Polyaromatic hydrocarbons in pollution: a heart-breaking matter.

Air pollution is associated with detrimental effects on human health, including decreased cardiovascular function. However, the causative mechanisms behind these effects have yet to be fully elucidated. Here we review the current epidemiological, clinical and experimental evidence linking pollution with cardiovascular dysfunction. Our focus is on particulate matter (PM) and the associated low molecular weight polycyclic aromatic hydrocarbons (PAHs) as key mediators of cardiotoxicity. We begin by reviewing the growing epidemiological evidence linking air pollution to cardiovascular dysfunction in humans. We next address the pollution-based cardiotoxic mechanisms first identified in fish following the release of large quantities of PAHs into the marine environment from point oil spills (e.g. Deepwater Horizon). We finish by discussing the current state of mechanistic knowledge linking PM and PAH exposure to mammalian cardiovascular patho-physiologies such as atherosclerosis, cardiac hypertrophy, arrhythmias, contractile dysfunction and the underlying alterations in gene regulation. Our aim is to show conservation of toxicant pathways and cellular targets across vertebrate hearts to allow a broad framework of the global problem of cardiotoxic pollution to be established. AhR; Aryl hydrocarbon receptor. Dark lines indicate topics discussed in this review. Grey lines indicate topics reviewed elsewhere.

Association of size-fractionated indoor particulate matter and black carbon with heart rate variability in healthy elderly women in Beijing.

Associations between size-fractionated indoor particulate matter (PM) and black carbon (BC) and heart rate variability (HRV) and heart rate (HR) in elderly women remain unclear. Twenty-nine healthy elderly women were measured for 24-hour HRV/HR indices. Real-time size-fractionated indoor PM and BC were monitored on the same day and on the preceding day. Mixed-effects models were applied to investigate the associations between pollutants and HRV/HR indices. Increases in size-fractionated indoor PM were significantly associated with declines in power in the high-frequency band (HF), power in the low-frequency band (LF), and standard deviation of all NN intervals (SDNN). The largest decline in HF was 19% at 5-minute moving average for an interquartile range (IQR) increase (24 µg/m3 ) in PM0.5 . The results showed that smaller particles could lead to greater reductions in HRV indices. The reported associations were modified by body mass index (BMI): Declines in HF at 5-minute average for an IQR increase in PM0.5 were 34.5% and 1.0% for overweight (BMI ≥25 kg/m2 ) and normal-weight (BMI <25 kg/m2 ) participants, respectively. Moreover, negative associations between BC and HRV indices were found to be significant in overweight participants. Increases in size-fractionated indoor PM and BC were associated with compromised cardiac autonomic function in healthy elderly women, especially overweight ones.

Cardiovascular benefits of reducing personal exposure to traffic-related noise and particulate air pollution: A randomized crossover study in the Beijing subway system.

To assess the cardiovascular benefits of protecting against particulate air pollution and noise, we conducted a randomized crossover study with 40 young healthy college students from March to May 2017 in the underground subway, Beijing. Participants each received 4 treatments (no intervention phase [NIP], respirator intervention phase [RIP], headphone intervention phase [HIP], respirator plus headphone intervention phase [RHIP]) in a randomized order during 4 different study periods with 2-week washout intervals. We measured personal exposure to particulate matter (PM), noise and electrocardiogram (ECG) parameters (heart rate variability (HRV), heart rate (HR) and ST segment changes), ambulatory blood pressure (BP) continuously for 4 hours to investigate the cardiovascular effects. Compared with NIP, most of the HRV parameters increased, especially high frequency (HF) [21.1% (95% CI: 15.7%, 26.9%), 18.2% (95% CI: 12.8%, 23.9%), and 35.5% (95% CI: 29.3%, 42.0%) in RIP, HIP, and RHIP, respectively], whereas ST segment elevation and HR decreased for all 3 modes of interventions. However, no significant differences were observed in BP among the 4 treatments. In summary, short-term wearing of a respirator and/or headphone may be an effective way to minimize cardiovascular risk induced by air pollution in the subway by improving autonomic nervous function.

On the origins and genetic diversity of South American chickens: one step closer.

Local chicken populations are a major source of food in the rural areas of South America. However, very little is known about their genetic composition and diversity. Here, we analyzed five populations from South America to investigate their maternal genetic origin and diversity, hoping to mitigate the lack of information on local chicken populations from this region. We also included three populations of chicken from the Iberian Peninsula and one from Easter Island, which are potential sources of the first chickens introduced in South America. The obtained sequencing data from South American chickens indicate the presence of four haplogroups (A, B, E and D) that can be further subdivided into nine sub-haplogroups. Of these, four (B1, D1a, E1a(b), E1b) were absent from local Iberian Peninsula chickens and one (D1a) was present only on Easter Island. The presence of the sub-haplogroups A1a(b) and E1a(b) in South America, previously only observed in Eastern Asia, and the significant population differentiation between Iberian Peninsula and South American populations, suggest a second maternal source of the extant genetic pool in South American chickens.

New concepts for expressing forced expiratory volume in 1 s arising from survival analysis.

Spirometric lung function is partly determined by sex, age and height (Ht). Commonly, lung function is expressed as a percentage of the predicted value (PP) in order to account for these effects. Since the PP method retains sex, age and Ht bias, forced expiratory volume in 1 s (FEV(1)) standardised by powers of Ht and by a new sex-specific lower limit (FEV(1) quotient (FEV(1)Q)) were investigated to determine which method best predicted all-cause mortality in >26,967 patients and normal subjects. On multivariate analysis, FEV(1)Q was the best predictor, with a hazard ratio for the worst decile of 6.9 compared to 4.1 for FEV(1)PP. On univariate analysis, the hazard ratios were 18.8 compared to 6.1, respectively; FEV(1) x Ht(-3) was the next-best predictor of survival. Median survival was calculated for simple cut-off values of FEV(1)Q and FEV(1) x Ht(-3). These survival curves were accurately fitted (r(2) = 1.0) by both FEV(1)Q and FEV(1) x Ht(-3) values expressed polynomially, and so an individual's test result could be used to estimate survival (with sd for median survival of 0.22 and 0.61 yrs, respectively). It is concluded that lung function impairment should be expressed in a new way, here termed the FEV(1)Q, or, alternatively, as FEV(1) x Ht(-3), since these indices best relate spirometric lung function to all-cause mortality and survival.

Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study.

There is some evidence that chronic obstructive pulmonary disease (COPD) and metabolic syndrome may be related, perhaps through systemic inflammation, which is common to both. However, the association between the two conditions has not yet been clearly shown. The present study involved 7,358 adults aged > or =50 yrs from a population-based survey who underwent spirometry, a structured interview and measurement of fasting metabolic marker levels. Airflow obstruction (forced expiratory volume in 1 s/forced vital capacity ratio of less than the lower limit of normal) was present in 6.7%, and the International Diabetes Federation metabolic syndrome criteria were met by 20.0%. The risk of metabolic syndrome was higher in those with airflow obstruction than in those without (odds ratio (OR) 1.47; 95% confidence interval (CI) 1.12-1.92), after controlling for potential confounders. Of the five components of metabolic syndrome, only central obesity was significantly associated with airflow obstruction (OR 1.43; 95% CI 1.09-1.88) after adjusting for body mass index. A similar association was observed in both never and current smokers. In this Chinese sample, airflow obstruction was associated with metabolic syndrome, and, in particular, its central obesity component. This may help explain the increased risk of cardiovascular diseases in COPD, and so could guide future clinical practice.

Passive smoking exposure and risk of COPD among adults in China: the Guangzhou Biobank Cohort Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in China, where the population is also exposed to high levels of passive smoking, yet little information exists on the effects of such exposure on COPD. We examined the relation between passive smoking and COPD and respiratory symptoms in an adult Chinese population. METHODS: We used baseline data from the Guangzhou Biobank Cohort Study. Of 20 430 men and women over the age of 50 recruited in 2003-06, 15,379 never smokers (6497 with valid spirometry) were included in this cross-sectional analysis. We measured passive smoking exposure at home and work by two self-reported measures (density and duration of exposure). Diagnosis of COPD was based on spirometry and defined according to the GOLD guidelines. FINDINGS: There was an association between risk of COPD and self-reported exposure to passive smoking at home and work (adjusted odds ratio 1.48, 95% CI 1.18-1.85 for high level exposure; equivalent to 40 h a week for more than 5 years). There were significant associations between reported respiratory symptoms and increasing passive smoking exposure (1.16, 1.07-1.25 for any symptom). INTERPRETATION: Exposure to passive smoking is associated with an increased prevalence of COPD and respiratory symptoms. If this association is causal, we estimate that 1.9 million excess deaths from COPD among never smokers could be attributable to passive smoking in the current population in China. Our findings provide strong evidence for urgent measures against passive smoking in China.

Using the lower limit of normal for the FEV1/FVC ratio reduces the misclassification of airway obstruction.

AIM: The prevalence of airway obstruction varies widely with the definition used. OBJECTIVES: To study differences in the prevalence of airway obstruction when applying four international guidelines to three population samples using four regression equations. METHODS: We collected predicted values for forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) and its lower limit of normal (LLN) from the literature. FEV(1)/FVC from 40 646 adults (including 13 136 asymptomatic never smokers) aged 17-90+years were available from American, English and Dutch population based surveys. The prevalence of airway obstruction was determined by the LLN for FEV(1)/FVC, and by using the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society/European Respiratory Society (ATS/ERS) or British Thoracic Society (BTS) guidelines, initially in the healthy subgroup and then in the entire population. RESULTS: The LLN for FEV(1)/FVC varied between prediction equations (57 available for men and 55 for women), and demonstrated marked negative age dependency. Median age at which the LLN fell below 0.70 in healthy subjects was 42 and 48 years in men and women, respectively. When applying the reference equations (Health Survey for England 1995-1996, National Health and Nutrition Examination Survey (NHANES) III, European Community for Coal and Steel (ECCS)/ERS and a Dutch population study) to the selected population samples, the prevalence of airway obstruction in healthy never smokers aged over 60 years varied for each guideline: 17-45% of men and 7-26% of women for GOLD; 0-18% of men and 0-16% of women for ATS/ERS; and 0-9% of men and 0-11% of women for BTS. GOLD guidelines caused false positive rates of up to 60% when applied to entire populations. CONCLUSIONS: Airway obstruction should be defined by FEV(1)/FVC and FEV(1) being below the LLN using appropriate reference equations.

Recent developments in nitric oxide donor drugs.

During the 1980s, the free radical, nitric oxide (NO), was discovered to be a crucial signalling molecule, with wide-ranging functions in the cardiovascular, nervous and immune systems. Aside from providing a credible explanation for the actions of organic nitrates and sodium nitroprusside that have long been used in the treatment of angina and hypertensive crises respectively, the discovery generated great hopes for new NO-based treatments for a wide variety of ailments. Decades later, however, we are still awaiting novel licensed agents in this arena, despite an enormous research effort to this end. This review explores some of the most promising recent advances in NO donor drug development and addresses the challenges associated with NO as a therapeutic agent.

WITHDRAWN: Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter.

BACKGROUND: Atrial fibrillation (AF) carries a high risk of stroke and other thromboembolic events. Appropriate use of drugs to prevent thromboembolism in patients with AF involves comparing the patient's risk of stroke to the risk of hemorrhage from medication use. OBJECTIVES: To quantify risk of stroke, major hemorrhage and death from using medications that have been rigorously evaluated for prevention of thromboembolism in AF. SEARCH STRATEGY: Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until December 1999. SELECTION CRITERIA: Included Randomized controlled trials of drugs to prevent thromboembolism in adults with non-postoperative AF. Excluded RCTS of patients with rheumatic valvular disease. DATA COLLECTION AND ANALYSIS: Data were abstracted by two reviewers. Odds ratios from all qualitatively similar studies were combined, with weighting by study size, to yield aggregate odds ratios for stroke, major hemorrhage, and death for each drug. MAIN RESULTS: Fourteen articles were included in this review. Warfarin was more efficacious than placebo for primary stroke prevention {aggregate odds ratio (OR) of stroke=0.30 [95% Confidence Interval (C.I.) 0.19,0.48]}, with moderate evidence of more major bleeding { OR= 1.90 [95% C.I. 0.89,4.04].}. Aspirin was inconclusively more efficacious than placebo for stroke prevention {OR=0.68 [95% C.I. 0.29,1.57]}, with inconclusive evidence regarding more major bleeds {OR=0.81[95% C.I. 0.37,1.78]}. For primary prevention, assuming a baseline risk of 45 strokes per 1000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was moderate evidence for fewer strokes among patients on warfarin than on aspirin {aggregate OR=0.64[95% C.I. 0.43,0.96]}, with only suggestive evidence for more major hemorrhage {OR =1.58 [95% C.I. 0.76,3.27]}. However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared to aspirin was low (5.5 per 1000 person-years) compared to an older group (15 per 1000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin. AUTHORS' CONCLUSIONS: The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke, although clearly there is a risk of hemorrhage. Although not definitively supported by the evidence, aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke, with less risk of hemorrhage than with warfarin. Further studies are needed of low- molecular weight heparin and aspirin in lower risk patients.

Down-regulation of vinculin upon MK886-induced apoptosis in LN18 glioblastoma cells.

Glioblastomas are a type of malignant brain tumor and are among the most difficult cancers to treat. One strategy to treat aggressive cancers is the use of drugs that target multiple signaling pathways. MK886 is a drug known to inhibit both 5- lipoxygenase-activating-protein (FLAP) and peroxisome proliferator activated receptor-alpha (PPAR-alpha). The objectives of this study were to investigate the ability of MK886 to induce apoptotic cell death in LN18 glioblastoma cells and to characterize the cell death mechanisms. MK886 induced massive apoptotic LN18 cell death that was manifested by the release of nucleosomes, annexinV binding to phosphatidylserine in the absence of nuclear staining, and changes in the fluorescent intensity of Mito Tracker Deep Red 633 indicating changes in mitochondrial oxidative function and mass. The alteration of the mitochondrial function implied that MK886 induced apoptosis in LN18 cells via a mitochondrial pathway. The broad caspases inhibitor ZVAD-FMK inhibited MK886-induced nucleosome release, but not annexinV binding or MK886-altered mitochondrial function. Real time RT-PCR demonstrated that LN18 cells expressed significant levels of FLAP and PPAR- alpha mRNAs. A low level of arachidonate 5-lipoxygenase (ALOX-5) mRNA was detected, but little, if any, arachidonate 12- lipoxygenase (ALOX-12) mRNA was present. In addition, MK886-induced apoptosis in LN18 cells was accompanied by a decrease in the protein and mRNA levels of vinculin, but not other focal adhesion proteins. In summary, the data presented here indicate that disruption of the actin-vinculin-cell-cytoskeleton matrix of the LN18 glioblastoma is a component of the MK886 induced apoptosis. In addition, MK886 treated LN18 cells could provide one model in which to investigate drugs that target lipoxygenase and PPAR-alpha pathways in the chemotherapeutic treatment of glioblastomas.

Whole-eye transplantation: a look into the past and vision for the future.

Blindness afflicts ~39 million people worldwide. Retinal ganglion cells are unable to regenerate, making this condition irreversible in many cases. Whole-eye transplantation (WET) provides the opportunity to replace diseased retinal ganglion cells, as well as the entire optical system and surrounding facial tissue, if necessary. Recent success in face transplantation demonstrates that this may be a promising treatment for what has been to this time an incurable condition. An animal model for WET must be established to further enhance our knowledge of nerve regeneration, immunosuppression, and technical aspects of surgery. A systematic review of the literature was performed to evaluate studies describing animal models for WET. Only articles in which the eye was completely enucleated and reimplanted were included. Study methods and results were compared. In the majority of published literature, WET can result in recovery of vision in cold-blooded vertebrates. There are a few instances in which mammalian WET models demonstrate survival of the transplanted tissue following neurovascular anastomosis and the ability to maintain brief electroretinogram activity in the new host. In this study we review in cold-blooded vertebrates and mammalian animal models for WET and discuss prospects for future research for translation to human eye transplantation.

Hepatic cellular distribution of cytochrome P-450 IA1 in rainbow trout (Oncorhynchus mykiss): an immunohisto- and cytochemical study.

Monoclonal antibody 1-12-3 reactive against scup (Stenotomus chrysops) cytochrome P450 E (a teleost CYP IA1) has been used to immunohistochemically localize CYP IA1 within hepatocytes and presumably sinusoidal endothelial and biliary epithelial cells of scup and trout. The goal of the present study was to extend immunohistochemical studies to the ultrastructural level determining intracellular locations of CYP IA1 in fish liver. Juvenile trout (5-10 g) were given i.p. injections once (50 micrograms/g b beta-naphthoflavone in cod liver oil; 0.5-ml injectate volume). After 5 days, livers were fixed (0.25% glutaraldehyde) via vascular in situ perfusion, removed, cut in 100-microns slices, infiltrated, and embedded in LR White monomer. Ultrathin sections of exposed livers were incubated in monoclonal antibody 1-12-3, rabbit anti-mouse IgG, and protein G colloidal gold. Membranes of granular endoplasmic reticulum in perinuclear regions of hepatocytes were consistently labeled. In addition, hepatocyte plasma membrane, particularly microvilli at bile canaliculi, was labeled. Biliary epithelial cells were labeled on luminal plasma membrane surrounding biliary passageway. Plasma membrane facing sinusoid and immediately subjacent cytoplasm was labeled in endothelial cells. Presence of CYP IA1 in sinusoidal endothelium could contribute to detoxication and/or bioactivation of blood borne chemicals. Granular endoplasmic reticulum was not uniformly labeled in hepatocytes. Rather, distribution seemed sequestered within highly specific regions and not dispersed along all membrane surfaces. Localization within biliary epithelial cells could signify potential of this cell type to bioactivate polycyclic aromatic hydrocarbons and may explain the common finding of biliary as well as hepatocytic tumors of trout liver.

A fast click-slow release strategy towards the HPLC-free synthesis of RNA.

A general strategy for purification of oligonucleotides synthesized by solid phase synthesis is described. It is based on a recently developed concept involving a bio-orthogonal inverse electron demand Diels-Alder reaction between trans-cyclooctene and tetrazine, termed 'click-to-release'. The strategy has been applied towards the synthesis and purification of a model hairpin RNA strand, as well as a 34 nt long aptamer.

Lack of association of human immunodeficiency virus seroconversion with visits to foreign ports in US Navy personnel.

BACKGROUND: The US Navy visits ports on all continents and many islands of the world, many of which are reported to have a high endemicity of human immunodeficiency virus (HIV) infection. The objective of this study was to determine whether visits to foreign ports by active-duty navy personnel were associated with increased risk of HIV infection. METHODS: The Naval Health Research Center in San Diego, Calif, maintains records of all HIV enzyme-linked immunosorbent assay and Western blot tests given in the navy. This information, along with career histories and ship movement data, was used in a nested case-control design to examine the relationship between visits to the 100 foreign ports most frequently visited by the navy and risk of HIV seroconversion. All visits to a port and total time in each port during the study period were examined. A total of 813 seroconverters were matched to 6993 seronegative active-duty controls by age, race, sex, occupational group, home port, and year of test. RESULTS: Estimated relative risks of seroconversion associated with visits to foreign ports showed no statistically significant excess risk of HIV infection for navy personnel after visits to any foreign port. CONCLUSIONS: These results do not imply that an individual's risk of acquisition of HIV would be less in a foreign port if the individual engaged in high-risk activity there. Rather, they imply that despite the mobility of the US Navy and the large variation in HIV seroprevalence rates throughout the world, navy personnel generally do not appear to be acquiring HIV infections abroad.

The development and characterization of a 57K single nucleotide polymorphism array for rainbow trout.

In this study, we describe the development and characterization of the first high-density single nucleotide polymorphism (SNP) genotyping array for rainbow trout. The SNP array is publically available from a commercial vendor (Affymetrix). The SNP genotyping quality was high, and validation rate was close to 90%. This is comparable to other farm animals and is much higher than previous smaller scale SNP validation studies in rainbow trout. High quality and integrity of the genotypes are evident from sample reproducibility and from nearly 100% agreement in genotyping results from other methods. The array is very useful for rainbow trout aquaculture populations with more than 40 900 polymorphic markers per population. For wild populations that were confounded by a smaller sample size, the number of polymorphic markers was between 10 577 and 24 330. Comparison between genotypes from individual populations suggests good potential for identifying candidate markers for populations' traceability. Linkage analysis and mapping of the SNPs to the reference genome assembly provide strong evidence for a wide distribution throughout the genome with good representation in all 29 chromosomes. A total of 68% of the genome scaffolds and contigs were anchored through linkage analysis using the SNP array genotypes, including ~20% of the genome assembly that has not been previously anchored to chromosomes.

Implementation of feeding guidelines in infants at risk of intestinal failure.

OBJECTIVE: To implement feeding guidelines to reduce advancement time and the incidence of parenteral nutrition-associated liver disease (PNALD) among intestinal surgical infants requiring parenteral nutrition (PN). STUDY DESIGN: Feeding guidelines with higher initial enteral nutrition (EN) volume and specific advancement criteria were implemented for surgical infants aged <6 months. Preimplementation and postimplementation outcomes were compared. RESULTS: There were 57 preimplementation and 33 postimplementation infants. The initial EN volume improved from 10 to 20 ml kg(-1) day(-1) (P<0.001). Time to reach 50% of goal calories from EN decreased by a median of 6 days (P=0.012) without a change in necrotizing enterocolitis incidence after resuming feeding. PNALD incidence decreased from 70% to 48% (P=0.046), and median peak direct bilirubin (DB) decreased from 5.6 to 2.3 mg dl(-1) (P=0.011). CONCLUSION: Feeding guideline implementation with higher initial feeding volume was well tolerated and resulted in faster achievement of 50% goal EN calories. PNALD incidence and peak DB were reduced.

The cochlear nuclei of snakes.

The cochlear nuclei of three burrowing snakes (Xenopeltis unicolor, Cylindrophis rufus, and Eryx johni) and three non-burrowing snakes (Epicrates cenchris, Natrix sipedon, and Pituophis catenifer) were studied. The posterior branch of the statoacoustic nerve and its posterior ganglion were destroyed and the degenerated nerve fibers and terminals traced to primary cochlear nuclei in 13 specimens of Pituophis catenifer. All these snake species possess three primary and one secondary cochlear nuclei. The primary cochlear nuclei consist of a small nucleus angularis located at the cerebello-medullary junction and a fairly large nucleus magnocellularis forming a dorsal cap over the cephalic end of the alar eminence. Nucleus magnocellularis may be subdivided into a medially placed group of rounder cells, nucleus magnocellularis medialis, and a laterally placed group of more ovate and paler-staining cells, nucleus magnocellularis lateralis. A small but well-defined secondary nucleus which showed no degenerated nerve terminals after nerve root section, nucleus laminaris, underlies the cephalic part of both nucleus magnocellularis medialis and nucleus magnocellularis lateralis. Larger and better-developed cochlear nuclei were found in burrowing species than in non-burrowing species of snakes. Of the three burrowing species studied, Xenopeltis showed the greatest development of cochlear nuclei; Eryx cochlear nuclei were not quite as large but were better differentiated than in Xenopeltis; and Cylindrophis cochlear nuclei were fairly large but not as well developed nor as well differentiated as in either Xenopeltis or Eryx. The cochlear nuclei of the three non-burrowing snakes, Epicrates, Natrix, and Pituophis, were not as large nor as well developed as those of the burrowing snakes. There is some, but not complete, correlation between cochlear development and papilla basilaris length and number of hair cells. Thus, Xenopeltis and Eryx, with well-developed cochlear nuclei, have relatively long papillae basilares; but the boid, Epicrates, with less well-developed cochlear nuclei, has a fairly well-developed papilla basilaris. Cylindrophis, a burrowing species, shows only a moderate degree of cochear nuclei and papilla basilaris development. The non-burrowers, Natrix and Pituophis, have both small cochlear nuclei and relatively short papillae basilares.