ORAL MUCOSITIS PREVENTION BY LOW-LEVEL LASER THERAPY IN HEAD-AND-NECK CANCER PATIENTS UNDERGOING CONCURRENT CHEMORADIOTHERAPY: A PHASE III RANDOMIZED STUDY

Purpose: Oral mucositis is a major complication of concurrent chemoradiotherapy (CRT) in head-and-neck cancer patients. Low-level laser (LLL) therapy is a promising preventive therapy. We aimed to evaluate the efficacy of LLL therapy to decrease severe oral mucositis and its effect on RT interruptions. Methods and Materials: In the present randomized, double-blind, Phase III study, patients received either gallium-aluminum-arsenide LLL therapy 2.5 J/cm(2) or placebo laser, before each radiation fraction. Eligible patients had to have been diagnosed with squamous cell carcinoma or undifferentiated carcinoma of the oral cavity, pharynx, larynx, or metastases to the neck with an unknown primary site. They were treated with adjuvant or definitive CRT, consisting of conventional RT 60-70 Gy (range, 1.8-2.0 Gy/d, 5 times/wk) and concurrent cisplatin. The primary endpoints were the oral mucositis severity in Weeks 2, 4, and 6 and the number of RT interruptions because of mucositis. The secondary endpoints included patient-reported pain scores. To detect a decrease in the incidence of Grade 3 or 4 oral mucositis from 80% to 50%, we planned to enroll 74 patients. Results: A total of 75 patients were included, and 37 patients received preventive LLL therapy. The mean delivered radiation dose was greater in the patients treated with LLL (69.4 vs. 67.9 Gy, p = .03). During CRT, the number of patients diagnosed with Grade 3 or 4 oral mucositis treated with LLL vs. placebo was 4 vs. 5 (Week 2, p = 1.0), 4 vs. 12 (Week 4, p = .08), and 8 vs. 9 (Week 6, p = 1.0), respectively. More of the patients treated with placebo had RT interruptions because of mucositis (6 vs. 0, p = .02). No difference was detected between the treatment arms in the incidence of severe pain. Conclusions: LLL therapy was not effective in reducing severe oral mucositis, although a marginal benefit could not be excluded. It reduced RT interruptions in these head-and-neck cancer patients, which might translate into improved CRT efficacy. (C) 2012 Elsevier Inc.

Enhanced Morbidity of Pectoralis Major Myocutaneous Flap Used for Salvage after Previously Failed Oncological Treatment and Unsuccessful Reconstructive Head and Neck Surgery

Introduction. The reconstruction of complex cervicofacial defects arising from surgical treatment for cancer is a real challenge for head and neck surgeons, especially in salvage reconstruction surgery and/or failed previous reconstruction. The pectoralis major myocutaneous flap (PMMF) has been widely used in these specific situations due to its reliability and low rate of failure or complications. Objectives. Identify factors that determine complications and influence the final outcome of the reconstructions with PMMF in salvage cancer surgery or in salvage reconstruction. Methods. A cross-sectional study design was used to evaluate a sample including 17 surgical patients treated over a period of ten years that met the inclusion criteria. Results. Reconstruction was successful in 13 cases (76.5%), with two cases of partial flap loss and no case of total loss. Complications occurred in 13 cases (76.5%) and were specifically related to the flap in nine instances (52.9%). An association was identified between the development of major complications and reconstruction of the hypopharynx (P = 0.013) as well as in patients submitted to surgery in association with radiation therapy as a previous cancer treatment (P = 0.002). The former condition is also associated with major reconstruction failure (P = 0.018). An even lower incidence of major complications was noted in patients under the age of 53 (P = 0.044). Conclusion. Older patients, with hypopharyngeal defects and submitted to previous surgery plus radiation therapy, presented a higher risk of complications and reconstruction failure with PMMF.

Whole-body computerized tomography and concomitant spine and head injuries A study of 355 cases

The authors present a prospective study on the coexistence of spinal injury (SI) and severe traumatic brain injury (TBI) in patients who were involved in traffic accidents and arrived at the Emergency Department of Hospital das Clinicas of the University of Sao Paulo between September 1, 2003 and December 31, 2009. A whole-body computed tomography was the diagnostic method employed in all cases. Both lesions were observed simultaneously in 69 cases (19.4%), predominantly in males (57 individuals, 82.6%). Cranial injuries included epidural hematoma, acute subdural hematoma, brain contusion, ventricular hemorrhage and traumatic subarachnoid hemorrhage. The transverse processes were the most fragile portion of the vertebrae and were more susceptible to fractures. The seventh cervical vertebra was the most commonly affected segment, with 24 cases (34.78%). The distribution of fractures was similar among the other cervical vertebrae, the first four thoracic vertebrae and the lumbar spine. Neurological deficit secondary to SI was detected in eight individuals (11.59%) and two individuals (2.89%) died. Traumatic subarachnoid hemorrhage was the most common intracranial finding (82.6%). Spinal surgery was necessary in 24 patients (34.78%) and brain surgery in 18 (26%). Four patients (5.79%) underwent cranial and spinal surgeries. The authors conclude that it is necessary a judicious assessment of the entire spine of individuals who presented in coma after suffering a brain injury associated to multisystemic trauma and whole-body CT scan may play a major role in this scenario.

Influence of Clinically Invisible, but Optical Coherence Tomography Detected, Optic Disc Margin Anatomy on Neuroretinal Rim Evaluation

PURPOSE. We previously demonstrated that most eyes have regionally variable extensions of Bruch's membrane (BM) inside the clinically identified disc margin (DM) that are clinically and photographically invisible. We studied the impact of these findings on DM- and BM opening (BMO)-derived neuroretinal rim parameters. METHODS. Disc stereo-photography and spectral domain optical coherence tomography (SD-OCT, 24 radial B-scans centered on the optic nerve head) were performed on 30 glaucoma patients and 10 age-matched controls. Photographs were colocalized to SD-OCT data such that the DM and BMO could be visualized in each B-scan. Three parameters were computed: (1) DM-horizontal rim width (HRW), the distance between the DM and internal limiting membrane (ILM) along the DM reference plane; (2) BMO-HRW, the distance between BMO and ILM along the BMO reference plane; and (3) BMO-minimum rim width (MRW), the minimum distance between BMO and ILM. Rank-order correlations of sectors ranked by rim width and spatial concordance measured as angular distances between equivalently ranked sectors were derived. RESULTS. The average DM position was external to BMO in all quadrants, except inferotemporally. There were significant sectoral differences among all three rim parameters. DM- HRW and BMO-HRW sector ranks were better correlated (median rho = 0.84) than DM- HRW and BMO-MRW (median rho = 0.55), or BMO-HRW and BMO-MRW (median rho = 0.60) ranks. Sectors with the narrowest BMO-MRW were infrequently the same as those with the narrowest DM-HRW or BMO-HRW. CONCLUSIONS. BMO-MRW quantifies the neuroretinal rim from a true anatomical outer border and accounts for its variable trajectory at the point of measurement. (Invest Ophthalmol Vis Sci. 2012;53:1852-1860) DOI:10.1167/iovs.11-9309

EFFECT OF HEAD GROUP AND CURVATURE ON BINDING OF THE ANTIMICROBIAL PEPTIDE TRITRPTICIN TO LIPID MEMBRANES

In this work we examine the interaction between the 13-residue cationic antimicrobial peptide (AMP) tritrpticin (VRRFPWWWPFLRR, TRP3) and model membranes of variable lipid composition. The effect on peptide conformational properties was investigated by means of CD (circular dichroism) and fluorescence spectroscopies. Based on the hypothesis that the antibiotic acts through a mechanism involving toroidal pore formation, and taking into account that models of toroidal pores imply the formation of positive curvature, we used large unilamellar vesicles (LUV) to mimic the initial step of peptide-lipid interaction, when the peptide binds to the bilayer membrane, and micelles to mimic the topology of the pore itself, since these aggregates display positive curvature. In order to more faithfully assess the role of curvature, micelles were prepared with lysophospholipids containing (qualitatively and quantitatively) head groups identical to those of bilayer phospholipids. CD and fluorescence spectra showed that, while TRP3 binds to bilayers only when they carry negatively charged phospholipids. binding to micelles occurs irrespective of surface charge, indicating that electrostatic interactions play a less predominant role in the latter case. Moreover, the conformations acquired by the peptide were independent of lipid composition in both bilayers and micelles. However, the conformations were different in bilayers and in micelles, suggesting that curvature has an influence on the secondary structure acquired by the peptide. Fluorescence data pointed to an interfacial location of TRP3 in both types of aggregates. Nevertheless, experiments with a water soluble fluorescence quencher suggested that the tryptophan residues are more accessible to the quencher in micelles than in bilayers. Thus, we propose that bilayers and micelles can be used as models for the two steps of toroidal pore formation. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Brainstem injury by penetrating head trauma with a knife

The authors describe a rare case about a traumatic lesion of brain and brain stem with a knife. In this case the patient had good clinical condition, diagnosed with TBI by infectious complications. We have highlighted the unusual diagnosis, proximity of vascular structures, the technique used in the treatment and the good outcome of the injury.

Solar-Terrestrial Signal Record in Tree Ring Width Time Series from Brazil

This work investigates the behavior of the sunspot number and Southern Oscillation Index (SOI) signal recorded in the tree ring time series for three different locations in Brazil: Humaita in Amaznia State, Porto Ferreira in So Paulo State, and Passo Fundo in Rio Grande do Sul State, using wavelet and cross-wavelet analysis techniques. The wavelet spectra of tree ring time series showed signs of 11 and 22 years, possibly related to the solar activity, and periods of 2-8 years, possibly related to El Nio events. The cross-wavelet spectra for all tree ring time series from Brazil present a significant response to the 11-year solar cycle in the time interval between 1921 to after 1981. These tree ring time series still have a response to the second harmonic of the solar cycle (5.5 years), but in different time intervals. The cross-wavelet maps also showed that the relationship between the SOI x tree ring time series is more intense, for oscillation in the range of 4-8 years.

Diet and the risk of head and neck cancer: a pooled analysis in the INHANCE consortium

We investigated the association between diet and head and neck cancer (HNC) risk using data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. The INHANCE pooled data included 22 case-control studies with 14,520 cases and 22,737 controls. Center-specific quartiles among the controls were used for food groups, and frequencies per week were used for single food items. A dietary pattern score combining high fruit and vegetable intake and low red meat intake was created. Odds ratios (OR) and 95% confidence intervals (CI) for the dietary items on the risk of HNC were estimated with a two-stage random-effects logistic regression model. An inverse association was observed for higher-frequency intake of fruit (4th vs. 1st quartile OR = 0.52, 95% CI = 0.43-0.62, p (trend) < 0.01) and vegetables (OR = 0.66, 95% CI = 0.49-0.90, p (trend) = 0.01). Intake of red meat (OR = 1.40, 95% CI = 1.13-1.74, p (trend) = 0.13) and processed meat (OR = 1.37, 95% CI = 1.14-1.65, p (trend) < 0.01) was positively associated with HNC risk. Higher dietary pattern scores, reflecting high fruit/vegetable and low red meat intake, were associated with reduced HNC risk (per score increment OR = 0.90, 95% CI = 0.84-0.97).

Upper airway expansion after rapid maxillary expansion evaluated with cone beam computed tomography

Objective: Cone-beam computed tomography (CBCT) is a reliable method of assessing the oral cavity and upper airways. We conducted this study to examine the changes introduced by rapid maxillary expansion in the nasal cavity, nasopharynx, and oropharynx as seen with images obtained by CBCT. Materials and Methods: We evaluated 15 patients with maxillary width deficiency treated with RME. Patients were subjected to CBCT at the beginning of RME and after the retention period of 4 months. Results: The nasal cavity presented a significant transverse increase in the lower third, in the anterior (1.08 mm +/- 0.15), medium (1.28 mm +/- 0.15), and posterior regions (0.77 mm +/- 0.12). No significant change occurred in the nasopharynx in volume (P = .11), median sagittal area (P = .33), or lower axial area (P = .29) resulting from the RME. A significant change was noted in the oropharynx in volume (P = .05), median sagittal area (P = .01), and lower axial area (P = .04) before and immediately after the RME. Conclusions: RME is able to increase the transverse width of the nasal cavity, but it does not have the same effect in the nasopharynx. Changes noted in the oropharynx may be due to the lack of a standardized position of the head and tongue at the time of image acquisition. (Angle Orthod. 2012;82:458-463.)

Effect of sequence of insemination after simultaneous thawing of multiple semen straws on conception rate to timed AI in suckled multiparous Nelore cows

The objective was to determine the effect of sequence of insemination after simultaneous thawing of multiple 0.5 mL semen straws on conception rate in suckled multiparous Nelore cows. The effect of this thawing procedure on in vitro sperm characteristics was also evaluated. All cows (N = 944) received the same timed AI protocol. Ten straws (0.5 mL) of frozen semen from the same batch were simultaneously thawed at 36 degrees C, for a minimum of 30 sec. One straw per cow was used for timed AI. Frozen semen from three Angus bulls was used. Timed AI records included sequence of insemination (first to tenth) and time of semen removal from thawing bath. For laboratory analyses, the same semen batches used in the field experiment were evaluated. Ten frozen straws from the same batch were thawed simultaneously in a thawing unit identical to that used in the field experiment. The following sperm characteristics were analyzed: sperm motility parameters, sperm thermal resistance, plasma and acrosomal membrane integrity, lipid peroxidation, chromatin structure, and sperm morphometry. Based on logistic regression, there were no significant effects of breeding group, body condition score, AI technician, and sire on conception rate, but there was an interaction between sire and straw group (P = 0.002). Semen from only one bull had decreased (P < 0.05) field fertility for the group of straws associated with the longest interval from thawing to AI. However, the results of the laboratory experiment were unable to explain the findings of the field experiment. Sperm width:length ratio of morphometric analysis was the single sperm characteristic with a significant interaction between sire and straw group (P = 0.02). It was concluded that sequence of insemination after simultaneous thawing of 10 semen straws can differently affect conception rates at timed AI, depending on the sire used. Nevertheless, the effects of this thawing environment on in vitro sperm characteristics, remain to be further investigated. (C) 2012 Elsevier Inc. All rights reserved.

A clinical experience of the supraclavicular flap used to reconstruct head and neck defects in late-stage cancer patients

The supraclavicular island flap has been widely used in head and neck reconstruction, providing an alternative to the traditional techniques like regional or free flaps, mainly because of its thin skin island tissue and reliable vascularity. Head and neck patients who require large reconstructions usually present poor clinical and healing conditions. An early experience using this flap for late-stage head and neck tumour treatment is reported. Forty-seven supraclavicular artery flaps were used to treat head and neck oncologic defects after cutaneous, intraoral and pharyngeal tumour resections. Dissection time, complications, donor and reconstructed area outcomes were assessed. The mean time for harvesting the flaps was 50 min by the senior author. All donor sites were closed primarily. Three cases of laryngopharyngectomy reconstruction developed a small controlled (salivary) leak that was resolved with conservative measures. Small or no strictures were detected on radiologic swallowing examinations and all patients regained normal swallowing function. Five patients developed donor site dehiscence. These wounds were treated with regular dressing until healing was complete. There were four distal flap necroses in this series. These necroses were debrided and closed primarily. The supraclavicular flap is pliable for head and neck oncologic reconstruction in late-stage patients. High-risk patients and modified radical neck dissection are not contraindications for its use. The absence of the need to isolate the pedicle offers quick and reliable harvesting. The arc of rotation on the base of the neck provides adequate length for pharyngeal, oral lining and to reconstruct the middle and superior third of the face. (C) 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Sperm head morphometry in ejaculates of adult marmosets (Callithrix jacchus): a model for studying sperm subpopulations and among-donor variations

In humans and other mammals, sperm morphology has been considered one of the most important predictive parameters of fertility. The objective was to determine the presence and distribution of sperm head morphometric subpopulations in a nonhuman primate model (Callithrix jacchus), using an objective computer analysis system and principal component analysis (PCA) methods to establish the relationship between the subpopulation distribution observed and among-donor variation. The PCA method revealed a stable number of principal components in all donors studied, that represented more than 85% of the cumulative variance in all cases. After cluster analysis, a variable number (from three to seven) sperm morphometric subpopulations were identified with defined sperm dimensions and shapes. There were differences in the distribution of the sperm morphometric subpopulations (P < 0.001) in all ejaculates among the four donors analyzed. In conclusion, in this study, computerized sperm analysis methods combined with PCA cluster analyses were useful to identify, classify, and characterize various head sperm morphometric subpopulations in nonhuman primates, yielding considerable biological information. In addition, because all individuals were kept in the same conditions, differences in the distribution of these subpopulations were not attributed to external or management factors. Finally, the substantial information derived from subpopulation analyses provided new and relevant biological knowledge which may have a practical use for future studies in human and nonhuman primate ejaculates, including identifying individuals more suitable for assisted reproductive technologies. (c) 2012 Elsevier Inc. All rights reserved.

Head-to-Head Comparison of Three Vaccination Strategies Based on DNA and Raw Insect-Derived Recombinant Proteins against Leishmania

Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines-is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor.

DNA repair gene excision repair cross complementing-group 1 (ERCC1) in head and neck squamous cell carcinoma: analysis of methylation and polymorphism (G19007A), protein expression and association with epidemiological and clinicopathological factors

Aims: To evaluate the associations of excision repair cross complementing-group 1 (ERCC1) (DNA repair protein) (G19007A) polymorphism, methylation and immunohistochemical expression with epidemiological and clinicopathological factors and with overall survival in head and neck squamous cell carcinoma (HNSCC) patients. Methods and results: The study group comprised 84 patients with HNSCC who underwent surgery and adjuvant radiotherapy without chemotherapy. Bivariate and multivariate analyses were used. The allele A genotype variant was observed in 79.8% of the samples, GG in 20.2%, GA in 28.6% and AA in 51.2%. Individuals aged more than 45 years had a higher prevalence of the allelic A variant and a high (83.3%) immunohistochemical expression of ERCC1 protein [odds ratio (OR) = 4.86, 95% confidence interval (CI): 1.2-19.7, P = 0.027], which was also high in patients with advanced stage (OR= 5.04, 95% CI: 1.07-23.7, P = 0.041). Methylated status was found in 51.2% of the samples, and was higher in patients who did not present distant metastasis (OR = 6.67, 95% CI: 1.40-33.33, P = 0.019) and in patients with advanced stage (OR = 5.04, 95% CI: 1.07-23.7, P = 0.041). At 2 and 5 years, overall survival was 55% and 36%, respectively (median = 30 months). Conclusion: Our findings may reflect a high rate of DNA repair due to frequent tissue injury during the lifetime of these individuals, and also more advanced disease presentation in this population with worse prognosis.