In vivo microstructural heterogeneity of white matter and cognitive correlates in aging using tissue compositional analysis of diffusion magnetic resonance imaging.

BACKGROUND: Age-related cognitive decline is linked to changes in the brain, particularly the deterioration of white matter (WM) microstructure that accelerates after the age of 60. WM deterioration is associated with mild cognitive impairment and dementia, but the origin and role of white matter signal abnormalities (WMSA) seen in standard MRI remain debated due to their heterogeneity. This study explores the potential of single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD), a novel technique that models diffusion data in terms of gray matter (TG ), white matter (Tw ), and cerebrospinal fluid (TC ), to differentiate WMSA from normal-appearing white matter and better understand the interplay between changes in WM microstructure and decline in cognition. METHODS: A total of 189 individuals from the GENIC cohort were included. MRI data, including T1-weighted and diffusion images, were obtained. Preprocessing steps were performed on the diffusion MRI data, followed by the SS3T-CSD. WMSA were segmented using FreeSurfer. Statistical analyses were conducted to assess the association between age, WMSA volume, 3-tissue signal fractions (Tw , TG , and TC ), and neuropsychological variables. RESULTS: Participants above 60 years old showed worse cognitive performance and processing speed compared to those below 60 (p < .001). Age was negatively associated with Tw in normal-appearing white matter (p < .001) and positively associated with TG in both WMSA (p < .01) and normal-appearing white matter (p < .001). Age was also significantly associated with WMSA volume (p < .001). Higher processing speed was associated with lower Tw and higher TG , in normal-appearing white matter (p < .01 and p < .001, respectively), as well as increased WMSA volume (p < .001). Similarly, lower MMSE scores correlated with lower Tw and higher TG in normal-appearing white matter (p < .05). High cholesterol and hypertension were associated with higher WMSA volume (p < .05). CONCLUSION: The microstructural heterogeneity within normal-appearing white matter and WMSA is associated with increasing age and cognitive variation, in cognitively unimpaired individuals. Furthermore, the 3-tissue signal fractions are more specific to potential white matter alterations than conventional MRI measures such as WMSA volume. These findings also support the view that the WMSA volumes may be more influenced by vascular risk factors than the 3-tissue metrics. Finally, the 3-tissue metrics were able to capture associations with cognitive tests and therefore capable of capturing subtle pathological changes in the brain in individuals who are still within the normal range of cognitive performance.

Degeneration of the cholinergic system in individuals with subjective cognitive decline: A systematic review.

BACKGROUND: Subjective cognitive decline (SCD) is a risk factor for future cognitive impairment and dementia. It is uncertain whether the neurodegeneration of the cholinergic system is already present in SCD individuals. We aimed to review the current evidence about the association between SCD and biomarkers of degeneration in the cholinergic system. METHOD: Original articles were extracted from three databases: Pubmed, Web of Sciences, and Scopus, in January 2023. Two researchers screened the studies independently. RESULTS: A total of 11 research articles were selected. SCD was mostly based on amnestic cognitive complaints. Cholinergic system biomarkers included neuroimaging markers of basal forebrain volume, functional connectivity, transcranial magnetic stimulation, or biofluid. The evidence showed associations between basal forebrain atrophy, poorer connectivity of the cholinergic system, and SCD CONCLUSIONS: Degenerative changes in the cholinergic system can be present in SCD. Subjective complaints may help when identifying individuals with brain changes that are associated with cognitive impairment. These findings may have important implications in targeting individuals that may benefit from cholinergic-target treatments at very early stages of neurodegenerative diseases.

Effects of Different Irrigation Regimes, Nitrogen Levels and Storage Conditions on Volatiles of 'Gala' Apple.

With a characteristic flavour and aroma, "Maçã de Alcobaça" are apples produced in the western region of the mainland of Portugal. Given the known influence of pre-harvest cultural techniques and post-harvest conservation methods on fruit quality, this work evaluated the effect of cultural factors and conservation methods on the volatile profile of 'Gala' apples. Tests were carried out during four seasons (2018 to 2021) in two 'Gala' apple orchards (F and S) maintained with different irrigation rates and nitrogen fertilisation [normal irrigation and normal nitrogen (Control, NINN), normal irrigation and excess nitrogen (NIEN), excess irrigation and normal nitrogen (EINN), excess irrigation and excess nitrogen (EIEN)], and under three storage conditions [Controlled Atmosphere + 1-methylcyclopropene (CA+1-MCP), Dynamic Controlled Atmosphere (DCA) and DCA+1-MCP]. The intact fruit volatiles were isolated by headspace solid-phase microextraction (HS-SPME) and analysed by Gas Chromatography with Flame Ionisation Detection and Gas Chromatography-Mass Spectrometry at harvest (T0) and after 8 months of storage (T8). HS-SPME volatiles from 'Gala' apples, obtained at T0 in control conditions, were characterised by trans,trans-α-farnesene dominance (36-69%), followed by hexyl acetate (5-23%) and hexyl hexanoate (3-9%). The four irrigation and nitrogen treatments did not evidence main changes in the apple volatile profile. Instead, storage conditions changed the ratio between compounds; previously undetected compounds attained high percentages and decreased the intensity of the dominant compounds in the control conditions. Although all storage conditions tested changed the volatile profile and emanation intensity, the effect was more accentuated in storage for 8 months with DCA+1-MCP.

Different combinations of monensin and narasin on growth performance, carcass traits, and ruminal fermentation characteristics of finishing beef cattle.

The objective of this study was to evaluate the effects of different combinations of monensin and narasin on finishing cattle. In Exp. 1, 40 rumen-cannulated Nellore steers [initial body weight (BW) = 231 ± 3.64 kg] were blocked by initial BW and assigned to one of the five treatments as follows: Control (CON): no feed additive in the basal diet during the entire feeding period; Sodium monensin (MM) at 25 mg/kg dry matter (DM) during the entire feeding period [adaptation (days 1-21) and finishing (days 22-42) periods]; Narasin (NN) at 13 mg/kg DM during the entire feeding period (adaptation and finishing periods); Sodium monensin at 25 mg/kg DM during the adaptation period and narasin at 13 mg/kg DM during the finishing period (MN); and narasin at 13 mg/kg DM during the adaptation period and sodium monensin at 25 mg/kg DM during the finishing period (NM). Steers fed MM had lower dry matter intake (DMI) during the adaptation period compared to NM (P = 0.02) but not compared to CON, MM, MN, or NN (P ≥ 0.12). No differences in DMI were observed among the treatments during the finishing (P = 0.45) or the total feeding period (P = 0.15). Treatments did not affect the nutrient intake (P ≥ 0.51) or the total apparent digestibility of nutrients (P ≥ 0.22). In Exp. 2, 120 Nellore bulls (initial BW = 425 ± 5.4 kg) were used to evaluate the effects of the same treatments of Exp. 1 on growth performance and carcass characteristics of finishing feedlot cattle. Steers fed NM had greater DMI during the adaptation period compared to CON, MM, and MN (P ≤ 0.03), but no differences were observed between NM and NN (P = 0.66) or between CON, MM, and NN (P ≥ 0.11). No other differences between treatments were observed (P ≥ 12). Feeding narasin at 13 mg/kg DM during the adaptation period increases the DMI compared to monensin at 25 mg/kg DM, but the feed additives evaluated herein did not affect the total tract apparent digestibility of nutrients, growth performance, or carcass characteristics of finishing cattle.

Effect of sires' expected progeny difference for scrotal circumference and juvenile ADG on the puberty of crossbred beef heifers.

The early attainment of puberty in heifers is essential for the profitability of the cow-calf farm. This study aimed to evaluate the impact of juvenile average daily gain (ADG) and sire's expected progeny difference (EPD) on puberty of crossbred beef heifers. Sixty Angus × Nellore heifers early weaned (age = 102 ± 4.3 d; initial BW = 103 ± 4.7 kg) were used in a 2 × 2 factorial arrangement. The factor 1 was the sire's EPD for scrotal circumference, in which heifers born from sires with positive EPD were considered precocious (P), and heifers born from sires with negative EPD were considered non-precocious (NP). The factor 2 was the high (HG; ADG = 0.9 kg; ad libitum) and medium ADG (MG; ADG = 0.7 kg) from 3rd to 7th month of age (1st phase). After 1st phase until puberty, all heifers were fed ad libitum (2nd phase). Statistical analysis was performed by SAS. There was an interaction between factors for DMI in the 1st phase (P = 0.02), which PHG heifers had higher DMI than NPHG. There was no effect on puberty rate, BW, age and BCS at puberty comparing HG vs. MG. However, favorable sires' EPD for scrotal circumference induced a higher proportion of puberty (P 87% vs. NP 59%) at 15 months of age. Thus, the ADG in juvenile age did not affect puberty rate, but sires with positive EPD increased puberty rate of Angus × Nellore heifers in heifers fed a high gain diet.

Effects of lasalocid, narasin, or virginiamycin supplementation on rumen parameters and performance of beef cattle fed forage-based diet.

Two experiments were designed to evaluate the impacts of supplementing lasalocid (LAS), narasin (NAR), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, and blood parameters (Exp. 1), as well as feed intake and performance (Exp. 2) of Nellore cattle consuming a forage-based diet. In Exp. 1, 32 rumen-fistulated Nellore steers (initial shrunk body weight [BW] = 355 ± 4.4 kg) were assigned to a randomized complete block design. Within block, animals were randomly assigned to one of four treatments: 1) forage-based diet without feed additives (CON), 2) CON diet plus 13 mg/kg of dry matter (DM) of NAR, 3) CON diet plus 20 mg/kg of DM of sodium LAS, or 4) CON diet plus 20 mg/kg of DM of VRM. No treatment effects were detected (P ≥ 0.32) for intake and apparent digestibility of nutrients. Steers fed NAR had the lowest (P ≤ 0.01) molar proportion of acetate on day 28, 56, and 112 vs. CON, LAS, and VRM steers, whereas acetate did not differ (P ≥ 0.25) between LAS, VRM, and CON steers from day 28 to 84. On day 112, steers fed LAS had a lower (P < 0.02) molar proportion of acetate vs. VRM and CON, whereas it did not differ between CON and VRM (P > 0.33). Steers receiving NAR had a greater (P ≤ 0.04) ruminal propionate vs. CON, LAS, and VRM, whereas LAS steers had greater (P < 0.04) propionate vs. CON and VRM steers on day 28 and 112, and it did not differ (P > 0.22) between CON and VRM. In Exp. 2, 160 Nellore bulls were blocked by initial shrunk BW (212 ± 3.1 kg) in a 140-d feedlot trial. Diets contained the same treatments used in Exp. 1. Bulls fed NAR had greater (P < 0.02) average daily gain (ADG) vs. CON and VRM, and similar (P = 0.17) ADG between NAR and LAS, whereas ADG did not differ (P > 0.28) between LAS, VRM, and CON bulls. A treatment effect was detected (P = 0.03) for dry matter intake, being greater in NAR vs. CON, LAS, and VRM bulls, and similar (P > 0.48) between CON, LAS, and VRM bulls. A tendency was detected (P = 0.09) for feed efficiency, which was greater (P < 0.02) in NAR bulls vs. CON and VRM, and similar (P = 0.36) between NAR and LAS bulls. From day 112 to 140, bulls receiving NAR were heavier (P < 0.03) vs. CON, LAS, and VRM bulls, but no differences were observed (P > 0.51) between CON, LAS, and VRM bulls. Collectively, ruminal fermentation profile and intake were impacted by NAR supplementation, which partially contributed to the enhanced performance of Nellore bulls receiving a forage-based diet.

Feed additives are nutritional tools that benefit dietary digestibility and nutrient utilization, alter ruminal fermentation routes, and improve cattle growth and efficiency, thus increasing productivity and profitability in beef cattle systems. Nonetheless, most of the current research focuses on supplementing feed additives in high-concentrate diets. Leaving a significant gap in understanding the influence of feed additives in cattle consuming forage-based diets, especially molecules capable of altering the fermentation process and, consequently, beef cattle performance. Therefore, this experiment aimed to evaluate the impacts of supplementing narasin (NAR), lasalocid (LAS), or virginiamycin (VRM) on rumen fermentation parameters, apparent nutrient digestibility, feed intake, and performance of Bos indicus Nellore cattle consuming a forage-based diet. Including commercially available feed additives into forage-based diets did not impact nutrient intake and digestibility of nutrients. The inclusion of NAR affected ruminal fermentation parameters toward propionate production, positively contributing to animal performance. Ruminal fermentation characteristics and animal growth were not impacted by dietary LAS and VRM, which could be attributed to the dose used in the current experiment, despite the manufacturer's recommendation. This research provides insights into NAR as an important feed additive for forage-based beef cattle diets.

The block design subtest of the Wechsler adult intelligence scale as a possible non-verbal proxy of cognitive reserve.

Objectives: To investigate the potential of the Block design subtest of the Wechsler Adults Intelligence Scale as a non-verbal proxy of cognitive reserve. Method: A total of 391 cognitively unimpaired participants were included in this study. The association between the Block design subtest and the Information subtest (an established verbal proxy of cognitive reserve) from the WAIS, as well as the association of the two subtests with a Cognitive Reserve Questionnaire (CRQ) were tested. In addition, multiple linear regression models were conducted to investigate the association of the Block design and Information subtests with cognitive performance. The capacity of the Block design subtest to minimize the negative effect of an older age over cognitive performance was also assessed and this effect was compared with that of the Information subtest. The four cognitive domains included were: verbal memory, visual-visuospatial memory, executive-premotor functions and processing speed. Results: The Block design subtest correlated positively with both the Information subtest and the CRQ. A statistically significant association was observed between the Block design subtest and all four cognitive domains. Higher scores in the Block design subtest minimized the negative effect of aging on the cognitive domains of visual-visuospatial memory and executive-premotor functions, in a similar way to the results obtained for the Information subtest. Conclusion: The Block design subtest is significantly correlated with two established proxies of cognitive reserve: it correlates with cognitive performance and high scores in Block design have the capacity to minimize the negative effect of an older age on cognitive performance. Therefore, the results suggest that the corrected Block design subtest could be considered as a non-verbal proxy of cognitive reserve.

Effects of injectable and intravaginal progesterone on ewes' reproductive performance at breeding season beginning.

Progesterone (P4) is a steroid hormone that has a regulatory role in the female reproductive system. Studies on the effects of injectable progesterone on ewes are scarce, mainly related to their reproductive responses in the breeding season. This study aimed to compare reproductive performance and serum P4 concentration using injectable or intravaginal P4 in ewes. Two hundred and forty and eight Santa Inês x Dorper ewes (BW; 52.67 ± 11.76 kg; mean ± SE), body condition score (BCS; 2.5 ± 0.8; scale of 1-5), were distributed in four treatments: (i) Control: without administration of P4; (ii) CIDR: intravaginal implantation of 330 mg of P4 for 7 days; (iii) 1P4: 15 mg of P4 intramuscular (IM); and (iv) 2P4I: 30 mg of P4 IM. The first 18 days of breeding season were considered the synchronization period. Except for ewes in the control group, all other ewes received 263 µg IM of cloprostenol sodium for lysis of eventual CL at 24 h before the P4 treatment. After the synchronization period, all ewes were kept together with males for extra 28 days in the breeding season. At the beginning of breeding season, 90% of the ewes had serum P4 concentration less than 1 ng/mL. The estrus rate was greater (P < 0.01) in ewes on the CIDR treatment, with similar estrus rate among the other treatments. The P4 implant was able to keep blood P4 concentration greater than 1 ng/mL in ewes that received an implant of P4 during the 7 days. After implant removal, there was a great increase in the estrus manifestation on ewes in the CIDR treatment, leading to an increase in pregnancy rate at the beginning of breeding season. The current study demonstrated that ewes that received an intramuscular injection of 15 or 30 mg of P4 had similar reproductive performance than ewes that did not receive any P4 intramuscular injection. However, when ewes were implanted with P4 (CIDR), these animals had an increase in estrus manifestation, leading to greater pregnancy earlier during the breeding season.

Specific pattern of linguistic impairment in Parkinson's disease patients with subjective cognitive decline and mild cognitive impairment predicts dementia.

OBJECTIVE: Parkinson's disease patients with subjective cognitive decline (PD-SCD) and mild cognitive impairment (PD-MCI) have an increased risk of dementia (PDD). Thus, the identification of early cognitive changes that can be useful predictors of PDD is a highly relevant challenge. Posterior cortically based functions, including linguistic processes, have been associated with PDD. However, investigations that have focused on linguistic functions in PD-MCI are scarce and none of them include PD-SCD patients. Our aim was to study language performance in PD-SCD and PD-MCI. Moreover, language subcomponents were considered as predictors of PDD. METHOD: Forty-six PD patients and twenty controls were evaluated with a neuropsychological protocol. Patients were classified as PD-SCD and PD-MCI. Language production and comprehension was assessed. Follow-up assessment was conducted to a mean of 7.5 years after the baseline. RESULTS: PD-MCI patients showed a poor performance in naming (actions and nouns), action generation, anaphora resolution and sentence comprehension (with and without center-embedded relative clause). PD-SCD showed a poor performance in action naming and action generation. Deficit in action naming was an independent risk factor for PDD during the follow-up. Moreover, the combination of deficit in action words and sentence comprehension without a center-embedded relative clause was associated with a greater risk. CONCLUSIONS: The results are of relevance because they suggest that a specific pattern of linguistic dysfunctions, that can be present even in the early stages of the disease, can predict future dementia, reinforcing the importance of advancing in the knowledge of linguistic dysfunctions in predementia stages of PD.

Fast three-dimensional image generation for healthy brain aging using diffeomorphic registration.

Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject-specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state-of-the-art deep learning-based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three-dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1-weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies-3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state-of-the-art results. The assumption of linear brain decay was accurate in these cohorts (R2  ∈ [.924, .940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning-based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points.

A deep learning model for brain age prediction using minimally preprocessed T1w images as input.

Introduction: In the last few years, several models trying to calculate the biological brain age have been proposed based on structural magnetic resonance imaging scans (T1-weighted MRIs, T1w) using multivariate methods and machine learning. We developed and validated a convolutional neural network (CNN)-based biological brain age prediction model that uses one T1w MRI preprocessing step when applying the model to external datasets to simplify implementation and increase accessibility in research settings. Our model only requires rigid image registration to the MNI space, which is an advantage compared to previous methods that require more preprocessing steps, such as feature extraction. Methods: We used a multicohort dataset of cognitively healthy individuals (age range = 32.0-95.7 years) comprising 17,296 MRIs for training and evaluation. We compared our model using hold-out (CNN1) and cross-validation (CNN2-4) approaches. To verify generalisability, we used two external datasets with different populations and MRI scan characteristics to evaluate the model. To demonstrate its usability, we included the external dataset's images in the cross-validation training (CNN3). To ensure that our model used only the brain signal on the image, we also predicted brain age using skull-stripped images (CNN4). Results: The trained models achieved a mean absolute error of 2.99, 2.67, 2.67, and 3.08 years for CNN1-4, respectively. The model's performance in the external dataset was in the typical range of mean absolute error (MAE) found in the literature for testing sets. Adding the external dataset to the training set (CNN3), overall, MAE is unaffected, but individual cohort MAE improves (5.63-2.25 years). Salience maps of predictions reveal that periventricular, temporal, and insular regions are the most important for age prediction. Discussion: We provide indicators for using biological (predicted) brain age as a metric for age correction in neuroimaging studies as an alternative to the traditional chronological age. In conclusion, using different approaches, our CNN-based model showed good performance using one T1w brain MRI preprocessing step. The proposed CNN model is made publicly available for the research community to be easily implemented and used to study ageing and age-related disorders.

Influence of mild cognitive impairment on clinical and functional prognosis in older candidates for cardiac surgery.

Introduction: In this study, we analyzed the prognostic impact of mild cognitive impairment (MCI) prior to cardiac surgery on 12-month clinical outcomes in older patients. Method: We performed a longitudinal prospective study of 48 patients undergoing cardiac surgery and 26 neurologically healthy participants aged 65 years or older. All participants underwent a neuropsychological assessment. Functional status, quality of life and frailty were assessed in candidates for surgery. One year after surgery, 24 patients remained in the study. Results: Mild cognitive impairment (MCI) was diagnosed in 35% of the patients at baseline. Postsurgical changes in functionality consisted of a tendency toward impaired basic activities of daily living (BADL) in the MCI group and a statistically significant worsening in instrumental activities of daily living (IADL) in women with MCI. Changes in quality of life consisted of a significant improvement in anxiety-depression in the MCI group and a tendency toward greater pain-discomfort in the non-MCI group. Cognitive status significantly declined only in the non-MCI group. Neither group showed significant changes in frailty. Relative risk analysis showed that patients with a diagnosis of MCI at baseline had a higher risk of cognitive decline at follow-up, while those without a diagnosis of MCI at baseline had a lower risk of impaired IADL. No association was found between MCI and resource use. Preoperative impairment in memory, visuospatial and executive functions was significantly associated with loss of quality of life at follow-up. Impairment of memory and visuospatial function was significantly associated with cognitive decline. Preserved memory was associated with a lower risk of impaired BADL at follow-up. Conclusion: The present study provides clue on the impact of MCI in candidates for cardiac surgery. Preoperative detection of cognitive impairment could be highly valuable to help guide pre- and post-operative management.

Cerebrovascular damage in subjective cognitive decline: A systematic review and meta-analysis.

BACKGROUND: Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer's Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers. METHOD: This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed. RESULTS: Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD. CONCLUSION: Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.

The effect of progesterone length in timed AI in ewes.

This study aimed to evaluate the reproductive performance of ewes submitted to timed AI protocol with 7 (D7) or 9 (D9) days of progesterone. A total of 220 crossbred ewes (Doper × Santa Ines) were distributed in the treatments according to body weight (52.67 ± 11.76 kg), body condition score (2.5 ± 0.8; scale of 1-5), and the female category (multiparous, nulliparous and primiparous). Ewes received an intravaginal device of 0.3 g of progesterone (CIDR® Easy breed) on day 0, keeping in ewes for 7 or 9 days, which were the experimental treatments. At the time of P4 withdrawal, ewes received 300 IU of eCG (Novormon®) and 6.70 mg of dinoprost tromethamine (Lutalyse®). Insemination by laparoscopy was performed between 46 and 59 h after device removal, lasting from 1 to 5 min/ewe, which did not differ between protocols. The estrus detection rate was higher in the 9-day protocol compared to the 7-day protocol (82% and 65%, respectively, P = 0.0096). However, the 7-day protocol tended to increase pregnancy rate on the TAI compared to the 9-day protocol (45% and 33%, respectively, P = 0.09). The plasma concentration of progesterone at device removal was higher in the 7-day protocol than in the 9-day protocol (2.35 and 1.22 ng/mL, respectively, P = 0.04). We conclude that reducing the length of the estrus synchronization protocol to 7 days is recommended, which improved the reproductive response in ewes.

The Cognitive Connectome in Healthy Aging.

Objectives: Cognitive aging has been extensively investigated using both univariate and multivariate analyses. Sophisticated multivariate approaches such as graph theory could potentially capture unknown complex associations between multiple cognitive variables. The aim of this study was to assess whether cognition is organized into a structure that could be called the "cognitive connectome," and whether such connectome differs between age groups. Methods: A total of 334 cognitively unimpaired individuals were stratified into early-middle-age (37-50 years, n = 110), late-middle-age (51-64 years, n = 106), and elderly (65-78 years, n = 118) groups. We built cognitive networks from 47 cognitive variables for each age group using graph theory and compared the groups using different global and nodal graph measures. Results: We identified a cognitive connectome characterized by five modules: verbal memory, visual memory-visuospatial abilities, procedural memory, executive-premotor functions, and processing speed. The elderly group showed reduced transitivity and average strength as well as increased global efficiency compared with the early-middle-age group. The late-middle-age group showed reduced global and local efficiency and modularity compared with the early-middle-age group. Nodal analyses showed the important role of executive functions and processing speed in explaining the differences between age groups. Conclusions: We identified a cognitive connectome that is rather stable during aging in cognitively healthy individuals, with the observed differences highlighting the important role of executive functions and processing speed. We translated the connectome concept from the neuroimaging field to cognitive data, demonstrating its potential to advance our understanding of the complexity of cognitive aging.

The interplay between gray matter and white matter neurodegeneration in subjective cognitive decline.

AIMS: To investigate the interplay between gray matter (GM) and white matter (WM) neurodegeneration in subjective cognitive decline (SCD), including thickness across the whole cortical mantle, hippocampal volume, and integrity across the whole WM. METHODS: We included 225 cognitively unimpaired individuals from a community-based cohort. Subjective cognitive complaints were assessed through 9 questions covering amnestic and non-amnestic cognitive domains. In our cohort, 123 individuals endorsed from one to six subjective cognitive complaints (i.e. they fulfilled the diagnostic criteria for SCD), while 102 individuals reported zero complaints. GM neurodegeneration was assessed through measures of cortical thickness across the whole mantle and hippocampal volume. WM neurodegeneration was assessed through measures of mean diffusivity (MD) across the whole WM skeleton. Mediation analysis and multiple linear regression were conducted to investigate the interplay between the measures of GM and WM neurodegeneration. RESULTS: A higher number of complaints was associated with reduced hippocampal volume, cortical thinning in several frontal and temporal areas and the insula, and higher MD across the WM skeleton, with a tendency to spare the occipital lobe. SCD-related cortical thinning and increased MD were associated with each other and jointly contributed to complaints, but the contribution of cortical thinning to the number of complaints was stronger. CONCLUSIONS: Neurodegeneration processes affecting the GM and WM seem to be associated with each other in SCD and include brain areas other than those typically targeted by Alzheimer's disease. Our findings suggest that SCD may be a sensitive behavioral marker of heterogeneous brain pathologies in individuals recruited from the community.

Effects of narasin supplementation frequency on intake, ruminal fermentation parameters, and nutrient digestibility of Bos indicus Nellore steers fed with forage-based diets.

The study aimed to evaluate if the frequency of narasin supplementation impacts dry matter intake, ruminal fermentation parameters, and apparent digestibility of nutrient in Nellore (Bos indicus) steers fed forage-based diets. A total of 32 rumen-cannulated Nellore steers (initial body weight [BW] = 317 ± 27 kg; age =18 ± 1 mo) were assigned to individual pens in a randomized complete block design according to their initial shrunk BW. Within block, steers were randomly assigned to 1 of 4 treatments: 1) forage-based diet without the addition of narasin (CON; n = 8), 2) CON diet plus 13 ppm of narasin every 24 h (N24; n = 8), 3) CON diet plus 26 ppm of narasin every 48 hours (N48; n = 8), or 4) CON diet plus 39 ppm of narasin every 72 hours (N72; n = 8). The experimental period lasted 30 d, with 18 d for diet adaptation and 12 d for sample collection. The experimental diets contained 95% of Tifton-85 (Cynodon dactylon spp.) haylage and 5% ground corn used as a delivery vehicle for narasin. Ruminal fluid was obtained from d 25 to 30 at 6 h after feeding to determine ruminal fermentation parameters. Narasin supplementation frequency did not affect (P ≥ 0.22) nutrient intake and total tract apparent digestibility. Steers fed N24 and N48 had reduced (P = 0.02) ruminal acetate concentration compared with CON and N72. Daily supply of narasin increased (P = 0.01) the molar proportion of propionate compared with CON and N72, and it did not differ between N24 vs. N48, N48 vs. N72, and N72 vs. CON. Also, N48 steers had greater (P = 0.01) rumen propionate concentration compared with CON. The N24 treatment decreased the Ac:Prop (P = 0.01) and AcBut:Prop (P = 0.02) ratio compared with CON and N72, while N48 had reduced (P = 0.01) Ac:Prop and AcBut:Prop ratio when compared with CON steers. Steers fed N24 and N48 had greater (P = 0.04) ruminal short-chain fatty acids compared with CON, but it did not differ (P > 0.11) between N24, N48, and N72. Supplementing narasin to steers fed forage-based diets decreased (P < 0.01) ruminal ammonia concentration compared with CON steers regardless of supplementation frequency, being the least result observed for N24 steers. Collectively, narasin supplementation frequency affected fermentation parameters without altering the nutrient intake and total tract apparent digestibility. Hence, decreasing frequency of narasin supplementation to Nellore steers fed a forage-based diet did not reduce the capacity to modulate rumen fermentation parameters.

Cerebrovascular Disease and Depressive Symptomatology in Individuals With Subjective Cognitive Decline: A Community-Based Study.

Subjective cognitive decline (SCD) may be the first sign of Alzheimer's disease (AD), but it can also reflect other pathologies such as cerebrovascular disease or conditions like depressive symptomatology. The role of depressive symptomatology in SCD is controversial. We investigated the association between depressive symptomatology, cerebrovascular disease, and SCD. We recruited 225 cognitively unimpaired individuals from a prospective community-based study [mean age (SD) = 54.64 (10.18); age range 35-77 years; 55% women; 123 individuals with one or more subjective cognitive complaints, 102 individuals with zero complaints]. SCD was assessed with a scale of 9 memory and non-memory subjective complaints. Depressive symptomatology was assessed with established questionnaires. Cerebrovascular disease was assessed with magnetic resonance imaging markers of white matter signal abnormalities (WMSA) and mean diffusivity (MD). We combined correlation, multiple regression, and mediation analyses to investigate the association between depressive symptomatology, cerebrovascular disease, and SCD. We found that SCD was associated with more cerebrovascular disease, older age, and increased depressive symptomatology. In turn, depressive symptomatology was not associated with cerebrovascular disease. Variability in MD was mediated by WMSA burden, presumably reflecting cerebrovascular disease. We conclude that, in our community-based cohort, depressive symptomatology is associated with SCD but not with cerebrovascular disease. In addition, depressive symptomatology did not influence the association between cerebrovascular disease and SCD. We suggest that therapeutic interventions for depressive symptomatology could alleviate the psychological burden of negative emotions in people with SCD, and intervening on vascular risk factors to reduce cerebrovascular disease should be tested as an opportunity to minimize neurodegeneration in SCD individuals from the community.

Functional Connectivity and Compensation of Phonemic Fluency in Aging.

Neural compensatory mechanisms associated with broad cognitive abilities have been studied. However, those associated with specific cognitive subdomains (e.g., verbal fluency) remain to be investigated in healthy aging. Here, we delineate: (a) neural substrates of verbal (phonemic) fluency, and (b) compensatory mechanisms mediating the association between these neural substrates and phonemic fluency. We analyzed resting-state functional magnetic resonance imaging from 133 right-handed, cognitively normal individuals who underwent the Controlled Oral Word Association Test (COWAT) to record their phonemic fluency. We evaluated functional connectivity in an established and extended language network comprising Wernicke, Broca, thalamic and anti-correlated modules. (a) We conducted voxel-wise multiple linear regression to identify the brain areas associated with phonemic fluency. (b) We used mediation effects of cognitive reserve, measured by the Wechsler Adult Intelligence Scale-Information subtest, upon the association between functional connectivity and phonemic fluency tested to investigate compensation. We found that: (a) Greater functional connectivity between the Wernicke module and brain areas within the anti-correlated module was associated with better performance in phonemic fluency, (b) Cognitive reserve was an unlikely mediator in younger adults. In contrast, cognitive reserve was a partial mediator of the association between functional connectivity and phonemic fluency in older adults, likely representing compensation to counter the effect of aging. We conclude that in healthy aging, higher performance in phonemic fluency at older ages could be attributed to greater functional connectivity partially facilitated by higher cognitive reserve, presumably reflecting compensatory mechanisms to minimize the effect of aging.

Functional results of swallowing and aspiration after oral cancer treatment and microvascular free flap reconstruction: A retrospective observational assessment.

This study aimed to assess the functional swallowing outcomes in cohort of oral cancer patients treated with tumor resection and reconstruction by means of microvascular free flaps. Duration from onset to the last examination was classified into three periods: less than 12 months, from 13 to 24 months, and more than 24 months. Type of feeding, dysphagia, and laryngeal aspiration were the dependent variables, and the study was mainly focused on the data from the multivariate analysis. Fifty-one patients were included in the study. Twenty-one patients had dysphagia, 11 showed stasis in vallecula and pyriform sinuses, 9 experienced laryngeal penetration, and 8 aspirations. Surgery combined with radiochemotherapy was associated with a higher prevalence of dysphagia (p = 0.03). Frequency of dysphagia was higher in the first year after treatment and less frequent after 24 months (p = 0.003). Dysphagia was associated with laryngeal penetration (p = 0.001), and this with aspiration (p < 0.0005). In conclusion, as it seems that the method of reconstruction has a major influence on swallowing, when there are relevant alternatives in the way the reconstruction is done, always the approach should be chosen that reduces dysphagia to a minimum.