Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity.

Upon immune challenge, recognition signals trigger insect immunity to remove the pathogens through cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua. This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua. This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.

Eosinophilic gastroenteritis as an uncommon cause of ascites recurrence in a young female.

Ascites appear as a clinical manifestation of various disorders, and the presence of raised levels of eosinophils in the peritoneal fluid characterizes eosinophilic ascites, which is an extremely rare disorder. Eosinophilic gastroenteritis is one of the uncommon causes of ascites. If not investigated thoroughly, ascites recurrence in a young female with a history of tuberculosis may be wrongly attributed to tuberculosis recurrence in an endemic country. The etiology of ascites in our case was correctly identified as the subserosal form of eosinophilic ascites. Oral corticosteroids form the mainstay of treatment in such cases. Eosinophilic gastroenteritis is a rare disease, but a thorough workup and a strong clinical suspicion may help in the successful diagnosis and treatment of such cases.

Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity.

Epoxyoctadecamonoenoic acids (EpOMEs) are epoxide derivatives of linoleic acid (9,12-octadecadienoic acid: LA). They are metabolized into dihydroxyoctadecamonoenoic acids (DiHOMEs) in mammals. Unlike in mammals where they act as adipokines or lipokines, EpOMEs act as immunosuppressants in insects. However, the functional link between EpOMEs and pro-immune mediators such as PGE2 is not known. In addition, the physiological significance of DiHOMEs is not clear in insects. This study analyzed the physiological role of these C18 oxylipins using a lepidopteran insect pest, Spodoptera exigua. Immune challenge of S. exigua rapidly upregulated the expression of the phospholipase A2 gene to trigger C20 oxylipin biosynthesis, followed by the upregulation of genes encoding EpOME synthase (SE51385) and a soluble epoxide hydrolase (Se-sEH). The sequential gene expression resulted in the upregulations of the corresponding gene products such as PGE2, EpOMEs, and DiHOMEs. Interestingly, only PGE2 injection without the immune challenge significantly upregulated the gene expression of SE51825 and Se-sEH. The elevated levels of EpOMEs acted as immunosuppressants by inhibiting cellular and humoral immune responses induced by the bacterial challenge, in which 12,13-EpOME was more potent than 9,10-EpOME. However, DiHOMEs did not inhibit the cellular immune responses but upregulated the expression of antimicrobial peptides selectively suppressed by EpOMEs. The negative regulation of insect immunity by EpOMEs and their inactive DiHOMEs were further validated by synthetic analogs of the linoleate epoxide and corresponding diol. Furthermore, inhibitors specific to Se-sEH used to prevent EpOME degradation significantly suppressed the immune responses. The data suggest a physiological role of C18 oxylipins in resolving insect immune response. Any immune dysregulation induced by EpOME analogs or sEH inhibitors significantly enhanced insect susceptibility to the entomopathogen, Bacillus thuringiensis.

Soluble Epoxide Hydrolase Contributes to Cell Senescence and ER Stress in Aging Mice Colon.

Aging, which is characterized by enhanced cell senescence and functional decline of tissues, is a major risk factor for many chronic diseases. Accumulating evidence shows that age-related dysfunction in the colon leads to disorders in multiple organs and systemic inflammation. However, the detailed pathological mechanisms and endogenous regulators underlying colon aging are still largely unknown. Here, we report that the expression and activity of the soluble epoxide hydrolase (sEH) enzyme are increased in the colon of aged mice. Importantly, genetic knockout of sEH attenuated the age-related upregulation of senescent markers p21, p16, Tp53, and ß-galactosidase in the colon. Moreover, sEH deficiency alleviated aging-associated endoplasmic reticulum (ER) stress in the colon by reducing both the upstream regulators Perk and Ire1 as well as the downstream pro-apoptotic effectors Chop and Gadd34. Furthermore, treatment with sEH-derived linoleic acid metabolites, dihydroxy-octadecenoic acids (DiHOMEs), decreased cell viability and increased ER stress in human colon CCD-18Co cells in vitro. Together, these results support that the sEH is a key regulator of the aging colon, which highlights its potential application as a therapeutic target for reducing or treating age-related diseases in the colon.

Aflatoxin B1 exposure disrupts the intestinal immune function via a soluble epoxide hydrolase-mediated manner.

Aflatoxin B1 (AFB1) contamination in food and feed leads to severe global health problems. Acting as the frontier immunological barrier, the intestinal mucosa is constantly challenged by exposure to foodborne toxins such as AFB1 via contaminated diets, but the detailed toxic mechanism and endogenous regulators of AFB1 toxicity are still unclear. Here, we showed that AFB1 disrupted intestinal immune function by suppressing macrophages, especially M2 macrophages, and antimicrobial peptide-secreting Paneth cells. Using an oxylipinomics approach, we identified that AFB1 immunotoxicity is associated with decreased epoxy fatty acids, notably epoxyeicosatrienoic acids, and increased soluble epoxide hydrolase (sEH) levels in the intestine. Furthermore, sEH deficiency or inhibition rescued the AFB1-compromised intestinal immunity by restoring M2 macrophages as well as Paneth cells and their-derived lysozyme and α-defensin-3 in mice. Altogether, our study demonstrates that AFB1 exposure impairs intestinal immunity, at least in part, in a sEH-mediated way. Moreover, the present study supports the potential application of pharmacological intervention by inhibiting the sEH enzyme in alleviating intestinal immunotoxicity and associated complications caused by AFB1 global contamination.

The epoxy fatty acid pathway enhances cAMP in mammalian cells through multiple mechanisms.

The cellular mechanism by which epoxy fatty acids (EpFA) improves disease status is not well characterized. Previous studies suggest the involvement of cellular receptors and cyclic AMP (cAMP). Herein, the action of EpFAs derived from linoleic acid (LA), arachidonic acid (ARA), and docosahexaenoic acid on cAMP levels was studied in multiple cell types to elucidate relationships between EpFAs, receptors and cells' origin. cAMP levels were enhanced in HEK293 and LLC-PK1 cells by EpFAs from LA and ARA. Using selective antagonists, the EpFA effects on cAMP levels appear dependent on the prostaglandin E2 receptor 2 (EP2) but not 4 (EP4). Human coronary artery smooth muscle cells responded similarly to the EpFAs. However, we were not able to show the involvement of any of the receptors tested in this cell type. The results pinpointed distinct cell lines and receptor subtypes that natively respond to EpFA.

Towards a super-resolution based approach for improved face recognition in low resolution environment.

The video surveillance activity generates a vast amount of data, which can be processed to detect miscreants. The task of identifying and recognizing an object in surveillance data is intriguing yet difficult due to the low resolution of captured images or video. The super-resolution approach aims to enhance the resolution of an image to generate a desirable high-resolution one. This paper develops a robust real-time face recognition approach that uses super-resolution to improve images and detect faces in the video. Many previously developed face detection systems are constrained by the severe distortion in the captured images. Further, many systems failed to handle the effect of motion, blur, and noise on the images registered on a camera. The presented approach improves descriptor count of the image based on the super-resolved faces and mitigates the effect of noise. Furthermore, it uses a parallel architecture to implement a super-resolution algorithm and overcomes the efficiency drawback increasing face recognition performance. Experimental analysis on the ORL, Caltech, and Chokepoint datasets has been carried out to evaluate the performance of the presented approach. The PSNR (Peak Signal-to-Noise-Ratio) and face recognition rate are used as the performance measures. The results showed significant improvement in the recognition rates for images where the face didn't contain pose expressions and scale variations. Further, for the complicated cases involving scale, pose, and lighting variations, the presented approach resulted in an improvement of 5%-6% in each case.

Improved ELISA for linoleate-derived diols in human plasma utilizing a polyHRP-based secondary tracer.

Dihydroxyoctadecenoic acids (DiHOMEs) are cytochrome P450 pathway-derived metabolites of linoleic acid, a highly abundant dietary fatty acid. They serve thermogenic functions at low concentrations but, at high concentrations, are involved in proinflammatory and deleterious outcomes in a wide range of pathologies. Hence, the development of a reliable analytical method is critical to elucidate their potential as biomarkers of health, and enzyme-linked immunoassay (ELISA)-based approaches offer unique benefits as alternatives to traditional liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems. Accordingly, an earlier ELISA for DiHOMEs was dramatically improved employing new secondary tracers and geared towards use in human plasma, a universal matrix in biomedical applications, as well as urine. Three ELISA formats, two utilizing polyHRP-based secondary labels for signal amplification, were compared. The best format involved a biotinylated detection antibody and a polyHRP-conjugated streptavidin tracer. Assay detectability was enhanced 20-fold, relative to the original immunoassay, and performance assessments validated precision, selectivity, and robustness. Fast and easy extraction-clean up steps yielded high analytical recovery and permitted the assay to operate in moderate concentrations (up to 20%) of plasma, expanding its practical relevance. Finally, the ELISA was applied towards detection of DiHOMEs in clinical samples and authenticated with complementary LC-MS/MS analysis. Hence, the method provides a valuable analytical tool to investigate the diverse and extensive roles of DiHOMEs in regulatory biology.

Effect of High-Intensity Power Training on Cognitive Function in Older Adults With Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Study.

We sought to determine the effects of 12 months of power training on cognition, and whether improvements in body composition, muscle strength, and/or aerobic capacity (VO2peak) were associated with improvements in cognition in older adults with type 2 diabetes (T2D). Participants with T2D were randomized to power training or low-intensity sham exercise control condition, 3 days per week for 12 months. Cognitive outcomes included memory, attention/speed, executive function, and global cognition. Other relevant outcomes included VO2peak, strength, and whole body and regional body composition. One hundred and three adults with T2D (mean age 67.9 years; standard deviation [SD] 5.9; 50.5% women) were enrolled and analyzed. Unexpectedly, there was a nearly significant improvement in global cognition (p = .05) in the sham group relative to power training, although both groups improved over time (p < .01). There were significant interactions between group allocation and body composition or muscle strength in the models predicting cognitive changes. Therefore, after stratifying by group allocation, improvements in immediate memory were associated with increases in relative skeletal muscle mass (r = 0.38, p = .03), reductions in relative body fat (r = -0.40, p = .02), and increases in knee extension strength were directly related to changes in executive function (r = -0.41, p = .02) within the power training group. None of these relationships were present in the sham group (p > .05). Although power training did not significantly improve cognition compared to low-intensity exercise control, improvements in cognitive function in older adults were associated with hypothesized improvements in body composition and strength after power training.

sEH-derived metabolites of linoleic acid drive pathologic inflammation while impairing key innate immune cell function in burn injury.

Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue. PUFA-derived oxylipins regulate a variety of biological functions. The cytochrome P450 (CYP450)­formed epoxy fatty acid metabolites of LA (EpOMEs) are hydrolyzed by the soluble epoxide hydrolase enzyme (sEH) to dihydroxyoctadecenoic acids (DiHOMEs). DiHOMEs are considered cardioprotective at low concentrations but at higher levels have been implicated as vascular permeability and cytotoxic agents and are associated with acute respiratory distress syndrome in severe COVID-19 patients. High EpOME levels have also correlated with sepsis-related fatalities; however, those studies failed to monitor DiHOME levels. Considering the overlap of burn pathophysiology with these pathologies, the role of DiHOMEs in the immune response to burn injury was investigated. 12,13-DiHOME was found to facilitate the maturation and activation of stimulated neutrophils, while impeding monocyte and macrophage functionality and cytokine generation. In addition, DiHOME serum concentrations were significantly elevated in burn-injured mice and these increases were ablated by administration of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a sEH inhibitor. TPPU also reduced necrosis of innate and adaptive immune cells in burned mice, in a dose-dependent manner. The findings suggest DiHOMEs are a key driver of immune cell dysfunction in severe burn injury through hyperinflammatory neutrophilic and impaired monocytic actions, and inhibition of sEH might be a promising therapeutic strategy to mitigate deleterious outcomes in burn patients.

Pancytopenia Secondary to SARS-CoV-2 Infection-a Case Report.

Pancytopenia is a condition when a person has a low count of all three types of blood cells, causing a triage of anaemia, leukopenia and thrombocytopenia. It should not be considered a disease in itself but rather a sign of a disease that needs to be further evaluated. Among the various causes, viral infections like the human immunodeficiency virus, cytomegalovirus, Epstein-Barr virus and parvovirus B19 have been implicated. Pancytopenia is a rare complication and is not commonly seen in patients with COVID-19 disease. Here, we report a case of pancytopenia in a previously immunocompetent elderly male patient with SARS-CoV-2 infection.

New Alkoxy- Analogues of Epoxyeicosatrienoic Acids Attenuate Cisplatin Nephrotoxicity In Vitro via Reduction of Mitochondrial Dysfunction, Oxidative Stress, Mitogen-Activated Protein Kinase Signaling, and Caspase Activation.

The usage of cisplatin, a highly potent chemotherapeutic, is limited by its severe nephrotoxicity. Arachidonic acid (ARA)-derived epoxyeicosatrienoic acids (EETs) and soluble epoxide hydrolase (sEH) inhibitors were shown to ameliorate this dose-limiting side effect, but both approaches have some pharmacological limitations. Analogues of EETs are an alternative avenue with unique benefits, but the current series of analogues face concerns regarding their structure and mimetic functionality. Hence, in this study, regioisomeric mixtures of four new ARA alkyl ethers were synthesized, characterized, and assessed as EET analogues against the concentration- and time-dependent toxicities of cisplatin in porcine proximal tubular epithelial cells. All four ether groups displayed bioisostere activity, ranging from marginal for methoxy- (1), good for n-propoxy- (4), and excellent for ethoxy- (2) and i-propoxy- (3). Compounds 2 and 3 displayed cytoprotective effects comparable to that of an EET regioisomeric mixture (5) against high, acute cisplatin exposures but were more potent against low to moderate, chronic exposures. Compounds 2 and 3 (and 5) acted through stabilization of the mitochondrial transmembrane potential and attenuation of reactive oxygen species, leading to reduced phosphorylation of mitogen-activated protein kinases p38 and JNK and decreased activation of caspase-9 and caspase-3. This study demonstrates that alkoxy- groups are potent and more metabolically stable bioisostere alternatives to the epoxide within EETs that enable sEH-independent activity. It also illustrates the potential of ether-based mimics of EETs and other epoxy fatty acids as promising nephroprotective agents to tackle the clinically relevant side effect of cisplatin without compromising its antineoplastic function.

Exploring Potential Carcinogenic Activity of Per- and Polyfluorinated Alkyl Substances Utilizing High-Throughput Toxicity Screening Data.

Per- and polyfluorinated alkyl substances (PFAS) are ubiquitous, persistent, and toxic chemicals that pose public health risks. Recent carcinogenicity concerns have arisen based on epidemiological studies, animal tumor findings, and mechanistic data. Thousands of PFAS exist; however, current understanding of their toxicity is informed by studies of a select few, namely, perfluorooctanoic acid and perfluorooctanesulfonic acid. Hence, the computational, high-throughput screening tool, the US EPA CompTox Chemical Dashboard's ToxCast, was utilized to explore the carcinogenicity potential of PFAS. Twenty-three major PFAS that had sufficient in vitro ToxCast data and covered a range of structural subclasses were analyzed with the visual analytics software ToxPi, yielding a qualitative and quantitative assessment of PFAS activity in realms closely linked with carcinogenicity. A comprehensive literature search was also conducted to check the consistency of analyses with other mechanistic data streams. The PFAS were found to induce a vast range of biological perturbations, in line with several of the International Agency for Research on Cancer-defined key carcinogen characteristics. Patterns observed varied by length of fluorine-bonded chains and/or functional group within and between each key characteristic, suggesting some structure-based variability in activity. In general, the major conclusions drawn from the analysis, that is, the most notable activities being modulation of receptor-mediated effects and induction of oxidative stress, were supported by literature findings. The study helps enhance understanding of the mechanistic pathways that underlie the potential carcinogenicity of various PFAS and hence could assist in hazard identification and risk assessment for this emerging and relevant class of environmental toxicants.

Adrenic Acid-Derived Epoxy Fatty Acids Are Naturally Occurring Lipids and Their Methyl Ester Prodrug Reduces Endoplasmic Reticulum Stress and Inflammatory Pain.

Adrenic acid (AdA, 22:4) is an ω-6 polyunsaturated fatty acid (PUFA), derived from arachidonic acid. Like other PUFAs, it is metabolized by cytochrome P450s to a group of epoxy fatty acids (EpFAs), epoxydocosatrienoic acids (EDTs). EpFAs are lipid mediators with various beneficial bioactivities, including exertion of analgesia and reduction of endoplasmic reticulum (ER) stress, that are degraded to dihydroxy fatty acids by the soluble epoxide hydrolase (sEH). However, the biological characteristics and activities of EDTs are relatively unexplored, and, alongside dihydroxydocosatrienoic acids (DHDTs), they had not been detected in vivo. Herein, EDT and DHDT regioisomers were synthesized, purified, and used as standards for analysis with a selective and quantitative high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. Biological verification in AdA-rich tissues suggests that basal metabolite levels are highest in the liver, with 16,17-EDT concentrations consistently being the greatest across the analyzed tissues. Enzyme hydrolysis assessment revealed that EDTs are sEH substrates, with greatest relative rate preference for the 13,14-EDT regioisomer. Pretreatment with an EDT methyl ester regioisomer mixture significantly reduced the onset of tunicamycin-stimulated ER stress in human embryonic kidney cells. Finally, administration of the regioisomeric mixture effectively alleviated carrageenan-induced inflammatory pain in rats. This study indicates that EDTs and DHDTs are naturally occurring lipids, and EDTs could be another therapeutically relevant group of EpFAs.

The Effect of High-Intensity Power Training on Habitual, Intervention and Total Physical Activity Levels in Older Adults with Type 2 Diabetes: Secondary Outcomes of the GREAT2DO Randomized Controlled Trial.

BACKGROUND: We examined the effect of power training on habitual, intervention and total physical activity (PA) levels in older adults with type 2 diabetes and their relationship to metabolic control. MATERIALS AND METHODS: 103 adults with type 2 diabetes were randomized to receive supervised power training or sham exercise three times/week for 12 months. Habitual, intervention, and total PA, as well as insulin resistance (HOMA2-IR) and glycosylated hemoglobin (HbA1c), were measured. RESULTS: Participants were aged 67.9 ± 5.5 yrs, with well-controlled diabetes (HbA1c = 7.1%) and higher than average habitual PA levels compared to healthy peers. Habitual PA did not change significantly over 12 months (p = 0.74), and there was no effect of group assignment on change over time in habitual PA over 0-6 (p = 0.16) or 0-6-12 months (p = 0.51). By contrast, intervention PA, leg press tonnage and total PA increased over both 6- and 12-month timepoints (p = 0.0001), and these changes were significantly greater in the power training compared to the sham exercise group across timepoints (p = 0.0001). However, there were no associations between changes in any PA measures over time and changes in metabolic profile. CONCLUSION: Structured high-intensity power training may be an effective strategy to enhance overall PA in this high-risk cohort.

N-Benzyl-linoleamide, a Constituent of Lepidium meyenii (Maca), Is an Orally Bioavailable Soluble Epoxide Hydrolase Inhibitor That Alleviates Inflammatory Pain.

Lepidium meyenii (maca), a plant indigenous to the Peruvian Andes, recently has been utilized globally for claimed health or recreational benefits. The search for natural products that inhibit soluble epoxide hydrolase (sEH), with therapeutically relevant potencies and concentrations, led to the present study on bioactive amide secondary metabolites found in L. meyenii, the macamides. Based on known and suspected macamides, 19 possible macamides were synthesized and characterized. The majority of these amides displayed excellent inhibitory potency (IC50 ≈ 20-300 nM) toward the recombinant mouse, rat, and human sEH. Quantitative analysis of commercial maca products revealed that certain products contain known macamides (1-5, 8-12) at therapeutically relevant total concentrations (≥3.29 mg/g of root), while the inhibitory potency of L. meyenii extracts directly correlates with the sum of concentration/IC50 ratios of macamides present. Considering both its in vitro efficacy and high abundance in commercial products, N-benzyl-linoleamide (4) was identified as a particularly relevant macamide that can be utilized for in vivo studies. Following oral administration in the rat, compound 4 not only displayed acceptable pharmacokinetic characteristics but effectively reduced lipopolysaccharide-induced inflammatory pain. Inhibition of sEH by macamides provides a plausible biological mechanism of action to account for several beneficial effects previously observed with L. meyenii treatments.

Development of potent inhibitors of the human microsomal epoxide hydrolase.

Microsomal epoxide hydrolase (mEH) hydrolyzes a wide range of epoxide containing molecules. Although involved in the metabolism of xenobiotics, recent studies associate mEH with the onset and development of certain disease conditions. This phenomenon is partially attributed to the significant role mEH plays in hydrolyzing endogenous lipid mediators, suggesting more complex and extensive physiological functions. In order to obtain pharmacological tools to further study the biology and therapeutic potential of this enzyme target, we describe the development of highly potent 2-alkylthio acetamide inhibitors of the human mEH with IC50 values in the low nanomolar range. These are around 2 orders of magnitude more potent than previously obtained primary amine, amide and urea-based mEH inhibitors. Experimental assay results and rationalization of binding through docking calculations of inhibitors to a mEH homology model indicate that an amide connected to an alkyl side chain and a benzyl-thio function as key pharmacophore units.

Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI.

Dementia affects 47 million individuals worldwide, and assuming the status quo is projected to rise to 150 million by 2050. Prevention of age-related cognitive impairment in older persons with lifestyle interventions continues to garner evidence but whether this can combat underlying neurodegeneration is unknown. The Study of Mental Activity and Resistance Training (SMART) trial has previously reported within-training findings; the aim of this study was to investigate the long-term neurostructural and cognitive impact of resistance exercise in Mild Cognitive Impairment (MCI). For the first time we show that hippocampal subareas particularly susceptible to volume loss in Alzheimer's disease (AD) are protected by resistance exercise for up to one year after training. One hundred MCI participants were randomised to one of four training groups: (1) Combined high intensity progressive resistance and computerised cognitive training (PRT+CCT), (2) PRT+Sham CCT, (3) CCT+Sham PRT, (4) Sham physical+sham cognitive training (SHAM+SHAM). Physical, neuropsychological and MRI assessments were carried out at baseline, 6 months (directly after training) and 18 months from baseline (12 months after intervention cessation). Here we report neuro-structural and functional changes over the 18-month trial period and the association with global cognitive and executive function measures. PRT but not CCT or PRT+CCT led to global long-term cognitive improvements above SHAM intervention at 18-month follow-up. Furthermore, hippocampal subfields susceptible to atrophy in AD were protected by PRT revealing an elimination of long-term atrophy in the left subiculum, and attenuation of atrophy in left CA1 and dentate gyrus when compared to SHAM+SHAM (p = 0.023, p = 0.020 and p = 0.027). These neuroprotective effects mediated a significant portion of long-term cognitive benefits. By contrast, within-training posterior cingulate plasticity decayed after training cessation and was unrelated to long term cognitive benefits. Neither general physical activity levels nor fitness change over the 18-month period mediated hippocampal trajectory, demonstrating that enduring hippocampal subfield plasticity is not a simple reflection of post-training changes in fitness or physical activity participation. Notably, resting-state fMRI analysis revealed that both the hippocampus and posterior cingulate participate in a functional network that continued to be upregulated following intervention cessation. Multiple structural mechanisms may contribute to the long-term global cognitive benefit of resistance exercise, developing along different time courses but functionally linked. For the first time we show that 6 months of high intensity resistance exercise is capable of not only promoting better cognition in those with MCI, but also protecting AD-vulnerable hippocampal subfields from degeneration for at least 12 months post-intervention. These findings emphasise the therapeutic potential of resistance exercise; however, future work will need to establish just how long-lived these outcomes are and whether they are sufficient to delay dementia.

Acute exercise decreases vaccine reactions following influenza vaccination among older adults.

Although valuable and effective in decreasing disease burden, influenza vaccination has low rates of efficacy, especially in those at most risk. Studies have shown that acute exercise can improve vaccine responses, most consistently with weaker antigens. Here we examined the effect of resistance exercise on the acute and longer-term responses to influenza vaccination among healthy older adults. Forty-six participants (47.8% male, mean 73.4 ±â€¯6.6 years) were randomised to perform one 45-min moderate-intensity resistance exercise session or sit quietly prior to the receipt of influenza vaccination. Acute exercise reduced vaccine reactions but had no effect on either antibody responses or development of influenza-like symptoms during six months of follow-up. Psychosocial and behavioural characteristics were examined for potential associations with the responses to vaccination. Participants (n = 36) vaccinated in the previous year had higher baseline antibody titres but not follow-up titres nor more frequent experience of influenza-like symptoms over 6 months compared to those unvaccinated in the previous year. These findings provide further support for the ability of acute exercise to reduce vaccine reactions and suggest risk factors for vaccine responses for future exploration.

Reliability and validity of a Mediterranean diet and culinary index (MediCul) tool in an older population with mild cognitive impairment.

Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test-retest reliability was assessed using intra-class correlation coefficients (ICC), Bland-Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland-Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test-retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=-2·30+0·17x) (95 % CI -0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.