilical cord blood among 20 PP obese [BMI (in kg/m2): 30.5-43.9] and 22 nonobese (BMI: 18.5-29.0) women aged 17-39 y. Placental TFR1 and FPN mRNA and protein expression were quantified via qPCR and Western blot. Maternal and neonatal markers of iron status and regulation, as well as inflammation, were measured. Descriptive and inferential statistical tests (e.g., Student t test, Pearson correlation) were used for data analysis. RESULTS: There was no difference in cord blood enrichment of 57Fe or placental mRNA or protein expression of TFR1 or FPN among the women with and without PP obesity. Maternal hepcidin was not correlated with cord blood enrichment of 57Fe or placental FPN mRNA or protein expression. Maternal log ferritin (corrected for inflammation) was inversely correlated with log percent enrichment of 57Fe in cord blood (partial r = -0.50; P < 0.01, controlled for marital status) and protein expression of TFR1 (r = -0.43; P = 0.01). CONCLUSIONS: Placental iron trafficking did not differ among women with and without PP obesity. Findings reinforce the importance of maternal iron stores in regulating placental iron trafficking.

Impact of Physical Activity and Weight Loss on Fat Mass, Glucose Metabolism, and Inflammation in Older African Americans with Osteoarthritis.

(1) Background: There are currently very few interventions performed within a community setting that compare the effects of physical activity (PA) versus PA plus weight loss on cancer and chronic disease risk in older African Americans. Therefore, we investigated the impact of an 8 week (24 session) PA intervention compared to a PA plus weight loss intervention on fat mass, glucose metabolism, and markers of inflammation in older, overweight and obese African Americans. (2) Methods: Subjects were randomized to a PA (n = 83) or PA plus weight loss (n = 72) intervention that met three times weekly for 8 weeks. At baseline and post-intervention, anthropometrics, body composition, systemic inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin 6), fasting glucose, insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were determined. (3) Results: Subjects had a mean age of 67 years (SD = 5.3) and were mostly women (88%). The PA plus weight loss group lost more total and visceral fat than the PA group (-4.0% vs. +0.6% and -4.1% vs. +3.7%, respectively, p < 0.01 for both). Changes in inflammation and glucose metabolism were similar between groups post-intervention. Within the PA plus weight loss group only, serum insulin and HOMA-IR decreased significantly. (4) Conclusions: PA combined with weight loss can decrease total and visceral fat mass and improve insulin sensitivity, confirming that these cancer- and chronic disease-related risk factors are influenced by relatively modest lifestyle changes in the short term.

Prepregnancy Obesity Is Not Associated with Iron Utilization during the Third Trimester.

BACKGROUND: An adequate maternal iron supply is crucial for maternal red blood cell (RBC) expansion, placental and fetal growth, and fetal brain development. Obese women may be at risk for poor iron status in pregnancy due to proinflammatory-driven overexpression of hepcidin leading to decreased iron bioavailability. OBJECTIVE: The objective of this study was to determine the impact of prepregnancy (PP) obesity on third-trimester maternal iron utilization. DESIGN: Using the stable isotope 57Fe, we measured iron utilization in the third trimester in PP obese [BMI (in kg/m2): ≥30] and nonobese (BMI: 18.5-29.9) women. We also assessed iron status, hepcidin, inflammation, erythropoietin, dietary iron intake, and gestational weight gain. Descriptive and inferential statistical tests (e.g., Student t test, Pearson correlation) were used for data analysis. RESULTS: Fifty pregnant women (21 PP obese, 29 PP nonobese) were included. Mean age was 27.6 ± 6.8 y and mean gestational age at time of 57Fe administration was 32.7 ± 0.7 wk. Anemia (hemoglobin <11 g/dL for non-black and <10.2 g/dL for black women) affected 38% of women (43% PP obese compared with 35% PP nonobese; P = 0.55). Women with PP obesity had significantly higher C-reactive protein (8.5 compared with 3.4 mg/L, P = 0.0007) and total body iron corrected for inflammation (6.0 compared with 4.3 mg/kg, P = 0.04) compared with the nonobese women. There was no difference in serum hepcidin or iron utilization between the PP BMI groups. CONCLUSION: This is the first study to assess the impact of PP obesity on maternal iron utilization. We found no difference in iron utilization in the third trimester of pregnancy in women with and without PP obesity. Despite higher frequency of anemia, women with PP obesity had less depleted body iron stores, suggesting some degree of iron sequestration. This finding should be followed up and extended to understand effects on fetal iron bioavailability.

A Systematic Review and Meta-Analysis on the Effects of Probiotic Species on Iron Absorption and Iron Status.

BACKGROUND: Strategies to prevent iron deficiency anemia (IDA) have varying effectiveness. The purpose of this systematic review of the literature and meta-analysis was to examine the effects of probiotics on iron absorption and iron status-related markers in humans. METHODS: We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) reporting guidelines. Relevant articles were identified from Embase, Pubmed, Scopus, and CINAHL from inception to February, 2019. We conducted a meta-analysis for eight studies examining the effect of the probiotic Lactobacillus plantarum 299v (Lp299v) on iron absorption. RESULTS: Fifteen studies reported in 12 articles were identified (N = 950). Our meta-analysis of eight studies using a random-effects model demonstrated a significant increase in iron absorption following administration of the probiotic Lp299v with a pooled standardized mean difference (an average intervention effect size) of 0.55 (95% CI 0.22-0.88, p = 0.001). Of the seven randomized clinical trials (RCTs) and nonrandomized clinical trials examining a range of probiotic species on iron status, only one study supplementing with Lp299v showed improvement in serum iron; no other studies reported improvement in iron status-related indices with probiotic treatment. CONCLUSIONS: Lp299v significantly improved iron absorption in humans. Future research should include the assessment of Lp299v effect on iron absorption and iron status in populations at high risk of IDA, including pregnant women.

Reactivity and Speciation of Anti-Diabetic Vanadium Complexes in Whole Blood and Its Components: The Important Role of Red Blood Cells.

Reactions with blood components are crucial for controlling the antidiabetic, anticancer, and other biological activities of V(V) and V(IV) complexes. Despite extensive studies of V(V) and V(IV) reactions with the major blood proteins (albumin and transferrin), reactions with whole blood and red blood cells (RBC) have been studied rarely. A detailed speciation study of Na3[V(V)O4] (A), K4[V(IV)2O2(citr)2]·6H2O (B; citr = citrato(4-)); [V(IV)O(ma)2] (C; ma = maltolato(-)), and (NH4)[V(V)(O)2(dipic)] (D; dipic = pyridine-2,6-dicarboxylato(2-)) in whole rat blood, freshly isolated rat plasma, and commercial bovine serum using X-ray absorption near-edge structure (XANES) spectroscopy is reported. The latter two compounds are potential oral antidiabetic drugs, and the former two are likely to represent their typical decomposition products in gastrointestinal media. XANES spectral speciation was performed by principal component analysis and multiple linear regression techniques, and the distribution of V between RBC and plasma fractions was measured by electrothermal atomic absorption spectroscopy. Reactions of A, C, or D with whole blood (1.0 mM V, 1-6 h at 310 K) led to accumulation of ∼50% of total V in the RBC fraction (∼10% in the case of B), which indicated that RBC act as V carriers to peripheral organs. The spectra of V products in RBC were independent of the initial V complex, and were best fitted by a combination of V(IV)-carbohydrate (2-hydroxyacid moieties) and/or citrate (65-85%) and V(V)-protein (15-35%) models. The presence of RBC created a more reducing environment in the plasma fraction of whole blood compared with those in isolated plasma or serum, as shown by the differences in distribution of V(IV) and V(V) species in the reaction products of A-D in these media. At physiologically relevant V concentrations (<50 µM), this role of RBC may promote the formation of V(III)-transferrin as a major V carrier in the blood plasma. The results reported herein have broad implications for the roles of RBC in the transport and speciation of metal pro-drugs that have broad applications across medicine.

Vanadium(V) and -(IV) complexes of anionic polysaccharides: Controlled release pharmaceutical formulations and models of vanadium biotransformation products.

Uncontrolled reactions in biological media are a main obstacle for clinical translation of V-based anti-diabetic or anti-cancer pro-drugs. We investigated the use of controlled-release pharmaceutical formulations to ameliorate this issue with a series of V(V) and (IV) complexes of anionic polysaccharides. Carboxymethyl cellulose, xanthan gum, or alginic acid formulations were prepared by the reactions of [VO4](3-) with one or two molar equivalents of biological reductants, L-ascorbic acid (AA) or L-cysteine (Cys), in the presence of excess polysaccharide at pH~7 or pH~4. XANES studies with the use of a previously developed library of model V(V), V(IV) and V(III) complexes showed that reactions in the presence of AA led mostly to the mixtures of five- and six-coordinate V(IV) species, while the reactions in the presence of Cys led predominantly to the mixtures of five- and six-coordinate V(V) species. The XANES spectra of some of these samples closely matched those reported previously for [VO4](3-) biotransformation products in isolated blood plasma, red blood cells, or cultured adipocytes, which supports the hypothesis that modified polysaccharides are major binders of V(V) and V(IV) in biological systems. Studies by EPR spectroscopy suggested predominant V(IV)-carboxylato binding in complexes with polysaccharides. One of the isolated products (a V(IV)-alginato complex) showed selective release of low-molecular-mass V species at pH~8, but not at pH~2, which makes it a promising lead for the development of V-containing formulations for oral administration that are stable in the stomach, but release the active ingredient in the intestines.

Cardiopulmonary exercise testing for predicting postoperative morbidity in patients undergoing hepatic resection surgery.

OBJECTIVES: Cardiopulmonary exercise testing (CPET) may predict which patients are at risk for adverse outcomes after major abdominal surgery. The primary aim of this study was to determine whether CPET variables are predicative of morbidity. METHODS: High-risk patients undergoing elective, one-stage, open hepatic resection were preoperatively assessed using CPET. Morbidity, as defined by the Postoperative Morbidity Survey (POMS), was assessed on postoperative day 3. RESULTS: A total of 104 patients underwent preoperative CPET and were included in the analysis. Of these, 73 patients (70.2%) experienced postoperative morbidity. Oxygen consumption at anaerobic threshold (V˙O2 at AT, ml/kg/min) was the only CPET predictor of postoperative morbidity on multivariable analysis, with an area under the curve (AUC) of 0.66 [95% confidence interval (CI) 0.55-0.76]. In patients requiring a major hepatic resection (three or more segments), a V˙O2 at AT of <10.2 ml/kg/min gave an AUC of 0.79 (95% CI 0.68-0.86) with 83.9% sensitivity and 52.0% specificity, 80.6% positive predictive value and 62.5% negative predictive value. CONCLUSIONS: The application of a cut-off value for V˙O2 at AT of <10.2 ml/kg/min in patients undergoing major hepatic resection may be useful for predicting which patients will experience morbidity.

Biotransformations of Antidiabetic Vanadium Prodrugs in Mammalian Cells and Cell Culture Media: A XANES Spectroscopic Study.

The antidiabetic activities of vanadium(V) and -(IV) prodrugs are determined by their ability to release active species upon interactions with components of biological media. The first X-ray absorption spectroscopic study of the reactivity of typical vanadium (V) antidiabetics, vanadate ([V(V)O4](3-), A) and a vanadium(IV) bis(maltolato) complex (B), with mammalian cell cultures has been performed using HepG2 (human hepatoma), A549 (human lung carcinoma), and 3T3-L1 (mouse adipocytes and preadipocytes) cell lines, as well as the corresponding cell culture media. X-ray absorption near-edge structure data were analyzed using empirical correlations with a library of model vanadium(V), -(IV), and -(III) complexes. Both A and B ([V] = 1.0 mM) gradually converged into similar mixtures of predominantly five- and six-coordinate V(V) species (∼75% total V) in a cell culture medium within 24 h at 310 K. Speciation of V in intact HepG2 cells also changed with the incubation time (from ∼20% to ∼70% V(IV) of total V), but it was largely independent of the prodrug used (A or B) or of the predominant V oxidation state in the medium. Subcellular fractionation of A549 cells suggested that V(V) reduction to V(IV) occurred predominantly in the cytoplasm, while accumulation of V(V) in the nucleus was likely to have been facilitated by noncovalent bonding to histone proteins. The nuclear V(V) is likely to modulate the transcription process and to be ultimately related to cell death at high concentrations of V, which may be important in anticancer activities. Mature 3T3-L1 adipocytes (unlike for preadipocytes) showed a higher propensity to form V(IV) species, despite the prevalence of V(V) in the medium. The distinct V biochemistry in these cells is consistent with their crucial role in insulin-dependent glucose and fat metabolism and may also point to an endogenous role of V in adipocytes.

Apple polyphenol extracts protect against aspirin-induced gastric mucosal damage in rats.

The protective role of two apple polyphenol extracts, Douglas-FB (FB) and Douglas-EF (EF), on gastric mucosal damage following aspirin ingestion was investigated in healthy rats. Polyphenol content of the apple extracts varied, with the EF extract having 20% w/w polyphenols and a high proportion of flavanols as epicatechin and procyanidin, whereas the FB extract comprised 12% w/w polyphenols, which were mostly flavonols as quercetin glycosides. Male Sprague-Dawley rats were allocated to control, FB and EF groups and fed the experimental diet during the 10-day trial. Control treatment rats received 1 mL of deionised water, whereas apple polyphenol treatment group rats, FB and EF received a concentration of 10(-2) m polyphenols in 1 mL deionised water daily via oral gavage. At the end of 10-day feeding period, rats were fasted overnight, and the following morning, aspirin (200 mg/kg) was given by oral gavage. Four hours after aspirin administration, the animals were euthanised, and samples taken for analysis. Both apple polyphenol extracts significantly reduced the ulcer area, ulcer lesion index and gastric injury score. The glutathione in gastric mucosa was increased significantly in rats given FB apple extract. Despite their different polyphenol compositions, FB and EF apple extracts assisted in protecting the gastric mucosa following acute aspirin administration in rats.

Quantifying the loss of methane through secondary gas mass transport (or 'slip') from a micro-porous membrane contactor applied to biogas upgrading.

Secondary gas transport during the separation of a binary gas with a micro-porous hollow fibre membrane contactor (HMFC) has been studied for biogas upgrading. In this application, the loss or 'slip' of the secondary gas (methane) during separation is a known concern, specifically since methane possesses the intrinsic calorific value. Deionised (DI) water was initially used as the physical solvent. Under these conditions, carbon dioxide (CO2) and methane (CH4) absorption were dependent upon liquid velocity (V(L)). Whilst the highest CO2 flux was recorded at high V(L), selectivity towards CO2 declined due to low residence times and a diminished gas-side partial pressure, and resulted in slip of approximately 5.2% of the inlet methane. Sodium hydroxide was subsequently used as a comparative chemical absorption solvent. Under these conditions, CO2 mass transfer increased by increasing gas velocity (VG) which is attributed to the excess of reactive hydroxide ions present in the solvent, and the fast conversion of dissolved CO2 to carbonate species reinitiating the concentration gradient at the gas-liquid interface. At high gas velocities, CH4 slip was reduced to 0.1% under chemical conditions. Methane slip is therefore dependent upon whether the process is gas phase or liquid phase controlled, since methane mass transport can be adequately described by Henry's law within both physical and chemical solvents. The addition of an electrolyte was found to further retard CH4 absorption via the salting out effect. However, their applicability to physical solvents is limited since electrolytic concentration similarly impinges upon the solvents' capacity for CO2. This study illustrates the significance of secondary gas mass transport, and furthermore demonstrates that gas-phase controlled systems are recommended where greater selectivity is required.

Reactivity of potential anti-diabetic molybdenum(VI) complexes in biological media: a XANES spectroscopic study.

The application of Mo(VI) complexes as anti-diabetic agents is a subject of considerable recent interest. The stability and speciation of [Mo(VI)O(4)](2-) and three analogs of known anti-diabetic V(IV) complexes ([Mo(VI)O(2)L(2)]; where LH=2,4-pentanedione, l-cysteine ethyl ester or N,N-diethyldithiocarbamic acid) in natural and simulated biological fluids (including blood and its components, cell culture media, and artificial digestion systems) were studied using MoK-edge XANES (X-ray absorption near-edge structure) spectroscopy of freeze-dried samples at 20K. All of the studied [MoO(2)L(2)] complexes decomposed extensively under simulated gastric and intestinal digestion conditions (3 h at 310 K), as well as in blood plasma or in cell culture medium (24 h at 310 K). The reaction products of [MoO(4)](2-) and [MoO(2)L(2)] with biological fluids could be satisfactorily modelled (using multiple linear regression analyses) as mixtures of tetrahedral and octahedral Mo(VI) species (with O-donor ligands) in various ratios, which were dependent on the nature of the medium rather than that of the initial Mo(VI) compounds. Red blood cells take up Mo(VI) predominantly in the form of [MoO(4)](2-). Implications of these results to the development of Mo(VI)-based anti-diabetics and to the mechanisms of natural uptake and metabolism of Mo(VI) are discussed.

Case series: Ultrasonography may assist epidural insertion in scoliosis patients.

PURPOSE: Epidural cannulation is a difficult technique in the patient undergoing scoliosis repair, due to axial rotation of the vertebral bodies, as well as angulation of the spinal processes. This case series was performed to investigate whether ultrasonography could facilitate epidural insertion in patients with scoliosis, by assessing the degree of vertebral body rotation. CLINICAL FEATURES: Eleven patients scheduled for corrective scoliosis surgery were studied. The spine was examined ultrasonically using a portable ultrasound system with a 38-mm linear probe in two-dimensional B mode. The angulation of the probe head (measured using an inclinometer held in alignment with its long axis) at which the echo signals from the laminae became level on the screen was taken to correspond to the degree of vertebral rotation. The least rotated (most neutral) vertebral interspace was located, and a supervised anesthesiology trainee then performed epidural catheter insertion, using a loss-of-resistance technique. Bupivacaine 0.125% with fentanyl 4 mug.mL(-1) was infused after surgery, and successful epidural placement was indicated by the presence of effective analgesia and loss of sensation to cold stimuli. In ten patients, the neutral space could be identified, while in one, the least rotated space was measured at 15 degrees from the horizontal. Epidural catheterization was successful in eight of 11 patients at the identified level. In two other patients, the space above was employed. The information was described as helpful in seven patients. CONCLUSION: We conclude that ultrasonography may have a potential role to facilitate insertion of epidural catheters in patients with scoliosis.

Influence of differential vascular remodeling on the coronary vasomotor response.

OBJECTIVES: Arterial remodeling may increase or decrease the luminal encroachment of atherosclerotic plaques in the coronary circulation. However, the factors determining the nature and consequences of the remodeling process remain poorly characterized. The study aims were to assess whether the pattern of vascular remodeling influences the physical and vasomotor responses of the coronary arteries in vivo in man. METHODS: Coronary vessel area, distensibility and stiffness were determined in positively, negatively and non-remodeled arterial segments using intravascular ultrasound and Doppler flow measurement. Epicardial vasomotor responses were determined following intracoronary boluses of acetylcholine (10(-6) and 10(-4) M), adenosine (24-30 microg) and nitroglycerin (200 microg). RESULTS: Fifty-six coronary arterial segments were studied in 25 patients. In comparison to non- and positively remodeled segments, negatively remodeled segments had a higher stiffness index (67+/-16 vs. 33+/-5 and 38+/-8, respectively; P<0.02) and appeared to have lower compliance and distensibility (0.66+/-0.17 vs. 1.65+/-0.54 and 0.94+/-0.18/mmHg; P=NS). Non-remodeled segments had a greater change in vessel area with 10(-6) M acetylcholine (4.9+/-0.8%), compared to positively and negatively remodeled segments (0.6+/-1.8% and -4.9+/-1.8%, respectively, P<0.05). A significant degree of preservation of vasodilatation to 10(-6) M acetylcholine was evident in positively remodeled compared with negatively remodeled segments (P<0.05). Nitroglycerin caused greater vasodilatation in non-remodeled segments (7.2+/-3.8%) than either positively or negatively remodeled segments (4.7+/-0.9 and 3.7+/-0.6%, respectively, P<0.05). CONCLUSIONS: Vascular remodeling is an important and major determinant of local epicardial vasomotor responses. Both structural and functional abnormalities are associated with negative remodeling that may contribute to the adverse effects of such lesions.