Midlife cerebrovascular risk factors increase risk of late life cognitive impairment and dementia, while their presence in patients with dementia may lead to cognitive improvement or stabilization in ...late life. Defining the best measure of blood pressure (BP) to be associated with cognitive decline remains debatable, also due to possible bidirectionality. BP variability, pulse pressure, systolic and diastolic BP have been associated with cognitive status, dementia risk and Alzheimer's disease biomarkers. Proper BP control notwithstanding, BP variability increases risk for pathophysiological change in the Alzheimer's disease continuum, implying the need for selection of anti-hypertensive drugs with neurobiological evidence of benefits.
Avermectins and moxidectin are antiparasitics widely used as active pharmaceutical ingredients in veterinary medicine, as well as in pesticide formulations for pest control in agriculture. Although ...the use of these compounds provides benefits to agribusiness, they can impact the environment, since a large part of these substances may reach the soil and water from the excreta of treated animals and following direct applications to crops. The present work had the objective of evaluating the dissipation behaviors of abamectin, doramectin, eprinomectin, ivermectin, and moxidectin in four native Brazilian soils of different textural classes (clay, sandy-clay, sandy, and sandy-clay-loam), following OECD Guideline 307. The studies were conducted in a climate chamber at 22 °C, 71% relative humidity, and protected from light. The dissipation studies were carried out with all drugs together, since no difference was verified when studies were done with each drug separately. The concentrations of the drugs in the soils were determined using an ultra-high performance liquid chromatograph coupled to a fluorescence detector or a tandem mass spectrometer. The dissipation half-life (DT50) values ranged from 9 to 16 days and the calculated GUS index values were in the range from −1.10 to 0.08, indicating low mobility of the drugs in the soils evaluated and low tendency for leaching. In addition, a field study was carried out to evaluate the dissipation of abamectin after application of a foliar pesticide in an orange crop. A DT50 of 9 days was determined, which was similar to that obtained under controlled conditions in the climate chamber (12 days), indicating that biotransformation was the primary process influencing the overall dissipation.
•Avermectins have low potential to contaminate groundwater.•Avermectins and moxidectin dissipate faster in sandy soils.•The DT50 for abamectin in the field study was 9 days.•DT50 of abamectin is shorter in the field than under laboratory conditions.•A LOQ of 0.1 ng g−1 of abamectin in soils is reached using SPE-UPLC-MS/MS.
Aluminum (Al) is one of the most found elements in nature in many forms, and human exposure can be quite common. Therefore, it is important to investigate the effects of exposure to Al mainly at low ...doses and for a prolonged period, in order to simulate human exposure in the periodontium, an important structure for support and protection of the teeth. This investigation aimed to study the aluminum chloride (AlCl
3
) toxicological effects in the mineral composition and micromorphology of the alveolar bone of rats. Two groups of eight male Wistar rats were used for the experiment. AlCl
3
group was exposed to AlCl
3
orally at a dose of 8.3 mg/kg/day for 60 days, while the control group received only distilled water. After that, the mandibles were collected and submitted to the following analyses: Fourier transform infrared spectroscopy, Raman spectroscopy, and X-ray microtomography analysis; blood was also collected for determination of Al circulating levels. Our data showed that AlCl
3
was capable of increasing Al circulating levels in blood. It was able to promote changes in the mineral content and triggers significant changes in the mineralized bone microstructure, such as number and thickness of trabeculae, being associated with alveolar bone-loss.
Background Periodontitis is a multifactorial inflammatory disease of tooth supporting tissues caused by oral biofilms, influenced by environmental and genetic factors, among others. Ethanol ...consumption has been considered a factor that enhances alveolar bone loss, especially in high doses. The present study aims to investigate the changes promoted by ethanol binge drinking per se or associated with ligature-induced periodontal breakdown on alveolar bone loss. Materials and methods Thirty-two Wistar rats were randomly allocated into four groups: control (C), ethanol (3g/kg/day; 3 days On-4 days Off protocol by gavage for 28 days, EtOH), experimental periodontitis (EP) and experimental periodontitis plus ethanol administration (EP+EtOH). On day 14th, periodontitis was induced by ligatures that were placed around the lower first molars. On day 28th, the animals were euthanized and mandibles were submitted to stereomicroscopy for exposed root area analysis and micro-computed tomography (micro-CT) for the evaluation of alveolar bone loss and microstructural parameters. Results The results revealed that ligature-induced alveolar bone loss is aggravated by ethanol binge drinking compared to controls (1.06 ± 0.10 vs 0.77 ± 0.04; p<0.0001). In addition, binge drinking per se altered the alveolar bone quality and density demonstrating a reduction in trabecular thickness, trabecular number parameter and bone density percentual. Periodontal disorder plus ethanol binge drinking group also demonstrated reduction of the quality of bone measured by trabecular thickness. Conclusions In conclusion, intense and episodic ethanol intake decreased alveolar bone quality in all microstructural parameters analyzed which may be considered a modifying factor of periodontitis, intensifying the already installed disease.
Swallowing in behavioral variant frontotemporal dementia MARIN, Sheilla de Medeiros Correia; MANSUR, Letícia Lessa; OLIVEIRA, Fabricio Ferreira de ...
Arquivos de neuro-psiquiatria,
01/2021, Volume:
79, Issue:
1
Journal Article
Peer reviewed
Open access
ABSTRACT
Background:
Swallowing and feeding problems may occur with the progression of behavioral variant frontotemporal dementia (bvFTD) and can impair the anticipatory and oral preparatory phases ...of swallowing.
Objective:
To characterize swallowing problems and the feeding situation of patients with bvFTD and to correlate the swallowing problems with functionality, executive functions, cognitive and behavioral features.
Methods:
Consecutive outpatients with bvFTD in mild, moderate and severe dementia stages were recruited along with their caregivers. Patients and caregivers were screened with the following scales: “Mini-Mental State Examination”, “Severe Mini-Mental State Examination”, “FTLD-modified Clinical Dementia Rating”, “Neuropsychiatric Inventory”, “Frontal Assessment Battery”, “Index of Independence in Activities of Daily Living”, “Swallowing Rating Scale” and “Assessment of Feeding and Swallowing Difficulties in Dementia”.
Results:
Overall, thirty patients with bvFTD were included along with their caregivers. Patients with bvFTD showed feeding and swallowing difficulties such as: messy to eat, passivity, coughing and choking, difficulty with some food consistencies and with specific food. Swallowing problems in bvFTD correlated with impaired functionality (p<0.05) and cognition (p<0.05), executive dysfunction (p<0.01) and behavioral features (p<0.01). Caregivers had great difficulty in managing the feeding situation during mealtime, with different characteristics in each dementia stage.
Conclusion:
Patients with bvFTD had inappropriate speed eating, passivity, coughing and choking starting in the mild dementia stage, and these problems worsen in the severe stage. Such difficulties affected caregiver performance during mealtime. The correlations indicated that swallowing difficulties tend to follow cognitive and behavioral decline in patients with bvFTD.
Introduction: The inherited risk of late-onset Alzheimer's disease (AD) is genetically determined. We aimed to examine associations of genetic variants of APOE and ACE with age at AD onset and with ...neuropsychiatric symptoms according to each dementia stage.
Methods: Consecutive outpatients with AD were assessed for demographic features, Clinical Dementia Rating scores, and the 10-item Neuropsychiatric Inventory, and genotyped for rs7412 and rs429358 (APOE haplotypes, Real-Time Polymerase Chain Reactions), and the ACE insertion/deletion polymorphism (Polymerase Chain Reactions). Combined genetic variants of APOE and ACE were associated with age at dementia onset, and with neuropsychiatric symptoms in each dementia stage (adjusted for sex and age at dementia onset).
Results: Over two-thirds of the 238 patients were women, whereas the mean age at dementia onset was 73.82 ± 6.2 years-old. APOE-ϵ4/ϵ4 carriers had earlier dementia onset (p<.001). The ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p=.37) but was not associated with age at dementia onset, regardless of APOE-ϵ4 carrier status. The only results that survived corrections for false discovery rates were higher scores of dysphoria for APOE-ϵ4 carriers (n=122) who also carried ACE deletion/deletion (p=.031). No results survived corrections for false discovery rates for APOE-ϵ4 non-carriers (n=116).
Conclusions: Though only the APOE-ϵ4/ϵ4 haplotype affected AD onset, effects of the ACE insertion/deletion polymorphism over behavioural features might differ according to APOE-ϵ4 carrier status in genetic associations.
Pharmacogenetic effects of statins on clinical changes in Alzheimer's disease (AD) could be mediated by epistatic interactions among relevant genetic variants involved in cholesterol metabolism.
To ...investigate associations of HMGCR (rs3846662), NR1H2 (rs2695121), or CETP (rs5882&rs708272) with cognitive and functional changes in AD, with stratification according to APOEɛ4 carrier status and lipid-lowering treatment with lipophilic statins.
Consecutive outpatients with late-onset AD were screened with cognitive tests, while caregivers scored functionality and global ratings, with prospective neurotranslational associations documented for one year.
Considering n = 190:142 had hypercholesterolemia, 139 used lipophilic statins; minor allele frequencies were 0.379 (rs2695121-T:46.3% heterozygotes), 0.368 (rs5882-G:49.5% heterozygotes), and 0.371 (rs708272-A:53.2% heterozygotes), all in Hardy-Weinberg equilibrium. For APOEɛ4 carriers: rs5882-GG protected from cognitive decline; rs5882-AA caused faster cognitive decline; carriers of rs2695121-CC or rs5882-AA were more susceptible to harmful cognitive effects of lipophilic statins; carriers of rs5882-GG or rs708272-AG had functional benefits when using lipophilic statins. APOEɛ4 non-carriers resisted any cognitive or functional effects of lipophilic statins, while invariability of rs3846662 (all AA) prevented the assessment of HMGCR effects. When assessing CETP haplotypes only: rs5882-GG protected from cognitive and functional decline, regardless of lipophilic statin therapy; lipophilic statins usually caused cognitive and functional harm to carriers of rs5882-A and/or rs708272-A; lipophilic statins benefitted cognition and functionality of carriers of rs5882-G and/or rs708272-G.
Reportedly protective variants of CETP and NR1H2 also slowed cognitive and functional decline particularly for APOEɛ4 carriers, and regardless of cholesterol variations, while therapy with lipophilic statins might affect carriers of specific genetic variants.
In this study, spectroscopic and thermoanalytical techniques were used to characterize the new chemical entity GQ-238 isolated and associated with pharmaceutical excipients (PEG 6000, PVP K-30 and ...Soluplus
®
). The GQ-238 is an indole-thiazolidine analogue with promising antiparasitic activity and effective against worm adult of the
Schistosoma mansoni
and the protozoan
Trypanosoma cruzi
in vitro. These parasites cause diseases considered debilitating, affecting millions of people worldwide. The objective of this research was to perform the physicochemical characterization of GQ-238. X-ray powder diffraction analysis indicated crystalline nature sample, and scanning electron microscopy (SEM) studies showed particles with crystalline needle-like habit. Differential scanning calorimetry showed a crystalline compound having a melting point of 271.4 °C (Δ
H
= 73.8 J g
−1
) and purity of 99.5%. Thermogravimetry showed that the substance was stable up to 290 °C with two-step degradation. Kinetic studies using isothermal and non-isothermal methods have shown that the thermal degradation of the compound follows zero-order kinetics and activation energy of 144.7 kJ mol
−1
. Therefore, the GQ-238 is presented as a pure crystalline powder with high thermal stability.
To identify knowledge gaps regarding new‐onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment ...Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre‐dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late‐onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre‐dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre‐dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.
Postoperative pain is one of the main negative symptoms resulting from surgery and the use of new methods to control this symptom is of ever‐increasing relevance. Opioid‐sparing strategies, such as ...multimodal analgesia, are trends in this scenario. Pregabalin is a well‐established treatment for neuropathic pain; however, it is still controversial in the surgical context for postoperative analgesia. This study investigated the effect of pregabalin on postoperative analgesia in patients undergoing abdominal hysterectomy. It is a prospective, randomised, double‐blind, placebo‐controlled clinical trial. Female patients undergoing abdominal hysterectomy were randomised to use pregabalin (group P1), 300 mg orally 2 h before surgery, or identical placebo pills (group P0). The main outcome includes the postoperative pain index by visual analogue scale (VAS) and McGill's pain questionnaire. Secondary outcomes include opioid consumption and the presence of adverse effects. A value of p < 0.05 was used to reject type I error. Fifty‐five patients were randomised amongst the groups. Patients in group P1 had lower pain rates by VAS scale, both at rest and in active motion, than group P0. In McGill's questionnaire, patients from group P1 also had lower pain rates (12 × 28.5). There was approximately twice as much opioid consumption amongst patients in group P0. Regarding side effects, there was a difference between the two groups only for dizziness, being more incident in group P1. This study suggests that pregabalin is an important adjuvant drug in treating postoperative pain in patients with abdominal hysterectomy.
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