Overestimation of sex differences in psychostimulant activity via comparisons of males and females from different behavioral groups.

Background: There are inconsistencies in the observation of sex differences in baseline activity and psychostimulant activity. To address this, we have developed the MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model. MISSING model proposes that sex similarities are observed when we compare similar behavioral groups of males and females, with sex differences occurring when we compare distinct groups of sexes, but this model has not been tested. Methods: To test this model, we identified within-sex groups of Sprague Dawley rats (male n = 22, female n = 23) by conducted normal mixtures clustering of baseline activity, cocaine activity (as distance traveled in cm over 90 min) and cocaine activity normalized-to-baseline activity (NBA) of all subjects. We employed 2-way ANOVA to determine the impact of within-sex heterogeneity on sex differences. We compared our cluster-based method to current median-split approaches. Results: Our new cluster-based method revealed three distinct clusters, each consisting of both males and females. We determined there were no sex differences in any of the variables when males and females from the same clusters were compared. The within-sex clusters for females were not defined by estrous phase. Median split analysis was ineffective in accurately identifying within-sex groups. Conclusions: Our results validate the MISSING model: there are no sex differences in psychostimulant activity except when we compare males and females from different behavioral groups. This has significant implications for how we proceed with research towards understanding the mechanism governing sex differences in psychostimulant activity.

The remarkable larval morphology of Rhaebo nasicus (Werner, 1903) (Amphibia: Anura: Bufonidae) with the erection of a new bufonid genus and insights into the evolution of suctorial tadpoles.

Tadpoles serve as crucial evidence for testing systematic and taxonomic hypotheses. Suctorial tadpoles collected in Guyana were initially assigned to Rhaebo nasicus through molecular phylogeny. Subsequent analysis of larval and adult morphological traits revealed synapomorphies within the clade encompassing R. nasicus and R. ceratophrys, prompting the recognition of a new genus described herein as Adhaerobufo. The new genus is distinguished from other bufonids by specific phenotypic traits including an enlarged, suctorial oral disc with distinct papillae arrangements, and the presence of certain muscles and narial vacuities at the larval stage. However, only a few adult external characteristics (e.g., enlarged eyelids, infraocular cream spot), seem to be reliably discriminative from related genera. This study underscores the significance of larval morphology in anuran systematics and offers new insights into the evolution of suctorial and gastromyzophorous larvae within bufonids.

The annual trend of suicide rates from 2010 to 2021 in patients with cannabis use disorder - a national registry study.

PURPOSE: The temporal trend of suicide in patients with cannabis use disorder (CUD) is important to investigate, considering the recent increases in THC concentration in cannabis products. This study describes the annual suicide rates in patients with CUD from 2010 to 2021. To investigate if any change in suicide rate was specific to CUD, we compared these suicide rates with corresponding data for patients with alcohol use disorders (AUD) and other substance use disorders (SUDs). METHOD: The study used a time series design. We used a national registry linkage between the Norwegian Cause of Death Registry and the Norwegian Patient Registry from 2010 to 2021, including patients with CUD (ICD-10 code F12), AUD (F10), or other SUDs (F11; F13-F16; F18-F19) who died by suicide, supplemented with the total number of patients treated with specific disorders to estimate the suicide rates. The trend was analyzed by comparing the annual suicide rate to 2010 and using Poisson regression, adjusting for gender, age, and mental disorders. RESULTS: We found increased annual incidence rate ratios for patients with CUD in 2018 (IRR = 2.14 (95% CI 1.14-3.99)) and onwards and an increasing time trend over the study period (IRR = 1.08 (1.05-1.12)). No increases in trends were found for AUD or other SUDs. The time trend for CUD was attenuated when adjusting for depressive or anxiety disorders (aIRR = 1.00 (0.92-1.08)) or other SUDs (aIRR = 0.96 (0.87-1.06)). CONCLUSIONS: Increasing suicide rates were found in patients with CUD. Comorbid anxiety and depression or other SUDs, but not other mental disorders, could partly explain these results.

Copper-PANI-graphite HB2 composite for eco-friendly efficient degradation of textile dyes: Advancements in wastewater treatment enhanced by solar radiation.

This research aimed to assess the potential of Cu50PANI@UG composite for sunlight drive photocatalytic dye degradation, targeting specifically Thymol Blue (TB) and Black NT (BNT) dyes and their mixture (DM). The Cu50PANI@UG composite was successfully synthesized via electropolymerization in acetonitrile/sulfuric acid mixture under atmospheric conditions. Photocatalytic experiments were conducted by exposing aqueous dye solutions to sunlight. N,N-dimethyl-p-nitrosoaniline (RNO) served as a molecular probe for detecting hydroxyl radicals (•OH). Additionally, experiments capturing free radicals were performed to identify active components, with a concomitant proposal of plausible degradation reaction mechanism for the Photo-Fenton-Like degradation into the Cu50PANI@UG composite + H2O2 + hv reaction system. Various operating parameters affecting dye degradation were evaluated, including catalyst dosage (from 0.27 to 0.67 g L-1), H2O2 concentration (from 16 to 64 mM), pH (from 3.0 to 9.0), and dye concentration (from 25 to 100 mg L-1). Optimization of key parameters such as pH, catalyst dosage, and H2O2 concentration was conducted. The highest degradation efficiency, ca. 100% of DM dye, was achieved within 35 min under optimized conditions, using Cu50PANI@UG composite as a catalytic precursor. These conditions were determined as follows: Catalyst dosage = 0.67 g L-1, pH = 3.0-6.0, H2O2 = 32-64 mM, and irradiation time of 35 min. The degradation percentage under the Response Surface Methodology (RSM) was utilized as a statistical tool to correlate influential parameters. Four consecutive reusability trials were performed to assess catalyst stability.

Use of connected injection device has a positive effect on catch-up growth in patients with growth disorders treated with growth hormone therapy.

Introduction: Human growth hormone (hGH) therapy in children can be administered by subcutaneous injection using either a manual non-connected device, which is a portable injection pen loaded with a pre-filled cartridge, or an electronic connected device. The electronic device is connected to a platform where adherence data is recorded and available for health care professionals (HCPs) and patient support programs. Real-world data used in the clinic, includes regular monitoring of adherence data which are shared with families during patients' visits and aim to determine the root causes of poor adherence. This study aimed to identify whether there are differences in growth during the first four years of treatment depending on the device, i.e. non-connected versus connected devices. Methods: This retrospective study reports treatment of either GH deficiency or short stature secondary to birth size small for gestational age (SGA) in 174 pediatric patients attending Miguel Servet Hospital, Zaragoza, Spain. hGH treatment was administered with manual non-connected devices in 87 patients and 87 patients used connected devices. Height was followed for 4 years after start of hGH therapy. Results: In total, 57% of subjects had GHD and 43% were SGA. Height standard deviation score (HSDS) at treatment start was higher (p<0.001) in the non-connected device group compared to the connected device group. Change of HSDS in the connected device group was significantly higher in the second (+0.13), third (+0.20) and fourth (+0.23) year of treatment compared to the non-connected group after adjustment for age and HSDS at treatment start, sex, indication, dose and Tanner stages during treatment, and timing of measurements. Discussion: These results support the use of the connected device for hGH treatment of pediatric growth disorders.

Effects of long-term treatment with recombinant growth hormone on growth outcome in children born small for gestational age: a systematic review.

Children born small for gestational age (SGA) are defined as those having birth weight and/or length below -2 SD for gestational age. In approximately 90% of cases, SGA children experience catch-up growth in the first two years of life and a subsequent regular growth rate, reaching normal adult height. However, in the remaining 10% of cases, SGA children fail to have catch-up growth, showing persistent short stature and a constantly impaired growth rate, leading to decreased adult height compared with both general population and their mid-parental height. Therefore, in these children GH treatment may be indicated to improve growth outcome. As it can be started in most countries from the age of 4 years and is usually recommended until the completion of puberty, long-term GH treatment in SGA children (namely, longer than three years) showed a persistent improvement in height and an initial improvement in growth rate in the first year of treatment, followed by a stable, regular growth rate over time. In the present article, we systematically reviewed the currently available reports about efficacy of long-term GH treatment in SGA children, with a particular focus on growth rate over time and adult height.

Eco-Friendly Electrosynthesis of Cu-PANI-Pencil Composite: Enhanced Their Current Value, Acid Sensing, Click Chemistry and Turn On-Off Sunlight Photo-Catalytical H2O2 Activation.

In this contribution, we report a straightforwardly and easily one-step synthesis of a small family of composites based in polyaniline grafted on HB2 graphite (PANI@UG) and their copper-doped derivatives (Cu50PANI@UG5-6). The PANI@UG composites were synthesized through electrochemical polymerization using cyclic voltammetry (CV) in three different acidic media: i) acetic acid (AcOH) at high and low concentration (12 and 1 M, using KCl as electrolytic support); ii) a mixture of AcOH and sulfuric acid (H2SO4, which have two roles: as electrolytic support and proton source) and iii) a mixture of acetonitrile (NCCH3) and H2SO4, under atmospheric conditions. Once the best conditions were achieved, our next step was focused on obtaining the Cu50PANI@UG5-6 composites using a solution of aniline and CuSO4 (50 mM) in AcOH:H2SO4 and NCCH3:H2SO4 solutions, respectively. All composites were characterized by CV, FT-IR, SEM and MALDI-TOF experiments. So, the current value was enhanced for the Cu50PANI@UG6 composite, which have three potential catalytical applications in: i) HClO4 acid sensing, ii) click chemistry and iii) sunlight drive photo-activation of H2O2.

Dietary and Lifestyle Strategies for Obesity.

The prevalence of obesity globally has tripled over the last half century, and currently affects around 650 million adults and 340 million children and adolescents (ages 5-19 years). Obesity contributes towards >50 co-morbidities and premature mortality. Obesity is a highly stigmatised condition that is associated with much mental and emotional distress and dysfunction. Thus, obesity is a major contributor to healthcare expenditure globally. Traditionally, the management of obesity stratifies into three major groups that include metabolic (bariatric) surgery, pharmacotherapies, and lifestyle (primarily dietary) strategies. Although listed as a separate category, dietary strategies for obesity remain a central component of any management plan, and often complement other surgical and pharmacotherapeutic options. Indeed, the effectiveness of any management approach for obesity relies upon successful behavioural changes, particularly relating to eating behaviours. In this concise review, we explore the foundational pillars of dietary strategies for obesity: sleep, listening, routine, de-stressing and optimisation of social conditions. We then discuss the importance of balancing dietary macronutrients (including dietary fibre, carbohydrates, protein and ultra-processed foods [UPFs]) as a key dietary strategy for obesity. Although we focus on general principles, we should provide bespoke dietary strategies for our patients, tailored to their individual needs. Rather than judging the utility of a diet based simply on its associated magnitude of weight loss, we should adopt a more holistic perspective in which a dietary strategy is valued for its overall health benefits, including the nurturing of our gut microbiota, to enable them to nurture and protect us.

Multifractal analysis of heart rate variability in pregnancy during sleep.

Understanding the complex dynamics of heart rate variability (HRV) during pregnancy is crucial for monitoring both maternal well-being and fetal health. In this study, we use the Multifractal Detrended Fluctuations Analysis approach to investigate HRV patterns in pregnant individuals during sleep based on RR interval maxima (MM fluctuations). In addition, we study the type of multifractality within MM fluctuations, that is, if it arises from a broad probability density function or from varying long-range correlations. Furthermore, to provide a comprehensive view of HRV changes during sleep in pregnancy, classical temporal and spectral HRV indices were calculated at quarterly intervals during sleep. Our study population consists of 21 recordings from nonpregnant women, 18 from the first trimester (early-pregnancy) and 18 from the second trimester (middle-pregnancy) of pregnancy. Results. There are statistically significant differences ( p -value < 0.05) in mean heart rate, rms heart rate, mean MM fluctuations, and standard deviation of MM fluctuations, particularly in the third and fourth quarter of sleep between pregnant and non-pregnant states. In addition, the early-pregnancy group shows significant differences ( p -value < 0.05) in spectral indices during the first and fourth quarter of sleep compared to the non-pregnancy group. Furthermore, the results of our research show striking similarities in the average multifractal structure of MM fluctuations between pregnant and non-pregnant states during normal sleep. These results highlight the influence of different long-range correlations within the MM fluctuations, which could be primarily associated with the emergence of sleep cycles on multifractality during sleep. Finally, we performed a separability analysis between groups using temporal and spectral HRV indices as features per sleep quarter. Employing only three features after Principal Component Analysis (PCA) to the original feature set, achieving complete separability among all groups appears feasible. Using multifractal analysis, our study provides a comprehensive understanding of the complex HRV patterns during pregnancy, which holds promise for maternal and fetal health monitoring. The separability analysis also provides valuable insights into the potential for group differentiation using simple measures such as mean heart rate, rms heart rate, and mean MM fluctuations or in the transformed feature space based on PCA.

Longitudinal Changes in Ki-67 Indices in Small-Intestinal Neuroendocrine Tumours and Their Impact on Survival.

INTRODUCTION: The purpose of this study was to evaluate longitudinal changes in Ki-67 indices of SI-NETs and assess the impact of these in overall survival (OS). METHODS: We screened 551 patients with SI-NETs diagnosed from 1993, through 2021, identified using the SI-NET databases from five European referral centres. Only patients with well-differentiated tumours and available baseline tumour samples and follow-up re-biopsies were included. For tumour grading, apart from 2017 WHO classification system, we applied a recently proposed SI-NET site-specific modified histopathological grading system with Ki-67 cut-offs of 5 and 10%. Uni- and multivariable regression analyses were used to determine whether there was a difference between OS in SI-NET patients stratified by increment of Ki-67 indices over time and/or progression to a higher grade. RESULTS: We included 45 patients. Median Ki-67 index at SI-NET diagnosis was 2% (range: 0.5-15%). Thirty-three patients had Ki-67 indices <5% (70.2%), 6 had Ki-67: 5-10% (12.8%), and 8 had Ki-67 ≥10% (17%). Mean time to re-biopsy was 48.8 months (SD: ±162.5). At re-biopsy, the median change in Ki-67 index (absolute value; follow-up minus time of diagnosis) was 1% (range: -10 to +38%). An increase in Ki-67 occurred in 20 patients (42.6%); in 14 patients, the change in Ki-67 resulted in progression to higher tumour grade following the modified grading system. Patients with an increment in Ki-67 ≥1% had a median OS of 32.9 months versus 80.5 months in patients without (HR = 5.6, 95% CI: 1.42-22.02; p = 0.014). When applying the novel modified histopathological grading system for SI-NETs, patients with grade progression had a median OS of 32.9 months versus 53.7 months in those without (HR = 4.61, 95% CI: 1.22-13.54; p = 0.022). At multivariable analysis, grade progression was confirmed as an independent predictor for death (HR = 7.2, 95% CI: 1.58-32.82; p = 0.011). CONCLUSIONS: Metachronous increment in Ki-67 indices and related grade progression over time following a site-specific modified histopathological grading system with Ki-67 cut-offs of 5 and 10% is observed in approximately 1/3 of SI-NETs subjected to re-biopsy and it is associated with worse survival outcomes.

Population Attributable Risk of Wheeze in 2-<6-Year-old Children, Following a Respiratory Syncytial Virus Lower Respiratory Tract Infection in The First 2 Years of Life.

BACKGROUND: There is limited evidence regarding the proportion of wheeze in young children attributable to respiratory syncytial virus lower respiratory tract infections (RSV-LRTI) occurring early in life. This cohort study prospectively determined the population attributable risk (PAR) and risk percent (PAR%) of wheeze in 2-<6-year-old children previously surveilled in a primary study for RSV-LRTI from birth to their second birthday (RSV-LRTI<2Y). METHODS: From 2013 to 2021, 2-year-old children from 8 countries were enrolled in this extension study (NCT01995175) and were followed through quarterly surveillance contacts until their sixth birthday for the occurrence of parent-reported wheeze, medically-attended wheeze or recurrent wheeze episodes (≥4 episodes/year). PAR% was calculated as PAR divided by the cumulative incidence of wheeze in all participants. RESULTS: Of 1395 children included in the analyses, 126 had documented RSV-LRTI<2Y. Cumulative incidences were higher for reported (38.1% vs. 13.6%), medically-attended (30.2% vs. 11.8%) and recurrent wheeze outcomes (4.0% vs. 0.6%) in participants with RSV-LRTI<2Y than those without RSV-LRTI<2Y. The PARs for all episodes of reported, medically-attended and recurrent wheeze were 22.2, 16.6 and 3.1 per 1000 children, corresponding to PAR% of 14.1%, 12.3% and 35.9%. In univariate analyses, all 3 wheeze outcomes were strongly associated with RSV-LRTI<2Y (all global P < 0.01). Multivariable modeling for medically-attended wheeze showed a strong association with RSV-LRTI after adjustment for covariates (global P < 0.0001). CONCLUSIONS: A substantial amount of wheeze from the second to sixth birthday is potentially attributable to RSV-LRTI<2Y. Prevention of RSV-LRTI<2Y could potentially reduce wheezing episodes in 2-<6-year-old children.

Correction: Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms.

Correction for 'Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms' by Lydia W. Njenga et al., Dalton Trans., 2023, 52, 5823-5847, https://doi.org/10.1039/D3DT00366C.

Early Mediterranean-Based Nutritional Intervention Reduces the Rate of Gestational Diabetes in Overweight and Obese Pregnant Women: A Post-Hoc Analysis of the San Carlos Gestational Prevention Study.

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before the 12th gestational week (GW) in women at high risk due to a body mass index (BMI) ≥ 25 kg/m2 reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI ≥ 25 kg/m2 were evaluated between 2015 and 2018, with 246 in the standard diet control group (CG) and 489 in the MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1% vs. 31.7%), relative risk (95% confidence interval), and 0.89 (0.78-0.99); p = 0.037. Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92); p = 0.019), obesity (0.51 (0.28-0.92); p = 0.041), waist circumference (WC) ≥ 89.5 cm (0.54 (0.31-0.94); p = 0.022), and MetS (0.56 (0.33-0.94); p = 0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI) ≥ 25 kg/m2, suggesting that its implementation should be routinely recommended from the first GWs.

Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health.

Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.

Postnatal Cardiometabolic Health After Metformin Use in Gestational Diabetes: A Secondary Analysis of the EMERGE Trial.

AIM: Women with GDM display adverse lifetime cardio-metabolic health. We examined whether early metformin in GDM could impact cardio-metabolic risk factors postpartum. RESEARCH DESIGN & METHODS: EMERGE, a double-blind, placebo-controlled trial randomized pregnancies 1:1 to placebo or metformin at GDM diagnosis and followed participants from randomization until 12±4 weeks postpartum. In total 478 pregnancies were available for postpartum maternal assessment, 237 and 241 assigned to metformin and placebo respectively. Weight (kg), body mass index (BMI) (kg/m2), waist circumference (cm) and blood pressure (mmHg) were measured, infant feeding method documented and bloods drawn for a 75 gram oral glucose tolerance test, fasting insulin, C peptide and lipid analysis. RESULTS: Despite similar weight and BMI at trial randomization, participants receiving metformin had significantly lower weight (79.5±15.9 vs 82.6±16.9kg; p=0.04) and BMI (29.3(5.6) vs 30.5(5.4); p=0.018) at the postpartum visit. However no difference in weight change from randomisation to 12 weeks postpartum was observed between metformin and placebo groups. Overall 29% (n=139) of the cohort met criteria for prediabetes or diabetes, with no positive impact with metformin. There were also no differences in measurements of insulin resistance, blood pressure or lipids between groups. CONCLUSION: Early metformin use in GDM did not impact important cardio-metabolic parameters in the early postpartum period despite significant benefits in weight gain and insulin use in pregnancy.

Plerixafor for pathogen-agnostic treatment in murine thigh infection and zebrafish sepsis.

Plerixafor is a CXCR4 antagonist approved in 2008 by the FDA for hematopoietic stem cell collection. Subsequently, plerixafor has shown promise as a potential pathogen-agnostic immunomodulator in a variety of preclinical animal models. Additionally, investigator-led studies demonstrated plerixafor prevents viral and bacterial infections in patients with WHIM syndrome, a rare immunodeficiency with aberrant CXCR4 signaling. Here, we investigated whether plerixafor could be repurposed to treat sepsis or severe wound infections, either alone or as an adjunct therapy. In a Pseudomonas aeruginosa lipopolysaccharide (LPS)-induced zebrafish sepsis model, plerixafor reduced sepsis mortality and morbidity assessed by tail edema. There was a U-shaped response curve with the greatest effect seen at 0.1 µM concentration. We used Acinetobacter baumannii infection in a neutropenic murine thigh infection model. Plerixafor did not show reduced bacterial growth at 24 h in the mouse thigh model, nor did it amplify the effects of a rifampin antibiotic therapy, in varying regimens. While plerixafor did not mitigate or treat bacterial wound infections in mice, it did reduce sepsis mortality in zebra fish. The observed mortality reduction in our LPS model of zebrafish was consistent with prior research demonstrating a mortality benefit in a murine model of sepsis. However, based on our results, plerixafor is unlikely to be successful as an adjunct therapy for wound infections. Further research is needed to better define the scope of plerixafor as a pathogen-agnostic therapy. Future directions may include the use of longer acting CXCR4 antagonists, biased CXCR4 signaling, and optimization of animal models.

Wound healing effects of biogenic gold nanoparticles synthesized using red wine extracts.

Gold nanoparticles (AuNPs) were synthesized using three red wine extracts (RW-Es); by varying temperature, pH, concentrations of RW-Es and gold salt. The RW-AuNPs were characterized by UV-vis, transmission electron microscopy (TEM), dynamic light scattering (DLS), and the Fourier Transform Infra-red Spectroscopy (FT-IR). Their stability was evaluated in water, foetal bovine serum (FBS), phosphate-buffered saline (PBS), and Dulbecco's Modified Eagle Medium (DMEM) by UV-Vis. The effect of the RW-Es and RW-AuNPs on KMST-6 cell cell viability was evaluated by MTT assay; and their wound healing effects were monitored by scratch assay. RW-AuNPs synthesis was observed by colour change, and confirmed by UV-Vis spectrum, with an absorption peak around 550 nm. The hydrodynamic sizes of the RW-AuNPs ranged between 10 and 100 nm. Polyphenols, carboxylic acids, and amino acids are some of functional groups in the RW-Es that were involved in the reduction of RW-AuNPs. The RW-AuNPs were stable in test solutions and showed no cytotoxicity to the KMST-6 cells up to 72 h. AuNPs synthesized from Pinotage and Cabernet Sauvignon enhanced proliferation of KMST-6 cells and showed potential as wound healing agents. Further studies are required to investigate the molecular mechanisms involved in the potential wound-healing effect of the RW-AuNPs.

Effects of resistance exercise and whey protein supplementation on cognitive function in older men: secondary analysis of a randomised, double-blind, placebo-controlled trial.

PURPOSE: Ageing is associated with cognitive decline. This study investigated the individual and combined effects of resistance exercise (RE) and whey protein supplementation (PRO) on cognitive function in older men. METHODS: In a pooled-groups analysis, 36 older men (age: 67 ± 4 years) were randomised to either RE (2 x/week; n = 18) or no exercise (NE; n = 18), and either PRO (2 × 25 g/d whey protein isolate; n = 18) or control (CON, 2 × 23.75 g maltodextrin/d; n = 18). A sub-analysis was also conducted between RE + CON (n = 9) and RE + PRO (n = 9). At baseline and 12 weeks, participants completed a battery of neuropsychological tests (CANTAB; Cambridge Cognition, UK) and neurobiological, inflammatory, salivary cortisol and insulin sensitivity biomarkers were quantified. RESULTS: PRO improved executive function z-score (+0.31 ± 0.08) greater than CON (+0.06 ± 0.08, P = 0.03) and there was a trend towards improved global cognitive function (P = 0.053). RE and RE + PRO did not improve any cognitive function domains (p ≥ 0.07). RE decreased tumor necrosis factor-alpha (P = 0.02) and interleukin-6 (P = 0.048) concentrations compared to NE, but changes in biomarkers did not correlate with changes in cognitive domains. Muscle strength (r = 0.34, P = 0.045) and physical function (ρ = 0.35-0.51, P < 0.05) outcomes positively correlated with cognitive function domains at baseline, but only Δskeletal muscle index correlated with Δepisodic memory (r = 0.34, P = 0.046) following the intervention. CONCLUSION: In older men, PRO improved cognitive function, most notably executive functioning. RE did not improve any cognitive function domains but did decrease biomarkers of systemic inflammation. No synergistic effects were observed.