Acute and Long-Term Management of Blunt Cerebrovascular Injury at a Quaternary Referral Level 1 Trauma Center: The Memphis Experience and Comparison of a New Scoring System.

BACKGROUND AND OBJECTIVES: The management of blunt cerebrovascular injuries (BCVIs) remains an important topic within trauma and neurosurgery today. There remains a lack of consensus within the literature and significant variation across institutions. The purpose of this study was to evaluate management of BCVI at a large, tertiary referral trauma center. METHODS: Institutional Review Board approval was obtained to conduct a retrospective review of patients with BCVI at our Level 1 Trauma Center. Computed tomography angiography was used to identify BCVI for each patient. Patient information was collected, and statistical analysis was performed. With the included risk factors for ischemic complications, a novel scoring system based on ischemic risk, the "Memphis Score," was developed and evaluated to grade BCVI. RESULTS: Two hundred seventeen patients with BCVI from July 2020 to August 2022 were identified. The most common mechanism of injury was motor vehicle collision (141, 65.0%). Vertebral arteries were the most common vessel injured (136, 51.1%) with most injuries occurring at a high cervical location (101, 38.0%). Denver Grade 1 injuries (89, 33.5%) and a Memphis Score of 1 were most frequent (172, 64.6%), and initial anticoagulation with heparin drip was initiated 56.7% of the time (123). Endovascular treatment was required in 24 patients (11.1%) and was usually performed in the first 48 hours (15, 62.5%). While Denver Grade (P = .019) and Memphis Score (P < .00001) were significantly higher in those patients undergoing endovascular treatment, only the Memphis Score demonstrated a significant difference between those patients who had stroke or worsening on follow-up imaging and those who did not (P = .0009). CONCLUSION: Although BCVI management has improved since early investigative efforts, institutions must evaluate and share their data to help clarify outcomes. The novel "Memphis Score" presents a standardized framework to communicate ischemic risk and guide management of BCVI.

A review of soybean processing byproducts and their use in swine and poultry diets.

Due to its importance in animal feed, soybean meal has been extensively studied to optimize its use in livestock diets. Despite extensive research, the industry has not fully characterized specific areas of soybean processing such as the inclusion of soybean byproducts added back to soybean meal during processing. Soybean processing byproducts can encompass a large variety of materials including weeds and foreign material, soybean hulls, gums, soapstocks, lecithins, spent bleaching clays, and deodorizer distillates. Despite the potential for being added back to soybean meal when a crushing plant is integrated with an oil refinery, there is currently limited information on the composition of many of these soybean processing byproducts and their subsequent effects on soybean meal quality and animal performance. Therefore, there may be opportunities for a new area of research focused on soybean processing byproducts and their optimal use within the livestock feed industry. This review summarizes the current information on soybean byproducts with a focus on identifying the areas with the greatest potential for future research in swine and poultry nutrition.

Erythema dyschromicum perstans-like eruptions induced by epidermal growth factor receptor inhibitors in patients with lung cancer.

INTRODUCTION: Cutaneous adverse reactions to epidermal growth factor receptor inhibitors (EGFRi) are some of the most common side effects that patients experience. However, cutaneous adverse reactions that cause dyspigmentation in patients have been rarely reported. Erythema dyschromicum perstans (EDP) is a rare pigmentary condition that causes ashy-grey hyperpigmented macules and patches, with a few cases reported from EGFRi in the literature. The disfiguration caused by this condition may negatively impact patients' quality of life. Our study aimed to describe the clinical characteristics of EDP induced by EGFRi to better recognize and manage the condition. METHODS: We conducted a multicenter retrospective review at three academic institutions to identify patients with EDP induced by EGFRi from 2017 to 2023 and included sixteen patients in our study. RESULTS: The median age of patients was 66 years old, with 63% female and 37% male (Table 1). The majority of our patients were Asian (88%). All patients had non-small cell lung cancer and most patients received osimertinib. Median time to EDP was 6 months. The most common areas of distribution were the head/neck region, lower extremities, and upper extremities. Various topical ointments were trialed; however, approximately less than half had improvement in their disease and most patients had persistent EDP with no resolution. All patients desired treatment except one with EDP on the tongue, and there was no cancer treatment discontinuation or interruption due to EDP. Table 1 Patient demographics and clinical characteristics of 16 patients with EDP induced by EGFRi Case no Demographics: age, race, and sex Fitzpatrick skin type Cancer type EGFR therapy Concomitant photosensitive drug(s) Time to EDP (months) Clinical features Distribution Symptoms Treatments and clinical course EDP status from most recent follow up 1 47 y/o Asian male III Stage IV NSCLC Erlotinib None Unknown Brown-blue-gray hyperpigmented patches Bilateral shins Left thigh Xerosis Pruritus Triamcinolone 0.1% ointment for 4 months, improvement of blue discoloration Tacrolimus 0.1% BID for 9 months, improvement but no resolution Ongoing 2 62 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown hyperpigmented patches Bilateral arms Back Forehead Neck Right shin None Tacrolimus 0.1% ointment for 1 year with minor improvement Ongoing 3 69 y/o Asian female IV Stage IV NSCLC Osimertinib None 4 Gray-brown macules and patches Chest Face Forehead Bilateral legs None Tacrolimus 0.1% ointment for 10 months, no improvement Ongoing 4 79 y/o White male II Stage IV NSCLC Osimertinib None 15 Mottled grey-blue hyperpigmented patches and plaques with mild scaling Bilateral arms Back Forehead Neck None Photoprotection, no improvement Ongoing 5 69 y/o Asian female III Stage IV NSCLC Osimertinib Ibuprofen 4 Blue-grey hyperpigmented macules and patches Abdomen Bilateral arms None Tacrolimus 0.1% ointment for 7 months, no improvement Ongoing 6 65 y/o Asian male III Stage IV NSCLC Osimertinib None 20 Hyperpigmented blue gray macules and patches Helix Bilateral shins None Photoprotection, no improvement Ongoing 7 66 y/o Asian female IV Stage IV NSCLC Erlotinib TMP-SMX 6 Ashy grey-brown thin plaques Back Forehead None 2.5% hydrocortisone ointment for 8 months, resolved Resolved 8 82 y/o Asian male III Stage III NSCLC Erlotinib Simvastatin 20 Ash-grey hyperpigmented patches Dorsal feet Forehead Scalp None Photoprotection Ongoing 9 57 y/o Asian female III Stage II NSCLC Erlotinib None 1 Bue-grey discoloration Tongue None No intervention Ongoing 10 51 y/o Asian female III Stage IV NSCLC Osimertinib None 9 Blue-grey hyperpigmented macules and patches Bilateral arms Axillae Groin Neck Trunk None 2.5% hydrocortisone ointment, triamcinolone 0.1% ointment, photoprotection with mild improvement Ongoing 11 67 y/o Asian male III Stage IV NSCLC Osimertinib None 7 Gray-blue macules and patches with mild background erythema and scaling Bilateral arms Ears Face Bilateral shins None Triamcinolone 0.1% ointment, protection for 6 months with mild improvement Ongoing 12 75 y/o Asian female IV Stage III NSCLC Osimertinib TMP-SMX 3 Gray-blue hyperpigmented patches Bilateral arms Abdomen Back Face Bilateral shins Pruritus Triamcinolone 0.1% and betamethasone 0.01% with relief of pruritus, lesions unchanged Triluma cream 6 months, mild improvement Ongoing 13 42 y/o Asian male IV Stage IV NSCLC Afatinib TMP-SMX 24 Grey-brown hyperpigmented patches Back Face None Hydroquinone 4% cream for 2 years with mild improvement Ongoing 14 74 y/o White female III Stage II NSCLC Osimertinib Atorvastatin 4 Grey-brown hyperpigmented patches Bilateral legs Trunk None Photoprotection Ongoing 15 64 y/o Asian female IV Stage IV NSCLC Osimertinib None 3 Gray-brown hyperpigmentation Abdomen Bilateral arms Back Bilateral legs Pruritus Triamcinolone 0.1% cream; No change, minimal concern to patient Ongoing 16 52 y/o Asian female IV Stage IV NSCLC Osimertinib None 42 Gray hyperpigmented patches with digitate shape Abdomen Bilateral flanks None Triamcinolone 0.1% cream Ongoing NSCLC, non-small cell lung cancer, TMP-SMX, Trimethoprim/Sulfamethoxazole CONCLUSIONS: We highlight the largest case series describing EDP from EGFR inhibitors, which mostly affected Asian patients with lung malignancy and on EGFR tyrosine kinase inhibitors. Clinicians should be able to recognize this condition in their patients and assess how it is affecting their quality of life, and refer to dermatology to help with management.

Improving Pneumococcal Vaccination Rates in Immunosuppressed Pediatric Patients with Rheumatic Disease.

Background: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Methods: Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. Results: There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Conclusions: Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.

Temperate phage-antibiotic synergy across antibiotic classes reveals new mechanism for preventing lysogeny.

A recent demonstration of synergy between a temperate phage and the antibiotic ciprofloxacin suggested a scalable approach to exploiting temperate phages in therapy, termed temperate phage-antibiotic synergy, which specifically interacted with the lysis-lysogeny decision. To determine whether this would hold true across antibiotics, we challenged Escherichia coli with the phage HK97 and a set of 13 antibiotics spanning seven classes. As expected, given the conserved induction pathway, we observed synergy with classes of drugs known to induce an SOS response: a sulfa drug, other quinolones, and mitomycin C. While some ß-lactams exhibited synergy, this appeared to be traditional phage-antibiotic synergy, with no effect on the lysis-lysogeny decision. Curiously, we observed a potent synergy with antibiotics not known to induce the SOS response: protein synthesis inhibitors gentamicin, kanamycin, tetracycline, and azithromycin. The synergy results in an eightfold reduction in the effective minimum inhibitory concentration of gentamicin, complete eradication of the bacteria, and, when administered at sub-optimal doses, drastically decreases the frequency of lysogens emerging from the combined challenge. However, lysogens exhibit no increased sensitivity to the antibiotic; synergy was maintained in the absence of RecA; and the antibiotic reduced the initial frequency of lysogeny rather than selecting against formed lysogens. Our results confirm that SOS-inducing antibiotics broadly result in temperate-phage-specific synergy, but that other antibiotics can interact with temperate phages specifically and result in synergy. This is the first report of a means of chemically blocking entry into lysogeny, providing a new means for manipulating the key lysis-lysogeny decision.IMPORTANCEThe lysis-lysogeny decision is made by most bacterial viruses (bacteriophages, phages), determining whether to kill their host or go dormant within it. With over half of the bacteria containing phages waiting to wake, this is one of the most important behaviors in all of biology. These phages are also considered unusable for therapy because of this behavior. In this paper, we show that many antibiotics bias this behavior to "wake" the dormant phages, forcing them to kill their host, but some also prevent dormancy in the first place. These will be important tools to study this critical decision point and may enable the therapeutic use of these phages.

Psoas force recruitment in full-body musculoskeletal movement simulations is restored with a geometrically informed cost function weighting.

Simulations of musculoskeletal models are useful for estimating internal muscle and joint forces. However, predicted forces rely on optimization and modeling formulations. Geometric detail is important to predict muscle forces, and greater geometric complexity is required for muscles that have broad attachments or span many joints, as in the torso. However, the extent to which optimized muscle force recruitment is sensitive to these geometry choices is unclear. We developed level, uphill and downhill sloped walking simulations using a standard (uniformly weighted, "fatigue-like") cost function with lower limb and full-body musculoskeletal models to evaluate hip muscle recruitment with different geometric representations of the psoas muscle under walking conditions with varying hip moment demands. We also tested a novel cost function formulation where muscle activations were weighted according to the modeled geometric detail in the full-body model. Total psoas force was less and iliacus, rectus femoris, and other hip flexors' force was greater when psoas was modeled with greater geometric detail compared to other hip muscles for all slopes. The proposed weighting scheme restored hip muscle force recruitment without sacrificing detailed psoas geometry. In addition, we found that lumbar, but not hip, joint contact forces were influenced by psoas force recruitment. Our results demonstrate that static optimization dependent simulations using models comprised of muscles with different amounts of geometric detail bias force recruitment toward muscles with less geometric detail. Muscle activation weighting that accounts for differences in geometric complexity across muscles corrects for this recruitment bias.

Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Evaluating the effects of benzoic acid on nursery and finishing pig growth performance.

Three studies were conducted evaluating the use of benzoic acid in swine diets. In experiment 1, 350 weanling barrows (DNA 200 × 400; initially 5.9 ±â€…0.04 kg) were allotted to one of the five dietary treatments with 14 pens per treatment. Diets were fed in three phases: phase 1 from weaning to day 10, phase 2 from days 10 to 18, and phase 3 from days 18 to 38. Treatment 1 contained no benzoic acid throughout all three phases (weaning to day 42). Treatment 2 included 0.50% benzoic acid throughout all three phases. Treatment 3 contained 0.50% benzoic acid in phases 1 and 2, and 0.25% benzoic acid in phase 3. Treatment 4 contained 0.50% benzoic acid in phases 1 and 2, and no benzoic acid in phase 3. Treatment 5 contained 0.50% benzoic acid in phase 1, 0.25% benzoic acid in phase 2, and no benzoic acid in phase 3. For the overall period, pigs fed 0.50% in the first two phases and 0.25% benzoic acid in the final phase had greater (P < 0.05) average daily gain (average daily gain) than pigs fed no benzoic acid through all three phases, or pigs fed 0.50% in the first two phases and no benzoic acid in the final phase, with pigs fed the other treatments intermediate. Pigs fed 0.50% in the first two phases and 0.25% benzoic acid in the final phase had improved (P < 0.05) gain-to-feed ratio (G:F) compared with pigs fed no benzoic acid throughout all three phases, pigs fed 0.50% in the first two phases and no benzoic acid in the third phase, or pigs fed 0.50%, 0.25%, and no benzoic acid, respectively. For experiment 2, a 101-d trial was conducted using two groups of 1,053 finishing pigs (2,106 total pigs; PIC 337 × 1,050; initially 33.3 ±â€…1.9 kg). Dietary treatments were corn-soybean meal-dried distillers grains with solubles-based with the addition of none, 0.25%, or 0.50% benzoic acid. Overall, pigs fed increasing benzoic acid had a tendency for increased average daily feed intake (linear, P = 0.083) but decreased G:F (linear, P < 0.05). In experiment 3, 2,162 finishing pigs (DNA 600 × PIC 1050; initially 31.4 ±â€…2.2 kg) were used in a 109-d trial. Dietary treatments were formulated with or without 0.25% benzoic acid. For the overall experimental period, pigs fed benzoic acid had increased (P < 0.05) G:F. In summary, feeding benzoic acid elicits improved growth performance when fed throughout the entire nursery period while improved G:F in growing-finishing pigs was observed in one experiment, but not in the other.

Catharanthine Modulates Mesolimbic Dopamine Transmission and Nicotine Psychomotor Effects via Inhibition of α6-Nicotinic Receptors and Dopamine Transporters.

Iboga alkaloids, also known as coronaridine congeners, have shown promise in the treatment of alcohol and opioid use disorders. The objective of this study was to evaluate the effects of catharanthine and 18-methoxycoronaridine (18-MC) on dopamine (DA) transmission and cholinergic interneurons in the mesolimbic DA system, nicotine-induced locomotor activity, and nicotine-taking behavior. Utilizing ex vivo fast-scan cyclic voltammetry (FSCV) in the nucleus accumbens core of male mice, we found that catharanthine or 18-MC differentially inhibited evoked DA release. Catharanthine inhibition of evoked DA release was significantly reduced by both α4 and α6 nicotinic acetylcholine receptors (nAChRs) antagonists. Additionally, catharanthine substantially increased DA release more than vehicle during high-frequency stimulation, although less potently than an α4 nAChR antagonist, which confirms previous work with nAChR antagonists. Interestingly, while catharanthine slowed DA reuptake measured via FSCV ex vivo, it also increased extracellular DA in striatal dialysate from anesthetized mice in vivo in a dose-dependent manner. Superfusion of catharanthine or 18-MC inhibited the firing rate of striatal cholinergic interneurons in a concentration dependent manner, which are known to potently modulate presynaptic DA release. Catharanthine or 18-MC suppressed acetylcholine currents in oocytes expressing recombinant rat α6/α3ß2ß3 or α6/α3ß4 nAChRs. In behavioral experiments using male Sprague-Dawley rats, systemic administration of catharanthine or 18-MC blocked nicotine enhancement of locomotor activity. Importantly, catharanthine attenuated nicotine self-administration in a dose-dependent manner while having no effect on food reinforcement. Lastly, administration of catharanthine and nicotine together greatly increased head twitch responses, indicating a potential synergistic hallucinogenic effect. These findings demonstrate that catharanthine and 18-MC have similar, but not identical effects on striatal DA dynamics, striatal cholinergic interneuron activity and nicotine psychomotor effects.

Ivermectin increases striatal cholinergic activity to facilitate dopamine terminal function.

Ivermectin (IVM) is a commonly prescribed antiparasitic treatment with pharmacological effects on invertebrate glutamate ion channels resulting in paralysis and death of invertebrates. However, it can also act as a modulator of some vertebrate ion channels and has shown promise in facilitating L-DOPA treatment in preclinical models of Parkinson's disease. The pharmacological effects of IVM on dopamine terminal function were tested, focusing on the role of two of IVM's potential targets: purinergic P2X4 and nicotinic acetylcholine receptors. Ivermectin enhanced electrochemical detection of dorsal striatum dopamine release. Although striatal P2X4 receptors were observed, IVM effects on dopamine release were not blocked by P2X4 receptor inactivation. In contrast, IVM attenuated nicotine effects on dopamine release, and antagonizing nicotinic receptors prevented IVM effects on dopamine release. IVM also enhanced striatal cholinergic interneuron firing. L-DOPA enhances dopamine release by increasing vesicular content. L-DOPA and IVM co-application further enhanced release but resulted in a reduction in the ratio between high and low frequency stimulations, suggesting that IVM is enhancing release largely through changes in terminal excitability and not vesicular content. Thus, IVM is increasing striatal dopamine release through enhanced cholinergic activity on dopamine terminals.

Predictors of Impairment and Self-Concept in Children and Adolescents with Persistent Tic Disorder.

This study examined predictors of, and associations between, self-concept, demographic variables, and clinical measures in fifty-eight children and adolescents with Persistent Tic Disorder (PTD; 44 males, Mage = 11.9 years, SD = 2.74). Participants completed measures that assessed self-concept, tic severity, tic-related impairment, and comorbid psychological symptoms. Results showed that generalized anxiety disorder, major depressive disorder, persistent depressive disorder, total tic severity, number and complexity of tics, and total and social tic-related impairment were associated with self-concept. Tic-related social impairment mediated the relationship between tic severity and self-concept. Exploratory analyses found that total tic severity, motor tic severity, and vocal tic severity, as well as the number, intensity, and interference of tics predicted social tic-related impairment. Results suggest that treatments to reduce the number and complexity of tics, with additional focus on navigating social interactions, may serve to decrease tic severity and impairment, and in turn, improve self-concept.

Epigenetics to clinicopathological features: a bibliometric analysis of H3 G34-mutant diffuse hemispheric glioma literature.

PURPOSE: Pediatric-type diffuse high-grade gliomas are the leading cause of cancer-related morbidity and mortality in children. More than 30% of diffuse hemispheric gliomas (DHG) in adolescents harbor histone H3 G34 mutations and are recognized by the World Health Organization as a distinct tumor entity. By reporting bibliometric characteristics of the most cited publications on H3 G34-mutant DHG (H3 G34 DHG), we provide an overview of emerging literature and speculate where future research efforts may lead. METHODS: One hundred fourteen publications discussing H3 G34 DHG were identified, categorized as basic science (BSc), clinical (CL), or review (R), and ranked by citation number. Various bibliometric parameters were summarized, and a comparison between article types was performed. RESULTS: Articles within this study represent principal investigators from 15 countries and were published across 63 journals between 2012 and 2024, with 36.84% of articles originating in the United States. Overall median values were as follows: citation count, 20 (range, 0-2591), number of authors, 9 (range, 2-78), and year of publication, 2020 (range, 2012-2024). Among the top ten most cited articles, BSc articles accounted for all ten reports. Compared to CL and R articles, BSc articles were published in journals with higher impact factors. CONCLUSION: We establish variability in bibliometric parameters for the most cited publications on H3 G34 DHG. Our findings demonstrate a paucity of high-impact and highly cited CL reports and acknowledge an unmet need to intersect basic mechanism with clinical data to inform novel therapeutic approaches.

Cross-Reactivity of 24 Cannabinoids and Metabolites in blood using the immunalysis cannabinoids direct enzyme-linked immunosorbent assay kit.

With a wider availability of synthetic and semi-synthetic cannabinoids in the consumer space, there is a growing impact on public health and safety. Forensic toxicology laboratories should keep these compounds in mind as they attempt to remain effective in screening for potential sources of human performance impairment. Enzyme-linked immunosorbent assay (ELISA) is a commonly utilized tool in forensic toxicology, as its efficiency and sensitivity make it useful for rapid and easy screening for a large number of drugs. This screening technique has lower specificity, which allows for broad cross-reactivity among structurally-similar compounds. In this study, the Cannabinoids Direct ELISA kit from Immunalysis was utilized to assess the cross-reactivities of 24 cannabinoids and metabolites in whole blood. The assay was calibrated with 5 ng/mL of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and the analytes of interest were evaluated at concentrations ranging from 5 to 500 ng/mL. Most parent compounds demonstrated cross-reactivity ≥ 20 ng/mL, with increasing alkyl side chain length relative to Δ9-tetrahydrocannabinol resulting in decreased cross-reactivity. Of the 24 analytes, only the carboxylic acid metabolites, 11-nor-9-carboxy-Δ8-tetrahydrocannabinol, 11-nor-9(R)-carboxy-hexahydrocannabinol, and 11-nor-9(S)-carboxy-hexahydrocannabinol, were cross-reactive at levels ≤ 10 ng/mL. Interestingly, 11-nor-9(R)-carboxy-hexahydrocannabinol demonstrated cross-reactivity at 5 ng/mL, where its stereoisomer 11-nor-9(S)-carboxy-hexahydrocannabinol, did not. As more information emerges about the prevalence of these analytes in blood specimens, it is important to understand and characterize their impact on current testing paradigms.

Ancient mitogenomes from Pre-Pottery Neolithic Central Anatolia and the effects of a Late Neolithic bottleneck in sheep (Ovis aries).

Occupied between ~10,300 and 9300 years ago, the Pre-Pottery Neolithic site of Asikli Höyük in Central Anatolia went through early phases of sheep domestication. Analysis of 629 mitochondrial genomes from this and numerous sites in Anatolia, southwest Asia, Europe, and Africa produced a phylogenetic tree with excessive coalescences (nodes) around the Neolithic, a potential signature of a domestication bottleneck. This is consistent with archeological evidence of sheep management at Asikli Höyük which transitioned from residential stabling to open pasturing over a millennium of site occupation. However, unexpectedly, we detected high genetic diversity throughout Asikli Höyük's occupation rather than a bottleneck. Instead, we detected a tenfold demographic bottleneck later in the Neolithic, which caused the fixation of mitochondrial haplogroup B in southwestern Anatolia. The mitochondrial genetic makeup that emerged was carried from the core region of early Neolithic sheep management into Europe and dominates the matrilineal diversity of both its ancient and the billion-strong modern sheep populations.

Diagnostic survey of analytical methods used to determine bone mineralization in pigs.

Pigs from 64 commercial sites across 14 production systems in the Midwest United States were evaluated for baseline biological measurements used to determine bone mineralization. There were three pigs selected from each commercial site representing: 1) a clinically normal pig (healthy), 2) a pig with evidence of clinical lameness (lame), and 3) a pig from a hospital pen that was assumed to have recent low feed intake (unhealthy). Pigs ranged in age from nursery to market weight, with the three pigs sampled from each site representing the same age or phase of production. Blood, urine, metacarpal, fibula, 2nd rib, and 10th rib were collected and analyzed. Each bone was measured for density and ash (defatted and non-defatted technique). A bone × pig type interaction (P < 0.001) was observed for defatted and non-defatted bone ash and density. For defatted bone ash, there were no differences among pig types for the fibulas, 2nd rib, and 10th rib (P > 0.10), but metacarpals from healthy pigs had greater (P < 0.05) percentage bone ash compared to unhealthy pigs, with the lame pigs intermediate. For non-defatted bone ash, there were no differences among pig types for metacarpals and fibulas (P > 0.10), but unhealthy pigs had greater (P < 0.05) non-defatted percentage bone ash for 2nd and 10th ribs compared to healthy pigs, with lame pigs intermediate. Healthy and lame pigs had greater (P < 0.05) bone density than unhealthy pigs for metacarpals and fibulas, with no difference observed for ribs (P > 0.10). Healthy pigs had greater (P < 0.05) serum Ca and 25(OH)D3 compared to unhealthy pigs, with lame pigs intermediate. Healthy pigs had greater (P < 0.05) serum P compared to unhealthy and lame pigs, with no differences between the unhealthy and lame pigs. Unhealthy pigs excreted significantly more (P < 0.05) P and creatinine in the urine compared to healthy pigs with lame pigs intermediate. In summary, there are differences in serum Ca, P, and vitamin D among healthy, lame, and unhealthy pigs. Differences in bone mineralization among pig types varied depending on the analytical procedure and bone, with a considerable range in values within pig type across the 14 production systems sampled.

There is little literature or data comparing bone diagnostic results for healthy, lame, and unhealthy pigs. Typically, diagnosticians assessing clinical lameness cases in pigs will measure bone mineralization along with histopathological evaluation to diagnose and assess the severity of metabolic bone disease. Bone ash is the primary method to determine bone mineralization, with the removal of the lipid in the bone (defatting) before the bone is ashed, compared to not removing the lipid before the ashing (non-defatted). Defatting the bone reduces the amount of variation across the bones compared to non-defatting. In this diagnostic survey, there was no difference among the healthy, lame, or unhealthy pigs when comparing defatted bone ash, however, unhealthy pigs had an increased bone ash percentage compared to the healthy and lame pigs when the bones were assessed using the non-defatted procedure. There was variation across production systems and pig types for serum vitamin D. When comparing the pig types, healthy pigs had increased serum Ca, P, and vitamin D [25(OH)D3] compared to the unhealthy pigs, with the lame pigs intermediate.

Technical note: utilization of various allotment strategies to evaluate variation and replications required to detect statistical significance in nursery pig research.

A total of 720 barrows (line 200 × 400, DNA genetics) were used in two 42-d nursery trials (initially 6.20 ±â€…0.12 kg and 5.63 ±â€…0.16 kg, respectively) to evaluate strategies for allotting pigs to pens in randomized controlled trials. At placement, the population was split into three cohorts with similar average weight and standard deviation and randomly assigned to one of the three allotment strategies. Strategy 1 (random) utilized a simple randomization strategy with each pig randomized to pens independent of all other pigs. Strategy 2 (body weight [BW] distribution) sorted each pig within the cohort into one of the five BW groups. One pig from each weight group was then randomly assigned to a pen such that distribution of BW within pen was uniform across pens. Strategy 3 (BW grouping) sorted pigs within the cohort into 3 BW categories: light, medium, and heavy. Within each BW category, pigs were randomized to pen to create pens of pigs from each BW category. Within each experiment, there were 72 pens with five pigs per pen and 24 pens per allotment strategy. For all strategies, once pigs were allotted to pens, pens were allotted to one of the two treatments for a concurrent trial. In experiment 1, environmental enrichment using ropes tied near the pan of the feeder was compared to a control with no enrichment. In experiment 2, treatment diets consisted of basal levels of Zn and Cu from the trace mineral premix for the duration of the study (110 and 17 mg/kg, respectively; control), or diets (supplemented control) with carbadox (50 g/ton; Mecadox, Phibro Animal Health, Teaneck, NJ) fed in phase 1 (days 0 to 22) and 2 (days 22 to 43), pharmacological levels of Zn and Cu (2,414 mg/kg Zn from ZnO; 168 mg/kg Cu from CuSO4) fed in phase 1, and only pharmacological levels of Cu (168 mg/kg Cu from CuSO4) fed in phase 2. These treatment designs were used to determine the impact on coefficient of variation (CV) and to estimate the number of replications required to find significant treatment differences based on allotment strategy. There were no meaningful allotment strategy × treatment interactions for either study. For between-pen CV, pigs allotted using BW distribution and BW grouping strategies had the lowest CV at allotment and final weight in both trials. For overall average daily gain in experiments 1 and 2 in experiment 2, the BW distribution strategy required the fewest replications to detect differences in performance. However, there is no meaningful difference between allotment strategies in replications required to detect significant differences for gain:feed ratio.

Decreasing variation between experimental units increases the likelihood of finding a statistically significant difference if one exists. Assignment of animals to experimental units (pens) may contribute to that variation. Therefore, the purpose of this trial was to investigate the effect that different methods of allotting pigs to pens (experimental unit) have on variation and in turn, the number of replications required to detect a significant difference of a given amount between treatments. The random strategy assigned pigs to pens in a completely random fashion. The body weight (BW) distribution strategy ordered pigs from lightest to heaviest and created five groups based on BW. Each pen was randomly assigned one pig from each of the five groups. The BW grouping strategy again ordered pigs from lightest to heaviest but split pigs into three groups based on BW and each pen was randomly assigned pigs from only one BW group such that there were pens of light pigs, pens of medium pigs, and pens of heavy pigs. Ultimately, the best allotment strategy depends on the parameter of interest. For final BW and overall ADG, the BW grouping method required the fewest pens to detect statistically significant differences.

Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

Unlocking the power of virtual networking for early-career researchers.

Many successful researchers in the biomedical sciences have benefitted from mentors and networks earlier in their career. However, early-career researchers from minoritized and underrepresented groups do not have the same access to potential mentors and networks as many of their peers. In this article we describe how 'cold emails' and social media platforms - notably Twitter/X and LinkedIn - can be used to build virtual networks, and stress the need to invest in maintaining networks once they have been established.

Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study.

BACKGROUND: Mirikizumab, a p19-directed interleukin-23 monoclonal antibody, is efficacious in inducing clinical remission at week 12 (W12) and maintaining clinical remission at W52 in patients with moderately to severely active ulcerative colitis. Results are presented from the open-label extension study through W104. METHODS: Clinical, symptomatic, quality-of-life, and adverse event outcomes are reported for mirikizumab induction responders and extended induction responders, including biologic-failed patients, who entered LUCENT-3, with data shown for W52 maintenance responders or remitters. Discontinuations or missing data were handled by nonresponder imputation (NRI), modified NRI (mNRI), and observed case (OC). RESULTS: Among W52 mirikizumab responders, clinical response at W104 was 74.5%, 87.2%, and 96.7% and clinical remission was 76.6%, 89.0%, and 98.3% for NRI, mNRI, and OC, respectively. Among W52 mirikizumab remitters, clinical response at W104 was 54.0%, 62.8%, and 70.1% and clinical remission was 65.6%, 76.1%, and 84.2%. Using mNRI, remission rates at W104 for W52 clinical remitters were 74.7% corticosteroid-free, 79.5% endoscopic, 63.9% histologic-endoscopic mucosal remission, 85.9% symptomatic, 59.8% bowel urgency, 80.5% Inflammatory Bowel Disease Questionnaire (using NRI), 71.2% histologic-endoscopic mucosal improvement, and 77.5% bowel urgency improvement. Previous biologic-failed vs not-biologic-failed patient data were generally similar. Extended induction mNRI clinical response was 81.9%. Serious adverse events were reported in 5.2% of patients; 2.8% discontinued treatment due to adverse events. CONCLUSIONS: Endoscopic, histologic, symptomatic, and quality-of-life outcomes support the long-term benefit of mirikizumab treatment up to 104 weeks in patients with ulcerative colitis, including biologic-failed patients, with no new safety concerns.

Long-term clinical response/remission, endoscopic, histologic, and symptomatic data from an open-label study in patients with moderately to severely active ulcerative colitis demonstrate that 2-year continuous mirikizumab treatment maintained clinical remission in a majority of induction clinical responders, regardless of previous biologic failure status.