FMR protein: Evidence of an emerging role in retinal aging?

Aging is a multifactorial process that affects the entire organism by cumulative alterations. Visual function impairments that go along with aging are commonly observed, causing lower visual acuity, lower contrast sensitivity, and impaired dark adaptation. Electroretinogram analysis revealed that the amplitudes of rod- and cone-mediated responses are reduced in aged mice and humans. Reports suggested that age-related changes observed in both rod and cone photoreceptor functionality were linked to oxidative stress regulation or free radical production homeostasis. Interestingly, several recent reports linked the fragile X mental retardation protein (FMRP) cellular activity with oxidative stress regulation in several tissue including brain tissue where FMRP participates to the response to stress via protein translation in neurite or is involved in free radical production and abnormal glutathione homeostasis. Based on these recent literatures, we raised the question about the effect of FMRP absence in the aging retina of Fmr1-/y compared to their WT littermates. Indeed, up to now, only young or adult mice (<6 months) were investigated and have shown a specific retinal phenotype. Herein, we demonstrated that Fmr1-/y mice do not present the aging effect on retinal function observed in WT littermates since ERG a- and b-waves amplitudes as well as oscillatory potentials amplitudes were not collapsed with age (12/18 months old). Absence of FMRP and its consequences seem to protect the retina against aging effect, rising a pivotal role of FMRP in retinal aging process.

Use of the traditional halibut hook of the Makah Tribe, the cibu.d, reduces bycatch in recreational halibut fisheries.

A previous study found that use of the traditional halibut hook (cibu.d) of the Makah Tribe in present day recreational Pacific halibut (Hippoglossus stenolepis) fisheries significantly reduced bycatch compared to paired 8/0 circle hooks. The study also found that the cibu.d had a significantly reduced catch of halibut, but that the reduction may have been due to manufacturing flaws in the cibu.d used in the study. In this two-phased study, we first compared the fishing performance of redesigned cibu.d made from four different materials: brass, stainless steel, plastic, and wood. In the second phase, we compared the fishing performance of the brass cibu.d with two common recreational fishing set-ups: a single large 16/0 circle hook and paired 8/0 circle hooks. The fishing performance of the redesigned cibu.d was not statistically different for cibu.d made of brass, stainless steel, or plastic. However, the cibu.d made from wood had significantly lower catch of halibut than the other cibu.d. We selected the brass cibu.d for the second phase of the study for continuity with the previous study of cibu.d and found that it had significantly less bycatch and a lower bycatch ratio than both the paired 8/0 and single 16/0 circle hooks. No significant differences were found in catch rates of halibut for paired 8/0 circle hooks, 16/0 circle hook, and the brass cibu.d. This study demonstrates that the improved catching performance of cibu.d on halibut and reduced bycatch compared to other popular approaches can be achieved by using brass cibu.d. Managers of recreational halibut fisheries should consider the use of cibu.d in areas where bycatch is a concern.

Experimental and computational studies of graphene oxide covalently functionalized by octylamine: electrochemical stability, hydrogen evolution, and corrosion inhibition of the AZ13 Mg alloy in 3.5% NaCl.

Recently, carbon allotropes were shown to play a key role in energy harvesting and as hydrophobic coatings on metal alloys. We have designed octylamine-functionalized graphene oxide materials for energy harvesting and as an anti-corrosion coating for metal alloy protection in a 3.5% NaCl medium. The material has been characterized by different techniques to confirm the structure and composition of the modified graphene oxide sheet: FTIR spectroscopy, XRD, Raman spectroscopy, FESEM and TEM. The electrochemical stability and corrosion inhibition efficiency were studied by electrochemical methods. The electrochemical stability increased with an increase in the applied voltage up to 500 mV, and the corrosion inhibition efficiency was shown to be 73%. The coating stability studies showed a long stability time in the corrosion medium.

Experimental and DFT studies of porous carbon covalently functionalized by polyaniline as a corrosion inhibition barrier on nickel-based alloys in acidic media.

In acidic medium, nickel alloys severely suffer from long term corrosion problems as a result of the breakdown of their passivating oxide. The present study considers polyaniline functionalized fish-scale graphitic carbon as an anticorrosion coating on the nickel alloy surface. The fish-scale porous carbon materials are characterized by XRD, ATR-FITR, UV, Raman, TGA, SS NMR, FESEM, and TEM methods. The surface of the alloy is covalently bound with a polyaniline long chain protonated polymer so that the polyaniline functionalized honeycomb fish-scale carbon structure can exchange electrons with the metal surface. The corrosion inhibition efficiency has been investigated in different acid media like sulfuric acid and hydrochloric acid by electrochemical methods. Polyaniline functionalized porous carbon showed in 1 M H2SO4 inhibition efficiency around 64% and in 1 M HCl inhibition efficiency was around 74%. The inhibition efficiency was higher in HCl because chloride ions were not able to penetrate the graphitic sheet. The novelty of this coating is in the fact that the polyaniline functionalized porous carbon has high conductivity and is electrochemically stable in acidic medium. It is able to donate electrons to the polarized metal surface.

Experimental and DFT studies on the ultrasonic energy-assisted extraction of the phytochemicals of Catharanthus roseus as green corrosion inhibitors for mild steel in NaCl medium.

Catharanthus roseus (Apocynaceae family) extract is rich in organic phytochemicals such as alkaloids, polyphenolic compounds, and flavonoids. It contains several functional entities such as fused heterocycles, and hydroxyl and carbonyl groups, which could be useful for corrosion inhibition of mild steel in NaCl environments. In the present work, ultrasonic energy was used to obtain the ethanolic extracts of root and stem which were then tested as corrosion inhibitors for mild steel in the presence of 3.5% NaCl. The corrosion inhibition process was studied by UV-visible spectroscopy, Fourier transform infrared spectroscopy, atomic force microscopy, weight loss, and electrochemical methods. After immersing in the corrosive medium, the microstructures of mild steel were investigated by scanning electron microscopy, X-ray diffraction, and ellipsometry. The extract of C. roseus showed excellent adsorption on mild steel surface as confirmed by DFT calculations. The results indicate that the extract of C. roseus acts as a mixed type corrosion inhibitor, where the stem extract is the most efficient inhibitor in 3.5% NaCl solution possibly due to the higher active area of stem phytochemicals.

Neodymium-decorated graphene oxide as a corrosion barrier layer on Ti6Al4V alloy in acidic medium.

Ti6Al4V alloy is light weight and is used in construction, oil industries and airbus, automobile, and bio implant materials. The native oxide layers of the alloy are not stable at high temperatures and strong mineral acid environments. The conventional epoxy-based layers are porous and the alloy finally fails in the harsh environment in the long term. Therefore, the carbon-based functional materials are being proposed as coating materials to overcome the alloy degradation. In the present contribution, we have used the neodymium-decorated graphene oxide as the corrosion inhibiting barrier for the Ti6Al4V alloy. As a novelty, we found that the few-layer graphene decorated with neodymium acts as a self-cleaning coating. The Nd-decorated graphene oxide were studied by XRD, TEM, FESEM, FTIR, UV, and Raman spectroscopy. The corrosion inhibition efficiency was studied by electrochemical methods.

Experimental and computational studies of a graphene oxide barrier layer covalently functionalized with amino acids on Mg AZ13 alloy in salt medium.

Magnesium alloys are promising materials for the biomedical and automobile industries. The Mg alloy's light-weight property leads to numerous industrial applications. However, the magnesium alloy oxide layers are not stable in salt environments. Organic inhibitors and epoxy coatings fail as long term barriers in such media. Recently, carbon based functionalized materials, graphene oxides, were shown to be promising materials for improving corrosion resistance in acid and salt environments. Our research considered graphene oxide covalently functionalized with the amino acid leucine to form anticorrosion coating materials. The functionalized materials were characterized by XRD, Raman, FESEM, HRTEM, FTIR, and AFM methods. The corrosion inhibition efficiency was monitored by electrochemical methods. The novelty of the functionalized graphene oxide materials is that they are water impermeable, and thus could enhance the anticorrosion resistance in salt environments.

Experimental and DFT studies of carbon nanotubes covalently functionalized with an imidazole derivative for electrochemical stability and green corrosion inhibition as a barrier layer on the nickel alloy surface in a sulphuric acidic medium.

Nickel-based alloys are used for various applications such as in automobiles, superalloys and ship making. Their stability in acidic environments, however, is often not sufficient due to their native oxide films not withstanding harsh conditions. Carbon-based materials, in contrast, have shown high stability in acidic environments. In the present work, 4,5-diphenyl-imidazole-functionalized carbon nanotubes were investigated as a corrosion-inhibiting barrier layer on nickel alloy surfaces. We studied the corrosion inhibition efficiency of the imidazole-functionalized carbon nanotubes coated on nickel alloys. The materials were characterized using microscopy and spectroscopy methods. DFT studies were performed as well. The corrosion inhibition was evaluated using electrochemical methods. The imidazole-functionalized CNTs were shown to be crystalline and to have tubular structures. They displayed excellent corrosion inhibition on the nickel alloy surface.

Evolution of 2D tin oxides on the surface of molten tin.

The exfoliation of two dimensional (2D) oxides, established on the surface of specific liquid metals, has recently been introduced. One such liquid metal is molten tin, which forms a variety of surface 2D oxides. However, the development behaviour of these surface tin oxides is still unknown. Here the evolution of stoichiometry and thickness from single-layer SnO to highly oxidised multi-layer SnO2 in ambient oxygen is explored.

Vocal fold paresis - a debilitating and underdiagnosed condition.

OBJECTIVES: To review the clinical signs of vocal fold paresis on laryngeal videostroboscopy, to quantify its impact on patients' quality of life and to confirm the benefit of laryngeal electromyography in its diagnosis. METHODS: Twenty-nine vocal fold paresis patients were referred for laryngeal electromyography. Voice Handicap Index 10 results were compared to 43 patients diagnosed with vocal fold paralysis. Laryngeal videostroboscopy analysis was conducted to determine side of paresis. RESULTS: Blinded laryngeal electromyography confirmed vocal fold paresis in 92.6 per cent of cases, with vocal fold lag being the most common diagnostic sign. The laryngology team accurately predicted side of paresis in 76 per cent of cases. Total Voice Handicap Index 10 responses were not significantly different between vocal fold paralysis and vocal fold paresis groups (26.08 ± 0.21 and 22.93 ± 0.17, respectively). CONCLUSION: Vocal fold paresis has a significant impact on quality of life. This study shows that laryngeal electromyography is an important diagnostic tool. Patients with persisting dysphonia and apparently normal vocal fold movement, who fail to respond to appropriate speech therapy, should be investigated for a diagnosis of vocal fold paresis.

A randomized study of a smartphone application compared with booklet to improve service user's knowledge of their legal rights.

BACKGROUND: The Mental Health Act 2001 has introduced significant changes to the process of admission to hospital for individuals affected by mental health disorders. This study aimed to determine whether a newly designed smartphone application could result in an improvement in service users' knowledge of their rights compared with the paper booklet. METHODS: This was a randomized study conducted in an outpatient and day-hospital in North Dublin. Participants were randomized to receive the information booklet as either a smartphone application or in the paper form. A questionnaire which was scored from 0 to 10 was devised and was completed at baseline and at 1-week follow-up. RESULTS: A total of 42 individuals completed the baseline and follow-up questionnaire and of these, 53.7% were female and the mean age was 38.2 years (s.d.±13.5). A total of 34.1% had a diagnosis of a psychotic disorder, 29.3% had a depressive disorder and 22% had bipolar-affective disorder. The mean score before the intervention in the total group was 3.5 (s.d.±2.2) and this increased to 5.8 (s.d.±2.2) at follow-up. Participants randomized to the smartphone application improving by a mean of 2.5 (s.d.±2.5), while those randomized to the booklet improving by a mean of 2.3 (s.d.±2.6), which was not statistically significant. CONCLUSIONS: Both forms of the information booklet showed improvement in service users' knowledge of their legal rights. It is possible that each individual will have preference for either a paper form or a smartphone form and this study suggests that both forms should be offered to each individual service user.

Revelation of intertwining organic and inorganic fractal structures in polymer coatings.

X-ray microtomography and serial block face scanning electron microscopy are used to reveal independent clusters of inorganic particles embedded within a polymer. These clusters are interpenetrating, of varying size, and have fractal dimensions that strongly influence transport and structure-property relations. This interpretation forms a baseline for designing hybrid materials for applications in self-healing, drug delivery, and membranes.

Upregulation of the esophago-UES relaxation response: a possible pathophysiological mechanism in suspected reflux laryngitis.

BACKGROUND: Inappropriate or excessive, non-swallow related, reflexive relaxation of the upper esophageal sphincter (UES) in response to esophageal distension may be the principal mechanism permitting retrograde trans-sphincteric flow during acid regurgitation. The neural pathways mediating reflexive UES relaxation in the human have received little attention. Patients with laryngitis demonstrate an increased acid reflux in the proximal esophagus. Such events, combined with an increased tendency for UES relaxation, might precipitate regurgitation into the pharynx. The aim was to determine whether the esophago-UES relaxation reflex induced by rapid esophageal distension is upregulated in patients with posterior laryngitis. METHODS: In 21 healthy volunteers and 14 patients with posterior laryngitis, UES responses to rapid air insufflation were examined. UES responses were monitored with perfused manometry catheter with a oval sleeve sensor. KEY RESULTS: The probability of triggering UES relaxation in response to the rapid esophageal air distension, for all volumes of insufflation, was higher in laryngitis (45%) than in health (17%). The minimum distension volume required to elicit an UES relaxation response was significantly lower in laryngitis patients when compared with controls. Patients who demonstrated a laryngoscopic response to a trial of omeprazole, were less likely to generate a distension-induced UES contractile response (5%) than patients who did not respond (23%). CONCLUSIONS & INFERENCES: The threshold for esophageal distension-induced UES relaxation is reduced in patients with laryngitis when compared with controls. This finding supports the hypothesis that in this population, a hypersensitive belch-like response may be one contributory mechanism of regurgitation when triggered by an abrupt spontaneous gastro-esophageal reflux event.

Calpains are activated by light but their inhibition has no neuroprotective effect against light-damage.

Calpain had been shown to be highly activated at one day after exposure to the damaging light (Perche et al. (2007)Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48:2753-2759.), suggesting that they might play a critical role in photoreceptor apoptosis induced by light. Therefore in the present study we investigate the role of calpain in light-induced photoreceptor cell death. In a first set of experiments, untreated albino Wistar rats were sacrificed at 0, 2, 4, 6, 12, 24 h of light exposure and at one day after the light was turned off (D1) to measure retinal calpain activity and to study calpain expression. In a second set of experiments, after control electroretinograms (ERGs), rats were uninjected or injected intravitreally with DMSO or the calpain inhibitor Mu-Phe-hPhe-FMK, before being exposed to the damaging light for 24 h. ERGs were then recorded at one day (D1) and fifteen days (D15) after the end of light exposure. Rats were sacrificed at D1 for apoptotic cell detection or D15 for histological analysis (ONL thickness). Calpain activity and expression significantly increased in Untreated retinas, from 0 h to D1. DMSO has no effect on calpain activity. Mu-Phe-hPhe-FMK significantly inhibited retinal calpain activity by 85% at 2 h of light exposure and still 48% at D1. However, Mu-Phe-hPhe-FMK has no effect on light-induced retinal degeneration as evidence by equivalent loss of function, equivalent loss of photoreceptor cells and an equivalent number of apoptotic cells in Mu-Phe-hPhe-FMK and DMSO retinas. Therefore, calpains are up-regulated by light stress but they do not have a pivotal role in photoreceptor apoptosis.

Transient protective effect of caspase inhibitors in RCS rat.

In most retinal degenerations in humans and in animal models, photoreceptor cells die by apoptosis. Although the biochemical features are similar in all apoptotic cells, different molecular events lead the cell to death. In the present study we used a rat model of inherited retinal degeneration, the RCS rats, to investigate the involvement of the proteases, caspases and/or calpains, in photoreceptor apoptosis. In the first experiments, rats were untreated or injected intravitreally at post natal day 27 (P27) with the large broad spectrum caspase inhibitor, ZVAD, the calpain inhibitor, MuhPhe, or with the vehicle, DMSO. Retinal status was evaluated at P35 and P42 by electroretinography, morphometry and apoptotic nuclei detection. DMSO and MuhPhe had no effect on RCS retinas as evidenced by equivalent loss of function and equivalent number of apoptotic cells than in untreated group. ZVAD transiently reduced apoptotic cells and preserved photoreceptor function at P35 but not at P42. These results suggest that caspases but not calpains are involved in retinal degeneration in the RCS. In the second experiments, RCS rats were injected twice at P27 and P35 with ZVAD or DMSO. Although ZVAD-treated retinas were preserved at P35 compared to the DMSO controls, the second injection of ZVAD did not extend the preserving effect to P42. Moreover, a single injection of ZVAD at P35 had no preserving effect at P42. All these data taken together suggest that caspases do not play a pivotal role after P35. In a fourth set of experiments, we used specific caspase inhibitors to elucidate which caspase was activated. The caspase-1/4 inhibitor (YVAD) or the caspase-3/7 inhibitor (DEVD) were injected intravitreally at P27 and retinal status was evaluated at P35 and P42. Electroretinograms and apoptotic nuclei detection demonstrated that YVAD and DEVD preserved photoreceptors at P35 but not at P42. These results suggest that both caspase-1/4 and caspase-3/7 play a major role in the apoptotic pathway between P27 and P35 in retinal degeneration of RCS rats. In this study, we show that 1/ the photoreceptor apoptotic process in the RCS rat involves caspases but not calpains, and 2/ the retinal degeneration seems to be composed of different phases involving different molecular players. Indeed, we have demonstrated that caspases are playing a major role at P35, but not at P42.

Using social judgement theory to model nurses' use of clinical information in critical care education.

Understanding the learning needs of students is a vital step in planning the delivery of effective education. Evaluating the impact of such interventions is not always easy and many methods rely on self-reported behaviour or simple changes in knowledge--whose relationship to action is not always clear. Using conjoint analysis, within the theoretical framework of social judgement theory, this study illustrates a novel means of examining nurses' use of clinical information when diagnosing hypovolemic shock in a series of simulated cases presented via computer. The study examines changes in information usage before and after a traditional lecture. The results show that nurses' information use is not linear and the utility for decision judgement derived from clinical information is not distributed equally. The study also suggests that some clinical information (for example, the Glasgow Coma Score) is not well understood and incorporated into clinical judgement. The study has implications for those designing and evaluating educational interventions and those studying information use, clinical judgement and decision making.

Predictors of outcome in an open label, therapeutic trial of high-dose omeprazole in laryngitis.

BACKGROUND: Gastroesophageal reflux is implicated in some cases of laryngitis. There are no established predictors of response to acid suppression therapy in suspected reflux laryngitis. AIM: In a population with laryngitis, the aim is to determine whether (a) omeprazole 20 mg tds (3 months) improves symptoms and laryngitis, and (b) the outcome in response to potent acid suppression can be predicted by esophageal and/or pharyngeal parameters during ambulatory pH monitoring or by other pretreatment variables. METHODS: From the 70 consecutive patients with laryngitis screened, 20 patients met the inclusion criteria (dysphonia >3 months; laryngoscopically demonstrated laryngitis); and 50 patients were excluded because of one or more criteria indicating alternative causes for laryngeal injury. The primary outcome measure was improvement of at least one level in a 4-point laryngitis grading at 3 months. Twenty-four-hour dual, pharyngo-esophageal pH monitoring was performed at baseline. Secondary outcomes (symptom questionnaire; computerized voice analysis) were measured at baseline, and at 6 and 12 wk. RESULTS: Response rates at 6 and 12 wk were 47% and 63%, respectively. GERD symptoms (heartburn (p= 0.03) and regurgitation (p= 0.0001)) improved. However, neither baseline GERD symptoms nor endoscopic findings predicted laryngoscopic or symptomatic response. Neither baseline laryngitis grade (p= 0.46) nor esophageal acid exposure on pH testing (p= 0.3) predicted outcome. Four of 20 patients demonstrated pharyngeal regurgitation on pH testing, all four of whom responded to potent acid suppression (p= 0.2). Computerized voice measures were not predictive of outcome, although fundamental frequency (Fo) was inversely related to baseline laryngoscopic grade. CONCLUSION: In a carefully defined population of patients with laryngitis (a) 63% have a laryngoscopic response to 3 months of potent acid suppression without significant improvement in laryngeal symptoms; (b) neither voice measures, esophageal acid exposure time, symptoms nor severity of laryngitis predict outcome; and (c) although numbers were small, all patients with a positive pharyngeal pH study responded to therapy and pharyngeal pH-metry may prove useful; (4) available evidence supports an empiric trial of high-dose proton pump inhibitors (PPI), for at least 12 wk, as the initial diagnostic step for suspected reflux laryngitis.

Spasmodic dysphonia: clinical features and effects of botulinum toxin therapy in 169 patients-an Australian experience.

Adductor spasmodic dysphonia (SD) is a focal laryngeal dystonia, characterised by strangled, effortful speech with breaks in pitch and phonation. Injection of laryngeal muscles with BTX is widely used in the treatment of SD. A consecutive series of 169 patients with SD, of whom 144 were treated with BTX injections, seen at St. Vincent's Hospital between 1983 and 1999 were studied prospectively. Patients underwent neurological, quantitative voice and otolaryngological assessment. Females (62.1%) outnumbered males (37.9%) and the mean age at diagnosis was 56 years (range 19-88). Adductor SD (89.4%) was more frequent than abductor SD (1.8%) or mixed SD (4.7%). Stridor was present in 14 patients (8.3%) and in 7 was the sole manifestation of the laryngeal dystonia. The median treatment outcome score was excellent in 63.2%, very good in 18.5%, satisfactory in 14.7% and unsatisfactory in 3.5%. Poorer treatment outcome was associated with abductor SD (OR = 4.69, CI [1.23, 17.92] p=0.024] and age >65 (OR = 2.83, CI [0.95, 8.42] p=0.049). Mild post-injection paralytic dysphonia was associated with longer lasting treatment (4.42 vs. 3.62 months p<0.001) and superior treatment outcome rating (1.37 vs. 1.81 p<0.001). We conclude that BTX injections are highly effective and severe adverse events are rare. Older age and abductor SD may confer a relatively poorer treatment outcome. Mild post-injection paralytic dysphonia may be a marker for more effective and lasting treatment in adductor SD.

Bilateral vocal cord palsy following interscalene brachial plexus nerve block.

Acute respiratory complications of an interscalene brachial plexus block include ipsilateral phrenic nerve and recurrent laryngeal nerve palsies. A 71-year-old woman who had undergone a total thyroidectomy for papillary carcinoma 35 years ago was administered a right interscalene brachial plexus block for a shoulder hemi-arthroplasty. Subsequently she developed acute respiratory distress associated with marked stridor secondary to an acute right vocal cord palsy, which was superimposed on what was assumed to be a preexisting left-sided vocal cord palsy. On extubation the patient was noted to develop stridor again necessitating reintubation and tracheostomy was performed two weeks later. The vocal cord palsies failed to resolve over the subsequent 18-month follow-up. We describe this case to highlight the significant risk of this procedure in patients with preexisting or suspected contralateral vocal cord palsy.

Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue.

Cyclin D1 and p16INK4A are molecules with pivotal roles in cell cycle control and the development of diverse human cancers, and overexpression of cyclin D1 and loss of p16INK4A expression are common genetic events in head and neck squamous cell carcinoma. The prognostic significance of these molecular events at different sites within the head and neck, however, remains controversial. Thus, we sought to determine the relationship between cyclin D1 and/or p16INK4A expression and disease outcome in squamous cell carcinoma of the anterior tongue. Immunohistochemical detection of nuclear proteins cyclin D1, p53, and p16INK4A, and the Ki-67 labeling index was undertaken in tissue sections from 148 tongue cancers treated by surgical resection. Nuclear antigen status was analyzed in relation to pathological variables, tumor recurrence, and patient survival. Statistical significance was assessed using chi2 analysis for pathological variables and the Kaplan-Meier method, log rank test, and the Cox proportional hazards model for survival parameters. Overexpression of cyclin D1 occurred in 68% of tumors (100 of 147) and was associated with increased lymph node stage (P = 0.014), increased tumor grade (P = 0.003), and reduced disease-free (P = 0.006) and overall (P = 0.01) survival. Loss of p16INK4A expression was demonstrated in 55% of tumors (78 of 143) and was associated with reduced disease-free (P = 0.007) and overall (P = 0.014) survival. Multivariate analysis confirmed that in addition to pathological stage and regional lymph node status, cyclin D1 overexpression and loss of p16INK4A expression are independent predictors of death from tongue cancer. Loss of p16INK4A in the presence of cyclin D1 overexpression conferred a significantly worse disease-free (P = 0.011) and overall (P = 0.002) survival at 5 years. p53 nuclear accumulation and the Ki-67 labeling index were not prognostic. These data indicate that cyclin D1 overexpression and loss of p16INK4A expression predict early relapse and reduced survival in squamous cell carcinoma of the anterior tongue. Simultaneous assessment of cyclin D1 and p16INK4A protein levels define subgroups of patients at increased risk of relapse and may be of clinical utility in optimizing therapy.