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Background and purpose We systematically reviewed available evidence for reports of neurological signs and symptoms in patients with COVID-19 to identify cases with severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection or immune-mediated reaction in the nervous system. Methods We followed PRISMA guidelines and used the MEDLINE, EMBASE, Google Scholar, MedRxiv and ChinaXiv databases to search for articles on COVID-19 and nervous system involvement that were published from 1 January to 24 April 2020. Data on design, sample size, neurological assessment and related work-up were extracted. Biases were assessed with the Newcastle-Ottawa scale. Results We analysed 27 publications on potential neuroinvasive or parainfectious neurological complications of COVID-19. The reports focused on smell and taste (n = 5) and evaluation of neurological symptoms and signs in cohorts (n = 5). There were cases of Guillain-Barré syndrome/Miller-Fisher syndrome/cranial neuropathy (seven cases), meningitis/encephalitis (nine cases) and various other conditions (five cases). The number of patients with examination of cerebrospinal fluid and, in particular, SARS-CoV-2 polymerase chain reaction was negligible. Two had a positive SARS-CoV-2 polymerase chain reaction examination of cerebrospinal fluid specimen. Study of potential parenchymal involvement with magnetic resonance imaging was rare. Only four reports received a rating of the highest quality standards. Conclusions This systematic review failed to establish comprehensive insights into nervous system manifestations of COVID-19 beyond immune-mediated complications in the aftermath of respiratory symptoms. The authors therefore provide guidance for more careful clinical, diagnostic and epidemiological studies to characterize the manifestations and burden of neurological disease caused by SARS-CoV-2 on behalf of the Infectious Disease Panel of the European Academy of Neurology.Background Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults. Methods We examined the association between liver fibrosis and cognitive performance among participants ages 60 years and greater in the United States National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease. Results Among 3,217 adult participants, the mean age was 69 years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% (95% CI, 4.0-6.0) had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (β, -0.39; 95% CI, -0.58, -0.21), language fluency (β, -0.46; 95% CI, -0.72, -0.21), and attention/concentration (β, -1.34; 95% CI, -2.25, -0.43), but not delayed recall (β, -0.10; 95% CI, -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease. Conclusion Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.Following the development of the tramadol crisis currently affecting countries in the Middle East, and Africa, there has been increasing international interest in the regulation of tramadol. This study investigates the misuse of tramadol in patients presenting to emergency departments across Europe. Data from 32 emergency departments in 21 countries were extracted from the Euro-DEN Plus database for the 4-year period from 1st January 2014 to 31st December 2017. Of the reported 24,957 emergency department presentations, tramadol misuse was reported in 105 (0.4% presentations). Tramadol misuse was most common in Bratislava (Slovakia) (n=11, 7.5% of all presentations to this centre), Riga (Latvia) (n=4, 4.9%) and Munich (Germany) (n=17, 2.9%). On arrival, 14 (13.3%) of presentations were in coma/GCS≤8 and nine of these had a respiratory rate less then 12 per minute. These presentations potentially pose a significant burden on EDs with a large proportion requiring admission to hospital for ongoing care.On March 11th, 2020, the WHO declared the SARS-Cov-2 pandemic. Syndromes have been detected in relation to COVID-19 such as encephalitis, acute necrotizing hemorrhagic encephalopathy and cerebrovascular complications. There are also cases of peripheral nervous system involvement. Our case would be the 3rd patient with MFS associated with COVID-19 as far as we know. We present a 51 years old female diagnosed with MFS two weeks after COVID-19. RT-PCR to SARS-CoV-2 was negative but IgG was positive. Most of the cases were mild or moderate with typical signs and symptoms. All were treated with IV immunoglobulin with good response in most cases. Despite the short evolution time of the cases surviving the current pandemic, the description of cases of post-infectious neurological syndromes suggests that this is probably not an infrequent complication in the subacute stage of Covid-19 disease.Objective To determine the association between oil pollution and miscarriage, stillbirth, and infant death in the Niger Delta region of Nigeria. Methods A retrospective cohort study was undertaken of pregnant women (aged 18-45 years) who attended selected health facilities in regions with high and low exposure to oil pollution from May 14, 2018, to September 27, 2018. A multistage sampling technique was used to randomly select a representative of women with high and low exposure to oil pollution. An interviewer-administered questionnaire was used for data collection. Bivariate and multivariable logistic regression analyses were employed to adjust for confounding factors of miscarriage, stillbirth, and infant death. Results In total, 1564 pregnant women were included in the study. Women with high exposure to oil pollution were more likely to experience stillbirth (odds ratio [OR] 1.806; 95% confidence interval [CI] 1.177-2.770) and infant death (OR 2.162; 95% CI 1.409-3.317). However, after adjusting for potential confounders, only infant death was associated with high exposure (adjusted OR 1.843; 95% CI 1.146-2.962). No association was found between miscarriage and high exposure to oil pollution. Conclusion Women with high exposure to oil pollution are at higher risk of infant death.COVID‐19 infection can cause a severe pneumonia which, in some cases, can lead to admission in intensive care unit for respiratory support.1 In severe cases, systemic thrombotic complication has been described, including cerebrovascular disease (5.7‐23% of cases).2,3The Lake Huron ecosystem is unique among the Laurentian Great Lakes in that its surface area encompasses three distinct basins. This ecosystem recently experienced significant ecological restructuring characterized by changes in primary production, species dominance and abundances, and top predator energy dynamics. However, much of the evidence for this restructuring has been largely derived from biomonitoring data derived from long term sampling of the lake's Main Basin. Here, we examined polychlorinated biphenyl (PCB) concentrations and the stable isotopes of carbon (δ13 C) and nitrogen (δ15 N) in rainbow smelt (Osmerus mordax), bloater (Coregonus hoyi) and round goby (Neogobius melanostomus) to determine spatial variability in these environmental markers as indicators of the ubiquity of trophic restructuring throughout Lake Huron. Stable isotopes indicated North Channel fish occupied trophic positions between 0.5 - 1.0 lower relative to Main Basin and Georgian Bay conspecifics, respectively. Sum PCB concentrations for 41 congeners were highest for fish from the Main Basin (27.5 ± 3.0 ng·g-1 wet wt) and Georgian Bay (26.3 ± 3.4 ng·g-1 ) relative to North Channel (13.6 ± 1.2 ng·g-1 ) fish. Discriminant functions analysis demonstrated basin-specific PCB congener profiles with individual species also having distinct profiles dependent on their basin of collection. These bioaccumulation patterns among Lake Huron forage fish mirror those reported for lake trout in this lake and indicate that the degree of food-web ecological restructuring in Lake Huron is not equivalent across the basins. Specifically, basin-specific PCB congener profiles demonstrated among Lake Huron secondary and top predator consumer species are likely dictated by cross-basin differences in zooplankton community ecology and trophodynamics that can regulate the efficiencies of prey energy transfer and PCB congener bioaccumulation patterns in aquatic food-webs. This article is protected by copyright. All rights reserved.The validity of soil toxicity databases for predicting ecological impacts in the field is rarely explored. This work was set up to test if laboratory toxicity data and the combined concepts of metal availability and mixture toxicity can predict ecological impact in mining-affected soils. Metal and arsenic (As) contamination gradients were sampled around five different mines in Mexico where plant cover and abundances exhibited clear dose-related responses. Soils were analyzed for total and isotopically exchangeable (labile) concentrations of Ni, Cu, Cd, Pb, and As and for soil properties affecting the availability of these elements. Six different indices of toxic doses were compared to evaluate their accuracy in describing the field response expressed as relative abundance and cover. Each index was based on a different method to calculate the sum of toxic units (ΣTU) in soil, with 1 TU equal to the concentration of the element in soil yielding 50% adverse effect on plants with median sensitivity as recorded inn on plant communities within factor 2, expressing the dose as soil labile concentrations and using the concentration addition concept in these mixed polluted environments. This article is protected by copyright. All rights reserved.Multiple linear regression (MLR) models for predicting chronic aluminum toxicity to a cladoceran (Ceriodaphnia dubia) and a fish (Pimephales promelas) as a function of three toxicity modifying factors (TMFs) - dissolved organic carbon (DOC), pH, and hardness - were previously published. However, the range over which data for these TMFs were available was somewhat limited. To address this limitation, additional chronic toxicity tests with these species were subsequently conducted to expand the DOC range up to 12 mg/L, the pH range up to 8.7, and the hardness range up to 428 mg/L. The additional toxicity data were used to update the chronic MLR models. The adjusted R2 for the C. dubia EC20 (20% effect concentration) model increased from 0.71 to 0.92 with the additional toxicity data, and the predicted R2 increased from 0.57 to 0.89. For P. promelas, the adjusted R2 increased from 0.87 to 0.92 and the predicted R2 increased from 0.72 to 0.87. The high predicted R2 relative to adjusted R2 indicates that the models for both species are not overly parameterized. When data for C. dubia and P. promelas were pooled, the adjusted R2 values were comparable to the species-specific models (0.90 and 0.88 for C. dubia and P. promelas, respectively). This indicates that chronic aluminum EC20s for C. dubia and P. promelas respond similarly to variation in DOC, pH, and hardness. Overall, the pooled model predicted EC20s that were within a factor of two of observed in 100% of the C. dubia tests and 94% of the P. promelas tests. This article is protected by copyright. All rights reserved.Caenorhabditis elegans is an established model organism in neurodegeneration and aging research. Oxidative stress and formation of advanced glycation endproducts (AGEs), as they occur under hyperglycemic conditions in diabetes mellitus, contribute to neuronal damage and lifespan reduction. Sulforaphane (SFN) is an indirect antioxidant, alpha-tocopherol (vitamin E) is a direct antioxidant that acts as a free radical scavenger. Aim of this study is to investigate the protective effects of SFN and vitamin E against glucotoxic damages to the neuronal system and lifespan in C. elegans. Culture conditions that mimic clinical hyperglycemia increased the formation of reactive oxygen species (ROS) (p less then 0.001) and the accumulation of methylglyoxal-derived advanced glycation endproducts (MG-derived AGEs) (p less then 0.01) with subsequent neuronal damage and neuronal dysfunction, ultimately leading to a significant shortening of lifespan (p less then 0.01). Treatment with both, 20 µmol/l SFN and 200 µg/ml vitamin E, completely prevented the increase in ROS and MG-derived AGEs, abolished the glucotoxic effects on neuronal structure and function, and preserved lifespan, resulting in a life expectancy similar to untreated controls. These data emphasize the relevance of indirect and direct antioxidants as potential therapeutic options for the prevention of glucotoxic pathologies.Background Anterior communicating artery (AComA) aneurysms are the most common intracranial aneurysm, accounting for 25 to 38% of all cases. In spite of the advent of modern neurointerventional treatments, they still represent a strong indication for clipping in certain anatomical and clinical conditions. However, AComA aneurysms are the deepest located aneurysms of the anastomotic circle of Willis, with a complex spatial orientation, and they are fed by bilateral branches of the anterior circulations. Although, on one hand, these aneurysms represent the most complex ones of the anterior circulation, on the other hand, the experience of young neurosurgeons is increasingly limited. Therefore, respecting operative guidelines is crucial to achieve the best aneurysm exclusion and avoid fatal intraoperative complications. Study objective We describe the technical algorithm we use to teach young neurosurgeons how to approach AComA aneurysms and help them to develop a procedural memory needed to perform an efficient and safe surgery. Materials and methods We reviewed our last 10 years of institutional experience of > 200 cases of clipping ruptured and unruptured AComA aneurysms, analyzing our technical refinements and the difficulties in teaching residents and young neurosurgeons how to establish fundamental key points and design a didactic algorithm that includes operative instructions and safety rules. Results We identified seven pragmatic technical key points regarding craniotomy, cisternostomy, gyrus rectus corticectomy, proximal control, perforators and Heubner preservation, aneurysm neck dissection, and clipping to use in a didactic algorithm for teaching residents and as operative instructions for inexperienced neurosurgeons. Conclusion In the setting of clipping AComA aneurysms, respect for surgical rules is of paramount importance to perform an efficacious and safe procedure and ensure the best aneurysm exclusion and preservation of neurovascular structures.Objective Auditory localisation is part of central auditory processing. The study examined the impact of hearing aids on the auditory localisation ability of non-linguistic stimuli in hearing impaired schoolchildren. Patients and methods Above threshold acoustic signals were presented to 20 children (7-17 years) in a free field condition with 45 loudspeakers placed on a semicircular array. All participants had a bilaterally symmetric moderate sensorineural hearing loss (WHO grade 2) and used behind the ear style (BTE) hearing aids with conventional earmolds. The children had to indicate the position of the signal by a laser pointer. Both high- and low-frequency noise bursts were employed in the tests to separately address spatial auditory processing based on interaural time differences and interaural intensity differences. The examination was performed with and without BTE hearing aids. Results There was no significant difference between results in the aided and the unaided condition neither for the different frequency bands nor for the signal positions. The auditory localisation of the hearing impaired children was reduced by 3°-4° for frontal and 5°-11° for lateral positions compared to normal-hearing children. There was no age-relation. Conclusions In our experimental setting, BTE hearing aids could not compensate the impaired auditory localisation ability of children with sensorineural hearing loss.Objectives The present study aimed to investigate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complex and the type of flowable composite (conventional or self-adhesive bioactive) on the fracture resistance of fractured incisors restored through reattachment technique. Materials and methods In this experimental in vitro study, 60 extracted bovine central mandibular incisors were randomly divided into six groups (n = 10) according to the reattachment technique. Their incisal edges were cut off to represent an enamel-dentin fracture. The fragment edges were reattached as follows Group 1-selective etching and bonding followed by conventional flowable composite; Group 2-selective etching and bonding followed by bioactive flowable composite; Group 3 was like Group 2 but without applying bonding; Groups 4, 5, and 6 were similar to Groups 1, 2, and 3, respectively, but both tooth fragments were pretreated with CPP-ACP-containing paste for 3 minutes. Fracture resistance was assessed by a universal testing machine. Statistical analysis Data were analyzed by SPSS-Statistical Package for the Social Sciences-software using one-way analysis of variance and Tukey post-hoc tests (α= 0.05). Results The highest and lowest fracture resistance was recorded in Groups 5 (15.96 MPa) and Group 6 (1.95 MPa), respectively, being significantly different from the other groups. The mean fracture resistance of Groups 3 and 6 was significantly lower than the other groups (p less then 0.05). However, Groups 1, 2, and 4 showed no difference in fracture resistance. Conclusion Bioactive composite was not superior to conventional composite for fragment reattachment, but using it in self-adhesive mode reduced the fracture strength significantly. Yet, pretreatment with CPP-ACP, followed by application of adhesive, improved the fracture resistance of bioactive composite.Objectives The aim of this study was to compare the effects of two margin designs (shoulderless and slight chamfer) with two occlusal thicknesses on fracture resistance and failure mode of the monolithic zirconia crowns. Materials and methods Forty nickel-chromium dies were duplicated from the previous two prepared teeth using a three-dimensional optical scanner. Nickel-chromium supporting dies were divided into two main groups (n = 20) according to the type of margin design group A, slight chamfer margin design and group B, shoulderless margin design. These groups were further divided into two subgroups according to the occlusal thicknesses (0.5 and 1 mm). The digital imaging of each die was done using a three-dimensional optical scanner, then zirconia blocks were milled by 5-axis machine. The crowns were cleaned by alcohol, air dried, and cemented by resin cement. Next, the crowns were subjected to 500 hot and cold cycles (30 seconds for each cycle). The samples were subjected to a static load until failureer design in all thicknesses. Although the restoration with reduced occlusal thickness has lower fracture resistance than 1 mm occlusal thickness, the 0.5 mm restorations still can tolerate occlusal forces.Background Surface disinfection is one of the elementary measures of infection prevention in healthcare facilities. However, the current widely used tissue dispenser systems can be microbially contaminated as a result of various causes and play a decisive role in the spread of pathogens. For this reason, these systems must be considered both as a source of infection in routine surveillance and as part of nosocomial outbreaks. Methods Tissue dispenser systems used at the University Hospital Leipzig (UKL) were extensively analyzed between 2016 and 2018 in accordance with the recommendations of the German Association for Applied Hygiene (VAH). Within this period, 1096 disinfectant solutions from dispenser systems were tested. Areas without or with infection risk were represented with equal distribution. To exclude the possibility of contamination by dosing units (DU), the microbial-hygienic tests were extended to the 135 decentralized DU at the UKL. Results Overall, a decline in contaminated disinfectant solutions was recorded over the study period (31% in 2016, 18% in 2017 and 8% in 2018). However, in 2017 as well as in 2018, more contaminants were recorded in high-risk areas. Specific follow-up examinations after training in handling and preparation of the systems resulted in a decrease of contaminated disinfection solutions at hospitals. The dominant microbial contamination was with Achromobacter spp. (81%), followed by Pseudomonas spp. (10%), vancomycin-resistant enterococci (VRE) (4%) and apathogenic environmental microorganisms (5%). The solutions taken from the dosing units (n=135) did not show any growth (91.1%). Bacillus spp. were detected in 8.2% and molds in 0.7% of solutions. Conclusion Contaminated dosing units as well as drinking water used for this purpose could be excluded as source of the pathogens detected in tissue dispenser systems. It is assumed that a lack of knowledge and a false sense of security led to incorrect handling of tissue dispenser systems when dealing with disinfectants.As more patients undergo total knee arthroplasty (TKA) each year, and the average age of patients gets younger, the patients are generally more active requiring a greater physiological demand and increasing range of motion on the prosthesis than the previous patients. However, there is no consensus on the optimal TKA tibial bearing design. We performed this systematic review to compare the clinical differences between mobile and fixed bearing constructs used in contemporary TKA. We searched PubMed, EMBASE, and Cochrane Library databases, identifying 515 total publications, including 17 randomized controlled trials (RCTs). A meta-analysis was performed, while the quality and bias of the evidence were rated according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) guidelines and the Cochrane Database questionnaire. The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Seventeen studies were includeal results. Trial registration number for PROSPERO was CRD42019126402.Coronavirus disease 2019 (COVID-19), caused by a new coronavirus, first appeared in late 2019. What initially seemed to be a mild influenza quickly revealed itself as a serious and highly contagious disease, and the planet was soon faced with a significant morbidity and mortality associated with this pathogen. For homeopathy, shunned during its 200 years of existence by conventional medicine, this outbreak is a key opportunity to show potentially the contribution it can make in treating COVID-19 patients. This should be done through performance of impeccably controlled, prospective, randomized clinical trials, with publication of their findings in well-ranked conventional medicine journals. If the homeopathy community fails to take advantage of this rare opportunity, it might wait another century for the next major pandemic.Background Hong Kong is geographically located in the province of Guangdong which, after Hubei, has been the region of China second-most affected by the COVID-19 pandemic. Compared to the pathognomonic symptoms of the named disease, homeopathic symptoms are always more helpful for homeopathic prescriptions. Aim This study reports and summarizes the homeopathic symptoms observed in 18 confirmed/suspected epidemiologically related cases in cluster outbreaks of COVID-19 in Hong Kong in early 2020. Methods Homeopathic symptoms from this case series were collected from 18 consecutive patients who, in addition to their concurrent conventional treatment or traditional Chinese medicine, actively sought help from homeopathy as an adjunctive measure for symptomatic relief from COVID-19. Cases were categorized according to outbreak clusters, focusing mainly on the homeopathic symptoms. In the analysis, frequency of all homeopathic medicines, common rubrics in all the cases, common rubrics in each of the top-ranked remedies, and differentiating symptoms for each top-ranked remedy were determined. Results Homeopathic symptoms of 18 cases, each identified as mild and belonging to one of six separate clusters, are reported. Eighteen common symptoms screened out of 79 selected rubrics constituted two sets of homeopathic symptom pictures Bryonia alba (n = 4) and Gelsemium sempervirens (n = 12). Eight and seven differentiating features, respectively, were identified for Bryonia alba and Gelsemium sempervirens. Conclusion The common symptoms of 18 mild COVID-19 cases constituted two sets of homeopathic symptom pictures, indicating Bryonia alba or Gelsemium sempervirens; they were indicated in 4 and 12 cases, respectively, out of the 18 in total.Introduction Therapeutic hypothermia (TH) improves the outcome in newborns with hypoxic-ischemic encephalopathy (HIE) and should be used in case of perinatal asphyxia and signs of moderate/severe HIE. Material/methods Frequency of HIE and the application of TH were extracted from the neonatal survey, a registry that collects data from all German hospitals, and from the hypothermia registry, established in 2010. The latter was also used to analyze short-term outcomes of the newborns. Results Between 2010 and 2017, 106 of Germany's 213 perinatal centers joined the registry. Response rates varied between 22 and 60%. The registry recorded 164 (IQR 115-224) TH cases per year in newborns with HIE. In the neonatal survey, 517 (382-664) TH and 543 (432-581) HIE cases were reported. Since 2014 there have been more cases of TH than HIE. After TH, 10.4% (8-13%) of the newborns died, 81% (78-82%) of the newborns were discharged home, 3.6% (3-5%) to a rehabilitation facility, and 5.4% (5-7%) transferred to another clinic. 89% (87-89%) were on complete oral feedings. Discussion After the introduction of TH in the clinical routine, the number of treated newborns increased continuously. Currently, the number of TH is higher than the number of children with HIE, which is difficult to explain, as the presence of a moderate or severe HIE is a mandatory requirement for TH. The data from the hypothermia registry showed no significant changes in mortality or neurological outcome over time.Molecular diagnostics are increasingly important to guide treatment decisions in oncologic patients. For instance, the presence of high-grade microsatellite-instability (MSI-high) is considered to be one of the major positive predictors of therapy response to immune-checkpoint inhibitors in patients with solid tumors. Based on impressive results from several immune-oncology trials, the American Food and Drug Administration (FDA) granted approval to immunotherapy in any previously treated, MSI-high solid cancer in 2017. Here, we report the clinical case of a young patient with MSI-high colorectal cancer. The case illustrates, that insurance companies in Germany are still reluctant to cover the cost of immunotherapy in this specific patient subgroup, which, in our opinion, results in an ethically problematic therapeutic dilemma.Background Dysplasia in Barrett's esophagus is focal and difficult to locate. The aim of this meta-analysis was to understand the spatial distribution of dysplasia in Barrett's esophagus before and after endoscopic ablation therapy. Methods A systematic search was performed of multiple databases to July 2019. The location of dysplasia prior to ablation was determined using a clock face orientation (right or left half of the esophagus). The location of dysplasia post-ablation was classified as within the tubular esophagus or at the top of the gastric folds (TGF). Results Thirteen studies with 2234 patients were identified. Pooled analysis from 6 studies (819 lesions in 802 patients) showed that before ablation, dysplasia was more commonly located in the right half versus the left half (OR 4.3; 95% CI [2.33-7.93]; p less then 0.01). Pooled analysis from 7 studies showed that dysplasia after ablation recurred in 101/1432 (7.05%; 95% CI [5.7-8.4%]) patients. Recurrence of dysplasia was located more commonly at the TGF (n=68) as compared to the tubular esophagus (n=34) (OR 5.33; 95% CI [1.75-16.21]; p less then 0.01). Of the esophageal lesions, 90% (27/30) were visible whereas only 46% (23/50) of the recurrent dysplastic lesions at TGF were visible (p less then 0.01). Conclusion Before ablation, dysplasia in Barrett's esophagus is found more frequently in the right half of the esophagus versus the left. Post-ablation recurrence is more commonly found in the top of the gastric folds and is non-visible as compared to the tubular esophagus, which is mainly visible.Background and study aim We previously reported for the first time the usefulness of artificial intelligence (AI) systems in detecting gastric cancers (GCs). However, the "original Convolutional Neural Network (O-CNN)" employed in the previous study had a relatively low positive predicted value (PPV). Therefore, we aimed to develop an advanced AI-based diagnostic system and evaluate its applicability for the classification of GC and gastric ulcers (GUs). Methods We constructed an "advanced CNN" (A-CNN) by adding a new training dataset (4,453 GU images from 1172 lesions) to the O-CNN, which had been trained using 13,584 GC and 373 GU images. The diagnostic performances of the A-CNN in terms of classifying GC and GU were retrospectively evaluated using an independent validation dataset (739 images from 100 early GCs and 720 images from 120 GUs) and compared with those of O-CNN by estimating the overall classification accuracy. Result The sensitivity, specificity, and PPV of A-CNN in classifying GC at the lesion level were 99% (95% CI [94.6-100]%), 93.3% (95% CI [87.3-97.1]%), and 92.5% (95% CI [85.8-96.7]%), respectively. These estimates for classifying GU were 93.3% (95% CI [87.3-97.1]%), 99% (95% CI [94.6-100]%), and 99.1% (95% CI [95.2-100]%), respectively. At the lesion level, the overall accuracies of O- and A-CNN for classifying GC and GU were 45.9% (GC 100%, GU 0.8%) and 95.9% (GC 99%, GU 93.3%), respectively. Conclusion The developed AI-based diagnostic system could effectively classify GCs and GUs.Background Diabetes insipidus (DI) is a recognized transient or permanent complication following transsphenoidal surgery (TSS) for pituitary tumors. Objective To describe significant experience with the incidence of DI after TSS, identifying predictive characteristics and describing our diagnosis and management of postoperative DI. Methods A retrospective analysis was performed of 700 patients who underwent endoscopic TSS for resection of pituitary adenoma (PA), Rathke cleft cyst (RCC), or craniopharyngioma. Inclusion criteria included at least 1 wk of follow-up for diagnosis of postoperative DI. Permanent DI was defined as DI symptoms and/or need for desmopressin more than 1 yr postoperatively. All patients with at least 1 yr of follow-up (n = 345) were included in analyses of permanent DI. Multivariable logistic regression models were constructed to identify predictors of transient or permanent postoperative DI. Results The overall rate of any postoperative DI was 14.7% (103/700). Permanent DI developed in 4.6% (16/345). The median follow-up was 10.7 mo (range 0.2-136.6). Compared to patients with PA, patients with RCC (odds ratio [OR] = 2.2, 95% CI 1.2-3.9; P = .009) and craniopharyngioma (OR = 7.0, 95% CI 2.9-16.9; P ≤ .001) were more likely to develop postoperative DI. Furthermore, patients with RCC (OR = 6.1, 95% CI 1.8-20.6; P = .004) or craniopharyngioma (OR = 18.8, 95% CI 4.9-72.6; P ≤ .001) were more likely to develop permanent DI compared to those with PA. Conclusion Although transient DI is a relatively common complication of endoscopic and microscopic TSS, permanent DI is much less frequent. The underlying pathology is an important predictor of both occurrence and permanency of postoperative DI.Purpose In patients with early ocular misalignment and nystagmus, vertical optokinetic stimulation reportedly increases the horizontal component of the nystagmus present during fixation, resulting in diagonal eye movements. We tested patients with infantile nystagmus syndrome but normal ocular alignment to determine if this crosstalk depends on strabismus. Methods Eye movements were recorded in seven patients with infantile nystagmus. All but one patient had normal ocular alignment with high-grade stereopsis. Nystagmus during interleaved trials of right, left, up, and down optokinetic stimulation was compared with waveforms recorded during fixation. Six patients with strabismus but no nystagmus were also tested. Results In infantile nystagmus syndrome, horizontal motion evoked a mostly jerk nystagmus with virtually no vertical component. A vertical optokinetic pattern produced nystagmus with a diagonal trajectory. It was not simply a combination of a vertical component from optokinetic stimulation and a horizontal component from the subject's congenital nystagmus, rather in six of seven patients, the slow-phase velocity of the horizontal component during vertical optokinetic stimulation differed from that recorded during fixation. In the six strabismus patients without nystagmus, responses to vertical optokinetic stimulation were normal. Conclusions In patients with congenital motor nystagmus, a vertical noise pattern drives a diagonal nystagmus. This appears to arise because of crosstalk between the vertical and horizontal components of the optokinetic system. This abnormal response to vertical stimulation is not caused by strabismus because it occurs in patients with infantile nystagmus without strabismus. Moreover, it is absent in patients with strabismus and no spontaneous nystagmus.Purpose To elucidate the molecular etiology of deepening of the upper eyelid sulcus (DUES) induced by prostaglandin (PG) analogs, a three-dimensional (3D) tissue culture system was employed using human orbital fibroblasts (HOFs). Methods During adipogenesis, changes in HOF 3D organoid sizes, as well as their lipids stained by BODIPY and expression of the extracellular matrix (ECM) by immunolabeling and/or quantitative PCR, were studied in the presence or absence of either 100-nM bimatoprost acid or 100-nM prostaglandin F2α. Results The size of the 3D organoids increased remarkably during adipogenesis, but such increases were significantly inhibited by the presence of PG analogs. Staining intensities by BODIPY and mRNA expression of peroxisome proliferator-activated receptor gamma were significantly increased upon adipogenesis but were not influenced by the presence of PG analogs. Unique changes in ECM expression observed with or without adipogenic differentiation were significantly modified by the presence of PG analogs. Conclusions Our present study indicates that PG analogs have the potential to modulate the ECM network within HOF 3D organoids. Thus, a 3D tissue culture system may be a suitable strategy for understanding the disease etiology of DUES.Purpose To investigate the impact of subretinal drusenoid deposits (SDD) and photoreceptor integrity on global and local geographic atrophy (GA) progression. Methods Eighty-three eyes of 49 patients, aged 50 years and older with GA secondary to age-related macular degeneration (AMD), were prospectively included in this study. Participants underwent spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging at baseline and after 12 months. The junctional zone and presence of SDD were delineated on SD-OCT and FAF images. Linear mixed models were calculated to investigate the association between GA progression and the junctional zone area, baseline GA area, age, global and local presence of SDD and unifocal versus multifocal lesions. Results The area of the junctional zone was significantly associated with the progression of GA, both globally and locally (all P 0.05). Conclusions Photoreceptor integrity and SDD are useful for predicting global and local growth in GA. Investigation of the junctional zone is merited because this area is destined to become atrophic. Photoreceptor loss visible on SD-OCT might lead to new structural outcome measurements visible before irreversible loss of retinal pigment epithelium occurs.Purpose Synucleinopathies such as multiple system atrophy (MSA) and Parkinson's disease are associated with a variety of visual symptoms. Functional and morphological retinal aberrations are therefore supposed to be valuable biomarkers for these neurodegenerative diseases. This study examined the retinal morphology and functionality resulting from human α-synuclein (α-Syn) overexpression in the transgenic Plp-α-Syn mouse model. Methods Immunohistochemistry on retinal sections and whole-mounts was performed on 8- to 11-week-old and 12-month-old Plp-α-Syn mice and C57BL/6N controls. Quantitative RT-PCR experiments were performed to study the expression of endogenous and human α-Syn and tyrosine hydroxylase (TH). We confirmed the presence of human α-Syn in the retina in western blot analyses. Multi-electrode array (MEA) analyses from light-stimulated whole-mounted retinas were used to investigate their functionality. Results Biochemical and immunohistochemical analyses showed human α-Syn in the retina of Plp-α-Syn mice. We found distinct staining in different retinal cell layers, most abundantly in rod bipolar cells of the peripheral retina. In the periphery, we also observed a trend toward a decline in the number of retinal ganglion cells. The number of TH+ neurons was unaffected in this human α-Syn overexpression model. MEA recordings showed that Plp-α-Syn retinas were functional but exhibited mild alterations in dim light conditions. Conclusions Together, these findings implicate an impairment of retinal neurons in the Plp-α-Syn mouse. The phenotype partly relates to retinal deficits reported in MSA patients. We further propose the suitability of the Plp-α-Syn retina as a biological model to study synuclein-mediated mechanisms.This is a surgical technique video of selective posterior callosotomy (SPC), a novel surgical procedure to alleviate refractory epileptic drop attacks.1 Departing from traditional approaches aiming the anterior half or the entire callosum, SPC sections the posterior half of the callosum sparing prefrontal connectivity.1 Drop attacks are generalized epileptic seizures characterized by sudden falls.1 These seizures are often seen in diffuse brain pathology associated with generalized or multifocal epilepsies, whose electroencephalogram (EEG) "fingerprint" is bilaterally synchronous epileptic discharges.1 Sectioning the callosum to control drop attacks follows the rationale that the rapid synchronization of discharges between motor and premotor regions of both hemispheres is the basis.1 The standard approach to callosotomies always contemplated the anterior fibers of the callosum.2 Literature reports that anterior sections lead to unsatisfactory control of drop attacks, and results are improved when extended intdeo acquisition, photo acquisition, and storage at operations, and the publication of this material.Background and importance Pseudoaneurysms involving the superficial temporal artery (STA), either iatrogenic or caused by direct trauma, are rare. The STA is prone to injury due to its long course throughout the scalp. Injuries can cause cosmetic defects and/or skin breakdown leading to further complications. Clinical presentation We report a case of delayed iatrogenic pseudoaneurysm of the STA after placement of an intracranial pressure monitor in the setting of acute traumatic brain injury. The patient had a delayed development of a pulsatile mass over his right frontal region, with computed tomography angiography concerning for a pseudoaneurysm of the STA. This was managed with surgical resection with complete resolution of symptoms at follow-up. Conclusion We review the literature regarding the etiology, pathogenesis, and management of these lesions. While iatrogenic injuries to the STA have been previously reported, this is a curious case related to placement of an intracranial pressure monitor. We recommend direct surgical resection of the pseudoaneurysm for cosmetic effect and prevention of further wound breakdown.It is possible to modify the natural emergence profile of the tooth using simple intrasulcular direct restorations. The shape of the intrasulcular part of the restoration will determine the design of the gingival contour.Pit latrines are promoted in resource-limited settings, but unpleasant odours may deter their use. In this study, latrines in rural Ethiopia were randomized to the addition of cooking ash, the addition of boiling water or neither. Study staff ranked odour on a 6-point scale before and approximately 24 h after intervention. Following intervention, odour grades were on average 0.2 points lower (95% confidence interval [CI] 0.7 lower to 0.3 higher) in ash-treated latrines and 0.4 points lower (95% CI 0.9 lower to 0.1 higher) in boiled water-treated latrines, although the difference between the three groups was not statistically significant (p = 0.21). Larger studies might detect a smaller difference.Early visual processing is surprisingly flexible even in the adult brain. This flexibility involves both long-term structural plasticity and online adaptations conveyed by top-down feedback. Although this view is supported by rich evidence from both human behavioral studies and invasive electrophysiology in nonhuman models, it has proven difficult to close the gap between species. In particular, it remains debated whether noninvasive measures of neural activity can capture top-down modulations of the earliest stages of processing in the human visual cortex. We previously reported modulations of retinotopic C1, the earliest component of the human visual evoked potential. However, these effects were selectively observed in the upper visual field (UVF). Here we test whether this asymmetry is linked to an interaction between differences in spatial resolution across the visual field and the specific stimuli used in previous studies. We measured visual evoked potentials in response to task-irrelevant, high-contrast textures of different densities in a comparatively large sample of healthy volunteers (N = 31) using high-density electroencephalogram. Our results show differential response profiles for upper and lower hemifields, with UVF responses saturating at higher stimulus densities. In contrast, lower visual field responses did not increase, and even showed a tendency toward a decrease at the highest density tested. We propose that these findings reflect feature- and task-specific pooling of signals from retinotopic regions with different sensitivity profiles. Such complex interactions between anatomic and functional asymmetries need to be considered to resolve whether human early visual cortex activity is modulated by top-down factors.Observational studies regarding the putative associations between dietary intake of homocysteine metabolism-related B-vitamins (vitamin B-6, folate, and vitamin B-12) and stroke risk have yielded inconsistent results. Thus, we conducted a systematic meta-analysis of prospective studies in order to examine the relation between the dietary (from diet and supplements) intake of these B-vitamins and the risk of stroke. PubMed and Web of Science were searched for relevant articles published through to 25 February, 2020, and RR of stroke in relation to dietary intake of vitamin B-6, folate, and vitamin B-12 were pooled using a random-effects model. Eleven publications of 12 prospective studies comprising 389,938 participants and 10,749 cases were included in the final analysis. We found that dietary intake of vitamin B-6 and folate were associated with a reduced risk of stroke, and this inverse association remained significant in studies with >10 y of follow-up periods and among participants without a pre-existing stroke event. A dose-response analysis revealed a linear inverse association between folate and vitamin B-6 intake and the risk of stroke, with a pooled RR of 0.94 (95% CI 0.90-0.98) and 0.94 (95% CI 0.89-0.99) for each 100 μg/d increment in folate intake and 0.5 mg/d increment in vitamin B-6 intake, respectively. In contrast, we found no significant association between dietary vitamin B-12 intake and the risk of stroke, with an RR of 1.01 (95% CI 0.97-1.06) per 3 μg/d increase. In conclusion, our findings suggest that increased intake of vitamin B-6 and folate is associated with a reduced risk of stroke, supporting the notion that increasing habitual folate and vitamin B-6 intake may provide a small but beneficial effect with respect to stroke.The use of robotic guidance for spinal instrumentation has become promising for its ability to offer the advantages of precision, accuracy, and reproducibility. However, utilization and adoption of robotic platforms for spine surgery remain limited especially in comparison to other surgical fields. We present here a case of a 71-yr-old man with a prior T4-pelvis long-segment fusion who presented with distal sacro-iliac instrumentation loosening with pseudarthrosis. He subsequently underwent construct revision with quad (bilateral dual) S2-alar-iliac screw fixation with navigated spinal robotic assistance (Mazor X Stealth Edition, Medtronic Sofamor Danek, Medtronic Inc, Dublin, Ireland). To our knowledge, this is the first video demonstrating the preoperative software planning and intraoperative workflow for placing quad S2-alar-iliac screws with navigated spinal robotic guidance using the Mazor X Stealth Edition. There is no identifying information in this video. Patient consent was obtained for the surgical procedure and for publishing of the material included in the video.One-step self-etch adhesive systems provide a clinical time gain, decreasing the number of clinical steps. When a clinician is able to follow a simpler process of adhesion there is less chance of adhesive failure.Our objective was to describe the clinical presentation of chikungunya virus (CHIKV) infection in patients living with HIV (PLHIV) during the 2014 Martinique outbreak. During the outbreak and the 6 following months, all PLHIV coming in our unit for a medical evaluation answered questions about potential CHIKV related symptoms, and had blood tests to assess the diagnosis. For patients coming in at the acute phase of infection, we are able to provide and analyze CD4+, CD8+ T-cells and HIV viral load evolution before, during and after CHIK infection. Among the 1 003 PLHIV in care in the center at the time of the outbreak, 188 (94 men and 94 women) had confirmed (following the WHO definition) CHIKV infection. Clinical presentation was common in 63% of the cases, severe and atypical forms were scarce. During the acute phase, CD4+ and CD8+ T-cells (evaluated in 30 PLHIV, 15 men and 15 women) absolute numbers dropped significantly, but returned to pre-CHIKV values after the acute phase. Reassuringly, CD4 and CD8 T cells proportions did not decrease during the acute phase. CHIKV infection had no significant impact on this anti-retroviral treated population.Background Neonates with hypoxic-ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied. Methods A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline. Results Sixteen neonates cooled for HIE received aminophylline starting at 25 ± 14 h of life. Within 12 h of starting aminophylline, UOP increased by 2.6 ± 1.9 mL/kg/h. SCr declined by 0.4 ± 0.2 mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group (p less then 0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group. Conclusions Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline. Impact The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia. Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline. Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.Background Three-dimensional printing (3DP) addresses distinct clinical challenges in pediatric care including congenital variants, compact anatomy, high procedural risk, and growth over time. We hypothesized that patient-specific applications of 3DP in pediatrics could be categorized into concise, discrete categories of use. Methods Terms related to "three-dimensional printing" and "pediatrics" were searched on PubMed, Scopus, Ovid MEDLINE, Cochrane CENTRAL, and Web of Science. Initial search yielded 2122 unique articles; 139 articles characterizing 508 patients met full inclusion criteria. Results Four categories of patient-specific 3DP applications were identified Teaching of families and medical staff (9.3%); Developing intervention strategies (33.9%); Procedural applications, including subtypes contour models, guides, splints, and implants (43.0%); and Material manufacturing of shaping devices or prosthetics (14.0%). Procedural comparative studies found 3DP devices to be equivalent or better than conventations of patient-specific use teaching, developing, procedural, and material uses. By classifying these applications, this review promotes understanding and incorporation of this expanding technology to improve the pediatric care.