Innervation of the Human Cavum Conchae and Auditory Canal: Anatomical Basis for Transcutaneous Auricular Nerve Stimulation

The innocuous transcutaneous stimulation of nerves supplying the outer ear has been demonstrated to be as effective as the invasive direct stimulation of the vagus nerve for the treatment of some neurological and nonneurological disturbances. Thus, the precise knowledge of external ear innervation is of maximal interest for the design of transcutaneous auricular nerve stimulation devices. We analyzed eleven outer ears, and the innervation was assessed by Masson’s trichrome staining, immunohistochemistry, or immunofluorescence (neurofilaments, S100 protein, and myelin-basic protein). In both the cavum conchae and the auditory canal, nerve profiles were identified between the cartilage and the skin and out of the cartilage. The density of nerves and of myelinated nerve fibers was higher out of the cartilage and in the auditory canal with respect to the cavum conchae. Moreover, the nerves were more numerous in the superior and posterior-inferior than in the anterior-inferior segments of the auditory canal. The present study established a precise nerve map of the human cavum conchae and the cartilaginous segment of the auditory canal demonstrating regional differences in the pattern of innervation of the human outer ear. These results may provide additional neuroanatomical basis for the accurate design of auricular transcutaneous nerve stimulation devices

Long-Term Mortality of Patients with an Alcohol-Related Wernicke-Korsakoff Syndrome

Aims: To characterize a series of contemporary patients with alcohol-related Wernicke's encephalopathy (WE) or Korsakoff's syndrome (KS) and to update the current prognosis of disease. Methods: Retrospective and prospective study of patients diagnosed with an alcohol-related WE or KS between 2002 and 2011 in a tertiary hospital. Socio-demographic, alcohol use characteristics, signs and symptoms, co-morbidity and blood parameters were obtained at admission. Patients were followed up until 2013 and causes of death were ascertained through the review of charts. Results: Sixty-one patients were included (51 with WE and 10 with KS). Among patients with WE, 78% were men and age at diagnosis was 57 years (interquartile range (IQR): 49-66). Twenty-three percent fulfilled the classic WE triad. Regarding Caine's criteria for WE, 70.6% presented with at least two out of four signs or symptoms. Median follow-up of patients with WE syndrome was 5.3 years (IQR: 2.6-8.8), the cumulated mortality was 45% and death rate of 7.4 × 100 person-years (95% confidence interval (CI): 4.8-10.9). Overall, 50% of patients would be expected to die within 8 years of WE episode and main causes of death included serious bacterial infections (44.5%) and cancer (33.3%). Conclusions: Survival of patients with an alcohol-related Wernicke-Korsakoff syndrome is poor; pursuing treatment of alcohol use disorder and early diagnosis of thiamine deficiency is a priority for improving clinical outcome

Maxillofacial metastasis of genitourinary origin. A report of 3 cases and review of the literature

Introduction: The maxillofacial region can harbour a wide range of primary tumours, as well as secondary tumours spreading from distant sites. Rare, though nevertheless important among the latter are genitourinary tumours, such as clear cell renal carcinoma and cervical cancer. Diagnosis of the maxillofacial metastasis sometimes precedes that of the original site, though in other cases the metastasis may arise many years after treatment of the primary tumour. Case report: We present three cases of maxillofacial metastasis of genitourinary tumours, two clear cell renal ade-nocarcinoma and squamous cell carcinoma of the uterine cervix. The patients were referred our hospital service for diagnosis and treatment, after having been initially evaluated for buccodental symptoms. Discussion: The appearance of a maxillofacial tumour, initially with the aspect of a primary tumour, may sometimes be the consequence of haematogenous dissemination from another site, such as these surprising cases originating in the genitourinary area. If disseminated metastatic disease is suspected, an extensive oncological screening should be done to evaluate the best therapeutic option in each patient. © Medicina Oral S. L

An infinite family of magnetized Morgan-Morgan relativistic thin disks

Applying the Horsk\'y-Mitskievitch conjecture to the empty space solutions of Morgan and Morgan due to the gravitational field of a finite disk, we have obtained the corresponding solutions of the Einstein-Maxwell equations. The resulting expressions are simply written in terms of oblate spheroidal coordinates and the solutions represent fields due to magnetized static thin disk of finite extension. Now, although the solutions are not asymptotically flat, the masses of the disks are finite and the energy-momentum tensor agrees with the energy conditions. Furthermore, the magnetic field and the circular velocity show an acceptable physical behavior.Comment: Submitted to IJTP. This paper is a revised and extended version of a paper that was presented at arXiv:1006.203

Reverse Logistics and Urban Logistics: Making a Link

5684This work is aimed at analyzing potential links between reverse logistics and urban logistics and describing opportunities for collaboration between both areas of research. A description of the current state-of-the-art is provided in order to highlight the main challenges faced by both disciplines. For example, regarding reverse logistics, new recovery options, marketing strategies for recovered products, and legislation issues on the return of products in specific contexts; in regards to urban logistics, long-term planning, stakeholders’ engagement, information management, efficiency, reliability and safety, and new business models are some of such key challenges. Despite the growing interest shown in both logistics areas and their relevance for companies and consumers, reverse logistics and urban logistics are two concepts that are still somewhat unknown and, above all, treated as being relatively separated. However, there exist some aspectswhere the two disciplines converge and thatmay represent opportunities for collaboration, for example, the proper treatment and management of urban waste, and the efficient management of commercial refunds and returns. In addition, other key issues, such as land use, city typology, infrastructures, and stakeholders’ engagement should be further analyzed in order to keep advancing in the description of links between both areas.S

A Single Nucleotide Polymorphism in the RASGRF2 Gene Is Associated with Alcoholic Liver Cirrhosis in Men

Background Genetic polymorphisms in the RAS gene family are associated with different diseases, which may include alcohol-related disorders. Previous studies showed an association of the allelic variant rs26907 in RASGRF2 gene with higher alcohol intake. Additionally, the rs61764370 polymorphism in the KRAS gene is located in a binding site for the let-7 micro-RNA family, which is potentially involved in alcohol-induced inflammation. Therefore, this study was designed to explore the association between these two polymorphisms and susceptibility to alcoholism or alcoholic liver disease (ALD). Methods We enrolled 301 male alcoholic patients and 156 healthy male volunteers in this study. Polymorphisms were genotyped by using TaqMan® PCR assays for allelic discrimination. Allelic and genotypic frequencies were compared between the two groups. Logistic regression analysis was performed to analyze the inheritance model. Results The A allele of the RASGRF2 polymorphism (rs26907) was significantly more prevalent among alcoholic patients with cirrhosis (23.2%) compared to alcoholic patients without ALD (14.2%). This difference remained significant in the group of patients with alcohol dependence (28.8% vs. 14.3%) but not in those with alcohol abuse (15.1% vs. 14.4%). Multivariable logistic regression analysis showed that the A allele of this polymorphism (AA or GA genotype) was associated with alcoholic cirrhosis both in the total group of alcoholics (odds ratio [OR]: 2.33, 95% confidence interval [CI]: 1.32–4.11; P = 0.002) and in the group of patients with alcohol dependence (OR: 3.1, 95% CI: 1.50–6.20; P = 0.001). Allelic distributions of the KRAS polymorphism (rs61764370) did not differ between the groups. Conclusions To our knowledge, this genetic association study represents the first to show an association of the RASGRF2 G>A (rs26907) polymorphism with ALD in men, particularly in the subgroup of patients with AD. The findings suggest the potential relevance of the RAS gene family in alcoholism and ALD

Treatment with Natalizumab in Relapsing–Remitting Multiple Sclerosis Patients Induces Changes in Inflammatory Mechanism

Natalizumab is a widely accepted drug for the relapsing–remitting subtype of multiple sclerosis (RRMS). The present longitudinal exploratory study in RRMS patients analyzes the effects of natalizumab treatment on the levels of pro-inflammatory and anti-inflammatory cytokine protein levels and also the frequency and suppressor function of regulatory T cells. Flow cytometry was used to determine cytokines and regulatory T cell frequency while regulatory T cell suppressor function was assayed in vitro at different time-points after starting with natalizumab. Results showed serum levels of pro-inflammatory interferon gamma and interleukin (IL)-12p70, as well as anti-inflammatory IL-4 and IL-10, were elevated just a few hours or days after first IV infusion of natalizumab. Interestingly, other cytokines like IL-5 or IL-13 were also elevated while pro-inflammatory IL-17, IL-2, and IL-1β increased only after a long-term treatment, suggesting different immune mechanisms. In contrast, we did not observe any effect of natalizumab treatment on regulatory T cell frequency or activity. In conclusion, these results suggest natalizumab has other immunological effects beyond VLA-4 interaction and inhibition of CNS extravasation, the relevance of which is as yet unknown and warrants further investigation

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study

Background: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.Aims: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.Methods: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.Results: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300 mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24 h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.Conclusions: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 +/- 20.6% vs 93.6 +/- 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 +/- 5.2 mm vs 19.9 +/- 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment