A 'Total Unique Variation Analysis' for Brain-Machine Interfaces.

When designing a fully implantable brain-machine interface (BMI), the primary aim is to detect as much neural information as possible with as few channels as possible. In this paper, we present a total unique variance analysis (TUVA) for evaluating the signal unique to each channel that cannot be predicted by linear combination of signals on other channels. TUVA is a statistical method for determining the total unique variance in multidimensional data, ordering channels from most to least informative, to aid in the design of maximally-efficacious BMIs. We demonstrate how this method can be applied to the design of BMIs by comparing TUVA values computed for simulated lead-field maps for high-channel-count electrocorticography (ECoG) with values computed for recordings in the interictal period in the context of surgery planning for epileptic resection.Clinical Relevance- This paper introduces a new statistical method for comparison of neural interface designs, focused on quantifying recording efficiency by minimizing channel crosstalk, which may help improve the risk-benefit profile of invasive neural recording.

Primary Melanoma miRNA Trafficking Induces Lymphangiogenesis.

Melanoma, the deadliest cutaneous tumor, initiates within the epidermis; during progression, cells invade into the dermis and become metastatic through the lymphatic and blood system. Before melanoma cell invasion into the dermis, an increased density of dermal lymphatic vessels is observed, generated by a mechanism which is not fully understood. In this study, we show that, while at the primary epidermal stage (in situ), melanoma cells secrete extracellular vesicles termed melanosomes, which are uptaken by dermal lymphatic cells, leading to transcriptional and phenotypic pro-lymphangiogenic changes. Mechanistically, melanoma-derived melanosomes traffic mature let-7i to lymphatic endothelial cells, which mediate pro-lymphangiogenic phenotypic changes by the induction of type I IFN signaling. Furthermore, transcriptome analysis upon treatment with melanosomes or let-7i reveals the enhancement of IFI6 expression in lymphatic cells. Because melanoma cells metastasize primarily via lymphatic vessels, our data suggest that blocking lymphangiogenesis by repressing either melanosome release or type I IFN signaling will prevent melanoma progression to the deadly metastatic stage.

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

The Effect of Proton Pump Inhibitors on Early Implant Failure A Retrospective Cohort Study.

Background and Objectives: Maintenance of a firm and long-term stable osseointegration is the primary goal of implant dentistry. Time is used to define implant failure characteristics. Early implant failure (EIF) occurs up to one year after loading. Recent studies indicated an association between proton pump inhibitors (PPI) therapy and failure of osseointegration. The present study assessed whether the use of PPIs is a risk factor to EIF. Materials and methods: A retrospective cohort study including 687 patients and 2971 dental implants. The study group (PPIs users) comprised 17.3% (119) individuals and 18.7% (555) implants. The remaining cohort (82.7% (568) individuals and 81.3% (2416) implants) served as control. The information was taken from the patients' files. The following information was collected: age, gender, physical status, systemic diseases, HbA1C values before and after implant-supported prosthesis delivery in cases of diabetes mellitus, smoking, implant location, number of implants per individual, bone augmentation, implant brand, length and width, and EIF. EIF was defined as implant removal within a period of up to 12 months from loading. Results: EIF in PPIs vs. non-PPIs users was 19.3% vs. 14.3% (p = 0.16) at patient level and 5.4% vs. 3.5% at implant level (p = 0.03). Univariate analysis yielded factors significantly associated with PPIs use, including older age, physical status of the American Society of Anesthesiology (ASA) 3, hypertension, hyperlipidemia, diabetes mellitus, osteoporosis, cardiovascular accident (CVA), location (anterior mandible), shorter and narrower implants, and higher number of implants per individual. Multivariate analysis yielded statistically significant OR of 1.91; p = 0.01 for EIF following PPIs use and 2.3; p < 0.001 for location in anterior mandible. Conclusions: Patients and their healthcare providers are advised to carefully consider the potential risks of taking PPIs prior to dental implant surgery. Further research is needed to confirm these risks and elucidate systemic and local factors that may be involved in such outcomes.

Clinical outcomes of single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy for locally advanced cervical cancer: A multi-institution initial experience.

Purpose: The aim of the study was to evaluate the safety and clinical outcomes of single application multi-fractionated computed tomography (CT)-guided interstitial high-dose-rate brachytherapy given in four fractions in locally advanced cervical cancer. Material and methods: Patients with locally advanced cervical cancer stage IIB-IVA treated definitively with external radiation ± weekly cisplatin, followed by single application multi-fractionated CT-guided interstitial high-dose-rate brachytherapy in four fractions were included. Dosimetry data, clinical response, and toxicity records were reviewed. Results: Between January 2018 and December 2022, twenty-two patients were included. Clinical stage distribution was as follows: IIB - 13.6%, IIIB - 27.3%, IIIC - 22.7%, and IVA - 36.4%. Mean high-risk clinical target volume (HR-CTV) was 66.19 ±32.69 cm3, and HR-CTV D90 dose was 86.8 ±1.7 Gy. 2 cc doses to bladder, rectum, and sigmoid were 84.6 ±2.8 Gy, 71.5 ±2.4 Gy, and 65.6 ±4.0 Gy, respectively. Mean overall treatment time was 66 ±21 days. With a median follow-up of 11.5 months (range, 5-44 months), median survival and local control were not achieved. One-year local control rate, one-year progression-free survival, and one-year overall survival were 82%, 66%, and 78%, respectively. Univariate analysis showed overall treatment time to be the only variable associated with all oncologic outcomes. For acute toxicity, grade 3 toxicity in four patients and grade 4 toxicity of infection in one patient were observed. For late toxicity, grade 3 gastrointestinal toxicity was noted in two patients. Conclusions: Initial results suggest that single application multi-fractionated CT-guided interstitial brachytherapy given in four fractions in locally advanced cervical cancer seems to be feasible and safe, but additional evidence is needed to generate more validated conclusions.

Evaluating differential expression of fibrosis-related genes and their correlation with blood vessel density in chronic cutaneous graft-versus-host disease.

BACKGROUND: Sclerodermoid graft-versus-host disease (GVHD) is the most severe form of chronic GVHD (cGVHD) and represents a considerable therapeutic challenge. Due to the scarcity of human studies on sclerodermoid cGVHD, the pathogenesis of this entity is not fully understood. OBJECTIVE: To identify the differential expression of fibrosis-related genes in skin lesions of human lichenoid and sclerodermoid cGVHD and to assess the expression of their corresponding proteins. METHODS: PCR array analysis was performed on RNA extracted from three skin biopsies of sclerodermoid cGVHD patients and three normal skin samples, for fibrosis-related gene expression profiles followed by evaluation of their corresponding protein expressions. The expressions of Tissue inhibitor of metalloproteinase 3 (TIMP3), matrix metalloproteinase 1 (MMP1), TIMP1, and TIMP2 were further studied by immunohistochemistry. Demographic, clinical and immunohistochemical parameters of the two cGVHD groups and the control group were compared. The Pearson correlation coefficient was used to assess the correlation between data among the study groups. RESULTS: We identified 44 upregulated and 14 downregulated genes in the skin samples of sclerodermoid cGVHD compared to the control group. TIMP3 was positive in 13/21 biopsies of cGVHD and in one biopsy of the control group. The average staining intensity was significantly higher in the cGVHD group compared to the control group. TIMP3 was expressed mainly in dermal blood vessels. cGVHD specimens with positive TIMP3 staining had a statistically significantly higher total microvascular area than the negative specimens. CONCLUSION: TIMP3 levels are increased in both subtypes of cGVHD and are associated with increased dermal vascularity.

Hair cortisol in polycystic ovary syndrome.

The aim of the study was to evaluate adrenal axis hyperactivation measuring hair cortisol levels, and its influence on the relationship among metabolic parameters, inflammation markers and androgens in adult women with PCOS. 44 women (18-34 years) with PCOS diagnosis and a control group of 49 healthy women (19-35 years) were included. In both gropus body mass index (BMI) was calculated and waist circumference (WC) was measured. Hair cortisol, total serum testosterone (TT), serum cortisol, 25 OH vitamin D (25OHD), insulin, high sensitivity C-reactive protein (hsCRP), triglycerides (TG), HDL cholesterol (HDL), glucose and leptin were measured. Bioavailable testosterone (bioT) was calculated. Hair cortisol concentration was higher and significantly different in PCOS patients compared to the control group (130 vs 63 pg/mg of hair, p < 0.001). Subsequently, patients with PCOS were divided into two groups according to hair cortisol levels: group 1 with normal hair cortisol concentration and group 2 with levels above the upper limit of the reference values (128 pg/mg of hair). In group 2, TT significantly correlated with 25OHD, hsCRP, TG/HDL index, BMI, WC, insulin and HOMA (p < 0.05); bioT correlated with hsCRP and leptin (p < 0.05). Finally, 25OHD was inversely correlated with leptin and with TG/HDL index (p < 0.05). High hair cortisol concentration in patients with PCOS confirmed hyperactivation of the HPA axis. The associations observed were only found in patients with PCOS with high hair cortisol levels (> 128 pg/mg of hair), showing a possible effect of HPA axis in these associations.

Immediate Maxillary Full-Arch Rehabilitation of Periodontal Patients with Terminal Dentition Using Tilted Implants and Bone Augmentation: A 5-Year Retrospective Cohort Study.

BACKGROUND: All-on-four protocols with tilted implants in the maxilla are used to rehabilitate the terminal dentition of the severe generalized periodontitis patients. Data on long-term biological complications are scarce. METHODS: Eighty-four axial and forty-six tilted immediate implants have been placed in the extraction sockets of 23 patients according to a four-six implants protocol combined with ridge augmentation. Within 72 h, a provisional prosthesis was cemented to the implants; after 6 months, a cemented ceramic-metallic prosthesis was delivered. The patients were followed for up to 5 years. RESULTS: The 5-year survival rate of the straight and tilted implants was 100% and 97.8, and the prosthetic one was 100%. Marginal bone loss (MBL) of the straight implants was 0.42 ± 0.67 and 0.59 ±1.01 mm on the mesial and distal sides; for the tilted, it was 0.37 ± 0.68 and 0.34 ±0.62 mm, and the differences were not statistically significant. Implant position, smoking, keratinized mucosal width, and cantilever did not affect MBL. Peri-implant mucositis involved 29.4% and 22.2% of the straight and tilted implants, respectively; peri-implantitis involved 5.8% and 4.4% of the straight and tilted implants, respectively, without statistical significance. CONCLUSIONS: This immediate loading protocol's 5-year survival and success rates were high. No difference between the straight and tilted implants was found regarding survival, success rates, and MBL.

Simplified urethral score system for predicting complex anterior urethroplasty.

OBJECTIVE: To assess U-score individual values as urethral complex surgery predictors. METHODS: Cross-sectional study including patients who received anterior urethroplasty from 2011 to 2019. U-score (etiology (1-2 points), number of strictures (1-2 points), anatomic location (1-2 points) and length (1-3 points)) was measured individually and globally. Surgical complexity was defined as low (anastomotic, buccal mucosal graft, and augmented anterior urethroplasty), and high complexity (double buccal mucosal graft, flap, and graft/flap combination). U-score components were included as complex surgery predictor and as main variable with individual probability values estimations and comparisons. Risk complex surgery probability groups were established. RESULTS: 654 patients were included. Mean age was 57.2 years. Low complexity surgery was performed in 464 patients (259 anastomotic, 144 graft, 61 augmented anterior urethroplasty) and high complexity was done in 190 (53 double buccal mucosa graft, 27 flap, 110 graft/flap comb.). In multivariate analysis length, number of strictures and location were predictors of complexity. Introducing U-Score as only variable in univariate model predicted an OR 8.52 (95%CI 6.1-11). Simplified U-score grouping set obtained by complex probability was: low risk (4-5 points), medium risk (6 points) and high risk of complexity (7-9 points) Predicted risk of complex surgery probability (95%CI) for low, median and high risk group were 1.6 (0-2.9), 19.1 (13.8-25.9) and 77.9 (61.6-88.7), respectively. CONCLUSIONS: U-score can be used as a tool to predict complex urethral surgery. We present a simplified U-score risk tool to assess individual complex anterior urethroplasty probability.

New multiproxy data obtained from the sedimentary fill of the Ría de Ferrol, NW Iberia.

Several gravity cores and vibro-cores were recovered from selected sites in the inner sector of Ría de Ferrol, NW Iberia (Muñoz Sobrino et al., 2021) [1]. These sediment cores were obtained during the surveys ECOMER-2014 and ECOMER-2015, developed from 2014 to 2015 on-board the R/V Mytilus (Consejo Superior de Investigación Científica) and the Amarradores Mil (Amarradores del Puerto y Ría de Ferrol, S.L.), respectively. Sedimentary and other multiproxy data presented here belong to four selected sediment cores located in the innermost part of the study area. Two were recovered using a gravity corer and another two using a vibro-corer. The depth of the cores and samples obtained is referred to the NMMA (the mean sea level in Alicante), which is the Spanish orthometric datum. One half of each core was subjected to non-destructive analysis using an ITRAX core scanner providing X-ray fluorescence (XRF) elemental data. Particle size distribution was characterised by laser diffraction. For radiocarbon dating, well-preserved articulated valves, small remains of wood and very organic bulk sediment from one location free of biogenic gas were selected. Palynological analyses were performed on selected sections of the sediment. All samples were spiked with Lycopodium spores for absolute palynomorph estimation and analysed using 400x and 600x magnifications. The ratio of dinoflagellate cyst concentrations to pollen, fern spore and dinoflagellate cyst concentrations (D/P ratio, ranging between 0 and 1) was calculated for each sample to show the temporal variation. Combined seismic, lithological, elemental, chronological and palynological data enable reconstructing the environmental changes that occurred during the local marine transgression. Besides, the combination of evidence identified may also be applied to other areas or periods in order to perform local reconstructions of changing coastal ecosystems. This type of high-resolution spatial-temporal reconstructions of past changes in estuarine environments may be a valuable tool for modelling, predicting and managing the changes and threats linked to the global warming and sea-level rise associated.

Implementing a protocol to prevent incisional hernia in high-risk patients: a mesh is a powerful tool.

PURPOSE: The small bites (SB) technique for closure of elective midline laparotomies (EMLs) and a prophylactic mesh (PM) in high-risk patients are suggested by the guidelines to prevent incisional hernias (IHs) and fascial dehiscence (FD). Our aim was to implement a protocol combining both the techniques and to analyze its outcomes. METHODS: Prospective data of all EMLs were collected for 2 years. Results were analyzed at 1 month and during follow-up. The incidence of HI and FD was compared by groups (M = Mesh vs. S = suture) and by subgroups depending on using SB. RESULTS: A lower number of FD appeared in the M group (OR 0.0692; 95% CI 0.008-0.56; P = 0.01) in 197 operations. After a mean follow-up of 29.23 months (N = 163; min. 6 months), with a lower frequency of IH in M group (OR 0.769; 95% CI 0.65-0.91; P < 0.0001). (33) The observed differences persisted after a propensity matching score: FD (OR 0.355; 95% CI 0.255-0.494; P < 0.0001) and IH (OR 0.394; 95% CI 0.24-0.61; P < 0.0001). On comparing suturing techniques by subgroups, both mesh subgroups had better outcomes. PM was the main factor related to the reduction of IH (HR 11.794; 95% CI 4.29-32.39; P < 0.0001). CONCLUSION: Following the protocol using PM and SB showed a lower rate of FD and HI. A PM is safe and effective for the prevention of both HI and FD after MLE, regardless of the closure technique used.

Safety and efficacy of urethroplasty based on age groups.

OBJECTIVE: To analyze the results and complications after urethroplasty based on patient age groups. As secondary objective, we analyzed the impact of operative complexity on each age group. MATERIAL AND METHODS: This is a retrospective cohort study that include male patients who underwent urethroplasty between January 2011 and December 2018. Data was obtained from the patients' electronic health records. Patients were grouped as follows: <60 years, 60-79 years and >80 years. Variables evaluated were history, comorbidities, previous surgeries and operative complexity. Restenosis-free survival and complications presented in each group were determined according to the Clavien-Dindo classification system. The SPSS® program was used for statistical analysis. RESULTS: A total of 783 patients were included, and the mean follow-up was 19 months. The estimated 2-year restenosis-free survival in the population under 60, 60-79 and over 80 years was 87, 87 and 93.9% (IC 95%), respectively. Univariate analysis showed that the age group was not a predictor of restenosis. Complex surgery is the only predictor of recurrence, increasing the risk by 60% (HR 1.64, 95% CI 1.05-2.56, p = 0.029). There was an overall complication rate of 30.8%, and 62% of these were Clavien ≤ II. We found no association between the frequency of complications and age. CONCLUSIONS: Urethroplasty is safe and effective regardless of age group. There are no statistically significant differences in outcomes and complications shown by the age group comparison. There were no significant differences when analyzing the impact of complex surgeries among the different age groups. The data indicate that age alone should not be taken as an absolute exclusion criterion for patients needing urethral reconstruction.

Prevalencia y factores de riesgo del comportamiento anormal estereotipado aerofagia en el caballo criollo colombiano / Prevalence and Risk Factors of Abnormal Stereotyped Crib-Biting Behavior in the Colombian Creole Horse

RESUMEN La aerofagia es la estereotipia clásica más común en los equinos, con una etiología poca entendida; sin embargo, se reconoce por ser de naturaleza multifactorial. Además, se ha asociado con efectos negativos sobre la salud de los equinos portadores. El objetivo de este estudio fue describir los factores de riesgo y la frecuencia de presentación de la aerofagia en una población de caballos criollos colombianos (CCC). Fueron encuesta-dos 42 criaderos, entre los que se presentó un total de 1063 CCC (488 machos y 575 hembras). De esta población, el 5,27% (56 animales) fue plenamente identificado con aerofagia. Esta prevalencia fue superior a la mayoría de otros reportes de Sur América. La aerofagia, posiblemente obedeció tanto a factores inherentes al animal como a factores externos relacionados con el manejo; sin embargo, se requiere el diseño de estudios longitudinales sobre prácticas de manejo y de líneas dentro de la raza para cuantificar y validar la información relacionada con la posible predisposición genética o racial a la aerofagia y a otras estereotipias y comportamientos anormales observados en estos animales.

ABSTRACT Crib-biting is the most common classic stereotype in equines, with a poorly understood etiology; however, it is recognized for being multifactorial in nature. Furthermore, it has been associated with negative effects on the health of horses. The objective of this study was to describe the risk factors and the frequency of presentation of crib-biting in a population of Colombian Creole Horses (CCC by its Spanish acronym). We surveyed Forty-two properties, which meant a total of 1063 CCC (488 males and 575 females). Of this population, 5,27% (56 animals) were fully identified with crib-biting. This prevalence was higher than most other reports in South America. Crib-biting is possibly due to both inherent of the animal and external factors related to management; however, the design of longitudinal studies on management practices and genetic lines within the breed is required to quantify and validate the information related to the possible genetic or racial predisposition for this and other stereotypes and abnormal behaviors observed in horses.

Influence of BRAF and PIK3CA mutations on the efficacy of FOLFIRI plus bevacizumab or cetuximab as first-line therapy in patients with RAS wild-type metastatic colorectal carcinoma and <3 baseline circulating tumour cells: the randomised phase II VISNÚ-2 study.

BACKGROUND: We explored the influence of BRAF and PIK3CA mutational status on the efficacy of bevacizumab or cetuximab plus 5-fluorouracil/leucovorin and irinotecan (FOLFIRI) as first-line therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: VISNÚ-2 was a multicentre, randomised, phase II study. Patients with RAS wild-type mCRC and <3 circulating tumour cells/7.5 ml blood were stratified by BRAF/PIK3CA status (wild-type versus mutated) and number of affected organs (1 versus >1), and allocated to bevacizumab (5 mg/kg every 2 weeks) or cetuximab (400 mg/m2 then 250 mg/m2 weekly) plus FOLFIRI [irinotecan 180 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 400 mg/m2 (bolus) then 2400 mg/m2 (46-h continuous infusion) every 2 weeks]. The primary endpoint was progression-free survival (PFS). All analyses were exploratory. RESULTS: Two hundred and forty patients with BRAF/PIK3CA wild-type (n = 196) or BRAF- and/or PIK3CA-mutated tumours (n = 44) were enrolled. Median PFS was 12.7 and 8.8 months in patients with BRAF/PIK3CA wild-type and BRAF/PIK3CA-mutated tumours, respectively [hazard ratio (HR) = 1.22; 95% confidence interval (CI) 0.80-1.85; P = 0.3602]. In the BRAF- and/or PIK3CA-mutated cohort, median PFS was 2.8, 8.8 and 15.0 months in patients with BRAF/PI3KCA-mutated (n = 8), BRAF-mutated/PI3KCA wild-type (n = 16) and BRAF wild-type/PI3KCA-mutated (n = 20) tumours, respectively (P = 0.0002). PFS was similar with bevacizumab plus FOLFIRI versus cetuximab plus FOLFIRI in BRAF/PIK3CA wild-type (HR = 0.99; 95% CI 0.67-1.45; P = 0.9486) and BRAF/PIK3CA-mutated tumours (HR = 1.11; 95% CI 0.53-2.35; P = 0.7820). The most common grade 3/4 treatment-related adverse events were neutropenia, diarrhoea and asthenia in both treatment groups. CONCLUSIONS: BRAF/PIK3CA status influences outcomes in patients with RAS wild-type mCRC but does not appear to assist with the selection of first-line targeted therapy.

Gamification and Game-Based Strategies for Dermatology Education: Narrative Review.

BACKGROUND: Game-based approaches, or gamification, are popular learning strategies in medical education for health care providers and patients alike. Gamification has taken the form of serious educational games and simulations to enable learners to rehearse skills and knowledge in a safe environment. Dermatology learners in particular may benefit from gamification methods, given the visual and procedural nature of the field. OBJECTIVE: This narrative review surveys current applications of gamification within general medical training, in the education of dermatology students, and in dermatology patient outreach. METHODS: A literature search was performed using PubMed, Google Scholar, and ResearchGate to access and review relevant medical education- and dermatology-related gamification studies published in peer-reviewed journals. Two independent researchers with education and experience in dermatology screened publications to select studies featuring a diversity of gamification approaches and study subjects for in-depth examination. RESULTS: A total of 6 general medical education-related and 7 dermatology-specific gamification studies were selected. Gamification generally increased motivation and engagement, improved reinforcement of learning objectives, and contributed to more enjoyable and positive educational experiences compared to traditional modes of instruction. Enhancing examination scores, building confidence, and developing stronger team dynamics were additional benefits for medical trainees. Despite the abundance of gamification studies in general medical education, comparatively few instances were specific to dermatology learning, although large organizations such as the American Academy of Dermatology have begun to implement these strategies nationally. Gamification may also a provide promising alternative means of diversifying patient education and outreach methods, especially for self-identification of malignant melanoma. CONCLUSIONS: Serious games and simulations in general medical education have successfully increased learner motivation, enjoyment, and performance. In limited preliminary studies, gamified approaches to dermatology-specific medical education enhanced diagnostic accuracy and interest in the field. Game-based interventions in patient-focused educational pilot studies surrounding melanoma detection demonstrated similar efficacy and knowledge benefits. However, small study participant numbers and large variability in outcome measures may indicate decreased generalizability of findings regarding the current impact of gamification approaches, and further investigation in this area is warranted. Additionally, some relevant studies may have been omitted by the simplified literature search strategy of this narrative review. This could be expanded upon in a secondary systematic review of gamified educational platforms.

Motor neuroprosthesis implanted with neurointerventional surgery improves capacity for activities of daily living tasks in severe paralysis: first in-human experience.

BACKGROUND: Implantable brain-computer interfaces (BCIs), functioning as motor neuroprostheses, have the potential to restore voluntary motor impulses to control digital devices and improve functional independence in patients with severe paralysis due to brain, spinal cord, peripheral nerve or muscle dysfunction. However, reports to date have had limited clinical translation. METHODS: Two participants with amyotrophic lateral sclerosis (ALS) underwent implant in a single-arm, open-label, prospective, early feasibility study. Using a minimally invasive neurointervention procedure, a novel endovascular Stentrode BCI was implanted in the superior sagittal sinus adjacent to primary motor cortex. The participants undertook machine-learning-assisted training to use wirelessly transmitted electrocorticography signal associated with attempted movements to control multiple mouse-click actions, including zoom and left-click. Used in combination with an eye-tracker for cursor navigation, participants achieved Windows 10 operating system control to conduct instrumental activities of daily living (IADL) tasks. RESULTS: Unsupervised home use commenced from day 86 onwards for participant 1, and day 71 for participant 2. Participant 1 achieved a typing task average click selection accuracy of 92.63% (100.00%, 87.50%-100.00%) (trial mean (median, Q1-Q3)) at a rate of 13.81 (13.44, 10.96-16.09) correct characters per minute (CCPM) with predictive text disabled. Participant 2 achieved an average click selection accuracy of 93.18% (100.00%, 88.19%-100.00%) at 20.10 (17.73, 12.27-26.50) CCPM. Completion of IADL tasks including text messaging, online shopping and managing finances independently was demonstrated in both participants. CONCLUSION: We describe the first-in-human experience of a minimally invasive, fully implanted, wireless, ambulatory motor neuroprosthesis using an endovascular stent-electrode array to transmit electrocorticography signals from the motor cortex for multiple command control of digital devices in two participants with flaccid upper limb paralysis.

Safety and efficacy of urethroplasty based on age groups. / Seguridad y eficacia de la uretroplastia según grupos etarios.

OBJECTIVE: To analyze the results and complications after urethroplasty based on patient age groups. As secondary objective, we analyzed the impact of operative complexity on each age group. MATERIAL AND METHODS: This is a retrospective cohort study that include male patients who underwent urethroplasty between January 2011 and December 2018. Data was obtained from the patients' electronic health records. Patients were grouped as follows: < 60 years, 60-79 years and > 80 years. Variables evaluated were history, comorbidities, previous surgeries and operative complexity. Restenosis-free survival and complications presented in each group were determined according to the Clavien-Dindo classification system. The SPSS® program was used for statistical analysis. RESULTS: A total of 783 patients were included, and the mean follow-up was 19 months. The estimated 2-year restenosis-free survival in the population under 60, 60-79 and over 80 years was 87, 87 and 93.9% (IC 95%), respectively. Univariate analysis showed that the age group was not a predictor of restenosis. Complex surgery is the only predictor of recurrence, increasing the risk by 60% (HR 1.64, 95% CI 1.05-2.56, p = 0.029). There was an overall complication rate of 30.8%, and 62% of these were Clavien ≤ II. We found no association between the frequency of complications and age. CONCLUSIONS: Urethroplasty is safe and effective regardless of age group. There are no statistically significant differences in outcomes and complications shown by the age group comparison. There were no significant differences when analyzing the impact of complex surgeries among the different age groups. The data indicate that age alone should not be taken as an absolute exclusion criterion for patients needing urethral reconstruction.

The Burden of Skin and Subcutaneous Diseases in the United States From 1990 to 2017.

Importance: Skin and subcutaneous diseases affect the health of millions of individuals in the US. Data are needed that highlight the geographic trends and variations of skin disease burden across the country to guide health care decision-making. Objective: To characterize trends and variations in the burden of skin and subcutaneous tissue diseases across the US from 1990 to 2017. Design, Setting, and Participants: For this cohort study, data were obtained from the Global Burden of Disease (GBD), a study with an online database that incorporates current and previous epidemiological studies of disease burden, and from GBD 2017, which includes more than 90 000 data sources such as systematic reviews, surveys, population-based disease registries, hospital inpatient and outpatient data, cohort studies, and autopsy data. The GBD separated skin conditions into 15 subcategories according to incidence, prevalence, adequacy of data, and standardized disease definitions. GBD 2017 also estimated the burden from melanoma of the skin and keratinocyte carcinoma. Data analysis for the present study was conducted from September 9, 2019, to March 31, 2020. Main Outcomes and Measures: Primary study outcomes included age-standardized disability-adjusted life-years (DALYs), incidence, and prevalence. The data were stratified by US states with the highest and lowest age-standardized DALY rate per 100 000 people, incidence, and prevalence of each skin condition. The percentage change in DALY rates in each state was calculated from 1990 to 2017. Results: Overall, age-standardized DALY rates for skin and subcutaneous diseases increased from 1990 (821.6; 95% uncertainty interval [UI], 570.3-1124.9) to 2017 (884.2; 95% UI, 614.0-1207.9) in all 50 states and the District of Columbia. The degree of increase varied according to geographic location, with the largest percentage change of 0.12% (95% UI, 0.09%-0.15%) in New York and the smallest percentage change of 0.04% (95% UI, 0.02%-0.07%) in Colorado, 0.04% (95% UI, 0.01%-0.06%) in Nevada, 0.04% (95% UI, 0.02%-0.07%) in New Mexico, and 0.04% (95% UI, 0.02%-0.07%) in Utah. The age-standardized DALY rate, incidence, and prevalence of specific skin conditions differed among the states. New York had the highest age-standardized DALY rate for skin and subcutaneous disease in 2017 (1097.0 [95% UI, 764.9-1496.1]), whereas Wyoming had the lowest age-standardized DALY rate (672.9 [95% UI, 465.6-922.3]). In all 50 states and the District of Columbia, women had higher age-standardized DALY rates for overall skin and subcutaneous diseases than men (women: 971.20 [95% UI, 676.76-1334.59] vs men: 799.23 [95% UI, 559.62-1091.50]). However, men had higher DALY rates than women for malignant melanoma (men: 80.82 [95% UI, 51.68-123.18] vs women: 42.74 [95% UI, 34.05-70.66]) and keratinocyte carcinomas (men: 37.56 [95% UI, 29.35-49.52] vs women: 14.42 [95% UI, 10.01-20.66]). Conclusions and Relevance: Data from the GBD suggest that the burden of skin and subcutaneous disease was large and that DALY rate trends varied across the US; the age-standardized DALY rate for keratinocyte carcinoma appeared greater in men. These findings can be used by states to target interventions and meet the needs of their population.

Postoperative urinary extravasation does not impact anterior urethroplasty surgical outcomes: a Latin American large cohort study.

OBJECTIVE: To determine the prevalence of postoperative urinary extravasation (POUE) following anterior urethroplasty, to analyze factors associated with its occurrence, and to study the impact of POUE on surgical success. MATERIALS AND METHODS: Retrospective cohort study including all male patients who have undergone a urethroplasty at our center between 2011 and 2018. Subjects with posterior location stricture, those who did not undergo routine radiographic follow-up, or patients with inadequate follow-up were excluded. Urinary extravasation was defined as presence of evident contrast extravasation on the postoperative voiding cystourethrogram (VCUG). Impact was determined as "need-for-reoperation". Uni- and multivariate analysis were performed to determine clinical and demographic variables associated with occurrence of extravasation and postoperative stricture. RESULTS: A total of 783 men underwent a urethroplasty and 630 fulfilled inclusion criteria. Urinary extravasation prevalence was 12.2%, and there was a "need-for-reoperation" in 1.1% of cases. On uni- and multivariate analysis, greatest stricture length (HR: 1.07 (1-1.2), p = 0.05) and penile urethral location (HR: 2.29 (1.1-4.6), p = 0.021) showed to be POUE predictors. POUE did not show to be a risk factor for postoperative stricture (HR: 1.57, 95% CI (0.8-3), p = 0.173). However, reoperation group  showed to be a risk factor (HR: 6.6, 95% CI 1.4-31, p = 0.019). CONCLUSIONS: Prevalence of POUE was 12.2%. Stricture length and penile urethral strictures were POUE predictors. POUE occurrence with successful conservative management did not appear to have impact on urethroplasty outcomes as it did not predict re-stricture. POUE was reoperation cause in 1.1% of total cases.