Addressing the sources of inter-subject variability in E-field parameters in anodal tDCS stimulation over motor cortical network.

Objetive: .Although transcranial direct current stimulation constitutes a non-invasive neuromodulation technique with promising results in a great variety of applications, its clinical implementation is compromised by the high inter-subject variability reported. This study aims to analyze the inter-subject variability in electric fields (E-fields) over regions of the cortical motor network under two electrode montages: the classical C3Fp2 and an alternative P3F3, which confines more the E-field over this region.Approach.Computational models of the head of 98 healthy subjects were developed to simulate the E-field under both montages. E-field parameters such as magnitude, focality and orientation were calculated over three regions of interest (ROI): M1S1, supplementary motor area (SMA) and preSMA. The role of anatomical characteristics as a source of inter-subject variability on E-field parameters and individualized stimulation intensity were addressed using linear mixed-effect models.Main results.P3F3 showed a more confined E-field distribution over M1S1 than C3Fp2; the latter elicited higher E-fields over supplementary motor areas. Both montages showed high inter-subject variability, especially for the normal component over C3Fp2. Skin, bone and CSF ROI volumes showed a negative association with E-field magnitude irrespective of montage. Grey matter volume and montage were the main sources of variability for focality. The curvature of gyri was found to be significantly associated with the variability of normal E-fields.Significance.Computational modeling proves useful in the assessment of E-field variability. Our simulations predict significant differences in E-field magnitude and focality for C3Fp2 and P3F3. However, anatomical characteristics were also found to be significant sources of E-field variability irrespective of electrode montage. The normal E-field component better captured the individual variability and low rate of responder subjects observed in experimental studies.

Clinical differentiation of inflammatory bowel disease (IBD) in Latin America and the Caribbean.

ABSTRACT: The aim of the present study was to describe the epidemiological and clinical characteristics of inflammatory bowel disease (IBD), including medical and surgical treatments, in several countries in Latin America and the Caribbean.IBD is recognized as a global health problem because its incidence and prevalence have increased significantly over the last few years.This multicenter retrospective cohort study included 4714 patients with IBD diagnosed from 9 countries in Latin America and the Caribbean: Colombia, Cuba, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela.Crohn disease (CD) was more frequent in Puerto Rico (71.9%), the Dominican Republic (61.0%), and Peru (53.1%). Ulcerative colitis was more frequent in Colombia (78.6%), Venezuela (78.2%), Mexico (75.5%), Cuba (69.9%), Ecuador (64.1%), and Uruguay (60.9%). The following clinical characteristics were more frequent in the Caribbean: penetrating behavior in CD, steroid dependence, steroid resistance, intolerance to thiopurines, extraintestinal manifestations, surgeries, hospitalizations due to IBD, and family history of IBD. The factors associated with the use of biological therapy were pancolitis in ulcerative colitis, penetrating behavior in CD, steroid resistance and dependence, presence of extraintestinal manifestations, and the need for surgery.This study from Latin America and the Caribbean demonstrated the different epidemiological and clinical characteristics of IBD.

In vivo cholinergic basal forebrain degeneration and cognition in Parkinson's disease: Imaging results from the COPPADIS study.

INTRODUCTION: We aimed to assess associations between multimodal neuroimaging measures of cholinergic basal forebrain (CBF) integrity and cognition in Parkinson's disease (PD) without dementia. METHODS: The study included a total of 180 non-demented PD patients and 45 healthy controls, who underwent structural MRI acquisitions and standardized neurocognitive assessment through the PD-Cognitive Rating Scale (PD-CRS) within the multicentric COPPADIS-2015 study. A subset of 73 patients also had Diffusion Tensor Imaging (DTI) acquisitions. Volumetric and microstructural (mean diffusivity, MD) indices of CBF degeneration were automatically extracted using a stereotactic CBF atlas. For comparison, we also assessed multimodal indices of hippocampal degeneration. Associations between imaging measures and cognitive performance were assessed using linear models. RESULTS: Compared to controls, CBF volume was not significantly reduced in PD patients as a group. However, across PD patients lower CBF volume was significantly associated with lower global cognition (PD-CRStotal: r = 0.37, p < 0.001), and this association remained significant after controlling for several potential confounding variables (p = 0.004). Analysis of individual item scores showed that this association spanned executive and memory domains. No analogue cognition associations were observed for CBF MD. In covariate-controlled models, hippocampal volume was not associated with cognition in PD, but there was a significant association for hippocampal MD (p = 0.02). CONCLUSIONS: Early cognitive deficits in PD without dementia are more closely related to structural MRI measures of CBF degeneration than hippocampal degeneration. In our multicentric imaging acquisitions, DTI-based diffusion measures in the CBF were inferior to standard volumetric assessments for capturing cognition-relevant changes in non-demented PD.

Detectability of Gravitational Waves from High-Redshift Binaries.

Recent nondetection of gravitational-wave backgrounds from pulsar timing arrays casts further uncertainty on the evolution of supermassive black hole binaries. We study the capabilities of current gravitational-wave observatories to detect individual binaries and demonstrate that, contrary to conventional wisdom, some are, in principle, detectable throughout the Universe. In particular, a binary with rest-frame mass ≳10^{10}M_{⊙} can be detected by current timing arrays at arbitrarily high redshifts. The same claim will apply for less massive binaries with more sensitive future arrays. As a consequence, future searches for nanohertz gravitational waves could be expanded to target evolving high-redshift binaries. We calculate the maximum distance at which binaries can be observed with pulsar timing arrays and other detectors, properly accounting for redshift and using realistic binary waveforms.

Cool Roofs in Guangzhou, China: Outdoor Air Temperature Reductions during Heat Waves and Typical Summer Conditions.

In this paper, we simulate temperature reductions during heat-wave events and during typical summer conditions from the installation of highly reflective "cool" roofs in the Chinese megacity of Guangzhou. We simulate temperature reductions during six of the strongest historical heat-wave events over the past decade, finding average urban midday temperature reductions of 1.2 °C. In comparison, we simulate 25 typical summer weeks between 2004 and 2008, finding average urban midday temperature reductions of 0.8 °C, indicating that air temperature sensitivity to urban albedo in Guangzhou varies with meteorological conditions. We find that roughly three-fourths of the variance in air temperature reductions across all episodes can be accounted for by a linear regression, including only three basic properties related to the meteorological conditions: mean daytime temperature, humidity, and ventilation to the greater Guangzhou urban area. While these results highlight the potential for cool roofs to mitigate peak temperatures during heat waves, the temperature reductions reported here are based on the upper bound case, which increases albedos of all roofs (but does not modify road albedo or wall albedo).

Influence of diabetes mellitus on postoperative complications and failure in head and neck free flap reconstruction: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis to determine whether diabetic patients have an increased rate of postoperative complications compared to nondiabetic patients after head and neck free flap reconstruction. A systematic review of PubMed Database between 1966 and 2012 was performed. RevMan 5.0 was used for meta-analysis. A retrospective medical chart review of 7890 patients to identify those who had a failed microsurgical reconstruction of the head and neck region at Chang Gung Memorial Hospital was also carried out. The result revealed that patients with diabetes mellitus have a 1.76 increased risk of complications (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.11-2.79) with minimal heterogeneity (I( 2) = 22%; p = .28). The prevalence of diabetes mellitus in patients with failed free flaps for head and neck reconstruction is 15%. The incidence of diabetes mellitus in these patients with failed free flaps is 2.3 times higher than in the general population.

Primary tuberculosis of the palate.

Tuberculosis (TB) is a life-threatening infectious disease with a high world incidence. However, TB with oral expression is considered rare. The importance of recognising this entity lies in its early diagnosis and treatment, as it can be easily confused with neoplastic or traumatic ulcers. We present a case of a primary TB located in the hard palate and gingiva in an 88-year-old woman.

E-cadherin and ß-catenin expression in well-differentiated and moderately-differentiated oral squamous cell carcinoma: relations with clinical variables.

The aim of this study was to establish the expression and localisation of E-cadherin and ß-catenin in oral squamous cell carcinomas (SCC) so that we could correlate the findings with prognostically-relevant clinicopathological variables. E-cadherin and ß-catenin expression in normal oral mucosa and in oral squamous cell carcinomas were examined immunohistochemically, and their association with clinicopathological factors and prognosis were then analysed in 69 patients who had been operated on for oral SCC. E-cadherin expression was found in all 69 cases: in 11 cases (16%) it was weak; in 21 (30%) moderate, and in 37 (54%) high. ß-Catenin expression was found in 64 cases (93%): in 18 cases (26%) cell-membrane expression was weak; in 26 (38%) it was moderate; in 19 (28%) it was high, and in one case (1%) there was cytoplasmic staining. No nuclear staining was detected. E-cadherin was significantly associated with histological grade (p=0.002) and alcohol consumption (p=0.05), and ß-catenin was significantly associated with nodal stage (p=0.02), TNM stage (p=0.009), and E-cadherin expression (p=0.01). However, none of them were independent prognostic factors in the disease-specific survival analysis. E-cadherin is closely linked to ß-catenin expression in oral SCC and to tumour differentiation. Alcohol consumption could increase the aggressiveness of SCC, leading to reduced expression of E-cadherin. ß-catenin could be an early marker for the identification of occult metastases in patients with oral SCC.

Focal adhesion kinase overexpression: correlation with lymph node metastasis and shorter survival in oral squamous cell carcinoma.

BACKGROUND: Focal adhesion kinase (FAK) has been identified as a key mediator in tumor progression. The objective of this study was to determine the role of FAK as a predictor of neck node metastasis and poor prognosis in oral squamous cell carcinomas (OSCCs). METHODS: FAK expression in normal oral mucosa and in 69 OSCCs was examined by immunohistochemistry, and the percentage of stained cells was recorded. The correlation of these findings with clinicopathologic variables and survival was studied. RESULTS: FAK expression in OSCCs was heterogeneous: 33.3% of cases showed weak expression; 23.2%, moderate expression, and 33.3% cases showed high expression. FAK expression significantly correlated with tumor size (p = .010), neck node metastasis (p = .01), and local tumor recurrence (p = .01). FAK expression was an independent prognostic factor in the survival analysis (p = .017). CONCLUSIONS: Increased expression of FAK may play a role in invasiveness and metastasis of OSCCs, which contribute to poor prognosis and low survival.

In oral squamous cell carcinoma, high FAK expression is correlated with low P53 expression.

Focal adhesion kinase (FAK) and p53 have been associated with metastatic activity and a poor prognosis in oral squamous cell carcinoma (OSCC). Recently, a feedback mechanism in which FAK regulates p53 has been proposed. The present study aims to determine the role of p53 in FAK regulation in these tumors. FAK and p53 expression was examined by immunohistochemistry in normal oral mucosa and in 67 oral squamous cell carcinomas. p16(INK4a) was also studied in view of its association with human papillomavirus infection. The association between FAK and p53 was subsequently analyzed. FAK expression in OSCCs was heterogeneous: 22 (33 %) cases showed weak expression, 16 (24 %) showed moderate expression, and 22 (33 %) cases showed high expression. Regarding p53, 31 of 67 (46 %) available tumor specimens showed negative staining, and 36 of 67 (54 %) showed positive nuclear staining for p53. FAK expression was inversely correlated with p53 expression (Fisher's exact test, p = 0.005). There was no association between p16(INK4a) and p53 or FAK expression. In conclusion, our results support the hypothesis that FAK activity might be involved in the down-regulation of p53 expression in OSCC.

Retrospective analysis of 314 orbital fractures.

OBJECTIVE: The aim of this study was to retrospectively review the orbital fractures treated at our institution, especially epidemiologic aspects, treatment options, and postoperative sequelae. STUDY DESIGN: Three hundred fourteen patients with orbital fractures treated at the Department of Oral and Maxillofacial Surgery of the Central University Hospital in Asturias (Spain) between 2000 and 2006 were retrospectively reviewed. The patients were evaluated by age, gender, etiology, diagnostic tools, fracture pattern, treatment, and complications. RESULTS: The most common causes of injury were motor vehicle accidents (29.6%), followed by falls (27.4%). Men in the sixth decade were most affected. One hundred forty-four patients (46%) underwent internal fixation with titanium miniplates, and 17 (5.4%) required orbit floor implants. The most frequent sequelae were infraorbital nerve hypoesthesia (24.5%), enophthalmos (3.8%), and diplopia (2.2%). CONCLUSIONS: In our area of 1 million inhabitants, falls are the second cause of orbital fractures, which can be attributed to the large aged population. Postoperative complications cannot be definitely evaluated until a few months after the surgery.

Bilateral carcinoma in situ of Wharton's duct after chronic obstructive sialadenitis: inflammation as the cause of malignancy?

A case of bilateral carcinoma in situ of Wharton's duct after chronic sialadenitis is reported. The patient, a 54-year-old man, complained of recurrent pain and swelling in the left lower submandibular region. Computed tomography showed large stones in the hilar area of both submandibular glands. The patient underwent bilateral submandibular excision. Histologic and immunohistochemical examination revealed squamous metaplasia with areas of carcinoma in situ in both right and left ducts adjacent to the calculus. To the best of our knowledge, this is the first case report in the literature describing an association between obstructive sialadenitis and carcinoma in situ of Wharton's duct. We discuss etiologic factors and chronic inflammation as a possible cause of malignancy.

Survival after free flap reconstruction in patients with advanced oral squamous cell carcinoma.

PURPOSE: The purpose of the present study was to assess the effect of free-flap reconstruction on the survival of patients treated for oral squamous cell carcinoma. PATIENTS AND METHODS: The present study was based on a retrospective cohort of 98 patients. Of the 98 patients, 49 underwent surgical reconstruction with microvascular tissue transfer (test group) and in 49 (control group), only local or regional flaps were used. RESULTS: For the free-flap group, the average follow-up period was 34.6 months. For the control group, the average follow-up was 39.8 months. At the end of the follow-up period, 23 (47%) and 33 (67.3%) patients had died of oral squamous cell carcinoma in the microvascular reconstructive and control group, respectively. The difference in the final status between the 2 groups was statistically significant (P = .03). In the free-flap group, the mean and median survival time was 65 and 60 months. In the locoregional flap group, the mean and median survival time was 54 and 24 months, respectively. No difference was seen in the survival time between the free-flap and local flap groups (P = .2). Univariate Kaplan-Meier analysis revealed that positive surgical margins were significantly associated with shortened survival in the free-flap group and that recurrence was significant in both reconstructive groups. On multivariate Cox regression analysis, the status of the resection margin (P = .07) and tumor recurrence (P < .0005) showed a significant relationship with survival. CONCLUSION: Patients with free-flap reconstruction of surgically created defects after oral cancer resection showed a trend toward better 5-year survival.

Clinical and immunohistochemical analysis of orbital metastasis from prostate carcinoma.

Orbital tumors can present with different symptoms, especially ophthalmic disturbances. We describe 1 patient with an orbital metastasis from prostate carcinoma presenting with proptosis and give details of his presentation, diagnostic tools, and treatment. This is a rare case. Possible ocular spread of prostate adenocarcinoma and the diagnostic techniques used are discussed. It is stressed that immunohistochemical studies and comparison with primary tumor may be essential for a definitive diagnosis. The treatment of prostate orbital metastases is also reviewed.

Merkel cell carcinoma: Our experience in this rare pathology

Merkel cell carcinoma (MCC) was first described in 1972 by Toker, who described five cases of the so-called“trabecular carcinoma of the skin”. MCC is a rare, aggressive skin cancer that affects mainly the elderly. Sun exposedareas are mainly affected, specially the head and neck. Immunohistochemical analysis is essential to reacha correct diagnosis. According to the origin of MCC, the tumor expresses both epithelial and neuroendocrinemarkers. MCC has a propensity for recurrence, regional and distant metastases. Several treatment options areavailable, such as surgical excision or Moh’s surgery, accompanied by neck dissection or radio and chemotherapyin advanced cases. The present study aims to evaluate the clinical behaviour and the evolution of five cases of thisdisease that were treated at our institution (reference to 1100000 inhabitants) in the last five years. It is stressed onthe bad prognosis of this pathology, which presents high rates of locoregional recurrence, even though the recentadvances in radio and chemotherapy (AU)

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Posttraumatic frontal mucocele.

Mucoceles of the frontal sinus are expansive cysts filled of the mucus secreted by goblet cells interspersed in the ciliated mucosa. The aim of this article was to present a case of a frontal mucocele that was developed in a 31-year-old man 19 years after having had a frontal sinus fracture. This is a rare entity. Frontal sinus fractures must be treated by a multidisciplinary team to avoid all possible sequelae. An adequate primary management of frontal sinus fractures is essential to prevent complications. This may include conservative attitude, reduction and fixation with miniplates, obliteration, cranialization, or grafting. Removal of any rest of epithelium is mandatory in this sense.

Clinical significance of annexin A2 downregulation in oral squamous cell carcinoma.

BACKGROUND: The purpose of this study was to determine the expression of Annexin A2 (ANXA2) in normal oral epithelium and in oral carcinomas to correlate these findings with prognostically relevant variables. METHODS: ANXA2 expression in normal oral mucosa and in 106 oral squamous cell carcinomas was examined by immunohistochemistry. RESULTS: ANXA2 expression was detected in basal and suprabasal cell layers of normal epithelium, and immunostaining was preferentially membrane-localized. ANXA2 expression was significantly correlated with the histopathological grade, tumor size, and recurrence, but ANXA2 expression was not an independent prognostic factor. CONCLUSION: The reduction of ANXA2 expression in poorly differentiated tumors is expected to result in a loss of function aimed at the coordination of membrane signaling enzyme complexes. The consequences may manifest as an alteration of epithelial tissue growth and remodeling which eventually exert an influence on tumor progression and metastasis.

Synchronous squamous cell carcinoma and chronic lymphocytic leukemia of the palate.

Although multiple synchronous malignancies of the same histological type have been described frequently in the upper aerodigestive tract, this is a less frequent phenomenon when dealing with tumors of different lineage. We present a case of a man who developed simultaneously an oral squamous cell carcinoma and chronic lymphocytic lymphoma of the palate without any previous risk factors. To the best of our knowledge, this is the first case well documented in the literature of synchronous oral squamous cell carcinoma and chronic lymphocytic lymphoma of the palate in the same sample. The presence of multiple primary malignancies of different histological types not only complicates the treatment but also worsens the prognosis of the patient.

Merkel cell carcinoma: our experience in this rare pathology.

Merkel cell carcinoma (MCC) was first described in 1972 by Toker, who described five cases of the so-called "trabecular carcinoma of the skin ". MCC is a rare, aggressive skin cancer that affects mainly the elderly. Sun exposed areas are mainly affected, specially the head and neck. Immunohistochemical analysis is essential to reach a correct diagnosis. According to the origin of MCC, the tumor expresses both epithelial and neuroendocrine markers. MCC has a propensity for recurrence, regional and distant metastases. Several treatment options are available, such as surgical excision or Moh's surgery, accompanied by neck dissection or radio and chemotherapy in advanced cases. The present study aims to evaluate the clinical behaviour and the evolution of five cases of this disease that were treated at our institution (reference to 1100000 inhabitants) in the last five years. It is stressed on the bad prognosis of this pathology, which presents high rates of locoregional recurrence, even though the recent advances in radio and chemotherapy.

Unilateral absence of submandibular gland secondary to stones. Aplasia versus early atrophy

Major salivary gland absence is a rare disorder. The cause of congenital absence of the salivary glands has not been determined, but it may be associated with ectodermal defects of the first and second branchial arches. Isolated absence of a unilateral submandibular gland is an unusual entity with less than ten cases reported in the literature.The etiopathogenesis of isolated absence of a major salivary gland without other developmental anomaliesis still unclear. The formation of a sialolith within the remaining Wharton’s duct, associated with isolated aplasia(versus atrophy) of a unilateral submandibular gland has been recently reported. We describe in this work two cases of sialolithiasis within the ipsilateral remaining Wharton´s duct in patients with isolated absence of a unilateral submandibular gland. In the cases reported, absence of the submandibular gland may have been the result ofthe complete acinar atrophy secondary to an early obstruction of Wharton´s duct (AU)

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