Search

IntroductionIn a nested case-control study, we examined how cerebral perfusion relates to cognitive status and amyloid in the oldest-old (i.e., 90 years of age and older).MethodsStudy participants included 113 dementia-free older adults (76 cognitively normal [CN]; 37 cognitively impaired, no dementia [CIND]) from the 90+ Study (mean age = 92.9, SD = 2.4). We quantified regional perfusion from arterial spin labeling-MRI (magnetic resonance imaging) and amyloid deposition from florbetapir-positron emission tomography (PET) in a region comprising the posterior cingulate and precuneus (PCC+PCu), and additionally quantified perfusion in other regions important for cognitive decline (medial temporal lobe, inferior parietal lobe, and orbitofrontal cortex).ResultsParticipants with CIND displayed lower perfusion in the PCC+PCu relative to participants who were CN, but there was no statistically significant difference between the groups in amyloid burden in this region. In addition, participants with CIND exhibited lower inferior parietal and higher orbitofrontal perfusion.DiscussionCerebral perfusion is related to cognitive status in the oldest-old independent of amyloidosis.HighlightsCerebral perfusion and amyloid positron emission tomography (PET) were measured in older adults: 90 years of age and older. Perfusion but not amyloid differed between cognitively impaired and normal groups. Frontal and parietal regions linked to cognitive decline had altered perfusion. Perfusion is related to cognitive status in the oldest-old independent of amyloid.

Background and objectivesAmyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.MethodsThis was a longitudinal, observational community-based cohort study. We included participants with 18F-florbetapir PET and MRI data from the 90+ Study. Amyloid load was measured using the standardized uptake value ratio in the precuneus/posterior cingulate with eroded white matter mask as reference. WMH volume was log-transformed. All imaging measures were standardized using sample means and SDs. HV and log-WMH volume were normalized by total intracranial volume using the residual approach. Global cognitive performance was measured by the Mini-Mental State Examination (MMSE) and modified MMSE (3MS) tests, repeated every 6 months. We used linear mixed-effects models with random intercepts; random slopes; and interaction between time, time squared, and imaging variables to estimate the associations of imaging variables with cognitive level and cognitive decline. Models were adjusted for demographics, APOE genotype, and health behaviors.ResultsThe sample included 192 participants. The mean age was 92.9 years, 125 (65.1%) were female, 71 (37.0%) achieved a degree beyond college, and the median follow-up time was 3.0 years. A higher amyloid load was associated with a lower cognitive level (βMMSE = -0.82, 95% CI -1.17 to -0.46; β3MS = -2.77, 95% CI -3.69 to -1.84). A 1-SD decrease in HV was associated with a 0.70-point decrease in the MMSE score (95% CI -1.14 to -0.27) and a 2.27-point decrease in the 3MS score (95% CI -3.40 to -1.14). Clear nonlinear cognitive trajectories were detected. A higher amyloid burden and smaller HV were associated with faster cognitive decline. WMH volume was not significantly associated with cognitive level or decline.DiscussionAmyloid burden and hippocampal atrophy are associated with both cognitive level and cognitive decline in the oldest old. Our findings shed light on how different pathologies contributed to driving cognitive function in the oldest old.

BACKGROUND: The Anti-Amyloid in Asymptomatic Alzheimers Disease (A4) Study failed to show a treatment benefit with solanezumab, but the longitudinal consequences of elevated amyloid were observed in study participants with objective decline on the Preclinical Alzheimer Cognitive Composite (PACC) and subjective decline on the combined Cognitive Function Index (participant + study partner CFI), during the trial period. OBJECTIVES: We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study. DESIGN: Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally. SETTING: The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States. PARTICIPANTS: 1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab. MEASUREMENTS: The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined. RESULTS: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile. CONCLUSION: Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load.

The use of bioinert materials is crucially important for medicine and bioengineering. The most popular systems in this context are oligo- and poly(ethylene glycols) (OEGs and PEGs), applied generally in different forms as bulk materials, thin films, and functional molecular groups. Here, I review the fabrication, properties, and applications of porous hydrogel PEG films (PHFs) and nanosheets (PHNs) formed by thermally activated crosslinking of amino- and epoxy-terminated, star-branched PEG oligomers with variable molecular weight. These systems possess various useful characteristics, including tunable thickness and porosity, hydrogel properties, bioinertness, robustness, and extreme elasticity. They can serve as the basis for composite materials, advanced nanofabrication, and lithography, bioinert supports for high-resolution transmission electron microscopy, susceptible elements in micro-electromechanical systems, and basic building blocks of temperature, humidity, chemical, and biological sensors. Representative examples of the respective applications are provided. Even though these examples span a broad field-from nanoengineering to biosensing, the applications of the PHFs and PHNs are certainly not limited to these cases but can be specifically adapted and extended to other fields, such as tissue engineering and drug delivery, relying on versatility and tunability of these systems. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the methods used for ripening fruits by sellers and to examine the knowledge regarding the health risks associated with the use of calcium carbide (CaC2) among both fruit sellers and consumers in Ado-Ekiti. Methods: The study employed a cross-sectional design, utilizing a semi-structured questionnaire administered in major markets within Ado-Ekiti. Knowledge levels were categorized into good (> 70% score), fair (50–69% score), and poor (< 50% score). One way Analysis of variance (ANOVA) and Independent sample t-test was used to indicate knowledge score difference with respect to socio demographic characteristics. Results: The study involved 357 consumers and 20 fruit sellers, with a majority being females (54.9% of consumers; 80.0% of sellers) and aged predominantly between 18–27 years and 28–39 years. The findings revealed that the use of CaC2 (50%) and natural ripening methods (100%) were common among fruit sellers. Sellers cited cancer (60%), bacterial infections (35%), and chest tightness (15%) as associated risks with CaC2 usage. Similarly, consumers expressed concerns about consuming CaC2-ripened fruits, attributing risks such as abdominal burns (70%), cancer (70.6%), and diarrhoea (67.3%). A significant proportion of sellers (90%) exhibited poor knowledge regarding the risks associated with CaC2, while 24.6% of consumers demonstrated fair knowledge on the subject. Conclusion: The study identified common fruit ripening practices among sellers. Fruit sellers showed poor knowledge, while consumers displayed fair to poor understanding of health risks linked to calcium carbide use in artificial fruit ripening. [ABSTRACT FROM AUTHOR]

Aims Physical symptoms impact patients with heart failure (HF) despite treatment advancements; however, our understanding of the pathogenic mechanisms underlying HF symptoms remains limited, including sex differences therein. The objective of this study was to quantify associations between sympathetic markers [norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DHPG)] and physical symptoms in patients with HF and to explore sex differences in these associations. Methods and results We performed a secondary analysis of combined data from two studies: outpatients with HF (n = 111), and patients prior to left ventricular assist device implantation (n = 38). Physical symptoms were measured with the Heart Failure Somatic Perception Scale (HFSPS) dyspnoea and early/subtle symptom subscales and the Functional Assessment in Chronic Illness Therapy Fatigue Scale (FACIT-F) to capture dyspnoea, early symptoms of decompensation, and fatigue. Norepinephrine and DHPG were measured with high-performance liquid chromatography with electrochemical detection. Multivariate linear regression was used to quantify associations between symptoms and sympathetic markers. The sample (n = 149) was 60.8 ± 15.7 years, 41% women, and 71% non-ischaemic aetiology. Increased plasma NE and NE:DHPG ratio were associated with worse FACIT-F scores (P = 0.043 and P = 0.013, respectively). Increased plasma NE:DHPG ratio was associated with worse HFSPS early/subtle symptoms (P = 0.025). In sex-stratified analyses, increased NE:DHPG ratio was associated with worse FACIT-F scores (P = 0.011) and HFSPS early/subtle scores (P = 0.022) among women but not men. Conclusion In patients with HF, sympathetic dysfunction is associated with worse fatigue and early/subtle physical symptoms with associations stronger in women than men. [ABSTRACT FROM AUTHOR]

Adiabatic calorimeter experiments have quantified the sulfuric acid‐catalyzed reaction of ethylene oxide (EO) with water to form ethylene glycol (EG) and higher glycols. Conditions were selected relevant to industrial safety, such as a scenario of reverse flow of acid from a scrubber to an EO tank. Concentrations of 25–95 wt% EO with acidified water of pH 3.0 down to pH –0.7 were examined. In some experiments, EG was also added to the mix. The best fit apparent reaction rate expression exhibits a 1.5 order in EO concentration, third order in water concentration, nearly first order in acid concentration, and an activation energy of 76,500 kJ/kmol. The reaction model provides an adequate fit of adiabatic self‐heat rate versus temperature, pressure rate versus temperature, pressure versus time, and temperature versus time data for a large number of APTAC (Automatic Pressure Tracking Adiabatic Calorimeter) experiments. The model builds on one previously developed for the neutral reactions of EO with water and EGs. A case study involving a sulfuric acid‐contaminated EO railcar is presented. The reaction model can help quantify the behavior of EO contaminated with sulfuric acid solution below about 120°C. Above this temperature, other reaction pathways not characterized in this study become more prominent. [ABSTRACT FROM AUTHOR]

In this study, the gold nanoparticles (Au NPs) are capped with a novel, well‐defined double hydrophilic block copolymer, poly (ethylene glycols)‐block‐poly(mono‐2‐(methacryloyloxy) ethyl succinate) (PEG‐b‐PSEMA). The PEG‐b‐PSEMA, with long side chains and relatively narrow dispersity index, is successfully prepared by aqueous electrochemically mediated atom transfer radical polymerization using a PEG‐Br macroinitiator (Mn≈2000 g mol−1). By simply mixing PEG‐b‐PSEMA and Au precursor before adding reductants, coulombic interactions occur between the Au precursor and the carboxylate group of the PSEMA, as a result dense Au NPs are formed. This enables the Au NPs to remain dispersed even in the presence of temperature variations, pH adjustments, and incubation in organic solvents. Au NPs were endowed by PEG‐b‐PSEMA with more remarkable catalytic activity in organic solvents of 4‐nitrophenol into 4‐aminophenol than by sodium citrate (Au@citrate) and MeO‐PEG‐OH (Au@PEG). In addition, PEG‐b‐PSEMA‐stabilized Au NPs (Au@PEG‐b‐PSEMA) were also tested for the dye degradation property against Rhodamine‐B in only pH 10 basic solution, and over 99% of dye degradation can be achieved in 9 min. PEG‐b‐PSEMA induces coulombic interactions with Au NPs, providing outstanding stability for catalytic applications in organic or specific acidic‐base environments. [ABSTRACT FROM AUTHOR]

Rationale: Acute caustic ingestion from suicidal intent is not usual in emergency departments in developed countries. One of the substances commonly ingested by suicidal patients, phosphoric acid, tends to cause multi-system derangements. Patient’s Concern: A 41-year-old male patient presented with complaints of throat discomfort, severe generalized abdominal pain, and multiple episodes of hematemesis after ingesting a restroom cleaning solution. Diagnosis: Poisoning by acute caustic ingestion (containing <30% phosphoric acid and <4% ethylene glycol). Interventions: The patient was administered 50 mL of 8.4% sodium bicarbonate solution followed by an isotonic sodium bicarbonate solution running at 500 mL/h, a hyperkalemia kit, ceftriaxone, metronidazole, omeprazole, and atropine. The patient then underwent urgent hemodialysis. Outcomes: The patient suffered gastrointestinal bleeding as a result of local caustic injury. In addition, his course of illness was complicated by severe acidemia from high anion gap metabolic acidosis and deranged electrolytes (hyperphosphatemia, hyperkalemia, and hypocalcemia). He developed multi-organ failure and eventually demised. Lessons: The clinician needs to be mindful of the multi-system complications arising from such a caustic ingestion. These patients need to be monitored closely for deterioration, and have prompt management of the various arising complications, to reduce the high morbidity and mortality associated with this condition. [ABSTRACT FROM AUTHOR]

Integrated ethylene oxide/ethylene glycols (EO/EG) plants are prominent energy consumers in the petrochemical sector, particularly concerning high‐pressure steam (HPS) usage which holds the potential for substantial energy savings. This study focuses on an unexplored territory: Examining the impact of EO catalyst type, selectivity, and glycols production capacity on HPS import in a plant in the Pars Special Economic Energy Zone (PSEEZ). Utilizing Python3 for data preprocessing and ordinary least squares linear regression analysis, we evaluate how varying catalyst loads and production scenarios influence HPS import. Regression models are created, encompassing normal and efficient HPS import scenarios, yielding positive outcomes in terms of correlation, mean error percentage, and R2 analysis. Comparing normal and efficient HPS import models highlights potential savings, uncovering opportunities to conserve between 45 and over 200 tonnes per day of HPS. We also explore the plant's HPS behaviour under 1% selectivity and production capacity reductions. Notably, catalyst activity decline markedly escalates HPS import for hybrid catalysts, while selectivity decline decreases HPS import for high‐activity catalysts. The models demonstrate that HPS import is ~150 tonnes per day more sensitive to a 1% change in selectivity compared to production capacity. Moreover, when comparing high activity and hybrid catalyst scenarios in normal and efficient cases, the most substantial HPS import difference arises under conditions of low selectivity, amounting to nearly 200 tonnes per day. Our methodology applies to other EO/EG plants. It is incorporated into our plant's energy management system, enabling continuous monitoring of steam import behaviour relative to catalyst and plant performance. [ABSTRACT FROM AUTHOR]

Background: There had been a sudden surge of unusually severe and rapidly progressing acute kidney injury (AKI) incidence in Indonesia since August 2022 which did not correspond to the rise of COVID-19 incidence. We suspected this was related to ethylene glycol (EG) and diethylene glycol (DEG) intoxication. This study is aimed at describing the clinical and laboratory characteristics of AKI related to D(EG) intoxication in order to spread awareness of the possibility of intoxication in cases of rapidly progressing AKI with unknown etiology. Methods: We conducted a cross-sectional study by collecting secondary data from the pediatric AKI registry at a national referral hospital in Jakarta, Indonesia. Data on children admitted from January to November 2022 with diagnosis of stage 3 AKI based on KDIGO criteria were included. Data regarding demographics, symptoms prior to anuria, laboratory results, infection panel including COVID-19 status, treatment administered, and mortality were analyzed. Results: Sixteen patients tested positive for EG and DEG, all with history of consuming syrup-based medications. High anion gap metabolic acidosis was observed in majority of patients with mean pH 7.33 ± 0.07 and mean anion gap 15.6 ± 7.8 mEq/L. No patient had high osmolal gap (mean osmolal gap 3.46 ± 4.68). One deceased patient, who had kidney biopsy performed, showed severe damage and calcium oxalate crystals in the kidney tissue. Mortality was recorded in six patients (37.5%). Conclusion: Careful history taking of patient's clinical course, including consumption of syrup-based medications and laboratory findings, might aid clinicians to establish a working diagnosis of D(EG) intoxication without needing to wait for blood toxicology test. Early diagnosis and therapy are crucial to prevent substantial mortality. [ABSTRACT FROM AUTHOR]

As compact and efficient heat exchange equipment, helically coiled tube-in-tube heat exchangers (HCTT heat exchangers) are widely used in many industrial processes. However, the thermal-hydraulic research of liquefied natural gas (LNG) as the working fluid in HCTT heat exchangers is rarely reported. In this paper, the characteristics of HCTT heat exchangers, in which LNG flows in the inner tube and ethylene glycol-water solution flows in the outer tube, are studied by numerical simulations. The influences of heat transfer characteristics and pressure drops of the HCTT heat transfers are studied by changing the initial flow velocity, the helical middle diameter, and the helical pitch. The results indicate that different initial flow velocities in the inner tube and the outer tube of the HCTT heat exchanger have little influence on the secondary flow of the fluid in the helical tubes, and the overall flow characteristics tend to be stable. The smaller helical middle diameter of the HCTT heat exchanger leads to the shorter fluid flow length, the smaller resistance along the tubes and the increase of initial pressure under the condition of constant inlet velocity, which promotes the occurrence of secondary flow. The axial flow of fluid promotes the destruction of heat transfer boundary layer and gains strength of the turbulence and heat transfer efficiency. With the increase of the helical pitch of the HCTT heat exchanger, the turbulent intensity and the heat transfer efficiency are also increased. Moreover, the improvement of the flow state of the HCTT exchanger in a longer helical pitch also enhances the heat exchange efficiency. [ABSTRACT FROM AUTHOR]

Metal‐coordinated hydrogels can form a percolated network with transient bonds due to metal ions‐functional group coordination. Each metal ion can link with more than one ligand, leading to intricate speciation of bonding modes. While the mechanics of transient gels made with four‐arm polymers are often studied, less is known about how increasing the number of arms affects the modulus. Using shear rheology, the modulus of hydrogels prepared from four‐, six‐, and eight‐armed poly(ethylene glycols), functionalized with histidine ligands that complex with nickel (II) ions is measured. These gels have matched polymer wt.% and varied pH to compare their moduli. It is considered whether the modulus can be described by established polymer network models by calculating the speciation of metal‐coordinated cross‐links and then incorporating it into a phantom network prediction. This study finds that 1) increasing the number of polymer arms increases the modulus, 2) the phantom network allows reasonable modulus approximation for four‐arm and six‐arm gels, and 3) the modulus of eight‐arm gels exceeds the phantom network prediction. Since polymer cores act as chemical cross‐links and metal‐coordinated cross‐links form network strands, it is possible that increasing the number of metal‐coordinated linkages per molecule reinforces the chemical cross‐link at the polymer core. [ABSTRACT FROM AUTHOR]

BackgroundGreater subjective cognitive changes on the Cognitive Function Index (CFI) was previously found to be associated with elevated amyloid (Aß) status in participants screening for the A4 Study, reported by study partners and the participants themselves. While the total score on the CFI related to amyloid for both sources respectively, potential differences in the specific types of cognitive changes reported by either participants or their study partners was not investigated.ObjectivesTo determine the specific types of subjective cognitive changes endorsed by participants and their study partners that are associated with amyloid status in individuals screening for an AD prevention trial.Design, setting, participantsFour thousand four hundred and eighty-six cognitively unimpaired (CDR=0; MMSE 25-30) participants (ages 65-85) screening for the A4 Study completed florbetapir (Aß) Positron Emission Tomography (PET) imaging. Participants were classified as elevated amyloid (Aß+; n=1323) or non-elevated amyloid (Aß-; n=3163).MeasurementsPrior to amyloid PET imaging, subjective report of changes in cognitive functioning were measured using the CFI (15 item questionnaire; Yes/Maybe/No response options) and administered separately to both participants and their study partners (i.e., a family member or friend in regular contact with the participant). The impact of demographic factors on CFI report was investigated. For each item of the CFI, the relationship between Aß and CFI response was investigated using an ordinal mixed effects model for participant and study partner report.ResultsIndependent of Aß status, participants were more likely to report 'Yes' or 'Maybe' compared to the study partners for nearly all CFI items. Older age (r= 0.06, p

Ethylene glycol 2-ethylhexyl ether (EGEHE) is a solvent used in a variety of applications.We report disposition and metabolism of EGEHE following a single gavage or dermal administration of 50, 150 or 500 mg/kg [14C]EGEHE in rats and mice and in vitro in rat hepatocytes.EGEHE was cleared rapidly in rat hepatocytes (half-life ∼4 min) with no sex difference.EGEHE was well- and moderately absorbed following oral administration (rats: 80-96%, mice: 91-95%) and dermal application (rats: 25-37%, mice: 22-24%), respectively, and rapidly excreted in urine.[14C]EGEHE-derived radioactivity was distributed to tissues (oral: 2.3-7.2%, dermal: 0.7-2.2%) with liver and kidney containing the highest levels in both species.EGEHE was extensively metabolised with little to no parent detected in urine. The alkoxyacetic acid metabolite, which has previously been shown to mediate toxicities of other shorter-chain ethylene glycol ethers, was not detected.There were no apparent dose, species or sex differences in disposition and metabolism of EGEHE, except that the exhaled volatile compounds were greater in mice (19-20%) compared with rats (

ObjectiveTo understand the time course of β-amyloid (Aβ) deposition in the brain, which is crucial for planning therapeutic trials of Aβ-lowering therapies in Alzheimer disease (AD).MethodsTwo samples of participants from the Alzheimer's Disease Neuroimaging Initiative were studied with [18F]Florbetapir (FBP) Aβ PET and followed for up to 9 years. Sample A included 475 cognitively normal (CN) older people and those with mild cognitive impairment (MCI) and AD and sample B included 220 CN Aβ- individuals. We examined the trajectory of FBP over time in sample A and the incidence rate of conversion from negative to positive Aβ PET scans in sample B.ResultsThe relationship between time and brain Aβ was sigmoidal, taking 6.4 years to transition from amyloid negative to positive and another 13.9 years to the onset of MCI. Aβ deposition rates began to slow only 3.8 years after reaching the positivity threshold. The incidence rate for scan positivity was 38/1,000 person-years, and factors associated with conversion were age, baseline FBP, and being a female APOE ε4 carrier. Among CN Aβ- individuals, FBP slopes were associated with rates of memory decline and brain tau measured with [18F]Flortaucipir PET 5 years after baseline.ConclusionsLowering brain Aβ must be accomplished early in the evolution of AD. Transitions of PET scans from Aβ- to Aβ+ should be predictable, and it is reasonable to expect that lowering rates of Aβ even in early stages could produce clinically significant benefits.

Supportive care is the cornerstone of the poisoned patient's treatment, waiting for eventual antidotes to act. We recently treated a case of a severe Ethylene Glycol intoxication with early-onset veno-arterial ECMO. The patient was taken to our Emergency Department with the suspicion of acute cerebrovascular accident, since he was found unconscious at home. The arterial blood gas and blood tests showed a severe metabolic acidosis with high serum lactates and creatinine levels. The cerebral Computed Tomography was negative. The rapid increase in serum lactates suggested Ethylene Glycol intoxication. Although the patient was not in shock yet, arterial and venous introducers were placed in to the femoral vessels so that when the patient showed the first signs of cardiogenic shock, veno-arterial ECMO could be initiated in a very short time. The hemodynamic state progressively improved and V-A ECMO was removed after 16 h of support with complete recovery. [ABSTRACT FROM AUTHOR]

BackgroundImaging biomarkers have the potential to distinguish between different brain pathologies based on the type of ligand used with PET. AV-45 PET (florbetapir, Amyvid™) is selective for the neuritic plaque amyloid of Alzheimer's disease (AD), while AV-133 PET (florbenazine) is selective for VMAT2, which is a dopaminergic marker.ObjectiveTo report the clinical, AV-133 PET, AV-45 PET, and neuropathological findings of three clinically diagnosed dementia patients who were part of the Avid Radiopharmaceuticals AV133-B03 study as well as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND).MethodsThree subjects who had PET imaging with both AV-133 and AV-45 as well as a standardized neuropathological assessment were included. The final clinical, PET scan, and neuropathological diagnoses were compared.ResultsThe clinical and neuropathological diagnoses were made blinded to PET scan results. The first subject had a clinical diagnosis of dementia with Lewy bodies (DLB); AV-133 PET showed bilateral striatal dopaminergic degeneration, and AV-45 PET was positive for amyloid. The final clinicopathological diagnosis was DLB and AD. The second subject was diagnosed clinically with probable AD; AV-45 PET was positive for amyloid, while striatal AV-133 PET was normal. The final clinicopathological diagnosis was DLB and AD. The third subject had a clinical diagnosis of DLB. Her AV-45 PET was positive for amyloid and striatal AV-133 showed dopaminergic degeneration. The final clinicopathological diagnosis was multiple system atrophy and AD.ConclusionPET imaging using AV-133 for the assessment of striatal VMAT2 density may help distinguish between AD and DLB. However, some cases of DLB with less-pronounced nigrostriatal dopaminergic neuronal loss may be missed.

Purpose. To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model. Methods. An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes. Results. The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3 ′ -untranslated region (3 ′ -UTR) and miR-23 was confirmed by the dual-luciferase reporter assay. Conclusion. In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model. [ABSTRACT FROM AUTHOR]

Poly(ethylene glycols) are complex polymers often added to pharmaceutical formulations to improve drug solubility and delivery. One of the main challenges when using chromatographic techniques coupled to mass spectrometry is the unselective ionization of poly(ethylene glycols) oligomers. Additionally, when the chain length is large enough, multiple charged species are formed, further complicating the mass spectra and processing. This study uses the advanced oligomer separation provided by supercritical fluid chromatography with a mass spectrometry approach that selectively ionizes poly(ethylene glycols) as ammoniated molecules to simplify data analysis and facilitate batch‐to‐batch comparisons. Several visual representations of the response of the ionization events based on the polymer molecular weight and the repeating unit were used to elucidate trends in ionization. Evaluation of the influence of the oligomer length and end‐group on the electrospray ionization of the polymer allowed the development of a process to enable selective ionization for these complex polymers. [ABSTRACT FROM AUTHOR]

Calcium carbide (CaC2) and ethylene glycol (EG) are the two commonly used fruit ripening agents. The toxic effects of these chemicals on internal organs were reported in experimental animals. Even though the adverse effects of these compounds have been investigated for many years, there are no sufficient data available with regard to genotoxic effects. The present study evaluates the genotoxic effect of chronic exposures of CaC2 and EG in Wistar albino rats. CaC2 and EG were administered to the rats orally for 180 days. Chromosomal aberrations and micronuclei formation were analysed in bone marrow and peripheral blood cells. Comet assay was performed to analyse the DNA strand break. The toxic effects of the chemicals were analysed by MTT assay with normal human intestinal epithelial (IEC-6) cells. Upon chronic exposure, CaC2 and EG caused chromosomal aberrations, micronuclei formation and DNA strand breaks extensively in bone marrow and peripheral blood cells. In MTT assay, the chemicals were found to be toxic to IEC-6 cells with IC50 values at 160 and 200 μg/mL for CaC2 and EG, respectively. The results show that these chemicals have a potential to cause genomic level of toxicity which may lead to carcinogenic event at a chronic level exposure. The study warns to reinforce the administrative measures against the use of CaC2 and EG for fruit ripening process. – Industrial grade CaC2 and EG show genotoxicity at the chronic exposure in animals at lower doses. – In vitro cytotoxicity by CaC2 and EG towards IEC-6 cell line exhibited dose dependent decrease of cell proliferation. – Chromosomal aberrations, micronuclei formation, DNA breakage (comet assay) suggest potentially pre-mutagenic lesions by the toxicity. – These chemicals have the potential for genotoxic and carcinogenic effect. – The study warns the health risks of consumption of fruits ripened with calcium carbide and ethylene glycol. [ABSTRACT FROM AUTHOR]

Objective: We aimed to test the hypothesis that elevated neocortical β-amyloid (Aβ), a hallmark feature of Alzheimer's disease (AD), predicts sex-specific cognitive trajectories in clinically normal older adults, with women showing greater risk of decline than men. Method: Florbetapir Aβ positron emission tomography (PET) was acquired in 149 clinically normal older adults (52% female, Mage = 74). Participants underwent cognitive testing at baseline and during annual follow-up visits over a timespan of up to 5.14 years. Mixed-effects regression models evaluated whether relations between baseline neocortical Standardized Uptake Value Ratio (SUVR) and composite scores of episodic memory, executive functioning, and processing speed were moderated by sex (male/female) and apolipoprotein E (APOE) status (ε4 carrier/noncarrier). Results: Higher baseline SUVR was associated with longitudinal decline in episodic memory in women (b = -1.32, p < .001) but not men (b = -0.30, p = .28). Female APOE ε4 carriers with elevated SUVR showed particularly precipitous declines in episodic memory (b = -4.33, p < .001) whereas other cognitive domains were spared. SUVR did not predict changes in executive functioning or processing speed, regardless of sex (ps >.63), though there was a main effect of SUVR on processing speed (b = 2.50, p = .003). Conclusions: Clinically normal women with elevated Aβ are more vulnerable to episodic memory decline than men. Understanding sex-related differences in AD, particularly in preclinical stages, is crucial for guiding precision medicine approaches to early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

IntroductionAbnormal gene expression patterns may contribute to the onset and progression of late-onset Alzheimer's disease (LOAD).MethodsWe performed transcriptome-wide meta-analysis (N = 1440) of blood-based microarray gene expression profiles as well as neuroimaging and cerebrospinal fluid (CSF) endophenotype analysis.ResultsWe identified and replicated five genes (CREB5, CD46, TMBIM6, IRAK3, and RPAIN) as significantly dysregulated in LOAD. The most significantly altered gene, CREB5, was also associated with brain atrophy and increased amyloid beta (Aβ) accumulation, especially in the entorhinal cortex region. cis-expression quantitative trait loci mapping analysis of CREB5 detected five significant associations (P < 5 × 10-8 ), where rs56388170 (most significant) was also significantly associated with global cortical Aβ deposition measured by [18 F]Florbetapir positron emission tomography and CSF Aβ1-42 .DiscussionRNA from peripheral blood indicated a differential gene expression pattern in LOAD. Genes identified have been implicated in biological processes relevant to Alzheimer's disease. CREB, in particular, plays a key role in nervous system development, cell survival, plasticity, and learning and memory.

Background: The noradrenergic systems in the brain maintain cognitive functions including attention/concentration and establishment of long‐term memory. In addition, hypofunction of noradrenergic systems is supposed to be involved in the pathophysiology of Alzheimer's disease. In this study, we tried to examine the possible associations of concentrations of basal salivary 3‐methoxy‐4‐hydroxyphenylglycol (sMHPG), a major metabolite of noradrenaline, and brain volume changes during 4 years in elderly people living in a rural community. Methods: The survey was conducted twice in Kurokawa‐cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 226 residents. Measurements of sMHPG and brain MRIs were collected at Time 1 (2005–2007). Follow‐up brain MRIs were taken at Time 2 (2009–2011). A total of 70 participants (18 men, mean age 71.9 ± 4.8 years; 52 women, mean age 72.0 ± 4.3 years) completed this survey. Concentrations of sMHPG at baseline were divided into two groups using the mean value (12.83 ng/ml). We compared the brain volumes between groups with higher and lower sMHPG concentrations over time using voxel‐based morphometry implemented with statistical parametric mapping. Results: In participants with higher sMHPG concentrations at baseline, brain volumes including right precuneus were significantly larger 4 years after baseline than those with lower sMHPG concentrations at baseline. No interaction between sMHPG concentration and MRI acquisition interval was found. Conclusion: Our results suggest that higher sMHPG concentrations in elderly people might be associated with maintenance of brain volume, especially in brain regions closely related to cognitive function. [ABSTRACT FROM AUTHOR]

This work presents the manufacturing by 3D printing in lateral position C, of five samples made of PETG material. Polyethylene terephthalate glycol, commonly known as PETG or PET-G, is a thermoplastic polyester that provides significant chemical resistance, durability, and excellent formability for manufacturing. PETG can be easily vacuumed and pressure-formed as well as heat-bent thanks to its low forming temperatures. This makes it exceptionally popular for consumer and commercial applications that involve 3D printing, or other heat-forming manufacturing techniques. Additionally, PETG is well-suited for fabrication techniques like die cutting, routing, and bending. 3D printing has more and more applications in all industrial fields and is a modern additive manufacturing process. Among the many advantages of using this process are the use of a digital model in the design phase, a very high material efficiency in the execution phase as well as a significant reduction in the costs related to the tools and equipment required. This work is part of a larger study in which tensile specimens are fabricated using three printing positions and three types of filaments. The manufactured samples are intended to be later used for tensile tests. [ABSTRACT FROM AUTHOR]

BackgroundMeasuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer's disease (AD).ObjectiveTo examine associations between plasma GFAP and cortical Aβ deposition in older adults across the typical aging-to-AD dementia spectrum.MethodsWe studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, N = 37) covering the spectra of clinical severity (CDR Sum of Boxes; CDR-SB) and Aβ-PET burden. Aβ-PET was completed with either florbetapir or Pittsburgh Compound B and standardized uptake value ratios were converted to the Centiloid (CL) scale for analyses. All participants with CDR-SB > 0 were Aβ-PET positive, while clinically normal participants (CDR-SB = 0) were a mix of Aβ-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aβ-PET, and clinical severity.ResultsIn both cohorts, plasma GFAP increased linearly with Aβ-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aβ-PET burden, the association between Aβ and GFAP became curvilinear (inverted U-shape; quadratic model R2 change = 0.165, p = 0.009), and Aβ-PET interacted with CDR-SB (R2 change = 0.164, p = 0.007): older adults with intermediate functional impairment (CDR-SB = 0.5-4.0) showed a weak (negative) association between Aβ-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB > 4.0) showed a strong, negative association of higher Aβ-PET CLs with lower plasma GFAP.ConclusionThe relationship between astrocytic integrity and cortical Aβ may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.

We evaluated the associations of subjective (self-reported everyday cognition [ECog]) and objective cognitive measures with regional amyloid-β (Aβ) and tau accumulation in 86 clinically normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative. Regression analyses were conducted to identify whether individual ECog domains (Memory, Language, Organization, Planning, Visuospatial, and Divided Attention) were equally or differentially associated with regional [18F]florbetapir and [18F]flortaucipir uptake and how these associations compared to those obtained with objective cognitive measures. A texture analysis, the weighted 2-point correlation, was used as an additional approach for estimating the whole-brain tau burden without positron emission tomography intensity normalization. Although the strongest models for ECog domains included either tau (planning and visuospatial) or Aβ (memory and organization), the strongest models for all objective measures included Aβ. In Aβ-negative participants, the strongest models for all ECog domains of executive functioning included tau. Our results indicate differential associations of individual subjective cognitive domains with Aβ and tau in clinically normal adults. Detailed characterization of ECog may render a valuable prescreening tool for pathological prediction.

ObjectiveTo determine the time required for a preclinical Alzheimer disease population to decline in a meaningful way, use estimates of decline to update previous clinical trial design assumptions, and identify factors that modify β-amyloid (Aβ)-related decline.MethodsIn 1,120 cognitively unimpaired individuals from 3 international cohorts, we estimated the relationship between Aβ status and longitudinal changes across multiple cognitive domains and assessed interactions between Aβ and baseline factors. Power analyses were performed to explore sample size as a function of treatment effect.ResultsCognitively unimpaired Aβ+ participants approach mild cognitive impairment (MCI) levels of performance 6 years after baseline, on average. Achieving 80% power in a simulated 4-year treatment trial, assuming a 25% treatment effect, required 2,000 participants/group. Multiple factors interacted with Aβ to predict cognitive decline; however, these findings were all cohort-specific. Despite design differences across the cohorts, with large sample sizes and sufficient follow-up time, the Aβ+ groups declined consistently on cognitive composite measures.ConclusionsA preclinical AD population declines to the cognitive performance of an early MCI population in 6 years. Slowing this rate of decline by 40%-50% delays clinically relevant impairment by 3 years-a potentially meaningful treatment effect. However, assuming a 40%-50% drug effect highlights the difficulties in preclinical AD trial design, as a more commonly assumed treatment effect of 25% results in a required sample size of 2,000/group. Designers of preclinical AD treatment trials need to prepare for larger and longer trials than are currently being considered. Interactions with Aβ status were inconsistent and not readily generalizable.

The study of individuals with autosomal dominant Alzheimer's disease affords one of the best opportunities to characterize the biological and cognitive changes of Alzheimer's disease that occur over the course of the preclinical and symptomatic stages. Unifying the knowledge gained from the past three decades of research in the world's largest single-mutation autosomal dominant Alzheimer's disease kindred - a family in Antioquia, Colombia with the E280A mutation in the Presenilin1 gene - will provide new directions for Alzheimer's research and a framework for generalizing the findings from this cohort to the more common sporadic form of Alzheimer's disease. As this specific mutation is virtually 100% penetrant for the development of the disease by midlife, we use a previously defined median age of onset for mild cognitive impairment for this cohort to examine the trajectory of the biological and cognitive markers of the disease as a function of the carriers' estimated years to clinical onset. Studies from this cohort suggest that structural and functional brain abnormalities - such as cortical thinning and hyperactivation in memory networks - as well as differences in biofluid and in vivo measurements of Alzheimer's-related pathological proteins distinguish Presenilin1 E280A mutation carriers from non-carriers as early as childhood, or approximately three decades before the median age of onset of clinical symptoms. We conclude our review with discussion on future directions for Alzheimer's disease research, with specific emphasis on ways to design studies that compare the generalizability of research in autosomal dominant Alzheimer's disease to the larger sporadic Alzheimer's disease population.

This work reports the mechanochemical synthesis of organic compounds involving carbon–carbon (C–C), carbon–nitrogen (C–N), and carbon–oxygen (C–O). The solid-state synthesis of ω-poly(ethylene glycols) functionalized with different cyclic anhydrides and the obtainment of curcumin Schiff bases and curcumin multicomponent derivatives are also reported. The mechanochemical method was also used in the Steglich esterification using curcumin derivatives. 1H NMR, 13C NMR, MIR, XRPD, and HPLC techniques were performed to confirm the synthesis of each compound. [ABSTRACT FROM AUTHOR]

Traditional herbal remedies have been used for treating nephrolithiasis, but the relevant scientific evidence is limited. Zaleya pentandra (L.) C. Jeffrey is traditionally used for the prevention of kidney stones in various cultures. However, its efficacy has not been scientifically studied. This study aimed to investigate the antiurolithic activity of Zaleya pentandra, and validate its traditional used for preventing kidney stones. The crude ethanolic extract of Z. pentandra (Zp.Crd) was evaluated through in vitro and in vivo studies. In vitro experiments assessed its impact on crystal count and morphology in metastable calcium oxalate solutions. In vivo studies involved diuretic and ethylene glycol-induced calcium oxalate crystal formation in male Wistar rats. Zp.Crd transforms calcium oxalate crystals from harmful calcium oxalate monohydrate (COM) to calcium oxalate dihydrate (COD). In vivo , Zp.Crd exhibited dose-dependent (30–300 mg/kg) diuretic activity in rats by significantly increasing urinary sodium (Na+) and potassium (K+) excretion, similar to the standard diuretic hydrochlorothiazide (HCT). In the urolithiasis model, Zp.Crd exhibited dose-dependent antiurolithic effects by reducing kidney crystals and significantly altering lithogenic factors induced by ethylene glycol, including crystalluria, oxaluria, calcium, creatinine, and urea, in the urine and serum of treated rats. Zp.Crd also exhibited antioxidant effects, effectively combating oxidative lithogenic stress in rats. Zp.Crd has been shown to demonstrate antiurolithic activity against CaOx stones through CaOx crystal inhibition, diuretic activity, antioxidant properties, hypocalciuric effects, and hypercitrauric actions. The findings underscore Zp.Crd's potential as a viable alternative or supplemental therapy to current urolithiasis treatments, paving the door for further clinical trials and its inclusion into modern medical practices. [Display omitted] • The study bridges traditional use of Zaleya pentandra as an antiurolithic remedy with modern scientific validation. • Zaleya pentandra exhibits multiple mechanisms against calcium oxalate stones, including in vitro and in vivo experimental studies. • Findings demonstrate that the antiurolithiatic and diuretic effects of Zaleya pentandra are dose-dependent, with significant results observed at various doses. • Zaleya pentandra shows significant antioxidant properties, contributing to its overall efficacy in managing oxidative stress associated with kidney stone formation. [ABSTRACT FROM AUTHOR]

The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus , with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD 3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L - Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD. [Display omitted] • QDP primarily contains pectin-type heteropolysaccharides and inhibits the formation of CaOx monohydrate crystals effectively. • QDWE reduced ethylene glycol-induced CaOx kidney stone formation, oxidative stress, and kidney dysfunction in rats. • QDWE alleviates ethylene glycol-induced CaOx kidney stones in rats via OPN/CD44 and NLRP3 pathways. [ABSTRACT FROM AUTHOR]

ObjectiveExtensive cortical β-amyloid (Aβ positivity) has been linked to cognitive decline, but the clinical significance of elevations in Aβ within the negative range is unknown.MethodsWe examined amyloid and cognitive trajectories (memory, executive function) in 142 cognitively normal older individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative who were Aβ-negative at baseline and who had at least 2 [18F]-florbetapir PET scans over 3.9 ± 1.4 years. We determined whether Aβ accumulation was associated with longitudinal changes in memory or executive function.ResultsAmong baseline-negative individuals, florbetapir slope (mean annual increase 0.002 ± 0.008 standardized uptake value ratio units/y) was not related to age, sex, education, APOE4 status, baseline memory or executive function, temporoparietal glucose metabolism, baseline hippocampal volume, or hippocampal volume change; but it was related to higher baseline cortical florbetapir, indicating that Aβ accumulation was ongoing at baseline in those who accumulated during the study. Over the course of follow-up, 13 individuals converted to florbetapir+ and 14 nearly nonoverlapping individuals converted to mild cognitive impairment or Alzheimer disease. Amyloid accumulation among baseline-negative individuals was associated with poorer longitudinal memory performance (p = 0.019), but it was not associated with changes in executive function. Reducing the sample to individuals with at least 3 timepoints to estimate the florbetapir slope strengthened the relationship further between florbetapir accumulation and memory decline (p = 0.007).ConclusionsMemory decline accompanies Aβ accumulation in otherwise healthy, Aβ-negative older adults. Amyloid increases within the negative range may represent the earliest detectable indication of pathology with domain-specific cognitive consequences.

BackgroundAmyloid deposition is a potential contributor to postoperative cognitive dysfunction. The authors hypothesized that 6-week global cortical amyloid burden, determined by F-florbetapir positron emission tomography, would be greater in those patients manifesting cognitive dysfunction at 6 weeks postoperatively.MethodsAmyloid deposition was evaluated in cardiac surgical patients at 6 weeks (n = 40) and 1 yr (n = 12); neurocognitive function was assessed at baseline (n = 40), 6 weeks (n = 37), 1 yr (n = 13), and 3 yr (n = 9). The association of 6-week amyloid deposition with cognitive dysfunction was assessed by multivariable regression, accounting for age, years of education, and baseline cognition. Differences between the surgical cohort with cognitive deficit and the Alzheimer's Disease Neuroimaging Initiative cohorts (normal and early/late mild cognitive impairment) was assessed, adjusting for age, education, and apolipoprotein E4 genotype.ResultsThe authors found that 6-week abnormal global cortical amyloid deposition was not associated with cognitive dysfunction (13 of 37, 35%) at 6 weeks postoperatively (median standard uptake value ratio [interquartile range]: cognitive dysfunction 0.92 [0.89 to 1.07] vs. 0.98 [0.93 to 1.05]; P = 0.455). In post hoc analyses, global cortical amyloid was also not associated with cognitive dysfunction at 1 or 3 yr postoperatively. Amyloid deposition at 6 weeks in the surgical cohort was not different from that in normal Alzheimer's Disease Neuroimaging Initiative subjects, but increased over 1 yr in many areas at a rate greater than in controls.ConclusionsIn this study, postoperative cognitive dysfunction was not associated with 6-week cortical amyloid deposition. The relationship between cognitive dysfunction and regional amyloid burden and the rate of postoperative amyloid deposition merit further investigation.

ObjectiveTo identify the pathophysiologic mechanisms and clinical significance of anosognosia for cognitive decline in mild cognitive impairment.MethodsWe stratified 468 patients with amnestic mild cognitive impairment into intact and impaired awareness groups, determined by the discrepancy between the patient and the informant score on the Everyday Cognition questionnaire. Voxel-based linear regression models evaluated the associations between self-awareness status and baseline β-amyloid load, measured by [18F]florbetapir, and the relationships between awareness status and regional brain glucose metabolism measured by [18F]fluorodeoxyglucose at baseline and at 24-month follow-up. Multivariate logistic regression tested the association of awareness status with conversion from amnestic mild cognitive impairment to dementia.ResultsWe found that participants with impaired awareness had lower [18F]fluorodeoxyglucose uptake and increased [18F]florbetapir uptake in the posterior cingulate cortex at baseline. In addition, impaired awareness in mild cognitive impairment predicted [18F]fluorodeoxyglucose hypometabolism in the posterior cingulate cortex, left basal forebrain, bilateral medial temporal lobes, and right lateral temporal lobe over 24 months. Furthermore, participants with impaired awareness had a nearly 3-fold increase in likelihood of conversion to dementia within a 2-year time frame.ConclusionsOur results suggest that anosognosia is linked to Alzheimer disease pathophysiology in vulnerable structures, and predicts subsequent hypometabolism in the default mode network, accompanied by an increased risk of progression to dementia. This highlights the importance of assessing awareness of cognitive decline in the clinical evaluation and management of individuals with amnestic mild cognitive impairment.

ImportanceThe ability to predict the pathology underlying different neurodegenerative syndromes is of critical importance owing to the advent of molecule-specific therapies.ObjectiveTo determine the rates of positron emission tomography (PET) amyloid positivity in the main clinical variants of primary progressive aphasia (PPA).Design, setting, and participantsThis prospective clinical-pathologic case series was conducted at a tertiary research clinic specialized in cognitive disorders. Patients were evaluated as part of a prospective, longitudinal research study between January 2002 and December 2015. Inclusion criteria included clinical diagnosis of PPA; availability of complete speech, language, and cognitive testing; magnetic resonance imaging performed within 6 months of the cognitive evaluation; and PET carbon 11-labeled Pittsburgh Compound-B or florbetapir F 18 brain scan results. Of 109 patients referred for evaluation of language symptoms who underwent amyloid brain imaging, 3 were excluded because of incomplete language evaluations, 5 for absence of significant aphasia, and 12 for presenting with significant initial symptoms outside of the language domain, leaving a cohort of 89 patients with PPA.Main outcomes and measuresClinical, cognitive, neuroimaging, and pathology results.ResultsTwenty-eight cases were classified as imaging-supported semantic variant PPA (11 women [39.3%]; mean [SD] age, 64 [7] years), 31 nonfluent/agrammatic variant PPA (22 women [71.0%]; mean [SD] age, 68 [7] years), 26 logopenic variant PPA (17 women [65.4%]; mean [SD] age, 63 [8] years), and 4 mixed PPA cases. Twenty-four of 28 patients with semantic variant PPA (86%) and 28 of 31 patients with nonfluent/agrammatic variant PPA (90%) had negative amyloid PET scan results, while 25 of 26 patients with logopenic variant PPA (96%) and 3 of 4 mixed PPA cases (75%) had positive scan results. The amyloid positive semantic variant PPA and nonfluent/agrammatic variant PPA cases with available autopsy data (2 of 4 and 2 of 3, respectively) all had a primary frontotemporal lobar degeneration and secondary Alzheimer disease pathologic diagnoses, whereas autopsy of 2 patients with amyloid PET-positive logopenic variant PPA confirmed Alzheimer disease. One mixed PPA patient with a negative amyloid PET scan had Pick disease at autopsy.Conclusions and relevancePrimary progressive aphasia variant diagnosis according to the current classification scheme is associated with Alzheimer disease biomarker status, with the logopenic variant being associated with carbon 11-labeled Pittsburgh Compound-B positivity in more than 95% of cases. Furthermore, in the presence of a clinical syndrome highly predictive of frontotemporal lobar degeneration pathology, biomarker positivity for Alzheimer disease may be associated more with mixed pathology rather than primary Alzheimer disease.

In this work, the effect of ethylene glycol oligomers and polymers of various molecular masses on the structural transformations of deoxyribonucleic acid (DNA) is studied exclusively by viscometry. The main goal of this study was to understand how polyethylene glycol (PEG) interacts, which binds to calf thymus DNA (ctDNA). This paper presents the results of these studies. It has been found that ethylene glycols with molecular masses of 600 and 1000, apparently due to their smallness, do not have a noticeable effect on the sizes of DNA macromolecules in the studied concentration ranges. For ethylene glycols with molecular masses of 6000 and 7000, a clearly expressed complex course of the dependence of the intrinsic viscosity of DNA solutions on the polymer content was established. A decrease in the viscosity of solutions was observed, which was interpreted as a result of a decrease in the size of DNA macromolecules. It was assumed that with a change in the concentration of ethylene glycols in the system, an increase in the density of DNA macromolecules occurs due to a change in the balance of hydrophobic-hydrophilic interactions. The results of the study in the presence of 20 000 molecular masses of PEG in a DNA solution practically exclude the presence of interaction between DNA and PEG molecules at such molecular masses. [ABSTRACT FROM AUTHOR]

Poisoning, drug overdose, and adverse drug effects continue to be a common encounter, especially in the intensive care unit (ICU). Patients are often critically ill or have a potential to rapidly deteriorate and warrant ICU admission. Adults suffering from overdoses rarely give a complete and accurate description of the quantity or type of medications ingested. In most adult cases, multiple substances are involved. A tentative diagnosis in most overdose and poisoning cases can be made by physical examination and simple laboratory tests (electrolyte panel, creatinine, serum osmolarity, urinalysis, etc). Supportive care, with particular attention to airway management, oxygenation, and circulation, is the mainstay of treatment. Basic treatment principles include limiting the amount of toxin absorbed, enhancing the elimination of ingested toxin, and preventing the conversion of non-toxic compounds to toxic metabolites. Drugs or poisons, where specific antidotes or effective therapies exist (especially acetaminophen, salicylates, methanol, ethylene glycol, and digitalis), should be aggressively sought and treated after initial stabilization has been accomplished. For those drugs or poisons where specific quantitative tests are available, levels should be obtained before treatment and may be repeated as clinically indicated. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the second leading cause of cancer death. Although Regorafenib showed survival benefits in patients with CRC, reports imply the recurrence of malignant phenotype resulting from chemotherapy. Evidence demonstrated that a5β1 integrin plays an important role in the Regorafenib treatment, which, may be led to resistance. In this study, the effects of /siRNA or/ and Quercetin loaded DDAB-mPEG-PCLnanoparticles could reverse this resistance phenotype in colon cancer cells in vitro. Methods: Regorafenib-resistant Ls-180 colon cancer cell line was developed by long-term exposure to Regorafenib. Quercetin and Regorafenib were separately encapsulated into mPEG-PCL micelles through the nano-precipitation method and characterized by DLS. Optimized doses of Quercetin and Regorafenib were used for combination therapy of resistant cells followed cytotoxicity study using MTT. Gene expression levels of the β1 subunit of integrin were determined by the real-time method of RT-PCR. Results: Developed Regorafenib resistant LS-180 showed to have Regorafenib IC50 of 38.96 ± 1.72 µM whereas IC50 in non-resistant cells were 8.51 ± 0.29 µM, which meaningful was lower statistically compared to that of a resistant one. The β1 mRNA level of whole α5β1 integrin was significantly higher in the resistant cells compared to those of non-resistant ones. Gene expression levels in each siRNA-loaded nanoparticle and Quercetin-loaded one were lower than that in mock experiments. Finally, when these two types of nanoparticles were used to treat resistant cells, gene expression decrease of integrin indicated a greater effect that could be capable of reverse resistancy. Conclusion: Results of this study demonstrated another confirmation of involving integrins in cancer resistance following chemotherapy using Regorafenib. Also, it indicated how using siRNA targeting integrin could enhance the plant derivatives like Quercetin effects to reverse resistance in vitro. [ABSTRACT FROM AUTHOR]