The need for early intervention for psychosis to persist throughout the COVID-19 pandemic and beyond.

In the last three decades, early intervention for psychosis (EIP) services have been established worldwide and have resulted in superior symptomatic and functional outcomes for people affected by psychotic disorders. These improved outcomes are a result of reducing delays to treatment and the provision of specialised, holistic interventions. The COVID-19 pandemic poses significant challenges to the delivery of these services, such as undetected cases or long delays to treatment. Furthermore, the COVID-19 pandemic will likely increase the mental health needs of communities, including the incidence of psychotic disorders. In this perspective piece, we provide suggestions as to how EIP services can adapt within this environment, such as utilising novel technologies. Finally, we argue that despite the economic consequences of the pandemic, the funding for mental health services, including EI services, should be increased in line with the need for these services during and beyond the pandemic.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Supplementation of Merino ewes with vitamin E plus selenium increases α-tocopherol and selenium concentrations in plasma of the lamb but does not improve their immune function.

Vitamin E and selenium have been reported to improve immune function across a range of species. Ewes lambing on poor-quality dry pasture in autumn in Western Australia are at risk of being deficient in vitamin E and selenium at lambing thus predisposing their lambs to deficiencies and increasing the risk of infection and disease. This study tested the hypotheses that (i) supplementation of autumn-lambing ewes with vitamin E plus selenium in late gestation will increase the concentrations of vitamin E and selenium in plasma in the ewe and lamb and (ii) that the increased concentrations of vitamin E and selenium in plasma in the lambs will improve their innate and adaptive immune responses and thus survival. Pregnant Merino ewes were divided into a control group (n=58) which received no supplementation or a group supplemented with vitamin E plus selenium (n=55). On days 111, 125 and 140 of pregnancy ewes in the vitamin E plus selenium group were given 4 g all-rac-α-tocopherol acetate orally. On day 111 the ewes were also given 60 mg of selenium as barium selenate by subcutaneous injection. The concentrations of α-tocopherol and selenium were measured in ewes and/or lambs from day 111 of pregnancy to 14 weeks of age±10 days (weaning). Immune function of the lamb was assessed by analysing the numbers and phagocytic capacities of monocytes and polymorphonuclear leucocytes and plasma IgG and anti-tetanus toxoid antibody concentrations between birth and 14 weeks of age±10 days. Maternal supplementation with vitamin E plus selenium increased the concentration of α-tocopherol in plasma (1.13 v. 0.67 mg/l; P<0.001) and selenium in whole blood (0.12 v. 0.07 mg/l; P<0.01) of the ewes at lambing compared with controls. Supplementation also increased the concentration of α-tocopherol (0.14 v. 0.08 mg/l; P<0.001) and selenium (0.08 v. 0.05 mg/l; P<0.01) in lambs at birth compared with controls. There was no significant effect of supplementation on immune function or survival in the lambs.

Evaluating the Renal Safety of Investigational New Drugs: Where Should We Be Going?

We the authors work in the US Food and Drug Administration (FDA) review division responsible for the therapeutic agents for primary renal disease. We also field consultative inquiries regarding off-target adverse renal effects of drugs intended to treat other diseases. We do neither basic science research on renal diseases nor clinical studies of new drugs, but we are professional spectators of both. We offer here our thoughts on the challenge of identifying renal safety signals in the preclinical space and in the earliest phases of clinical development.

The importance of mindfulness in psychosocial distress and quality of life in dermatology patients.

BACKGROUND: Mindfulness, defined as purposively and nonjudgementally paying attention in the present moment, could be used within psychosocial interventions to reduce the distress associated with social anxiety and avoidance found in many skin conditions. However, little is known about the relationship between naturally occurring levels of mindfulness and distress in dermatology patients. OBJECTIVES: To examine the relationship between mindfulness and psychosocial distress in a dermatological population. It was hypothesized that higher levels of mindfulness would be associated with lower levels of social anxiety, anxiety, depression and skin shame, and with better quality of life. METHODS: Adult dermatology outpatients (n = 120) from one hospital completed items assessing subjective severity, skin shame, fear of negative evaluation, anxiety and depression, quality of life, and levels of mindfulness. RESULTS: Considering depression, 14% reported mild, 5% moderate and 2·5% severe symptoms. For anxiety, 22% reported mild, 23% moderate and 6% severe symptoms. In addition, 33·4% reported clinically significant social anxiety. After controlling for subjective severity, mindfulness explained an additional 19% of the variance in depression, 39% in anxiety, 41% in social anxiety, 13% in skin shame and 6% in dermatological quality of life. One specific facet of mindfulness (acting with awareness) was found to be the most consistent predictor of distress. CONCLUSIONS: The findings indicate that higher levels of mindfulness are associated with lower distress. This suggests that facilitating mindfulness may be helpful in reducing distress in dermatology patients, and the use of mindfulness techniques warrants further investigation.

Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy.

Bone loss is a significant clinical problem for female cancer survivors (FCS) and increases fracture risk. The aim of the Yale Fitness Intervention Trial (Yale FIT) was to determine the effects of a 12-month aerobic-resistance exercise intervention compared to a home-based physical activity group on bone outcomes [bone mineral density (BMD)] and biomarkers bone turnover). Early postmenopausal FCS (N = 154) were randomized to the exercise intervention (3 times/week) or to a home-based physical activity group. Calcium (1200 mg) and Vitamin D (400 IU) supplements were provided to both groups. BMD was measured at baseline and 12 months. No significant difference in BMD was observed for the exercise vs home-based group. However, subjects on Tamoxifen or no endocrine therapy did not significantly lose BMD, with the exception of the femoral neck (FN). In contrast subjects on aromatase inhibitors (AIs) had significant BMD loss at all sites. The majority of subjects had sufficient serum levels of Vitamin D (>20 ng/mL) but there was significantly less bone loss in subjects in the 20-29 ng/mL range at the LS (p = 0.01), hip (p = 0.03), and GT (p = 0.008) compared to lower or higher levels. Exercise stimulates bone remodeling but the intervention was not superior for BMD outcomes at one year. The dose of the osteogenic stimulus in the intervention has been effective in preserving BMD in healthy postmenopausal women but it may be inadequate for survivors with chemotherapy-induced menopause and for those on adjuvant AI therapy.

Ionophore strategy affects growth performance and carcass characteristics in feedlot steers.

One hundred ninety-two steers (BW = 354 ± 23.5 kg) were used in a randomized block design to evaluate the effects of ionophore and ractopamine hydrochloride (RH) supplementation strategies on performance and carcass characteristics. Twelve pens of 4 steers were assigned to each of the following treatments: unsupplemented control (CON), laidlomycin propionate (12.1 mg/kg DM) with or without RH (LPRH and LP, respectively), and monensin sodium (36.4 mg/kg DM) with RH (MSRH). Steers were fed for 151 d, of which respective treatments received RH (Actogain; Zoetis, Florham Park, NJ) at a rate of 300 mg/(animal · d) for the final 32 d. Laidlomycin was removed from the LPRH treatment during this period, as no combination feeding has been approved. Upon harvest, carcass data were collected by trained personnel, and subsequent analysis of the LM was conducted to estimate tenderness using Warner-Bratzler shear force (WBSF). Prior to RH supplementation, both LP and LPRH had greater ADG ( ≤ 0.02) and G:F ( < 0.01) than CON, whereas MSRH was intermediate. During the final 32 d, MSRH improved G:F ( ≤ 0.02) compared to all other treatments and tended to increase ADG over unsupplemented controls ( = 0.05). Cattle receiving LP without RH had significantly greater BW at d 151 than CON ( = 0.02), whereas both RH treatments tended to improve final BW ( ≤ 0.09). Ionophores improved ADG ( ≤ 0.03) and G:F ( < 0.01) for the entire feeding period, and although LP-supplemented cattle had greater DMI for the final 32 d than both RH treatments ( ≤ 0.01), intakes for the 151-d trial were similar among treatments. Carcass weights were greater ( = 0.04) in cattle fed LP with no RH than CON, where cattle yielded an average of 12 kg more HCW. Ractopamine increased LM area in MSRH-supplemented cattle ( = 0.03) and tended to increase LM area for steers receiving LPRH ( = 0.07). Longissimus steaks of MSRH-supplemented cattle had greater WBSF values than CON ( = 0.04) after 7 d of postmortem aging and greater WBSF values than LPRH steaks after 28 d ( = 0.03). All other carcass and WBSF measurements were similar among treatments. The results of this study indicate that LP supplementation without RH may yield a performance similar to and carcass responses associated with the administration of a ß-agonist. These results also suggest that performance and carcass characteristics for cattle fed LP are similar to those of cattle fed monensin throughout the feeding period.

Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: Effects of fat composition and gender.

BACKGROUND AND AIMS: We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. METHODS AND RESULTS: Thirty adults (mean age 27.8 y, BMI 23.2 kg/m(2)) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60 and 390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P = 0.027) whilst SFA + LC n-3 PUFA improved FMD at 240 min (P = 0.003). In males, insulin infusion attenuated the increase in FMD with SFA + LC n-3 PUFA (P = 0.049), with SI 10% greater with SFA + LC n-3 PUFA than SFA (P = 0.041). CONCLUSION: This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. This trial was registered at clinical trials.gov as NCT01351324 on 6th May 2011.

Follicle development, endocrine profiles and ovulation rate in adult Merino ewes: effects of early nutrition (pre- and post-natal) and supplementation with lupin grain.

In adult ewes, we tested whether ovarian function, including the response to short-term supplementation, was affected by the nutrition of their mothers during the pre-/post-natal period. A 2×2 factorial design was used with nutrition in early life (low or high) and a 6-day supplement (with or without) as factors. All ewes received three prostaglandin (PG) injections 7 days apart, and the supplement (lupin grain) was fed for 6 days from 2 days after the second until the third PG injection. We measured reproductive and metabolic hormones, studied follicle dynamics (ultrasonography), and evaluated granulosa cell numbers, aromatase activity and oestradiol (E2) concentrations in follicular fluid in healthy follicles at days 3 and 7 of supplementation. Ovulation rate was increased by 25% by exposure to high pre-/post-natal nutrition (1.5 vs 1.2; P<0.05), in association with a small decrease in FSH concentrations (P=0.06) and a small increase in insulin concentrations (P=0.07). The number of healthy antral follicles was not affected. Acute supplementation increased the number of granulosa cells (3.7±0.2 vs 3.0±0.2 million; P<0.05) in the largest follicle, and the circulating concentrations of E2 (4.6±0.3 vs 3.9±0.3 pmol/l; P<0.05) and glucose (3.4±0.03 vs 3.3±0.03 mmol/l; P<0.01). Both early life nutrition and acute supplementation appear to affect ovulation rate through changes in glucose-insulin homoeostasis that alter follicular responsiveness to FSH and therefore E2-FSH balance.

Earliest evidence for the use of pottery.

Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present (cal bp), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal bp (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers, perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.

Inactivation of Salmonella enterica serovar Typhimurium on fresh produce by cold atmospheric gas plasma technology.

Cold atmospheric gas plasma treatment (CAP) is an alternative approach for the decontamination of fresh and minimally processed food. In this study, the effects of growth phase, growth temperature and chemical treatment regime on the inactivation of Salmonella enterica serovar Typhimurium (S. Typhimurium) by Nitrogen CAP were examined. Furthermore, the efficacy of CAP treatment for decontaminating lettuce and strawberry surfaces and potato tissue inoculated with S. Typhimurium was evaluated. It was found that the rate of inactivation of S. Typhimurium was independent of the growth phase, growth temperature and chemical treatment regime. Under optimal conditions, a 2 min treatment resulted in a 2.71 log-reduction of S. Typhimurium viability on membrane filters whereas a 15 min treatment was necessary to achieve 2.72, 1.76 and 0.94 log-reductions of viability on lettuce, strawberry and potato, respectively. We suggest that the differing efficiency of CAP treatment on the inactivation of S. Typhimurium on these different types of fresh foods is a consequence of their surface features. Scanning electron microscopy of the surface structures of contaminated samples of lettuce, strawberry and potato revealed topographical features whereby S. Typhimurium cells could be protected from the active species generated by plasma.

Anoxia-induced release of colloid- and nanoparticle-bound phosphorus in grassland soils.

Particle-facilitated transport is a key mechanism of phosphorus (P) loss in agroecosystems. We assessed contributions of colloid- and nanoparticle-bound P (nPP; 1-415 nm) to total P released from grassland soils receiving biannual poultry litter applications since 1995. In laboratory incubations, soils were subjected to 7 days of anoxic conditions or equilibrated at pH 6 and 8 under oxic conditions and then the extract was size fractionated by differential centrifugation/ultrafiltration for analysis of P, Al, Fe, Si, Ti, and Ca. Selected samples were characterized by transmission electron microscopy-energy dispersive spectroscopy (TEM-EDS) and field flow fractionation (FFF-ICP-MS). Particles released were present as nanoaggregates with a mean diameter of 200-250 nm, composed of ~50-nm aluminosilicate flakes studded with Fe and Ti-rich clusters (<10 nm) that contained most of the P detected by EDS. Anoxic incubation of stimulated nPP release with seasonally saturated soils released more nPP and Fe(2+)(aq) than well-drained soils; whereas, nonreductive particle dispersion, accomplished by raising the pH, yielded no increase in nPP release. This suggests Fe acts as a cementing agent, binding to the bulk soil P-bearing colloids that can be released during reducing conditions. Furthermore, it suggests prior periodic exposure to anoxic conditions increases susceptibility to redox-induced P mobilization.

A meta-analysis of the effectiveness of psychological interventions for adults with skin conditions.

Skin conditions can be associated with heightened levels of psychological morbidity, suggesting the need for psychological interventions. A number of specific interventions (such as habit reversal) have been developed. However, to date, there has not been a systematic review of the effectiveness of psychological interventions. We sought to systematically evaluate the effectiveness of psychological interventions designed to improve the severity of and adjustment to skin conditions in adults. Database, archival and citation searches were conducted. Studies were included if participants were allocated to either a psychological intervention (excluding educational interventions and complementary therapies) or a comparison condition, and if they measured outcomes relevant to the skin condition. Twenty-two studies met these inclusion criteria. Effect sizes for each intervention were computed and we also coded a number of potential moderators of intervention efficacy. Psychological interventions were found to have a medium-sized effect on skin conditions (g = 0·54). The type of skin condition, age of sample, nature of the intervention, time interval between the end of the intervention and follow-up, and type of outcome measure all moderated the effect of interventions on outcomes. For example, interventions had a medium effect on the severity of the condition (g = 0·40) and psychosocial outcomes (g = 0·53), and a medium-to-large effect on itch/scratch reactions (g = 0·67). Psychological interventions are beneficial for people with skin conditions. However, more research is needed to extend the variety and focus of the psychological interventions that are available. Studies are also needed to explore the longer-term benefits of such interventions.

Cysteine modification reveals which subunits form the ligand binding site in human heteromeric 5-HT3AB receptors.

The ligand binding site of Cys-loop receptors is formed by residues on the principal (+) and complementary (-) faces of adjacent subunits, but the subunits that constitute the binding pocket in many heteromeric receptors are not yet clear. To probe the subunits involved in ligand binding in heteromeric human 5-HT(3)AB receptors, we made cysteine substitutions to the + and - faces of A and B subunits, and measured their functional consequences in receptors expressed in Xenopus oocytes. All A subunit mutations altered or eliminated function. The same pattern of changes was seen at homomeric and heteromeric receptors containing cysteine substitutions at A(R92) (- face), A(L126)(+), A(N128)(+), A(I139)(-), A(Q151)(-) and A(T181)(+), and these receptors displayed further changes when the sulphydryl modifying reagent methanethiosulfonate-ethylammonium (MTSEA) was applied. Modifications of A(R92C)(-)- and A(T181C)(+)-containing receptors were protected by the presence of agonist (5-HT) or antagonist (d-tubocurarine). In contrast modifications of the equivalent B subunit residues did not alter heteromeric receptor function. In addition a double mutant, A(S206C)(-)(/E229C)(+), only responded to 5-HT following DTT treatment in both homomeric and heteromeric receptors, indicating receptor function was inhibited by a disulphide bond between an A+ and an A- interface in both receptor types. Our results are consistent with binding to an A+A- interface at both homomeric and heteromeric human 5-HT(3) receptors, and explain why the competitive pharmacologies of these two receptors are identical.

Integrative mRNA profiling comparing cultured primary cells with clinical samples reveals PLK1 and C20orf20 as therapeutic targets in cutaneous squamous cell carcinoma.

Identifying therapeutic targets for cancer treatment relies on consistent changes within particular types or sub-types of malignancy. The ability to define either consistent changes or sub-types of malignancy is often masked by tumor heterogeneity. To elucidate therapeutic targets in cutaneous squamous cell carcinoma (cSCC), the most frequent skin neoplasm with malignant potential, we have developed an integrated approach to gene expression profiling beginning with primary keratinocytes in culture. Candidate drivers of cSCC development were derived by first defining a set of in vitro cancer genes and then comparing their expression in a range of clinical data sets containing normal skin, cSCC and the benign hyper-proliferative condition psoriasis. A small interfering RNA (siRNA) screen of the resulting 21 upregulated genes has yielded targets capable of reducing xenograft tumor volume in vivo. Small-molecule inhibitors for one target, Polo-like kinase-1 (PLK1), are already in clinical trials for other malignancies, and our data show efficacy in cSCC. Another target, C20orf20, is identified as being overexpressed in cSCC, and siRNA-mediated knockdown induces apoptosis in vitro and reduces tumor growth in vivo. Thus, our approach has shown established and uncharacterized drivers of tumorigenesis with potent efficacy as therapeutic targets for the treatment of cSCC.

Quality of life in thalassemia: a comparison of SF-36 results from the thalassemia longitudinal cohort to reported literature and the US norms.

Thalassemia is a chronic, inherited blood disorder, which, in its most severe form, causes life-threatening anemia. Advances in treatment have led to increased life expectancy however the need for chronic blood transfusions and chelation therapy remains a significant burden for patients. Our study compared health related quality of life (HRQOL) from the Thalassemia Clinical Research Network's (TCRNs) Thalassemia Longitudinal Cohort (TLC) study to US norms and assessed association with clinical variables. There were 264 patients over age 14 who completed the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF36v2) baseline assessment. When compared to US norms, TLC patients had statistically significant (P < 0.05) worse HRQOL on five of the eight subscales (physical functioning, role-physical, general health, social functioning, and role-emotional) and on both summary scales (physical component summary and mental component summary). Women, older patients, and those with more disease complications and side effects from chelation reported lower HRQOL. In general, adolescents and adults with thalassemia report worse HRQOL than the US population, despite contemporary therapy. The SF-36 should become a standard instrument for assessing HRQOL in thalassemia to determine predictors of low HRQOL which may be better addressed by a multidisciplinary team.

Novel biomarkers of acute kidney toxicity.

Novel biomarkers of kidney toxicity are powerful tools not only with respect to their clinical applications but also because of their impact on drug development. These biomarkers can influence the assessment of efficacy of new drugs for kidney diseases as well as the risk management for new drugs. The science behind these novel biomarkers reflects the evolution over the past decade of genomic and proteomic platforms that have transformed the discovery and development of new biomarkers for preclinical and clinical applications in drug development. Several of these biomarkers are in use as transcriptomic biomarkers in animal models as well as translational proteomic biomarkers in animal models and in humans. Their ability to detect kidney damage earlier than is possible with currently accessible biomarkers is being given qualification through regulatory biomarker-qualification programs, which will help establish consensus for their widespread use.

Effect of acarbose on acute acidosis.

A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level. It is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. The ability of acarbose to reduce the incidence of acidosis and the comparative efficacies of acarbose, sodium bicarbonate, and monensin were tested in 3 acute acidosis challenge experiments in cattle. Rumen-cannulated Holstein steers were challenged with a mixture of 48.4% cornstarch, 48.4% ground corn, 2.1% sodium caseinate, and 1.1% urea with or without test substance. The challenge was administered at a rate of 12.5 g/kg of body weight (BW) as a slurry through the cannula directly into the rumen. Ruminal pH was monitored at 10-min intervals throughout the study. Animals were removed from study and rumen contents replaced if they exhibited acute acidosis as defined as pH <4.5. If acidosis was not observed within 24 h, animals were subjected to a second challenge. Ruminal fluid samples were taken for measurement of VFA and lactate concentrations at various intervals after the challenge. In experiment 1, the carbohydrate challenge induced acidosis in 4 of 4 control animals and 0 of 4 animals treated with 2.14 or 21.4 mg of acarbose/kg of BW in the challenge based on the criterion of pH <4.5. In experiment 2, the carbohydrate challenge induced acidosis in 4 of 7 control animals and 1 of 7 animals when 1.07 mg of acarbose/kg of BW was included in the challenge. In experiment 3, acidosis was induced in 7 of 7 animals in the control, 1% sodium bicarbonate, and 12 mg of monensin/kg of dry matter intake groups and in 3 of 8 steers administered 1.07 mg of acarbose/kg of BW in the challenge. Increases in lactate concentrations and decreases in total VFA associated with acute acidosis were mitigated by acarbose. Thus, acarbose, an amylase and glucosidase inhibitor, prevented or reduced the incidence of acidosis in an acute challenge model in steers and was more effective than monensin or sodium bicarbonate.