Prepubescent Electronic Cigarette Exposure Affects Sexual Motivation and Puberty in Female But Not Male Long-Evans Rats.

INTRODUCTION: A method for delivering vaporized nicotine to animals has been developed using e-cigarette devices. The present experiment was designed to measure the effects of e-cigarette nicotine on pubertal onset and development of reproductive behavior in female and male Long-Evans rats. AIM AND METHODS: Rats received daily 10-min sessions of electronic-cigarette vaporized nicotine (5% Virginia Tobacco JUUL Pods) or room air in a whole-body exposure chamber (postnatal day 28-31). Pubertal onset was monitored daily (ie, vaginal opening in females, preputial separation in males). Two weeks later, rats were tested for sexual motivation using the partner-preference paradigm, whereby subjects were given the opportunity to approach either a sexual partner or a same-sex social partner. Four weeks later, partner preference was assessed again, 10 min after rats were re-exposed to their same prepubertal treatment. RESULTS: We found that prepubescent electronic-cigarette vaporized nicotine disrupted puberty and sexual motivation in female but not male rats. In vaped females, vaginal opening was delayed and less time was spent with the male stimulus compared to room-air controls. In contrast, no effect of e-cigarette vapor was observed on pubertal onset or on any measures of sexual behavior in male rats. No effects were observed in either female or male rats on the second partner-preference test. CONCLUSIONS: Prepubescent vaporized nicotine affected the development of reproductive physiology and behavior in female rats but not in male rats, whereas an additional acute exposure to nicotine vapor had no effect in either female or male adult rats. IMPLICATIONS: Given the prevalence of increasingly younger users, more animal research is needed to explore the effects of e-cigarette smoking on multiple developmental systems including reproductive physiology and behavior. This model could be useful in exploring multiple behavioral and physiological endpoints in both sexes. Adjustments to the duration of exposure and control conditions will be necessary for future experiments to best model human use.

A Single 10-Minute E-cigarette Vapor Exposure Reduces Tidal Volume and Minute Ventilation in Normoxia and Normobaric Hypoxia in Adult Rats.

The present study investigated the effects of a single 10-minute exposure to e-cigarette vapor on ventilation in adult male Long-Evans rats. Ventilation was recorded using awake, unrestrained whole-body plethysmography. Baseline recordings were taken the day before full-body exposure to either room air (n = 9; air control group) or e-cigarette vapor (n = 9; treatment group). Post-exposure recordings were taken immediately after the 10-minute room air or vapor exposure. As part of the ventilation protocol, in addition to recording the subject's ventilation in room air, the subjects were also exposed to 10% oxygen (balanced with nitrogen) to assess the effects of e-cigarette vapor on an increased drive to breathe. Ventilation data were analyzed using a 2x2x2 mixed-model ANOVA measuring treatment (vape vs. air) x time (baseline vs. post-treatment) x condition (normoxia vs. hypoxia) for breathing frequency, tidal volume, and minute ventilation. Breathing frequency increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), with no effect of time (baseline vs. post-treatment) for either group. Tidal volume increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), and an effect of time (baseline vs. post-treatment) was observed (p = 0.010) for the vape group. Minute ventilation increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), and an effect of time (baseline vs. post-treatment) was observed (p < 0.001) for the vape group. In conclusion, immediately following a single 10-minute e-cigarette vapor exposure, both tidal volume and minute ventilation were reduced during normoxia and normobaric hypoxia, indicating a decrease in ventilation after a single 10-minute e-cigarette vapor exposure. Furthermore, this exposure also blunted the physiological response to acute hypoxia exposure. Subjects in the vape group, while breathing more rapidly as expected, experienced shallower breathing than the air group during hypoxia. The findings in this study confirm that vaping could result in reduced lung function.

Improvement of Pretibial Myxedema Following Administration of Teprotumumab.

Pretibial myxedema (PTM) is a rare complication of Graves' disease. It is characterized by non-pitting edema with hyperpigmented hyperkeratotic papules and plaques on bilateral lower legs. Effective treatments for patients with PTM are lacking. The etiology of PTM is unknown; however, it may be similar to the mechanism of thyroid-associated ophthalmopathy (TAO). Activated fibroblasts produce inflammatory cytokines and synthesize excessive glycosaminoglycans (GAG) that accumulate in the dermis and subcutaneous tissue. A recent, novel pathway implicates IGF-1 receptor as a mediator in this process. We present two patients with refractory PTM that improved following treatment with teprotumumab, an IGF-1 receptor inhibitor approved for use in TAO. J Drugs Dermatol. 2022;21(11):1252-1254. doi:10.36849/JDD.6854.

Time Domains of Hypoxia Responses and -Omics Insights.

The ability to respond rapidly to changes in oxygen tension is critical for many forms of life. Challenges to oxygen homeostasis, specifically in the contexts of evolutionary biology and biomedicine, provide important insights into mechanisms of hypoxia adaptation and tolerance. Here we synthesize findings across varying time domains of hypoxia in terms of oxygen delivery, ranging from early animal to modern human evolution and examine the potential impacts of environmental and clinical challenges through emerging multi-omics approaches. We discuss how diverse animal species have adapted to hypoxic environments, how humans vary in their responses to hypoxia (i.e., in the context of high-altitude exposure, cardiopulmonary disease, and sleep apnea), and how findings from each of these fields inform the other and lead to promising new directions in basic and clinical hypoxia research.

Pharmacokinetics of orally administered single-dose ponazuril in cats.

Cats and kittens in animal shelters and catteries regularly suffer from severe gastrointestinal coccidiosis, which can be fatal, and there are no drugs labeled for feline coccidiosis in the United States. Ponazuril, a triazine-class drug, is increasingly used at a dose of 50 mg/kg/d, orally, for three to five days in shelter environments for coccidiosis. A single oral dose of ponazuril paste 15% (Marquis® ; Merial) at 50 mg/kg was administered to six healthy adult cats. Sample analysis was completed via high-performance liquid chromatography. Plasma concentrations peaked at 7.49 ± 2.06 µg/ml at 14.67 ± 7.45 hr post-administration. This study shows that ponazuril achieved a plasma concentration that inhibits growth of similar organisms after a single oral dose in cats. Further studies are necessary to optimize dosing for the treatment of clinical coccidiosis in cats.

Updating anatomy and physiology lab delivery: shifting from a paper-based to an online lab instruction platform, just in time for a global pandemic.

This paper describes how an anatomy and physiology laboratory class transitioned from a paper-based lab to an online learning platform that updated the curriculum to rely more on face-to-face small group collaboration and peer teaching. Student perceptions of the new format were positive, but halfway through the transition a global pandemic challenged the new instruction method. The face-to-face curriculum had to be adjusted to a virtual format that lacked in-person interaction between the instructor and the students. This switch to virtual labs had an adverse effect on both student perception and student performance in the second half of the semester. Our observations underscore the importance of creating an interactive community when teaching virtually.

Pharmacokinetic characterization of fluorocoxib D, a cyclooxygenase-2-targeted optical imaging agent for detection of cancer.

SIGNIFICANCE: Fluorocoxib D, N-[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, is a water-soluble optical imaging agent to detect cyclooxygenase-2 (COX-2)-expressing cancer cells. AIM: We evaluated the pharmacokinetic and safety properties of fluorocoxib D and its ability to detect cancer cells in vitro and in vivo. APPROACH: Pharmacokinetic parameters of fluorocoxib D were assessed from plasma collected at designated time points after intravenous administration of 1 mg / kg fluorocoxib D in six research dogs using a high-performance liquid chromatography analysis. Safety of fluorocoxib D was assessed for 3 days after its administration using physical assessment, complete blood count, serum chemistry profile, and complete urinalysis in six research dogs. The ability of fluorocoxib D to detect COX-2-expressing cancer cells was performed using human 5637 cells in vitro and during rhinoscopy evaluation of specific fluorocoxib D uptake by canine cancer cells in vivo. RESULTS: No evidence of toxicity and no clinically relevant adverse events were noted in dogs. Peak concentration of fluorocoxib D (114.8 ± 50.5 ng / ml) was detected in plasma collected at 0.5 h after its administration. Pretreatment of celecoxib blocked specific uptake of fluorocoxib D in COX-2-expressing human 5637 cancer cells. Fluorocoxib D uptake was detected in histology-confirmed COX-2-expressing head and neck cancer during rhinoscopy in a client-owned dog in vivo. Specific tumor-to-normal tissue ratio of detected fluorocoxib D signal was in an average of 3.7 ± 0.9 using Image J analysis. CONCLUSIONS: Our results suggest that fluorocoxib D is a safe optical imaging agent used for detection of COX-2-expressing cancers and their margins during image-guided minimally invasive biopsy and surgical procedures.

Effect of site of sample collection and prandial state on blood glucose concentrations measured with a portable blood glucose meter in healthy dogs.

OBJECTIVE: To compare glucose concentrations in peripheral venous and capillary blood samples collected from dogs before and after consumption of a meal and measured with a veterinary-specific portable blood glucose meter (PBGM). ANIMALS: 12 dogs (96 blood samples). PROCEDURES: A veterinary-specific PBGM was used to measure blood glucose concentrations. Glucose concentrations in capillary blood samples obtained from the carpal pad, medial aspect of a pinna, and oral mucosa were compared with glucose concentrations in blood samples obtained from a lateral saphenous vein. Samples were collected after food was withheld for 12 hours and again 2 hours after consumption of a meal. RESULTS: Location of capillary blood collection had a significant effect on glucose concentrations measured with the PBGM. Glucose concentration in capillary blood collected from the medial aspect of the pinna did not differ significantly from the glucose concentration in peripheral venous blood samples, whereas glucose concentrations in blood samples collected from the carpal pad and oral mucosa differed significantly from the glucose concentration in peripheral venous blood samples. There was no significant difference between preprandial and postprandial blood glucose concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Glucose concentrations in capillary blood collected from the medial aspect of the pinna of dogs better reflected glucose concentrations in venous blood than concentrations measured in capillary blood collected from the carpal pad or oral mucosa.

Effects of a synbiotic on the fecal microbiome and metabolomic profiles of healthy research cats administered clindamycin: a randomized, controlled trial.

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.

Child Weight Gain Trajectories Linked To Oral Microbiota Composition.

Gut and oral microbiota perturbations have been observed in obese adults and adolescents; less is known about their influence on weight gain in young children. Here we analyzed the gut and oral microbiota of 226 two-year-olds with 16S rRNA gene sequencing. Weight and length were measured at seven time points and used to identify children with rapid infant weight gain (a strong risk factor for childhood obesity), and to derive growth curves with innovative Functional Data Analysis (FDA) techniques. We showed that growth curves were associated negatively with diversity, and positively with the Firmicutes-to-Bacteroidetes ratio, of the oral microbiota. We also demonstrated an association between the gut microbiota and child growth, even after controlling for the effect of diet on the microbiota. Lastly, we identified several bacterial genera that were associated with child growth patterns. These results suggest that by the age of two, the oral microbiota of children with rapid infant weight gain may have already begun to establish patterns often seen in obese adults. They also suggest that the gut microbiota at age two, while strongly influenced by diet, does not harbor obesity signatures many researchers identified in later life stages.

Short and long-term effects of a synbiotic on clinical signs, the fecal microbiome, and metabolomic profiles in healthy research cats receiving clindamycin: a randomized, controlled trial.

BACKGROUND: Antibiotic-associated gastrointestinal signs (AAGS) occur commonly in cats. Co-administration of synbiotics is associated with decreased AAGS in people, potentially due to stabilization of the fecal microbiome and metabolome. The purpose of this double-blinded randomized-controlled trial was to compare AAGS and the fecal microbiome and metabolome between healthy cats that received clindamycin with a placebo or synbiotic. METHODS: 16 healthy domestic shorthair cats from a research colony were randomized to receive 150 mg clindamycin with either a placebo (eight cats) or commercially-available synbiotic (eight cats) once daily for 21 days with reevaluation 603 days thereafter. All cats ate the same diet. Food consumption, vomiting, and fecal score were recorded. Fecal samples were collected daily on the last three days of baseline (days 5-7), treatment (26-28), and recovery (631-633). Sequencing of 16S rRNA genes and gas chromatography time-of-flight mass spectrometry was performed. Clinical signs, alpha and beta diversity metrics, dysbiosis indices, proportions of bacteria groups, and metabolite profiles were compared between treatment groups using repeated measures ANOVAs. Fecal metabolite pathway analysis was performed. P < 0.05 was considered significant. The Benjamini & Hochberg's False Discovery Rate was used to adjust for multiple comparisons. RESULTS: Median age was six and five years, respectively, for cats in the placebo and synbiotic groups. Hyporexia, vomiting, diarrhea, or some combination therein were induced in all cats. Though vomiting was less in cats receiving a synbiotic, the difference was not statistically significant. Bacterial diversity decreased significantly on days 26-28 in both treatment groups. Decreases in Actinobacteria (Bifidobacterium, Collinsella, Slackia), Bacteriodetes (Bacteroides), Lachnospiraceae (Blautia, Coprococcus, Roseburia), Ruminococcaceae (Faecilobacterium, Ruminococcus), and Erysipelotrichaceae (Bulleidia, [Eubacterium]) and increases in Clostridiaceae (Clostridium) and Proteobacteria (Aeromonadales, Enterobacteriaceae) occurred in both treatment groups, with incomplete normalization by days 631-633. Derangements in short-chain fatty acid, bile acid, indole, sphingolipid, benzoic acid, cinnaminic acid, and polyamine profiles also occurred, some of which persisted through the terminal sampling timepoint and differed between treatment groups. DISCUSSION: Cats administered clindamycin commonly develop AAGS, as well as short- and long-term dysbiosis and alterations in fecal metabolites. Despite a lack of differences in clinical signs between treatment groups, significant differences in their fecal metabolomic profiles were identified. Further investigation is warranted to determine whether antibiotic-induced dysbiosis is associated with an increased risk of future AAGS or metabolic diseases in cats and whether synbiotic administration ameliorates this risk.

INSIGHT responsive parenting intervention reduces infant's screen time and television exposure.

BACKGROUND: Sedentary behaviors, including screen time, in childhood have been associated with an increased risk for overweight. Beginning in infancy, we sought to reduce screen time and television exposure and increase time spent in interactive play as one component of a responsive parenting (RP) intervention designed for obesity prevention. METHODS: The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) study is a randomized trial comparing a RP intervention with a safety control intervention. Primiparous mother-newborn dyads (N = 279) were randomized after childbirth. Research nurses delivered intervention content at infant ages 3, 16, 28, and 40 weeks and research center visits at 1 and 2 years. As one component of INSIGHT, developmentally appropriate messages on minimizing screen time, reducing television exposure in the home, and promoting parent-child engagement through interactive play were delivered. Mothers self-reported their infant's screen time at ages 44 weeks, 1, 1.5, 2 and 2.5 years; interactive play was reported at 8 and 20 weeks and 2 years. RESULTS: More RP than control parents reported their infants met the American Academy of Pediatrics' no screen time recommendation at 44 weeks (53.0% vs. 30.2%) and at 1 year on weekdays (42.5% vs. 27.6%) and weekends (45.5% vs. 26.8%), but not after age 1 year. RP mothers and RP children had less daily screen time than controls at each time point (p ≤ 0.01). Fewer RP than control group mothers reported the television was ever on during infant meals (p < 0.05). The frequency of tummy time and floor play did not differ by study group; approximately 95% of infants spent time in restrictive devices (i.e. swing) at 8 and 20 weeks. At 2 years of age, there were no study group differences for time children spent in interactive play. CONCLUSION: From infancy to early childhood, the INSIGHT RP intervention reduced screen time and television exposure, but did not increase the frequency or amount of interactive play. TRIAL REGISTRATION: clinicaltrials.gov NCT01167270 . Registered on 21 July 2010.

Association of Salivary MicroRNA Changes With Prolonged Concussion Symptoms.

Importance: Approximately one-third of children who experience a concussion develop prolonged concussion symptoms. To our knowledge, there are currently no objective or easily administered tests for predicting prolonged concussion symptoms. Several studies have identified alterations in epigenetic molecules known as microRNAs (miRNAs) following traumatic brain injury. No studies have examined whether miRNA expression can detect prolonged concussion symptoms. Objective: To evaluate the efficacy of salivary miRNAs for identifying children with concussion who are at risk for prolonged symptoms. Design, Setting, and Participants: This prospective cohort study at the Penn State Medical Center observed 52 patients aged 7 to 21 years presenting for evaluation of concussion within 14 days of initial head injury, with follow-up at 4 and 8 weeks. Exposures: All patients had a clinical diagnosis of concussion. Main Outcomes and Measures: Salivary miRNA expression was measured at the time of initial clinical presentation in all patients. Patients with a Sport Concussion Assessment Tool (SCAT3) symptom score of 5 or greater on self-report or parent report 4 weeks after injury were designated as having prolonged symptoms. Results: Of the 52 included participants, 22 (42%) were female, and the mean (SD) age was 14 (3) years. Participants were split into the prolonged symptom group (n = 30) and acute symptom group (n = 22). Concentrations of 15 salivary miRNAs spatially differentiated prolonged and acute symptom groups on partial least squares discriminant analysis and demonstrated functional relationships with neuronal regulatory pathways. Levels of 5 miRNAs (miR-320c-1, miR-133a-5p, miR-769-5p, let-7a-3p, and miR-1307-3p) accurately identified patients with prolonged symptoms on logistic regression (area under the curve, 0.856; 95% CI, 0.822-0.890). This accuracy exceeded accuracy of symptom burden on child (area under the curve, 0.649; 95% CI, 0.388-0.887) or parent (area under the curve, 0.562; 95% CI, 0.219-0.734) SCAT3 score. Levels of 3 miRNAs were associated with specific symptoms 4 weeks after injury; miR-320c-1 was associated with memory difficulty (R, 0.55; false detection rate, 0.02), miR-629 was associated with headaches (R, 0.47; false detection rate, 0.04), and let-7b-5p was associated with fatigue (R, 0.45; false detection rate, 0.04). Conclusions and Relevance: Salivary miRNA levels may identify the duration and character of concussion symptoms. This could reduce parental anxiety and improve care by providing a tool for concussion management. Further validation of this approach is needed.

Continuous radiotelemetric monitoring of intragastric pH in a dog with peptic ulceration.

CASE DESCRIPTION A 6-year-old castrated male Boxer was evaluated for a 5-week history of frequent vomiting, melena, and signs of abdominal pain following accidental ingestion of 5 to ten 15-mg meloxicam tablets (approx ingested dose, 3.1 to 6.2 mg/kg [1.4 to 2.8 mg/lb]). CLINICAL FINDINGS Clinical signs persisted despite 3 weeks of treatment with sucralfate (41.8 mg/kg [19 mg/lb], PO, q 8 h) and omeprazole (0.8 mg/kg [0.36 mg/lb], PO, q 24 h). Results of a CBC and serum biochemical analysis were unremarkable. Abdominal ultrasonography revealed peptic ulceration, and esophagogastroduodenoscopy confirmed the presence of severe proximal duodenal ulceration. TREATMENT AND OUTCOME A radiotelemetric pH-monitoring capsule was placed in the gastric fundus under endoscopic guidance for continuous at-home monitoring of intragastric pH and response to treatment. Treatment was continued with sucralfate (as previously prescribed) and omeprazole at an increased administration frequency (0.8 mg/kg, PO, q 12 h). Intragastric pH was consistently ≥ 3.0 for > 75% of the day during treatment, with the exception of 1 day when a single dose of omeprazole was inadvertently missed. Ulceration and clinical signs completely resolved. CLINICAL RELEVANCE Continuous radiotelemetric monitoring of intragastric pH in the dog of this report was useful for confirming that treatment achieved a predetermined target pH and for demonstrating the impact of missed doses. Duodenal ulceration resolved with twice-daily but not once-daily omeprazole administration. Findings suggested that twice-daily administration of omeprazole may be necessary to achieve this target pH and that a pH ≥ 3.0 for 75% of the day may promote healing of peptic ulcers in dogs.

Incidence of incompatible crossmatch results in dogs admitted to a veterinary teaching hospital with no history of prior red blood cell transfusion.

OBJECTIVE To determine the incidence of incompatible crossmatch results in dogs without a history of prior RBC transfusion and to evaluate changes in Hct following RBC administration for transfusion-naïve dogs that did and did not have crossmatching performed. DESIGN Retrospective study. ANIMALS 169 client-owned dogs. PROCEDURES Information obtained from the medical records included signalment, pretransfusion Hct or PCV, and crossmatching results where applicable. Dogs that underwent major crossmatching (n = 149) as part of pretransfusion screening were each crossmatched with 3 potential donors. Donor blood was obtained from a commercial source and tested negative for dog erythrocyte antigens (DEAs) 1.1, 1.2, and 7 but positive for DEA 4. Mean change in Hct after transfusion was compared between crossmatch-tested dogs (57/91 that subsequently underwent RBC transfusion) and 20 other dogs that underwent RBC transfusion without prior crossmatching by statistical methods. RESULTS 25 of 149 (17%) dogs evaluated by crossmatching were incompatible with 1 or 2 of the 3 potential donors. All 149 dogs were compatible with ≥ 1 potential donor. Mean ± SD change in Hct after transfusion was significantly higher in dogs that had crossmatching performed (12.5 ± 8.6%) than in dogs that did not undergo crossmatching (9.0 ± 4.3%). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated immunologic incompatibility can exist between first-time transfusion recipients and potential blood donor dogs. The clinical importance of these findings could not be evaluated, but considering the potential for immediate or delayed hemolytic transfusion reactions or shortened RBC life span, the authors suggest veterinarians consider crossmatching all dogs prior to transfusion when possible.

Minocycline blocks glial cell activation and ventilatory acclimatization to hypoxia.

Ventilatory acclimatization to hypoxia (VAH) is the time-dependent increase in ventilation, which persists upon return to normoxia and involves plasticity in both central nervous system respiratory centers and peripheral chemoreceptors. We investigated the role of glial cells in VAH in male Sprague-Dawley rats using minocycline, an antibiotic that inhibits microglia activation and has anti-inflammatory properties, and barometric pressure plethysmography to measure ventilation. Rats received either minocycline (45mg/kg ip daily) or saline beginning 1 day before and during 7 days of chronic hypoxia (CH, PiO2 = 70 Torr). Minocycline had no effect on normoxic control rats or the hypercapnic ventilatory response in CH rats, but minocycline significantly (P < 0.001) decreased ventilation during acute hypoxia in CH rats. However, minocycline administration during only the last 3 days of CH did not reverse VAH. Microglia and astrocyte activation in the nucleus tractus solitarius was quantified from 30 min to 7 days of CH. Microglia showed an active morphology (shorter and fewer branches) after 1 h of hypoxia and returned to the control state (longer filaments and extensive branching) after 4 h of CH. Astrocytes increased glial fibrillary acidic protein antibody immunofluorescent intensity, indicating activation, at both 4 and 24 h of CH. Minocycline had no effect on glia in normoxia but significantly decreased microglia activation at 1 h of CH and astrocyte activation at 24 h of CH. These results support a role for glial cells, providing an early signal for the induction but not maintenance of neural plasticity underlying ventilatory acclimatization to hypoxia.NEW & NOTEWORTHY The signals for neural plasticity in medullary respiratory centers underlying ventilatory acclimatization to chronic hypoxia are unknown. We show that chronic hypoxia activates microglia and subsequently astrocytes. Minocycline, an antibiotic that blocks microglial activation and has anti-inflammatory properties, also blocks astrocyte activation in respiratory centers during chronic hypoxia and ventilatory acclimatization. However, minocycline cannot reverse ventilatory acclimatization after it is established. Hence, glial cells may provide signals that initiate but do not sustain ventilatory acclimatization.

The impact of inflammation on respiratory plasticity.

Breathing is a vital homeostatic behavior and must be precisely regulated throughout life. Clinical conditions commonly associated with inflammation, undermine respiratory function may involve plasticity in respiratory control circuits to compensate and maintain adequate ventilation. Alternatively, other clinical conditions may evoke maladaptive plasticity. Yet, we have only recently begun to understand the effects of inflammation on respiratory plasticity. Here, we review some of common models used to investigate the effects of inflammation and discuss the impact of inflammation on nociception, chemosensory plasticity, medullary respiratory centers, motor plasticity in motor neurons and respiratory frequency, and adaptation to high altitude. We provide new data suggesting glial cells contribute to CNS inflammatory gene expression after 24h of sustained hypoxia and inflammation induced by 8h of intermittent hypoxia inhibits long-term facilitation of respiratory frequency. We also discuss how inflammation can have opposite effects on the capacity for plasticity, whereby it is necessary for increases in the hypoxic ventilatory response with sustained hypoxia, but inhibits phrenic long term facilitation after intermittent hypoxia. This review highlights gaps in our knowledge about the effects of inflammation on respiratory control (development, age, and sex differences). In summary, data to date suggest plasticity can be either adaptive or maladaptive and understanding how inflammation alters the respiratory system is crucial for development of better therapeutic interventions to promote breathing and for utilization of plasticity as a clinical treatment.

Gene × Environment Interactions in Schizophrenia: Evidence from Genetic Mouse Models.

The study of gene × environment, as well as epistatic interactions in schizophrenia, has provided important insight into the complex etiopathologic basis of schizophrenia. It has also increased our understanding of the role of susceptibility genes in the disorder and is an important consideration as we seek to translate genetic advances into novel antipsychotic treatment targets. This review summarises data arising from research involving the modelling of gene × environment interactions in schizophrenia using preclinical genetic models. Evidence for synergistic effects on the expression of schizophrenia-relevant endophenotypes will be discussed. It is proposed that valid and multifactorial preclinical models are important tools for identifying critical areas, as well as underlying mechanisms, of convergence of genetic and environmental risk factors, and their interaction in schizophrenia.

Cryopreserved platelet concentrate transfusions in 43 dogs: a retrospective study (2007-2013).

OBJECTIVE: To clinically characterize a group of thrombocytopenic dogs that received cryopreserved platelet concentrate (cPC) transfusion, assess efficacy of cPC treatment in improving patient outcome, and compare treated dogs to a control population of thrombocytopenic dogs that did not receive cPC transfusions. DESIGN: Retrospective study. SETTING: University teaching hospital. ANIMALS: Eighty-six client-owned dogs (43 in treatment group, 43 in control group). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records of thrombocytopenic dogs that received cPC transfusions and those of thrombocytopenic dogs that did not receive cPC (control population) from January 2007 through March 2013 were reviewed. Dogs receiving cPC were statistically more likely than controls to have a platelet trigger for cPC transfusion (P = 0.01), lower platelet count (P = 0.009) and hematocrit at presentation (P = 0.001), and lower hematocrit after cPC (P = 0.02). Although there was a statistically significant increase in platelet count from pre- to post-cPC transfusion (P = 0.002), cPC was not found to be effective in improving clinical bleeding or increasing survival compared to the control group. No other characteristics were statistically different between groups. No dogs receiving cPC had an acute transfusion reaction during hospitalization. CONCLUSIONS: In the population described in this study, cPC was not found to increase survival, but was well tolerated. Controlled, prospective studies are necessary to determine indications for and efficacy of cPC transfusions.