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Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) is used to assist brain tumor resection, especially for high-grade gliomas but also for low-grade gliomas, metastasis, and meningiomas. With the increasing use of this technique, even to assist biopsies, high-grade glioma-mimicking lesions had misled diagnosis by showing 5-ALA fluorescence in non-neoplastic lesions such as radiation necrosis and inflammatory or infectious disease. Since only isolated reports have been published, we systematically review papers reporting non-neoplastic lesion cases with 5-ALA according with the PRISMA guidelines, present our series, and discuss its pathophysiology. In total, 245 articles were identified and 12 were extracted according to our inclusion criteria. Analyzing 27 patients, high-grade glioma was postulated as preoperative diagnosis in 48% of the cases. Microsurgical resection was performed in 19 cases (70%), while 8 patients were submitted to biopsy (30%). We found 4 positive cases in demyelinating disease (50%), 4 in brain abscess (80%), 1 in neurocysticercosis (33%), 1 in neurotoxoplasmosis, infarction, and hematoma (100%), 4 in inflammatory disease (80%), and 3 in cortical dysplasia (100%). New indications are being considered especially in benign lesion biopsies with assistance of 5-ALA. Using fluorescence as an aid in biopsies may improve procedure time, number of samples, and necessity of intraoperative pathology. Further studies should include this technology to encourage more beneficial uses.

Among the several approaches described to the jugular foramen (JF), the retrosigmoid infralabyrinthine (suprajugular) approach was one of the most recently described.To describe the indications, limitations, and operative nuances of the suprajugular approach.We provided a pertinent review of the anatomy, indications, preoperative evaluation, surgical steps and nuances, and postoperative management.The suprajugular approach is suitable for tumors occupying the intracranial compartment with limited extension into the JF. Volume, width, and configuration of the foramen dictate the feasibility of the approach. Tumors invading the venous system are not suitable for this approach. Preoperative 3-dimensional MRI and computed tomography are used to evaluate intrajugular extension, relationship between the tumor and the jugular bulb (JB), venous system invasion, and shape of the JF. During surgery, exposition of the entire posterior border of the sigmoid sinus is needed and removing the bone over the JB. After identification of the JF, the jugular notch and intrajugular process of the roof of the foramen are removed and intrajugular resection is completed. In cases of high-riding JB, it may be gently pushed down to allow visualization of the anterior foramen. In cases of JB laceration, it may be repaired using a muscle patch and usually does preclude further resection.The suprajugular approach is variation of the retrosigmoid approach that, when properly indicated, provides excellent exposure of the medial JF, with most anatomical variations and intraoperative complications predicted by a comprehensive preoperative evaluation.

Lipoid proteinosis (LP) or Hyalinosis Cutis et Mucosae or Urbach-Wiethe disease is a rare autosomal recessive genodermatosis characterized by an amorphous hyaline material deposition in the skin mucosa and viscera. The clinical symptoms of this disease often begin in childhood, which persist throughout life. Skin manifestations include inflammation, scaling, acne, and eventually ulceration, and hyaline amorphous deposits in these areas of the wound cause a waxy and thick appearance on the skin. In addition, wounds leave atrophic scars like chickenpox.Herein, we present the first case of LP in the north of Iran; although LP is a sporadic disease, it occurs all around the world, with about 400 cases worldwide having been reported thus far.We report the case of a 28-year-old female patient with a history of skin lesions on her face, scalp, extremities, and buttock, as well as hoarse cry, respiratory problems, dysphagia, and migraine since childhood. There was no evidence of other clinical presentations. A biopsy was taken from the lesions, and the patient was diagnosed with LP. A laryngeal laser was performed for the patient, and peeling creams were used for her skin lesions.According to previous findings, there has been no case report of LP with systemic symptoms in the north of Iran.

BackgroundESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees.MethodologyNational representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher’s exact test, were used.ResultsNational representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system.ConclusionSince the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

Fertility, health, education, and other outcomes of interest to demographers are the product of an individual's genetic makeup and their social environment. Yet, gene × environment (G×E) research deploys a limited toolkit on the genetic side to study the gene–environment interplay, relying on polygenic scores (PGSs) that reflect the influence of genetics on levels of an outcome. In this article, we develop a genetic summary measure better suited for G×E research: variance polygenic scores (vPGSs), which are PGSs that reflect genetic contributions to plasticity in outcomes. First, we use the UK Biobank (N ∼ 408,000 in the analytic sample) and the Health and Retirement Study (N ∼ 5,700 in the analytic sample) to compare four approaches to constructing PGSs for plasticity. The results show that widely used methods for discovering which genetic variants affect outcome variability fail to serve as distinctive new tools for G×E. Second, using the PGSs that do capture distinctive genetic contributions to plasticity, we analyze heterogeneous effects of a UK education reform on health and educational attainment. The results show the properties of a useful new tool for population scientists studying the interplay of nature and nurture and for population-based studies that are releasing PGSs to applied researchers.

Objectives Focal hyperintensity in the dorsal brainstem (HDB) has been described in large cerebellopontine angle tumours and is thought to represent vestibular nuclei degeneration, but its functional significance has not been thoroughly investigated. Our aim was to analyse its relationship to imaging characteristics of the tumour and inner-ear structures and to vestibulocochlear functional tests. Methods We retrospectively reviewed 54 patients with a histological diagnosis of vestibular schwannoma (VS). Magnetic resonance imaging tumour characteristics (size, cystic composition and distance from the cochlear aperture), signal intensity ratio of the cochlea and vestibule in fluid-attenuated inversion recovery (FLAIR) and fast imaging employing steady-state acquisition (FIESTA)/fast spin-echo imaging with variable flip angles (CUBE) and vestibulocochlear function tests (audiometry, auditory brainstem response (ABR) and video head impulse testing (vHIT)) were obtained. Statistical analyses were performed to evaluate their relation to focal HDB. Results Focal HDB was found in 22% of VS. It was significantly associated with large ( p Conclusions Focal HDB in patients with VS was associated with increased signal intensity ratio of the cochlea on FLAIR in patients with VS but not directly to the results of vestibulocochlear function tests.

Background Baboon syndrome is a rare, type IV hypersensitivity reaction causing a maculopapular rash. Tamoxifen is an antineoplastic agent, working as an estrogen receptor antagonist, also called a selective estrogen receptor modulator. A variety of rashes were reported with Tamoxifen use to‐date except baboon syndrome. The Tamoxifen‐induced baboon syndrome seems to be reversible, as discontinuation of the drug improves clinical outcomes. Aim Herein, we present the first case of Tamoxifen‐induced baboon syndrome which occurred 8 years after initiation of Tamoxifen use. Patients A 44‐year‐old woman presented with papulovesicular eruption on her body and erythema on her face for a duration of 6 months. There was no evidence of ocular or mucosal involvement. She was diagnosed with breast cancer and treated with tamoxifen 10 mg twice daily over the past 8 years. She was not taking other medications or over‐the‐counter supplements at the time of presentation. The patient underwent urgent skin biopsies of two lesions on her buttock and thigh. No organisms were seen on Gram stain. The patient's skin biopsy revealed extensive hyperorthokeratosis, minimal parakeratosis, hypergranulosis, and lichenoid interface dermatitis in the irregularly acanthotic epidermis supporting diagnosis of fixed drug eruption. Following a multidisciplinary discussion, the patient was diagnosed with baboon syndrome or symmetrical drug‐related intertriginous and flexural exanthema (SDRIFE) associated with Tamoxifen. Results Hence, Tamoxifen was immediately discontinued and treated with oral steroid along with topical agents. She showed improvement of clinical abnormalities within days after discontinuation of Tamoxifen. Conclusions Given the widespread use of Tamoxifen in the management of patients with breast cancer, it is important that healthcare professionals monitor for rare, however clinically significant, and potentially life‐threatening dermatological manifestations of Tamoxifen use, such as baboon syndrome.

A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1–4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1–3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1–4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine’s efficacy.

Background AA is an acquired dermatosis distributed universally, with multifactorial etiology. It affects the hair follicle with or without nail involvement, resulting in an acute nonscarring alopecia with a relapsing course.1 Being a relatively common skin disease, LPP (lichen planopilaris) is initiated by a chronic lymphocytic inflammation that selectively destructs the hair follicles and eventually leads to scarring alopecia. Also, even though there is enough literature available for the co-existence of AA and LPP with each other and their association with other autoimmune conditions, there are only very few reports on the anatomical concomitance of both disorders.3 AIMS: Although the incidence of not only one but two autoimmune diseases in an immunosuppressed individual is very unusual, we hereby report a case of co-localization of AA and LPP in a patient receiving immunosuppression due to a previous history of SLE (Systemic lupus erythematosus). Patients A 37-year-old woman, housewife, presented to our office with general alopecia on the scalp since about two years ago (Figure 1), particularly on the vertex which was accompanied by mild itching and trichodynia. She had a history of hypothyroidism and lupus erythematosus arthritis. She had been receiving long-term treatment with prednisolone, hydroxychloroquine, azathioprine, and levothyroxine but had not been treated for hair loss. Despite being on all of the above-mentioned immunosuppressants, the patient developed AA and LPP which are both immune-mediated diseases. Results In addition to continuing her oral immunosuppressants, the patient was treated with Minoxidil 5% and Clobetasol solution as well as a higher dose of Azathioprine than she was receiving beforehand. Approximately, 3 months into the treatment, the follicular hyperkeratosis and scalp erythema resolved. Also, hair growth could be seen on AA spots. Conclusion Our case report is indicating the possibly mutual immunopathogenesis of these two T cell-mediated disorders. Furthermore, we want to bring attention to the probability of new autoimmune diseases occurring even during treatment with immunosuppressive medications.

The study performed a comparison of short-term results after high intensity electromagnetic treatment and electrostimulation for improvement of urinary incontinence., Objectives Pelvic floor muscles (PFMs) weakening and urinary incontinence (UI) represent health issues that have a negative impact on daily life. This study compares the immediate efficiency of high-intensity focused electromagnetic (HIFEM) therapy and electrostimulation for the treatment of weakened PFMs, accompanied by the UI. Methods Ninety-five parous women were considered for the study. Symptomatic patients received either HIFEM or electrostimulation treatment. Treated patients completed 10 therapies scheduled 2 to 3 times per week (HIFEM) or every other day (electrostimulation). Patients underwent examination by 3-dimensional transperienal ultrasound at the baseline and posttreatments. Levator-urethra gap, anteroposterior diameter, laterolateral diameter of levator hiatus, and hiatal area were measured. In addition, Pelvic Floor Disability Index 20 questionnaire and subjective evaluation of patient’s intimate health were assessed. Results Enrolled patients were divided into group I (n = 50, HIFEM), group II (n = 25, electrostimulation), and group III (n = 20, control) according the indication and treatment modality. Three-dimensional ultrasounds showed positive changes in dynamics of the pelvic floor posttreatment (decreased anteroposterior diameter, laterolateral diameter, and hiatal area). However, the significant (P < 0.05) changes of pelvic floor integrity were observed only in group I. In addition, group I achieved greater level of improvement in Pelvic Floor Disability Index 20 questionnaire compared with group II (52% and 18% respectively; P < 0.001). Substantially fewer patients in group I reported urine leakage after treatments. Conclusions Posttreatment results suggest that HIFEM technology is suitable for treatment of PFMs weakening and showed to be more effective when compared with electrostimulation in short-term. Therefore, we recommend HIFEM as treatment option for weakened PFMs and UI.

biIntroduction:/i/bInfantile hydrocephalus (HCP) is a condition in which there is an abnormal buildup of cerebrospinal fluid in the ventricles within the first few months of life, which puts pressure on surrounding brain tissues. Compression of the developing brain increases the risk of secondary brain injury and cognitive disabilities.biMethods:/i/bIn this study, we used diffusion-weighted imaging and resting-state functional magnetic resonance imaging to investigate the effects of ventricle dilatation on structural and functional brain networks in children with shunted infantile HCP and examined how these brain changes may impact executive function.biResults:/i/bWe found that children with HCP have altered structural and functional connectivity between and within large-scale networks. Moreover, hyperconnectivity between the ventral attention and default mode network in children with HCP correlated with reduced executive function scores. Compared with typically developing age-matched control participants, our patient population also had lower fractional anisotropy in posterior white matter.biDiscussion:/i/bOverall, these findings suggest that infantile HCP has long-term effects on brain network connectivity, white matter development, and executive function in children at school age. Future work will examine the relationship between ventricular volumes before shunt placement in infancy and brain network development throughout childhood.

Objective The stability of the transverse expansion in passive self-ligating bracket treatments is a debated topic in orthodontics. However, to date, only 3 reports are available in the literature, with the maximum follow-up of 3 years after the end of therapy. The present study aims to evaluate the stability of orthodontic treatment with self-ligating brackets in a 6-year follow-up period of time. Materials and methods A sample of 56 non-extractive cases (of whom 33 females, mean age 16.9, SD = 9.0 years) consecutively treated with Damon® system was retrospectively selected. All patients received fixed retainers from canine to canine in both arches at the end of treatment, and no removable retainers were provided. The mean values of the transverse intercusp, transverse centroid and transverse lingual distances were evaluated for all teeth from canines to second molars in both arches. Each measure was calculated at four timepoints: before treatment (T0), at the end of treatment (T1), one year after treatment (T2) and six years after treatment (T3). Transverse diameters were measured for all teeth, starting from the canines to the second molars, for a total of 1680 observations, and subsequently compared in order to evaluate intra-treatment and post-treatment modifications. Results There were increases in all transverse dental measurements during active treatment. A statistically significant (p Conclusion The 6-year follow-up analysis detected that the initial transverse expansion showed a statistically significant relapse in premolars. No relapse was detected at the level of canines, due to the presence of fixed retainers, and minimal at first molars.

Triple-negative breast cancers (TNBCs) are highly aggressive and metastatic. To date, finding efficacious targeted therapy molecules might be the only window of hope to cure cancer. Fibromodulin (FMOD), is ectopically highly expressed on the surface of Chronic Lymphocytic Leukemia (CLL) and bladder carcinoma cells; thus, it could be a promising molecule for targeted therapy of cancer. The objective of this study was to evaluate cell surface expression of FMOD in two TNBC cell lines and develop an antibody-drug conjugate (ADC) to target FMOD positive TNBC in vitro and in vivo.Two TNBC-derived cell lines 4T1 and MDA-MB-231 were used in this study. The specific binding of anti-FMOD monoclonal antibody (mAb) was evaluated by flow cytometry and its internalization was verified using phAb amine reactive dye. A microtubulin inhibitor Mertansine (DM1) was used for conjugation to anti-FMOD mAb. The binding efficacy of FMOD-ADC was assessed by immunocytochemistry technique. The anti-FMOD mAb and FMOD-ADC apoptosis induction were measured using Annexin V-FITC and flow cytometry. Tumor growth inhibition of anti-FMOD mAb and FMOD-ADC was evaluated using BALB/c mice injected with 4T1 cells.Our results indicate that both anti-FMOD mAb and FMOD-ADC recognize cell surface FMOD molecules. FMOD-ADC could induce apoptosis in 4T1 and MDA-MB-231 cells in vitro. In vivo tumor growth inhibition was observed using FMOD-ADC in 4T1 inoculated BALB/c mice.Our results suggests high cell surface FMOD expression could be a novel bio-marker TNBCs. Furthermore, FMOD-ADC could be a promising candidate for targeting TNBCs.

Neurovascular compression syndromes have well characterized clinical symptoms, but precise identification of the pathologic contact between the nerves and vessels can be challenging at neuroimaging. Considering that neurovascular contacts are frequent imaging findings in asymptomatic patients, correct visualization of pathological contact is crucial for the diagnosis and surgical planning. We have used magnetic resonance imaging fusion by overlaying color-coded T1-weighted postcontrast onto high-resolution T2-weighted images to better delineate imaging findings by enhancing vascular structures.

Helicobacter pylori (H. pylori) is a major human pathogenic bacterium that survives in the gastric mucosa. The aim of this study is to evaluate the expression of the target gene network of miR-155-5p in H. pylori-related gastritis using a combination of public gene expression datasets and web-based platforms. To evaluate the expression of genes related to gastritis, we used two datasets from Gene Expression Omnibus (GEO) database. Then, we determined the overlaps between the predicted miR-155-5p target genes and gastritis-dysregulated GEO datasets genes; in the next step, we identified the possible miR-155-5p target-DEGs (Target-Differentially Expressed Genes). Also, we performed multiple bioinformatics analyses to identify the most important targets and downstream pathways associated with this miRNA. Using the UCSC cancer genomic browser analysis tool, we investigated the expression of hub genes in relation to gastric cancer and H. pylori infection, as well as the potential role of hub genes in gastritis, inflammation, and cancer. In this regard, 28 differentially expressed target genes of miR-155-5p were identified. Most of the captured target genes were correlated with the host immune response and inflammation. Based on the specific patterns of expression in gastritis and cancer, CD9, MST1R, and ADAM10 were candidates for the most probable targets of miR-155-5p. Although the focus of this study is primarily on bioinformatics, we think that our findings should be experimentally validated before they can be used as potential therapeutic and diagnostic tools.

Intermediate nerve schwannomas (INS) are extremely rare lesions in literature. They have been described mimicking facial nerve schwannomas, but not vestibular schwannomas (VS). We aimed to review the previously published cases, as well as the evidence to believe that they are far more common, though usually misdiagnosed as facial or VS. We performed a review of PubMed/Medline and Embase of "intermediate nerve schwannoma," "facial nerve schwannoma," "greater superficial petrosal nerve schwannoma," "geniculate ganglion schwannoma," and "chorda tympani schwannoma" to identify all cases of INS, following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement. Furthermore, 2 cases operated at our center are shown to exemplify the proposed hypotheses. No article was excluded from review. Thirteen cases of INS, 11 cases of chorda tympani schwannoma, and 18 cases of greater superficial petrosal nerve schwannoma were found in literature. In facial nerve schwannomas, the predilection of schwannomas for sensory nerves, and the ability to preserve the motor facial nerve during tumor resection support the hypothesis of intermediate nerve as the nerve of origin. For VSs, the different arachnoidal arrangement of medial VS, the sharing of pia mater by the intermediate nerve and vestibular nerve, and the medial Obersteiner-Redlich zone of the intermediate nerve, support the hypothesis of intermediate nerve origin of some VS. The correct identification of the intermediate nerve as a nerve of origin of cerebellopontine angle schwannomas is of uttermost importance, especially when mistaken for VS, as this may account for the heterogeneity of facial and cochlear outcomes after surgery.

OBJECTIVES Tumor factors that influence vestibular function in vestibular schwannoma (VS) have not been properly described. We evaluated whether cystic VSs have different vestibular function than solid VS. Tumor size on vestibular function was also evaluated. STUDY DESIGN Cross-sectional study. SETTING Tertiary referral center. PATIENTS Forty-one cases of sporadic, untreated VS. INTERVENTION Evaluation with video head impulse test and MRI. MAIN OUTCOME MEASURES Tumors were classified as solid, heterogeneous, or cystic and by size using the Hannover classification. Vestibulo-ocular reflex (VOR) gain was correlated to tumor size and cystic status. RESULTS Large VS had worse VOR gain than small lesions (p

The purpose of this study was to investigate and determine the relations between mandibular third molar (M3) impaction types and mandibular angle and condylar fractures.A retrospective study was conducted in patients with mandibular angle and condylar fractures referred to the Oral and Maxillofacial Surgery Department of the Shahid Kamyab Hospital (Mashhad, Iran) from 2013 to 2018. Data sources were patients' hospital documents and panoramic radiographs. Predictor variables were the presence and position of impacted M3s. The Pell-Gregory classification was used to identify the horizontal and vertical positions of impaction. The impaction angulation was determined using the Schiller classification. Outcome variables were the presence of angle and condylar fractures. Data were analyzed using SPSS 16 (IBM Corp, Armonk, NY) and χThe study sample consisted of 117 patients (63.2% with condylar fractures, 30.8% with angle fractures, and 6% with concomitant fractures of the condyle and angle). Most patients (88.9%) with angle fracture had impacted M3s; however, impacted M3s were absent in 59.5% of condylar fracture cases. Mesioangular and vertical positions were the most prevalent impaction angulation types in patients with mandibular angle fracture. Classes II and B were the most frequent horizontal and vertical impaction types, respectively, according to the Pell-Gregory classification. There was a statistically significant difference between fracture site and the presence or absence of impacted M3s (P .001). Moreover, a significant relation was observed between horizontal impaction type and fracture site in patients with impacted M3s (P = .001).The presence of impacted M3s increased the risk of angle fractures and simultaneously decreased the risk of condylar fractures. Fractures of the angle region were more commonly seen in patients with superficially impacted (vs deeply impacted) M3s.

Background Idiopathic normal pressure hydrocephalus (INPH) is characterized by gait disturbance, urinary incontinence and cognitive decline. Symptoms are potentially reversible and treatment is based on cerebrospinal fluid shunting. The tap test (TT) is used to identify patients that will benefit from surgery. This procedure consists of the withdrawal of 20 to 50 mL of cerebrospinal fluid (CSF) through a lumbar puncture (LP) after which the symptoms of the triad are tested. Improvement in the quality and speed of gait are already recognized but cognitive improvement depends on several factors such as tests used, the time elapsed after LP for re-testing, and the number of punctures. Serial punctures may trigger similar conditions as external lumbar drainage (ELD) to the organism. Objective This study aimed to identify how serial punctures affect cognition to increase the sensitivity of the test and consequently the accuracy of surgical indication. Methods Sixty-one patients with INPH underwent baseline memory and executive tests repeatedly following the 2-Step Tap Test protocol (2-STT – two procedures of 30 mL lumbar CSF drainage separated by a 24-h interval). The baseline scores of INPH patients were compared with those of 55 healthy controls, and with intragroup post-puncture scores of the 2-STT. Results The group with INPH had lower performance than the control group in all cognitive tests (RAVLT, Stroop, CFT, FAR-COWA, FAB, MMSE, orientation, mental control), except for the forward digit span test (p = 0.707). After conducting LP procedures, the Stroop test (words, colors and errors), RAVLT (stage A1, A6 and B1), and CFT (immediate and delayed R) scores were equal to those of the control group (p > 0.05). The INPH group presented significant improvement after the first puncture in MMSE (p = 0.031) and in the Stroop Test (points) (p Conclusion Progressive cognitive improvement occurred over the 2-STT and changes were more significant after the second LP in all cognitive domains except for RAVLT (A7). Encephalic alert system ‘arousal’ seems to participate in early improvements observed during 2-STT. The second LP increased the sensitivity of the drainage test to detect changes in cognitive variables, and consequently improved the quality of the method.

Background Single-stage surgical treatment of cranial intraosseous meningiomas includes complete tumor resection followed by aesthetic reconstruction. Tailored tumor resection with a computer-aided design/computer-aided manufacturing custom-made implant for the defect has been advocated in recent years to achieve a satisfactory cosmetic result with reduced operative time and fewer complications. However, several technical nuances related to the area of osseous removal may compromise cranioplasty. Methods We present 2 cases of intraosseous meningiomas (sphenoid wing and retromastoid) to illustrate a step-by-step approach, from preoperative planning to single-step surgery. Results For each case, a customized frame template delimiting bone removal was designed using cranial sutures as anatomical landmarks for precise placement of the cranioplasty template over the area of interest. Conclusions Custom templates based in cranial sutures may benefit single-step frame-guided resection and reconstruction of intraosseous tumors with compelling results.

Background Acute Generalized Exanthematous Pustulosis (AGEP)is a rare, severe skin reactionmainly caused by medications such as antibiotics, anti fungals, Calcium channel blockers and Anti malarias. Although it resolves spontaneously in most patients, systemic corticosteroids are neededin severe cases. Aims In order to determine the drug that is causing this condition, patch testing must be performed. Hydroxychloroquine is a medication that is used for the treatment of rheumatic and dermatologic conditions. And although it has been rarely seen to cause this reaction, we report a case of Hydroxychloroquine-induced (HCQ) AGEP which was confirmed by Patch testing. Patients A woman 49 years of age with an18 month history of mild, untreated Rheumatoid Arthritis experienced an acute episode of arthritis in her right elbow. Upon going to a rheumatologist, Prednisolone 5 mg BID and HCQ 200 mg daily were administered for a 30-day period. But after only 17 days of this treatment, the patient developed generalized erythema and painful pustular eruptions. Prednisolone dosage was changedto 7.5 mg per day andHCQ was discontinued one day afterthe appearance of eruptions. The diffuse erythema started improving a week after the patient's hospitalization.Considering the factthat our patient was receiving multiple potentially causative medications, patch testing was necessary to distinguish the drug responsible for this reaction. Results After the patch testing was done, HCQ-induced AGEP was confirmed. Conclusions Patch testing is the gold standard of determining the responsible drug for an AGEP reaction. It should also be kept in mind that HCQ, although rarely, can cause this condition.

The virion proteins of Kaposi sarcoma-associated herpesvirus (KSHV) were initially characterized in 2005 in two separate studies that combined the detection of 24 viral proteins and a few cellular components via LC-MS/MS or MALDI-TOF. Despite considerable advances in the sensitivity and specificity of mass spectrometry instrumentation in recent years, leading to significantly higher yields in detections, the KSHV virion proteome has not been revisited. In this study, we have re-examined the protein composition of purified KSHV virions via ultra-high resolution Qq time-of-flight mass spectrometry (UHR-QqTOF). Our results confirm the detection of all previously reported virion proteins, in addition to 17 other viral proteins, some of which have been characterized as virion-associated using other methods, and 10 novel proteins identified as virion-associated for the first time in this study. These results add KSHV ORF9, ORF23, ORF35, ORF48, ORF58, ORF72/vCyclin, K3, K9/vIRF1, K10/vIRF4, and K10.5/vIRF3 to the list of KSHV proteins that can be incorporated into virions. The addition of these proteins to the KSHV virion proteome provides novel and important insight into early events in KSHV infection mediated by virion-associated proteins. Data are available via ProteomeXchange with identifier PXD022626.

Macrophages are a critical member of the innate immune system and can intensify tumor invasiveness and assist the growth of neoplastic cells. Moreover, they have the capability to reinforce immunosuppression and angiogenesis. Various investigations suggest that health-related issues, including inflammatory disorders and neoplastic diseases may be caused by environmental toxicant exposure. However, it is still unclear what role these environmental toxicants play in causing carcinogenesis by disturbing the mechanisms of migration, polarization, differentiation, and immune-stimulatory functions of macrophages. Accordingly, in this article, we will explore the interaction between environmental chemicals and inflammatory macrophage processes at the molecular level and their association with tumor progression and carcinogenesis.

Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. However, little is known of the molecular mechanisms of action. Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF-7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG), and inositol triphosphate (IP3). In contrast, silencing of AKR1B10 in breast cancer cells BT-20 and colon cancer cells HCT-8 led to decrease of these lipid messengers. Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. This in turn modulated the phosphorylation of protein kinase C (PKC) isoforms PKCδ (Thr505), PKCµ (Ser744/748), and PKCα/βII (Thr638/641) and activity of the PKC-mediated c-Raf/MEK/ERK signaling cascade. A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. In these cells, phospho-p90RSK, phospho-MSK, and Cyclin D1 expression was increased by AKR1B10, and pharmacological inhibition of the ERK signaling cascade with MEK1/2 inhibitors U0126 and PD98059 eradicated induction of phospho-p90RSK, phospho-MSK, and Cyclin D1. In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway.

OBJECTIVEIn clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled.METHODSThe patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1–2 mg/hour) and HES (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery.RESULTSPooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22–0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17–0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09–0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated.CONCLUSIONSProphylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept.Clinical trial registration no.: DRKS 00000328 (https://drks-neu.uniklinik-freiburg.de/drks_web/)

Summary This study investigated the effects of different doses of epidural fentanyl on the time to onset of epidural analgesia in women in early labour. We hypothesised that onset of epidural labour analgesia (the primary outcome defined as time in minutes from completion of epidural bolus to the first uterine contraction with a numeric pain rating scale [NPRS] score ≤ 3) would be faster with 100 μg of fentanyl epidural bolus compared with 20 μg or 50 μg. Epidural labour analgesia was initiated with 20 μg of fentanyl (F20 group), 50 μg (F50 group) or 100 μg (F100 group) along with 10 ml bupivacaine 0.08% as the loading dose. We randomly allocated 105 patients, with 35 patients in each group. Median (IQR [range]) time to achieve NPRS ≤ 3 was 18 (11–30 [6–20]) min in F20, 10 (8–19 [4–30]) min in F50 and 10 (6–16 [3–30]) min in F100 groups. There was a significant difference in onset times comparing F100 with F20 (p

Evidence of a high interobserver variability of the subjective House-Brackmann facial nerve grading system (HBGS) would justify cost- and time-consuming technological enhancements of objective classifications for facial nerve paresis. A total of 112 patients were recruited for a randomized multi-center trial to investigate the efficacy of prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery. For the present investigation both treatment groups were pooled for the assessment of facial nerve function preoperatively, in the early postoperative course and 1 year after the surgery. Facial nerve function was documented photographically at rest and in motion and classified according to the HBGS by three independent observers (neurosurgeon, neurologist, ENT) and by the investigator of each center. Interobserver variability was considerably different with respect to the three time points depending upon the severity of facial nerve paresis. Preoperative facial nerve function was normal or only mildly impaired (HB grade I or II) and was assessed consistently in 97%. Facial nerve function deteriorated during the early postoperative course and was subsequently documented without dissent in only 36%, with one grade difference in 45%, two grade difference in 17% and three grade difference in 2%. One year after surgery, facial nerve function predominantly improved resulting in a consistent assessment in 66%. Differing ratings were observed in 34% with one grade deviation in 88% and of two grades in 12%. Patients with differing ratings of two or more grades exhibited considerably worse facial nerve function (p

Curcumin is an anticancer agent, but adverse effects and low bioavailability are its main drawbacks, which drives efforts in chemical modifications of curcumin. This study evaluated antiproliferative activity and cancer cell selectivity of a curcumin derivative, curcumin nicotinate (CN), in which two niacin molecules were introduced. Our data showed that CN effectively inhibited proliferation and clonogenic growth of colon (HCT116), breast (MCF-7) and nasopharyngeal (CNE2, 5-8F and 6-10B) cancer cells with IC50 at 27.7 &mu, M, 73.4 &mu, M, 64.7 &mu, M, 46.3 &mu, M, and 31.2 &mu, M, respectively. In cancer cells, CN induced apoptosis and cell cycle arrest at G2/M phase through a p53-mediated mechanism, where p53 was activated, p21 and pro-apoptotic proteins Bid and Bak were upregulated, and PARP was cleaved. In non-transformed human mammary epithelial cells MCF10A, CN at 50 &micro, M had no cytotoxicity and p53 was not activated, but curcumin at 12.5 &micro, M activated p53 and p21 and inhibited MCF10A cell growth. These data suggest that CN inhibits cell growth and proliferation through p53-mediated apoptosis and cell cycle arrest with cancer cell selectivity.

BACKGROUND Fixed Drug Eruption (FDE) is a drug reaction involving the skin and less commonly the mucosal membranes. Tamsulosin is an alpha-1 adrenergic receptor blocker used to treat benign prostatic hyperplasia. Dizziness and headache are among its most common side effects (Singapore Med J, 2018;59:336). Although cutaneous drug eruption has been reported with other alpha-1 adrenergic receptor blockers. AIMS Drug rash due to Tamsulosin is relatively uncommon (Singapore Med J, 2018;59:336). In this case we report an incidence of fixed drug eruption due to Tamsulosin. PATIENTS A 54 year old male, with benign prostatic hyperplasia was referred to our office for evaluation of certain eruptions, having developed his hyper-pigmented patches after 2 weeks of using oral 0.4 mg Tamsulosin per day. Based on the clinical course and the skin biopsy we diagnosed the condition as Tamsulosin associated fixed drug eruption. The most important therapeutic measure was discontinuing Tamsulosin medication. Following this, his eruptions improved remarkably in a few days without complications. RESULTS According to previous findings, there has been no case report on fixed drug eruption caused by Tamsulosin. CONCLUSION Our case is a relatively mild form of fixed drug eruption. Therefore it should be kept in mind that a severe cutaneous drug eruption might occur after Tamsulosin administration.

Significance Metagenomic or social genetic effects—how the genetic makeup of organisms around an individual impacts an individual’s phenotype—have been demonstrated for animals. However, in humans, where experimental manipulation is less feasible, such metagenomic effects of peers have largely been suggestive. Here, we leverage as-if-random variation in same-grade peers to document metagenomic effects on adolescent smoking outcomes. The effect of grade-mates’ genotypes is larger in magnitude than many other predictors of smoking, including ego’s own genotype, being male, and family income. Further, a minority with high genetic propensities to smoke can affect the smoking behavior of an entire grade. This approach offers a way to integrate genetic and environmental influences on human phenotypes., Recent scholarship suggests that the genomes of those around us affect our own phenotypes. Much of the empirical evidence for such “metagenomic” effects comes from animal studies, where the socio-genetic environment can be easily manipulated. Among humans, it is more difficult to identify such effects given the nonrandom distribution of genes and environments. Here we leverage the as-if-random distribution of grade-mates’ genomes conditional on school-level variation in a nationally representative sample. Specifically, we evaluate whether one’s peers’ genetic propensity to smoke affects one’s own smoking behavior net of one’s own genotype. Results show that peer genetic propensity to smoke has a substantial effect on an individual’s smoking outcome. This is true not only when the peer group includes direct friends, and therefore where the individual plays an active role in shaping the metagenomic context but also when the peer group includes all grade-mates and thus in cases where the individual does not select the metagenomic environment. We explore these effects further and show that a small minority with high genetic risk to smoke (‘bad apples’) can greatly affect the smoking behavior of an entire grade. The methodology used in this paper offers a potential solution to many of the challenges inherent in estimating peer effects in nonexperimental settings and can be utilized to study a wide range of outcomes with a genetic basis. On a policy level, our results suggest that efforts to reduce adolescent smoking should take into account metagenomic effects, especially bad apples, within social networks.

Gamma Knife® radiosurgery (GKRS) for trigeminal neuralgia is an effective treatment with at least a 50% reduction of pain in 75-95% of patients. Objective: To present the first series of patients treated for trigeminal neuralgia using GKRS in Latin America. Methods: Retrospective analysis. Analysis consisted of time to improvement of symptoms, best Barrow Neurological Institute scale (BNI) score after procedure, time without pain, time to recurrence and post-procedural hypoesthesia. Results: Nineteen cases of classical trigeminal neuralgia were analyzed and three cases of symptomatic trigeminal neuralgia were described. Mean time from symptom onset to radiosurgery was 99.6 months, and 78.9% of patients had undergone invasive procedures before treatment. Patients were followed for a mean of 21.7 months. BNI I was achieved in 36.8%, IIIa in 21.1%, IIIb in 21.1%, IV in 5.3% and V in 15.7%. New hypoesthesia developed in 12.1% patients, which was associated with achieving BNI I after the procedure (p < 0.05). Time from diagnosis to GKRS was higher in patients who failed to achieve BNI I (143 vs. 76 months). The distance from the root entry zone in patients who achieved BNI I was greater than patients who did not (1.94 vs. 1.14 mm). Mean distance from the root entry zone in patients with new hypoesthesia was 2.85 mm vs. 1.06 mm (p = 0.06). Conclusion: Clinical response to GKRS is related to the time between diagnosis and procedure, thus its indication should be considered early in the management of these patients. RESUMO A radiocirurgia por Gamma Knife (GKRS) para neuralgia do trigêmeo é um tratamento comprovado, com redução de pelo menos 50% da dor em 75-95% dos casos. Objetivo: Apresentar a primeira série de pacientes tratados por neuralgia do trigêmeo com GKRS na America Latina. Métodos: Análise retrospectiva. A análise consistiu no tempo até melhora do sintoma, melhor escala do Barrow Neurological Institute (BNI) depois do procedimento, tempo sem dor, tempo até recorrência e hipoestesia pós-procedimento. Resultados: Dezenove casos de neuralgia do trigêmeo clássica foram analisados e três casos de neuralgia do trigêmeo sintomática foram descritos. Tempo médio entre começo dos sintomas e GKRS foi de 99,6 meses e 78,9% dos pacientes já tinham sido submetidos a procedimento invasivo prévio. O tempo de acompanhamento médio foi de 21,7 meses. BNI I foi conseguido em 36,8%, IIIa em 21,1%, IIIb em 21,1%, IV em 5,3% e V em 15,7%. Nova hipoestesia apareceu em 12,1% dos casos, o que foi associado a conseguir BNI I pós-procedimento (p < 0,05). Tempo desde o diagnóstico até GKRS foi maior em pacientes que não conseguiram BNI I (143 vs. 76 meses). Distância da zona de entrada do nervo em pacientes que conseguiram BNI I foi maior (1,94 vs. 1,14mm). Distância do zona de entrada do nervo em pacientes com nova hipoestesia foi de 2,85mm vs. 1,06mm (p = 0,06) Conclusão: A resposta à GKRS está relacionada ao tempo entre diagnóstico e procedimento, pelo que a indicação de GKRS deve ser considerada cedo no tratamento desses pacientes.

The retrosigmoid suprajugular approach provides a less-aggressive approach for a subset of tumors of the jugular foramen. We described the retrosigmoid suprajugular approach with its advantages, caveats, and indications. A Samii-B2 glossopharyngeal nerve schwannoma is shown to exemplify the procedure. The retrosigmoid suprajugular approach provides an excellent option for tumors with a variable extension into the cerebellopontine cistern and limited extension into the jugular foramen. It is less destructive than the other approaches and allows a good exposure to the posterior part of the jugular foramen.

OBJECT A pilot study of prophylactic nimodipine and hydroxyethyl starch treatment showed a beneficial effect on facial and cochlear nerve preservation following vestibular schwannoma (VS) surgery. A prospective Phase III trial was undertaken to confirm these results. METHODS An open-label, 2-arm, randomized parallel group and multicenter Phase III trial with blinded expert review was performed and included 112 patients who underwent VS surgery between January 2010 and February 2013 at 7 departments of neurosurgery to investigate the efficacy and safety of the prophylaxis. The surgery was performed after the patients were randomly assigned to one of 2 groups using online randomization. The treatment group (n = 56) received parenteral nimodipine (1–2 mg/hr) and hydroxyethyl starch (hematocrit 30%–35%) from the day before surgery until the 7th postoperative day. The control group (n = 56) was not treated prophylactically. RESULTS Intent-to-treat analysis showed no statistically significant effects of the treatment on either preservation of facial nerve function (35 [67.3%] of 52 [treatment group] compared with 34 [72.3%] of 47 [control group]) (p = 0.745) or hearing preservation (11 [23.4%] of 47 [treatment group] compared with 15 [31.2%] of 48 [control group]) (p = 0.530) 12 months after surgery. Since tumor sizes were significantly larger in the treatment group than in the control group, logistic regression analysis was required. The risk for deterioration of facial nerve function was adjusted nearly the same in both groups (OR 1.07 [95% CI 0.34–3.43], p = 0.91). In contrast, the risk for postoperative hearing loss was adjusted 2 times lower in the treatment group compared with the control group (OR 0.49 [95% CI 0.18–1.30], p = 0.15). Apart from dose-dependent hypotension (p < 0.001), no clinically relevant adverse reactions were observed. CONCLUSIONS There were no statistically significant effects of the treatment. Despite the width of the confidence intervals, the odds ratios may suggest but do not prove a clinically relevant effect of the safe study medication on the preservation of cochlear nerve function after VS surgery. Further study is needed before prophylactic nimodipine can be recommended in VS surgery.

This case report discussed a combined surgical-orthodontic rescue of two impacted teeth in a large dentigerous cyst by the means of fixed orthodontic appliances. After careful evaluation of the 3D radiographic exams, extraction of the deciduous elements was carried out, followed by marsupialization and orthodontic traction of the impacted teeth. Surgical procedures, pre- and posttreatment records and orthodontic biomechanical evaluations are discussed.

Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients’ quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.

The illustrious Colombian Professor Salomón Hakim provided the annals of neurology with one of the most brilliant and original bodies of research on record, developing the concept of normal pressure hydrocephalus, as well as proving that ventricular shunting is an effective treatment. Thus, Professor Hakim proved that some of the dementias, at that time considered senile, could be successfully treated. Here the authors present an historical review of his main contributions, which continue to influence the study of dementia to this day. RESUMO O ilustre professor colombiano Salomón Hakim deixou como legado nos anais da neurologia uma das mais brilhantes e originais séries de pesquisa da história, desenvolvendo o conceito de hidrocefalia de pressão normal, bem como introduzindo a derivação ventricular como tratamento efetivo. Assim, Hakim provou que algumas das demências até então consideradas senis tinham possibilidade de tratamento bem-sucedido. Aqui os autores apresentarão uma revisão histórica de suas maiores contribuições, que continuam a influenciar o estudo de demências até os nossos dias.

Restless legs syndrome (RLS) is a disorder commonly found in patients with Parkinson's disease, with descriptions for both conditions impairing dopaminergic transmission in central nervous system. Previous studies in varied populations indicate an association between the presence of RLS and increased cardiovascular risk and, so far, there are no consistent studies of this association in Parkinson's disease. Objective: To analyze the influence of RLS on cardiovascular risk in patients with Parkinson's disease. Methods: We reviewed the medical records of 202 patients diagnosed with Parkinson's disease and verified the presence of RLS, cardiovascular comorbidities, blood pressure measurements, lipid profiles and Framingham Risk Scores. Results: Statistically significant higher values of total cholesterol were found for the RLS group (mean 216.6 mg/dL), as well as for LDL cholesterol (mean 145 mg/dL). No statistical difference was found among the other factors. Conclusion: Patients with Parkinson's disease and RLS have a higher prevalence of dyslipidemia than patients without RLS, suggesting a correlation between restless legs and hyperlipidemia. It is questioned whether the dopaminergic substrate is the main factor in the genesis of the syndrome, as even with the use of dopaminergic agonists by both groups, it was possible to observe differences between groups. The hypothesis of the real interference of the syndrome treatment as a protective factor for cardiovascular risk was generated. RESUMO Síndrome das pernas inquietas é um distúrbio comumente encontrado em pacientes com doença de Parkinson (DP), havendo descrições para ambas as condições de prejuízos na transmissão dopaminérgica no sistema nervoso central. Estudos prévios em populações diversas indicam associação entre a presença da síndrome e aumento do risco cardiovascular, não havendo, até o momento, pesquisas consistentes a respeito desta associação em DP. Objetivo: Analisar a influência da síndrome das pernas inquietas no risco cardiovascular em pacientes com DP. Métodos: Foram revisados prontuários de 202 pacientes com diagnóstico de DP e verificada a presença de síndrome das pernas inquietas, comorbidades cardiovasculares, aferições de pressão arterial, lipidograma e escore de Framingham. Resultados: Valores maiores e estatisticamente significativos de colesterol total foram encontrados para o grupo com pernas inquietas (média de 216.6 mg/dL), assim como para colesterol LDL (média de 145 mg/dL). Não foi encontrada diferença estatística entre os demais fatores. Conclusões: Pacientes com DP e síndrome das pernas inquietas têm maior prevalência de dislipidemia do que pacientes sem a síndrome, o que sugere correlação entre síndrome das pernas inquietas e hiperlipidemia. É posto em prova o substrato dopaminérgico como principal na gênese da síndrome, uma vez que, mesmo sob o uso de agonistas dopaminérgicos por ambos os grupos, foi possível observar diferenças entre os estratos. Gerada a hipótese da real interferência do tratamento da síndrome como fator de proteção para o risco cardiovascular.

According to our research, just few studies described 5-Aminolevulinic acid (5-ALA) use for spinal injuries resection. 5-ALA is known to be especially useful in certain spinal tumor entities such as meningiomas, ependymomas, hemangiopericytomas, and metastasis of central nervous system primary tumors. In contrast, 5-ALA has limited value in other histopathological tumoral entities, as neurinomas and carcinoma metastasis. We describe a microsurgical resection of a spinal cord melanoma through fluorescence-guided technique using 5-ALA in a 36-year-old man. Strong 5-ALA tumor enhancement was evidenced, resulting in gross-total resection. To our knowledge, this is the first case of nonglial intramedullary metastasis with 5-ALA positive staining. We believe that this tool, 5-ALA, could aid in the resection, identification, and differentiation of medullary metastasis.

BACKGROUND Identification of the nerve of origin in vestibular schwannoma (VS) is an important prognostic factor for hearing preservation surgery. Thus far, vestibular functional tests and magnetic resonance imaging have not yielded reliable results to preoperatively evaluate this information. The development of the video head impulse test (vHIT) has allowed a precise evaluation of each semicircular canal, and its localizing value has been tested for some peripheral vestibular diseases, but not for VS. OBJECTIVE To correlate patterns of semicircular canal alteration on vHIT to intraoperative identification of the nerve of origin of VSs. METHODS A total 31 patients with sporadic VSs were preoperatively evaluated with vHIT (gain of vestibule-ocular reflex, overt and covert saccades on each semicircular canal) and then the nerve of origin was surgically identified during surgical resection via retrosigmoid approach. vHIT results were classified as normal, isolated superior vestibular nerve (SVN) pattern, isolated inferior vestibular nerve (IVN) pattern, predominant SVN pattern, and predominant IVN pattern. Hannover classification, cystic component, and distance between the tumor and the end of the internal auditory canal were also considered for analysis. RESULTS Three patients had a normal vHIT, 12 had an isolated SVN pattern, 5 had an isolated IVN pattern, 7 had a predominant SVN pattern, and 4 had a predominant IVN pattern. vHIT was able to correctly identify the nerve of origin in 89.7% of cases (100% of altered exams). CONCLUSION The pattern of semicircular canal dysfunction on vHIT has a localizing value to identify the nerve of origin in VSs.

Vestibular schwannomas (VS) are the most common lesions of cerebellopontine angle (CPA) corresponding to 76-91 % of the cases. Usually, these lesions present typical CT and MRI findings. Non-schwannomatous tumors restricted to the internal auditory meatus (IAM) are rare and their preoperative radiological diagnosis may be difficult. This article describes nine surgically treated intrameatal non-schwannomatous lesions (NSL) and reviews the literature. In the last 16 years, a total of 471 patients with diagnosis of VS were operated on in our department. Preoperatively, 42 patients had diagnosis of intrameatal schwannomas, but surgery revealed in nine cases NSL (3 meningiomas, 3 arachnoiditis/neuritis, 1 cavernoma, 1 vascular loop, and 1 arachnoid cyst). Most frequent symptoms presented by patients with NSL were hearing loss 89 % (8/9) of patients, tinnitus 78 % (7/9), and vertigo 33 % (3/9). Almost all lesions (8/9) presented MRI findings of isointense signal in T1W with contrast enhancement. The only exception was the arachnoid cyst with intracystic bleeding, which was hyperintense in T1W that is not enhanced with contrast. This series shows an occurrence of 21.4 % of non-schwannomatous tumors in 42 cases of lesions restricted to the IAM. Whenever a solely intrameatal enhanced tumor is detected, it is necessary to think about other diagnostic possibilities rather than VS. Therapeutic management may be changed, specially if radiosurgical treatment is considered.

Objective Evaluate the feasibility of an adequate exposure with anatomical preservation of labyrinth structures through retrosigmoid transmeatal approach (RSA) in surgeries for resection of acoustic neuromas/vestibular schwannomas (VS). Method Thirty patients underwent surgical resection and were preoperatively evaluated with fine slice high definition CT scans and 3D-MRI volumetric reconstructions. Extension of internal auditory canal (IAC) opening during surgery was measured using 3 mm right-angle calibrated hook and neuronavigation parameters. Postoperatively, the extension of IAC opening and integrity of the labyrinth were confirmed through preoperatively images procedures. Results The preoperative length of IACs varied between 7.8 and 12.0 mm (mean 9.3 mm, SD 0.98, 95%CI 8.9 to 9.6, and median 9.0 mm). Postoperative images demonstrated adequate opening of the IAC and semicircular channels integrity. Conclusion A complete drilling of the posterior wall of IAC through the RSA is feasible and allows direct visualization of the IAC-fundus without damaging the semicircular canals. Objetivo Avaliar a possibilidade de exposição adequada preservando anatomia das estruturas labirínticas pelo acesso retrosigmóide-transmeatal (RSA) nas ressecções de schwannomas do vestibular (VS). Método Trinta pacientes foram submetidos à ressecção cirúrgica e avaliados no pré-operatório com tomografias de alta definição e reconstruções de ressonância magnética 3D. A extensão da abertura do conduto auditivo interno (CAI) foi medida e confirmada com parâmetros de neuronavegação. No pós-operatório, a extensão da abertura e a integridade do labirinto foram confirmadas por imagens de tomografia computadorizada. Resultados A extensão do CAI no pré-operatório apresentou variação de 7,8-12 mm (média 9,3 mm, DP 0,98, IC95% de 8,9-9,6 e mediana 9 mm). Imagens pós-operatórias demonstraram abertura adequada do IAC e integridade dos canais semicirculares. Conclusão A abertura completa da parede posterior do CAI pelo RSA é possível e permite a visualização direta do fundo do conduto sem prejudicar os canais semicirculares.

Background Overshunting-associated myelopathy (OSAM) is a very rare complication of ventricular shunt therapy, and only 11 previous cases have been reported in the literature. We report the successful surgical management of a case of OSAM in a patient with bilateral jugular vein occlusion and congenital hydrocephalus. Case Description A 45-year-old patient with shunt-dependent, congenital hydrocephalus presented to our department with an 8-year history of progressive tetraparesis and gait disturbance. The patient was wheelchair-dependent. A new magnetic resonance imaging scan of the head revealed slit ventricle syndrome and dural enhancement due to shunt overdrainage. Magnetic resonance imaging and a computed tomography–phlebography of the cervical spine revealed engorgement of the epidural venous plexus with secondary compression of the spinal cord and myelomalacia. Surgery was performed, during which we implanted a shunt valve. The patient recovered from surgery without any new deficits. The tetraparesis improved during the inpatient hospital stay. Computed tomography–phlebography was performed 5 days after surgery and showed that the epidural venous plexus anterior to the cervical spinal cord had returned to nearly normal size. On follow-up examination 3 months after surgery, the patient's strength had improved, and he was able to walk short distances with assistance and with ankle foot orthosis on the right side. Conclusions OSAM has to be considered according to the Monro–Kellie doctrine and is affected by an engorgement of the epidural cervical venous plexus, which can produce cervical myelopathy. Because it can be treated simply by increasing the shunt resistance, surgeons should be aware of the rarely detected overdrainage complication.

Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M).

Introduction The endoscope is thought to provide an improved exposure of the internal auditory meatus after retrosigmoid craniotomy for microsurgical resection of intrameatal tumors. The aim of this study is to quantify the differences in internal acoustic meatus (IAM) exposure comparing microscopic and endoscopic visualization. Methods A retrosigmoid approach was performed on 5 cadaver heads. A millimeter gauge was introduced into the internal auditory meatus, and examinations with a surgical microscope and 0°, 30° and 70° rigid endoscopes were performed. The extent of IAM depth visualized with the microscope and the different angled endoscopes were analyzed. Results The microscopic view allowed an average IAM depth visualization of 2.8 mm. The endoscope allowed an improved exposure of IAM in all cases. The 0°, 30° and 70° endoscopes permitted an exposure that was respectively 96% (5.5 mm), 139% (6.7 mm) and 200% (8.4 mm) more lateral than the microscopic view. Angled optics, however, provided an image distortion, specifically the 70° endoscope. Conclusions The endoscope provides a superior visualization of the IAM compared to the microscope when using a retrosigmoid approach. The 30° endoscope represented an ideal compromise of superior visualization with marginal image distortion. Additional implementation of the endoscope into microsurgery of intrameatal tumors likely facilitates complete tumor removal and might spare facial and vestibulocochlear function. This article is protected by copyright. All rights reserved.

Kaposi sarcoma herpesvirus (KSHV/HHV-8) is a B cell tropic human pathogen, which is present in vivo in monotypic immunoglobulin λ (Igλ) light chain but polyclonal B cells. In the current study, we use cell sorting to infect specific B cell lineages from human tonsil specimens in order to examine the immunophenotypic alterations associated with KSHV infection. We describe IL-6 dependent maturation of naïve B lymphocytes in response to KSHV infection and determine that the Igλ monotypic bias of KSHV infection in vivo is due to viral induction of BCR revision. Infection of immunoglobulin κ (Igκ) naïve B cells induces expression of Igλ and isotypic inclusion, with eventual loss of Igκ. We show that this phenotypic shift occurs via re-induction of Rag-mediated V(D)J recombination. These data explain the selective presence of KSHV in Igλ B cells in vivo and provide the first evidence that a human pathogen can manipulate the molecular mechanisms responsible for immunoglobulin diversity., Author summary Kaposi sarcoma herpesvirus (KSHV) infection of human B cells is poorly understood. KSHV infection in humans is heavily biased towards B cells with a specific subtype of antibody molecule (lambda light chain rather than kappa light chain). This has been a conundrum in the field for years because there is no known physiological distinction between B cells with different light chains that might provide a mechanism for this bias. Here, we develop a novel system for infecting B cells from human tonsil with KSHV and tracking how the virus alters the cells over time. Using this system, we demonstrate a number of KSHV-driven alterations in B cells, including the fact that KSHV infection of kappa light chain positive B cells drives them to become lambda light chain positive by re-inducing recombination events that are normally restricted to B cell development in the bone marrow. We believe that this study is the first demonstration that a virus can alter immunoglobulin specificity via direct infection of B cells.

Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors.In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295.Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4-45·2]; p0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1-39.8]; p0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported.Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab.Eli Lilly and Company.

Beta oscillations are associated with motor function and are thought to play a role in movement impairment. In a recent magnetoencephalography (MEG) study, Rossiter et al. ( J Neurophysiol 112: 2053–2058, 2014) found a disruption in the modulation of movement-related beta oscillations in stroke patients that correlated with motor impairment. We discuss how beta oscillatory measures characterize motor impairment, the implications of stroke variability, and the potential role of GABA in modulating oscillations following stroke and during stroke recovery.

Chiari I malformation (CM-I) is classically defined as a cerebellar tonsillar herniation (⩾5 mm) through the foramen magnum. A decreased posterior fossa volume, mainly due to basioccipital hypoplasia and sometimes platybasia, leads to posterior fossa overcrowding and consequently cerebellar herniation. Regardless of radiological findings, embryological genetic hypothesis or any other postulations, the real cause behind this malformation is yet not well-elucidated and remains largely unknown. The aim of this paper is to approach CM-I under a broader and new perspective, conjoining anthropology, genetics and neurosurgery, with special focus on the substantial changes that have occurred in the posterior cranial base through human evolution. Important evolutionary allometric changes occurred during brain expansion and genetics studies of human evolution demonstrated an unexpected high rate of gene flow interchange and possibly interbreeding during this process. Based upon this review we hypothesize that CM-I may be the result of an evolutionary anthropological imprint, caused by evolving species populations that eventually met each other and mingled in the last 1.7 million years.

In the work on the social determinants of health, it has long been recognized that, among the strongest (if not the strongest) predictor of morbidity and mortality, is educational attainment—that is, the number of years of formal schooling (1). To what extent the relationship between education and longevity is a causal one running from schooling to health has been of intense interest to social scientists. Of course, ill health can truncate a schooling career, but there is also adequate reason to suspect that formal schooling does indeed improve health and well-being through a number of channels ranging from improved impulse control (2) to better ability to understand health risks (3) to improved economic circumstances (4). The extent to which we can isolate the mechanisms behind this strong relationship will help us design better interventions to promote health and health equity (not to mention, to mitigate the adverse effects of ill health on education and its related outcomes).

Intracranial aneurysm (IA) rupture is responsible for 80% of spontaneous arachnoid hemorrhages and associated with an extremely high mortality rate. Two possible surgical interventions are endovascular embolization and microsurgical clipping. Three-dimensional (3D) prototyping models help in surgical planning minimizing perioperative risks in both methods and reducing operating time. Methods 3D biomodels were printed with flexible material (elastomer) using angiotomographic DICOM acquired images and compared to 3D digital subtraction angiography (DSA) images. Results 3D biomodels represented the aneurysm angioarchitecture exactly, especially the neck and domus features. Conclusion Elastomers 3D biomodels proved to be a trustworthy representation of the angiotomographic images and could be used to help surgical planning in IA treatment. RESUMO A ruptura dos aneurismas intracranianos é responsável por 80% das hemorragias subaracnóideas espontâneas e está associada a uma taxa de mortalidade extremamente alta. Duas intervenções cirúrgicas viáveis são embolização endovascular e clipagem microcirúrgica. Os modelos de prototipagem tridimensional (3D) auxiliam no planejamento cirúrgico e na diminuição dos riscos intra-operatórios nos dois procedimentos e redução do tempo da cirurgia. Métodos Foram impressos biomodelos em 3D com material flexível (elastômero) utilizando imagens DICOM de angiotomografia e comparados com imagens de angiografia por subtração digital em 3D (DAS). Resultados Biomodelos em 3D representam com exatidão a angioarquitetura do aneurisma, particularmente os detalhes do colo e domus. Conclusão Biomodelos em 3D com elastômeros mostraram ser uma representação confiável das imagens angiotomográficas, podendo ser utilizados no planejamento cirúrgico no tratamento de IA.