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The antibiotic administration in dairy livestock is a current widespread practice. The purpose of the study was to evaluate whether milk from antibiotic‐treated animals, following the application of the withdrawal time and fully complying with European requirements in relation to residue content, affected the development of lactic acid bacteria. Forty‐five raw milk samples were collected after the withdrawal period and analysed to verify their compliance with the European maximum limits using four commercial screening tests. Lactobacillus delbrueckii subsp. bulgaricus growth and acidifying activity were delayed from 5 to 8 h in milk from cow treated with β‐lactams and sulfonamides present in low concentration (cephalosporins < 15 μg/kg; penicillins < 8 μg/kg; sulfonamides < 10 μg/kg) and their effect persisted over time. No influences were detected in Streptococcus thermophilus and Lb. helveticus development. The use of antibiotics can hamper the starter performances, opening questions about the safety of dairy products and human health. [ABSTRACT FROM AUTHOR]

Frailty and delirium are two common geriatric syndromes sharing several clinical characteristics, risk factors, and negative outcomes. Understanding their interdependency is crucial to identify shared mechanisms and implement initiatives to reduce the associated burden. This literature review summarizes scientific evidence on the complex interplay between frailty and delirium; clinical, epidemiological, and pathophysiological commonalities; and current knowledge gaps. We conducted a PubMed systematic search in June 2023, which yielded 118 eligible articles out of 991. The synthesis of the results—carried out by content experts—highlights overlapping risk factors, clinical phenotypes, and outcomes and explores the influence of one syndrome on the onset of the other. Common pathophysiological mechanisms identified include inflammation, neurodegeneration, metabolic insufficiency, and vascular burden. The review suggests that frailty is a risk factor for delirium, with some support for delirium associated with accelerated frailty. The proposed unifying framework supports the integration and measurement of both constructs in research and clinical practice, identifying the geroscience approach as a potential avenue to develop strategies for both conditions. In conclusion, we suggest that frailty and delirium might be alternative—sometimes coexisting—manifestations of accelerated biological aging. Clinically, the concepts addressed in this review can help approach older adults with either frailty or delirium from a different perspective. From a research standpoint, longitudinal studies are needed to explore the hypothesis that specific pathways within the biology of aging may underlie the clinical manifestations of frailty and delirium. Such research will pave the way for future understanding of other geriatric syndromes as well. [ABSTRACT FROM AUTHOR]

Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro‐ and anti‐inflammatory cytokine production and its intranasal administration reduces allergic airway inflammation in mice. Despite its benefits, there are concerns about the use of live probiotic bacteria due to potential systemic infections and gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83‐EVs) might offer a safer alternative to live bacteria. This study characterizes EcO83‐EVs and investigates their interaction with host cells, highlighting their potential as postbiotic therapeutics. EcO83‐EVs were isolated, purified, and characterised following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Ex vivo studies conducted in human nasal epithelial cells showed that EcO83‐EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83‐EVs interact with nasal‐associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. Mechanistically, EcO83‐EVs activate the NF‐κΒ signalling pathway, resulting in the nitric oxide production. EcO83‐EVs demonstrate significant potential as a postbiotic alternative to live bacteria, offering a safer option for therapeutic applications. Further research is required to explore their clinical use, particularly in mucosal vaccination and targeted immunotherapy strategies. [ABSTRACT FROM AUTHOR]

This article examines the use of automated insulin delivery (AID) devices in children and adolescents with type 1 diabetes (T1D). The study analyzes data from 613 participants and finds that time spent in the target glucose range (TITR) varied among different subgroups. The study suggests that TITR could be a useful metric for assessing glycaemic outcomes in AID users. The results show that higher TITR levels are associated with better glycaemic control, and the study emphasizes the importance of using the automatic mode and selecting the appropriate insulin-to-carbohydrate ratio (ICR) for each meal. However, the study acknowledges limitations in the inclusion of different AID algorithms and the lack of raw glucose data. Overall, the findings suggest that TITR can provide valuable information in evaluating glucose profiles in individuals using AID systems. [Extracted from the article]

Herein we report the development of an oxidative amination process for the streamlined synthesis of pyridones from cyclopentenones. Cyclopentenone building blocks can undergo in situ silyl enol ether formation, followed by the introduction of a nitrogen atom into the carbon skeleton with successive aromatisation to yield pyridones. The reaction sequence is operationally simple, rapid, and carried out in one pot. The reaction proceeds under mild conditions, exhibits broad functional group tolerance, complete regioselectivity, and is well scalable. The developed method provides facile access to the synthesis of 15N‐labelled targets, industrially relevant pyridone products and their derivatives in a fast and efficient way. [ABSTRACT FROM AUTHOR]

Summary: Background: The diagnosis of monogenic obesity is burdened by frequent variants of uncertain significance (VUS). We describe our real‐life approach of variant reassessment over time and we assess whether inconclusive variants are decreasing in monogenic obesity. Methods: We tested for monogenic obesity (genes: LEPR, POMC, ADCY3, PCSK1, CARTPT, SIM1, MRAP2, LEP, NTRK2, BDNF, KSR2, MAGEL2, SH2B1, MC4R, MC3R) in 101 children/adolescents (11.7 [7.3–13.7] years, 3.6 [3.3–4.0] z‐BMI) in Verona and 183 (11.3 [8.4–12.2] years, 3.2 [2.7–3.9] z‐BMI) in Naples from January 2020 to February 2023. In March–July 2024 we reassessed the baseline variants by updated software interpretation and literature renavigation. Results: We initially found 20 VUS, 4 Likely Pathogenic (LP), 5 Likely Benign (LB) and 1 benign variant in 33 individuals. At follow‐up, 6 VUS were reclassified as benign/LB, one LP as pathogenic and 3 LB as benign. Overall, 10/30 variants (6/18 in Verona, 3/11 in Naples and a variant found in both centres) were reclassified, leading to a less uncertain report for 13 of 33 variant‐carrying patients. Monogenic obesity was diagnosed in 3 probands in Verona and 4 in Naples, carrying variants at MC4R or NTRK2. Conclusion: Our variant reassessment was effective to improve classification certainty for the 39% of patients and suggested that the molecular diagnosis of monogenic obesity is becoming more accurate over time. [ABSTRACT FROM AUTHOR]

Aim: The aim was to examine the prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), a risk factor for atherosclerotic cardiovascular disease, and its association with glycaemic control metrics in children and adolescents with type 1 diabetes (T1D). Materials and Methods: We enrolled 244 children and adolescents with T1D (115 girls, mean age: 16.2 ± 3.2 years). The diagnosis of MASLD was defined by the presence of hepatic steatosis on ultrasonography in combination with at least one of five common cardiometabolic risk factors. Metrics of short‐term and long‐term glycaemic control, blood pressure, lipids, anthropometric characteristics and three genetic variants strongly related to MASLD susceptibility (rs738409 [patatin‐like phospholipase domain‐containing 3], rs58542926 [transmembrane 6 superfamily member 2] and rs1260326 [glucokinase regulator]) were assessed. Characteristics of these subjects with and without MASLD were compared using the unpaired Student t test, Mann–Whitney test or χ2 test as appropriate. Logistic regression analyses were performed to determine the main independent predictors of MASLD. Results: The prevalence of MASLD was 27.5% in children and adolescents with T1D. Blood pressure, total cholesterol, low‐density lipoprotein (LDL) cholesterol, non‐high‐density lipoprotein cholesterol, HbA1c and time above range (TAR) were significantly higher in subjects with MASLD than in those without MASLD. Mean HbA1c values from diabetes onset (adjusted odds ratio [OR]: 1.703, 95% confidence interval [CI]: 1.040–2.787, p = 0.034), TAR (adjusted OR: 1.028, 95% CI: 1.009–1.047, p = 0.006) and plasma LDL cholesterol (adjusted OR: 1.045, 95% CI: 1.013–1.078, p = 0.004) were independently associated with the presence of MASLD. Conclusions: MASLD is a common condition in children and adolescents with T1D. The mean HbA1c values from diabetes onset, TAR and LDL cholesterol levels were the independent predictors of MASLD. [ABSTRACT FROM AUTHOR]

Inorganic black materials possessing hydrophilicity are scarce but can be of great importance in areas such as solar water evaporation and solar steam generation. Herein, for the first time, transition‐metal selenite hydrates (specifically, Earth‐abundant metals Ni and Co) not only possess high solar absorbance (>96 %) in the solar spectral range (UV–vis–NIR) but also excellent hydrophilicity, which plays a key role in water transport in the solar steam generation. The hydrophilic behavior in selenite hydrates originates from trapped "water of hydration" inside its crystal lattice, which can easily form hydrogen bonds with other water molecules, facilitating water transport. Owing to the abovementioned properties, the studied selenite hydrates are tested for solar water evaporation, showing excellent water evaporation rates of 1.83 and 2.34 kg m−2 h−1 for nickel selenite hydrate and cobalt selenite hydrate, exceeding the theoretical limit of 1.47 kg m−2 h−1. [ABSTRACT FROM AUTHOR]

Extracellular matrix (ECM) is a major component of the tumor environment, promoting the establishment of a pro-invasive behavior. Such environment is supported by both tumor- and stromal-derived metabolites, particularly lactate. In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) are major contributors of secreted lactate, able to impact on metabolic and transcriptional regulation in cancer cells. Here, we describe a mechanism by which CAF-secreted lactate promotes in PCa cells the expression of genes coding for the collagen family. Lactate-exploiting PCa cells rely on increased α-ketoglutarate (α-KG) which activates the α-KG-dependent collagen prolyl-4-hydroxylase (P4HA1) to support collagen hydroxylation. De novo synthetized collagen plays a signaling role by activating discoidin domain receptor 1 (DDR1), supporting stem-like and invasive features of PCa cells. Inhibition of lactate-induced collagen hydroxylation and DDR1 activation reduces the metastatic colonization of PCa cells. Overall, these results provide a new understanding of the link between collagen remodeling/signaling and the nutrient environment exploited by PCa. Synopsis: Lactate, which is highly enriched in the prostate cancer environment, supports collagen remodeling and sensing in prostate cancer cells. Lactate-dependent metabolic rewiring sustains collagen hydroxylation via P4HA1 activation. De novo synthetized collagen activates discoidin domain receptor 1 (DDR1). P4HA1-DDR1-STAT3 axis is crucial for stemness and invasiveness of prostate cancer cells. Lactate, which is highly enriched in the prostate cancer environment, supports collagen remodeling and sensing in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has limited therapeutic options, is highly metastatic and characterized by early recurrence. Lipid metabolism is generally deregulated in TNBC and might reveal vulnerabilities to be targeted or used as biomarkers with clinical value. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation which is facilitated by the presence of polyunsaturated fatty acids (PUFA). Here we identify fatty acid desaturases 1 and 2 (FADS1/2), which are responsible for PUFA biosynthesis, to be highly expressed in a subset of TNBC with a poorer prognosis. Lipidomic analysis, coupled with functional metabolic assays, showed that FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents and that targeting FADS1/2 by both genetic interference and pharmacological approach renders those tumors ferroptosis-resistant while unbalancing PUFA/MUFA ratio by the supplementation of exogenous PUFA sensitizes resistant tumors to ferroptosis induction. Last, inhibiting lipid droplet (LD) formation and turnover suppresses the buffering capacity of LD and potentiates iron-dependent cell death. These findings have been validated in vitro and in vivo in mouse- and human-derived clinically relevant models and in a retrospective cohort of TNBC patients. Synopsis: The availability of intracellular polyunsaturated fatty acids (PUFA) depends on fatty acid desaturases 1 and 2 (FADS1/2), expressed at higher levels in aggressive triple-negative breast cancers (TNBC) highly susceptible to ferroptosis. FADS1/2 are highly expressed in a subset of TNBC with a poorer prognosis. FADS1/2 high-expressing TNBC are susceptible to ferroptosis-inducing agents. FADS1/2 ablation decreases PUFA/MUFA ratio and renders TNBC insensitive to pro-ferroptosis agents. Lipid droplets (LD) maintain PUFA/MUFA intracellular balance and when targeted enhance cell death triggered by ferroptosis induction. The availability of intracellular polyunsaturated fatty acids depends on FADS1/2 desaturases, expressed at higher levels in aggressive triple-negative breast cancers highly susceptible to ferroptosis. [ABSTRACT FROM AUTHOR]

Sonochemical synthesis can be a facile, fast, efficient, versatile and economical way to prepare a large variety of conventional or novel nanostructured materials (metallic, magnetic, semiconducting, polymeric, etc.). In this work, zinc oxide nanocrystals were synthesized by irradiating and heating at 90 °C in a commercial ultrasonic bath a water solution of zinc nitrate hexahydrate and ammonia solution or hexamethylenetetramine as base catalysts. The evolution of the powder morphology and its crystalline structure were investigated at different times of ultrasonic irradiation (0–9 hours) and compared with those of samples obtained by only heating the solutions in a muffle furnace in order to enlighten the growth mechanism. It resulted that: i) the crystal morphology depends on the selected base, ii) for samples obtained by using ultrasounds, the homogeneity of the powders depends on the irradiation time, iii) by comparing all samples obtained at 7 hours of heating, the aspect ratio of the crystals is higher for those that also underwent to ultrasounds. [ABSTRACT FROM AUTHOR]

The integrity of the tympanic membrane is an important factor when deciding treatment and therapeutic recommendations for dogs with ear disease; however, otoscopic examination may be difficult to perform due to features of external ear canal disease or patient compliance. CT is useful for the evaluation of middle ear disease, including cases in which middle ear disease is detected incidentally. The tympanic membrane is detectable using CT, but anecdotally, apparent focal defects or discontinuities of the tympanic membrane are often seen in patients with and without ear disease. The purpose of this prospective, observer agreement study was to determine if perforations of the tympanic membrane are reliably detectable on CT. Fifteen cadaver dogs underwent CT and video otoscopy to verify the integrity of each tympanic membrane. Cadavers were randomly assigned to have the tympanic membranes left intact or to undergo a myringotomy on either the left, the right, or both sides. CT was performed immediately following the myringotomies. Four blinded evaluators evaluated the pre‐ and post‐myringotomy scans for a total of 30 scans (60 tympanic membranes). Average accuracy was low (44%), and interobserver agreement for all four evaluators was fair. Although the tympanic membrane is visible on CT, perforations of the tympanic membrane are unlikely to be accurately detected or excluded. The appearance of an intact tympanic membrane or defect in the membrane on CT should not be used as criteria to guide clinical treatment recommendations based on this cadaver model. [ABSTRACT FROM AUTHOR]

Aim: Hypoglycaemic events are linked to microvascular and macrovascular complications in people with type 1 diabetes. We aimed to evaluate the efficacy of glucose sensor [real‐time continuous glucose monitoring (RT‐CGM)] with predictive alarm (PA) in reducing the time spent below the range (%TBR <70 mg/dl) in a group of adolescents with type 1 diabetes (AwD). Materials and Methods: This was a crossover, monocentric and randomized study. RT‐CGM was set with Alarm on Threshold (AoT) at 70 mg/dl) or PA for hypoglycaemia (20 m before threshold). Twenty AwD were enrolled and randomized to either a PA/AoT or AoT/PA treatment sequence, in a 1:1 ratio. The two groups (PA vs. AoT) were compared using two‐way repeated measures ANOVA taking account of the carryover effect. Results: AwD using PA for hypoglycaemia spent less time in severe hypoglycaemia (%TBR2 <54 mg/dl; 0.32 ± 0.31 vs. 0.91 ± 0.90; p <.02) and hypoglycaemia (%TBR <70 mg/dl; 1.68 ± 1.06 vs. 2.90 ± 2.05; p <.02), with better glycaemia risk index (51.3 ± 11.0 vs. 61.5 ± 12.6; p ≤.01). Conclusion: The use of RT‐CGM with PA for hypoglycaemia technology in AwD using multiple daily insulin injection treatment could significantly reduce the risk of having hypoglycaemic events resulting in an improved quality of glucose control. Clinical Trial Registration number: NCT05574023. [ABSTRACT FROM AUTHOR]

Background: We evaluated the prognostic role of 13‐gene DNA methylation analysis by oral brushing repeatedly performed during the follow‐up of patients surgically treated for oral cancer. Methods: This is a nested case–control study including 61 patients for a total of 64 outcomes (2/61 patients experienced multiple relapses). Samples were collected at baseline (4–10 months after OSCC resection) and repeatedly every 4–10 months until relapse or death. DNA methylation scores were classified as persistently positive, persistently negative, or mixed. Results: Twenty cases who had persistently positive scores and 30 cases with mixed scores had, respectively, an almost 42‐fold (p < 0.001) and 32‐fold (p = 0.006) higher likelihood of relapse, compared to 14 patients with persistently negative scores. The last score before reoccurrence was positive in 18/19 secondary events. Conclusions: The 13‐gene DNA methylation analysis may be considered for the surveillance of patients treated for oral carcinoma. [ABSTRACT FROM AUTHOR]

Given the prevalence of molecules containing nitro groups in organic synthesis, innovative methods to expand the reactivity of this functional group are of interest in both industrial and academic settings. In this report, a metal‐free intramolecular benzylic sp3 C−H amination is disclosed using aryl nitro compounds as aryl nitrene precursors. Organosilicon reagent N,N'‐bis(trimethylsilyl)‐4,4'‐bipyridinylidene (Si‐DHBP) served as an efficient reductant in the transformation, enabling the in situ generation of aryl nitrene species for the direct, metal‐free synthesis of unprotected 2‐arylindolines from the corresponding nitroarene compounds. [ABSTRACT FROM AUTHOR]

This paper presents the results of a numerical study aimed at assessing the effectiveness of an innovative steel modular retrofit system on improving the in‐plane lateral capacity of unreinforced masonry (URM) load‐bearing structures. The investigated retrofit solution consists of modular steel frames fastened to the external surface of masonry piers through chemical anchors. Distinct element models are built and calibrated against experimental data coming from a series of in‐plane quasi‐static tests performed on piers in both bare and retrofitted conditions. Two different masonry typologies are considered herein: one made up with solid clay bricks and lime mortar, assembled in a header bond pattern, and the other with typical Italian hollow clay units and cement‐lime mortar, arranged in a Flemish bond pattern. A simplified microscale approach, combined with a mesh‐refinement strategy, is adopted to decrease computational demand without losing numerical accuracy. All in‐plane failure mechanisms, such as mortar and unit tensile failures, as well as masonry crushing for high compressive stresses, are included in the developed numerical models. Moreover, a methodology to explicitly account for the contribution of the investigated retrofit in the distinct element method (DEM) framework is presented and discussed. The proposed modeling strategy yielded a good prediction in terms of lateral stiffness, lateral strength, hysteretic response, and crack pattern for unreinforced and strengthened specimens. A novel set of metrics is proposed to quantitatively assess the retrofit performance benefits. [ABSTRACT FROM AUTHOR]

Background: Combined chemoradiation offers a promising therapeutic strategy for dogs with glioma. The alkylating agents temozolomide (TMZ) and lomustine (CCNU) penetrate the blood‐brain barrier, and doses for dogs are established. Whether such combinations are clinically advantageous remains to be explored together with tumour‐specific markers. Objective: To investigate if triple combination of lomustine, temozolomide and irradiation reduces canine glioma cell survival in vitro. Methods: We evaluated the sensitising effect of CCNU alone and in combination with TMZ‐irradiation in canine glioma J3T‐BG cells and long‐term drug‐exposed subclones by using clonogenic survival and proliferation assays. Bisulphite‐SEQ and Western Blot were used to investigate molecular alterations. Results: TMZ (200 μM) or CCNU alone (5 μM) reduced the irradiated survival fraction (4 Gy) from 60% to 38% (p = 0.0074) and 26% (p = 0.0002), respectively. The double‐drug combination reduced the irradiated survival fraction (4 Gy) more potently to 12% (p < 0.0001). After long‐term drug exposure, both subclones show higher IC50 values against CCNU and TMZ. For CCNU‐resistant cells, both, single‐drug CCNU (p = 0.0006) and TMZ (p = 0.0326) treatment combined with irradiation (4 Gy) remained effective. The double‐drug‐irradiation combination reduced the cell survival by 86% (p < 0.0001), compared to 92% in the parental (nonresistant) cell line. For TMZ‐resistant cells, only the double‐drug combination with irradiation (4 Gy) reduced the cell survival by 88% (p = 0.0057) while single‐drug treatment lost efficacy. Chemoresistant cell lines demonstrated higher P‐gp expression while MGMT‐methylation profile analysis showed a general high methylation level in the parental and long‐term treated cell lines. Conclusions: Our findings indicate that combining CCNU with TMZ‐irradiation significantly reduces canine glioma cell survival. Such a combination could overcome current challenges of therapeutic resistance to improve overall patient survival. [ABSTRACT FROM AUTHOR]

Introduction: We recently developed a non‐invasive sampling procedure for oral squamous cell carcinoma (OSCC) detection based on DNA methylation analysis of a panel of 13 genes. Oral cancer, as well as acute and chronic inflammatory diseases, may influence the methylation level of several genes in the oral cavity. In the present study, we evaluated the presence of periodontal disease (PD) and the methylation status using our 13‐gene panel. Methods: Oral brushing specimens were collected from three different patient groups: 23 gingival OSCC patients, 15 patients affected by PD, and 15 healthy volunteers lacking evidence of PD. DNA methylation analysis was performed and each sample was determined to be positive or negative based on a predefined cut‐off value. Results: Positive results were found for 23/23 OSCC patients, 3/15 PD patients, and 0/15 samples from healthy volunteers. The GP1BB and MIR193 genes in the PD group exhibited mean methylation levels similar to OSCC patients. ZAP70 showed different methylation levels among three groups. Conclusion: Preliminary data identified shared epigenetic alterations between PD and OSCC patients in two inflammatory genes (GP1BB and MIR193). This study may help to identify potential links between the two diseases and serve as a starting point for the future research focused on pathogenesis. [ABSTRACT FROM AUTHOR]

Biofluorescence of mammalian pelage may serve to hide prey from predators sensitive to ultraviolet radiation, among other potential functions. To date biofluorescence has been documented in nocturnal‐crepuscular and fossorial mammals that are active under low‐light conditions. Giraffes are primarily diurnal, but biofluorescent pelage might offer camouflage from their nocturnal felid predators. Using a full‐spectrum camera we qualitatively analyzed UV reflectance and absorption in giraffe pelage from a museum specimen. We found no trace of UV biofluorescence in the giraffe pelage, suggesting that this trait may not be ecologically or biologically relevant in giraffes. The function of biofluorescence in mammals remains elusive, but our study contributes to the growing body of data about biofluorescence, or its lack thereof, in diurnal versus nocturnal‐crepuscular or fossorial mammal species. [ABSTRACT FROM AUTHOR]

Objective: The present retrospective study investigated the effect of chronic intake of proton pump inhibitors, selective serotonin uptake inhibitors, anti‐inflammatory, and antihypertensive drugs on the survival of dental implants and on the occurrence of peri‐implantitis. Materials and methods: Survival analyses for implant failure and peri‐implantitis were performed patient level for each drug subcategory and for risk factors. The HR for each drug was calculated with adjusted models as compared with a control group made of subjects not assuming the specific drug. Multilevel logistic regression was used to explore the influence of implant‐level and patient‐level variables on the outcomes. Results: A total of 270 subjects receiving 1118 dental implants were included, with a mean follow‐up time of 5.19 ± 4.22 years. After 10 years, the survival rate was 86.9% (patient level), and according to survival analysis, 61.3% of subjects were free from peri‐implantitis. The use of anti‐inflammatory medicines produced a significant effect (p =.04) on peri‐implantitis as compared to subjects not using the drug, with a 2.7‐year drop in the mean survival time. The HR was slightly above the level of significance in a semiadjusted model (p =.058). The multilevel analysis found a significant effect on the entire sample and not when considering only subjects with implants with more than 1‐year follow‐up. Conclusions: We found a possible relationship between anti‐inflammatory drug use and the occurrence of peri‐implantitis in the examined cohort of patients, and no correlation for the other drugs. [ABSTRACT FROM AUTHOR]

We report the synthesis of coordinatively unsaturated cationic rhodium complexes bearing the sterically encumbered electron‐rich NHC ligand IPr*OMe. The COD (1,5‐cyclooctadiene) complex [Rh(IPr*OMe)(COD)]BF4 adopts a tilted, pseudo‐square planar coordination geometry, where bonding to the ipso‐carbon of the NHC aryl substituent was observed in the solid state. Hydrogenation of this complex afforded a metastable dihydride complex [Rh(IPr*OMe)(H)2]BF4 with an unusual internal coordination to an arene of the ligand. In the absence of a hydrogen atmosphere, spontaneous reductive elimination of H2 afforded a rhodium complex [Rh(IPr*OMe)]BF4 with a single chelating ligand that stabilizes the highly unsaturated metal by two‐fold π‐face donation as suggested by NMR spectroscopy and computational studies. This unusual complex might serve as a versatile precatalyst for a variety of transformations. [ABSTRACT FROM AUTHOR]

Plasmonic catalysis has revealed improved product yield and selectivity in various chemical transformation reactions over the past decade. In this report, the effect of tertiary amine (‐NR3) functionalization on the surface of hierarchically‐porous zeotype (HP‐AlPO‐5) materials to enhance the plasmon‐mediated catalysis, utilizing a combination of the plasmonic antenna (Au) and catalytic reactor (Pd) nanoparticles (NPs) was investigated. The catalysts have been characterized using enhanced techniques such as HAADF‐STEM, FT‐EXAFS, and probe‐based FT‐IR to reveal the proximity and interaction between bimetallic NPs, and thermal stability of amines in the presence of Au or PdAu NPs. Interestingly, a four‐fold enhancement in the Suzuki‐Miyaura coupling reaction product yield was obtained over PdAu/HP‐AlPO‐5‐NR3 when compared with the analogous plasmonic catalyst with no amine functionalization under visible light irradiation. A range of amines were functionalized and their influence in the nucleation, uniform growth and stabilization of catalytic active site (Pd) and formation of electron‐rich species under visible light irradiation has also been investigated. The presence of tertiary amine in the nanostructured catalyst enhanced the turnover number (TON) significantly under light irradiation conditions in comparison to dark conditions. This study provides an enriched understanding of plasmon‐driven chemistry, where the maximized reaction rate enhancement requires the existence of active metal species and the formation of electron‐enriched species under light irradiation conditions. [ABSTRACT FROM AUTHOR]

Hierarchical nanostructures have attracted considerable research attention due to their applications in the catalysis field. Herein, we design a versatile hierarchical nanostructure composed of NiMoO4 nanorods surrounded by active MoS2 nanosheets on an interconnected nickel foam substrate. The as‐prepared nanostructure exhibits excellent oxygen evolution reaction performance, producing a current density of 10 mA cm−2 at an overpotential of 90 mV, in comparison with 220 mV necessary to reach a similar current density for NiMoO4. This behavior originates from the structural/morphological properties of the MoS2 nanosheets, which present numerous surface‐active sites and allow good contact with the electrolyte. Besides, the structures can effectively store charges, due to their unique branched network providing accessible active surface area, which facilitates intermediates adsorptions. Particularly, NiMoO4/MoS2 shows a charge capacity of 358 mAhg−1 at a current of 0.5 A g−1 (230 mAhg−1 for NiMoO4), thus suggesting promising applications for charge‐storing devices. [ABSTRACT FROM AUTHOR]

Objectives: In the present study we evaluated the effectiveness of the use of a novel autologous bone substitute derived directly from processing the extracted tooth in the upper premolar area to preserve a suitable esthetic score and functionality. Material and Methods: Fourteen bone-level implants with platform switching were inserted in 12 patients immediately after atraumatic extraction of premolars for restorative or endodontic reasons. The implant buccal bone gap was filled using autologous tooth extracted-derived material. Clinical and radiographic parameters, including Pink Esthetic Score (PES) were evaluated at 6 months. Results: A total of 10 patients accounting for 11 implants were included. PES showed a suitable esthetic result, and all the implant-prosthetic rehabilitation reported full satisfaction for masticatory function, phonetics, and aesthetics. Bone levels were stable and not affected by implant location, lesion type, or bone quality. Conclusion: Radiographically the autologous bone substitute used appears stable in the surgical site and there is good continuity between the autologous bone and the graft. No adverse effects such as periodontal inflammation, infection, or graft rejection was reported. [ABSTRACT FROM AUTHOR]

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A rhodium‐catalyzed anti‐Markovnikov hydroiodination of aromatic and aliphatic terminal alkynes is reported. Depending on the choice of ligand and substrate, either (E)‐ or (Z)‐configured alkenyl iodides are obtained in high to exclusive isomeric purity. The reaction exhibits a broad substrate scope and high functional group tolerance, employing easily accessible or commercially available aliphatic iodides as HI surrogates through a shuttle process. The synthesized vinyl iodides were applied in several C−C and C−heteroatom bond‐forming reactions with full retention of the stereoselectivity. The developed method could be used to significantly shorten the total synthesis of a marine cis‐fatty acid. Additionally, initial deuterium‐labeling experiments and stoichiometric reactions shed some light on the potential reaction mechanism. [ABSTRACT FROM AUTHOR]

Copyright of Angewandte Chemie is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Shuttle hetero‐difunctionalization reaction, in which two chemically distinct functional groups are transferred between two molecules, has long been an unmet goal due to the daunting challenges in controlling the chemo‐, regio‐, and stereoselectivity. Herein, we disclose an electrochemistry enabled shuttle reaction (e‐shuttle) to selectively transfer one RS− and one X− group between β‐halosulfides and unsaturated hydrocarbons via a consecutive paired electrolysis mechanism. The preferential anodic oxidation of one anion over the other, which is controlled by their distinct redox potentials, plays a pivotal role in controlling the high chemoselectivity of the process. This easily scalable methodology enables the construction of a myriad of densely functionalized β‐halo alkenyl sulfides in unprecedented chemo‐, regio‐, and stereoselectivity using benign surrogates, e.g. 2‐bromoethyl sulfide, avoiding the handling of corrosive and oxidative RS–Br reagents. In a broader context, these results open up new strategies for selective shuttle difunctionalization reactions. [ABSTRACT FROM AUTHOR]

Objective: To profile clinically non‐aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)‐post‐transcriptional regulators and therapy targets. Design: Retrospective observational study. Patients and Measurements: A total of 64 non‐aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with ≥1‐year follow‐up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control. Results: We found at least one mutation in 17 tumours, including 6/64 non‐aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non‐aggressive PAs/PITNETs (p <.05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non‐aggressive ones (p <.05). For X‐linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non‐aggressive PAs/PITNETs (p <.05). In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X‐linked genes methylation level was lower. Conclusions: Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA‐post‐transcriptional regulators and targets of antineoplastic therapies are different in non‐aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic‐epigenetic analysis, in association with clinico‐radiological‐pathological data, may be of help in predicting PA/PitNET behaviour. [ABSTRACT FROM AUTHOR]

Animal color pattern is a phenotypic trait that may mediate assortative mixing (also known as homophily), whereby similar looking individuals have stronger social associations. Masai giraffe (Giraffa camelopardalis tippelskirchi) coat spot patterns show high variation and some spot traits appear to be heritable. Giraffes also have high visual acuity, which may facilitate intraspecific communication and recognition based on spot patterns. Giraffe groupings are dynamic, merging and splitting throughout the day, but females form long‐term associations. We predicted that adult female giraffes show stronger associations with other females that have similar spot pattern traits. We quantified the spot pattern characteristics of 399 adult female Masai giraffes and determined the pattern similarity among pairs (dyads) in their social network. We then tested for an association between coat pattern similarity (spot size, shape, and orientation) and dyadic association strength, and quantified assortative mixing. The strength of social associations was positively correlated with similarity in spot shape. Our results are compatible with assortativity by coat patterns that are similar between mother and offspring, potentially reflecting an effect of relatedness on both pattern similarity and female social associations. These results offer evidence that spot pattern could function as a visual cue for intraspecific communication and kin or individual recognition in a fission‐fusion species. [ABSTRACT FROM AUTHOR]

Summary: Increased intestinal permeability has an important role in metabolic dysregulation. In this cross‐sectional study, we examined whether serum intestinal permeability marker zonulin and related pro‐inflammatory molecules were associated with the oral disposition index, a predictor for the development of type 2 diabetes, in a cohort of children and adolescents with overweight and obesity. Ninety‐two children and adolescents were recruited [Male: 43; 12.7 (2.35) years; BMI SDS: 2.7 (0.96)]. Anthropometric and clinical parameters, lipid profile, glucose metabolism and plasma levels of zonulin, lipopolysaccharide‐binding protein and Interleukin‐6 were measured. We found an association between oral disposition index and zonulin (β = −0.243; p = 0.019) and age (β = −0.307; p = 0.004), independent of sex and BMI SDS [R2 = 0.16; p = 0.005]. Our results show an association between serum zonulin concentration and oral disposition index supporting the hypothesis of increased intestinal permeability as a possible risk factor for glucose metabolism dysregulation in children and adolescents with obesity. [ABSTRACT FROM AUTHOR]

Aims: To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). Materials and Methods: Cross‐sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5–17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high‐density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. Results: The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06–1.68) for MetS (p = 0.02), 3.19 (2.51–4.05) for HUA (p < 0.0001) and 3.72 (2.65–5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. Conclusions: HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study. [ABSTRACT FROM AUTHOR]

This article, published in Veterinary Record Case Reports, describes a case of severe respiratory distress in a 2-year-old Aberdeen Angus heifer due to oropharyngeal trauma from a balling/bolus gun injury. The heifer presented with symptoms such as tachycardia, tachypnea, and open-mouth breathing. Initial treatment included the placement of an emergency temporary tracheostomy tube, which resulted in the resolution of the respiratory symptoms. Diagnostic measures such as upper airway radiography and endoscopy were used to detect the oropharyngeal trauma. Prompt intervention with a temporary tracheostomy tube was found to be beneficial in cases of bovine respiratory distress. The article emphasizes the importance of diagnostic evaluation and highlights that cases with oesophageal involvement may have less successful management outcomes compared to cases with limited oropharyngeal trauma. [Extracted from the article]

Malaria is the most serious mosquito‐borne parasitic disease, caused mainly by the intracellular parasite Plasmodium falciparum. The parasite invades human red blood cells and releases extracellular vesicles (EVs) to alter its host responses. It becomes clear that EVs are generally composed of sub‐populations. Seeking to identify EV subpopulations, we subject malaria‐derived EVs to size‐separation analysis, using asymmetric flow field‐flow fractionation. Multi‐technique analysis reveals surprising characteristics: we identify two distinct EV subpopulations differing in size and protein content. Small EVs are enriched in complement‐system proteins and large EVs in proteasome subunits. We then measure the membrane fusion abilities of each subpopulation with three types of host cellular membranes: plasma, late and early endosome. Remarkably, small EVs fuse to early endosome liposomes at significantly greater levels than large EVs. Atomic force microscope imaging combined with machine‐learning methods further emphasizes the difference in biophysical properties between the two subpopulations. These results shed light on the sophisticated mechanism by which malaria parasites utilize EV subpopulations as a communication tool to target different cellular destinations or host systems. Synopsis: Plasmodium falciparum invades human red blood cells and releases two extracellular vesicle subsets secreted by infected cells. These EV subpopulations harbor different protein cargo and have specific mechanical membrane properties, suggesting distinct host cell targets. Two distinct subsets of malaria‐derived EVs with different sizes are identified using asymmetric flow field‐flow fractionation.Small EVs are rich in complement system proteins, whereas large EVs contain 20S proteasome subunits.Small EVs are more efficient in fusing under endosomal conditions as compared to the large subset.The EV subpopulations possess distinct membrane mechanical properties, suggesting different lipid compositions. [ABSTRACT FROM AUTHOR]

Convolutional neural networks (CNNs) are commonly used as artificial intelligence (AI) tools for evaluating radiographs, but published studies testing their performance in veterinary patients are currently lacking. The purpose of this retrospective, secondary analysis, diagnostic accuracy study was to compare the error rates of four CNNs to the error rates of 13 veterinary radiologists for evaluating canine thoracic radiographs using an independent gold standard. Radiographs acquired at a referral institution were used to evaluate the four CNNs sharing a common architecture. Fifty radiographic studies were selected at random. The studies were evaluated independently by three board‐certified veterinary radiologists for the presence or absence of 15 thoracic labels, thus creating the gold standard through the majority rule. The labels included "cardiovascular," "pulmonary," "pleural," "airway," and "other categories." The error rates for each of the CNNs and for 13 additional board‐certified veterinary radiologists were calculated on those same studies. There was no statistical difference in the error rates among the four CNNs for the majority of the labels. However, the CNN's training method impacted the overall error rate for three of 15 labels. The veterinary radiologists had a statistically lower error rate than all four CNNs overall and for five labels (33%). There was only one label ("esophageal dilation") for which two CNNs were superior to the veterinary radiologists. Findings from the current study raise numerous questions that need to be addressed to further develop and standardize AI in the veterinary radiology environment and to optimize patient care. [ABSTRACT FROM AUTHOR]

Copyright of Infant Mental Health Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Photogeneration of Reactive Oxygen Species (ROS) finds applications in fields as different as nanomedicine, art preservation, air and water depollution and surface decontamination. Here we present photocatalytic nanoparticles (NP) that are active only at acidic pH while they do not show relevant ROS photo‐generation at neutral pH. This dual responsivity (to light and pH) is achieved by stabilizing the surface of TiO2 NP with a specific organic shell during the synthesis and it is peculiar of the achieved core shell‐structure, as demonstrated by comparison with commercial photocatalytic TiO2 NP. For the investigation of the photocatalytic activity, we developed two methods that allow real time detection of the process preventing any kind of artifact arising from post‐treatments and delayed analysis. The reversibility of the pH response was also demonstrated as well as the selective photo‐killing of cancer cells at acidic pH. [ABSTRACT FROM AUTHOR]

Background: The ability to rate delirium severity is key to providing optimal care for persons with Alzheimer's Disease and Related Dementias (ADRD). Such ratings would allow clinicians to assess response to treatment, recovery time and prognosis, nursing burden and staffing needs, and to provide nuanced, appropriate patient‐centered care. Given the lack of existing tools, we defined content domains for a new delirium severity instrument for use in individuals with mild to moderate ADRD, the DEL‐S‐AD. Methods: We built upon our previous study in which we created a content domain framework to inform development of a general delirium severity instrument, the DEL‐S. We engaged a new expert panel to discuss issues of measurement in delirium and dementia and to determine which content domains from the prior framework were useful in characterizing delirium severity in ADRD. We also asked panelists to identify new domains. Our panel included eight interdisciplinary members with expertise in delirium and dementia. Panelists participated in two rounds of review followed by two surveys over 2 months. Results: Panelists endorsed the same content domains as for general delirium severity, including Cognitive, Level of Consciousness, Inattention, Psychiatric‐Behavioral, Emotional Dysregulation, Psychomotor Features, and Functional; however, they excluded six of the original subdomains which they considered unhelpful in the context of ADRD: cognitive impairment; anxiety; fear/sense of unease; depression; gait/walking; and incontinence. Debated measurement challenges included assessment at one point in time versus over time, accounting for differences in clinical settings, and accurate assessment of symptoms related to delirium versus dementia. Conclusions: By capturing a range of characteristics of delirium severity potentially present in patients with ADRD, a population that may already have attention, functional, and emotional changes at baseline, the DEL‐S‐AD provides a novel rating tool that will be useful for clinical and research purposes to improve patient care. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Ecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The precursors have significant influence on the catalytic activity of nonprecious electrocatalysts for effective water splitting. Herein, we report active electrocatalysts based on cobalt oxide (Co3O4) hierarchical nanostructures derived from four different precursors of cobalt (acetate, nitrate, chloride, and sulfate salts) using the low‐temperature aqueous chemical growth method. It has been found that the effect of precursor on the morphology of nanostructured material depends on the synthetic method. The Co3O4 nanostructures exhibited cubic phase derived from these four precursors. The Co3O4 nanostructures obtained from chloride precursor have demonstrated improved oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) compared to other precursors due relatively higher content of Co3O4 nanostructures at the surface of material. An overpotential of 400 mV versus reversible hydrogen electrode (RHE) at 10 mA cm−2 was observed for HER. The Co3O4 nanostructures derived from the chloride precursor have shown favorable reaction kinetics via 34 mV dec−1 value of the Tafel slope for HER reaction. The Co3O4 nanostructures derived from chloride precursor have also shown an excellent HER durability for 15 hr in alkaline media. Furthermore, the OER functional characterization was carried out onto Co3O4 nanostructures derived from chloride precursor exhibited 220 mV overpotential at 10 mA cm−2 and Tafel slope of 56 mV dec−1. Importantly, the reason behind the favorable catalytic activity of Co3O4 nanostructures derived from chloride precursor was linked to one order of magnitude smaller charge transfer resistance and higher amount of Co3O4 content at the surface of nanostructures than the Co3O4 nanostructures derived from other precursors. The performance of Co3O4 nanostructures derived from chloride precursor via the wet chemical method suggests that cobalt chloride precursor could be of great interest for the development of efficient, stable, nonprecious, and environmentally friendly electrocatalysts for the chemical energy conversion and storage devices. [ABSTRACT FROM AUTHOR]

The construction of RC frame structures with masonry infills is part of the traditional building practice in many European countries and worldwide. Several studies have been recently conducted to improve further the understanding of the seismic response of masonry infills, which are mainly focused on weak/slender clay masonry panels representing a common typology of the past, whereas very limited research has been devoted to stronger/thicker masonry infills, which nowadays are being adopted with increasing frequency in newly designed RC structures for their excellent thermal and acoustic performance. In order to fill this gap, within a systematic experimental and numerical research program, the in‐plane and out‐of‐plane experimental response of 'strong' masonry infills has been investigated at the Eucentre and the University of Pavia. In particular, this paper presents the framework and discusses the results of out‐of‐plane static cyclic tests on full‐scale, single‐storey, single‐bay RC frame specimens infilled with 35 cm thick tongue and groove clay unit walls, the related damage propagation and the failure mechanisms. The in‐plane/out‐of‐plane experimental interaction evaluated in terms of stiffness and strength reduction and period increase in function of previous in‐plane damage is also introduced, with the aim of providing a simplified out‐of‐plane strength verification within the European codified design procedures. [ABSTRACT FROM AUTHOR]

Fat grafting is a well‐established method in plastic surgery. Despite many technical advances, standardised recommendations for the use of prophylactic antibiotics in fat grafting are not available. This retrospective multicentre study aims to analyse the use of prophylactic antibiotics in fat grafting and to compare complication rates for different protocols. A retrospective medical chart review of 340 patients treated with fat grafting of the breast from January 2007 to March 2019 was performed in three plastic surgery centres. Complications, outcomes, and antibiotic regimes were analysed. The Clavien‐Dindo classification was applied. All patients received perioperative antibiotic prophylaxis: 33.8% (n = 115) were treated with a single shot (group 1), 66.2% (n = 225) received a prolonged antibiotic scheme (group 2). There was no significant difference in the number of sessions (P =.475). The overall complication rate was 21.6% (n = 75), including graft resorption, fat necrosis, infection, and wound healing problems. Complication rates were not significantly different between groups. Risk factors for elevated complication rates in this specific patient group are smoking, chemotherapy, and irradiation therapy. The complication rate for lipografting of the breast is low, and it is not correlated to the antibiotic protocol. The use of prolonged prophylactic antibiotics does not lower the complication rate. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B12, B6, and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B6, B12, and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B6, B12, and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi‐controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B12, and four vitamin B6. Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B6, B12, and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B6, B12, and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine. [ABSTRACT FROM AUTHOR]