A Flexible Theory for Catalysis: Learning Alkaline Oxygen Reduction on Complex Solid Solutions within the Ag-Pd-Pt-Ru Composition Space.

Compositionally complex materials such as high-entropy alloys and oxides have the potential to be efficient platforms for catalyst discovery because of the vast chemical space spanned by these novel materials. Identifying the composition of the most active catalyst materials, however, requires unraveling the descriptor-activity relationship, as experimentally screening the multitude of possible element ratios quickly becomes a daunting task. In this work, we show that inferred adsorption energy distributions of *OH and *O on complex solid solution surfaces within the space spanned by the system Ag-Pd-Pt-Ru are coupled to the experimentally observed electrocatalytic performance for the oxygen reduction reaction. In total, the catalytic activity of 1582 alloy compositions is predicted with a cross-validated mean absolute error of 0.042 mA/cm2 by applying a theory-derived model with only two adjustable parameters. Trends in the discrepancies between predicted electrochemical performance values of the model and the measured values on thin film surfaces subsequently provide insight into the alloys' surface compositions during reaction conditions. Bridging this gap between computationally modeled and experimentally observed catalytic activities, not only reveals insight into the underlying theory of catalysis but also takes a step closer to realizing exploration and exploitation of high-entropy materials.

Complex-Solid-Solution Electrocatalyst Discovery by Computational Prediction and High-Throughput Experimentation*.

Complex solid solutions ("high entropy alloys"), comprising five or more principal elements, promise a paradigm change in electrocatalysis due to the availability of millions of different active sites with unique arrangements of multiple elements directly neighbouring a binding site. Thus, strong electronic and geometric effects are induced, which are known as effective tools to tune activity. With the example of the oxygen reduction reaction, we show that by utilising a data-driven discovery cycle, the multidimensionality challenge raised by this catalyst class can be mastered. Iteratively refined computational models predict activity trends around which continuous composition-spread thin-film libraries are synthesised. High-throughput characterisation datasets are then used as input for refinement of the model. The refined model correctly predicts activity maxima of the exemplary model system Ag-Ir-Pd-Pt-Ru. The method can identify optimal complex-solid-solution materials for electrocatalytic reactions in an unprecedented manner.

Bayesian Optimization of High-Entropy Alloy Compositions for Electrocatalytic Oxygen Reduction*.

Active, selective and stable catalysts are imperative for sustainable energy conversion, and engineering materials with such properties are highly desired. High-entropy alloys (HEAs) offer a vast compositional space for tuning such properties. Too vast, however, to traverse without the proper tools. Here, we report the use of Bayesian optimization on a model based on density functional theory (DFT) to predict the most active compositions for the electrochemical oxygen reduction reaction (ORR) with the least possible number of sampled compositions for the two HEAs Ag-Ir-Pd-Pt-Ru and Ir-Pd-Pt-Rh-Ru. The discovered optima are then scrutinized with DFT and subjected to experimental validation where optimal catalytic activities are verified for Ag-Pd, Ir-Pt, and Pd-Ru binary alloys. This study offers insight into the number of experiments needed for optimizing the vast compositional space of multimetallic alloys which has been determined to be on the order of 50 for ORR on these HEAs.

TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling.

Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1ß was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407-416.

Symmetry controlled excited state dynamics.

Symmetry effects in internal conversion are studied by means of two isomeric cyclic tertiary aliphatic amines in a velocity map imaging (VMI) experiment on the femtosecond timescale. It is demonstrated that there is a delicate structural dependence on when coherence is preserved after the transition between the 3p and 3s Rydberg states. N-Methyl morpholine (NMM) shows unambiguous preserved coherence, consistent with previous work, which is decidedly switched off by the repositioning of oxygen within the ring. From the differences in these dynamics, and an examination of the potential energy surface following the normal modes of vibration, it becomes clear that there is a striking dependence on atom substitution, which manifests itself in the permitted modes of vibration that take the system out of the Franck-Condon region through to the 3s minimum. It is shown that the non Fermi-like behaviour of NMM is due to a conical intersection (CI) between the 3px and 3s states lying directly along the symmetry allowed path of steepest descent out of the Franck-Condon region. NMI, where the symmetry has been changed, is shown to undergo internal conversion in a more Fermi-like manner as the energy spreads through the available modes ergodically.

Putting the Disulfide Bridge at Risk: How UV-C Radiation Leads to Ultrafast Rupture of the S-S Bond.

We investigate the ultrafast photoinduced dynamics of the cyclic disulfide 1,2-dithiane upon 200 nm excitation by time-resolved photoelectron spectroscopy and show that the S-S bond breaks on an ultrafast time scale. This stands in stark contrast to excitation at longer wavelengths where the initially excited S1 state evolves as the wavepacket is guided towards a conical intersection with S0 by a torsional motion involving a partially broken bond between the sulfur atoms. This process at lower excitation energy allows for efficient (re-)population of S0 , rendering dithiane intact. At 200 nm, in contrast, the excitation leads to a manifold of higher excited states, Sn , that are primarily of Rydberg character. We are able to follow the gradual transition from the initially excited state to the dissociative receiver state in real time. The Rydberg states are intersected by a repulsive valence state that mediates a transition to the repulsive S2 surface. Therefore, we propose that the resulting diradical will eventually break apart on a longer timescale. The findings imply that upon going from UV-B to UV-C light the structural integrity of the disulfide moiety is compromised and proteins irradiated in this range will not be able to reform the initial tertiary structure, leading to loss of function.

Health Benefits of Long-Term Weight-Loss Maintenance.

Obesity is a chronic and complex medical condition associated with a large number of complications affecting most organs and systems through multiple pathways. Strategies for weight management include behavioral, pharmacological, and surgical interventions, all of which can result in a reduction in obesity-related comorbidities and improvements in quality of life. However, subsequent weight regain often reduces the durability of these improvements. The objective of this article is to review evidence supporting the long-term effects of intentional weight loss on morbidity, mortality, quality of life, and health-care cost. Overall, considerable evidence suggests that intentional weight loss is associated with clinically relevant benefits for the majority of obesity-related comorbidities. However, the degree of weight loss that must be achieved and sustained to reap these benefits varies widely between comorbidities.

Low-molecular-weight carbohydrate Pentaisomaltose may replace dimethyl sulfoxide as a safer cryoprotectant for cryopreservation of peripheral blood stem cells.

BACKGROUND: Cryopreserved hematopoietic stem cell products are widely used for certain hematologic malignancies. Dimethyl sulfoxide (DMSO) is the most widely used cryoprotective agent (CPA) today, but due to indications of cellular toxicity, changes of the cellular epigenetic state, and patient-related side effects, there is an increasing demand for DMSO-free alternatives. We therefore investigated whether Pentaisomaltose (PIM), a low-molecular-weight carbohydrate (1 kDa), can be used for cryopreservation of peripheral blood stem cells, more specifically hematopoietic progenitor cell apheresis (HPC(A)) product. STUDY DESIGN AND METHODS: We cryopreserved patient or donor HPC(A) products using 10% DMSO or 16% PIM and quantified the recovery of CD34+ cells and CD34+ subpopulations by multicolor flow cytometry. In addition, we compared the frequency of HPCs after DMSO and PIM cryopreservation using the colony-forming cells (CFCs) assay. RESULTS: The mean CD34+ cell recovery was 56.3 ± 23.7% (11.4%-97.3%) and 58.2 ± 10.0% (45.7%-76.9%) for 10% DMSO and 16% PIM, respectively. The distribution of CD34+ cell subpopulations was similar when comparing DMSO or PIM as CPA. CFC assay showed mean colony numbers of 70.7 ± 25.4 (range, 37.8-115.5) and 67.7 ± 15.7 (range, 48-86) for 10% DMSO and 16% PIM, respectively. CONCLUSION: Our findings demonstrate that PIM cryopreservation of HPC(A) products provides recovery of CD34+ cells, CD34+ subpopulations, and CFCs similar to that of DMSO cryopreservation and therefore may have the potential to be used for cryopreservation of peripheral blood stem cells.

Comparative effectiveness and safety of gastric bypass, sleeve gastrectomy and adjustable gastric banding in a population-based bariatric program: prospective cohort study.

BACKGROUND: Bariatric surgery in Canada is primarily delivered within publicly funded specialty clinics. Previous studies have demonstrated that bariatric surgery is superior to intensive medical management for reduction of weight and obesity-related comorbidities. Our objective was to compare the effectiveness and safety of laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (LSG) and adjustable gastric banding (LAGB) in a publicly funded, population-based bariatric treatment program. METHODS: We followed consecutive bariatric surgery patients for 2 years. The primary outcome was weight change (in kilograms). Between-group changes were analyzed using multivariable regression. Last-observation-carried-forward imputation was used for missing data. RESULTS: We included 150 consecutive patients (51 RYGB; 51 LSG; 48 LAGB) in our study. At baseline, mean age was 43.5 ± 9.5 years, 87.3% of patients were women, and preoperative body mass index (BMI) was 46.2 ± 7.4. Absolute and relative (% of baseline) weight loss at 2 years were 36.6 ± 19.5 kg (26.1 ± 12.2%) for RYGB, 21.4 ± 16.0 kg (16.4 ± 11.6%) for LSG and 7.0 ± 9.7 kg (5.8 ± 7.9%) for LAGB (p < 0.001). Change in BMI was greater for the RYGB (-13.0 ± 6.6) than both the LSG (-7.6 ± 5.7) and the LAGB (-2.6 ± 3.5) groups (p < 0.001). The reduction in diabetes, hypertension and dyslipidemia was greater after RYGB than after LAGB (all p < 0.05). There were no deaths. The anastomotic and staple leakage rate was 1.3%. CONCLUSION: In a publicly funded, population-based bariatric surgery program, RYGB and LSG demonstrated greater weight loss than the LAGB procedure. Bypass resulted in the greatest reduction in obesity-related comorbidities. All procedures were safe.

BACKGROUND: Au Canada, la chirurgie bariatrique est effectuée principalement dans des cliniques spécialisées financées par le secteur public. Des études ont démontré que les interventions de cette nature sont supérieures à la prise en charge médicale intensive pour la perte de poids et la réduction des affections comorbides liées à l'obésité. L'objectif de notre étude était de comparer l'efficacité et l'innocuité de la dérivation gastrique Roux-en-Y par laparoscopie (DGRY), de la gastrectomie longitudinale (GL) et de la gastroplastie par anneau gastrique modulable (GAGM) dans le cadre d'un programme de traitement bariatrique basé sur la population financé par les deniers publics. METHODS: Nous avons suivi pendant 2 ans des patients ayant subi une chirurgie bariatrique. Le résultat primaire à l'étude était la variation pondérale (en kilogrammes). Nous avons analysé la variation intergroupe au moyen d'une régression multivariable et utilisé la méthode d'imputation des données manquantes par report de la dernière observation. RESULTS: Nous avons retenu 150 patients consécutifs (51 DGRY; 51 GL; 48 GAGM). Au début de l'étude, l'âge moyen était de 43,5 ± 9,5 ans, 87,3 % des patients étaient des femmes, et leur indice de masse corporelle (IMC) avant l'opération était de 46,2 ± 7,4. Après 2 ans, la perte de poids moyenne (pourcentage du poids de départ) était de 36,6 ± 19,5 kg (26,1 ± 12,2 %) pour la DGRY, de 21,4 ± 16,0 kg (16,4 ± 11,6 %) pour la GL, et de 7,0 ± 9,7 kg (5,8 ± 7,9 %) pour la GAGM (p < 0,001). La variation de l'IMC était plus grande pour le groupe DGRY (13,0 ± 6,6) que pour les 2 autres groupes (7,6 ± 5,7 pour la GL et 2,6 ± 3,5 pour la GAGM; p < 0,001). L'incidence sur le diabète, l'hypertension et la dyslipidémie était également plus grande après la DGRY qu'après la GAGM (p < 0,05 pour tous). Il n'y a eu aucun décès. Le taux de fuites anastomotiques et liées aux sutures était de 1,3 %. CONCLUSION: Dans le cadre d'un programme de chirurgie bariatrique basé sur une population et financé par le secteur public, la DGRY et la GL ont entraîné une plus grande perte de poids que la GAGM. La dérivation a donné lieu à la plus forte réduction des affections comorbides liées à l'obésité. Toutes les interventions se sont avérées sécuritaires.

Case study of a non-destructive treatment method for the remediation of military structures containing polychlorinated biphenyl contaminated paint.

Restricted by federal regulations and limited remediation options, buildings contaminated with paint laden with polychlorinated biphenyls (PCBs) have high costs associated with the disposal of hazardous materials. As opposed to current remediation methods which are often destructive and a risk to the surrounding environment, this study suggests a non-metal treatment system (NMTS) and a bimetallic treatment system (BTS) as versatile remediation options for painted industrial structures including concrete buildings, and metal machine parts. In this field study, four areas of a discontinued Department of Defense site were treated and monitored over 3 weeks. PCB levels in paint and treatment system samples were analyzed through gas chromatography/electron capture detection (GC-ECD). PCB concentrations were reduced by 95 percent on painted concrete and by 60-97 percent on painted metal with the majority of the PCB removal occurring within the first week of application. Post treatment laboratory studies including the utilization of an activated metal treatment system (AMTS) further degraded PCBs in BTS and NMTS by up to 82 percent and 99 percent, respectively, indicating that a two-step remediation option is viable. These findings demonstrate that the NMTS and BTS can be an effective, nondestructive, remediation process for large painted structures, allowing for the reuse or sale of remediated materials that otherwise may have been disposed.

Weight loss required by the severely obese to achieve clinically important differences in health-related quality of life: two-year prospective cohort study.

BACKGROUND: Guidelines and experts describe 5% to 10% reductions in body weight as 'clinically important'; however, it is not clear if 5% to 10% weight reductions correspond to clinically important improvements in health-related quality of life (HRQL). Our objective was to calculate the amount of weight loss required to attain established minimal clinically important differences (MCIDs) in HRQL, measured using three validated instruments. METHODS: Data from the Alberta Population-based Prospective Evaluation of Quality of Life Outcomes and Economic Impact of Bariatric Surgery (APPLES) study, a population-based, prospective Canadian cohort including 150 wait-listed, 200 medically managed and 150 surgically treated patients were examined. Two-year changes in weight and HRQL measures (Short-Form (SF)-12 physical (PCS; MCID = 5) and mental (MCS; MCID = 5) component summary score, EQ-5D Index (MCID = 0.03) and Visual Analog Scale (VAS; MCID = 10), Impact of Weight on Quality of Life (IWQOL)-Lite total score (MCID = 12)) were calculated. Separate multivariable linear regression models were constructed within medically and surgically treated patients to determine if weight changes achieved HRQL MCIDs. Pooled analysis in all 500 patients was performed to estimate the weight reductions required to achieve the pre-defined MCID for each HRQL instrument. RESULTS: Mean age was 43.7 (SD 9.6) years, 88% were women, 92% were white, and mean initial body mass index was 47.9 (SD 8.1) kg/m2. In surgically treated patients (two-year weight loss = 16%), HRQL MCIDs were reached for all instruments except the SF-12 MCS. In medically managed patients (two-year weight loss = 3%), MCIDs were attained in the EQ-index but not the other instruments. In all patients, percent weight reductions to achieve MCIDs were: 23% (95% confidence interval (CI): 17.5, 32.5) for PCS, 25% (17.5, 40.2) for MCS, 9% (6.2, 15.0) for EQ-Index, 23% (17.3, 36.1) for EQ-VAS, and 17% (14.1, 20.4) for IWQOL-Lite total score. CONCLUSIONS: Weight reductions to achieve MCIDs for most HRQL instruments are markedly higher than the conventional threshold of 5% to 10%. Surgical, but not medical treatment, consistently led to clinically important improvements in HRQL over two years. TRIAL REGISTRATION: Clinicaltrials.gov NCT00850356.

Weight loss and outcomes in wait-listed, medically managed, and surgically treated patients enrolled in a population-based Bariatric program: prospective cohort study.

BACKGROUND: Multidisciplinary bariatric care is increasingly being delivered in Canada within publicly funded regional programs. Demand is high, wait lists are long, and clinical effectiveness is unknown. OBJECTIVE: To examine the "real-world" outcomes associated with a publicly funded, population-based regional bariatric (medical and surgical) program. RESEARCH DESIGN: Prospective observational cohort. SUBJECTS: Five hundred consecutive patients (150 wait-listed, 200 medically treated, 150 surgically treated) from the Edmonton Weight Wise program were enrolled. MEASURES: The primary outcome was weight change (kg). Between-group changes were analyzed using multivariable regression adjusted for age, sex, and baseline weight and "last-observation-carried-forward" was used for missing data. Subjects transitioning between groups (wait-list to medical or medical to surgery) were censored when crossing over. RESULTS: At baseline, mean age was 43.7 ± 9.6 years, mean body mass index was 47.9 ± 8.1 kg/m, and 88% were female. A total of 412 subjects (82%) completed 2-year follow-up and 143 (29%) subjects crossed over to the next treatment phase. Absolute and relative (% of baseline) mean weight reductions were 1.5 ± 8.5 kg (0.9 ± 6.1%) for wait-listed, 4.1 ± 11.6 kg (2.8 ± 8.1%) for medically treated, and 22.0 ± 19.7 kg (16.3 ± 13.5%) for surgically treated (P<0.001) subjects. For surgery, weight reductions were 7.0 ± 9.7 kg (5.8 ± 7.9%) with banding, 21.4 ± 16.0 kg (16.4 ± 11.6%) with sleeve gastrectomy, and 36.6 ± 19.5 kg (26.1 ± 12.2%) with gastric bypass (P<0.001). Rates of hypertension, diabetes, and dyslipidemia decreased to a significantly greater degree with surgery than medical management (P<0.001) and stayed the same or increased in wait-listed subjects. CONCLUSIONS: Population-based bariatric care, particularly bariatric surgery, was clinically effective. Weight and cardiometabolic risk was relatively stable wait-listed patients receiving "usual care."

Characteristics of an autologous leukocyte and platelet-rich fibrin patch intended for the treatment of recalcitrant wounds.

We have investigated the physical, biochemical, and cellular properties of an autologous leukocyte and platelet-rich fibrin patch. This was generated in an automated device from a sample of a patient's blood at the point of care. Using microscopy, cell counting, enzyme-linked immunosorbent assay, antibody arrays, and cell culture assays, we show that the patch is a three-layered membrane comprising a fibrin sheet, a layer of platelets, and a layer of leukocytes. Mean recovery of platelets from the donated blood was 98% (±95%CI 0.8%). Mean levels of platelet-derived growth factor AB, human transforming growth factor beta 1, and vascular endothelial growth factor extracted from the patch were determined as 127 ng (±95% CI 20), 92 ng (±95%CI 17), and 1.35 ng (±95%CI 0.37), respectively. We showed a continued release of PDGF-AB over several days, the rate of which was increased by the addition of chronic wound fluid. By comparison with traditional platelet-rich plasma, differences in immune components were found. The relevance of these findings was assessed by showing a mitogenic and migratory effect on cultured human dermal fibroblasts. Further, we showed that fibrocytes, a cell type important for acute wound healing, could be grown from the patch. The relevance of these findings in relation to the use of the patch for treating recalcitrant wounds is discussed.

Adiposity indices in the prediction of insulin resistance in prepubertal Colombian children.

OBJECTIVE: To compare BMI with abdominal skinfold thickness (ASF), waist circumference and waist-to-height ratio in the prediction of insulin resistance (IR) in prepubertal Colombian children. DESIGN: We calculated age- and sex-specific Z-scores for BMI, ASF, waist circumference, waist-to-height ratio and three other skinfold-thickness sites. Logistic regression with stepwise selection (P = 0·80 for entry and P = 0·05 for retention) was performed to identify predictors of IR and extreme IR, which were determined by age- and sex-specific Z-scores to identify the ≥ 90th and ≥ 95th percentile of homeostasis model assessment (HOMAIR), respectively. We used receiver operating characteristic curves to compare the area under the curve between models. SETTING: Bucaramanga, Colombia. SUBJECTS: Children (n 1261) aged 6-10 years in Tanner stage 1 from a population-based study. RESULTS: A total of 127 children (seventy girls and fifty-seven boys) were classified with IR, including sixty-three children (thirty-three girls and thirty boys) classified with extreme IR. Only ASF and BMI Z-scores were retained as predictors of IR by stepwise selection. Adding ASF Z-score to BMI Z-score improved the area under the curve from 0·794 (95 % CI 0·752, 0·837) to 0·811 (95 % CI 0·770, 0·851; P for contrast = 0·01). In predicting extreme IR, the addition of ASF Z-score to BMI Z-score improved the area under the curve from 0·837 (95 % CI 0·790, 0·884) to 0·864 (95 % CI 0·823, 0·905; P for contrast = 0·01). CONCLUSIONS: ASF Z-score predicted IR independent of BMI Z-score in our population of prepubertal children. ASF and BMI Z-scores together improved IR risk stratification compared with BMI Z-score alone, opening new perspectives in the prediction of cardiometabolic risk in prepubertal children.

Production of Human Neurogenin 2-Inducible Neurons in a Three-Dimensional Suspension Bioreactor.

The derivation of neuronal lineage cells from human induced pluripotent stem cells (hiPSCs) marked a milestone in brain research. Since their first advent, protocols have been continuously optimized and are now widely used in research and drug development. However, the very long duration of these conventional differentiation and maturation protocols and the increasing demand for high-quality hiPSCs and their neural derivatives raise the need for the adoption, optimization, and standardization of these protocols to large-scale production. This work presents a fast and efficient protocol for the differentiation of genetically modified, doxycycline-inducible neurogenin 2 (iNGN2)-expressing hiPSCs into neurons using a benchtop three-dimensional (3D) suspension bioreactor. In brief, single-cell suspensions of iNGN2-hiPSCs were allowed to form aggregates within 24 h, and neuronal lineage commitment was induced by the addition of doxycycline. Aggregates were dissociated after 2 days of induction and cells were either cryopreserved or replated for terminal maturation. The generated iNGN2 neurons expressed classical neuronal markers early on and formed complex neuritic networks within 1 week after replating, indicating an increasing maturity of neuronal cultures. In summary, a detailed step-by-step protocol for the fast generation of hiPSC-derived neurons in a 3D environment is provided that holds great potential as a starting point for disease modeling, phenotypic high-throughput drug screenings, and large-scale toxicity testing.

The more the better: on the formation of single-phase high entropy alloy nanoparticles as catalysts for the oxygen reduction reaction.

High entropy alloys (HEAs) are an important new material class with significant application potential in catalysis and electrocatalysis. The entropy-driven formation of HEA materials requires high temperatures and controlled cooling rates. However, catalysts in general also require highly dispersed materials, i.e., nanoparticles. Only then a favorable utilization of the expensive raw materials can be achieved. Several recently reported HEA nanoparticle synthesis strategies, therefore, avoid the high-temperature regime to prevent particle growth. In our work, we investigate a system of five noble metal single-source precursors with superior catalytic activity for the oxygen reduction reaction. Combining in situ X-ray powder diffraction with multi-edge X-ray absorption spectroscopy, we address the fundamental question of how single-phase HEA nanoparticles can form at low temperatures. It is demonstrated that the formation of HEA nanoparticles is governed by stochastic principles and the inhibition of precursor mobility during the formation process favors the formation of a single phase. The proposed formation principle is supported by simulations of the nanoparticle formation in a randomized process, rationalizing the experimentally found differences between two-element and multi-element metal precursor mixtures.

Synergistic effects of prenatal hypoxia and postnatal high-fat diet in the development of cardiovascular pathology in young rats.

We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.

Reimplantation of cultivated human bone cells from the posterior maxilla for sinus floor augmentation. Histological results from a randomized controlled clinical trial.

OBJECTIVES: The aim of the present randomized clinical study was to evaluate histologically whether the addition of cultivated, autogenous bone cells to a composite graft of deproteinized bovine bone mineral (DBBM) and autogenous bone (AB) for sinus floor augmentation (SFA) enhance bone formation compared with what achieved after SFA with DBBM + AB alone. MATERIAL AND METHODS: Twenty patients with remaining posterior maxillary alveolar crest height of less than 3 mm received SFA after randomization either with an DBBM and AB composite in a 1 : 1 ratio or with DBBM + AB supplemented with autogenous bone cells, which were cultivated from a bone biopsy harvested earlier from the tuberosity area. Four months after SFA, two cylindrical biopsies were taken from the augmented sinuses concomitantly with the implant site preparation by means of a trephine bur. An additional biopsy was taken from the tuberosity area. Bone density at the augmented sinus and the tuberosity area and the height of augmentation were estimated on non-decalcified histological sections prepared from the biopsies. A relative bone density index (RBD) was also calculated by dividing bone density at the augmented sinus with bone density at the tuberosity area. RESULTS: All patients but one could receive two implants after SFA; in one patient, only one implant could be placed. All implants were osseointegrated and could be loaded. Median bone density in the sinus was 30% and 25% in the cell seeded and no-cells added DBBM + AB groups, respectively. Bone augmentation height averaged 6.0 and 5.4 mm and RBD averaged 0.48 and 0.73 in the cell seeded and no-cells added DBBM + AB groups, respectively. None of the differences between groups was statistically significant. CONCLUSIONS: Cultivated autogenous bone cell seeded to a DBBM + AB composite did not significantly improve bone formation (density and height) after SFA, compared with what was achieved with DBBM + AB alone. Both approaches resulted into enough bone to support implant placement and osseointegration.