ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy.

PURPOSE: Preclinical studies support a protective role for omega-3 fatty acids (FAs) on diabetic retinopathy (DR), but these observations have not been confirmed in randomized trials. We present randomized evidence for the effects of omega-3 FAs on DR outcomes. DESIGN: A substudy of the A Study of Cardiovascular Events iN Diabetes (ASCEND) double-blind, randomized, placebo-controlled trial of 1 g omega-3 fatty acids (containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid) daily for the primary prevention of serious cardiovascular events, in 15 480 UK adults at least 40 years of age, with diabetes. PARTICIPANTS: Fifteen thousand four hundred eighty adults at least 40 years of age from the United Kingdom with diabetes from the ASCEND cohort. METHODS: Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review. Log-rank and stratified log-rank methods were used for intention-to-treat analyses of time until the main outcomes of interest. MAIN OUTCOME MEASURES: The primary efficacy endpoint was time to the first postrandomization recording of referable disease, a composite of referable retinopathy (R2 or R3a/s) or referable maculopathy (M1) based on the grading criteria defined by the United Kingdom National Screening Committee. Secondary and tertiary outcomes included the referable disease outcome stratified by the severity of DR at baseline, any progression in retinopathy grade, and incident diabetic maculopathy. RESULTS: Linkage data were obtained for 7360 participants (48% of those who were randomized in ASCEND). During their mean follow-up of 6.5 years, 548 participants (14.8%) had a referable disease event in the omega-3 FAs group, compared with 513 participants (13.9%) in the placebo group (rate ratio, 1.07; 95% confidence interval, 0.95-1.20; P = 0.29). There were no statistically significant between-group differences in the proportion of events for either of the secondary or tertiary outcomes. CONCLUSIONS: Representing the largest prospective test of its kind to date, these data exclude any clinically meaningful benefits of 1 g daily omega-3 FAs on DR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

ASCEND-Eye: Effects of Aspirin on Diabetic Retinopathy.

PURPOSE: Preclinical studies support a protective role for aspirin in early diabetic retinopathy (DR), but the findings from randomized trials are limited. We present randomized evidence for the efficacy and safety of aspirin on DR outcomes. DESIGN: A substudy of the A Study of Cardiovascular Events in Diabetes (ASCEND) double-masked, randomized, placebo-controlled trial of 100 mg aspirin daily for the primary prevention of serious cardiovascular events in people with diabetes. PARTICIPANTS: Fifteen thousand four hundred eighty United Kingdom adults at least 40 years of age with diabetes. METHODS: Linkage to electronic National Health Service Diabetic Eye Screening Programme records in England and Wales and confirmation of participant-reported eye events via medical record review were carried out. Log-rank methods were used for intention-to-treat analyses of time until the first primary efficacy and safety outcomes. MAIN OUTCOME MEASURES: The primary efficacy end point was the first record of referable disease after randomization, a composite of referable retinopathy or referable maculopathy based on the grading criteria defined by the United Kingdom National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed, defined as clinically significant bleeding in the eye that resulted in unresolved visual loss or required an urgent intervention such as laser photocoagulation, vitreoretinal surgery, intraocular injection, or a combination thereof. RESULTS: Linkage data were obtained for 7360 participants (48% of those randomized in ASCEND). During the mean follow-up of 6.5 years, 539 participants (14.6%) experienced a referable disease event in the aspirin group, compared with 522 participants (14.2%) in the placebo group (rate ratio, 1.03; 95% confidence interval [CI], 0.91-1.16; P = 0.64). No statistically significant between-group difference was found in the proportions of sight-threatening eye bleed events (57 participants [0.7%] and 64 participants [0.8%], respectively; rate ratio, 0.89; 95% CI, 0.62-1.27). DISCUSSION: These data exclude any clinically meaningful benefits of aspirin for DR, but give reassurance regarding the ophthalmologic safety of aspirin. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Bioactive Glass Modified with Zirconium Incorporation for Dental Implant Applications: Fabrication, Structural, Electrical, and Biological Analysis.

Implantology is crucial for restoring aesthetics and masticatory function in oral rehabilitation. Despite its advantages, certain issues, such as bacterial infection, may still arise that hinder osseointegration and result in implant rejection. This work aims to address these challenges by developing a biomaterial for dental implant coating based on 45S5 Bioglass® modified by zirconium insertion. The structural characterization of the glasses, by XRD, showed that the introduction of zirconium in the Bioglass network at a concentration higher than 2 mol% promotes phase separation, with crystal phase formation. Impedance spectroscopy was used, in the frequency range of 102-106 Hz and the temperature range of 200-400 K, to investigate the electrical properties of these Bioglasses, due to their ability to store electrical charges and therefore enhance the osseointegration capacity. The electrical study showed that the presence of crystal phases, in the glass ceramic with 8 mol% of zirconium, led to a significant increase in conductivity. In terms of biological properties, the Bioglasses exhibited an antibacterial effect against Gram-positive and Gram-negative bacteria and did not show cytotoxicity for the Saos-2 cell line at extract concentrations up to 25 mg/mL. Furthermore, the results of the bioactivity test revealed that within 24 h, a CaP-rich layer began to form on the surface of all the samples. According to our results, the incorporation of 2 mol% of ZrO2 into the Bioglass significantly improves its potential as a coating material for dental implants, enhancing both its antibacterial and osteointegration properties.

Extensive Investigation on the Effect of Niobium Insertion on the Physical and Biological Properties of 45S5 Bioactive Glass for Dental Implant.

Dental implants have emerged as one of the most consistent and predictable treatments in the oral surgery field. However, the placement of the implant is sometimes associated with bacterial infection leading to its loss. In this work, we intend to solve this problem through the development of a biomaterial for implant coatings based on 45S5 Bioglass® modified with different amounts of niobium pentoxide (Nb2O5). The structural feature of the glasses, assessed by XRD and FTIR, did not change in spite of Nb2O5 incorporation. The Raman spectra reveal the Nb2O5 incorporation related to the appearance of NbO4 and NbO6 structural units. Since the electrical characteristics of these biomaterials influence their osseointegration ability, AC and DC electrical conductivity were studied by impedance spectroscopy, in the frequency range of 102-106 Hz and temperature range of 200-400 K. The cytotoxicity of glasses was evaluated using the osteosarcoma Saos-2 cells line. The in vitro bioactivity studies and the antibacterial tests against Gram-positive and Gram-negative bacteria revealed that the samples loaded with 2 mol% Nb2O5 had the highest bioactivity and greatest antibacterial effect. Overall, the results showed that the modified 45S5 bioactive glasses can be used as an antibacterial coating material for implants, with high bioactivity, being also non-cytotoxic to mammalian cells.

Genetic associations of adult height with risk of cardioembolic and other subtypes of ischemic stroke: A mendelian randomization study in multiple ancestries.

BACKGROUND: Taller adult height is associated with lower risks of ischemic heart disease in mendelian randomization (MR) studies, but little is known about the causal relevance of height for different subtypes of ischemic stroke. The present study examined the causal relevance of height for different subtypes of ischemic stroke. METHODS AND FINDINGS: Height-associated genetic variants (up to 2,337) from previous genome-wide association studies (GWASs) were used to construct genetic instruments in different ancestral populations. Two-sample MR approaches were used to examine the associations of genetically determined height with ischemic stroke and its subtypes (cardioembolic stroke, large-artery stroke, and small-vessel stroke) in multiple ancestries (the MEGASTROKE consortium, which included genome-wide studies of stroke and stroke subtypes: 60,341 ischemic stroke cases) supported by additional cases in individuals of white British ancestry (UK Biobank [UKB]: 4,055 cases) and Chinese ancestry (China Kadoorie Biobank [CKB]: 10,297 cases). The associations of genetically determined height with established cardiovascular and other risk factors were examined in 336,750 participants from UKB and 58,277 participants from CKB. In MEGASTROKE, genetically determined height was associated with a 4% lower risk (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.94, 0.99; p = 0.007) of ischemic stroke per 1 standard deviation (SD) taller height, but this masked a much stronger positive association of height with cardioembolic stroke (13% higher risk, OR 1.13 [95% CI 1.07, 1.19], p < 0.001) and stronger inverse associations with large-artery stroke (11% lower risk, OR 0.89 [0.84, 0.95], p < 0.001) and small-vessel stroke (13% lower risk, OR 0.87 [0.83, 0.92], p < 0.001). The findings in both UKB and CKB were directionally concordant with those observed in MEGASTROKE, but did not reach statistical significance: For presumed cardioembolic stroke, the ORs were 1.08 (95% CI 0.86, 1.35; p = 0.53) in UKB and 1.20 (0.77, 1.85; p = 0.43) in CKB; for other subtypes of ischemic stroke in UKB, the OR was 0.97 (95% CI 0.90, 1.05; p = 0.49); and for other nonlacunar stroke and lacunar stroke in CKB, the ORs were 0.89 (0.80, 1.00; p = 0.06) and 0.99 (0.88, 1.12; p = 0.85), respectively. In addition, genetically determined height was also positively associated with atrial fibrillation (available only in UKB), and with lean body mass and lung function, and inversely associated with low-density lipoprotein (LDL) cholesterol in both British and Chinese ancestries. Limitations of this study include potential bias from assortative mating or pleiotropic effects of genetic variants and incomplete generalizability of genetic instruments to different populations. CONCLUSIONS: The findings provide support for a causal association of taller adult height with higher risk of cardioembolic stroke and lower risk of other ischemic stroke subtypes in diverse ancestries. Further research is needed to understand the shared biological and physical pathways underlying the associations between height and stroke risks, which could identify potential targets for treatments to prevent stroke.

Kefir milk consumption decreases sperm alterations due to the high-fat diet in adult male rats.

Over the past decades, an increase of male infertility through the decrease of sperm count has been noted. It has been suggested that environmental factors and lifestyle could a negative impact over sperm quality. Among these factors, the consumption of foods high in fat, which leads to overweight and obesity, can negatively influence fertility. The present study was designed to highlight the protective effect of Kefir, natural probiotic, against the decline in sperm quality related to fat high diet. Thirty adult rats were divided into four groups: Control (1 ml/100 g of body weight (bw) of semi-shimmed cow milk), KM (1 ml/100 g bw of Kefir milk), HFD (1 ml/100 g bw of semi-shimmed cow milk + high-fat diet) and KM/HFD (1 ml/100 g bw Kefir milk + high-fat diet). After 60 days of treatment, sperm quality, biochemical assays of lipids profil, blood cell count and histological examination in testis were assessed. The results described an improved of sperm density (64.28 106  ml vs 54.14 106  ml), viability (70.50% vs 55.33%), mobility (65.40% vs 63.60%) and morphological abnormalities (52% vs 25%) in the KM/HFD group compared to HFD group. In the same group, the lipid profil (Triglycerides (128.39 mg/dl vs 102.85 mg/dl), C-LDL (13.65 mg/dl vs 15.32 mg/dl) and C-HDL (23.21 mg/dl vs 19.15 mg/dl)) was corrected compared to HFD group. The histological observation of testis revealed a normal spermatogenesis compared to seminiferous tubules of HFD group, which showed a serious disruption and damage of testicular epithelium exerted by the high-fat diet. These findings corroborated the previous beneficial effect of Kefir and brought new insights into its beneficial effect against deteriorated spermatogenesis in obese adult rats.

In vivo exposure to a new 2-cyano-2-p-nitrophenyl-N-benzylthioamide decreases doxorubicin-triggered structural damages in the mature testis.

The use of doxorubicin (DOX) in clinical practice continues to be challenged by its severe toxicity. DOX cytotoxic activity is not only directed against malignant tumours, given that the treatment will damage healthy tissues as well leading to irreversible injuries. This study aimed to address the in vivo effects of DOX and its co-administration with a new analog of thioamide; thiocyanoacetamide (TA) on the germinal epithelium. Thus, male rats received either intravenous injection (iv) of 0.03 mg/kg of body weight/week, 0.9% NaCl and were regarded as the control group (CTR), treated with DOX (3.7 mg/kg/week iv), TA [10 mg/kg/day intragastrically (ig)] or a co-supplementation of DOX and TA. After 50 days, the left testes were dissected and used for toluidine blue, periodic acid-Schiff (PAS) staining (to evaluate the change in polysaccharides/glycoproteins content), and transmission electron microscopy (TEM) (to assess the morphological damages). To estimate the impact of the test compounds on mitochondrial biogenesis, the expression of NAD-dependent deacetylase sirtuin-3 (SIRT-3) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were evaluated by immunofluorescence. Apoptotic cells were observed using Hoechst 33324 fluorescent staining. Data showed testicular injuries in the DOX-treated group, manifested by a significant decrease in total germ cell (GC) number, alteration of Sertoli cell (SC) nucleolus, anchoring junction, along with modifications of the basement membrane (BM) regularity and increase in apoptotic cell count. Mitochondrial aspect and SIRT-3 and PGC-1α expression in the testis were unaffected by the DOX. Co-therapy increased GC number, decreased apoptotic cell count, and restored the BM and anchoring junction regular aspects. This study provides novel insights into understanding DOX-mediated impairment in rats' testis and might offer some basis for the emerging new alternative therapeutic schemes in male patients undergoing chemotherapy.

The Effect of Iron Oxide Insertion on the In Vitro Bioactivity, and Antibacterial Properties of the 45S5 Bioactive Glass.

The aging population and increasing incidence of trauma among younger age groups have heightened the increasing demand for reliable implant materials. Effective implant materials must demonstrate rapid osseointegration and strong antibacterial properties to ensure optimal patient outcomes and decrease the chance of implant rejection. This study aims to enhance the bone-implant interface by utilizing 45S5 bioglass modified with various concentrations of Fe3O4 as a coating material. The effect of the insertion of Fe3O4 into the bioglass structure was studied using Raman spectroscopy which shows that with the increase in Fe3O4 concentration, new vibration bands associated with Fe-related structural units appeared within the sample. The bioactivity of the prepared glasses was evaluated using immersion tests in simulated body fluid, revealing the formation of a calcium phosphate-rich layer within 24 h on the samples, indicating their potential for enhanced tissue integration. However, the sample modified with 8 mol% of Fe3O4 showed low reactivity, developing a calcium phosphate-rich layer within 96 h. All the bioglasses showed antibacterial activity against the Gram-positive and Gram-negative bacteria. The modified bioglass did not present significant antibacterial properties compared to the bioglass base.

Influence of the Addition of Zinc, Strontium, or Magnesium Oxides to the Bioglass 45S5 Network on Electrical Behavior.

45S5 Bioglass has been widely used in regenerative medicine due to its ability to dissolve when inserted into the body. Its typically amorphous structure allows for an ideal dissolution rate for the formation of the hydroxyapatite layer, which is important for the development of new bone. This bioactive capacity can also be controlled by adding other oxides (e.g., SrO, ZnO, and MgO) to the 45S5 Bioglass network or by storing electrical charge. Ions such as zinc, magnesium, and strontium allow for specific biological responses to be added, such as antibacterial action and the ability to increase the rate of osteoblast proliferation. The charge storage capacity allows for a higher rate of bioactivity to be achieved, allowing for faster attachment to the host bone, decreasing the patient's recovery time. Therefore, it is necessary to understand the variation in the structure of the bioglass with regard to the amount of non-bridging oxygens (NBOs), which is important for the bioactivity rate not to be compromised, and also its influence on the electrical behavior relevant to its potential as electrical charge storage. Thus, several bioactive glass compositions were synthesized based on the 45S5 Bioglass formulation with the addition of various concentrations (0.25, 0.5, 1, and 2, mol%) of zinc, strontium, or magnesium oxides. The influence of the insertion of these oxides on the network was evaluated by studying the amount of NBOs using Raman spectroscopy and their implication on the electrical behavior. Electrical characterization was performed in ac (alternating current) and dc (direct current) regimes.

Exploring the Impact of Copper Oxide Substitution on Structure, Morphology, Bioactivity, and Electrical Properties of 45S5 Bioglass®.

In recent decades, the requirements for implantable medical devices have increased, but the risks of implant rejection still exist. These issues are primarily associated with poor osseointegration, leading to biofilm formation on the implant surface. This study focuses on addressing these issues by developing a biomaterial for implant coatings. 45S5 bioglass® has been widely used in tissue engineering due to its ability to form a hydroxyapatite layer, ensuring a strong bond between the hard tissue and the bioglass. In this context, 45S5 bioglasses®, modified by the incorporation of different amounts of copper oxide, from 0 to 8 mol%, were synthesized by the melt-quenching technique. The incorporation of Cu ions did not show a significant change in the glass structure. Since the bioglass exhibited the capacity for being polarized, thereby promoting the osseointegration effectiveness, the electrical properties of the prepared samples were studied using the impedance spectroscopy method, in the frequency range of 102-106 Hz and temperature range of 200-400 K. The effects of CuO on charge transport mobility were investigated. Additionally, the bioactivity of the modified bioglasses was evaluated through immersion tests in simulated body fluid. The results revealed the initiation of a Ca-P-rich layer formation on the surface within 24 h, indicating the potential of the bioglasses to enhance the bone regeneration process.

Dielectric Characterization of Solutions of Galactomannan Extracted from Adenanthera pavonina L.: Effects of Purification and Ethanol Concentration.

Galactomannans are polysaccharides obtained from legume seed extraction. They present a chemical structure consisting of D-mannose chains linked by glycosidic bonds and galactose branches. The main focus lies in their use as thickeners in the food industry, aimed at improving the dielectric properties of food during heating processes within the radiofrequency and microwave ranges. In this work, the prepared galactomannan samples were electrically analyzed through impedance spectroscopy, which is a powerful physical technique. From the experimental measurements, the dielectric permittivity and loss tangent of the galactomannan solutions were analyzed and the electrical modulus formalism was used to study the dielectric relaxations. Crude galactomannans exhibited higher values of permittivity, conductivity, and losses compared to purified galactomannans. Increasing ethanol concentration in galactomannan purification causes an increase in the permittivity and conductivity of galactomannan solutions. In a 1% solution, at 1 kHz, the permittivity increased from 378.56 to 538.09, while in the 2% solution, this increase was from 656.22 to 1103.24. Regarding the conductivity, at the same frequency, the increase was from 1.6 × 10-3 to 3.3 × 10-3 Ω-1m-1 and from 2.9 × 10-3 to 5.5 × 10-3 Ω-1m-1, respectively. The rise of the ethanol concentration in galactomannan purification led to a decrease in the relaxation time, from 448.56 to 159.15 µs and from 224.81 to 89.50 µs in the solution with 1 and 2%, respectively. The results suggest that galactomannan from Adenanthera pavonina L. has potential for use in the food industry.

Evidence for overdispersion in the distribution of malaria parasites and leukocytes in thick blood smears.

BACKGROUND: Microscopic examination of stained thick blood smears (TBS) is the gold standard for routine malaria diagnosis. Parasites and leukocytes are counted in a predetermined number of high power fields (HPFs). Data on parasite and leukocyte counts per HPF are of broad scientific value. However, in published studies, most of the information on parasite density (PD) is presented as summary statistics (e.g. PD per microlitre, prevalence, absolute/assumed white blood cell counts), but original data sets are not readily available. Besides, the number of parasites and the number of leukocytes per HPF are assumed to be Poisson-distributed. However, count data rarely fit the restrictive assumptions of the Poisson distribution. The violation of these assumptions commonly results in overdispersion. The objectives of this paper are to investigate and handle overdispersion in field-collected data. METHODS: The data comprise the records of three TBSs of 12-month-old children from a field study of Plasmodium falciparum malaria in Tori Bossito, Benin. All HPFs were examined systemically by visually scanning the film horizontally from edge to edge. The numbers of parasites and leukocytes per HPF were recorded and formed the first dataset on parasite and leukocyte counts per HPF. The full dataset is published in this study. Two sources of overdispersion in data are investigated: latent heterogeneity and spatial dependence. Unobserved heterogeneity in data is accounted for by considering more flexible models that allow for overdispersion. Of particular interest were the negative binomial model (NB) and mixture models. The dependent structure in data was modelled with hidden Markov models (HMMs). RESULTS: The Poisson assumptions are inconsistent with parasite and leukocyte distributions per HPF. Among simple parametric models, the NB model is the closest to the unknown distribution that generates the data. On the basis of model selection criteria AIC and BIC, HMMs provided a better fit to data than mixtures. Ordinary pseudo-residuals confirmed the validity of HMMs. CONCLUSION: Failure to take overdispersion into account in parasite and leukocyte counts may entail important misleading inferences when these data are related to other explanatory variables (malariometric or environmental). Its detection is therefore essential. In addition, an alternative PD estimation method that accounts for heterogeneity and spatial dependence should be seriously considered in epidemiological studies with field-collected parasite and leukocyte data.

Barium Titanate/Gadolinium Ferrite: A New Material Composite to Store Energy.

This work investigates the dielectric properties of barium titanate/gadolinium ferrite ceramic composites, with different concentrations of each material. Our objective was to increase the storage ability of this material, finding a compromise between high permittivity and low dielectric losses. A two-step sintering procedure was used in the preparation of the composites to attain the desired results. Their morphological, structural and electrical properties were tested using scanning electron microscopy, X-Ray powder diffraction and impedance spectroscopy, respectively. Dielectric characterizations were performed on the frequency band of 100 Hz-1 MHz and for different temperatures (180-380 K). The best compromise between barium titanate and gadolinium ferrite in the composition was calculated in order to obtain a potential material for electrical energy storage. The sample with 25% gadolinium ferrite presented the best results. The dielectric constant reached values of the order of 2000, at 1 kHz and 340 K. It was also important not to have very high losses, and this was confirmed by the calculated loss tangent.

ASCEND-Eye: Rationale, design and baseline characteristics for a sub-study of the ASCEND randomised trial, exploring the effects of aspirin and omega-3 fatty acids on diabetic retinopathy and age-related macular degeneration.

Background: Aspirin and omega-3 fatty acids (FAs) have potential disease-modifying roles in diabetic retinopathy (DR) and age-related macular degeneration (AMD), but randomized evidence of these effects is limited. We present the rationale and baseline characteristics of ASCEND-Eye, a sub-study of the double-blind, 2x2 factorial design, randomized placebo-controlled ASCEND (A Study of Cardiovascular Events iN Diabetes) trial of 100 mg aspirin daily and, separately, 1g omega-3 FAs daily for the primary prevention of serious cardiovascular events, in 15,480 British adults, aged 40 years or older with diabetes. Methods: Eye events will be derived from three sources: 1) participant follow-up questionnaires from ASCEND, 2) electronic NHS Diabetic Eye Screening Programme (DESP) data and 3) responses to the National Eye Institute's Visual Function Questionnaire-25 (NEI-VFQ-25) sent to a subset of participants after the main trial ended. Analytic cohorts and outcomes relevant to these data sources are described. The primary outcome is referable diabetic eye disease, a secondary outcome is incident AMD events. Results: Participant-reported events were ascertained for the full cohort of randomized individuals who were followed up over 7.4 years in ASCEND (n = 15,480). Linked DESP data were available for 48% of those (n = 7360), and 57% completed the NEI-VFQ-25 (n = 8839). The baseline characteristics of these three cohorts are presented. Discussion: Establishing the risks and benefits of drugs commonly taken by people with diabetes, the elderly, or both, and finding new treatments for DR and AMD is important. ASCEND-Eye provides the opportunity to evaluate the effect of aspirin and, separately, omega-3 FAs for both conditions. Study registration: Eudract No. 2004-000991-15; Multicentre Research Ethics Committee Ref No. 03/8/087; ClinicalTrials.gov No. NCT00135226; ISRCTN No. ISRCTN60635500.

Antibacterial Biomaterial Based on Bioglass Modified with Copper for Implants Coating.

Biofilm-related implant infections pose a substantial threat to patients, leading to inflammation in the surrounding tissue, and often resulting in implant loss and the necessity for additional surgeries. Overcoming this implantology challenge is crucial to ensure the success and durability of implants. This study shows the development of antibacterial materials for implant coatings by incorporating copper into 45S5 Bioglass®. By combining the regenerative properties of Bioglass® with the antimicrobial effects of copper, this material has the potential to prevent infections, enhance osseointegration and improve the long-term success of implants. Bioglasses modified with various concentrations of CuO (from 0 to 8 mol%) were prepared with the melt-quenching technique. Structural analysis using Raman and FTIR spectroscopies did not reveal significant alterations in the bioglasses structure with the addition of Cu. The antibacterial activity of the samples was assessed against Gram-positive and Gram-negative bacteria, and the results demonstrated significant inhibition of bacterial growth for the bioglass with 0.5 mol% of CuO. Cell viability studies indicated that the samples modified with up to 4 mol% of CuO maintained good cytocompatibility with the Saos-2 cell line at extract concentrations up to 25 mg/mL. Furthermore, the bioactivity assessment demonstrated the formation of a calcium phosphate (CaP)-rich layer on the surfaces of all bioglasses within 24 h. Our findings show that the inclusion of copper in the bioglass offers a significant enhancement in its potential as a coating material for implants, resulting in notable advancements in both antibacterial efficacy and osteointegration properties.

Extraction of Pectin from Orange Peel and Study of Its Protective Effect Against Loperamide-Induced Impaired Gastrointestinal Motor Functions and Oxidative Stress in Rats.

Pectin is a polysaccharide attached to carbohydrates. These are substances exclusively of plant origin. The aim of the present study is to evaluate the laxative effects of orange peel pectin extract (OPPE) against constipation induced by loperamide (LOP) in rats. Rats were equally divided into six groups and treated daily 1 week as follows: Control, LOP (3 mg/kg, body weight [b.w.], Per Os [p.o.]), LOP+yohimbine (2 mg/kg, b.w., i.p.), and LOP+OPPE (6.25, 12.5, and 25 mg/kg, b.w., p.o.). At the end of the experiment, the effects of OPPE were assessed by fecal parameters (numbers, weight, and water content), gastrointestinal transit, gastric emptying, serum metabolic parameter changes, intestinal and colon mucosa oxidative stress, and the histological examination. The defecation test showed that administration of LOP (3 mg/kg, b.w., p.o.) leads to the production of remarkable constipation. Indeed, the number and water content of stools decreased (25.50 [n/24 h] and 29.86%) significantly (P < .05). Acute pretreatment with OPPE significantly and dose dependently accelerated the stool moistening and allowed an increase of stool weight (2.85, 3.61, 3.93 [g/24 h/rat]) as well as the frequency of defecation (47.36, 54.54, and 56.26 [n/24 h]). OPPE also significantly (P < .05) and dose dependently increased the intestinal motility (70.78%, 73.33%, and 75.01%) and gastric emptying. LOP-induced reduction (P < .05) of intestinal secretion was accompanied by a colonic and small bowel oxidative stress status and histological changes, which was attenuated by OPPE treatment. The findings of this study indicate that OPPE possesses an important role in the gastrointestinal motility regulation, and thus lend pharmacological credence to the suggested use of the natural pectin for the treatment, management, and/or control of constipation.

Oxidized phospholipids on apolipoprotein B-100 versus plasminogen and risk of coronary heart disease in the PROCARDIS study.

BACKGROUND AND AIMS: Oxidized phospholipids carried on the apolipoprotein B-100 (OxPL-apoB) component of Lp(a) are predictive of coronary heart disease (CHD), but the role of oxidized phospholipids carried on plasminogen (OxPL-PLG) is unknown. We examined the independent effects of OxPL-apoB and OxPL-PLG for risk of CHD before and after adjustment for Lp(a). METHODS: Plasma levels of OxPL-apoB, OxPL-PLG, plasminogen and Lp(a) were measured in the PROCARDIS study of early-onset CHD (906 cases/858 controls). Multivariable logistic regression was used to estimate the odds ratios (OR) for each biomarker with CHD after adjustment for established risk factors. RESULTS: Mean levels of OxPL-apoB were higher in cases than controls, but levels of OxPL-PLG and plasminogen were similar. For OxPL-apoB, individuals in the top vs bottom fifth had 2-fold higher age and sex-adjusted OR of CHD (OR = 2.61 [95%CI: 1.91, 3.55]), which were partially attenuated after adjustment for established risk factors. The findings for OxPL-apoB and CHD in PROCARDIS were comparable with those of a meta-analysis of all such studies. However, the associations of OxPL-apoB with CHD were fully attenuated by additional adjustment for Lp(a) (OR = 0.93 [0.54,1.60]). Neither OxPL-PLG nor plasminogen were associated with CHD. Overall, there were no differences in the predictive value for CHD of high vs normal levels (<20th or >80th percentile) of OxPL-apoB, OxPL-PLG, plasminogen or Lp(a) after stratifying for each other. CONCLUSIONS: These results highlight the context-dependency of OxPL in plasma and suggest that their associated risk of CHD is chiefly mediated by their carriage on Lp(a).

Weight loss in a cardiovascular trial population identifies people at future risk of dementia.

Introduction: Populations at increased risk of dementia need to be identified for well-powered trials of preventive interventions. Weight loss, which often occurs in pre-clinical dementia, could identify a population at sufficiently high dementia risk. Methods: In 12,975 survivors in the Heart Protection Study statin trial of people with, or at high risk of, cardiovascular disease, the association of weight change over 5 years during the trial with post-trial dementia recorded in electronic hospital admission and death records (n = 784) was assessed, after adjustment for age, sex, treatment allocation, and deprivation measures. Results: Among the 60% without substantial weight gain (≤2 kg weight gain), each 1 kg weight loss was associated with a risk ratio for dementia of 1.04 (95% confidence interval, 1.02-1.07). Weight loss ≥4 kg and cognitive function below the mean identified participants aged ≥67 years with a 13% 10-year dementia risk. Discussion: The combination of weight loss and high vascular risk identified individuals at high risk of dementia who could be recruited to dementia prevention trials.

A Biomarker-based Biological Age in UK Biobank: Composition and Prediction of Mortality and Hospital Admissions.

BACKGROUND: Chronological age is the strongest risk factor for most chronic diseases. Developing a biomarker-based age and understanding its most important contributing biomarkers may shed light on the effects of age on later-life health and inform opportunities for disease prevention. METHODS: A subpopulation of 141 254 individuals healthy at baseline were studied, from among 480 019 UK Biobank participants aged 40-70 recruited in 2006-2010, and followed up for 6-12 years via linked death and secondary care records. Principal components of 72 biomarkers measured at baseline were characterized and used to construct sex-specific composite biomarker ages using the Klemera Doubal method, which derived a weighted sum of biomarker principal components based on their linear associations with chronological age. Biomarker importance in the biomarker ages was assessed by the proportion of the variation in the biomarker ages that each explained. The proportions of the overall biomarker and chronological age effects on mortality and age-related hospital admissions explained by the biomarker ages were compared using likelihoods in Cox proportional hazard models. RESULTS: Reduced lung function, kidney function, reaction time, insulin-like growth factor 1, hand grip strength, and higher blood pressure were key contributors to the derived biomarker age in both men and women. The biomarker ages accounted for >65% and >84% of the apparent effect of age on mortality and hospital admissions for the healthy and whole populations, respectively, and significantly improved prediction of mortality (p < .001) and hospital admissions (p < 1 × 10-10) over chronological age alone. CONCLUSIONS: This study suggests that a broader, multisystem approach to research and prevention of diseases of aging warrants consideration.

Effects of Within-Person Variability in Spot Urinary Sodium Measurements on Associations With Blood Pressure and Cardiovascular Disease.

Randomized trials of salt restriction have consistently demonstrated that decreasing salt consumption lowers blood pressure, but results of observational studies of salt intake and cardiovascular disease have been conflicting. After excluding individuals with prevalent cardiovascular or kidney disease in the prospective UK Biobank study, we examined the within-person variability in spot urinary sodium excretion and its impact on associations with systolic blood pressure and risk of incident cardiovascular disease. Spearman correlation coefficients were used to assess within-person variability in spot urinary sodium, and associations between sodium and blood pressure were assessed using linear regression in participants with measurements at baseline (N=355 134) and after 9 years (N=33 915). Cox regression was used to assess associations with the risk of cardiovascular disease over the same follow-up period (N=5566 events). The within-person variability in urinary sodium was extreme, with a self-correlation coefficient of 0.35 over 4 years. Each 100 mmol/L higher usual urinary sodium was associated with 3.09 mm Hg higher systolic blood pressure (95% CI, 2.7­3.48) at baseline, but had no association at 9 years (0.97 [−0.44 to 2.37]). Likewise, there was no association between urinary sodium and risk of cardiovascular disease over the same follow-up period (hazard ratio, 1.05, [0.87­1.26]). While spot urinary sodium measurements were associated with immediate effects on blood pressure at baseline, the extreme within-person variability in urinary sodium precluded detection of associations with future blood pressure at resurvey or risk of cardiovascular disease. The limitations of observational studies, irrespective of study size, should be recognized when assessing public policy on salt restriction.