Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review.

PURPOSE OF REVIEW: Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens. RECENT FINDINGS: However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

Synthesis, Structures, and Magnetic Investigations of Nickel Phosphates: Ni2(PO4)(OH), Ni7(PO4)3(HPO4)(OH)3, and NaNiPO4 Including Potential Haldane Behavior.

Three novel nickel-phosphate structures are reported, Ni2(PO4)(OH) (I), Ni7(PO4)3(HPO4)(OH)3 (II), and NaNiPO4 (III). Each new system was prepared via a high-temperature hydrothermal synthesis at 600-650 °C. All three compounds are built of quasi-one-dimensional (quasi-1-D) Ni2+ containing chains with varying phosphate bridging modes and were characterized by single crystal X-ray diffraction and magnetic susceptibility. All three compounds display very different magnetic behavior. Anisotropic magnetic data is reported for Ni2(PO4)(OH) (I) exhibiting slow antiferromagnetic ordering in the high-temperature regime with substructures that begin to form below 32 K at different field strengths. These characteristics affirm I as being one of the few Haldane-like material candidates. The Ni7(PO4)3(HPO4)(OH)3 (II) material is a member of the unusual ellenbergerite structural family and displays complex inter- and intrachain magnetic interactions while NaNiPO4 (III) shows antiferromagnetic ordering near 18 K. This magnetic behavior is correlated with their structures.

Resource pulses shape seasonal and individual variation in the diet of an omnivorous carnivore.

Resource pulses are ecologically important phenomenon that occur in most ecosystems globally. Following optimal foraging theory, many consumers switch to pulsatile foods when available, examples of which include fruit mast and vulnerable young prey. Yet how the availability of resource pulses shapes the ecology of predators is still an emerging area of research; and how much individual variation there is in response to pulses is not well understood. We hypothesized that resource pulses would lead to dietary convergence in our population, which we tested by tracking both population-level and individual coyote diets for 3 years in South Carolina, USA. We (1) described seasonal dietary shifts in relation to resource pulses; (2) compared male and female diets across seasons; and (3) tested this dietary convergence hypothesis by quantifying individual dietary variation both across and within periods when resource pulses were available. We found that pulses of white-tailed deer fawns and blackberries composed over half of coyote diet in summer, and persimmon fruits were an important component in fall. Male and female coyotes generally had similar diets, but males consumed more deer in fall, perhaps driven by scavenging more. We found support for our dietary convergence hypothesis, where individuals had more similar diets during resource pulses compared to a non-pulse period. We also found that this convergence happened before peak availability, suggesting a non-symmetric response to pulse availability. We show that nearly all coyotes eat fawns, suggesting that targeted efforts to remove "fawn killers" would be in vain. Instead, given how quickly coyotes collectively converge on resource pulses, our findings show that resource pulses could potentially be used by managers to alter the behavior of apex predators. More broadly, we open a new line of inquiry into how variation in individual foraging decisions scales up to shape the effects of resource pulses on ecological communities.

Synthesis, characterization and reactivity of a Mn(III)-hydroxido complex as a biomimetic model for lipoxygenase.

Manganese hydroxido (Mn-OH) complexes supported by a tripodal N,N',N″-[nitrilotris(ethane-2,1-diyl)]tris(P,P-diphenylphosphinic amido) ([poat]3-) ligand have been synthesized and characterized by spectroscopic techniques including UV-vis and electron paramagnetic resonance (EPR) spectroscopies. X-ray diffraction (XRD) methods were used to confirm the solid-state molecular structures of {Na2[MnIIpoat(OH)]}2 and {Na[MnIIIpoat(OH)]}2 as clusters that are linked by the electrostatic interactions between the sodium counterions and the oxygen atom of the ligated hydroxido unit and the phosphinic (P=O) amide groups of [poat]3-. Both clusters feature two independent monoanionic fragments in which each contains a trigonal bipyramidal Mn center that is comprised of three equatorial deprotonated amide nitrogen atoms, an apical tertiary amine, and an axial hydroxido ligand. XRD analyses of {Na[MnIIIpoat(OH)]}2 also showed an intramolecular hydrogen bonding interaction between the MnIII-OH unit and P=O group of [poat]3-. Crystalline {Na[MnIIIpoat(OH)]}2 remains as clusters with Na+---O interactions in solution and is unreactive toward external substrates. However, conductivity studies indicated that [MnIIIpoat(OH)]- generated in situ is monomeric and reactivity studies found that it is capable of cleaving C-H bonds, illustrating the importance of solution-phase speciation and its direct effect on chemical reactivity. Synopsis: Manganese-hydroxido complexes were synthesized to study the influence of H-bonds in the secondary coordination sphere and their effects on the oxidative cleavage of substrates containing C-H bonds.

Contribution of Electrostatic CH3-π Interactions to Recognition of Histone Asymmetric Dimethylarginine by the SPIN1 Triple Tudor Domain.

Methylation of arginine (Arg) residues on histones creates a new binding epitope, enabling recognition by aromatic cage binding pockets in Tudor domains; these protein-protein interactions (PPIs) govern gene expression. Despite their biological importance, the molecular details of methylated Arg recognition are poorly understood. While the desolvation, hydrogen bonding, and guanidinium stacking of methylated Arg have been explored in model systems and proposed to contribute to binding, direct interactions between the methyl groups and the aromatic residues in the binding pocket have not previously been investigated. Herein, we mechanistically study the CH3-π interactions between the SPIN1 triple Tudor domain and histone asymmetric dimethylarginine. We find that these CH3-π interactions are electrostatically tunable, exhibiting cation-π character, albeit attenuated relative to cation-π interactions with quaternary ammonium ions, offering key insight into how methylation of Arg alters its binding epitope to enable new PPIs.

Reproducible protocol for the extraction and semi-automated quantification of macroscopic charcoal from soil.

Charcoal fragments preserved in soils or sediments are used by scientists to reconstruct fire histories and thereby improve our understanding of past vegetation dynamics and human-plant relationships. Unfortunately, most published methods for charcoal extraction and analysis are incompletely described and are therefore difficult to reproduce. To improve the standardization and replicability of soil charcoal analysis, as well as to facilitate accessibility for non-experts, we developed a detailed, step-by-step protocol to isolate charcoal from soil and to efficiently count and measure charcoal fragments. The extraction phase involves the chemical soaking and wet sieving of soils followed by the collection of macrocharcoal (≥500 µm). The analysis phase is performed semi-automatically using the open-source software ImageJ to count and measure the area, length, and width of fragments from light stereo microscope images by means of threshold segmentation. The protocol yields clean charcoal fragments, a set of charcoal images, and datasets containing total charcoal mass, number of fragments, and morphological measurements (area, length, and width) for each sample. We tested and validated the protocol on 339 soil samples from tropical savannas and forests in eastern lowland Bolivia. We hope that this protocol will be a valuable resource for scientists in a variety of fields who currently study, or wish to study, macroscopic charcoal in soils as a proxy for past fires.

Controlling rates and reversibilities of elimination reactions of hydroxybenzylammoniums by tuning dearomatization energies.

Hydroxybenzylammonium compounds can undergo a reversible 1,4- or 1,6-elimination to afford quinone methide intermediates after release of the amine. These molecules are useful for the reversible conjugation of payloads to amines. We hypothesized that aromaticity could be used to alter the rate of reversibility as a distinct thermodynamic driving force. We describe the use of density functional theory (DFT) calculations to determine the effect of aromaticity on the rate of release of the amine from hydroxybenzylammonium compounds. Namely, the aromatic scaffold affects the dearomatization reaction to reduce the kinetic barrier and prevent the reversibility of the amine elimination. We consequently synthesized a small library of polycyclic hydroxybenzylammoniums, which resulted in a range of release half-lives from 18 minutes to 350 hours. The novel mechanistic insight provided herein significantly expands the range of release rates amenable to hydroxybenzylammonium-containing compounds. This work provides another way to affect the rate of payload release in hydroxybenzylammoniums.

Improved Diffusion-Weighted Hyperpolarized 129Xe Lung MRI with Patch-Based Higher-Order, Singular Value Decomposition Denoising.

RATIONALE AND OBJECTIVES: Hyperpolarized xenon (129Xe) MRI is a noninvasive method to assess pulmonary structure and function. To measure lung microstructure, diffusion-weighted imaging-commonly the apparent diffusion coefficient (ADC)-can be employed to map changes in alveolar-airspace size resulting from normal aging and pulmonary disease. However, low signal-to-noise ratio (SNR) decreases ADC measurement certainty, and biases ADC to spuriously low values. Further, these challenges are most severe in regions of the lung where alveolar simplification or emphysematous remodeling generate abnormally high ADCs. Here, we apply Global Local Higher Order Singular Value Decomposition (GLHOSVD) denoising to enhance image SNR, thereby reducing uncertainty and bias in diffusion measurements. MATERIALS AND METHODS: GLHOSVD denoising was employed in simulated images and gas phantoms with known diffusion coefficients to validate its effectiveness and optimize parameters for analysis of diffusion-weighted 129Xe MRI. GLHOSVD was applied to data from 120 subjects (34 control, 39 cystic fibrosis (CF), 27 lymphangioleiomyomatosis (LAM), and 20 asthma). Image SNR, ADC, and distributed diffusivity coefficient (DDC) were compared before and after denoising using Wilcoxon signed-rank analysis for all images. RESULTS: Denoising significantly increased SNR in simulated, phantom, and in-vivo images, showing a greater than 2-fold increase (p < 0.001) across diffusion-weighted images. Although mean ADC and DDC remained unchanged (p > 0.05), ADC and DDC standard deviation decreased significantly in denoised images (p < 0.001). CONCLUSION: When applied to diffusion-weighted 129Xe images, GLHOSVD improved image quality and allowed airspace size to be quantified in high-diffusion regions of the lungs that were previously inaccessible to measurement due to prohibitively low SNR, thus providing insights into disease pathology.

The use of point of care gastric ultrasound and anesthesia management in pediatric patients with preoperative fasting non-adherence scheduled for elective surgical procedures: a retrospective study.

BACKGROUND: Failure to adhere to perioperative fasting requirements increases aspiration risk and can lead to delay or cancellation of surgery. Point of care gastric ultrasound may guide decision-making to delay, cancel or proceed with surgery. METHODS: This study aimed to describe gastric contents using point of care gastric ultrasound in pediatric patients with known fasting guideline violations presenting for elective surgery. This was a single-center retrospectivechart review of gastric ultrasound scans in patients presenting for elective surgeries with "nothing by mouth" violation (per fasting guidelines) or unclear fasting status. The primary outcome is description of gastric contents using point of care ultrasound. The ultrasound findings were classified as low-risk for aspiration (empty, clear fluid < 1.5 ml/kg), high-risk (solids, clear fluid > 1.5 ml/kg), or inconclusive study. Gastric ultrasound findings were communicated to the attending anesthesiologist. For patients proceeding without delay the estimated time saved was defined as the difference between ultrasound scan time and presumed case start time based on American Society of Anesthesiologists fasting guidelines. RESULTS: We identified 106 patients with a median age of 4.8 years. There were 31 patients (29.2%) that had ultrasound finding of high-risk gastric contents. These patients had cases that were delayed, cancelled or proceeded with rapid sequence intubation. Sixty-six patients (62.3%) were determined to be low-risk gastric contents and proceeded with surgery without delay. For these patients, a median of 2.6 h was saved. No aspiration events were recorded for any patients. CONCLUSIONS: It is feasible to use preoperative point of care gastric ultrasound to determine stomach contents and risk-stratify pediatric patients presenting for elective surgical procedures with fasting non-adherence. Preoperative gastric ultrasound may have a role in determining changes in anesthetic management in this patient population.

Mechanical Circulatory Support in Pediatric Myocarditis: Support Strategies and Outcomes in a Nationally Representative Cohort.

Background: Myocarditis is a common cause of pediatric heart failure which may require mechanical circulatory support (MCS). The purpose of this study is to describe MCS strategies used in a nationwide cohort of pediatric patients with myocarditis, identify trends over time, and compare outcomes between MCS strategies. Methods: This study utilized the Kids' Inpatient Database (KID), a national sample of administrative discharge data. KID admissions from 2003-2016 were queried using ICD-9/10 codes to identify those with a diagnosis of myocarditis. MCS outcomes were compared using logistic regression. Results: Of 5,661 admissions for myocarditis, MCS was used in 424 (7.5%), comprised of extracorporeal membrane oxygenation (ECMO) in 312 (73.6%), including 32 (10.2%) instances of extracorporeal cardiopulmonary resuscitation (ECPR), temporary ventricular assist devices (tVAD) in 28 (6.6%), durable VAD (dVAD) in 42 (9.9%) and combination MCS in 42 (9.9%). MCS use increased over time (p=0.031), but MCS strategies did not significantly change. Mortality was high in the MCS group (28.3%). There was no difference in odds of death in the VAD only or combination MCS group compared to the non-ECPR ECMO group (p=0.07 and p=0.65, respectively). Conclusion: MCS is used in 1 in 13 pediatric myocarditis cases, and MCS use is increasing over time with ECMO remaining the most frequently used modality. Mortality remains high in patients that receive MCS but does not differ between those receiving VAD or combination MCS as compared to non-ECPR ECMO on unadjusted analysis. Further prospective analysis is required to evaluate the relative effectiveness of MCS modalities in this disease.

Biomechanical Principles of Intramedullary Nails in Veterinary and Human Medicine.

Intramedullary nails are specialized metal rods inserted into the medullary cavity of a fractured bone and secured to reduce load on the fracture site, provide stability, and permit healing. The purpose of this review is to highlight the biomechanics of orthopaedic intramedullary nailing, as well as discuss the biomechanical considerations that have shaped implant design and fixation technique in veterinary and human medicine. Relevant studies were included from the PubMed database and Google Scholar for discussion on the basic science and nail design of intramedullary nails. Implant design and implementation continues to progress, with new innovative designs currently under investigation. A lack of consensus remains on the superior implant material. Recent studies, particularly in human populations, have supported the use of reaming based on reoperation rates, nonunion rates, and dynamization. Design modifications, such as the expandable intramedullary nails and angle-stable interlocking designs, have been investigated as methods of improving cortical contact and resisting torsional stress. Intramedullary nailing is a valuable stabilization technique for long bone fractures across a variety of species. The technology continues to undergo design improvements in both veterinary and human medicine.

Changes in Parent-Student Text Message and Phone Call Communication During the Transition to College as Predictors of Cannabis and Simultaneous Use During the First Year.

Parent communication can be protective against cannabis use among young adults. However, changes in parent-student communication frequency naturally occur during the transition from high school to college. Recent research suggests declines in parent-student communication frequency predict increased drinking and consequences during the first year of college, yet these effects on other risky behaviors are unknown. The current study investigated whether post-matriculation changes in frequency of texting/calling with parents predict cannabis use and simultaneous use of cannabis and alcohol, and whether pre-matriculation cannabis and simultaneous use predict changes in communication. First-year students (N = 287, 61.3% female, 50.9% White) reported cannabis and simultaneous use pre- and post-matriculation (T1 & T3) and changes in frequency of texting/calling their mother/father per day (T2). Negative binomial hurdle models examined whether T2 changes in communication frequency predicted T3 cannabis and simultaneous use, and logistic regression models examined whether T1 cannabis and simultaneous use predicted T2 changes in communication frequency. Results revealed that increasing (vs. decreasing) frequency of calling with mothers and texting with fathers was protective against cannabis use, whereas increasing frequency of calling with fathers was associated with greater risk of use. Changes in communication did not significantly predict simultaneous use, nor did pre-matriculation cannabis or simultaneous use predict changes in either mode of communication with parents during the college transition. These findings highlight that changes in mother and father communication may be both beneficial and detrimental to cannabis use depending on the parent and mode of communication. Implications for these findings are discussed.

Cognitive Disengagement Syndrome-Clinical Interview (CDS-CI): Psychometric support for caregiver and youth versions.

Cognitive disengagement syndrome (CDS), formerly termed sluggish cognitive tempo, is a set of symptoms characterized by excessive daydreaming, mental confusion, and slowed behavior/thinking. CDS is distinct from symptoms of attention-deficit/hyperactivity disorder (ADHD) and other psychopathologies and uniquely associated with functional impairment. However, despite significant progress in developing and evaluating rating scale measures of CDS, no clinical interview of CDS exists with established psychometric properties that can facilitate a multimethod approach assessing CDS. Accordingly, the present study evaluated the psychometric properties of the semistructured Cognitive Disengagement Syndrome-Clinical Interview (CDS-CI). The CDS-CI and the ADHD inattention (ADHD-IN) and hyperactive-impulsivity (ADHD-HI) modules from the Kiddie Schedule of Affective Disorders and Schizophrenia for School-Age Children (K-SADS) were administered to a sample of early adolescents (N = 341, ages 10-12 years) and their caregivers. Adolescents and caregivers also completed rating scale measures of CDS and ADHD symptoms. The CDS-CI demonstrated high internal consistency and interrater reliability. CDS-CI scores showed excellent same-source discriminant validity from K-SADS, ADHD-IN, and ADHD-HI scores and encouraging convergent and discriminant validity with rating scale measures, especially for caregivers. Above and beyond K-SADS, ADHD-IN, and ADHD-HI scores, higher parent and adolescent CDS-CI scores were both significantly associated with greater functional impairment. A threshold of ≥ 6 out of 15 symptoms was selected as an initial threshold for determining clinically elevated CDS using the CDS-CI. Findings provide psychometric support for the CDS-CI as a tool in the multimethod assessment of CDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Suillus hypogaeus: First record of a truffle Suillus.

Suillus (order Boletales) is a diverse genus of epigeous, mushroom-forming fungi native to temperate forests across the Northern Hemisphere; however, some species are also present in areas where Pinaceae has been introduced in the Southern Hemisphere. Unlike the closely related genus Rhizopogon, there are no described hypogeous, sequestrate species of Suillus. Here, we describe Suillus hypogaeus, the first known species of the genus with hypogeous, sequestrate sporocarps. Collections were made on Marys Peak in Benton County, Oregon, USA, at an elevation of 800 m in forests dominated by Pseudotsuga menziesii var. menziesii. The peridium is white, quickly staining pink to purple-reddish where bruised or cut. The gleba is pale yellow when young, becoming purple with maturity, and the basidiospores are obovoid, light yellow in KOH, and amyloid in Melzer's reagent. Multilocus molecular phylogenetic analyses support the placement of S. hypogaeus among the Larix specialists in the spectabilis group of Suillus. Although Larix and Pseudotsuga are sister genera, Larix does not occur on Marys Peak or elsewhere in western Oregon. Suillus hypogaeus, therefore, represents both an independent origin of the hypogeous, sequestrate sporocarp within the Boletales and an independent host shift between Larix and Pseudotsuga within the genus Suillus.

Development towards a novel screening method for nipecotic acid bioisosteres using molecular imprinted polymers (MIPs) as alternative to in vitro cellular uptake assays.

Impaired expression of GABA transporters (GATs) is closely related to the pathogenesis of among others Parkinson's disease and epilepsy. As such, lipophilic nipecotic acid analogs have been extensively studied as GAT1-addressing drugs and radioligands but suffer from limited brain uptake due to the zwitterionic properties of the nipecotic acid moiety. Bioisosteric replacement of the carboxylic acid group is a promising strategy to improve the brain uptake, though it requires knowledge on the binding of these isosteres to GAT1. To screen nipecotic acid isosteres for their affinity to GAT1 in a time- and cost-effective manner, this research aims to develop a molecular imprinted polymer (MIP) that mimics the natural binding site of GAT1 and can act as an alternative screening tool to the current radiometric and mass spectrometry cellular-based assays. To this end, a nipecotic acid MIP was created using the electropolymerization of ortho-phenylenediamine (oPD) by cyclic voltammetry (CV). The optimization of the generated receptor layer was achieved by varying the scan rate (50-250 mV/s) and number of CV cycles (5-12), yielding an optimized MIP with an average imprinting factor of 2.6, a linear range of 1-1000 nm, and a theoretical LOD of 0.05 nm, as analyzed by electrical impedance spectroscopy (EIS). Selectivity studies facilitated the investigation of major binding interactions between the MIP and the substrate, building an experimental model that compares characteristics of various analogs. Results from this model indicate that the substrate carboxylic acid group plays a more important role in binding than an amine group, after comparing the binding of cyclohexanecarboxylic acid (average IF of 1.7) and piperidine (average IF of 0.46). The research culminates in a discussion regarding the feasibility of the in vitro model, comparing the synthetic system against the biological performance of GAT1. Thus, evaluating if it is possible to generate a synthetic GAT1 mimic, and if so, provide directions for follow-up research.

Assessment of Elemental Deficiency of Crossbred Dairy Cows and Mineral Composition in Natural Feed and Nutritional Supplements in the Northern and Northwestern Provinces in Sri Lanka.

This study assessed the elemental status of cross-bred dairy cows in small holder farms in Sri Lanka, with the aim to establish the elemental baseline and identify possible deficiencies. For this purpose, 458 milk, hair, serum and whole blood samples were collected from 120 cows in four regions of Northern and Northwestern Sri Lanka, (namely Vavaniya, Mannar, Jaffna and Kurunegala). Farmers also provided a total of 257 samples of feed, which included local fodder as well as 79 supplement materials. The concentrations of As, Ca, Cd, Co, Cr, Cu, Fe, I, K, Mg, Mn, Mo, Na, Ni, Pb, Se, V and Zn were determined by inductively coupled plasma mass spectrometry (ICP-MS). Evaluation of the data revealed that all cows in this study could be considered deficient in I and Co (18.6-78.5 µg L-1 I and 0.06-0.65 µg L-1 Co, in blood serum) when compared with deficiency upper boundary levels of 0.70 µg L-1 Co and 50 µg L-1 I. Poor correlations were found between the composition of milk or blood with hair, which suggests that hair is not a good indicator of mineral status. Most local fodders meet dietary requirements, with Sarana grass offering the greatest nutritional profile. Principal component analysis (PCA) was used to assess differences in the elemental composition of the diverse types of feed, as well as regional variability, revealing clear differences between forage, concentrates and nutritional supplements, with the latter showing higher concentrations of non-essential or even toxic elements, such as Cd and Pb.

Bi-directional and multi-modal effects of dexamphetamine on spatial binding windows in healthy individuals.

OBJECTIVES: Stimuli that are separated by a short window of space or time, known as spatial and temporal binding windows (SBW/TBWs), may be perceived as separate. Widened TBWs are evidenced in schizophrenia, although it is unclear if the SBW is similarly affected. The current study aimed to assess if dexamphetamine (DEX) may increase SBWs in a multimodal visuo-tactile illusion, potentially validating usefulness as an experimental model for multimodal visuo-tactile hallucinations in schizophrenia, and to examine a possible association between altered binding windows (BWs) and working memory (WM) suggested by previous research. METHODS: A placebo-controlled, double-blinded, and counter-balanced crossover design was employed. Permuted block randomisation was used for drug order. Healthy participants received DEX (0.45 mg/kg, PO, b.i.d.) or placebo (glucose powder) in capsules. The Rubber Hand Illusion (RHI) and Wechsler Adult Intelligence Scale Spatial Span was employed to determine whether DEX would alter SBWs and WM, respectively. Schizotypy was assessed with a variety of psychological scales. RESULTS: Most participants did not experience the RHI even under normal circumstances. Bi-directional and multimodal effects of DEX on individual SBWs and schizotypy were observed, but not on WM. CONCLUSIONS: Bidirectional multimodal effects of DEX on the RHI and SBWs were observed in individuals, although not associated with alterations in WM.

Efficacy of a Haemonchus contortus vaccine under field conditions in young alpacas.

Anthelmintic resistance to Haemonchus contortus creates increasing management challenges with small ruminants and camelids. The commercial vaccine, Barbervax®, contains H11 and H-gal-GP antigens, derived from gut mucosal membrane enzymes of H. contortus involved in digesting blood. Antibody neutralization of these antigens causes failure of H. contortus to digest blood, resulting in parasite death. H11 and H-gal-GP are considered "hidden" antigens, meaning the host immune system does not encounter these proteins under natural infection. Therefore, repeat immunization is required to maintain protective humoral responses. One previous study evaluated the safety of Barbervax® in camelids but the efficacy could not be assessed due to lack of successful infection in the controls. The objective of the current study was to evaluate clinical parameters of anemia, fecal egg counts (FECs), and humoral immune responses of healthy alpacas after immunizing with Barbervax® compared to non-vaccinated controls, all under natural environmental exposure on parasite-laden pastures. A crossover-like study was performed where twenty alpacas (298 ± 66 days of age) were assigned to be initially vaccinated with Barbervax® (n=10) or receive no treatment (n=10). Three doses of Barbervax® were administered at three-week intervals. Feces and blood were collected on Day -10, 0, 21, 43, 64, 85, 106, and 135 to evaluate FECs, packed cell volume (PCV), and antibody titers. Each group was kept on separate adjacent pastures. Tracer sheep (n=2 per study group) were introduced on Day 43 for a three-week period to ensure parasite acquisition. For the crossover-like component on Day 85, the initial non-vaccinated group was administered Barbervax® with dosing repeated on Day 106 and 135. Results indicated all initially vaccinated alpacas produced antibody titers to vaccine antigen that corresponded to lower mean FECs compared to the initially non-vaccinated group. A reduced mean FEC in the vaccinate group was observed 21 days after peak antibody titers. Similarly, when pooled vaccinate antibody titers were noted to wane on Day 106, an increase in FEC was observed at the following time point (Day 135). Conclusions from our study support the use of Barbervax® to reduce H. contortus burdens in alpacas. Furthermore, a less than 30-day lag time between antibody titer and resultant effect in FECs was observed. Additional studies assessing the ability of Barbervax® to reduce H. contortus burdens during subsequent grazing seasons would provide even greater information regarding the use of Barbervax® within alpaca herds to modulate H. contortus infections, refugia, and anthelmintic use.