Autophagic response to exercise in peripheral blood mononuclear cells from young men is intensity-dependent and is altered by exposure to environmental heat.

Autophagy is essential to maintaining cellular homeostasis in all eukaryotic cells and to tolerance of acute stressors such as starvation, heat, and recovery after exercise. Limited information exists regarding the exercise intensity-dependent autophagic response in humans, and it is unknown how environmental heat stress may modulate this response. Therefore, we evaluated autophagy and accompanying pathways of cellular stress [the heat-shock response (HSR), apoptosis, and acute inflammation] in peripheral blood mononuclear cells (PBMCs) from 10 young men (mean [SD]; 22 [2] years) before, immediately after and up to 6-h postexercise recovery from 30 min of low-, moderate-, and high-intensity semirecumbent cycling [40%, 55%, and 70% of maximal oxygen consumption (V̇o2max), respectively] in a temperate environment (25°C) and at 70% of V̇o2max in a hot environment (40°C). Changes in protein content were analyzed via Western blot. Each increase in exercise intensity was associated with elevations in mean body temperature. LC3-II increased after moderate-intensity exercise, with further increases after high-intensity exercise (P < 0.05). However, an increase in beclin-2 and ULK1, with a decrease in p62 was only observed after high-intensity exercise, which was paralleled by elevated TNF-α and cleaved-caspase-3, with the HSR peaking at 6 h after exercise (P < 0.05). When exercise was performed in the heat, greater LC3-II and cleaved-caspase-3 accumulation were observed; however, beclin-2 declined in recovery (P < 0.05). Therefore, our findings indicate that autophagy in PBMCs during exercise may be associated with greater heat strain exhibited during increasing exercise intensities, which is modulated by exposure to heat.

Temporal patterns of multi-morbidity in 570157 ischemic heart disease patients: a nationwide cohort study.

BACKGROUND: Patients diagnosed with ischemic heart disease (IHD) are becoming increasingly multi-morbid, and studies designed to analyze the full spectrum are few. METHODS: Disease trajectories, defined as time-ordered series of diagnoses, were used to study the temporality of multi-morbidity. The main data source was The Danish National Patient Register (NPR) comprising 7,179,538 individuals in the period 1994-2018. Patients with a diagnosis code for IHD were included. Relative risks were used to quantify the strength of the association between diagnostic co-occurrences comprised of two diagnoses that were overrepresented in the same patients. Multiple linear regression models were then fitted to test for temporal associations among the diagnostic co-occurrences, termed length two disease trajectories. Length two disease trajectories were then used as basis for constructing disease trajectories of three diagnoses. RESULTS: In a cohort of 570,157 IHD disease patients, we identified 1447 length two disease trajectories and 4729 significant length three disease trajectories. These included 459 distinct diagnoses. Disease trajectories were dominated by chronic diseases and not by common, acute diseases such as pneumonia. The temporal association of atrial fibrillation (AF) and IHD differed in different IHD subpopulations. We found an association between osteoarthritis (OA) and heart failure (HF) among patients diagnosed with OA, IHD, and then HF only. CONCLUSIONS: The sequence of diagnoses is important in characterization of multi-morbidity in IHD patients as the disease trajectories. The study provides evidence that the timing of AF in IHD marks distinct IHD subpopulations; and secondly that the association between osteoarthritis and heart failure is dependent on IHD.

Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: focus on fundamentals of physiology.

NEW FINDINGS: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its 'natural' posture, and thus optimises the ventilation-perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life-threatening hypoxaemia in COVID-19 and other types of critical illness with respiratory failure. ABSTRACT: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID-19-associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation-perfusion ( V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ ) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral-to-dorsal) V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient is present in both postures, but with better V ̇ A -- Q ̇ ${\dot V_{\rm{A}}}\hbox{--}\dot Q$ matching in the prone position. In ARDS and CARDS, the vertical V ̇ A / Q ̇ ${\dot V_{\rm{A}}}/\dot Q$ ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life-threatening hypoxaemia in patients with ARDS and CARDS.

A real-time PCR regimen for testing environmental samples for Salmonella enterica subsp. enterica serovars of concern to the poultry industry, with special focus on Salmonella Enteritidis.

A real-time PCR (qPCR) regimen, using up to six genetic targets, was developed to rapidly detect Salmonella and in particular identify Salmonella Enteritidis. The test regimen was first evaluated using a reference culture collection of Salmonella to confirm the appropriateness of the selected targets, which included up to three genetic markers for discrimination of Salmonella Enteritidis from other Salmonella serovars commonly found in poultry facilities. The qPCR procedure was then compared with culture methods used to detect Salmonella using a collection of enrichment broths previously generated from 239 environmental samples collected from a large number of hatchery facilities across Canada over several years. The qPCR regimen facilitated specific detection of Salmonella Enteritidis, and on a sample basis, it showed excellent agreement with the culture methods. Moreover, in many cases, qPCR detected Salmonella earlier in the culture process than did the culture method. Application of this method will significantly shorten test times and allow more timely identification of infected poultry premises, thereby improving present programmes aimed at controlling Salmonella Enteritidis at the environmental source.

Flow-directed PCA for monitoring networks.

Measurements recorded over monitoring networks often possess spatial and temporal correlation inducing redundancies in the information provided. For river water quality monitoring in particular, flow-connected sites may likely provide similar information. This paper proposes a novel approach to principal components analysis to investigate reducing dimensionality for spatiotemporal flow-connected network data in order to identify common spatiotemporal patterns. The method is illustrated using monthly observations of total oxidized nitrogen for the Trent catchment area in England. Common patterns are revealed that are hidden when the river network structure and temporal correlation are not accounted for. Such patterns provide valuable information for the design of future sampling strategies.

Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation.

Severe malarial anemia [SMA, hemoglobin (Hb) <5.0 g/dL] is a leading cause of global morbidity and mortality among children residing in Plasmodium falciparum transmission regions. Exploration of molecular pathways through global gene expression profiling revealed that SMA was characterized by decreased HSPA1A, a heat shock protein (Hsp) 70 coding gene. Hsp70 is a ubiquitous chaperone that regulates Nuclear Factor-kappa B (NF-κB) signaling and production of pro-inflammatory cytokines known to be important in malaria pathogenesis (e.g., IL-1ß, IL-6 and TNF-α). Since the role of host Hsp70 in malaria pathogenesis is unexplored, we investigated Hsp70 and molecular pathways in children with SMA. Validation experiments revealed that leukocytic HSP70 transcripts were reduced in SMA relative to non-severe malaria, and that intraleukocytic hemozoin (PfHz) was associated with lower HSP70. HSP70 was correlated with reticulocyte production and Hb. Since glutamine (Gln) up-regulates Hsp70, modulates NF-κB activation, and attenuates over-expression of pro-inflammatory cytokines, circulating Gln was measured in children with malaria. Reduced Gln was associated with increased risk of developing SMA. Treatment of cultured peripheral blood mononuclear cells (PBMCs) with PfHz caused a time-dependent decrease in Hsp70 transcripts/protein, and NF-κB activation. Gln treatment of PBMCs overcame PfHz-induced suppression of HSP70 transcripts/protein, reduced NF-κB activation, and suppressed over-expression of IL-1ß, IL-6 and TNF-α. Findings here demonstrate that SMA is characterized by reduced intraleukocytic HSP70 and circulating Gln, and that PfHz-induced suppression of HSP70 can be reversed by Gln. Thus, Gln supplementation may offer important immunotherapeutic options for futures studies in children with SMA.

The effect of insulin resistance and exercise on the percentage of CD16(+) monocyte subset in obese individuals.

UNLABELLED: Obesity is a low-grade chronic inflammation condition, and macrophages, and possibly monocytes, are involved in the pathological outcomes of obesity. Physical exercise is a low-cost strategy to prevent and treat obesity, probably because of its anti-inflammatory action. We evaluated the percentage of CD16(-) and CD16(+) monocyte subsets in obese insulin-resistant individuals and the effect of an exercise bout on the percentage of these cells. Twenty-seven volunteers were divided into three experimental groups: lean insulin sensitive, obese insulin sensitive and obese insulin resistant. Venous blood samples collected before and 1 h after an aerobic exercise session on a cycle ergometer were used for determination of monocyte subsets by flow cytometry. Insulin-resistant obese individuals have a higher percentage of CD16(+) monocytes (14.8 ± 2.4%) than the lean group (10.0 ± 1.3%). A positive correlation of the percentage of CD16(+) monocytes with body mass index and fasting plasma insulin levels was found. One bout of moderate exercise reduced the percentage of CD16(+) monocytes by 10% in all the groups evaluated. Also, the absolute monocyte count, as well as all other leukocyte populations, in lean and obese individuals, increased after exercise. This fact may partially account for the observed reduction in the percentage of CD16(+) cells in response to exercise. Insulin-resistant, but not insulin-sensitive obese individuals, have an increased percentage of CD16(+) monocytes that can be slightly modulated by a single bout of moderate aerobic exercise. These findings may be clinically relevant to the population studied, considering the involvement of CD16(+) monocytes in the pathophysiology of obesity. Copyright © 2016 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDY: Obesity is now considered to be an inflammatory condition associated with many pathological consequences, including insulin resistance. It is proposed that insulin resistance contributes to the aggravation of the inflammatory dysfunction in obesity. The effect of obesity on the percentage of monocytes was previously observed in class II and III obese individuals who presented other alterations in addition to insulin resistance. In this study we observed that insulin-resistant obese individuals, but not insulin-sensitive ones, had an increased percentage of CD14(+) CD16(+) monocytes. This fact shows that a dysfunction of the monocyte percentage in class I obese individuals is only seen when this condition is associated with insulin resistance.

Assessing the safety and efficacy of drugs used in preparing the nose for diagnostic and therapeutic procedures: a systematic review.

BACKGROUND: Local anaesthetics and vasoconstrictors are essential for pain control and to aid intra-operative haemostasis in nasal procedures. They also improve access, and reduce discomfort when performing nasal endoscopy. There are no clear guidelines on preparing the nose despite evermore diagnostic and therapeutic procedures utilising the nose as a point of access. OBJECTIVE OF REVIEW: This review aims to identify nasal preparations used in diagnostic and therapeutic nasal procedures and to examine their safety and efficacy. TYPE OF REVIEW: Systematic review. SEARCH STRATEGY: A search was carried out using PubMed, MEDLINE, Ovid EMBASE, the Cochrane library and references from the included articles. EVALUATION METHOD: The inclusion criteria included: full-text English language articles with regard to nasal preparation for surgery. Case reports, systematic reviews, meta-analysis, double-blind placebo controlled randomised trials (RCTs) and case series were included. RESULTS: A total of 53 articles were retrieved: 13 articles on nasal preparation for operative procedures, six on functional endoscopic sinus surgery and 22 on nasendoscopy as well as six case reports. Cocaine was the most widely used topical preparation for operative procedures but was associated with more side-effects; thus, topical tetracaine and levobupivacaine infiltration are alternatives with equivalent efficacy but reduced adverse effects. All articles reviewed for functional endoscopic sinus surgery used a mixture containing lidocaine, adrenaline or both. Flexible nasendoscopy causes minimal patient discomfort and preparation is only recommended in selected patients, in contrast to rigid nasendoscopy which requires preparation. CONCLUSION: For operative procedures, such as septorhinoplasty, a single agent tetracaine or levobupivicaine provides an improved surgical field. In functional endoscopic sinus surgery, lidocaine-adrenaline preparations have resulted in significantly better surgical and patient outcomes. There is little evidence to support the routine use of pre-procedural nasal preparation for flexible nasendoscopy. Those undergoing rigid endoscopy conversely always require the use of a vasoconstrictor and local anaesthetic. Pre-procedure assessment of patients is recommended, with agents being reserved for those with low pain thresholds, high anxiety and small nasal apertures presenting resistance to the insertion of the endoscope.

Design and validation of the Regional Anaesthesia Procedural Skills Assessment Tool.

The aim of this study was to create and evaluate the validity, reliability and feasibility of the Regional Anaesthesia Procedural Skills tool, designed for the assessment of all peripheral and neuraxial blocks using all nerve localisation techniques. The first phase was construction of a 25-item checklist by five regional anaesthesia experts using a Delphi process. This checklist was combined with a global rating scale to create the tool. In the second phase, initial validation by 10 independent anaesthetists using a test-retest methodology was successful (Cohen kappa ≥ 0.70 for inter-rater agreement, scores between test to retest, paired t-test, p > 0.12). In the third phase, 70 clinical videos of trainees were scored by three blinded international assessors. The RAPS tool exhibited face validity (p < 0.026), construct validity (p < 0.001), feasibility (mean time to score < 3.9 min), and overall reliability (intraclass correlation coefficient 0.80 (95% CI 0.67-0.88)). The Regional Anaesthesia Procedural Skills tool used in this study is a valid and reliable assessment tool to score the performance of trainees for regional anaesthesia.

Revisiting the phylogeography and demography of European badgers (Meles meles) based on broad sampling, multiple markers and simulations.

Although the phylogeography of European mammals has been extensively investigated since the 1990s, many studies were limited in terms of sampling distribution, the number of molecular markers used and the analytical techniques employed, frequently leading to incomplete postglacial recolonisation scenarios. The broad-scale genetic structure of the European badger (Meles meles) is of interest as it may result from historic restriction to glacial refugia and/or recent anthropogenic impact. However, previous studies were based mostly on samples from western Europe, making it difficult to draw robust conclusions about the location of refugia, patterns of postglacial expansion and recent demography. In the present study, continent-wide sampling and analyses with multiple markers provided evidence for two glacial refugia (Iberia and southeast Europe) that contributed to the genetic variation observed in badgers in Europe today. Approximate Bayesian computation provided support for a colonisation of Scandinavia from both Iberian and southeastern refugia. In the whole of Europe, we observed a decline in genetic diversity with increasing latitude, suggesting that the reduced diversity in the peripheral populations resulted from a postglacial expansion processes. Although MSVAR v.1.3 also provided evidence for recent genetic bottlenecks in some of these peripheral populations, the simulations performed to estimate the method's power to correctly infer the past demography of our empirical populations suggested that the timing and severity of bottlenecks could not be established with certainty. We urge caution against trying to relate demographic declines inferred using MSVAR with particular historic or climatological events.

Survival and function following pharyngo-laryngo-oesophagectomy in Wales: a twelve-year case series.

OBJECTIVE: Treatment of locally advanced hypopharyngeal cancer can cause significant morbidity and late toxicity. Pharyngo-laryngo-oesophagectomy can achieve adequate surgical margins, but data on survival and functional outcome are limited, especially in Wales. This study aimed to describe mortality, morbidity and functional outcome following pharyngo-laryngo-oesophagectomy in a Welsh population. METHOD: This study was a retrospective case note review of pharyngo-laryngo-oesophagectomy cases in Wales over 12 years. RESULTS: Fifteen patients underwent pharyngo-laryngo-oesophagectomy; all but one underwent gastric pull-up. Median survival and disease-free survival were 17 months (range, 2-53 months) and 14 months. Censored 3-month, 1-year and 3-year survival was 93, 71 and 50 per cent, respectively. Common Terminology Criteria for Adverse Events grading of long-term dysphagia was 1 in 58 per cent, 2 in 33 per cent and 3 in 8 per cent, and 87.5 per cent achieved a 'moderate' or 'good' voice rehabilitation. CONCLUSION: These results demonstrate favourable survival and reasonable functional outcome following pharyngo-laryngo-oesophagectomy, suggesting pharyngo-laryngo-oesophagectomy should be considered in all appropriate surgical candidates.

Autophagy and heat: a potential role for heat therapy to improve autophagic function in health and disease.

Autophagy is a crucial cell survival mechanism that involves the degradation and recycling of old or damaged organelles and proteins to maintain cellular homeostasis. Impairments in autophagy are central to the pathogenesis of many conditions including metabolic and neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, and aging. Although various pharmacological agents may be able to stimulate autophagic function, to our knowledge, few interventions exist that have been deemed safe and effective in humans. An emerging body of evidence suggests that targeting the autophagic pathway via passive heating (heat therapy) may stimulate autophagic function. Therefore, the primary focus of the present review is to analyze the mechanisms in which passive heating induces autophagy as defined by in vitro and in vivo (animal and human) models. Our secondary focus is to examine the implications of utilizing passive heating to restore dysfunctional autophagy in chronic disease and aging. Finally, we discuss potential therapeutic strategies to implement passive heating to stimulate autophagic function in humans.

Using isolation-by-distance-based approaches to assess the barrier effect of linear landscape elements on badger (Meles meles) dispersal.

As the European badger (Meles meles) can be of conservation or management concern, it is important to have a good understanding of the species' dispersal ability. In particular, knowledge of landscape elements that affect dispersal can contribute to devising effective management strategies. However, the standard approach of using Bayesian clustering methods to correlate genetic discontinuities with landscape elements cannot easily be applied to this problem, as badger populations are often characterized by a strong confounding isolation-by-distance (IBD) pattern. We therefore developed a two-step method that compares the location of pairs of related badgers relative to a putative barrier and utilizes the expected spatial genetic structure characterized by IBD as a null model to test for the presence of a barrier. If a linear feature disrupts dispersal, the IBD pattern characterising pairs of individuals located on different sides of a putative barrier should differ significantly from the pattern obtained with pairs of individuals located on the same side. We used our new approach to assess the impact of rivers and roads of different sizes on badger dispersal in western England. We show that a large, wide river represented a barrier to badger dispersal and found evidence that a motorway may also restrict badger movement. Conversely, we did not find any evidence for small rivers and roads interfering with badger movement. One of the advantages of our approach is that potentially it can detect features that disrupt gene flow locally, without necessarily creating distinct identifiable genetic units.

Fitness measures in selection analyses: sensitivity to the overall number of offspring produced in a lifetime.

Age at first (alpha) and last (omega) breeding are important life-history traits; however, the direction and strength of selection detected on traits may vary depending on the fitness measure used. We provide the first estimates of lifetime breeding success (LBS) and lambda(ind) (the population growth rate of an individual) of European badgers Meles meles, by genotyping 915 individuals, sampled over 18 years, for 22 microsatellites. Males are slightly larger than females, and the opportunity for selection was slightly greater for males, as predicted. lambda(ind) and LBS both performed well in predicting the number of grand-offspring, and both detected selection for a late omega, until the age of eight. Differential selection (S'(alpha)) for an early alpha, however, was only detected using LBS, not with lambda(ind). In declining populations (lambda(ind) < 1) selection favours reproduction later in life, whereas early reproduction is selected in increasing populations (lambda(ind) > 1). As 41% of badgers were assigned only one offspring (lambda(ind) < 1), whereas 40% were assigned more than two (lambda(ind) > 1), this cancelled out S'(alpha) measured by lambda(ind).

Using genetic methods to investigate dispersal in two badger (Meles meles) populations with different ecological characteristics.

Understanding the dispersal behaviour of a species is important for understanding its ecology and evolution. Dispersal in the Eurasian badger (Meles meles) is believed to be very limited, with social groups forming primarily through the retention of offspring. However, most of our knowledge of dispersal in this species comes from studies of high-density populations in the United Kingdom, where badgers are atypical in their behaviour, physiology, ecology and prey specialization. In this study we use genetic methods to compare dispersal patterns in a British and a Swiss population that differ in their ecology and demography. We present well-supported evidence that badgers disperse much further in the low-density continental population, where dispersal may also be female biased. Limited dispersal thus seems not to be an intrinsic behavioural characteristic of the species. Rather, dispersal patterns seem to vary depending on population demography and, ultimately, habitat quality and characteristics. This could have important management consequences, as dispersal can affect the impact of local extinction, and host dispersal has a particularly important role in disease transmission. Even though concentrated studies of a species in a single location may not provide representative data for the species, there are few mammalian studies that compare demography and dispersal patterns across contrasting habitats. Our results provide an example of phenotypic plasticity and suggest that dispersal is determined by the interaction of individual, social and environmental factors that may differ between populations.

Sucrose co-administration reduces the toxic effect of lectin on gut permeability and intestinal bacterial colonization.

INTRODUCTION: Legume lectins can have toxic effects when consumed without adequate cooking, occasionally leading to an acute gastroenteritis. Lectins are sugar binging proteins and may use this property to execute their toxic effects; these toxic effects may be secondary to increased gut bacteria and intestinal permeability. However, whether or not sucrose rescues these toxic effects by decreasing gut bacterial concentration and intestinal permeability is unknown. AIM: Our aim was to test the hypothesis that sucrose may reduce toxic effects of legume lectins by protecting barrier function, bacterial overgrowth and bacterial translocation. METHODS: Twenty-four rats were randomized to an ad libitum diet of either standard rat chow, a chow containing 26% crude red kidney beans or a chow containing 26% crude red kidney beans supplemented with 1 mM sucrose in drinking water for 24 h. After 12-h fast, rats were gavaged with sugar probes; breath gas and urine were collected for 5 h. Intestine and liver tissues were then collected. Mucosa-associated total bacterial count were measured by targeting the 16s rRNA gene. Four groups of in vitro Caco-2 cell lines were treated with PBS, 200 µg/ml phytohemagglutinin (PHA), 1 mM sucrose and both 200 µg/ml PHA and 1 mM sucrose, respectively, and trans-epithelial resistance was measured. RESULTS: Rats fed crude red kidney beans for 24 h showed significant weight loss when compared to controls (P < 0.05), as well as increased intestinal permeability (P < 0.05), increased bacterial load (P < 0.05) and increased bacterial translocation to the liver (P < 0.05). Sucrose rescues the drop in trans-epithelial resistance due to PHA in CaCO2-cells (P < 0.05). CONCLUSIONS: Sucrose reduced crude red kidney beans induced increase in intestinal permeability, bacterial load and translocation. Since red kidney beans are an important source of dietary protein in the world, their potential toxicity when inadequately cooked may be rescued by a suitable complementary diet.

Inclusion of psyllium in milk replacer for neonatal calves. 2. Effects on volatile fatty acid concentrations, microbial populations, and gastrointestinal tract size.

Fermentable fibers such as psyllium increase volatile fatty acid (VFA) concentrations in the lower digestive tract and increase the gastrointestinal tract (GIT) mass of many mammals. We reasoned that psyllium inclusion in milk replacer might produce similar effects in neonatal dairy calves, which could lead to improved growth and health. Male Holstein calves were fed a milk replacer (22% crude protein, 20% fat) either without or with psyllium (1.1% of dry matter, DM) from 2 d through 28 d of age. Milk replacer was reconstituted to 12.5% DM and fed at 12% of calf body weight, adjusted weekly. Water was offered ad libitum but no starter was fed. Three calves per treatment were harvested weekly to sample digesta from the reticulo-rumen, abomasum, jejunum, proximal colon, and distal colon, and to determine length and mass of GIT components. Psyllium in milk replacer increased the proportion of butyrate in reticulo-rumen contents from 2.4 to 3.2% of total but did not affect total VFA concentrations. Total VFA concentrations were very low in the jejunum but psyllium tended to increase total VFA, acetate, and valerate concentrations; valerate accounted for 15.9 and 16.7% of total VFA (molar basis) for control and psyllium calves, respectively. Psyllium increased total VFA concentrations in the proximal and distal colon by 104.4 and 45.6%, respectively, but had little effect on the profile of VFA. Psyllium in milk replacer increased populations of bifidobacteria (from 9.7 to 10.3 log(10) cfu/g of DM) and lactobacilli (from 8.2 to 9.4 log(10) cfu/g of DM) in the reticulo-rumen, but did not affect populations in jejunum or colon. Calves fed psyllium had 12.0% greater total GIT mass and 9.4% greater GIT as a percentage of body weight. Psyllium tended to increase mass of the reticulo-rumen and significantly increased mass of duodenum (34.2%), jejunum (14.5%), and colon (14.6%). Density of intestinal tissues from calves fed psyllium-supplemented milk replacer was 25.9% greater in the jejunum and 25.3% greater in the ileum, and tended to be greater in duodenum and colon than tissue from control calves. Supplementation of psyllium to milk replacer increased fermentation in the colon, mass of the total GIT, and populations of bifidobacteria and lactobacilli in the reticulo-rumen.