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Objective language proficiency measures have been found to provide better and more consistent estimates of bilinguals' language processing than self-rated proficiency (e.g., Tomoschuk et al., 2019; Wen & van Heuven, 2017a). However, objectively measuring language proficiency is often not possible because of a lack of quick and freely available language proficiency tests (Park et al., 2022). Therefore, quick valid vocabulary tests, such as LexTALE (Lemhöfer & Broersma, 2012) and its extensions (e.g., LexITA: Amenta et al., 2020; LEXTALE-FR: Brysbaert, 2013; LexPT: Zhou & Li, 2022) have been developed to reliably assess language proficiency of speakers of various languages. The present study introduces a Lexical Test for Malay Speakers (LexMAL), which estimates language proficiency for Malay first language (L1) and second language (L2) speakers. An initial 180-item LexMAL prototype was evaluated using 60 Malay L1 and 60 L2 speakers in Experiment 1. Sixty words and 30 nonwords with the highest discriminative power that span across the full difficulty range were selected for the final LexMAL based on point-biserial correlations and an item response theory analysis. The validity of LexMAL was demonstrated through a reliable discrimination between L1 and L2 speakers, significant correlations between LexMAL scores and performance on other Malay language tasks (i.e., translation accuracy and cloze test scores), and LexMAL outperforming self-rated proficiency. A validation study (Experiment 2) with the 90-item final LexMAL tested with a different group of Malay L1 (N = 61) and L2 speakers (N = 61) replicated the findings of Experiment 1. LexMAL is freely available for researchers at www.lexmal.org ., (© 2023. The Author(s).)

Purpose: Tumor hypoxia is an adverse prognostic factor in head and neck squamous cell carcinoma (HNSCC). We assessed whether patients with hypoxic HNSCC benefited from the addition of nimorazole to definitive intensity modulated radiation therapy (IMRT)., Methods and Materials: NIMRAD was a phase 3, multicenter, placebo-controlled, double-anonymized trial of patients with HNSCC unsuitable for concurrent platinum chemotherapy or cetuximab with definitive IMRT (NCT01950689). Patients were randomized 1:1 to receive IMRT (65 Gy in 30 fractions over 6 weeks) plus nimorazole (1.2 g/m 2 daily, before IMRT) or placebo. The primary endpoint was freedom from locoregional progression (FFLRP) in patients with hypoxic tumors, defined as greater than or equal to the median tumor hypoxia score of the first 50 patients analyzed (≥0.079), using a validated 26-gene signature. The planned sample size was 340 patients, allowing for signature generation in 85% and an assumed hazard ratio (HR) of 0.50 for nimorazole effectiveness in the hypoxic group and requiring 66 locoregional failures to have 80% power in a 2-tail log-rank test at the 5% significance level., Results: Three hundred thirty-eight patients were randomized by 19 centers in the United Kingdom from May 2014 to May 2019, with a median follow-up of 3.1 years (95% CI, 2.9-3.4). Hypoxia scores were available for 286 (85%). The median patient age was 73 years (range, 44-88; IQR, 70-76). There were 36 (25.9%) locoregional failures in the hypoxic group, in which nimorazole + IMRT did not improve FFLRP (adjusted HR, 0.72; 95% CI, 0.36-1.44; P = .35) or overall survival (adjusted HR, 0.96; 95% CI, 0.53-1.72; P = .88) compared with placebo + IMRT. Similarly, nimorazole + IMRT did not improve FFLRP or overall survival in the whole population. In total (N = 338), 73% of patients allocated nimorazole adhered to the drug for ≥50% of IMRT fractions. Nimorazole + IMRT caused more acute nausea compared with placebo + IMRT (Common Terminology Criteria for Adverse Events version 4.0 G1+2: 56.6% vs 42.4%, G3: 10.1% vs 5.3%, respectively; P < .05)., Conclusions: Addition of the hypoxia modifier nimorazole to IMRT for locally advanced HNSCC in older and less fit patients did not improve locoregional control or survival., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The concentration of drugs in a driver's system can change between an impaired driving arrest or crash and the collection of a biological specimen for drug testing. Accordingly, delays in specimen collection can result in the loss of critical information that has the potential to affect impaired driving prosecution. The objectives of the study were: (1) to identify factors that influence the time between impaired-driving violations and specimen collections (time-to-collection) among crash-involved drivers, and (2) to consider how such delays affect measured concentrations of drugs, particularly with respect to common drug per se limits., Method: Study data included blood toxicology results and crash-related information from 8,923 drivers who were involved in crashes and arrested for impaired driving in Wisconsin between 2019 and 2021. Analyses examined how crash timing and severity influenced time-to-collection and the effects of delays in specimen collection on blood alcohol concentrations (BACs) and blood delta-9-tetrahydrocannabinol (THC) concentrations., Results: The mean time-to-collection for the entire sample was 1.80 h. Crash severity had a significant effect on time-to-collection with crashes involving a fatality having the longest duration ( M = 2.35 h) followed by injury crashes ( M = 2.06 h) and noninjury crashes ( M = 1.69 h). Time of day also affected time-to-collection; late night and early morning hours were associated with shorter durations. Both BAC ( r  = -0.11) and blood THC concentrations ( r  = -0.16) were significantly negatively correlated with time-to-collection., Conclusions: Crash severity and the time of day at which a crash occurs can result in delays in the collection of blood specimens after impaired driving arrests. Because drugs often continue to be metabolized and eliminated between arrest and biological specimen collection, measured concentrations may not represent the concentrations of drugs that were present at the time of driving. This has the potential to affect drug-impaired driving prosecution, particularly in jurisdictions whose laws specify per se impairment thresholds.

Without preventative intervention, youth with a history of foster care (FC) involvement have a high likelihood of developing depression and anxiety (DA) symptoms. The current study used integrative data analysis to harmonize data across four foster and kinship parent-mediated interventions (and seven randomized control trials) designed to reduce youth externalizing and other problem behaviors to determine if, and for how long, these interventions may have crossover effects on youth DA symptoms. Moderation of intervention effects by youth biological sex, developmental period, number of prior placements, and race/ethnicity was also examined. Youth (N = 1891; 59% female; ages 4 to 18 years) behaviors were assessed via the Child Behavior Checklist, Parent Daily Report, and Eyberg Child Behavior Inventory at baseline, the end of the interventions (4-6 months post baseline), and two follow-up assessments (9-12 months and 18-24 months post baseline), yielding 4830 total youth-by-time assessments. The interventions were effective at reducing DA symptoms at the end of the interventions; however, effects were only sustained for one program at the follow-up assessments. No moderation effects were found. The current study indicates that parent-mediated interventions implemented during childhood or adolescence aimed at reducing externalizing and other problem behaviors had crossover effects on youth DA symptoms at the end of the interventions. Such intervention effects were sustained 12 and 24 months later only for the most at-risk youth involved in the most intensive intervention., (© 2023. Society for Prevention Research.)

Translation equivalents are widely used in bilingual research concerning word processing (e.g., Eddington & Tokowicz, 2013; Jouravlev & Jared, 2020) and second-language vocabulary learning (e.g., Bracken et al., 2017; Degani et al., 2014). Although translation norms exist in several languages, to date there are no Malay-English translation norms. This study presents the first Malay-English translation norms collected with highly proficient Malay-English bilinguals. Furthermore, the study investigates the impact of lexical characteristics on translation ambiguity. The forward translation (FT) task (N = 30) collected English translations for 1004 Malay words selected from the Malay Lexicon Project (Yap et al., 2010), and subsequently the backward translation (BT) task (N = 30) gathered Malay translations for 845 English words obtained from the FT phase. The data revealed a high prevalence of translation ambiguity in both translation directions. Specifically, verbs, adjectives, and class-ambiguous words were more translation-ambiguous than nouns. Furthermore, within-language semantic variability and word length were positively correlated with translation ambiguity, whereas word frequency only correlated with translation ambiguity in FT. Word length and word frequency of the source words and their translations were positively correlated. Intriguingly, only in FT were bilinguals with higher Malay proficiency more likely to provide accurate and dominant translations for the Malay words. These findings contrast with those reported in translation norming studies involving other language pairs. The translation norms provide a useful resource for bilingual language studies involving Malay-English bilinguals., (© 2022. The Psychonomic Society, Inc.)

Background: The efffect of administering of probiotics or twice-daily omeprazole on glucocorticoid-induced gastric bleeding in dogs is unknown., Hypothesis: Compare gastrointestinal bleeding among dogs administered placebo, prednisone (2 mg/kg q24h), prednisone with omeprazole (1 mg/kg q12h), or prednisone with probiotics (Visbiome, 11.2-22.5 billion CFU/kg q24h) for 28 days., Animals: Twenty-four healthy research dogs., Methods: Double-blinded, placebo-controlled randomized trial. Clinical signs and endoscopic gastrointestinal mucosal lesion scores at baseline (t 1 ), day 14 (t 2 ), and day 28 (t 3 ) were compared using split-plot repeated-measures mixed-model ANOVAs., Results: Fecal score differed by treatment-by-time (F[6,40] = 2.65, P < .03), with higher scores in groups receiving prednisone at t 3 than t 1 . Nineteen of thirty-three episodes of diarrhea occurred in the prednisone with omeprazole group. Gastric mucosal lesion scores differed by treatment-by-time (F[6,60] = 2.86, P = .05), among treatment groups (F[3,60] = 4.9, P = .004), and over time (F[2,60] = 16.5, P < .001). Post hoc analysis revealed lesion scores increased over time for all groups receiving prednisone. At t 3 , scores for the prednisone (8.7 ± 4.9) and prednisone with probiotics (8.7 ± 4.9) groups differed significantly from placebo (1.8 ± 1.8; P ≤ .04), whereas scores for the prednisone with omeprazole (6.5 ± 5.5) group did not differ from placebo (P = .7). Ulcers occurred only in dogs receiving prednisone., Conclusions and Clinical Importance: Prednisone-induced gastric bleeding. Co-administration of omeprazole partially mitigated bleeding, but a similar protective benefit was not demonstrated by co-administration of the evaluated probiotic., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Owing to advances in radiotherapy, the physical properties of radiation can be optimized to enable individualized treatment; however, optimization is rarely based on biological properties and, therefore, treatments are generally planned with the assumption that all tumours respond similarly to radiation. Radiation affects multiple cellular pathways, including DNA damage, hypoxia, proliferation, stem cell phenotype and immune response. In this Review, we summarize the effect of these pathways on tumour responses to radiotherapy and the current state of research on genomic classifiers designed to exploit these variations to inform treatment decisions. We also discuss whether advances in genomics have generated evidence that could be practice changing and whether advances in genomics are now ready to be used to guide the delivery of radiotherapy alone or in combination., (© 2022. Springer Nature Limited.)

Background: Ensuring menstrual cup safety is paramount, yet a menstrual cup safety assessment scheme is lacking. This paper presents a quadripartite scheme, showing how it can be applied., Methods: The Tampax Menstrual Cup was evaluated in the safety assessment scheme: (1) Biocompatibility and chemical safety of cup constituents. Extractables were obtained under different use condition; exposure-based risk assessments (EBRA) were conducted for extractables exceeding thresholds of toxicological concern. (2) Physical impact to vaginal mucosa. After physical evaluations, the Tampax Cup and another cup were assessed in a randomised double-blinded, two-product, two-period cross-over clinical trial (65 women, mean age 34.2 years). (3) Impact to vaginal microbiota (in vitro mixed microflora assay and evaluation of vaginal swabs). (4) In vitro growth of Staphylococcus aureus and toxic shock syndrome toxin-1 (TSST-1) production., Findings: Biocompatibility assessments and EBRA of cup constituents showed no safety concerns. In the randomised clinical trial, all potentially product-related adverse effects were mild, vaginal exams were unremarkable, no clinically relevant pH changes occurred, post-void residual urine volume with and without cup were similar, and self-reported measures of comfort along with reports of burning, itching and stinging between cups were comparable. Cup use had no effect on microbial growth in vitro or in the 62 subjects who completed the trial or on in vitro TSST-1 production., Interpretation: The quadripartite safety assessment scheme allows evaluation of menstrual cup safety. The Tampax Cup is safe and well-tolerated upon intended use. As with all feminine hygiene products, post-market safety surveillance confirmed this conclusion., Funding: By Procter & Gamble., Competing Interests: Declaration of interests VPS, MAF, AGT, JLSS, PH, KLK, JMP, TRB, JMAN and KEW are employed by The Procter & Gamble Company (P&G), a consumer products corporation that produces and markets menstrual cups. These authors received no funding in cash or kind for their contribution to this manuscript (beyond the salaries paid) but do hold P&G company stock. UGS was hired by P&G to draft the current manuscript and received payment for working hours. The authors alone are responsible for the writing of and contents of this manuscript., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

•There is a lack of prospective level I evidence for the use of PBT for most adult cancers including oropharyngeal squamous cell carcinoma (OPSCC).•TORPEdO is the UK's first PBT clinical trial and aims to determine the benefits of PBT for OPSCC.•Training and support has been provided before and during the trial to reduce variations of contouring and radiotherapy planning.•There is a strong translational component within TORPEdO. Imaging and physics data along with blood, tissue collection will inform future studies in refining patient selection for IMPT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: To characterize gastrointestinal transit times (GITTs) and pH in dogs, and to compare to data recently described for cats., Animals: 7 healthy, colony-housed Beagles., Procedures: The GITTs and pH were measured using a continuous pH monitoring system. For the first period (prefeeding), food was withheld for 20 hours followed by pH capsule administration. Five hours after capsule administration, dogs were offered 75% of their historical daily caloric intake for 1 hour. For the second period (postfeeding), food was withheld for 24 hours. Dogs were allowed 1 hour to eat, followed by capsule administration. Both periods were repeated 3 times. The GITTs and pH were compared to published feline data., Results: The mean ± SD transit times in dogs for the pre- and postfeeding periods, respectively, were esophageal, 3 ± 5 minutes and 13 ± 37 minutes; gastric, 31 ± 60 minutes and 829 ± 249 minutes; and intestinal, 795 ± 444 minutes and 830 ± 368 minutes. The mean ± SD gastrointestinal pH in dogs for the pre- and postfeeding periods, respectively, were esophageal, 6.6 ± 0.6 and 5.7 ± 1.0; gastric, 3.0 ± 1.4 and 1.8 ± 0.3; intestinal, 7.9 ± 0.3 and 7.7 ± 0.6; first-hour small intestinal, 7.6 ± 0.5 and 7.1 ± 0.4; and last-hour large intestinal, 7.9 ± 0.6 and 7.7 ± 1.0. The first-hour small intestinal pH and total transit times varied between dogs and cats depending on feed period (P = .002 and P = .04, respectively). Post hoc analysis revealed significantly shorter total transit times in dogs prefeeding (P = .005; mean ± SD for cats, 2,441 ± 1,359 minutes; for dogs, 828 ± 439 minutes) and postfeeding (P = .03; mean ± SD for cats, 3,009 ± 1,220 minutes; for dogs, 1,671 ± 513 minutes). Total transit time for dogs was also shorter pre- versus postfeeding (P = .003)., Clinical Relevance: GITT is faster in Beagles compared to cats, but gastrointestinal pH are similar when fed the same diet.

Purpose: There is a need to refine the selection of patients with oropharyngeal squamous cell carcinoma (OPSCC) for treatment de-escalation. We investigated whether pretreatment absolute lymphocyte count (ALC) predicted overall survival (OS) benefit from the addition of concurrent chemotherapy to radical radiotherapy., Patients and Methods: This was an observational study of consecutive OPSCCs treated by curative-intent radiotherapy, with or without concurrent chemotherapy (n = 791) with external, independent validation from a separate institution (n = 609). The primary end point was OS at 5 years. Locoregional control (LRC) was assessed using competing risk regression as a secondary end point. Previously determined prognostic factors were used in a multivariable Cox proportional hazards model to assess the prognostic importance of ALC and the interaction between ALC and cisplatin chemotherapy use., Results: Pretreatment ALC was prognostic for 5-year OS on multivariable analysis (hazard ratio [HR] 0.64; 95% CI, 0.42 to 0.98; P = .04). It also predicted benefit from the use of concurrent cisplatin chemotherapy, with a significant interaction between cisplatin chemotherapy and pretreatment ALC (likelihood ratio test, P = .04): higher ALC count reduced the 5-year OS benefit compared with radiotherapy alone (HR 2.53; 95% CI, 1.03 to 6.19; P = .043). This was likely driven by an effect on LRC up to 5 years (interaction subdistribution HR 2.29; 95% CI, 0.68 to 7.71; P = .094). An independent validation cohort replicated the OS (HR 2.53; 95% CI, 0.98 to 6.52; P = .055) and LRC findings (interaction subdistribution HR 3.43; 95% CI, 1.23 to 9.52; P = .018)., Conclusion: For OPSCC, the pretreatment ALC is prognostic for OS and also predicts benefit from the addition of cisplatin chemotherapy to radiotherapy. These findings require prospective evaluation, and could inform the selection of good prognosis patients for a de-escalation trial., Competing Interests: Kate GarcezHonoraria: EisaiConsulting or Advisory Role: IpsenTravel, Accommodations, Expenses: Eisai Tim IllidgeConsulting or Advisory Role: Takeda, Nordic NanovectorSpeakers' Bureau: Takeda, Bristol Myers Squibb, RocheResearch Funding: AstraZeneca/MedImmune, MSD OncologyTravel, Accommodations, Expenses: Roche Lip LeeResearch Funding: Debiopharm Group (Inst) Andrew SykesHonoraria: Sanofi David J. ThomsonConsulting or Advisory Role: Merck & CoNo other potential conflicts of interest were reported.

Background and Purpose: There is renewed interest in hypofractionated radiotherapy, but limited data and a lack of consensus to support use for head and neck cancer. In this multicentre analysis we compared outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with conventional and accelerated, mildly hypofractionated radiotherapy without chemotherapy., Materials and Methods: A multi-centre, observational study of consecutive OPSCCs treated between 2015 and 2018. Patients underwent curative-intent radiotherapy (oropharyngeal and bilateral neck) using conventionally fractionated (70 Gy in 35 fractions over 7 weeks, n = 97) or accelerated, mildly hypofractionated (65-66 Gy in 30 fractions over 6 weeks, n = 136) radiotherapy without chemotherapy. Locoregional control (LRC) and overall survival (OS) were compared. Patients alive and cancer-free at a minimum of 2 years post-radiotherapy (n = 151, 65%) were sent an MD Anderson Dysphagia Inventory (MDADI) questionnaire to assess swallow function., Results: LRC and OS were similar across schedules (p = 0.78 and 0.95 respectively, log-rank test). Enteral feeding rates during radiotherapy appeared higher in the 7-week group though this did not reach statistical significance (59% vs 48%, p = 0.08). Feeding rates were similar at 1 year post radiotherapy for both groups (10% vs 6%, p = 0.27). 107 patients returned MDADI questionnaires (71%); there were no differences between the 6- and 7-week groups for median global (60.0 vs 60.0, p = 0.99) and composite (65.8 vs 64.2, p = 0.44) MDADI scores., Conclusion: Patients with OPSCC treated with radiotherapy alone have similar swallowing outcomes, LRC and OS following accelerated, mild hypofractionation and standard fractionation schedules, supporting its use as a standard-of-care option for patients unsuitable for concurrent chemotherapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Analysis of steroid and thyroid hormones is often performed in blood serum. Occasionally though, plasma samples are submitted in lieu of serum for exotic species such as tigers. However, blood tube anticoagulants may affect hormone values. We compared serum and heparin plasma results for 7 hormones in tigers. Serum and plasma samples were collected from 25 tigers and analyzed for progesterone, 17-hydroxyprogesterone, cortisol, androstenedione, testosterone, estradiol, and thyroxine. Using Lin concordance correlation, serum and heparin plasma measures agreed for all hormones except cortisol. However, Passing-Bablok regression only found agreement between serum and heparin plasma measures for androstenedione, testosterone, and estradiol. Median values between the 2 sample types were significantly ( p < 0.05) different for progesterone, 17-hydroxyprogesterone, cortisol, and thyroxine. Our results suggest that, for the aforementioned hormones, serum and heparin plasma values may not always be comparable.

Objectives: High-energy Proton Beam Therapy (PBT) commenced in England in 2018 and NHS England commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level of provision., Methods: Invitations were sent to 41 colleagues working in PBT, most at one UK centre, to contribute by completing a spreadsheet. 39 responded: 23 (59%) completed the spreadsheet; 16 (41%) declined, arguing that clinical outcome data are lacking, but joined six additional site-specialist oncologists for two consensus meetings. The spreadsheet was pre-populated with incidence data from Cancer Research UK and radiotherapy use data from the National Cancer Registration and Analysis Service. 'Mechanisms of Benefit' of reduced growth impairment, reduced toxicity, dose escalation and reduced second cancer risk were examined., Results: The most reliable figure for percentage of radical radiotherapy patients likely to benefit from PBT was that agreed by 95% of the 23 respondents at 4.3%, slightly larger than current provision. The median was 15% (range 4-92%) and consensus median 13%. The biggest estimated potential benefit was from reducing toxicity, median benefit to 15% (range 4-92%), followed by dose escalation median 3% (range 0 to 47%); consensus values were 12 and 3%. Reduced growth impairment and reduced second cancer risk were calculated to benefit 0.5% and 0.1%., Conclusions: The most secure estimate of percentage benefit was 4.3% but insufficient clinical outcome data exist for confident estimates. The study supports the NHS approach of using the evidence base and developing it through randomised trials, non-randomised studies and outcomes tracking., Advances in Knowledge: Less is known about the percentage of patients who may benefit from PBT than is generally acknowledged. Expert opinion varies widely. Insufficient clinical outcome data exist to provide robust estimates. Considerable further work is needed to address this, including international collaboration; much is already underway but will take time to provide mature data.

Background: Cats with moderate to advanced chronic kidney disease (CKD) often display clinical signs such as vomiting and decreased appetite, and frequently receive omeprazole or other acid suppressants despite a lack of evidence to support their use., Hypothesis/objectives: To evaluate the effect of once-daily PO omeprazole on appetite in cats with CKD. We hypothesized that omeprazole would improve subjective appetite assessments in cats with CKD., Animals: Fourteen client-owned cats with International Renal Interest Society (IRIS) stage 2 or 3 CKD and hyporexia., Methods: Cats were prospectively enrolled in a multi-institutional, double-blinded, randomized, crossover study to evaluate the effect of a 14-day trial of once-daily PO omeprazole (1 mg/kg) or placebo (lactose gel capsule) on vomiting frequency and appetite. A daily log was completed by the owner during all treatment and rest periods to assess appetite using a subjective, qualitative, and 5-point scoring system. Mixed model analyses of variance were performed to determine if average daily percentage food consumed or appetite score, as measured by subjective owner assessment, differed between treatments., Results: Compared to placebo, a negligible but statistically significant difference in percentage of food consumed was observed between treatments (P = .04) with once-daily omeprazole treatment resulting in a 2.7% increase in food consumption compared to placebo. No significant difference, however, was found in appetite score, body weight, or serum creatinine concentration between treatments., Conclusions and Clinical Importance: Once-daily omeprazole does not markedly increase appetite in cats with CKD and should not be used as a first-line treatment in the absence of evidence of gastrointestinal ulceration., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Antibiotic-associated gastrointestinal signs occurred in 100% of dogs administered enrofloxacin with metronidazole in a previous study, and signs partially were mitigated by synbiotics. The objective of this randomized, double-blinded, placebo-controlled trial was to compare the fecal microbiome and metabolome of dogs administered enrofloxacin and metronidazole, followed by either a placebo or a bacterial/yeast synbiotic combination. Methods: Twenty-two healthy research dogs were randomized to two treatment groups. There were three study periods: baseline, treatment, and washout. Dogs were administered enrofloxacin (10 mg/kg qd) and metronidazole (12.5 mg/kg BID), followed 1 h later by placebo or a commercially-available synbiotic combination (BID), per os for 21 days with reevaluation 56 days thereafter. Fecal samples were collected on days 5-7 (baseline), 26-28, and 82-84. The fecal microbiome was analyzed by qPCR and sequencing of 16S rRNA genes; time-of-flight mass spectrometry was used to determine metabolomic profiles. Split plot repeated measures mixed model ANOVA was used to compare results between treatment groups. P < 0.05 was considered significant, with Benjamini and Hochberg's False Discovery Rate used to adjust for multiple comparisons. Results: Alpha diversity metrics differed significantly over time in both treatment groups, with incomplete recovery by days 82-84. Beta diversity and the dysbiosis index differed significantly over time and between treatment groups, with incomplete recovery at days 82-84 for dogs in the placebo group. Significant group-by-time interactions were noted for 15 genera, including Adlercreutzia, Bifidobacterium, Slackia, Turicibacter, Clostridium (including C. hiranonis ) [ Ruminococcus ], Erysipelotrichaceae&#95;g&#95; , [ Eubacterium ], and Succinivibrionaceae&#95;g&#95; . Concurrent group and time effects were present for six genera, including Collinsella, Ruminococcaceae&#95;g &#95;, and Prevotella . Metabolite profiles differed significantly by group-by-time, group, and time for 28, 20, and 192 metabolites, respectively. These included short-chain fatty acid, bile acid, tryptophan, sphingolipid, benzoic acid, and cinnaminic acid metabolites, as well as fucose and ethanolamine. Changes in many taxa and metabolites persisted through days 82-84. Conclusion: Antibiotic administration causes sustained dysbiosis and dysmetabolism in dogs. Significant group-by-time interactions were noted for a number of taxa and metabolites, potentially contributing to decreased antibiotic-induced gastrointestinal effects in dogs administered synbiotics., Competing Interests: JW and JS have received past honoraria from Nutramax Laboratories Veterinary Sciences, Inc. for development of educational materials and public speaking. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whittemore, Price, Moyers and Suchodolski.)

The incorporation of retention-time information into a fully rotatable and interactive three-dimensional (3D), "Kendrick-like" normalized mass map (NMM) using a single software platform is reported. Surprising discoveries were made about the elution pattern of block ethoxylate-propoxylate oligomers (ca. 2800 Da) in the supercritical fluid after combined SFC-Orbitrap FTMS analysis. The 3D NMM also facilitated identification of impurities using interactive graphics tools within the map. By selecting map glyphs, associated reconstructed ion chromatograms were automatically generated. Last, since Kendrick and Kendrick-like mapping (NMM) are chemical-formula-based, incorporating retention time in 3D space allows the possibility of resolving isomers in the map.

Purpose: For oropharynx squamous cell carcinoma (OPSCC) this study aimed to: (i) compare 5-year overall survival (OS) stratification by AJCC/UICC TNM versions 7 (TNMv7) and 8 (TNMv8), (ii) determine whether changes to T and N stage groupings improve prognostication and (iii) develop and validate a model incorporating additional clinical characteristics to improve 5-year OS prediction., Material and Methods: All OPSCC treated with curative-intent at our institution between 2011 and 2017 were included. The primary endpoint was 5-year OS. Survival curves were produced for TNMv7 and TNMv8. A three-way interaction between T, N stage and p16 status was evaluated for improved prognostication. Cox proportional hazards modelling was used to derive a new predictive model., Results: Of 750 OPSCC cases, 574 (77%) were p16-positive. TNMv8 was more prognostic than TNMv7 (concordance probability estimate [CPE] ± SE = 0.72 ± 0.02 vs 0.53 ± 0.02). For p16-positive disease, TNMv8 discriminated stages II vs I (HR 2.32, 95% CI 1.47-3.67) and III vs II (HR 1.75, 95% CI 1.13-2.72). For p16-negative disease, TNMv7 and TNMv8 demonstrated poor hazard discrimination. Different T, N stage and p16-status combinations did not improve prognostication after adjusting for other factors (CPE = 0.79 vs 0.79, p = 0.998). A model for p16-positive and p16-negative OPSCC including additional clinical characteristics improved 5-year OS prediction beyond TNMv8 (c-index 0.76 ± 0.02)., Conclusions: TNMv8 is superior to TNMv7 for p16-positive OPSCC, but both performed poorly for p16-negative disease. A novel model incorporating additional clinical characteristics improved 5-year OS prediction for both p16-positive and p16-negative disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Rebound tonometry (RBT) can be used to measure intraocular pressure (IOP) in children unable to tolerate measurement with applanation tonometry (AT) while awake. RBT readings are often 2-3 mm Hg higher than AT. We have experienced children with a repeatedly higher difference between RBT and AT measurements (≥6 mm Hg). The purpose of this study was to identify demographic and ocular characteristics that contribute to this artifactuous discrepancy., Methods: The medical records of pediatric patients with IOP measured by RBT followed by AT within 6 months without intervening surgery or change in medical management were retrospectively reviewed to identify potential predictors of greater difference between RBT and AT readings., Results: A total of 123 eyes of 65 patients were included. In patients with normal IOP (≤24 mm Hg), 18.5% had a ≥6 mm Hg difference between RBT and AT, with RBT being higher. Risk factors for this included presence of persistent fetal vasculature (PFV), increased corneal diameter, and higher initial RBT value (>20). In patients with elevated IOP (>24 mm Hg), 77% had ≥6 mm Hg difference, with larger corneal diameter being the sole predictor. Eyes were less likely to have significant RBT-AT difference if there was corneal opacity or iris abnormalities in eyes with elevated IOP (>24 mm Hg)., Conclusions: In some children, RBT readings are ≥ 6 mm Hg higher than AT readings. Caution should be taken when interpreting RBT values in patients with PFV, increased corneal diameter, and higher initial RBT values., (Copyright © 2021 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time, this leads to morphological and visual appearance changes associated with premature ageing. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm) and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids using in vitro and ex vivo skin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67 and filaggrin. A retinoic acid receptor-alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results from ex vivo skin found that RP and ROL have higher penetration levels compared with RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14-hydroxy-4,14-retro-retinol (14-HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Radiology can be a challenging subject for students and finding new techniques that help improve their understanding could have positive effects in their clinical practice. The purpose of this prospective experimental study was to implement the use of color-coded, three-dimensional-printed, handheld equine carpus models into a radiographic anatomy course and evaluate the impact objectively and subjectively using quizzes and student response surveys. A first-year veterinary class was randomly divided into two similarly sized groups (groups A and B) for an equine normal radiographic anatomy laboratory. Both groups experienced the same laboratory structure; however, each student in group B received a handheld three-dimensional-printed equine carpus. Both groups received a quiz at the end of their laboratory consisting of 10 multiple-choice questions related to the equine carpus. An anonymous survey regarding the laboratory was emailed to students after the laboratory. One week later, the same 10 questions in randomized order were administered via a pop-quiz. Students believed both quizzes would count toward their final course grade. There was no statistically significant difference in grades between groups on either quiz (P > .05). However, based on survey responses, group B students felt the carpus made the laboratory more enjoyable and improved their comprehension of the material, whereas group A students felt the carpus would have increased their enjoyment and improved their comprehension. The implementation of three-dimensional-printed anatomic models may be useful to enhance enjoyment and perceived comprehension of veterinary students; however, there is currently insufficient evidence to suggest these models improve academic performance., (© 2020 American College of Veterinary Radiology.)

Identifying similarities and differences in the brain metabolome during different states of consciousness has broad relevance for neuroscience and state-dependent autonomic function. This study focused on the prefrontal cortex (PFC) as a brain region known to modulate states of consciousness. Anesthesia was used as a tool to eliminate wakefulness. Untargeted metabolomic analyses were performed on microdialysis samples obtained from mouse PFC during wakefulness and during isoflurane anesthesia. Analyses detected 2,153 molecules, 91 of which could be identified. Analytes were grouped as detected during both wakefulness and anesthesia ( n = 61) and as unique to wakefulness ( n = 23) or anesthesia ( n = 7). Data were analyzed using univariate and multivariate approaches. Relative to wakefulness, during anesthesia there was a significant ( q < 0.0001) fourfold change in 21 metabolites. During anesthesia 11 of these 21 molecules decreased and 10 increased. The Kyoto Encyclopedia of Genes and Genomes database was used to relate behavioral state-specific changes in the metabolome to metabolic pathways. Relative to wakefulness, most of the amino acids and analogs measured were significantly decreased during isoflurane anesthesia. Nucleosides and analogs were significantly increased during anesthesia. Molecules associated with carbohydrate metabolism, maintenance of lipid membranes, and normal cell functions were significantly decreased during anesthesia. Significant state-specific changes were also discovered among molecules comprising lipids and fatty acids, monosaccharides, and organic acids. Considered together, these molecules regulate point-to-point transmission, volume conduction, and cellular metabolism. The results identify a novel ensemble of candidate molecules in PFC as putative modulators of wakefulness and the loss of wakefulness. NEW & NOTEWORTHY The loss of wakefulness caused by a single concentration of isoflurane significantly altered levels of interrelated metabolites in the prefrontal cortex. The results support the interpretation that states of consciousness reflect dynamic interactions among cortical neuronal networks involving a humbling number of molecules that comprise the brain metabolome.

This study quantified eight small-molecule neurotransmitters collected simultaneously from prefrontal cortex of C57BL/6J mice ( n = 23) during wakefulness and during isoflurane anesthesia (1.3%). Using isoflurane anesthesia as an independent variable enabled evaluation of the hypothesis that isoflurane anesthesia differentially alters concentrations of multiple neurotransmitters and their interactions. Machine learning was applied to reveal higher order interactions among neurotransmitters. Using a between-subjects design, microdialysis was performed during wakefulness and during anesthesia. Concentrations (nM) of acetylcholine, adenosine, dopamine, GABA, glutamate, histamine, norepinephrine, and serotonin in the dialysis samples are reported (means ± SD). Relative to wakefulness, acetylcholine concentration was lower during isoflurane anesthesia (1.254 ± 1.118 vs. 0.401 ± 0.134, P = 0.009), and concentrations of adenosine (29.456 ± 29.756 vs. 101.321 ± 38.603, P < 0.001), dopamine (0.0578 ± 0.0384 vs. 0.113 ± 0.084, P = 0.036), and norepinephrine (0.126 ± 0.080 vs. 0.219 ± 0.066, P = 0.010) were higher during anesthesia. Isoflurane reconfigured neurotransmitter interactions in prefrontal cortex, and the state of isoflurane anesthesia was reliably predicted by prefrontal cortex concentrations of adenosine, norepinephrine, and acetylcholine. A novel finding to emerge from machine learning analyses is that neurotransmitter concentration profiles in mouse prefrontal cortex undergo functional reconfiguration during isoflurane anesthesia. Adenosine, norepinephrine, and acetylcholine showed high feature importance, supporting the interpretation that interactions among these three transmitters may play a key role in modulating levels of cortical and behavioral arousal. NEW & NOTEWORTHY This study discovered that interactions between neurotransmitters in mouse prefrontal cortex were altered during isoflurane anesthesia relative to wakefulness. Machine learning further demonstrated that, relative to wakefulness, higher order interactions among neurotransmitters were disrupted during isoflurane administration. These findings extend to the neurochemical domain the concept that anesthetic-induced loss of wakefulness results from a disruption of neural network connectivity.

Background: Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects., Hypothesis/objectives: Determine the effects of clopidogrel and prednisone on platelet function., Animals: Twenty-four healthy dogs., Methods: Double-blinded, placebo-controlled randomized trial. Platelet function was evaluated using a platelet function analyzer and impedance aggregometry (days 0, 14, and 28) for dogs treated with placebo, clopidogrel (2-3 mg/kg/d), prednisone (2 mg/kg/d), or prednisone with clopidogrel PO for 28 days. Results were categorized as nonresponder versus responder (platelet function analyzer), and inadequate, ideal, or excessive response (aggregometry). Results were compared using mixed model, split-plot repeated measures analysis of variance and generalized estimating equation proportional odds models. P < .05 was considered significant., Results: Closure times differed by treatment (F [3, 20] = 10.5; P < .001), time (F [2, 40] = 14.3; P < .001), and treatment-by-time (F [6, 40] = 3.4; P = .01). Area under the curve (AUC) differed by treatment (F [3, 20] = 19.6; P < .001), time (F [2, 40] = 35.4; P < .001), and treatment-by-time (F [6, 40] = 13.5; P < .001). Based on closure times, 5/6 dogs each in the clopidogrel and prednisone/clopidogrel groups were responders. All dogs in the prednisone/clopidogrel group were overcontrolled based on AUC (days 14 and 28), whereas 5/6 (day 14) and 2/6 (day 28) dogs treated with clopidogrel were overcontrolled. Compared to clopidogrel, dogs receiving prednisone/clopidogrel were 11 times (P = .03) more likely to have an excessive response., Conclusions and Clinical Importance: Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Professional quality of life is the quality a person feels in relation to work. For critical care nurses, it is composed of compassion satisfaction and compassion fatigue. Professional quality of life is affected by work environment. The American Association of Critical-Care Nurses (AACN) has identified 6 standards for a healthy work environment., Objective: To explore which of the AACN healthy work environment standards have the strongest impact on professional quality of life in critical care nurses., Methods: In an exploratory, cross-sectional survey of nurses working in 4 adult critical care units of a single health care facility, professional quality of life was assessed using the Professional Quality of Life Scale (ProQOL), and work environment was evaluated using the AACN Healthy Work Environment Assessment Tool., Results: Participants reported compassion satisfaction and burnout levels as average and secondary traumatic stress levels as high. The composite average for all 6 AACN healthy work environment standards was good. A multiple regression analysis revealed true collaboration, effective decision-making, and authentic leadership as significant predictors of compassion satisfaction. Authentic leadership was the only predictor of burnout. Appropriate staffing, meaningful recognition, and authentic leadership were predictors of secondary traumatic stress., Conclusion: Authentic leadership is the strongest predictor of compassion satisfaction, burnout, and secondary traumatic stress. Therefore, improving leadership should be a priority in intensive care units seeking to improve nurses' professional quality of life., (©2020 American Association of Critical-Care Nurses.)

Glucocorticoid administration is a risk factor for thromboembolism in hypercoagulable dogs, and it is unknown if aspirin counteracts glucocorticoid-induced hypercoagulability. The objective was to determine the effects of sustained aspirin and prednisone administration on platelet function and thromboxane synthesis. Our hypothesis was that aspirin would consistently inhibit platelet function and thromboxane synthesis when administered with or without prednisone. In 24 healthy dogs, platelet aggregometry and urine 11-dehydro-thromboxane-B 2 (11-dTXB 2 )-to-creatinine ratios were measured on days 0, 14, and 28. Dogs were administered placebos, aspirin (2 mg/kg/d), prednisone (2 mg/kg/d), or prednisone/aspirin combination therapy PO for 28 days in a randomized double-blinded study. Aspirin response was based on a >25% reduction in platelet aggregation compared to pre-treatment values. Results were compared using mixed model, split-plot repeated measures ANOVAs. P < 0.05 was considered significant. AUC differed significantly by time [ F (2,40) = 10.2, P < 0.001] but not treatment or treatment-by-time. On day 14, 2 dogs were aspirin responders (aspirin, 1; placebo, 1). On day 28, 3 dogs were aspirin responders (aspirin, 2; prednisone/aspirin, 1). Urine 11-dTXB 2 -to-creatinine ratios differed significantly by group [ F (3,20) = 3.9, P = 0.024] and time [ F (2,40) = 8.7, P < 0.001), but not treatment-by-time. Post-hoc analysis revealed significant differences between aspirin and placebo groups ( P =0.008), aspirin and prednisone/aspirin groups ( P = 0.030), and placebo and prednisone groups ( P = 0.030). In healthy dogs, sustained aspirin, prednisone, and combination therapy do not inhibit platelet aggregation, and when used as individual therapies, aspirin and prednisone decreased thromboxane synthesis. Additional studies using varied platelet function methodologies in hypercoagulable dogs are necessary., (Copyright © 2019 Thomason, Mooney, Price and Whittemore.)

Background: Dogs with immune-mediated disease often receive glucocorticoids with clopidogrel, but ulcerogenic effects of current protocols are unknown., Hypothesis/objectives: To compare gastrointestinal endoscopic findings among dogs administered clopidogrel, prednisone, and combination treatment., Animals: Twenty-four healthy research dogs., Methods: Double-blinded, placebo-controlled randomized trial. Dogs received placebo, clopidogrel (2-3 mg/kg q24h), prednisone (2 mg/kg q24h), or prednisone with clopidogrel PO for 28 days. Attitude, food intake, vomiting, and fecal score were determined daily. Clinicopathologic testing was performed at baseline and on day 28. Gastrointestinal hemorrhages, erosions, and ulcers were numerated by 2 blinded investigators for endoscopies performed on days 0, 14, and 28, and endoscopic mucosal lesion scores were calculated. Results were compared using mixed model, split-plot repeated measures ANOVAs and generalized estimating equation proportional odds models as appropriate. P < .05 was considered significant., Results: Clinical signs of gastrointestinal bleeding were not noted. Endoscopic mucosal lesion scores differed significantly by group (F[3, 20] = 12.8, P < .001) and time (F[2, 40] = 8.3, P < .001). Posthoc analysis revealed higher lesion scores in the prednisone-receiving groups (P ≤ .006 for each) and on day 14 (P ≤ .007 for each). Ulcers were identified in 4 dogs administered prednisone and 3 dogs administered prednisone/clopidogrel. Odds of having endoscopic mucosal lesion scores ≥4 were 7-times higher for dogs in prednisone (95%CI 1.1, 43.0; P = .037) and prednisone-clopidogrel (95%CI 1.1, 43.4; P = .037) groups than those in the placebo group., Conclusions and Clinical Importance: Gastrointestinal bleeding and ulceration occur commonly in healthy dogs administered prednisone or prednisone/clopidogrel treatment, but not clopidogrel monotherapy. Though lesions are severe in many cases, they are not accompanied by clinical signs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs., Hypothesis/objectives: To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4., Animals: Nine healthy Beagle dogs., Methods: Randomized 2-way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance., Results: There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice-daily group., Conclusions and Clinical Importance: These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Purpose of Review: Congenital fibrosis of the extraocular muscles (CFEOM) is caused by abnormal development of the innervation of extraocular muscles. We update the recent literature regarding the clinical, anatomic, genetic, and molecular characteristics of CFEOM. Surgical considerations are addressed., Recent Findings: CFEOM is broken down into three main subtypes, CFEOM1, CFEOM2, and CFEOM3. Several recent reports of individuals, as well as family pedigrees, highlight the phenotypic heterogeneity of CFEOM. Intracranial and intraorbital radiologic findings have enhanced our understanding of the disease pathophysiology. Molecular genetics research has increased our understanding of the development of extraocular muscles and their innervation as well as pathophysiology of CFEOM., Summary: Our understanding of the pathophysiology of CFEOM has increased with the recent contributions from neuroimaging, molecular genetics, and pedigree analysis. Surgical management of patients with CFEOM continues to be challenging.

Background: Dogs with immune-mediated disease are often coadministered glucocorticoids and aspirin, but ulcerogenic effects of current protocols are unknown., Objectives: To compare gastrointestinal changes among dogs administered aspirin, prednisone, and combination treatment., Animals: Twenty-four healthy research dogs., Methods: Double-blinded, placebo-controlled randomized trial of dogs administered placebo, aspirin (2 mg/kg q24h), prednisone (2 mg/kg q24h), or combination treatment PO for 28 days. Clinical signs were recorded daily, with laboratory work performed at baseline and day 28. Gastrointestinal mucosal hemorrhages, erosions, and ulcers were numerated for endoscopic studies performed on days 0, 14, and 28; endoscopic mucosal lesion scores were calculated. Results were compared using mixed model repeated-measures analyses of variance and generalized estimating equation proportional odds models. P < .05 was considered significant., Results: Gastric mucosal lesion scores differed by treatment-by-time (F[6, 40] = 4.4, P = .002), treatment (F[3, 20] = 7.1, P = .002), and time (F[2, 40] = 18.9, P < .001). Post hoc analysis revealed increased scores in the aspirin (day 14 only), prednisone, and prednisone/aspirin groups during treatment. Ulcers were identified on 14 studies, representing 10 dogs. Dogs receiving prednisone and prednisone/aspirin had 11.1 times (95% CI, 1.7-73.6) and 31.5 times (95% CI, 3.5-288.0) higher odds, respectively, of having endoscopic mucosal lesion scores ≥4 than dogs receiving placebo (P ≤ .01)., Conclusions and Clinical Importance: Gastrointestinal bleeding occurs commonly in dogs administered aspirin, prednisone, or prednisone/aspirin treatment, with higher lesion scores for dogs receiving combination treatment. Even severe lesions are not accompanied by clinical signs., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Objective: The purpose of this study was to assess the effect of headphone use and covariates on indirect radial Doppler flow systolic arterial blood pressure (BP) measurements in dogs., Methods: Between May and August 2018, 100 privately-owned dogs were enrolled. Blood pressure was measured in lateral recumbency, with and without headphones, using a randomized crossover design. The initial BP, mean of BP 2-6, weight, BCS, MCS, anxiety score, and heart rate were recorded. Mixed effects crossover analyses and Spearman rank correlation coefficients were determined., Results: Eighty-four dogs completed the study. Eleven dogs were removed due to excessive anxiety, 10 of which were in the non-headphone first group. The number of dogs diagnosed as hypertensive did not differ between measurement types (19 vs. 18), with seven dogs categorized as hypertensive during both periods. Significant differences in BP were identified ( F [1, 80] = 4.3, P  = 0.04) due to higher results for measurements taken without headphones for BP 1, but not BP 2-6. Systolic BP was positively correlated with anxiety score, age, and weight., Conclusions and Clinical Relevance: Though BP 1 was significantly higher when taken without headphones, this pattern did not persist for BP 2-6. Lack of association between BP 2-6 results and measurement type could reflect exclusion of dogs most sensitive to white coat hypertension, acclimation to technique, or improved sound quality of headphones. Given significantly higher BP 1 results and disproportionate exclusion of dogs due to anxiety when measurements first were taken without headphones, use of headphones is recommended to improve accuracy of results., Competing Interests: The authors declare there are no competing interests.

Objective: To propose a late-onset mechanism for uveitis-glaucoma-hyphema (UGH) syndrome caused by Soemmering ring cataract (SRC) and describe surgical outcomes., Design: Retrospective interventional case series., Participants: Patients developing UGH from anterior displacement of a haptic from a SRC., Methods: A retrospective chart review was conducted of all patients referred to an anterior segment surgeon (J.C.H.) for intraocular lens (IOL) reposition/exchange between January 2003 and June 2017. Inclusion criteria consisted of all eyes with (i) a diagnosis of UGH syndrome, and (ii) SRC causing anterior displacement of a sulcus-fixated haptic with iris-haptic touch. Outcome measures were change in best corrected visual acuities (BCVA) and resolution of UGH findings., Results: Seven eyes of 7 patients developed UGH secondary to a SRC causing contact between the IOL optic/haptic and the iris/uvea. Diagnosis of UGH was made at a mean 9.1 years after IOL implantation; this was statistically different compared with UGH eyes with other mechanisms from our full UGH cohort (mean 5.4 years; p = 0.0367). The mean preoperative LogMAR BCVA of 0.45 improved to 0.37 after surgical intervention (p = 0.27). Resolution (or nearly full resolution) of UGH findings was achieved in all cases after SRC extraction and lens repositioning/exchange., Conclusions: Late-onset UGH syndrome can be caused by SRC. Surgical removal of the SRC with IOL repositioning within the capsular bag resolves most if not all components of UGH. Anterior segment ultrasound biomicroscopy is a helpful modality for determining if a SRC is present by demonstrating anatomic relationships commonly obscured by a miotic pupil., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: Synbiotics decrease antibiotic-associated gastrointestinal signs (AAGS) in cats, but data supporting synbiotic use to ameliorate AAGS in dogs are lacking., Objectives: To determine if administration of synbiotics mitigates AAGS in dogs., Animals: Twenty-two healthy research dogs., Methods: Randomized, double-blinded, placebo-controlled, 2-way, 2-period, crossover study with an 8-week washout period. Each period included a 1-week baseline and 3-week treatment phase. Dogs received enrofloxacin (10 mg/kg PO q24h) and metronidazole (12.5 mg/kg PO q12h), followed 1 hour later by a bacterial/yeast synbiotic combination or placebo. Food intake, vomiting, and fecal score were compared using repeated-measures crossover analyses, with P < .05 considered significant., Results: Hyporexia, vomiting, and diarrhea occurred in 41% (95% confidence interval [CI], 21-64), 77% (95% CI, 55-92), and 100% (95% CI, 85-100) of dogs, respectively, during the first treatment period. Derangements in food intake were smaller in both periods for dogs receiving synbiotics (F-value, 5.1; P = .04) with treatment-by-period interactions (F-value, 6.0; P = .02). Days of vomiting differed over time (F-value, 4.7; P = .006). Fecal scores increased over time (F-value, 33.5; P < .001), were lower during period 2 (F-value, 14.5; P = .001), and had treatment-by-period effects (F-value, 4.8; P = .04)., Conclusions and Clinical Importance: Enrofloxacin/metronidazole administration is associated with a high frequency of AAGS. Synbiotic administration decreases food intake derangements. The presence of milder AAGS in period 2 suggests that clinical effects of synbiotics persist >9 weeks after discontinuation, mitigating AAGS in dogs being treated with antibiotics followed by placebo., (© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Background: The purpose of this study was to determine whether heparinized saline (HS) would be more effective in maintaining the patency of central venous catheters (CVCs) in dogs compared to 0.9% sodium chloride. This was a prospective randomized blinded study conducted at a University Veterinary Teaching Hospital., Methods: A total of 24 healthy purpose-bred dogs were randomized into two groups: a treatment and a control group. A CVC was placed in the jugular vein of each dog. Each dog in the treatment group had their CVC flushed with 10 IU/mL HS, while dogs in the control group had their CVC flushed with 0.9% sodium chloride every 6 h for 72 h. Immediately prior to flushing, each catheter was evaluated for patency by aspiration of blood. The catheter site was also evaluated for phlebitis, and a rectal temperature was obtained in each dog every 6 h. Prothrombin (PT) and activated partial thromboplastin (aPTT) times were evaluated prior to the administration of any flush solution. Results were then compared to values obtained 72 h later., Results: All CVCs in both groups were patent after 72 h, which was demonstrated by aspiration of blood and ease of flushing the catheter. Two CVCs in the 0.9% sodium chloride group had a negative aspiration at hour 12 and 36, respectively. One CVC in the HS group had a negative aspiration at hour 18. Signs of phlebitis occurred in three dog: two in the 0.9% sodium chloride group and one in the HS group. No dog was hyperthermic (>103 °F). Two catheters were inadvertently removed by dogs in the HS group during the study. There were no significant differences in catheter patency, incidence of phlebitis, or incidence of negative aspirations between both groups. aPTT and PT values remained within the normal reference range for all dogs in both groups. Ultimately, 0.9% sodium chloride was as effective as 10 IU/mL HS in maintaining the patency of CVCs for up to 72 h in healthy dogs. Further evaluation in clinical patients is warranted., Competing Interests: The authors declare that they have no competing interests.

Objective: To describe the frequency of renal tubular vacuolization (RTV) as a surrogate of osmotic nephrosis and assess hyperosmolar agents as predictors of RTV severity., Design: Retrospective study (February 2004-October 2014)., Setting: Veterinary teaching hospital., Animals: Fifty-three client-owned, critically ill dogs that had a postmortem examination., Interventions: None., Measurements and Main Results: The frequency, severity, and location of RTV were determined in small group of critically ill dogs postmortem. Logistic regression was performed to assess cumulative 6% HES (670/0.75) and mannitol dose as predictors for RTV severity with presenting serum creatinine concentration, cumulative furosemide dose, and duration of hospitalization as covariates. RTV was noted in 45 (85%) of 53 critically ill dogs and was most commonly located to the medullary rays (68%). Cumulative 6% HES (670/0.75) dose (P = 0.009) and presenting serum creatinine concentration (P = 0.027) were significant predictors of RTV severity. For every 1 mL/kg increase in 6% HES (670/0.75) dose that a dog received, there was 1.6% increased chance of having more severe RTV (OR 1.016; 95% CI 1.004-1.029). In addition, for every 88.4 μmol/L (1 mg/dL) increase in presenting serum creatinine, there was a 22.7% increased chance of having more severe RTV (OR 1.227; 95% CI 1.023-1.472). Cumulative mannitol (P = 0.548) and furosemide (P = 0.136) doses were not significant predictors of RTV severity., Conclusion: In a small group of critically ill dogs, there was a high frequency of RTV identified on postmortem examination. Administration of 6% HES (670/0.75) and presenting serum creatinine concentration were significant predictors of RTV severity. Larger prospective studies are needed to determine the etiology and significance of RTV in dogs., (© Veterinary Emergency and Critical Care Society 2019.)

Reduction in antibiotic-associated gastrointestinal signs (AAGS) in people co-administered probiotics is believed to result from shifts in the microbiome and metabolome. Amelioration of AAGS in cats secondary to synbiotic administration has recently been demonstrated. Thus, the aim of this randomized, double-blinded, placebo-controlled trial was to characterize associated changes in the fecal microbiome and metabolome. Sixteen healthy research cats received clindamycin with food, followed 1 h later by either a placebo or synbiotic, daily for 21 days. Fecal samples were collected during baseline, antibiotic administration, and 6 weeks after antibiotic discontinuation. Sequencing of 16S rRNA genes was performed, and mass spectrometry was used to determine fecal metabolomic profiles. Results were compared using mixed-model analyses, with P < 0.05 considered significant. Alpha and beta diversity were altered significantly during treatment, with persistent changes in the Shannon and dysbiosis indices. The relative abundance of Actinobacteria ( Adlercreutzia, Bifidobacterium, Collinsella, Slackia ), Bacteroidia ( Bacteroides, Prevotella ), Ruminococcaceae ( Faecalibacterium, Ruminococcus ), Veillonellaceae ( Megamonas, Megasphaera, Phascolarctobacterium ) and Erysipelotrichaceae ([ Eubacterium ]) decreased and relative abundance of Clostridiaceae ( Clostridium ) and Proteobacteria ( Enterobacteriaceae ) increased during treatment, followed by variable return to baseline relative abundances. Derangements in short-chain fatty acid (SCFA), bile acid, tryptophan, sphingolipid, polyamine, benzoic acid, and cinnaminic acid pathways occurred with significant group by time, group, and time interactions for 10, 5, and 106 metabolites, respectively. Of particular note were changes related to polyamine synthesis. Further investigation is warranted to elucidate the role of these alterations in prevention of AAGS in cats, people, and other animals treated with synbiotics.

Eight adult tigers ( Panthera tigris) underwent a complete echocardiographic examination following sedation with medetomidine, midazolam, and induction of general anesthesia using ketamine and isoflurane (phase 1). Atipamezole was used to antagonize medetomidine (phase 2) and a second echocardiographic examination was performed. Physiologic tricuspid and pulmonic regurgitations were common findings in the sample population and one tiger was excluded from final analyses due to the finding of a ventricular septal defect. Measurements and mean arterial pressure were assessed for statistically significant differences between the two examination phases as well as gender and weight. There was a statistically significant difference between interventricular septum thickness at end systole, ejection fraction, and mean arterial pressure between anesthetic phases while fractional shortening and left ventricular internal dimension at end-systole approached, but did not reach, statistical significance between phases. Weight was found to be a statistically significant predictor of stroke volume and left ventricular internal dimension at end-diastole. The echocardiographic measurements obtained during this study can be used as guidelines for future examinations in adult tigers. The effects of medetomidine on these measurements and systolic function should be taken into account when performing echocardiograms and monitoring anesthetic events.

This paper evaluates a novel high variability phonetic training paradigm that involves presenting spoken words in adverse conditions. The effectiveness, generalizability, and longevity of this high variability phonetic training in adverse conditions was evaluated using English phoneme contrasts in three experiments with Malaysian multilinguals. Adverse conditions were created by presenting spoken words against background multi-talker babble. In Experiment 1, the adverse condition level was set at a fixed level throughout the training and in Experiment 2 the adverse condition level was determined for each participant before training using an adaptive staircase procedure. To explore the effectiveness and sustainability of the training, phonemic discrimination ability was assessed before and immediately after training (Experiments 1 and 2) and 6 months after training (Experiment 3). Generalization of training was evaluated within and across phonemic contrasts using trained and untrained stimuli. Results revealed significant perceptual improvements after just three 20-minute training sessions and these improvements were maintained after 6 months. The training benefits also generalized from trained to untrained stimuli. Crucially, perceptual improvements were significantly larger when the adverse conditions were adapted before each training session than when it was set at a fixed level. As the training improvements observed here are markedly larger than those reported in the literature, this indicates that the individualized phonetic training regime in adaptive adverse conditions (HVPT-AAC) is highly effective at improving speech perception., Competing Interests: The authors have declared that no competing interests exist.

We describe the clinical course of an 11-year-old girl diagnosed with lipemia retinalis as the presenting sign of diabetes mellitus type 1 with severe secondary hypertriglyceridemia. By performing serial multimodal imaging studies, we provide a comprehensive description of the clinical manifestations associated with severe hypertriglyceridemia to promote recognition of this rare clinical diagnosis., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Overexpression of EGFR is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC who respond to EGFR-targeted tyrosine kinase inhibitors (TKIs) eventually develop acquired resistance. Strategies to identify HNSCC patients likely to benefit from EGFR-targeted therapies, together with biomarkers of treatment response, would have clinical value. Methods: Functional MRI and 18 F-FDG PET were used to visualize and quantify imaging biomarkers associated with drug response within size-matched EGFR TKI-resistant CAL 27 (CAL R ) and sensitive (CAL S ) HNSCC xenografts in vivo , and pathological correlates sought. Results: Intrinsic susceptibility, oxygen-enhanced and dynamic contrast-enhanced MRI revealed significantly slower baseline R 2 ∗ , lower hyperoxia-induced Δ R 2 ∗ and volume transfer constant K trans in the CAL R tumors which were associated with significantly lower Hoechst 33342 uptake and greater pimonidazole-adduct formation. There was no difference in oxygen-induced ΔR 1 or water diffusivity between the CAL R and CAL S xenografts. PET revealed significantly higher relative uptake of 18 F-FDG in the CAL R cohort, which was associated with significantly greater Glut-1 expression. Conclusions: CAL R xenografts established from HNSCC cells resistant to EGFR TKIs are more hypoxic, poorly perfused and glycolytic than sensitive CAL S tumors. MRI combined with PET can be used to non-invasively assess HNSCC response/resistance to EGFR inhibition.