"One size does not fit all" - Barriers to and facilitators of physical activity in adolescents with epilepsy.

OBJECTIVE: To explore the barriers to physical activity and to identify the support needed to facilitate physical activity in adolescents with epilepsy (AWE). METHODS: AWE (aged 11-16 years) and their caregivers completed survey-based open questions regarding perceived barriers to, and facilitators of physical activity in young people with epilepsy. The responses were analysed using Thematic Analysis. RESULTS: Themes concerning barriers to physical activity included concerns about seizure safety, general anxiety and anxiety related to seizures, stigma/negative attitudes associated with having epilepsy, tiredness, and perceived lack of physical competence. Themes regarding the support needed to facilitate physical activity included better education amongst staff/coaches about epilepsy (e.g., seizure management/prevention, associated fatigue/tiredness), improvements in societal attitudes towards epilepsy, flexibility/tailoring of activities to the child's needs (e.g., need for breaks), and peer support for young people with epilepsy to encourage engagement in physical activity. CONCLUSIONS: There is a perception among AWE and caregivers, that significant barriers exist with regard to engaging in physical activity for young people with epilepsy. Barriers are related to concerns about seizure management but also wider safety and social issues. A number of facilitators were identified to promote physical activity engagement in AWE, including education for staff and caregivers, peer support, and tailoring activities to the adolescent's needs. There is a need to develop interventions to reduce barriers to physical activity in young people with epilepsy.

Factors associated with typical enteropathogenic Escherichia coli infection among children <5 years old with moderate-to-severe diarrhoea in rural western Kenya, 2008-2012.

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37-3.17), and convulsions (aOR 2.83, 95% CI 1.12-7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3-3.6) and wasted (OR 2.5, 95% CI 1.3-4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47-5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

Selective HDAC6 inhibition decreases early stage of lupus nephritis by down-regulating both innate and adaptive immune responses.

We have demonstrated previously that histone deacetylase (HDAC6) expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) New Zealand Black (NZB)/White F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for 5 weeks. As the mice aged, we determined autoantibody production and cytokine levels by enzyme-linked immunosorbent assay (ELISA) and renal function by measuring proteinuria. At the termination of the study, we performed a comprehensive analysis on B cells, T cells and innate immune cells using flow cytometry and examined renal tissue for immune-mediated pathogenesis using immunohistochemistry and immunofluorescence. Our results showed a reduced germinal centre B cell response, decreased T follicular helper cells and diminished interferon (IFN)-γ production from T helper cells in splenic tissue. Additionally, we found the IFN-α-producing ability of plasmacytoid dendritic cells was decreased along with immunoglobulin isotype switching and the generation of pathogenic autoantibodies. Renal tissue showed decreased immunoglobulin deposition and reduced inflammation as judged by glomerular and interstitial inflammation. Taken together, these studies show selective HDAC6 inhibition decreased several parameters of disease pathogenesis in lupus-prone mice. The decrease was due in part to inhibition of B cell development and response.

Diarrhoea, enteric pathogen detection and nutritional indicators among controls in the Global Enteric Multicenter Study, Kenya site: an opportunity to understand reference populations in case-control studies of diarrhoea.

Given the challenges in accurately identifying unexposed controls in case-control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within 'control' children (0-59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea ('MSD pathogens') in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and 'any' (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case-control studies examining diarrhoea.

Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses.

Squamous cell carcinoma (SCC) is the most common cancer affecting the equine eye, with a higher incidence documented in Haflinger horses. Recently, a missense variant in the gene damage specific DNA binding protein 2 (DDB2, p.Thr338Met) on ECA12 was identified as a risk factor for the development of limbal SCC in Haflinger horses. SCC also occurs on the nictitating membrane; therefore, investigating the role of this missense variant in nictitating membrane SCC is warranted. In this study, a common ancestor was identified among Haflinger horses affected with limbal SCC or with nictitating membrane SCC, thus supporting a recessive risk factor for the development of cancer at both ocular locations. Analysis of genotype data from Haflinger horses with and without nictitating membrane SCC revealed that the same region on ECA12 associated with limbal SCC was also associated with nictitating membrane SCC (P < 2.04 × 10-5 ). Fine mapping of this locus using 25 cases and 49 controls supported the hypothesis that DDB2:c.1013C>T, p.Thr338Met, is a risk factor for nictitating membrane SCC, as 88% of our cases were homozygous for this variant and no other polymorphism was more strongly associated (P = 4.13 × 10-14 ). These data indicate that the genetic risk is the same for the development of both limbal and nictitating membrane SCC in Haflinger horses and validates utilization of genetic testing of the DDB2 variant for both clinical management and the guidance of mating decisions.

Ventral hippocampal neurons inhibit postprandial energy intake.

Evidence suggests that the memory of a recently ingested meal limits subsequent intake. Given that ventral hippocampal (vHC) neurons are involved in memory and energy intake, the present experiment tested the hypothesis that vHC neurons contribute to the formation of a memory of a meal and inhibit energy intake during the postprandial period. We tested (1) whether pharmacological inactivation of vHC neurons during the period following a sucrose meal, when the memory of the meal would be undergoing consolidation, accelerates the onset of the next sucrose meal and increases intake and (2) whether sucrose intake increases vHC expression of the synaptic plasticity marker activity-regulated cytoskeletal-associated protein (Arc). Adult male Sprague-Dawley rats were trained to consume a 32% sucrose solution daily at the same time and location. On the experimental day, the rats were given intra-vHC infusions of the GABAA receptor agonist muscimol or vehicle after they finished their first sucrose meal. Compared to vehicle infusions, postmeal intra-vHC muscimol infusions decreased the latency to the next sucrose meal, increased the amount of sucrose consumed during that meal, increased the total number of sucrose meals and the total amount of sucrose ingested. In addition, rats that consumed sucrose had higher levels of Arc expression in both vHC CA1 and CA3 subfields than cage control rats. Collectively, these findings are the first to show that vHC neurons inhibit energy intake during the postprandial period and support the hypothesis that vHC neurons form a memory of a meal and inhibit subsequent intake. © 2016 Wiley Periodicals, Inc.

Renal-infiltrating CD11c+ cells are pathogenic in murine lupus nephritis through promoting CD4+ T cell responses.

Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE), causing morbidity and mortality in 40-60% of SLE patients. The pathogenic mechanisms of LN are not completely understood. Recent studies have demonstrated the presence of various immune cell populations in lupus nephritic kidneys of both SLE patients and lupus-prone mice. These cells may play important pathogenic or regulatory roles in situ to promote or sustain LN. Here, using lupus-prone mouse models, we showed the pathogenic role of a kidney-infiltrating CD11c+ myeloid cell population in LN. These CD11c+ cells accumulated in the kidneys of lupus-prone mice as LN progressed. Surface markers of this population suggest their dendritic cell identity and differentiation from lymphocyte antigen 6 complex (Ly6C)low mature monocytes. The cytokine/chemokine profile of these renal-infiltrating CD11c+ cells suggests their roles in promoting LN, which was confirmed further in a loss-of-function in-vivo study by using an antibody-drug conjugate (ADC) strategy targeting CX3 CR1, a chemokine receptor expressed highly on these CD11c+ cells. However, CX3 CR1 was dispensable for the homing of CD11c+ cells into lupus nephritic kidneys. Finally, we found that these CD11c+ cells co-localized with infiltrating T cells in the kidney. Using an ex- vivo co-culture system, we showed that renal-infiltrating CD11c+ cells promoted the survival, proliferation and interferon-γ production of renal-infiltrating CD4+ T cells, suggesting a T cell-dependent mechanism by which these CD11c+ cells promote LN. Together, our results identify a pathogenic kidney-infiltrating CD11c+ cell population promoting LN progression, which could be a new therapeutic target for the treatment of LN.

Short-term effects of povidone iodine and sodium fluoride therapy on plaque levels and microbiome diversity.

OBJECTIVES: The objective of this study is to evaluate the effect of short-term changes in the oral microbial ecology of dental plaque and plaque levels after topical treatment of a combination of 10% povidone iodine (PI) and 5% sodium fluoride varnish (FV). MATERIALS AND METHODS: A single group design intervention study on 12 pediatric patients, who underwent two baseline plaques samplings before the intervention, were enrolled in the study. A modified mixed dentition Silness-Löe plaque index score was used to assess plaque accumulation and microbial composition was assessed by amplicon sequencing analysis of the 16S rRNA V4 region. RESULTS: Dental plaque accumulation (P = 0.0424) was reduced after 1 week using PI/FV application. This reduction was not observed between the two double-baseline visits. 16S rRNA analysis showed that the single PI/FV therapy did not have dramatic shifts in the plaque microbiome community depicted by hierarchical cluster and principle component analysis. More subtle changes were found when analyzing the Shannon diversity index after the application of PI/FV vs two baselines prior to combination therapy. CONCLUSIONS: The bacteria within the dental biofilms showed resilience in maintaining the overall community diversity but reduced biofilm accumulation following PI/FV therapy. Repeated uses of PI/FV may augment plaque control during dental rehabilitation in children.

N-Acetyl-l-cysteine effects on multi-species oral biofilm formation and bacterial ecology.

UNLABELLED: Future therapies for the treatment of dental decay have to consider the importance of preserving bacterial ecology while reducing biofilm adherence to teeth. A multi-species plaque-derived (MSPD) biofilm model was used to assess how concentrations of N-acetyl-l-cysteine (NAC) (0, 0·1, 1, 10%) affected the growth of complex oral biofilms. Biofilms were grown (n = 96) for 24 h on hydroxyapatite discs in BMM media with 0·5% sucrose. Bacterial viability and biomass formation was examined on each disc using a microtitre plate reader. In addition, fluorescence microscopy and Scanning Electron Microscopy was used to qualitatively examine the effect of NAC on bacterial biofilm aggregation, extracellular components and bacterial morphology. The total biomass was significantly decreased after exposure of both 1% (from 0·48, with a 95% confidence interval of (0·44, 0·57) to 0·35, with confidence interval (0·31, 0·38)) and 10% NAC (0·14 with confidence interval (0·11, 0·17)). 16S rRNA amplicon sequencing analysis indicated that 1% NAC reduced biofilm adherence while preserving biofilm ecology. SIGNIFICANCE AND IMPACT OF THE STUDY: As a compound with a wide safety margin, N-acetyl-l-cysteine (NAC) has the potential to be used as a long term anti-plaque bacteriostatic agent for managing chronic dental decay without substantially altering biofilm's bacterial ecology. The potential anti-caries benefit of NAC is directly related to reducing the biofilm coverage which reduces the degree of acid generation and the amount of time that the surface is exposed to a lower pH.

Overnight improvements in two REM sleep-sensitive tasks are associated with both REM and NREM sleep changes, sleep spindle features, and awakenings for dream recall.

Memory consolidation is associated with sleep physiology but the contribution of specific sleep stages remains controversial. To clarify the contribution of REM sleep, participants were administered two REM sleep-sensitive tasks to determine if associated changes occurred only in REM sleep. Twenty-two participants (7 men) were administered the Corsi Block Tapping and Tower of Hanoi tasks prior to and again after a night of sleep. Task improvers and non-improvers were compared for sleep structure, sleep spindles, and dream recall. Control participants (N = 15) completed the tasks twice during the day without intervening sleep. Overnight Corsi Block improvement was associated with more REM sleep whereas Tower of Hanoi improvement was associated with more N2 sleep. Corsi Block improvement correlated positively with %REM sleep and Tower of Hanoi improvement with %N2 sleep. Post-hoc analyses suggest Tower of Hanoi effects-but not Corsi Block effects-are due to trait differences. Sleep spindle density was associated with Tower of Hanoi improvement whereas spindle amplitude correlated with Corsi Block improvement. Number of REM awakenings for dream reporting (but not dream recall per se) was associated with Corsi Block, but not Tower of Hanoi, improvement but was confounded with REM sleep time. This non-replication of one of 2 REM-sensitive task effects challenges both 'dual-process' and 'sequential' or 'sleep organization' models of sleep-dependent learning and points rather to capacity limitations on REM sleep. Experimental awakenings for sampling dream mentation may not perturb sleep-dependent learning effects; they may even enhance them.

Laser Capture Microdissection of Feline Streptomyces spp Pyogranulomatous Dermatitis and Cellulitis.

Suspected Streptomyces spp infections were identified in 4 cats at UC Davis Veterinary Medical Teaching Hospital between 1982 and 2011. Three had ulcerated, dark red mycetomas involving the dermis, subcutis, and fascia with fistulous tracts and/or regional lymphadenopathy. One cat had pyogranulomatous mesenteric lymphadenitis. Granulomatous inflammation in all cats contained colonies of Gram-positive, non-acid-fast organisms. All 4 cats failed to respond to aggressive medical and surgical treatment and were euthanized. Laser capture microdissection (LCM) was used to selectively harvest DNA from the affected formalin-fixed, paraffin-embedded (FFPE) tissues. Cloned amplicons from LCM-derived tissue confirmed the presence of Streptomyces spp in the dermatitis cases. Amplicons from the remaining cat with peritoneal involvement aligned with the 16S ribosomal RNA gene for Actinomycetales. Usually considered a contaminant, Streptomyces spp can be associated with refractory pyogranulomatous dermatitis and cellulitis in cats with outdoor access. LCM is useful in the diagnosis of bacterial diseases where contamination may be an issue.

A comparative study of educational provision for children with neurogenetic syndromes: parent and teacher survey.

BACKGROUND: A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. METHOD: Parents (n = 381) and teachers (n = 204) of school-aged children with one of the four syndromes in the UK and Ireland were surveyed in a range of areas concerning the child's educational provision. Areas surveyed included school placement, views on the needs of children with the syndromes, desired changes to current provision and perceived teacher knowledge. RESULTS: School placement in mainstream settings decreased with age in all of the syndromes. Males with the syndromes were more likely to be in specialised educational settings with the exception of WS. Teachers reported limited input on initial or subsequent training for all of the syndromes. The majority of teachers did not view the needs of children with syndromes as different from other children with intellectual disability (ID) although there were significant differences between the syndromes. Changes deemed necessary to provision by parents and teachers differed between the syndromes indicating the existence of perceptions of syndrome specific needs. The lowest perceived level of teacher knowledge was in the VCFS group. CONCLUSION: The majority of teachers of children with neurogenetic syndromes report limited knowledge of the syndromes, but also a lack of belief that the children's needs are different from the majority of children with ID. Differences between the syndromes in some areas of provision suggest that a child's syndrome does impact on educational provision in some areas.

ASD, ADHD, mental health conditions and psychopharmacology in neurogenetic syndromes: parent survey.

BACKGROUND: There are a number of neurogenetic syndromes with well described behavioural phenotypes including fragile X syndrome, Prader-Willi syndrome, Williams syndrome and velo-cardio-facial syndrome (VCFS). Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and psychiatric conditions are often associated with the syndromes. METHOD: Parents (n = 381) of school-aged children with one of the four syndromes in the UK and Ireland were asked whether their child had been professionally diagnosed with ASD, ADHD or a mental health condition. Parents were also asked whether their child had been prescribed medication for behavioural or psychiatric reasons. RESULTS: The highest level of reported diagnoses of ASD and ADHD was in fragile X syndrome. In all syndrome groups, lower rates of diagnosis were reported in comparison to previously published research. Prescribing of medication for behavioural/psychiatric reasons was highest in fragile X syndrome although the highest usage of melatonin was in Williams syndrome. CONCLUSION: Reasons for a lower recognition of ASD, ADHD and mental health conditions in clinical practice compared with research studies may include 'diagnostic overshadowing' due to presence of intellectual disability and a genetic syndrome. However, there may also be a lack of belief in the utility of such diagnoses in neurogenetic syndromes among relevant professionals and/or lack of access to professionals with sufficient expertise in the recognition of such diagnoses in those with neurogenetic syndromes. The low rates of prescribing of medication for behavioural/psychiatric reasons may reflect the low level of clinical diagnoses or lack of belief in the utility of psychopharmacology in this population.

Biofilm community diversity after exposure to 0·4% stannous fluoride gels.

AIMS: To test the effect of 0·4% stannous fluoride (SnF2 ) glycerine-based gels on specific portions of the bacterial community in both a clinical observational study and in vitro multispecies plaque-derived (MSPD) biofilm model. METHODS AND RESULTS: Potential changes to specific portions of the bacterial community were determined through the Human Oral Microbial Identification Microarray (HOMIM). Both the observational clinical study and the biofilm model showed that short-term use of 0·4% SnF2 gel has little effect on the bacterial community depicted by hierarchical cluster analysis. The amount of plaque accumulation on a subject's teeth, which was measured by plaque index scores, failed to show statistical significant changes over the two baselines or after treatment (P = 0·9928). The in vitro results were similar when examining the effect of 0·4% SnF2 gels on biofilm adherence through a crystal violet assay (P = 0·1157). CONCLUSIONS: The bacteria within the dental biofilms showed resilience in maintaining the overall community diversity after exposure to 0·4% SnF2 topical gels. SIGNIFICANCE AND IMPACT OF THE STUDY: The study supports that the immediate benefits of using 0·4% SnF2 gels in children may be strictly from fluoride ions inhibiting tooth demineralization rather than delivering substantial antimicrobial effects.

Mental health in secondary school-aged children with epilepsy and their primary caregivers: A case control study.

PURPOSE: To describe the prevalence and associated factors of mental health problems in secondary school-aged (11-16 years) children with epilepsy and their primary caregivers compared to a control group without epilepsy. METHODS: Children with epilepsy (n = 60), controls (n = 49), and caregivers (n = 60 epilepsy and n = 49 control group) completed a measure of the child's mental health (Strengths and Difficulties Questionnaire; SDQ). Primary caregivers in both groups completed a measure of their own mental health (Depression, Anxiety, and Stress Scale-21; DASS-21). Factors associated with child and caregiver mental health in the epilepsy group were explored using linear regression. RESULTS: There were no significant differences between the epilepsy and control group regarding age, gender, ethnicity and socioeconomic status. A higher proportion of children with epilepsy scored in the at-risk range on the SDQ indicating more mental health problems than the control group, as reported by the children (45% vs. 24 %) (p = 0.026) and caregivers (52% vs. 14 %) (p < 0.001). Primary caregivers of children with epilepsy had more symptoms of depression (p = 0.001), anxiety (p = 0.028) and stress (p = 0.019) than caregivers in the control group. Children with epilepsy with greater motor coordination problems had greater mental health difficulties. Children with epilepsy with more mental health difficulties had caregivers with more difficulties and caregivers of children with earlier onset of seizures had more mental health difficulties. CONCLUSIONS: Epilepsy confers a high risk for mental health problems in adolescents and their primary caregivers. There is a need to better understand the relationship between caregiver and child mental health difficulties in epilepsy.

Schooling experiences in children with long-gap esophageal atresia compared with children with esophageal atresia and primary anastomosis: a Swedish study.

BACKGROUND: Children with long-gap esophageal atresia (LGEA) risk living with aerodigestive morbidity and mental health difficulties. No previous study has investigated their experiences of schooling, despite the importance of schools in children's development, learning and social relationships. We aimed to describe experiences of schooling in children with LGEA in Sweden in comparison with children with EA who had primary anastomosis. METHOD: Children with LGEA aged 3-17 were recruited nationwide in Sweden. One parent completed a survey on their child's school-based supports (according to definitions from the Swedish National Agency for Education), school absence, school satisfaction, school functioning (PedsQL 4.0), mental health (Strength and Difficulties Questionnaire) and current symptomatology. School data were compared between 26 children with LGEA to that from 95 children with EA who had PA, a hypothesized milder affected group. Mental health level was determined using validated norms; abnormal ≥ 90 percentile. Data were analyzed using descriptives, correlation and Mann-Whitney-U test. Significance level was p < 0.05. RESULTS: Formal school-based support was reported in 17 (65.4%) children with LGEA and concerned support with nutritional intake (60%), education (50%) and medical/special health needs (35%). The prevalence of school-based support was significantly higher compared to children with PA overall (36.8%, p = 0.013) and regarding nutritional intake support (20%, p < 0.001). In children with LGEA, school-based support was related to low birth weight (p = 0.036), young child age (p = 0.014), height ≤ -2SD for age/sex (p = 0.024) and an increased number of aerodigestive symptoms (p < 0.05). All children with LGEA who had abnormal mental health scores had school-based support, except for one child. Nine children with LGEA (36%) had school absence ≥ 1times/month the past year, more frequently because of colds/airway infections (p = 0.045) and GI-specific problems compared to PA (p = 0.003). School functioning scores were not significantly different from children with PA (p = 0.34) but correlated negatively with school-based support (< 0.001) and school absence (p = 0.002). One parent out of 26 reported their child's school satisfaction as "not good". CONCLUSIONS: Children with LGEA commonly receive school-based support, reflecting multifaceted daily needs and disease severity. School absence is frequent and related to poorer school functioning. Future research focusing on academic achievement in children with EA is needed.

A reproducible oral microcosm biofilm model for testing dental materials.

AIMS: Most studies of biofilm effects on dental materials use single-species biofilms, or consortia. Microcosm biofilms grown directly from saliva or plaque are much more diverse, but difficult to characterize. We used the Human Oral Microbial Identification Microarray (HOMIM) to validate a reproducible oral microcosm model. METHODS AND RESULTS: Saliva and dental plaque were collected from adults and children. Hydroxyapatite and dental composite discs were inoculated with either saliva or plaque, and microcosm biofilms were grown in a CDC biofilm reactor. In later experiments, the reactor was pulsed with sucrose. DNA from inoculums and microcosms was analysed by HOMIM for 272 species. Microcosms included about 60% of species from the original inoculum. Biofilms grown on hydroxyapatite and composites were extremely similar. Sucrose pulsing decreased diversity and pH, but increased the abundance of Streptococcus and Veillonella. Biofilms from the same donor, grown at different times, clustered together. CONCLUSIONS: This model produced reproducible microcosm biofilms that were representative of the oral microbiota. Sucrose induced changes associated with dental caries. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first use of HOMIM to validate an oral microcosm model that can be used to study the effects of complex biofilms on dental materials.

Role of L-type calcium channels in altered microvascular responses to propofol in hypertension.

BACKGROUND: Propofol acts as an L-type calcium channel (LTCC) antagonist to decrease peripheral resistance and initiate hypotension. This study investigated LTCC sensitivity/expression in hypertension and the role of LTCCs in exaggerated hypotension to propofol in this situation. METHODS: Age-matched 12- to 15-week-old normotensive rats [male Wistar Kyoto (WKY)] and spontaneously hypertensive rats (SHR) were used. Propofol (10 mg kg(-1), 10-50 mg kg(-1) h(-1) i.v.) was administered and the mesenteric microcirculation (<70 µm) observed with fluorescent in vivo microscopy using fluorescein isothiocyanate-conjugated bovine serum albumin (100 mg kg(-1) i.v.). Western blotting was used to measure tissue expression of the α(1C) LTCC subtype. Pressure myography was used to assess isolated mesenteric arterioles (<350 µm) in response to BAYK8644 (0.1 nM-1 µM), a specific LTCC channel agonist. RESULTS: Propofol dilated isolated arterioles {336.6 µM [mean (sd) change 16.2 (5.8)%]}. However, constriction to BAYK8644 was reduced at this concentration of propofol [EC(50)=8.3 (0.1) log mol(-1)] compared with controls [7.4 (0.1) log mol(-1), P<0.05], suggesting that propofol inhibited LTCCs. The sensitivity of LTCCs increased during hypertension, as in vivo there was a greater increase in mean arterial pressure (MAP) to BAYK8644 [10 µg kg(-1), WKY: 59.5 (9.3)%; SHR: 97.7 (6.3)%, P<0.05] with exaggerated constriction of arterioles [10 µg kg(-1), WKY: 9.1 (2.5)%; SHR: 19.1 (2.6)%, P<0.05]. Propofol also decreased MAP in SHR over time (P<0.05), but remained unchanged in WKY. Using western blotting, expression of α(1C) was greater in SHR compared with WKY (P<0.05). CONCLUSIONS: Propofol acts via LTCC channels, with increased channel expression and sensitivity in genetically hypertensive rats. We suggest that increased sensitivity and expression of LTCCs may be a mechanism for exaggerated hypertension during propofol anaesthesia.

Immunohistochemical characteristics of normal canine eyes.

Immunohistochemistry is widely utilized in diagnostic laboratories to study neoplastic and nonneoplastic diseases. Knowledge of the immunohistochemical characteristics of normal tissue is essential for interpretation of immunoreactivity in pathologic conditions. In this study, immunohistochemistry was performed with a broad panel of diagnostically relevant antibodies on 4 normal canine globes--namely, vimentin, pan-cytokeratin (AE1/AE3), cytokeratin 7, cytokeratin 8/18, cytokeratin 20, α-smooth muscle actin, muscle specific actin, desmin, Melan-A, microphthalmia transcription factor, S-100, glial fibrillary acidic protein, triple neurofilaments, neuron-specific enolase, chromogranin A, synaptophysin, laminin and CD31. Results include cytokeratin immunoreactivity limited to the conjunctival epithelium, corneal epithelium, and retinal pigment epithelium; distinct patterns of immunopositivity of muscle markers; and widespread immunoreactivity for vimentin and most neural/neuroendocrine markers. These findings in normal eyes provide the basis for interpretation of ocular immunohistochemistry in dogs. Published immunophenotypes of primary ocular neoplasms are also reviewed.