Acute effects of a ketone monoester, whey protein, or their coingestion on mTOR trafficking and protein-protein colocalization in human skeletal muscle.

We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their coingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their coingestion on mechanistic target of rapamycin (mTOR)-related protein-protein colocalization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24.2 ± 4.1 yr) ingested either: 1) 0.36 g·kg-1 bodyweight of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET + PRO). Muscle biopsies were obtained in the overnight postabsorptive state (basal conditions), and at 120 and 300 min in the postprandial period for immunofluorescence assessment of protein translocation and colocalization of mTOR-related signaling molecules. All treatments resulted in a significant (Interaction: P < 0.0001) decrease in tuberous sclerosis complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) colocalization at 120 min versus basal; however, the decrease was sustained at 300 min versus basal (P < 0.0001) only in KET + PRO. PRO and KET + PRO increased (Interaction: P < 0.0001) mTOR-Rheb colocalization at 120 min versus basal; however, KET + PRO resulted in a sustained increase in mTOR-Rheb colocalization at 300 min that was greater than KET and PRO. Treatment intake increased mTOR-wheat germ agglutinin (WGA) colocalization at 120 and 300 min (Time: P = 0.0031), suggesting translocation toward the fiber periphery. These findings demonstrate that ketone monoester intake can influence the spatial mechanisms involved in the regulation of mTORC1 in human skeletal muscle.NEW & NOTEWORTHY We explored the effects of a ketone monoester (KET), whey protein (PRO), or their coingestion (KET + PRO) on mTOR-related protein-protein colocalization and intracellular trafficking in human muscle. All treatments decreased TSC2-Rheb colocalization at 120 minutes; however, KET + PRO sustained the decrease at 300 min. Only PRO and KET + PRO increased mTOR-Rheb colocalization; however, the increase at 300 min was greater in KET + PRO. Treatment intake increased mTOR-WGA colocalization, suggesting translocation to the fiber periphery. Ketone bodies influence the spatial regulation of mTOR.

A multimodal exercise countermeasure prevents the negative impact of head-down tilt bed rest on muscle volume and mitochondrial health in older adults.

Mitochondrial dysfunctions are thought to contribute to muscle atrophy and weakness that develop during ageing and mechanical unloading caused by immobilization, bed rest and microgravity. Older adults are at greater risk of developing muscle and mitochondrial dysfunctions in response to unloading. Although exercise is well known to promote muscle and mitochondrial health, its protective effect during mechanical unloading in older adults remains largely unexplored. Here, we investigated the impact of 14 days of head-down tilt bed rest (HDBR) with and without a multimodal exercise countermeasure in older men and women (55-65 years). Leg muscle volume was assessed using magnetic resonance imaging. Biopsies of the vastus lateralis were performed to assess markers of mitochondrial content, respiration, reactive oxygen species (ROS) production and calcium retention capacity (mCRC). Indices of mitochondrial quality control (MQC), including markers of fusion (MFN1 and 2), fission (Drp1), mitophagy (Parkin) and autophagy (p62 and LC3I and II) were measured using immunoblots. Muscle cross-sections were stained for neural cell adhesion molecule (NCAM, a marker of denervation). HDBR triggered muscle atrophy, decreased mitochondrial content and respiration and increased mitochondrial ROS production. HDBR had no impact on mCRC or MQC markers but increased markers of autophagy and denervation. Exercise prevented the deleterious effects of HDBR on leg muscle volume, mitochondrial ROS production and markers of autophagy and denervation. Exercise also increased mitochondrial content and respiration without altering mCRC and MQC markers. Collectively, our results indicate that an exercise countermeasure that can be performed in bed is effective in protecting muscle and mitochondrial health during HDBR in older adults. KEY POINTS: Conditions associated with muscle unloading, such as immobilization, bed rest or microgravity, result in muscle atrophy and weakness, particularly in older adults. Mitochondrial dysfunctions are thought to contribute to muscle atrophy caused by unloading and ageing. However, whether exercise can counteract the deleterious effects of unloading in older adults remains largely unexplored. Here, we report that older adults exposed to 14 days of head-down tilt bed rest (HDBR) displayed upper leg muscle atrophy, a decrease in mitochondrial content and respiration, an increase in H2O2 emission, and an increase in autophagy and denervation markers. No impact of HDBR on mitochondrial quality control was observed. A multimodal exercise countermeasure prevented the deleterious effects of HDBR on upper leg muscle volume, mitochondrial reactive oxygen species emission, and markers of autophagy and denervation and increased mitochondrial content and respiration. These findings highlight the effectiveness of exercise in promoting muscle and mitochondrial health in older adults undergoing bed rest.

Myths and Methodologies: Understanding the health impact of head down bedrest for the benefit of older adults and astronauts. Study protocol of the Canadian Bedrest Study.

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest.

With the dead under the mat: the zombie ant extended phenotype under a new perspective.

Some parasitic fungi can increase fitness by modifying the behavior of their hosts. These behaviors are known as extended phenotypes because they favor parasitic gene propagation. Here, we studied three lineages of Ophiocordyceps, a fungus that infects ants, altering their conduct before death. According to fungal strategy, ants may die in leaf litter, with entwined legs in branches, under the moss mat, or biting plant tissue. It is critical for parasites that the corpses stay at these places because Ophiocordyceps exhibit iteroparity, possibly releasing spores in multiple life cycles. Thus, we assumed substrate cadaver permanence as a fungi reproductive proxy and corpse height as a proxy of cadaver removal. We hypothesize that biting vegetation and dying in higher places may increase the permanence of ant corpses while avoiding possible corpse predation on the forest floor. We monitored over a year more than 4000 zombie ants in approximately 15 km2 of undisturbed tropical forest in central Amazonia. Our results show a longer permanence of corpses with increasing ground height, suggesting that the parasites may have better chances of releasing spores and infecting new hosts at these places. We found that the zombie ants that last longer on the substrate die under the moss mat in tree trunks, not necessarily biting vegetation. The biting behavior appears to be the most derived and complex mechanism among Ophiocordyceps syndromes. Our results put these findings under a new perspective, proposing that seemingly less complex behavioral changes are ecologically equivalent and adaptative for other parasite lineages.

Antifungal efficacy of photodynamic therapy on Cryptococcus and Candida species is enhanced by Streptomyces spp. extracts in vitro.

The research on actinobacteria isolated from traditional medicinal plants is limited. Here, four new Streptomyces isolates (Ha1, Pp1, UzK and UzM) were obtained from the rhizospheres of Helianthus annuus, Pongamia pinnata and Ziziphus mauritiana, frequently utilized in Indian traditional medicine. The Streptomyces isolates aqueous extracts were studied alone against the growth of the Cryptococcus neoformans H99 reference strain, the fluconazole-tolerant T1-5796 and 89-610 strains, three histone deacetylase (HDAC) genes mutant strains, C. gattii NIH198, Candida albicans, C. glabrata, C. parapsilosis and C. tropicalis to determine minimum inhibitory concentration (MIC). Next, the extracts were employed in combination with aluminium-phthalocyanine chloride nanoemulsion-mediated photodynamic therapy to evaluate a possible interaction. We demonstrated that the C. neoformans T1-5796 fluconazole-tolerant strain was more severely inhibited by the Pp1 isolate extract (MIC: 6 mg mL-1) than H99, which was not inhibited. Growth inhibition of the HDAC null mutants was more prominent for the extract of the UzM isolate, showing inhibition at 2 mg mL-1. The UzM extract was also the most effective in hindering the Candida species proliferation, with MIC values ranging from 10 to 40 mg mL-1. The four Streptomyces extracts, especially UzK and UzM, significantly enhanced the antifungal effect of the photodynamic therapy. Our results indicate these Streptomyces isolates as sources of novel metabolites which could potentiate the effect of photodynamic therapy in controlling yeasts superficial infections.

How is the water footprint of the species Vachellia farnesiana, Amburana cearensis, and Handroanthus impetiginosus influenced by abiotic stresses as water deficit and salinity?

In semi-arid regions, is necessary to explore strategies to mitigate abiotic stresses such as water deficit and salinity. This study aimed to evaluate the stress tolerance capacity of three species subjected to different water regimes and salinity levels, based on dry matter production and water use efficiency (WUE). The species Handroanthus impetiginosus, Vachellia farnesiana, and Amburana cearensis were evaluated in combination with different water regimes (50%, 75%, and 100% of reference evapotranspiration - ET0) and salinity levels (0.18, 1.50, and 1.90 dS m-1). The results show that biomass accumulation increased at 50% and 75% ET0, while the WUE decreased at 100% ET0. The salinity level (1.90 dS m-1) caused reductions in leaf dry biomass (LDB), total dry biomass (TDB), LDB/TDB ratio, and WUE. The negative effects of high salinity on plant height were greater with the application of 75% ET0. The highest WUE was obtained at 50% ET0 for A. cearensis and H. impetiginosus, while V. farnesiana obtained the highest WUE at 75% ET0. A. cearensis exhibited the highest biomass accumulation (2.58 g) and WUE (0.21 g L-1). Overall, the species can tolerate drought and salinity conditions, being sensitive to high salinity concentrations during their initial growth.

The Caatinga is characterized by low water availability and soil salinization. Therefore, assessing the ability of native species to cope with these conditions allows for their utilization in reforestation programs in drought and salinity-exposed environments. Studies on the combined effects of these factors are scarce. The results indicated that native species show tolerance to drought and salinity conditions, albeit with some reductions in biomass production and water use efficiency at high NaCl concentrations. Among the species, A. cearensis performed the best under water and salinity stress conditions.

Can changes in land use in a semi-arid region of Brazil cause seasonal variation in energy partitioning and evapotranspiration?

Changes to forests due to deforestation, or their replacement by agricultural areas, alter evapotranspiration and the partitioning of available energy. This study investigated seasonal variations in the energy balance and evapotranspiration in landscapes under different levels of anthropogenic intervention in the semi-arid region of Brazil. Micrometeorological data was obtained from September 2020 to October 2022 for three areas of the semi-arid region: preserved Caatinga (CAA, native vegetation), Caatinga under regeneration (REGE) and a deforested area (DEFA). Here, we use the Bowen ratio energy balance method. Measurements were taken of global solar radiation, air temperature, relative humidity, vapour pressure deficit, rainfall, net radiation, latent heat flux, sensible heat flux, soil heat flux, evapotranspiration, volumetric soil water content and Normalised Difference Vegetation Index. Sensible heat flux was the dominant flux in both areas with 66% for preserved Caatinga vegetation, 63% for Caatinga under regeneration and 62% deforested area. The latent heat flux was equivalent to 28% of the net radiation for preserved Caatinga vegetation, Caatinga under regeneration and deforested area. The evapotranspiration in turn responded as a function of water availability, being higher during the rainy seasons, with average values of 1.82 mm day-1 for preserved Caatinga vegetation, 2.26 mm day-1 for Caatinga under regeneration and 1.25 mm day-1 for deforested area. The Bowen ratio presented values > 1 in deforested area, preserved Caatinga vegetation and Caatinga under regeneration. Thus, it can be concluded that the change in land use alters the energy balance components, promoting reductions in available energy and latent and sensible heat fluxes during the rainy-dry transition in the deforested area. In addition, the seasonality of energy fluxes depends on water availability in the environment.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures.

INTRODUCTION: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Innovative Pre-Clinical Data Using Peptides to Intervene in the Evolution of Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, relentless, and deadly disease. Little is known about its pathogenetic mechanisms; therefore, developing efficient pharmacological therapies is challenging. This work aimed to apply a therapeutic alternative using immunomodulatory peptides in a chronic pulmonary fibrosis murine model. BALB/c mice were intratracheally instilled with bleomycin (BLM) and followed for 30 days. The mice were treated with the immune modulatory peptides ToAP3 and ToAP4 every three days, starting on the 5th day post-BLM instillation. ELISA, qPCR, morphology, and respiratory function analyses were performed. The treatment with both peptides delayed the inflammatory process observed in the non-treated group, which showed a fibrotic process with alterations in the production of collagen I, III, and IV that were associated with significant alterations in their ventilatory mechanics. The ToAP3 and ToAP4 treatments, by lung gene modulation patterns, indicated that distinct mechanisms determine the action of peptides. Both peptides controlled the experimental IPF, maintaining the tissue characteristics and standard function properties and regulating fibrotic-associated cytokine production. Data obtained in this work show that the immune response regulation by ToAP3 and ToAP4 can control the alterations that cause the fibrotic process after BLM instillation, making both peptides potential therapeutic alternatives and/or adjuvants for IPF.

Factors partitioning physical frailty in people aging with HIV: A classification and regression tree approach.

OBJECTIVE: To estimate the extent to which comorbidity and lifestyle factors were associated with physical frailty in middle-aged and older Canadians living with HIV. DESIGN: Cross-sectional analysis of 856 participants from the Canadian Positive Brain Health Now cohort. METHODS: The frailty indicator phenotype was adapted from Fried's criteria using self-report items. Univariate logistic regression and classification and regression tree (CaRT) models were used to identify the most relevant independent contributors to frailty. RESULTS: In all, 100 men (14.0%) and 26 women (19.7%) were identified as frail (≥ 3/5 criteria) for an overall prevalence of 15.2%. Nine comorbidities showed an influential association with frailty. The most influential comorbidities were hypothyroidism [odds ratio (OR) = 2.55, 95% confidence interval (CI): 1.29-5.03] and arthritis (OR = 2.54, 95% CI: 1.58-4.09). Additionally, tobacco (OR = 1.79, 95% CI: 1.05-3.04) showed an association. Any level of alcohol consumption showed a protective effect for frailty. The CaRT model showed nine pathways that led to frailty. Arthritis was the most discriminatory variable followed by alcohol, hypothyroidism, tobacco, cancer, cannabis, liver disease, kidney disease, osteoporosis, lung disease and peripheral vascular disease. The prevalence of physical frailty for people with arthritis was 27.4%; with additional cancer or tobacco and alcohol the prevalence rates were 47.1% and 46.1%, respectively. The protective effect of alcohol consumption evident in the univariate model appeared again in the CaRT model, but this effect varied. Cognitive frailty (19.5% overall) and emotional frailty (37.9% overall) were higher than the prevalence of physical frailty. CONCLUSIONS: Specific comorbidities and tobacco use were implicated in frailty, suggesting that it is comorbidities causing frailty. However, some frailty still appears to be HIV-related. The higher prevalence of cognitive and emotional frailty highlights the fact that physical frailty should not be the only focus in HIV.

Understanding interactive processes: a review of CO2 flux, evapotranspiration, and energy partitioning under stressful conditions in dry forest and agricultural environments.

Arid and semiarid environments are characterized by low water availability (e.g., in soil and atmosphere), high air temperature, and irregularity in the spatio-temporal distribution of rainfall. In addition to the economic and environmental consequences, drought also causes physiological damage to crops and compromises their survival in ecosystems. The removal of vegetation is responsible for altering the energy exchange of heat and water in natural ecosystems and agricultural areas. The fluxes of CO2 are also changed, and environments with characteristics of sinks, which can be sources of CO2 after anthropic disturbances. These changes can be measured through methods such as sap flow, eddy covariance, remote sensing, and energy balance. Despite the relevance of each method mentioned above, there are limitations in their applications that must be respected. Thus, this review aims to quantify the processes and changes of energy fluxes, CO2, and their interactions with the surfaces of terrestrial ecosystems in dry environments. Studies report that the use of methods that integrate data from climate monitoring towers and remote sensing products helps to improve the accuracy of the determination of energy fluxes on a global scale, also helping to reduce the dissimilarity of results obtained individually. Through the collection of works in the literature, it is reported that several areas of the Brazilian Caatinga biome, which is a Seasonally Dry Tropical Forest have been suffering from changes in land use and land cover. Similar fluxes of sensible heat in areas with cacti and Caatinga can be observed in studies. On the other hand, one of the variables influenced mainly by air temperature is net radiation. In dry forest areas, woody species can store large amounts of carbon in their biomass above and belowground. The use of cacti can modify the local carbon budget when using tree crops together. Therefore, the study highlights the complexity and severity of land degradation and changes in CO2, water, and energy fluxes in dry environments with areas of forest, grassland, and cacti. Vegetation energy balance is also a critical factor, as these simulations are helpful for use in forecasting weather or climate change. We also highlight the need for more studies that address environmental conservation techniques and cactus in the conservation of degraded areas.

A reliable, reproducible flow cytometry protocol for immune cell quantification in human adipose tissue.

The ability to accurately identify and quantify immune cell populations within adipose tissue is important in understanding the role of immune cells in metabolic disease risk. Flow cytometry is the gold standard method for immune cell quantification. However, quantification of immune cells from adipose tissue presents a number of challenges because of the complexities of working with an oily substance and the rapid deterioration of immune cell viability before analysis can be performed. Here we present a highly reproducible flow cytometry protocol for the quantification of immune cells in human adipose tissue, which overcomes these issues.

Early Mobilization in Older Adults with Acute Cardiovascular Disease.

BACKGROUND: Early mobilization (EM) is beneficial in critical care units and in older hospitalized patients, but little is known about EM in older adults with acute cardiovascular disease. METHODS: Consecutive admissions of adults ≥80 years old to a Cardiac Intensive Care Unit (CICU) prior to and following implementation of a nurse-driven EM program were reviewed. Mobility was measured using the Level of Function (LOF) Mobility Scale, which ranges from 0 (bed immobile) to 5 (able to walk >20 meters). The primary outcome was discharge home. RESULTS: There were 412 patients included (N = 234, intervention; N = 178, preintervention). There was no difference in age between groups (overall 86.3 ± 4.8 years old) or sex (overall female N = 215, 52.2%). In the intervention group, functional impairment was present in 89 patients (38.0%) prehospitalization and in 209 patients (89.3%) on admission. Nearly half of patients (N = 107; 45.7%) improved their LOF by ≥1 during admission. Mobilization occurred during nearly all opportunities (838/850; 98.6%), and most mobility activities were completed (2,207/2,553; 86.4%). Adverse events were rare (5/2,207 activities [0.2% adverse event rate]) and transient. Patients in the intervention group were more likely than patients in the preintervention group to be discharged home (74.4 vs. 65.7%, P = 0.047, respectively) and had a lower rate of in-hospital death (6.4 vs. 14.6%, P = 0.006, respectively). There was no difference in mean length of hospital stay, 30-day emergency department visit or hospital re-admission. CONCLUSION: EM is safe in older adults in the CICU and is associated with reduced discharge to healthcare facility and in-hospital mortality.

Motoric cognitive risk syndrome and incident dementia in older adults from the Québec NuAge cohort.

BACKGROUND: The co-occurrence of slow walking speed and subjective cognitive complaint (SCC) in non-demented individuals defines motoric cognitive risk syndrome (MCR), which is a pre-dementia stage. There is no information on the association between MCR and incident dementia in Québec's older population. OBJECTIVE: The study aims to examine the association of MCR and its individual components (i.e. SCC and slow walking speed) with incident dementia in community-dwelling older adults living in the province of Québec (Canada). DESIGN: Québec older people population-based observational cohort study with 3 years of follow-up. SETTING: Community dwellings. SUBJECTS: A subset of participants (n = 1,098) in 'Nutrition as a determinant of successful aging: The Québec longitudinal study' (NuAge). METHODS: At baseline, participants with MCR were identified. Incident dementia was measured at annual follow-up visits using the Modified Mini-Mental State (≤79/100) test and Instrumental Activity Daily Living scale (≤6/8) score values. RESULTS: The prevalence of MCR was 4.2% at baseline and the overall incidence of dementia was 3.6%. MCR (Hazard Ratio (HR) = 5.18, with 95% confidence interval (CI) = [2.43-11.03] and P ≤ 0.001) and SCC alone (HR = 2.54, with 95% CI = [1.33-4.85] and P = 0.005) were associated with incident dementia, but slow walking speed was not (HR = 0.81, with 95%CI = [0.25-2.63] and P = 0.736). CONCLUSIONS: MCR and SCC are associated with incident dementia in NuAge study participants.

Impact of literacy on the functional connectivity of vision and language related networks.

Learning to read leads to functional and structural changes in cortical brain areas related to vision and language. Previous evidence suggests that the Visual Word Form Area (VWFA), a region devoted to the recognition of letter strings in literate persons, acts as an interface between both systems. While different studies have performed univariate analyses to study the effects of literacy on brain function, little is known about its impact on whole functional networks, especially when literacy is acquired during adulthood. We investigated functional connectivity in three groups of adults with different literacy status: illiterates, ex-illiterates (i.e., who learned to read during adulthood), and literates (i.e., who learned to read in childhood). We used a data-driven, multivariate whole brain approach (Independent Component Analysis [ICA]) combined with a region of interest (ROI) analysis in order to explore the functional connectivity of the VWFA with four ICA networks related to vision and language functions. ICA allowed for the identification of four networks of interest: left fronto-parietal, auditory, medial visual and lateral visual functional networks, plus a control right fronto-parietal network. We explored the effects literacy on the connectivity between the VWFA and these networks, trying furthermore to disentangle the roles of reading proficiency and age of acquisition (i.e., literacy status) in these changes. Results showed that functional connectivity between the VWFA and the left fronto-parietal and lateral visual networks increased and decreased, respectively, with literacy. Moreover, the functional coupling of the VWFA and the auditory network decreased with literacy. This study provides novel insights in the mechanisms of reading acquisition and brain plasticity, putting to light the emergence of the VWFA as a bridge between language and vision. Further studies are required to characterize the interplay of proficiency and age of reading acquisition, and its relevance to models of brain plasticity across lifespan.

Illiterate to literate: behavioural and cerebral changes induced by reading acquisition.

The acquisition of literacy transforms the human brain. By reviewing studies of illiterate subjects, we propose specific hypotheses on how the functions of core brain systems are partially reoriented or 'recycled' when learning to read. Literacy acquisition improves early visual processing and reorganizes the ventral occipito-temporal pathway: responses to written characters are increased in the left occipito-temporal sulcus, whereas responses to faces shift towards the right hemisphere. Literacy also modifies phonological coding and strengthens the functional and anatomical link between phonemic and graphemic representations. Literacy acquisition therefore provides a remarkable example of how the brain reorganizes to accommodate a novel cultural skill.

Glucose and protein metabolic responses to an energy- but not protein- restricted diet in type 2 diabetes.

AIMS: To test the effect of energy restriction with maintained protein intake on body composition and on insulin sensitivity of glucose and protein metabolism in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: After 3 days of an isoenergetic diet with 1.2 g/kg/d protein, obese adults with T2D (three women, two men) followed a 5-week diet providing 60% of energy requirements with 45% carbohydrate, and with protein maintained at pre-intervention level. Isotopic tracers were used to quantify whole-body glucose (3-3 H-glucose) and protein (13 C-leucine) metabolism pre- (day 4) and post-intervention (day 39), in the postabsorptive state and during a hyperinsulinaemic, isoglycaemic, isoaminoacidaemic clamp. Body composition was measured using dual-energy x-ray absorptiometry. RESULTS: After energy restriction, 6% weight loss occurred via total body (11%) and visceral fat losses (25%), but lean mass was preserved. Fasting glucose level, serum insulin level, homeostatic model assessment of insulin resistance index and C-peptide level decreased significantly (29%, 38%, 54% and 38%, respectively) as did other cardiometabolic risk factors. Between clamp studies, postabsorptive protein turnover and oxidation rates decreased (12% and 32%), resulting in less negative net balance, consistent with protein conservation. The rates of glucose turnover decreased, and glucose metabolic clearance rate improved (24%). During the clamp, protein flux was lower (9%) and breakdown suppressed (12%), and net balance became less negative but not different. Although glucose turnover did not differ, metabolic clearance improved by 47%. CONCLUSIONS: In obese adults with T2D, an energy-restricted diet with maintained protein intake of ~1.2 g/kg/d improved the kinetics of protein metabolism (particularly in the postabsorptive state), and preserved lean body mass and increased glucose metabolic clearance rate.

Sex differences in the relationship between dietary pattern adherence and cognitive function among older adults: findings from the NuAge study.

BACKGROUND: Consumption of a prudent dietary pattern rich in healthy nutrients is associated with enhanced cognitive performance in older adulthood, while a Western dietary pattern low in healthy nutrients is associated with poor age-related cognitive function. Sex differences exist in dietary intake among older adults; however, there is a paucity of research examining the relationship between sex-specific dietary patterns and cognitive function in later life. METHODS: The current study aimed to investigate sex differences in the relationship between sex-specific dietary pattern adherence and global cognitive function at baseline and over a 3-year follow-up in 1268 community-dwelling older adults (Mage = 74 years, n = 664 women, n = 612 men) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge). A 78-item Food Frequency Questionnaire was used to estimate dietary intake over the previous year. Sex-specific dietary pattern scores were derived using principal component analysis. Global cognition was assessed using the Modified Mini-Mental State Examination (3MS). RESULTS: Adjusted linear mixed effects models indicated that a healthy, prudent dietary pattern was not associated with baseline cognitive performance in men or women. No relationship was found between Western dietary pattern adherence and baseline cognitive function in women. Among men, adherence to an unhealthy, Western dietary pattern was associated with poorer baseline cognitive function (ß = - 0.652, p = 0.02, 95% CI [- 1.22, - 0.65]). No association was found between prudent or Western dietary patterns and cognitive change over time in men or women. CONCLUSIONS: These findings highlight the importance of conducting sex-based analyses in aging research and suggest that the relationship between dietary pattern adherence and cognitive function in late life may be sex-dependent.

Revisiting the hypothesis of syndromic frailty: a cross-sectional study of the structural validity of the frailty phenotype.

BACKGROUND: Fried's Phenotype Model of Frailty (PMF) postulates that frailty is a syndrome. Features of a syndrome are a heterogeneous population that can be split into at least two classes, those presenting and those not presenting the syndrome. Syndromes are characterized by a specific mixture of signs and symptoms which increase in prevalence, from less to more severe classes. So far, the null hypothesis of homogeneity - signs and symptoms of frailty cannot identify at least two classes - has been tested using Latent Class Analysis (LCA) on the five dichotomized components of PMF (unintentional weight loss, exhaustion, weakness, slowness, and low physical activity). The aim of this study is to investigate further the construct validity of frailty as a syndrome using the extension offered by Factor Mixture Models (FMM). METHODS: LCA on dichotomized scores and FMM on continuous scores were conducted to test homogeneity on the five PMF components in a sample of 1643 community-dwelling older adults living in Québec, Canada (FRéLE). RESULTS: With dichotomized LCA, three frailty classes were found: robust, prefrail and frail, and the hypothesis of homogeneity was rejected. However, in FMM, frailty was better represented as a continuous variable than as latent heterogeneous classes. Thus, the PMF measurement model of frailty did not meet the features of a syndrome in this study. CONCLUSION: Using the FRéLE cohort, the PMF measurement model validity is questioned. Valid measurement of a syndrome depends on an understanding of its etiological factors and pathophysiological processes, and on a modelling of how the measured components are linked to these processes. Without these features, assessing frailty in a clinical setting may not improve patient health. Research on frailty should address these issues before promoting its use in clinical settings.

Effect of two different pre-operative exercise training regimens before colorectal surgery on functional capacity: A randomised controlled trial.

BACKGROUND: Multimodal prehabilitation, including exercise training, nutritional therapy and anxiety reduction, has been shown to attenuate functional decline associated with surgery. Due to the growing interest in functional status as a targeted surgical outcome, a better understanding of the optimal prescription of exercise is critical. OBJECTIVE: The objective is to compare peri-operative functional trajectory in response to two different exercise training protocols within a 4-week, supervised, multimodal prehabilitation programme. DESIGN: This was a single blinded, single centre, randomised controlled study. Participants performed four assessments: at baseline, after prehabilitation (just before surgery), and at 1 and 2 months after surgery. PATIENTS: Adult patients scheduled for elective resection of nonmetastatic colorectal cancer were included provided there were no absolute contraindications to exercise nor poor language comprehension. INTERVENTION: Patients followed either high-intensity interval training (HIIT), or moderate intensity continuous training (MICT), as part of a 4-week multimodal prehabilitation programme. Both groups followed the same supervised resistance training, nutritional therapy and anxiety reduction interventions. All patients followed standardised peri-operative management. MAIN OUTCOME MEASURE: Changes in oxygen consumption at anaerobic threshold, measured with sequential cardio-pulmonary exercise testing, were assessed and compared between groups. RESULTS: Forty two patients were included in the primary analysis (HIIT n = 21 vs. MICT n = 21), with mean ±â€ŠSD age 64.5 ±â€Š11.2 years and 62% were men. At 2 months after surgery, 13/21 (62%) in HIIT and 11/21 (52%) in MICT attended the study visits. Both protocols significantly enhanced pre-operative functional capacity, with no difference between groups: mean (95% confidence interval) oxygen consumption at anaerobic threshold 1.97 (0.75 to 3.19) ml kg min in HIIT vs. 1.71 (0.56 to 2.85) in MICT, P = 0.753. At 2 months after surgery, the HIIT group showed a higher improvement in physical fitness: 2.36 (0.378 to 4.34) ml kg min, P = 0.021. No adverse events occurred during the intervention. CONCLUSION: Both MICT and HIIT enhanced pre-operative functional capacity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03361150.