Development and feasibility of a conceptual model for planning individualised physical exercise training (IPET) for older adults: a cross-sectional study.

OBJECTIVE: Older adults constitute a heterogeneous group, and the focus of the individual physical exercise is often subject to the reasoning and experience of health professionals or exercise physiologists who prescribe them. Thus, this is the first effort to explicitly conceptualise the planning of individualised physical exercise training (IPET) for older adults in an outpatient setting and investigate individual exercise preferences. DESIGN: The concept of IPET was developed by researchers, exercise physiologists and health professionals from a real-life outpatient setting using an iterative approach. Health indicators assessing aerobic capacity, strength, balance and musculoskeletal pain/discomfort sites form the basis of physical exercise recommendations. A cross-sectional study was conducted to assess the basis of implementing IPET. SETTING: Outpatient setting. PARTICIPANTS: We included 115 older adults (70 females) from an outpatient setting with a median age of 74 years. OUTCOME MEASURES: Health indicators assessing aerobic capacity, strength, balance and musculoskeletal pain/discomfort sites were collected and informed the concept of IPET that structures exercise programmes based on the individual citizen's needs and physical exercise preferences. Exceeding a health indicator cut-point results in exercise content mitigating the risk associated with the health indicator. RESULTS: We included 115 older adults (70 females) from an outpatient setting median age of 74 years. Approximately two-thirds of participants exceeded at least one health indicator cut-point for aerobic training. One-third of the participants exceeded the cut-point for upper extremity strength, and almost all participants >99% exceeded the cut-point for lower extremity strength. Approximately two-thirds of the participants exceeded the cut-point for functional/balance training. The most prevalent site of musculoskeletal pain was the lower extremities. Eight of 20 training combinations were used, clustering the 115 participants primarily in three main training combinations. DISCUSSION: This study shows that older adults vary in physical functioning, indicating that exercise preferences and rehabilitation needs are individual. TRIAL REGISTRATION NUMBER: NCT04862481.

Evaluation of a retinal oximetry image quality indicator in patients with cataract.

PURPOSE: To evaluate a new automated retinal oximetry image quality indicator with cataract as a clinical model. METHODS: Sixty-one eyes in 61 patients were imaged by the Oxymap T1 Retinal Oximeter at baseline and 25 eyes were also examined 3 weeks after cataract surgery. Image quality (0-10 on a continuous scale) was compared with standardized AREDS cataract grading and Pentacam lens densitometry. Associations with retinal oximetry measurements and visual acuity were examined. RESULTS: Image quality correlated with total, nuclear and posterior subcapsular cataract grades (ANOVA, p < 0.05), tended to be associated with lens densitometry and it improved from 4.3 ± 1.4 to 5.7 ± 1.0 (p < 0.05) after cataract surgery. Very low image quality, below 3, led to vessel detection failure in retinal oximetry images. Higher image qualities were linearly associated with higher measured retinal oxygen saturations (r = 0.52 in arteries and r = 0.46 in veins; p < 0.001). CONCLUSION: Retinal oximetry image quality deteriorated with increasing cataract density and improved after cataract surgery, supporting its use as a measure of optical clarity. The numerical quality indicator demonstrated a threshold below which images of poor optical quality should be discarded. Image quality affects the estimates of retinal oximetry parameters and should therefore be included in future analyses.

Outbreak of Bilateral Endophthalmitis After Immediate Sequential Bilateral Cataract Surgery.

Importance: Since bilateral simultaneous postoperative endophthalmitis (BSPOE) after immediate sequential bilateral cataract surgery (ISBCS) can be devastating for the patient, evaluating such cases in depth is important to maintaining patient safety. Objective: To evaluate whether a systemic breach of sterility was associated with an outbreak of BSPOE after ISBCSs performed on the same day at a single community-based eye clinic. Design, Setting, and Participants: This retrospective case series included all patients diagnosed with BSPOE at ophthalmology departments in Denmark following an infectious outbreak after ISBCSs performed at a single community-based eye clinic in December 2022. Exposure: Bilateral simultaneous postoperative endophthalmitis acquired after ISBCS. Main Outcome and Measures: Patient recovery from BSPOE after ISBCS was evaluated based on clinical and microbiological reports. Results: A woman aged 71 years, a man aged 84 years, and a woman aged 79 years consecutively presented with symptoms of endophthalmitis at regional eye departments 4 to 8 days after ISBCS performed on the same date at the same eye clinic. Five of 6 infected eyes underwent vitrectomy, and all eyes received an intravitreous injection of antibiotics. The same strain of Staphylococcus epidermidis was isolated in 4 of 5 eyes that underwent vitrectomy. Contamination of viscoelastics was ruled out with repeated cultures. One eye was eviscerated due to phthisis. In another patient, the final visual acuity of the eye most severely affected was 20/63 Snellen equivalents. Visual acuity of the remaining eyes recovered to 20/25 (3 eyes in 2 patients) and 20/20 (1 eye) Snellen equivalents. Conclusions and Relevance: The finding of the same strain of S epidermidis in all patient cultures suggests a systemic breach of sterility at the clinic on the day of ISBCS. The outcome of these cases emphasizes the need to adhere to a strict surgical methodology and sterile principles during ISBCS.

Dose-Response of Myofibrillar Protein Synthesis To Ingested Whey Protein During Energy Restriction in Overweight Postmenopausal Women: A Randomized, Controlled Trial.

BACKGROUND: Diet-induced weight loss is associated with a decline in lean body mass, as mediated by an impaired response of muscle protein synthesis (MPS). The dose-response of MPS to ingested protein, with or without resistance exercise, is well characterized during energy balance but limited data exist under conditions of energy restriction in clinical populations. OBJECTIVE: To determine the dose-response of MPS to ingested whey protein following short-term diet-induced energy restriction in overweight, postmenopausal, women at rest and postexercise. DESIGN: Forty middle-aged (58.6±0.4 y), overweight (BMI: 28.6±0.4), postmenopausal women were randomly assigned to 1 of 4 groups: Three groups underwent 5 d of energy restriction (∼800 kcal/d). On day 6, participants performed a unilateral leg resistance exercise bout before ingesting either a bolus of 15g (ERW15, n = 10), 35g (ERW35, n = 10) or 60g (ERW60, n = 10) of whey protein. The fourth group (n = 10) ingested a 35g whey protein bolus after 5 d of an energy balanced diet (EBW35, n = 10). Myofibrillar fractional synthetic rate (FSR) was calculated under basal, fed (FED) and postexercise (FED-EX) conditions by combining an L-[ring-13C6] phenylalanine tracer infusion with the collection of bilateral muscle biopsies. RESULTS: Myofibrillar FSR was greater in ERW35 (0.043±0.003%/h, P = 0.013) and ERW60 (0.042±0.003%/h, P = 0.026) than ERW15 (0.032 ± 0.003%/h), with no differences between ERW35 and ERW60 (P = 1.000). Myofibrillar FSR was greater in FED (0.044 ± 0.003%/h, P < 0.001) and FED-EX (0.048 ± 0.003%/h, P < 0.001) than BASAL (0.027 ± 0.003%/h), but no differences were detected between FED and FED-EX (P = 0.732) conditions. No differences in myofibrillar FSR were observed between EBW35 (0.042 ± 0.003%/h) and ERW35 (0.043 ± 0.003%/h, P = 0.744). CONCLUSION: A 35 g dose of whey protein, ingested with or without resistance exercise, is sufficient to stimulate a maximal acute response of MPS following short-term energy restriction in overweight, postmenopausal women, and thus may provide a per serving protein recommendation to mitigate muscle loss during a weight loss program. TRIAL REGISTRY: clinicaltrials.gov (ID: NCT03326284).

Changes in Muscle Mass and Strength During Follow-Up After One-Year Resistance Training Interventions in Older Adults.

ABSTRACT: Mertz, KH, Reitelseder, S, Rasmussen, MA, Bülow, J, Højfeldt, G, Jensen, M, Hjulmand, M, Lindberg, J, Kramer, MU, Bechshøft, R, and Holm, L. Changes in muscle mass and strength during follow-up after one-year resistance training interventions in older adults. J Strength Cond Res 37(10): 2064-2070, 2023-The aim of this study was to investigate if home-based resistance training compared with center-based resistance training was associated with better preservation of muscle mass and strength in older individuals, 6 months after the interventions ended. One hundred four healthy older individuals (>65 years) who had completed 1 year of either home-based light-intensity training with daily whey protein supplementation (LITW), center-based heavy resistance training with whey protein supplementation (HRTW), or daily whey protein supplementation alone (WHEY) returned for follow-up measurement 6 months after the interventions. Measures of muscle mass, strength, and power were assessed at the end of intervention as well as at follow-up. Furthermore, we compared changes in these parameters between subjects who continued resistance training (≥1 weekly training session) during follow-up (CONT) with those who stopped (STOP). Resistance training continuation during follow-up did not differ between HRTW and LITW (41 vs. 41%, P = 1.0) but was higher for both groups compared with WHEY (18%, P = 0.04-0.05). However, no between-group differences were observed between LITW/HRTW/WHEY in changes in muscle mass, strength, or power during follow-up. STOP was associated with a poorer preservation of quadriceps cross-sectional area compared with CONT (-1.7 cm 2 [-0.4 to -3.0], P = 0.01, effect size: 0.79). No effect of training continuation was observed on changes in muscle strength and power. In conclusion, maintenance of muscle mass and strength is not superior after home-based resistance training compared with center-based training. However, training continuation seems crucial for the maintenance of muscle mass, irrespective of the training intervention.

Effect of 1-year daily protein supplementation and physical exercise on muscle protein synthesis rate and muscle metabolome in healthy older Danes: a randomized controlled trial.

BACKGROUND: The skeletal muscle mass decreases with age and the responsiveness of aging muscles' protein synthesis rate (MPS) to protein intake seems to deteriorate. OBJECTIVE: This study investigated the impact of 12 months of protein supplementation with or without physical exercise training on the basal and postprandial MPS and the skeletal muscle metabolome of healthy older Danes (> 65 years, 29 females/37 males). METHODS: Subjects were randomized to follow one of five intervention groups: (1) carbohydrate, (2) collagen protein, (3) whey protein, (4) home-based light resistance training with whey protein, and (5) center-based heavy-load resistance training with whey protein. Before and after the intervention, a tracer infusion trial was conducted to measure basal and postprandial MPS in response to intake of a cocktail consisting of 20 g whey hydrolysate + 10 g glucose. In addition, the skeletal muscle metabolome was measured using gas chromatography-mass spectrometry (GC-MS) at basal state and 4 h after the intake of the cocktail. RESULTS: One year of daily protein or carbohydrate supplementation did not alter the basal and protein-stimulated postprandial muscle protein synthesis rate or the muscle metabolome of healthy older Danes. Basal MPS (%/h) at baseline for all subjects were 0.0034 ± 0,011 (mean ± SD). In contrast to previous studies, no difference was observed in basal MPS between males and females (p = 0.75). With the developed untargeted GC-MS methodology, it was possible to detect and tentatively annotate > 70 metabolites from the human skeletal muscle samples. CONCLUSION: One year of protein supplementation in comparison to an isocaloric-control supplement seems to affect neither the MPS at basal or postprandial state nor the skeletal muscle metabolome. CLINICAL TRIAL REGISTRY: Number: NCT02115698, clinicaltrials.gov/ct2/show/NCT02115698.

Even or skewed dietary protein distribution is reflected in the whole-body protein net-balance in healthy older adults: A randomized controlled trial.

BACKGROUND & AIM: For older adults, the dietary protein intake has shown to be skewed towards the evening meal. Resultingly, the vital source of essential amino acids could be insufficient after some meals, while after the evening meal the dietary protein could be suboptimally utilized for protein synthesis. The present study explored if an even distribution of the protein intake could improve the dietary amino acid absorption and whole-body protein net-balance. METHODS: Twenty-four healthy elderly males and females were included in a randomized controlled trial. Ten days of habituation to either an EVEN (n = 12) or SKEWED (n = 12) protein intake, was followed by a trial day. The total protein intake was controlled at 1.5 g/kg LBM, divided into 30% at each main meal in EVEN, and into 15% at breakfast and lunch and 60% at dinner in SKEWED. Snacks with 5% of the protein intake were served between meals. Energy intake in the meals and snacks were equal in both groups. Intrinsically labelled 2H5-phenylalanine minced meat was served as the dietary protein to assess the amino acid absorption. On the trial day, infusion of 2H8-phenylalanine and 2H2-tyrosine, and blood samples taken over 11 h were used to measure whole-body protein turnover. Vastus lateralis muscle biopsies were taken to measure 9 h muscle protein FSR. RESULTS: Amino acid absorption rates and concentrations were greater in EVEN compared to SKEWED protein intake. Whole-body protein breakdown rates were lower with similar protein synthesis rates, and consequently the net-balance was greater in EVEN after breakfast and lunch compared to SKEWED and were the same in both groups after dinner. Muscle protein FSR were not different between EVEN and SKEWED. CONCLUSIONS: The whole-body protein net-balance was more positive in EVEN compared to SKEWED for an extended time of the measured period, driven by a lower whole-body protein breakdown in EVEN. CLINICAL TRIALS REGISTRATION: NCT03870425, https://clinicaltrials.gov/ct2/show/NCT03870425.

MicroRNA sequence variation can impact interactions with target mRNA in cattle.

BACKGROUND: Small non-coding microRNAs (miRNAs) are important modulators at post-transcriptional levels. Single-nucleotide polymorphisms (SNPs) located in miRNA genes can alter the secondary structure of pre-miRNA to either impair or promote the miRNA maturation processes. Furthermore, SNPs located in the miRNA seed regions can stabilize or disturb miRNA-target interactions, thereby, quantitatively influence the expression of target genes. Therefore, the main objective of this study was to detect SNPs in bovine miRNAs using the whole-genome re-sequencing datasets of 1632 cattle of five breeds from the 1000 bull genomes project. RESULTS: In total, our study identified 1109, 334, and 130 SNPs in the miRNA precursor, mature, and seed regions, respectively. The heterozygosity values were generally less than 0.3, and the minor allele frequencies (MAFs) were mainly less than 0.1. Most SNPs were in Hardy-Weinberg equilibrium (HWE) (HWE-P > 0.05). Furthermore, we found that the majority of SNPs (MAF > 0.1 and HWE-P > 0.05) in the miRNA seed regions altered the repertoire of target genes, which in turn were enriched in different KEGG pathways or GO terms. Thus target prediction for bta-miR-2888 revealed loss of 309 target genes and gain of 691 target genes. The 691 gained target genes were significantly enriched in 60 KEGG pathways and 21 GO terms. CONCLUSION: In summary, our study identified candidate SNPs in miRNA precursor, mature, and seed regions that are likely to affect target RNA interactions, thereby potentially influencing cattle phenotypic traits.

Dietary protein requirements and recommendations for healthy older adults: a critical narrative review of the scientific evidence.

Adequate protein intake is essential for the maintenance of whole-body protein mass. Different methodological approaches are used to substantiate the evidence for the current protein recommendations, and it is continuously debated whether older adults require more protein to counteract the age-dependent loss of muscle mass, sarcopenia. Thus, the purpose of this critical narrative review is to outline and discuss differences in the approaches and methodologies assessing the protein requirements and, hence, resulting in controversies in current protein recommendations for healthy older adults. Through a literature search, this narrative review first summarises the historical development of the Food and Agriculture Organization/World Health Organization/United Nations University setting of protein requirements and recommendations for healthy older adults. Hereafter, we describe the various types of studies (epidemiological studies and protein turnover kinetic measurements) and applied methodological approaches founding the basis and the different recommendations with focus on healthy older adults. Finally, we discuss important factors to be considered in future studies to obtain evidence for international agreement on protein requirements and recommendations for healthy older adults. We conclude by proposing future directions to determine 'true' protein requirements and recommendations for healthy older adults.

Comparing Even with Skewed Dietary Protein Distribution Shows No Difference in Muscle Protein Synthesis or Amino Acid Utilization in Healthy Older Individuals: A Randomized Controlled Trial.

Sarcopenia is a multifactorial disease that limits autonomy for the growing elderly population. An optimal amount of dietary protein has shown to be important to maintain muscle mass during aging. Yet, the optimal distribution of that dietary protein has not been fully clarified. The aim of the present study was to examine whether an even, compared to a skewed, distribution of daily dietary protein leads to higher muscle protein synthesis and amino acid utilization. Twelve healthy males and twelve healthy females aged between 65 and 80 years were block randomized to either an even (EVEN, n = 12) or skewed (SKEWED, n = 12) dietary protein distribution for three daily main meals. Seven days of habituation were followed by three trial days, which were initiated by oral intake of deuterium oxide (D2O). The dietary protein throughout all trial meals was intrinsically labelled with 2H5-phenylalanine. Blood samples were drawn daily, and muscle biopsies were taken before and at the end of the trial to measure muscle protein synthesis (FSR) and muscle protein incorporation of the dietary-protein-derived tracer. Muscle protein FSR was no different between the two groups (EVEN 2.16 ± 0.13%/day and SKEWED 2.23 ± 0.09%/day, p = 0.647), and the muscle protein incorporation of the intrinsically labeled 2H5-phenylalanine tracer was not different between the two groups (EVEN 0.0049 ± 0.0004 MPE% and SKEWED 0.0054 ± 0.0003 MPE%, p = 0.306). In conclusion, the daily distribution pattern of the dietary protein did not affect muscle protein synthesis or the utilization of dietary protein.

Gut Microbiome and Its Cofactors Are Linked to Lipoprotein Distribution Profiles.

Increasing evidence indicates that the gut microbiome (GM) plays an important role in dyslipidemia. To date, however, no in-depth characterization of the associations between GM with lipoproteins distributions (LPD) among adult individuals with diverse BMI has been conducted. To determine such associations, we studied blood-plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 Danes aged 19-89 years. Stratification of LPD segregated subjects into three clusters displaying recommended levels of lipoproteins and explained by age and body-mass-index. Higher levels of HDL2a and HDL2b were associated with a higher abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL-1 and LDL-2 were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome-sequencing showed a higher abundance of biosynthesis of multiple B-vitamins and SCFA metabolism genes among healthier LPD profiles. Metagenomic-assembled genomes (MAGs) affiliated to Eggerthellaceae and Clostridiales were contributors of these genes and their relative abundance correlated positively with larger HDL subfractions. The study demonstrates that differences in composition and metabolic traits of the GM are associated with variations in LPD among the recruited subjects. These findings provide evidence for GM considerations in future research aiming to shed light on mechanisms of the GM-dyslipidemia axis.

Ubiquitin E3 ligase Atrogin-1 protein is regulated via the rapamycin-sensitive mTOR-S6K1 signaling pathway in C2C12 muscle cells.

Atrogin-1 and Muscle-specific RING finger protein 1 (MuRF1) are highly expressed in multiple conditions of skeletal muscle atrophy. The phosphoinositide 3-kinase (PI3K)/Akt/forkhead box (FoxO) signaling pathway is well known to regulate Atrogin-1 and MuRF1 gene expressions. However, Akt activation also activates the mechanistic target of rapamycin complex 1 (mTORC1), which induces skeletal muscle hypertrophy. Whether mTORC1-dependent signaling has a role in regulating Atrogin-1 and/or MuRF1 gene and protein expression is currently unclear. In this study, we showed that activation of insulin-mediated Akt signaling suppresses both Atrogin-1 and MuRF1 protein contents and that inhibition of Akt increases both Atrogin-1 and MuRF1 protein contents in C2C12 myotubes. Interestingly, inhibition of mTORC1 with a specific mTORC1 inhibitor, rapamycin, increased Atrogin-1, but not MuRF1, protein content. Furthermore, activation of AMP-activated protein kinase (AMPK), a negative regulator of the mTORC1 signaling pathway, also showed distinct time-dependent changes between Atrogin-1 and MuRF1 protein contents, suggesting differential regulatory mechanisms between Atrogin-1 and MuRF1 protein content. To further explore the downstream of mTORC1 signaling, we employed a specific S6K1 inhibitor, PF-4708671. We found that Atrogin-1 protein content was dose-dependently increased with PF-4708671 treatment, whereas MuRF1 protein content was decreased at 50 µM of PF-4708671 treatment. However, MuRF1 protein content was unexpectedly increased by PF-4708671 treatment for a longer period. Overall, our results indicate that Atrogin-1 and MuRF1 protein contents are regulated by different mechanisms, the downstream of Akt, and that Atrogin-1 protein content can be regulated by the rapamycin-sensitive mTOR-S6K1-dependent signaling pathway.

Co-ingestion of cluster dextrin carbohydrate does not increase exogenous protein-derived amino acid release or myofibrillar protein synthesis following a whole-body resistance exercise in moderately trained younger males: a double-blinded randomized controlled crossover trial.

PURPOSE: This study investigates if co-ingestion of cluster dextrin (CDX) augments the appearance of intrinsically labeled meat protein hydrolysate-derived amino acid (D5-phenylalanine), Akt/mTORC1 signaling, and myofibrillar protein fractional synthetic rate (FSR). METHODS: Ten moderately trained healthy males (age: 21.5 ± 2.1 years, body mass: 75.7 ± 7.6 kg, body mass index (BMI): 22.9 ± 2.1 kg/m2) were included for a double-blinded randomized controlled crossover trial. Either 75 g of CDX or glucose (GLC) was given in conjunction with meat protein hydrolysate (0.6 g protein * FFM-1) following a whole-body resistance exercise. A primed-continuous intravenous infusion of L-[15N]-phenylalanine with serial muscle biopsies and venous blood sampling was performed. RESULTS: A time × group interaction effect was found for serum D5-phenylalanine enrichment (P < 0.01). Serum EAA and BCAA concentrations showed a main effect for group (P < 0.05). Tmax serum BCAA was greater in CDX as compared to GLC (P < 0.05). However, iAUC of all serum parameters did not differ between CDX and GLC (P > 0.05). Tmax serum EAA showed a trend towards a statistical significance favoring CDX over GLC. The phosphorylation of p70S6KThr389, rpS6Ser240/244, ERK1/2Thr202/Tyr204 was greater in CDX compared to GLC (P < 0.05). However, postprandial myofibrillar FSR did not differ between CDX and GLC (P = 0.17). CONCLUSION: In moderately trained younger males, co-ingestion of CDX with meat protein hydrolysate does not augment the postprandial amino acid availability or myofibrillar FSR as compared to co-ingestion of GLC during the recovery from a whole-body resistance exercise despite an increased intramuscular signaling. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03303729 (registered on October 3, 2017).

Previous intravitreal injection as a risk factor of posterior capsule rupture in cataract surgery: a systematic review and meta-analysis.

PURPOSE: Intravitreal injections and cataract surgery are two common procedures in the elderly. Posterior capsular rupture (PCR) is a rare but important complication of cataract surgery. We systematically reviewed the literature on previous intravitreal injections as a risk factor of PCR and performed meta-analyses to provide pooled summary risk estimates. METHODS: We searched 13 literature databases on 1 June 2021 for studies evaluating the risk of PCR in eyes undergoing cataract surgery with data on previous intravitreal injections. Data extraction was made independently by two authors and discussed afterwards until reaching consensus. Random effects meta-analyses on the pooled odds ratio (OR) of PCR in eyes with previous intravitreal injections were made using MetaXL 5.3. RESULTS: Six studies on 1 051 097 eyes undergoing cataract surgery were eligible for the qualitative and quantitative review. Previous history of intravitreal injections was present in 7034 eyes (majority was anti-VEGF). Our meta-analyses revealed that any previous intravitreal injection was a risk factor for PCR with an OR of 2.30 (95% CI 1.39-3.81). For each previous intravitreal injection, the risk of PCR was OR 1.04 (95% CI 1.01-1.08) (equivalent of relative risk ~1.04). In other words, risk of PCR increases by 4% for each previous intravitreal injection. CONCLUSIONS: Previous intravitreal injection is a risk factor for PCR and should be taken into account when planning cataract surgery. However, to be regarded as a clinically significant risk of PCR, a substantial number of previous intravitreal injection (e.g. ≥10) should have been administered, considering that the a priori risk of PCR is very low (~1%).

Impact of tobacco use on corneal thickness and endothelial health: a systematic review with meta-analyses.

PURPOSE: To investigate the impact of tobacco use on corneal thickness and corneal endothelial health. METHODS: We searched the PubMed/MEDLINE, EMBASE, the Cochrane Central and all affiliated databases of the Web of Science on 20 July 2020. Two authors reviewed the studies and extracted the data in an independent fashion. Studies were reviewed qualitatively in the text, and central corneal thickness (CCT) and corneal endothelial characteristics (endothelial cell density, endothelial cell variability, average of endothelial cell size and endothelial cell hexagonality) were introduced for quantitative analyses. RESULTS: Eighteen studies (2077 were smokers and 6429 non-smokers) were identified, of which 17 studies provided data eligible for one or more of the quantitative analyses. When compared to non-smokers, smokers had a higher CCT (+3.3 µm, 95% CI: +0.9 to +5.7 µm, p = 0.007) and a lower endothelial cell density (-140 cells/mm2 , 95% CI: -30 to -250 cells/mm2 , p = 0.01). Other corneal endothelial measures did not differ significantly. CONCLUSION: Tobacco use is associated with a higher CCT and lower corneal endothelium cell density, but the clinical impact of these findings is small. Further studies are warranted on patients with a priori poor corneal health, where smoking may constitute an important risk of further progression, for example upon anterior segment surgery.

Human Blood Lipoprotein Predictions from 1H NMR Spectra: Protocol, Model Performances, and Cage of Covariance.

Lipoprotein subfractions are biomarkers for the early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time-consuming, and there is a need to develop a rapid method for cohort screenings. This study presents partial least-squares regression models developed using 1H nuclear magnetic resonance (NMR) spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. This study explores, for the first time, different regions of the 1H NMR spectrum representing signals of molecules in lipoprotein particles and different lipid species to develop parsimonious, reliable, and optimal prediction models. A total of 65 lipoprotein main and subfractions were predictable with high accuracy, Q2 of >0.6, using an optimal spectral region (1.4-0.6 ppm) containing methylene and methyl signals from lipids. The models were subsequently tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85-95%. In addition, an open software tool was developed to predict lipoproteins concentrations in human blood from standardized 1H NMR spectral recordings.

A frameshift deletion in the GDF9 gene in Icelandic Loa prolific sheep.

Several genetic variants have been shown to affect the mean number of offspring in different sheep breeds. Here, we analyzed samples from Icelandic sheep with the aim of identifying the genetic cause of the Icelandic Loa phenotype using three previously identified prolificacy genes as candidates. We demonstrate that a 4-bp frameshift deletion positioned in the mature region of the GDF9 protein in the Loa animals is a likely causal mutation for the observed increase in prolificacy; however, sequencing showed that not all ewes with a high number of offspring carried the deletion, suggesting the presence of a second mutation segregating within this group of animals.

Human Fecal Metabolome Reflects Differences in Body Mass Index, Physical Fitness, and Blood Lipoproteins in Healthy Older Adults.

This study investigated how body mass index (BMI), physical fitness, and blood plasma lipoprotein levels are related to the fecal metabolome in older adults. The fecal metabolome data were acquired using proton nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry on 163 healthy older adults (65-80 years old, 80 females and 83 males). Overweight and obese subjects (BMI ≥ 27) showed higher levels of fecal amino acids (AAs) (valine, alanine, and phenylalanine) compared to normal-weight subjects (BMI ≤ 23.5). Adults classified in the high-fitness group displayed slightly lower concentrations of fecal short-chain fatty acids, propionic acid, and AAs (methionine, leucine, glutamic acid, and threonine) compared to the low-fitness group. Subjects with lower levels of cholesterol in low-density lipoprotein particles (LDLchol, ≤2.6 mmol/L) displayed higher fecal levels of valine, glutamic acid, phenylalanine, and lactic acid, while subjects with a higher level of cholesterol in high-density lipoprotein particles (HDLchol, ≥2.1 mmol/L) showed lower fecal concentration of isovaleric acid. The results from this study suggest that the human fecal metabolome, which primarily represents undigested food waste and metabolites produced by the gut microbiome, carries important information about human health and should be closely integrated to other omics data for a better understanding of the role of the gut microbiome and diet on human health and metabolism.

Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response in Apoe knockout mice with an unhealthy lipoprotein distribution.

This study explores if unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Thus, if impairment of such anabolic response to protein consumption is seen by the LPD this may negatively affect the skeletal muscle mass. Muscle protein synthesis (MPS) was measured by puromycin labeling in Apolipoprotein E knockout (Apoe KO), characterized by an unhealthy LPD, and wild type mice post-absorptive at 10 and 20 weeks, and post-prandial after whey-protein feeding at 20 weeks. Hypertrophy signaling and amino acid sensing mechanisms were studied and gut microbiome diversity explored. Surprisingly, whey-protein feeding did not affect MPS. p-mTOR and p-4E-BP1 was increased 2 h after whey-protein feeding in both genotypes, but with general lower levels in Apoe KO compared to wild type. At 20 weeks of age, Apoe KO had a greater mRNA-expression for SNAT2, CD98, ATF4 and GCN2 compared to wild type. These responses were not associated with gut microbiota compositional differences. Regardless of LPD status, MPS was similar in Apoe KO and wild type. Surprisingly, whey-protein did not stimulate MPS. However, Apoe KO had lower levels of hypertrophy signaling, was amino acid deprived, and had impaired amino acid sensing mechanisms.