APOE×BDNF Interaction and Poorer Cognitive Outcomes Among Veterans With Mild Traumatic Brain Injury: An Exploratory Study.

OBJECTIVE: The authors examined the interaction between apolipoprotein E (APOE) ε4 and brain-derived neurotrophic factor (BDNF) Val66Met alleles on neuropsychological functioning among veterans with histories of mild traumatic brain injury (mTBI). METHODS: Participants were 78 veterans with mTBI (85% males; mean±SD age=32.95±7.00 years; mean time since injury=67.97±34.98 months) who completed a structured clinical interview and underwent a comprehensive neuropsychological assessment. Participants also provided a buccal swab for determination of their APOE and BDNF genotypes. Three cognitive composite scores were calculated from the neuropsychological assessment, reflecting visuospatial speed (seven variables), executive functioning (10 variables), and memory (eight variables). Two-way analyses of covariance (ANCOVAs) adjusted for age, sex, and race-ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning. RESULTS: ANCOVAs revealed no significant main effects of APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE-by-BDNF genotype interaction for all three cognitive composite measures (visuospatial speed: ηp2=0.055; executive functioning: ηp2=0.064; and memory: ηp2=0.068). Specifically, the ε4+/Met+ (N=8) subgroup demonstrated the poorest cognitive functioning relative to all other allele subgroups (ε4+/Met-: N=12, ε4-/Met+: N=23, and ε4-/Met-: N=35). CONCLUSIONS: This exploratory study is the first to show that, compared with other allele subgroups assessed, veterans with both ε4 and Met alleles demonstrated the poorest cognitive functioning across several cognitive domains known to be negatively affected in the context of mTBI. Further research with larger sample sizes is needed to replicate these findings.

Comparing neuropsychological, typical, and ADNI criteria for the diagnosis of mild cognitive impairment in Vietnam-era veterans.

OBJECTIVE: Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer's disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD. METHOD: 267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aß42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria. RESULTS: Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria. CONCLUSIONS: MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

Symptom attribution is a stronger predictor of PVT-failure than symptom endorsement in treatment-seeking Veterans with remote mTBI history: A pilot study.

OBJECTIVE: To examine relationships between performance validity testing (PVT), neurobehavioral symptom endorsement, and symptom attribution in Veterans with a history of mild traumatic brain injury (mTBI). METHOD: Participants included treatment-seeking Veterans (n = 37) with remote mTBI histories who underwent a neuropsychological assessment and completed a modified version of the Neurobehavioral Symptom Inventory (NSI) to assess symptom endorsement and symptom attribution (the latter evaluated by having Veterans indicate whether they believed each NSI symptom was caused by their mTBI). Veterans were divided into two subgroups, PVT-Valid (n = 25) and PVT-Invalid (n = 12). RESULTS: Independent samples t-tests showed that two of five symptom endorsement variables and all five symptom attribution variables were significantly different between PVT groups (PVT-Invalid > PVT-Valid; Cohen's d = 0.67-1.02). Logistic regression analyses adjusting for PTSD symptoms showed that symptom endorsement (Nagelkerke's R2 = .233) and symptom attribution (Nagelkerke's R2 = .279) significantly distinguished between PVT groups. According to the Wald criterion, greater symptom endorsement (OR = 1.09) and higher attribution of symptoms to mTBI (OR = 1.21) each reliably predicted PVT-failure. CONCLUSIONS: While both symptom endorsement and symptom attribution were significantly associated with PVT-failure, our preliminary results suggest that symptom attribution is a stronger predictor of PVT-failure. Results highlight the importance of assessing symptom attribution to mTBI in this population.

Genomic assessment reveals signal of adaptive selection in populations of the Spotted rose snapper Lutjanus guttatus from the Tropical Eastern Pacific.

Background: The lack of barriers in the marine environment has promoted the idea of panmixia in marine organisms. However, oceanographic conditions and habitat characteristics have recently been linked to genetic structure in marine species. The Tropical Eastern Pacific (TEP) is characterized by dynamic current systems and heterogeneous oceanographic conditions. The Gulf of Panama (part of the equatorial segment for the TEP) is influenced by a complex current system and heterogeneous environment, which has been shown to limit the gene flow for shoreline species. Next Generation Sequencing (NGS) has contributed to detect genetic differences in previously reported panmictic species by the assessment of loci associated with selection and to understand how selection acts affects marine populations. Lutjanus guttatus is a species distributed in the TEP for which previous studies using mitochondrial data recovered a panmictic pattern along its distributional range. In this study, we used SNP data of L. guttatus individuals sampled along its range to evaluate population genetic structure and investigate whether oceanographic factors influence the species' genetic architecture. Finally, we assessed the role of adaptive selection by evaluating the contribution of outlier and neutral loci to genetic divergence. Methods: The RADcap method was used to obtain 24 million paired reads for 123 individuals of L. guttatus covering nearly all its distributional area. Genetic variation was assessed using both spatial and non-spatial methods by comparing three different data sets: (i) a Combined Loci (CL dataset = 2003 SNPs); a search for putative loci under selection allowed the evaluation of (ii) Neutral Loci (NL dataset = 1858 SNPs) and (iii) Outlier Loci (OL dataset = 145 SNPs). We used the estimating effective migration surface (EEMS) approach to detect possible barriers to gene flow. Results: Genetic differences were found in the OL dataset, showing two clusters (Northern and Southern), whereas NL showed no differences. This result may be related to the Selection-Migration balance model. The limit between the Northern and Southern groups was in the Gulf of Panama, which has been previously identified as a barrier to gene flow for other species, mainly due to its heterogeneous oceanographic conditions. The results suggest that selection plays an important role in generating genetic differences in Lutjanus guttatus. A migration corridor was detected that coincides with the Costa Rica Coastal Current that flows from Central America to the Gulf of California, allowing the homogenization of the northern population. In the Southern cluster, a migration corridor was observed with the OL from Panama to Colombia, which could be associated with the currents found in the Gulf of Panama. Genetic variation found in the OL of Lutjanus guttatus highlights the usefulness of NGS data in evaluating the role of selection in population differentiation.

The application of artificial intelligence in the detection of basal cell carcinoma: A systematic review.

Basal cell carcinoma (BCC) is one of the most common types of cancer. The growing incidence worldwide and the need for fast, reliable and less invasive diagnostic techniques make a strong case for the application of different artificial intelligence techniques for detecting and classifying BCC and its subtypes. We report on the current evidence regarding the application of handcrafted and deep radiomics models used for the detection and classification of BCC in dermoscopy, optical coherence tomography and reflectance confocal microscopy. We reviewed all the articles that were published in the last 10 years in PubMed, Web of Science and EMBASE, and we found 15 articles that met the inclusion criteria. We included articles that are original, written in English, focussing on automated BCC detection in our target modalities and published within the last 10 years in the field of dermatology. The outcomes from the selected publications are presented in three categories depending on the imaging modality and to allow for comparison. The majority of articles (n = 12) presented different AI solutions for the detection and/or classification of BCC in dermoscopy images. The rest of the publications presented AI solutions in OCT images (n = 2) and RCM (n = 1). In addition, we provide future directions for the application of these techniques for the detection of BCC. In conclusion, the reviewed publications demonstrate the potential benefit of AI in the detection of BCC in dermoscopy, OCT and RCM.

Genetic differentiation in the genus Characodon: implications for conservation and taxonomy.

The subfamily Goodeinae is a group of fishes endemic to the Mexican highlands. Most of the species are restricted to small and isolated streams or springs. Within this subfamily, the genus Characodon is the earliest diverging lineage of which three species have been described: C. lateralis, C. audax, and C. garmani, with the latter, considered extinct. Characodon lateralis and C. audax are classed as endangered, and have been the subject of taxonomic controversy since their description: previous studies have recognized a genetic differentiation in two groups separated by the El Salto waterfall, but morphological analyses contradict these genetic results. We perform a phylogeographic study using the mitochondrial cytb gene and d-loop region to elucidate the evolutionary history of C. lateralis and C. audax. The results with both markers show the presence of two highly differentiated haplogroups; one distributed north and the other distributed south of the waterfall, with genetic distances of 1.7 and 13.1% with cytb and d-loop respectively, and divergence calculated to have occurred 1.41 Mya. Significant genetic structure was found within each haplogroup and suggests the existence of at least four Evolutionary Significant Units (ESUs) within the examined populations. The possible processes identified as contributing to the formation of differentiated genetic groups are isolation, low population size, recurrent bottlenecks, and the strong sexual selection exhibited by the genus.

DEVELOPMENT AND VALIDATION OF AN ENZYME-LINKED IMMUNOASSAY KIT FOR DIAGNOSIS AND SURVEILLANCE OF COVID-19

There is a massive demand to identify alternative methods to detect new cases of COVID-19 as well as to investigate the epidemiology of the disease. In many countries, importation of commercial kits poses a significant impact on their testing capacity and increases the costs for the public health system. We have developed an ELISA to detect IgG antibodies against SARS-CoV-2 using a recombinant viral nucleocapsid (rN) protein expressed in E. coli. Using a total of 894 clinical samples we showed that the rN-ELISA was able to detect IgG antibodies against SARS-CoV-2 with high sensitivity (97.5%) and specificity (96.3%) when compared to a commercial antibody test. After three external validation studies, we showed that the test accuracy was higher than 90%. The rN-ELISA IgG kit constitutes a convenient and specific method for the large-scale determination of SARS-Cov-2 antibodies in human sera with high reliability.

Will a little change do you good? A putative role of polymorphisms in COVID-19.

An alarming disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 has emerged as an unprecedented public health problem and ignited a world health crisis. As opposed to what was believed at the beginning of the pandemic, the virus has not only spread but persevere causing secondary waves and challenging the concept of herd immunity against viral infections. While the majority of SARS-CoV-2-infected individuals may remain asymptomatic, a fraction of individuals may develop low to high-grade severity signs and symptoms of COVID-19. The disease is multifactorial and can progress quickly, leading to severe complications and even death in a few days. Therefore, understanding the pre-existing factors for disease development has never been so pressing. In this scenario, the insights on the mechanisms underlying disease allied to the immune response developed during the viral invasion could shed light on novel predictive factors and prognostic tools for COVID-19 management and interventions. A recent genome-wide association study (GWAS) revealed several molecules that significantly impacted critically ill COVID-19 patients, leading to the core mechanisms of COVID-19 pathogenesis. Considering these findings and the fact that ACE-2 polymorphisms alone cannot explain disease progress and severity, this review aims at summarizing the most important and recent findings of the research and expert consensus of possible cytokine-related polymorphisms existing in the differential expression of paramount immune molecules that could be crucial for providing guidelines for decision-making and appropriate clinical management of COVID-19.

Cumulative risk of skin cancer in patients with Li-Fraumeni syndrome.

Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome, characterized by an early onset of various types of cancers. LFS is associated with a germline mutation in the TP53 gene. The risk of developing skin cancer in patients with LFS is unknown. To evaluate the cumulative risk of skin cancer in patients with LFS and to compare this risk to the general Dutch population. In this retrospective cohort study, all proven TP53 mutation carriers in the Netherlands Cancer Institute were included from their first visit to the Institute until June 2017. Medical charts and pathology reviews cross-referenced with PALGA, the nationwide network and registry of histo- and cytopathology were used to identify incident skin cancers. Cumulative risks were calculated by Kaplan-Meier analysis. Seventy-one patients (59% female) from 33 families were included. Ten patients (14%) developed a total of 19 skin cancers at a median age of 41 (25-65) years. The cumulative risk of skin cancer is 10.4% (95% CI 4.4-23.5%) at age 40, 25.2% (95% CI 12.3-47.6%) at age 60, and a at age 70 this risk is 44.6% (95% CI 22.9-73.9%). The cumulative risks of melanoma and basal cell carcinoma at age 70 are increased compared to the general Dutch population, namely 12.6% (95% CI 3.6-38.4%) and 34.6% (95% CI 15.4-66.2%), respectively. Patients with LFS have an increased risk of developing skin cancer. A dermatological consultation may be considered at least once in individuals with LFS to raise awareness for skin cancer and inform about risk factors.

Dynamic Tensile Stress-Compressive Stress Behavior of Thermoplastic Matrix Composite Materials Reinforced with Continuous Fiber for Automotive Damping and Anti-Vibration Structural Elements.

Continuous Fibers-Reinforced Thermoplastic Composites (CFRTP) are presented as light materials, capable of offering a short production time with the possibility of being recycled. These properties make them ideal for automotive applications, aiming to reduce the consumption and emission of polluting gases. This article analyzed the dynamic tensile stress-compressive stress behavior of CFRTP in structural elements of the car with anti-vibration and damping functions. The data available in the literature on the reliable and usual compliance of the properties required for CFRTP, to be applied in the automotive structural elements, is scarce and insufficient. In order to analyze whether CFRTP feeds the demanding requirements of car manufacturers and if they provide advantages over the metal materials currently used, this article developed a method of reliable verification of their dynamic tensile and compression behavior. The methodology developed could be used as a guide to characterizing any combination of vulcanized rubber adhesive joints with CFRTP, regardless of the materials and additives used. The results obtained showed that there exists CFRTP that fits the requirements of the car manufacturers for this type of component and also offers dynamic advantages over the materials currently used as anti-vibration elements.

A squamous cell carcinoma in a young woman with Lynch syndrome.

Lynch syndrome (LS) is an autosomal-dominant inherited disorder characterized by a predisposition to colorectal cancer and extracolonic cancers (particularly endometrium, ovary, stomach, small bowel, hepatobiliary tract, pancreas, urothelial tract, brain, and skin). Muir-Torre syndrome (MTS) is considered a phenotypical variant of LS, where patients develop sebaceous neoplasms and keratoacanthomas. Currently, only few studies and case reports suggest an association between LS and other skin cancers, such as Bowens' disease, melanoma and squamous cell carcinoma (SCC). In this case-report we describe the case of a 33-year-old woman with LS and a proven MSH2 germline mutation, presenting with a SCC on the right cheek. Immunohistochemistry lacked MSH2 and MSH6 protein staining. The tumor showed a discordance between immunohistochemistry and micro-satellite instability status, for which a clear explanation cannot be provided yet. To conclude whether this pattern is indicative for SCC occurring in LS patients, further analyses of other LS patients presenting with SCC should be carried out. Our patient's young age and skin type (Fitzpatrick phototype VI) suggest a possible link between LS and cutaneous SCC.

Molecular dynamics simulation for PBR pebble tracking simulation via a random walk approach using Monte Carlo simulation.

Using a Monte Carlo (MC) simulation, random walks were used for pebble tracking in a two-dimensional geometry in the presence of a biased gravity field. We investigated the effect of viscosity damping in the presence of random Gaussian fluctuations. The particle tracks were generated by Molecular Dynamics (MD) simulation for a Pebble Bed Reactor. The MD simulations were conducted in the interaction of noncohesive Hertz-Mindlin theory where the random walk MC simulation has a correlation with the MD simulation. This treatment can easily be extended to include the generation of transient gamma-ray spectra from a single pebble that contains a radioactive tracer. Then the inverse analysis thereof could be made to determine the uncertainty of the realistic measurement of transient positions of that pebble by any given radiation detection system designed for that purpose.

Cistitis intersticial y enterocistoplastia de parche amplio, en Hospital Higueras de Talcahuano / Intersticial cystitis and large plaster enterocystoplsty in Hospital Higueras, Talcahuano

Se analizaron 15 casos de cistitis intersticial con múltiples tratamientos, entre abril de 1996 a marzo de 2004, del Hospital las Higueras de Talcahuano, incluyéndose a las pacientes que cumplían con criterios clínicos (NIDDK), hallazgos cistoscópicos, biopsia y registro seriado de cartilla miccional. Los tratamientos evaluados fueron la hidrodistensión, instilación de Dimetilsulfóxido (DMSO), instilación de heparina y cirugía de agrandamiento vesical con íleon con distal sin cistectomía supratrigonal. El promedio de evolución sintomática antes del diagnóstico fue de 6,7 años. Las pacientes presentaban 25 micciones promedio por día con volumen miccional promedio de 112 cc, y capacidad máxima bajo anestesia de 487 cc (rango de 120 a 900 cc). El 87 por ciento refería mejoría transitoria con la hidrodistensión, con la heparina el 75 por ciento y el 44 por ciento de mejoría transitoria con DMSO. Las cuatro pacientes que requirieron de agrandamiento vesical se encuentran sin dolor, tienen adecuado vaciamiento y han retornado a sus actividades habituales. La mayor parte de nuestras pacientes han podido ser tratadas adecuadamente con medidas simples como la distensión vesical periódica a demanda y/o la instilación de sustancias. Fue adecuado reservar la ampliación vesical para casos extremos, obteniendo óptimos resultados con la técnica elegida.

[Brucella infective endocarditis on sclerodermic mitral valve. Report of a case]. / Endocarditis infecciosa brucelósica sobre válvula mitral esclerodérmica. A propósito de un caso.

We report the case of a 67 years old woman diagnosed of CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, telangiectasias) variant of generalized scleroderma, that suffered a Brucella endocarditis on mitral valve affected by the primary disease. We examine the cardiac lesions in progressive systemic sclerosis, pointing up the rare involvement of the valves, together with the evolution and treatment of Brucella endocarditis, uncommon entity.

Comparison of 6- with 9-week trials of adjunctive imipramine in postpsychotic depression.

Outcome at 6 weeks versus outcome at 9 weeks was compared in 23 patients with syndromally defined episodes of postpsychotic depression who underwent a trial of adjunctive imipramine added to their continuing treatment with fluphenazine decanoate and benztropine. The global outcome after 9 weeks was found to be superior. The implications of this finding for the treatment of secondary depressions in patients with schizophrenia and schizoaffective disorder is discussed.