Several pathologic processes might contribute to the degeneration of the cholinergic system in aging. We aimed to determine the contribution of amyloid, tau, and cerebrovascular biomarkers toward the ...degeneration of cholinergic white matter (WM) projections in cognitively unimpaired individuals.
The contribution of amyloid and tau pathology was assessed through CSF levels of the Aβ
ratio and phosphorylated tau (p-tau). CSF Aβ
levels were also measured. Cerebrovascular pathology was assessed using automatic segmentations of WM lesions (WMLs) on MRI. Cholinergic WM projections (i.e., cingulum and external capsule pathways) were modeled using tractography based on diffusion tensor imaging data. Sex and APOE ε4 carriership were also included in the analysis as variables of interest.
We included 203 cognitively unimpaired individuals from the H70 Gothenburg Birth Cohort Studies (all individuals aged 70 years, 51% female). WM lesion burden was the most important contributor to the degeneration of both cholinergic pathways (increase in mean square error IncMSE = 98.8% in the external capsule pathway and IncMSE = 93.3% in the cingulum pathway). Levels of Aβ
and p-tau also contributed to cholinergic WM degeneration, especially in the external capsule pathway (IncMSE = 28.4% and IncMSE = 23.4%, respectively). The Aβ
ratio did not contribute notably to the models (IncMSE<3.0%). APOE ε4 carriers showed poorer integrity in the cingulum pathway (IncMSE = 21.33%). Women showed poorer integrity of the external capsule pathway (IncMSE = 21.55%), which was independent of amyloid status as reflected by the nonsignificant differences in integrity when comparing amyloid-positive vs amyloid-negative women participants (T
= -1.55;
= 0.123).
In cognitively unimpaired older individuals, WMLs play a central role in the degeneration of cholinergic pathways. Our findings highlight the importance of WM lesion burden in the elderly population, which should be considered in the development of prevention programs for neurodegeneration and cognitive impairment.
The mortality rate of patients with anti-neutrophil cytoplasm antibody -associated vasculitis (AAV) is higher than the general population. To date, no studies have evaluated the factors associated ...with unfavorable outcomes in Brazilian patients, who represent a miscegenated population. Our objective was to identify clinical and laboratory features associated with mortality in Brazilian patients with AAV.One hundred twenty eight patients fulfilling the American College of Rheumatology and Chapel Hill Classification Criteria followed between 2000 and 2018 in our Rheumatology Outpatient Clinics were included. Data were obtained from an ongoing electronic database. Patients were divided into 2 groups (dead or alive in 2018), and disease activity (Birmingham vasculitis activity score BVAS), vasculitis-related damage (VDI), and laboratory parameters were compared at the most recent attendance and at the last attendance before death.Of the 128 patients followed, 78.9% had granulomatosis with polyangiitis, 16.4% had eosinophilic granulomatosis with polyangiitis, and 4.6% had microscopic polyangiitis. In 2018, 78 patients were alive, 25 had died, and 25 had lost contact. The main cause of death was infection. According to the univariate analysis, the Birmingham vasculitis activity score, VDI, and glucocorticoid dose were higher in the group of patients who died. Laboratorial features related to mortality were creatinine, hemoglobin, erythrocyte sedimentation ratio, and C-reactive protein (CRP). Logistic regression analysis showed that high VDI, creatinine levels, and CRP levels were independent factors associated with mortality. Survival was significantly decreased in patients with renal impairment.This is the first study to use this approach performed in a Brazilian population and it showed that damage index, renal impairment, and CRP levels were associated with mortality in a miscegenated population with AAV.
Since the last decade, several studies have reported the presence and effects of pharmaceutical residues in the marine environment, especially those of the antihypertensive class, such as losartan. ...However, there is little knowledge about the physiological effects of losartan in marine invertebrates regarding its behavior under possible coastal ocean acidification scenarios. The objective of this study was to evaluate biological effects on marine organisms at different levels of the biological organization caused by the compound losartan in water and sediment under coastal ocean acidification scenarios. Water and sediment samples were collected at five sites around the Santos Submarine Sewage outfall (SSO) and two sites around the Guarujá Submarine Sewage Outfall (GSO). Losartan was found in concentrations ranging from <LOD to 7.63 ng/L in water and from <LOQ to 3.10 ng/g in sediments. Statistical analysis showed interactive effects pH and losartan on the toxicity results. The water toxicity test with Echinometra lucunter embryos/larvae showed LOECs 50–100 mg/L, with values decreasing as the pH decreased. In the sediment assays, LOEC value for sea urchin embryo-larval development was 1.0 μg/g for all tested pHs. Regarding the lysosomal membrane stability assays with adult bivalves, a LOEC of 3000 ng/L was found for Perna perna in water exposure (both at pH 8.0 and 7.6). Effects for Mytella guyanensis were observed at environmentally relevant concentrations in sediment (LOEC = 3 ng/g at pH 8.0 and 7.6). This study demonstrated that coastal ocean acidification by itself causes effects on marine invertebrates, but can also increase the negative effects of losartan in waterborne exposure. There is a need to deepen the studies on the ecotoxicity of pharmaceutical residues and acidification of the marine environment.
Display omitted
•Losartan was quantified in samples of marine water (up to 7.63 ng/L) and sediment (up to 3.10 ng/g).•Sediment spiked with an environmental concentration of losartan affected lysosomal stability.•Losartan effects were pH dependent and pH effects were dependent on the concentration of losartan.•Ocean acidification exacerbates the negative effects of losartan in waterborne exposure.
Ocean coastal acidification can exacerbate negative effects of losartan to marine organisms.
Brain gray- and white matter changes is well described in alcohol-dependent elderly subjects; however, the effect of lower levels of alcohol consumption on the brain is poorly understood. We ...investigated the impact of different amounts of weekly alcohol consumption on brain structure in a population-based sample of 70-year-olds living in Gothenburg, Sweden. Cross-sectional data from 676 participants from The Gothenburg H70 Birth Cohort Study 2014–16 were included. Current alcohol consumers were divided into seven groups based on self-reported weekly amounts of alcohol consumption in grams (g) (0–50 g/week, used as reference group, 51–100 g/week, 101–150 g/week, 151–200 g/week, 201–250 g/week, 251–300 g/week, and > 300 g/week). Subcortical volumes and cortical thickness were assessed on T1-weighted structural magnetic resonance images using FreeSurfer 5.3, and white matter integrity assessed on diffusion tensor images, using tract-based statistics in FSL. General linear models were carried out to estimate associations between alcohol consumption and gray- and white matter changes in the brain. Self-reported consumption above 250 g/week was associated with thinning in the bilateral superior frontal gyrus, the right precentral gyrus, and the right lateral occipital cortex, in addition to reduced fractional anisotropy (FA) and increased mean diffusivity (MD) diffusively spread in many tracts all over the brain. No changes were found in subcortical gray matter structures. These results suggest that there is a non-linear relationship between alcohol consumption and structural brain changes, in which loss of cortical thickness only occur in non-demented 70-year-olds who consume more than 250 g/week.
Spinal intradural extramedullary (ID-EM) tumors are pathologies widely treated through a classical open approach. However, minimally invasive surgery is gaining traction as a comparable treatment ...option because it carries less morbidity and may reduce healthcare costs.This study aimed to compare the clinical and functional outcomes of open versus minimally invasive approaches for patients with ID-EM tumors. We performed a retrospective analysis on prospectively collected data from patients with ID-EM tumors submitted to surgery. Baseline features and operative variables were compared, including surgery duration and estimated blood loss (EBL). Postoperative data covered tumor histology, length of stay (LOS), complication(s), and neurological status (Medical Research Council (MRC) scale) at the last follow-up.In total, 46 patients were included: 30 (65.2%) operated through an open approach and 16 (34.8%) through a minimally invasive surgical (MIS) approach. The predominant histology type was schwannomas (43.5%). Lesions more frequently affected the lumbar spine (34.8%). The tumor dimensions were similar in both cohorts. The minimally invasive approach was on average 76.7 min faster and correlated positively with less EBL (140 mL less than that of the open approach). Patients in the MIS group had shorter LOSs (5.63 days vs. 17.27 days) and had fewer postoperative complications. No significant difference in functional outcome was found.MIS is as effective as the traditional approach in achieving comparable functional outcomes, with advantages such as shorter surgery durations, less blood loss, and shorter hospital LOSs.
Cervical spondylosis is the leading cause of cervical myelopathy. When surgery is indicated, it is commonly addressed through an anterior or posterior cervical approach, such as cervical discectomy ...and fusion (ACDF) or laminectomy and fusion (LMF). Besides their own merits, each one has specific approach- or device-related complications, such as dysphagia, significant postoperative pain, wound infection, adjacent segment degeneration (ASD), and pseudoarthrosis. Through a tissue-sparing minimally invasive technique, posterior cervical fusion (PCF) has shown unfolding compelling evidence of biomechanical stability, good clinical outcomes, and high fusion rates, with fewer complications and better econometrics. On the basis of our own experience, we discuss here the indications, advantages, and drawbacks of minimally invasive PCF.
Cervical spondylotic myelopathy (CSM) can be successfully decompressed via either anterior cervical corpectomy and fusion (ACCF) or posterior laminectomy with fusion (LMF). However, few studies have ...compared the isolated effect of both techniques on cervical sagittal balance, a surrogate end point for clinical outcomes.We aimed to compare the sagittal balance radiological outcomes of ACCF against LMF. A case-matched controlled study of radiological cervical alignment parameters (C0-2, C2-3, index angles, T1 slope, and sagittal vertical axis (SVA)) in two groups of patients was performed by using pre- and postoperative neutral cervical X-rays.In total, 34 patients were enrolled (ACCF n = 17; LMF n = 17). The mean preoperative C2-7 angle was similar (11.58 ± 16.00° for ACCF; 13.36 ± 12.21° for LMF) in both cohorts. Both led to a loss of lordosis (-2.68 ± 13.8°, p = 0.43; -2.94 ± 11.5°, p = 0.31, respectively). At the C0-2, the two operations induced opposite variations (-0.9 ± 8.0°, p = 0.709 for ACCF; 3.5 ± 15.4°, p = 0.357 for LMF). ACCF led to a significant increase in SVA (7.1 ± 11.9 mm, p = 0.002). The C2-3 disk angle more pronouncedly increased with LMF.Both techniques show an equivalent kyphotic effect, with a greater disadvantage for ACCF. The negative impact on SVA changes is greater with ACCF. Both affect the C0-2 unit, with a tendency for kyphosis with ACCF and one for lordosis with LMF. When choosing the appropriate decompression and fusion technique, preoperative sagittal balance parameters should be included in the decision-making process.
The armamentarium of surgical treatment options for lumbar spondylolisthesis (LS) includes decompression alone, stabilization with interlaminar devices, or instrumented fusion, through open or ...minimally invasive approaches. Despite its safe profuse use in distinctive lumbar spine disorders, using percutaneous pedicle screws (PPSs) alone to stabilize LS has never been described before. We performed a retrospective study of prospectively collected data, enrolling 24 patients with LS and scrutinizing clinical and radiological outcomes. A statistically significant decrease in visual analog scale (VAS) scores (p < 0.001) and Oswestry Disability Index (ODI) scores (p < 0.001) was observed, as was a reduction in the intake of acetaminophen after surgery (p = 0.022). In the long-term, PPS effectively reduced the index-level range of motion (p < 0.001), reduced preoperative slippage (p = 0.03), and maintained foraminal height, thus accounting for the positive clinical outcomes. It induced a significant segmental kyphotic effect (p < 0.001) that was compensated for by a favorable increase in the pelvic incidence minus lumbar lordosis (PI-LL) index (0.028).
Studies involving the interaction between musical mode and tempo on time perception have been carried out through comparisons between a single major mode and a single minor mode, presented in ...different tempi. However, classifying the modes only into major and minor has not been considered sufficient. The purpose of this study was to verify the influence of the musical mode and tempo interaction on time perception analyzing the effect of different modes performed in the slow, moderate and fast tempi. Fifty undergraduate students of both sexes individually listened to 12 musical excerpts (4 modes – Ionian, Mixolydian, Dorian and Aeolian – and 3 tempi – 72 bpm, 114 bpm, and 184 bpm), one excerpt at a time. After each excerpt, the participants performed a time-reproduction task, in which they had to press a button (beginning of the task), recal the duration of each excerpt and press a button again (end of the task). Results showed no interaction between mode and tempi and no differences between musical modes, regardless of tempo. However, regardless of the mode, excerpts in slow tempo was judged shorter than in moderate and fast tempi, respectively, and excerpts in moderate tempo was judged shorter than excerpts in fast tempo. These results can contribute to understanding the psychological processes of attention, memory and expectancy related to the perception of time in music listening situations.
•The tempo of the musical stimulus affects the subjective time.•The emotional valence of musical stimulus is modulated by emotional arousal.•The interaction of mode and tempo affects the subjective time.•Different modes associate with different emotions may affect subjective time.•The use of modes is a tool to a multidimensional approach in music.
PDF
