Anti-acetylated-tau immunotherapy is neuroprotective in tauopathy and brain injury.

BACKGROUND: Tau is aberrantly acetylated in various neurodegenerative conditions, including Alzheimer's disease, frontotemporal lobar degeneration (FTLD), and traumatic brain injury (TBI). Previously, we reported that reducing acetylated tau by pharmacologically inhibiting p300-mediated tau acetylation at lysine 174 reduces tau pathology and improves cognitive function in animal models. METHODS: We investigated the therapeutic efficacy of two different antibodies that specifically target acetylated lysine 174 on tau (ac-tauK174). We treated PS19 mice, which harbor the P301S tauopathy mutation that causes FTLD, with anti-ac-tauK174 and measured effects on tau pathology, neurodegeneration, and neurobehavioral outcomes. Furthermore, PS19 mice received treatment post-TBI to evaluate the ability of the immunotherapy to prevent TBI-induced exacerbation of tauopathy phenotypes. Ac-tauK174 measurements in human plasma following TBI were also collected to establish a link between trauma and acetylated tau levels, and single nuclei RNA-sequencing of post-TBI brain tissues from treated mice provided insights into the molecular mechanisms underlying the observed treatment effects. RESULTS: Anti-ac-tauK174 treatment mitigates neurobehavioral impairment and reduces tau pathology in PS19 mice. Ac-tauK174 increases significantly in human plasma 24 h after TBI, and anti-ac-tauK174 treatment of PS19 mice blocked TBI-induced neurodegeneration and preserved memory functions. Anti-ac-tauK174 treatment rescues alterations of microglial and oligodendrocyte transcriptomic states following TBI in PS19 mice. CONCLUSIONS: The ability of anti-ac-tauK174 treatment to rescue neurobehavioral impairment, reduce tau pathology, and rescue glial responses demonstrates that targeting tau acetylation at K174 is a promising neuroprotective therapeutic approach to human tauopathies resulting from TBI or genetic disease.

Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

First European Erwinia amylovora Lytic Bacteriophage Cocktails Effective in the Host: Characterization and Prospects for Fire Blight Biocontrol.

Fire blight, caused by the plant-pathogenic bacterium Erwinia amylovora, is a highly contagious and difficult-to-control disease due to its efficient dissemination and survival and the scarcity of effective control methods. Copper and antibiotics are the most used treatments but pose environmental and human health risks. Bacteriophages (phages) constitute an ecological, safe, and sustainable fire blight control alternative. The goal of this study was to search for specific E. amylovora phages from plant material, soil, and water samples in Mediterranean environments. A collection of phages able to specifically infect and lyse E. amylovora strains was generated from former fire blight-affected orchards in Eastern Spain. Following in vitro characterization, assays in immature fruit revealed that preventively applying some of the phages or their combinations delayed the onset of fire blight symptoms and reduced the disease's severity, suggesting their biocontrol potential in Spain and other countries. The morphological and molecular characterization of the selected E. amylovora phages classified them as members of the class Caudoviricetes (former Myoviridae family) and genus Kolesnikvirus. This study reveals Mediterranean settings as plausible sources of E. amylovora-specific bacteriophages and provides the first effective European phage cocktails in plant material for the development of sustainable fire blight management measures.

Detection of mecA Genes in Hospital-Acquired MRSA and SOSA Strains Associated with Biofilm Formation.

Methicillin-resistant (MR) Staphylococcus aureus (SA) and others, except for Staphylococcus aureus (SOSA), are common in healthcare-associated infections. SOSA encompass largely coagulase-negative staphylococci, including coagulase-positive staphylococcal species. Biofilm formation is encoded by the icaADBC operon and is involved in virulence. mecA encodes an additional penicillin-binding protein (PBP), PBP2a, that avoids the arrival of ß-lactams at the target, found in the staphylococcal cassette chromosome mec (SCCmec). This work aims to detect mecA, the bap gene, the icaADBC operon, and types of SCCmec associated to biofilm in MRSA and SOSA strains. A total of 46% (37/80) of the strains were S. aureus, 44% (35/80) S. epidermidis, 5% (4/80) S. haemolyticus, 2.5% (2/80) S. hominis, 1.25% (1/80) S. intermedius, and 1.25% (1/80) S. saprophyticus. A total of 85% were MR, of which 95.5% showed mecA and 86.7% ß-lactamase producers; thus, Staphylococcus may have more than one resistance mechanism. Healthcare-associated infection strains codified type I-III genes of SCCmec; types IV and V were associated to community-acquired strains (CA). Type II prevailed in MRSA mecA strains and type II and III in MRSOSA (methicillin-resistant staphylococci other than Staphylococcus aureus). The operon icaADBC was found in 24% of SA and 14% of SOSA; probably the arrangement of the operon, fork formation, and mutations influenced the variation. Methicillin resistance was mainly mediated by the mecA gene; however, there may be other mechanisms that also participate, since biofilm production is related to genes of the icaADBC operon and methicillin resistance was not associated with biofilm production. Therefore, it is necessary to strengthen surveillance to prevent the spread of these outbreaks both in the nosocomial environment and in the community.

Aptamers: A Cutting-Edge Approach for Gram-Negative Bacterial Pathogen Identification.

Early and accurate diagnoses of pathogenic microorganisms is essential to correctly identify diseases, treating infections, and tracking disease outbreaks associated with microbial infections, to develop precautionary measures that allow a fast and effective response in epidemics and pandemics, thus improving public health. Aptamers are a class of synthetic nucleic acid molecules with the potential to be used for medical purposes, since they can be directed towards any target molecule. Currently, the use of aptamers has increased because they are a useful tool in the detection of specific targets. We present a brief review of the use of aptamers to detect and identify bacteria or even some toxins with clinical importance. This work describes the advances in the technology of aptamers, with the purpose of providing knowledge to develop new aptamers for diagnoses and treatment of different diseases caused by infectious microorganisms.

Microentrepreneurs in Public Health Promotion: Implementation of a Street Vendor-Led COVID-19 Recovery Initiative in Los Angeles, California.

The COVID-19 pandemic exacerbated long-standing inequities, galvanizing new investments and community feedback to improve recovery programs. This implementation evaluation offers descriptive evidence of the feasibility of engaging street vendors to (1) facilitate linkage to services for undocumented Latinx communities, (2) strengthen health promotion by gathering community feedback, and (3) enhance economic opportunity by recognizing and addressing systemic challenges in which vendors operate. Future work should assess the effectiveness of mobilizing existing community messengers around entrenched social determinants of health. (Am J Public Health. 2024;114(S1):S78-S81. https://doi.org/10.2105/AJPH.2023.307453).

Quorum Quenching with a Diffusible Signal Factor Analog in Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia is a multidrug-resistant Gram-negative bacillus associated with nosocomial infections in intensive care units, and nowadays, its acquired resistance to trimethoprim-sulfamethoxazole (SXT) by sul genes within class 1 integrons is a worldwide health problem. Biofilm and motility are two of the major virulence factors in this bacterium and are auto-induced by the diffusible signal factor (DSF). In recent studies, retinoids have been used to inhibit (Quorum Quenching) these virulence factors and for their antimicrobial effect. The aim was to reduce biofilm formation and motility with retinoic acid (RA) in S. maltophilia SXT-resistant strains. Eleven SXT-resistant strains and two SXT-susceptible strains were tested for biofilm formation/reduction and planktonic/sessile cell viability with RA and SXT-MIC50/RA; motility (twitching, swimming, swarming) was measured with/without RA; and MLST typing was determined. The biofilm formation of the strains was classified as follows: 15.38% (2/13) as low, 61.54% (8/13) as moderate, and 23.08% (3/13) as high. It was significantly reduced with RA and SXT-MIC50/RA (p < 0.05); cell viability was not significantly reduced with RA (p > 0.05), but it was with SXT-MIC50/RA (p < 0.05); and swimming (p < 0.05) and swarming (p < 0.05) decreased significantly. MLST typing showed the first and novel strains of Mexican S. maltophilia registered in PubMLST (ST479-485, ST497, ST23, ST122, ST175, ST212, and ST300). In conclusion, RA reduced biofilm formation and motility without affecting cell viability; furthermore, antimicrobial synergism with SXT-MIC50/RA in different and novel STs of S. maltophilia was observed.

Slingshot homolog-1-mediated Nrf2 sequestration tips the balance from neuroprotection to neurodegeneration in Alzheimer's disease.

Oxidative damage in the brain is one of the earliest drivers of pathology in Alzheimer's disease (AD) and related dementias, both preceding and exacerbating clinical symptoms. In response to oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is normally activated to protect the brain from oxidative damage. However, Nrf2-mediated defense against oxidative stress declines in AD, rendering the brain increasingly vulnerable to oxidative damage. Although this phenomenon has long been recognized, its mechanistic basis has been a mystery. Here, we demonstrate through in vitro and in vivo models, as well as human AD brain tissue, that Slingshot homolog-1 (SSH1) drives this effect by acting as a counterweight to neuroprotective Nrf2 in response to oxidative stress and disease. Specifically, oxidative stress-activated SSH1 suppresses nuclear Nrf2 signaling by sequestering Nrf2 complexes on actin filaments and augmenting Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 interaction, independently of SSH1 phosphatase activity. We also show that Ssh1 elimination in AD models increases Nrf2 activation, which mitigates tau and amyloid-ß accumulation and protects against oxidative injury, neuroinflammation, and neurodegeneration. Furthermore, loss of Ssh1 preserves normal synaptic function and transcriptomic patterns in tauP301S mice. Importantly, we also show that human AD brains exhibit highly elevated interactions of Nrf2 with both SSH1 and Keap1. Thus, we demonstrate here a unique mode of Nrf2 blockade that occurs through SSH1, which drives oxidative damage and ensuing pathogenesis in AD. Strategies to inhibit SSH1-mediated Nrf2 suppression while preserving normal SSH1 catalytic function may provide new neuroprotective therapies for AD and related dementias.

Longitudinal in vivo monitoring of axonal degeneration after brain injury.

Traumatic brain injury (TBI)-induced axonal degeneration leads to acute and chronic neuropsychiatric impairment, neuronal death, and accelerated neurodegenerative diseases of aging, including Alzheimer's and Parkinson's diseases. In laboratory models, axonal degeneration is traditionally studied through comprehensive postmortem histological evaluation of axonal integrity at multiple time points. This requires large numbers of animals to power for statistical significance. Here, we developed a method to longitudinally monitor axonal functional activity before and after injury in vivo in the same animal over an extended period. Specifically, after expressing an axonal-targeting genetically encoded calcium indicator in the mouse dorsolateral geniculate nucleus, we recorded axonal activity patterns in the visual cortex in response to visual stimulation. In vivo aberrant axonal activity patterns after TBI were detectable from 3 days after injury and persisted chronically. This method generates longitudinal same-animal data that substantially reduces the number of required animals for preclinical studies of axonal degeneration.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Isolation and Identification of Multidrug-Resistant Klebsiella pneumoniae Clones from the Hospital Environment.

Global dispersion, hospital outbreaks, and lineage relationships between emerging antibiotic-resistant strains such as Klebsiella pneumoniae are of public health interest. This study aimed to isolate and identify K. pneumoniae clones from third-level healthcare hospitals in Mexico to establish their multidrug-resistant phenotype, phylogeny, and prevalence. Biological and abiotic surface samples were used to isolate K. pneumoniae strains and to test their antibiotic susceptibility to classify them. The housekeeping genes: gapA, InfB, mdh, pgi, phoE, ropB, and tonB were used for multilocus sequence typing (MLST). Phylogenetic networks were constructed with 48 strains. Isolated strains (93) were mainly from urine and blood, 96% were resistant to ampicillin as expected, 60% were extended-spectrum ß-lactamases (ESBL), 98% were susceptible to ertapenem and meropenem and 99% were susceptible to imipenem, 46% were multi-drug resistant (MDR), 17% were extensively-drug resistant (XDR), 1% were pan-drug resistant (PDR), and 36% were not classified. The tonB, mdh, and phoE genes were the most variable, and the InfB gene showed positive selection. The most prevalent sequence types (STs) were ST551 (six clones), ST405 (six clones), ST1088 (four clones), ST25 (four clones), ST392 (three clones), and ST36 (two clones). ST706 was PDR, and ST1088 clones were MDR; neither of these STs has been reported in Mexico. The strains analyzed were from different hospitals and locations; thus, it is important to maintain antibiotic surveillance and avoid clone dissemination to prevent outbreaks, adaptation to antibiotics, and the transmission of antibiotic resistance.

Evaluation of the Community Health Worker Model for COVID-19 Response and Recovery.

Community health workers (CHWs), or promotores de salud, have long played a role in health promotion, but the COVID-19 pandemic has brought renewed attention to the functions, sustainability, and financing of CHW models. ¡Andale! ¿Que Esperas? was a 12-month (June 2021-May 2022) campaign that expanded the CHW workforce to increase COVID-19 vaccination rates in structurally vulnerable, Latinx communities across California. This mixed-methods evaluation aims to elucidate (1) the role of CHWs in COVID-19 response, recovery, and rebuilding and (2) the importance, needs, and perils of CHW models in the COVID-19 era and beyond. CHWs facilitated 159,074 vaccinations and vaccine appointments by countering mis/disinformation, addressing mental health and social needs, building digital competencies, and meeting people where they are, all of which expanded access and instilled confidence in the COVID-19 vaccine. CHWs' success in engaging the community lies in their shared lived experience as well as their accessibility and recognition in the community, enabling their role in both immediate response and long-term recovery. Funding instability imperils the advances made by CHWs, and efforts are needed to institutionalize the CHW workforce with sustainable funding models. While Medicaid reimbursement models exist in some states, these models are often limited to healthcare services, overlooking a critical function of the CHW model: building community resilience and mobilizing the community for social change.

Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia / Recommendations for the use of neurophysiological techniques in the diagnosis of brain death from the Clinical Neurophysiology Society of the Communities of Valencia and Murcia

En España, el trasplante de órganos constituye uno de los mayores retos y trabajo en equipo de los centros hospitalarios. Se estima que en 2020 España aportó a la Unión Europea el 19% de la totalidad de los donantes. El diagnóstico de apoyo confirmatorio recomienda por ley algunas técnicas complementarias en determinados casos, entre ellas las técnicas neurofisiológicas, en especial el uso del electroencefalograma y los potenciales evocados. Estos casos plantean al neurofisiólogo clínico la toma acertada de decisiones tanto clínicas como técnicas para su correcta realización e interpretación. Hasta ahora no existe a nivel nacional un consenso de realización de estas técnicas. Es una revisión bibliográfica actualizada sobre las técnicas neurofisiológicas (electroencefalograma y potenciales evocados), con análisis mediante método Delphi y juicio de expertos del grupo de trabajo de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia. Las técnicas neurofisiológicas permiten ser un apoyo en el diagnóstico de muerte encefálica, tanto de forma confirmatoria como para acortar tiempos de observación. Para su realización se precisan unos mínimos estándares técnicos que permitan realizar de forma óptima los estudios. Especialmente hay que tener en cuenta la medicación, la situación hemodinámica, la ausencia de hipotermia y el grupo de edad. Presentamos la primera guía en castellano elaborada por la Sociedad de Neurofisiología de las Comunidades de Valencia y Murcia para la realización en nuestros hospitales de las técnicas neurofisiológicas en el diagnóstico de muerte encefálica.(AU)

In Spain organ transplantation constitutes one of the greatest challenges and teamwork of hospital centres. It is estimated that in the year 2020 Spain contributed 19% of all donors to the European Union. The confirmatory support diagnosis recommends by law some complementary techniques in certain cases, including neurophysiological techniques, especially the use of electroencephalogram and evoked potentials. These cases require the clinical neurophysiologist to make the right clinical and technical decisions for the correct performance and interpretation of the same. To date, there is no national consensus on the performance of these techniques. Updated bibliographic review on neurophysiological techniques (electroencephalogram and evoked potentials). Analysis by Delphi method and expert judgment of the working group of the Clinical Neurophysiology Society of the Communities of Valencia and Murcia. Neurophysiological techniques can be a support in the diagnosis of encephalic death, both confirmatory and to shorten observation times. In order to perform them, minimum technical standards are required to allow optimal performance of the studies, especially taking into account medication, hemodynamic situation, absence of hypothermia, and age group. We present the first guide in Spanish elaborated by the Society of Neurophysiology of the Communities of Valencia and Murcia for the performance in our hospitals of neurophysiological techniques in the diagnosis of brain death.(AU)

[Recommendations for the use of neurophysiological techniques in the diagnosis of brain death from the Clinical Neurophysiology Society of the Communities of Valencia and Murcia]. / Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.

In Spain organ transplantation constitutes one of the greatest challenges and teamwork of hospital centres. It is estimated that in the year 2020 Spain contributed 19% of all donors to the European Union. The confirmatory support diagnosis recommends by law some complementary techniques in certain cases, including neurophysiological techniques, especially the use of electroencephalogram and evoked potentials. These cases require the clinical neurophysiologist to make the right clinical and technical decisions for the correct performance and interpretation of the same. To date, there is no national consensus on the performance of these techniques. Updated bibliographic review on neurophysiological techniques (electroencephalogram and evoked potentials). Analysis by Delphi method and expert judgment of the working group of the Clinical Neurophysiology Society of the Communities of Valencia and Murcia. Neurophysiological techniques can be a support in the diagnosis of encephalic death, both confirmatory and to shorten observation times. In order to perform them, minimum technical standards are required to allow optimal performance of the studies, especially taking into account medication, hemodynamic situation, absence of hypothermia, and age group. We present the first guide in Spanish elaborated by the Society of Neurophysiology of the Communities of Valencia and Murcia for the performance in our hospitals of neurophysiological techniques in the diagnosis of brain death.

TITLE: Recomendaciones para el empleo de técnicas neurofisiológicas en el diagnóstico de muerte encefálica de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia.En España, el trasplante de órganos constituye uno de los mayores retos y trabajo en equipo de los centros hospitalarios. Se estima que en 2020 España aportó a la Unión Europea el 19% de la totalidad de los donantes. El diagnóstico de apoyo confirmatorio recomienda por ley algunas técnicas complementarias en determinados casos, entre ellas las técnicas neurofisiológicas, en especial el uso del electroencefalograma y los potenciales evocados. Estos casos plantean al neurofisiólogo clínico la toma acertada de decisiones tanto clínicas como técnicas para su correcta realización e interpretación. Hasta ahora no existe a nivel nacional un consenso de realización de estas técnicas. Es una revisión bibliográfica actualizada sobre las técnicas neurofisiológicas (electroencefalograma y potenciales evocados), con análisis mediante método Delphi y juicio de expertos del grupo de trabajo de la Sociedad de Neurofisiología Clínica de las Comunidades de Valencia y Murcia. Las técnicas neurofisiológicas permiten ser un apoyo en el diagnóstico de muerte encefálica, tanto de forma confirmatoria como para acortar tiempos de observación. Para su realización se precisan unos mínimos estándares técnicos que permitan realizar de forma óptima los estudios. Especialmente hay que tener en cuenta la medicación, la situación hemodinámica, la ausencia de hipotermia y el grupo de edad. Presentamos la primera guía en castellano elaborada por la Sociedad de Neurofisiología de las Comunidades de Valencia y Murcia para la realización en nuestros hospitales de las técnicas neurofisiológicas en el diagnóstico de muerte encefálica.

Challenges and opportunities for the future of recreational boat scrapping: The Spanish case.

Recreational boating is a leisure and sports activity that has aroused growing interest among users, tourists, and the general public. However, in the last decade, a problem has arisen concerning the abandonment of recreational boats. It is a problem that has become even more acute in times of economic recession. It is, therefore, necessary to find an urgent solution in order to reduce potential environmental risks. This work aims to analyze the state of the question through bibliometrics to know which topics are trending and contrast these findings with a Delphi analysis. The main results focus on the need for greater agility in the court adjudication process and the need for a specific legal framework for the scrapping of recreational craft. In conclusion, it is vital to integrate the circular economy into shipbuilding and scrapping processes to ensure the sustainability of the sector and the environment.

Numerical Analysis of the ACL, with Sprains of Different Degrees after Trauma.

Nowadays, cruciate ligament injuries have increased in incidence, since practicing a sport or physical activity has become a trend in current societies. Although this lifestyle generates multiple benefits, as a consequence, injury has also increased. Due to its nature and complexity, the ligaments of the knee are those that are most frequently affected, mainly the ACL (anterior cruciate ligament). This tissue reacts to overexertion or movements out of range, either caused by the exercise itself or caused by trauma caused by the practice of physical activity, causing various degrees of sprain. Whatever the etiology of these injuries, they will require a therapy indicated for each degree of injury. This therapy initially entails immobilization of the affected area and later; physical therapy will be required to a lesser or greater degree. Commonly, in the physiotherapy of these injuries, rehabilitation exercises are prescribed, where the physiotherapist asks a patient to use equipment with an estimated weight. However, the effectiveness of a generalized therapy in this way does not always give the expected results. This is related to the fact that these therapies are standardized and do not consider some factors such as the remaining muscle fibres that are not directly affected by the sprain, which does not mean that they should not be considered. Therefore, in the present work, a biomodel of a human knee has been developed and used to evaluate numerically how the ACL acts under an external load, when there are different degrees of injuries, caused by trauma. Four case studies were considered: Case 1 (control case) where the ACL is healthy, Case 2 where the ACL presents a 1st-degree sprain, Case 3 where the ACL presents a 2nd-degree sprain, and finally Case 4 where the ACL presents a 3rd-sprain grade. After performing the analyses, in the control case, it was found that it presents a balance between tensile and compressive stresses. While in the 4th case, the most critical tensile stress decreases while compression stresses increase. This shows that the ligament, having considerable damage, no longer works as it should and can eventually damage the collateral structures. It was found that, when there was a sprain, where the continuity of the ligament is compromised, a second torsional moment occurs in the ACL which causes the tissue fibres not to act according to their normal physiology or in a healthy state. The results obtained from the present study provide the possibility of predicting where the following injuries will occur by considering the von Mises failure criterion. Likewise, they will allow to improve the therapeutic procedures considering not only the injured structure but also the system as a whole.

Standardizing Care of Neuro-oncology Patients Using a Customized Electronic Medical Record Toolkit.

OBJECTIVE: To develop and implement a customized toolkit within the electronic medical record (EMR) to standardize care of patients with brain tumors. PATIENTS AND METHODS: We built a customized structured clinical documentation support toolkit to capture standardized data at office visits. We detail the process by which this toolkit was conceptualized and developed. Toolkit development was a physician-led process to determine a work flow and necessary elements to support best practices as defined by the neuro-oncology clinical team. RESULTS: We have developed in our EMR system a customized work flow for clinical encounters with neuro-oncology patients. In addition to providing a road map for clinical care by our neuro-oncology team, the toolkit is designed to maximize discrete data capture. Several hundred fields of discrete data are captured through the toolkit in the context of our routine office visits. We describe the characteristics of patients seen at our clinic, the adoption of the toolkit, current initiatives supported by the toolkit, and future applications. CONCLUSION: The EMR can be effectively structured to standardize office visits and improve discrete data capture. This toolkit can be leveraged to support quality improvement and practice-based research initiatives at the point of care in a neuro-oncology practice.

Variable Effects of PD-Risk Associated SNPs and Variants in Parkinsonism-Associated Genes on Disease Phenotype in a Community-Based Cohort.

Genetic risk factors for Parkinson's disease (PD) risk and progression have been identified from genome-wide association studies (GWAS), as well as studies of familial forms of PD, implicating common variants at more than 90 loci and pathogenic or likely pathogenic variants at 16 loci. With the goal of understanding whether genetic variants at these PD-risk loci/genes differentially contribute to individual clinical phenotypic characteristics of PD, we used structured clinical documentation tools within the electronic medical record in an effort to provide a standardized and detailed clinical phenotypic characterization at the point of care in a cohort of 856 PD patients. We analyzed common SNPs identified in previous GWAS studies, as well as low-frequency and rare variants at parkinsonism-associated genes in the MDSgene database for their association with individual clinical characteristics and test scores at baseline assessment in our community-based PD patient cohort: age at onset, disease duration, Unified Parkinson's Disease Rating Scale I-VI, cognitive status, initial and baseline motor and non-motor symptoms, complications of levodopa therapy, comorbidities and family history of neurological disease with one or more than one affected family members. We find that in most cases an individual common PD-risk SNP identified in GWAS is associated with only a single clinical feature or test score, while gene-level tests assessing low-frequency and rare variants reveal genes associated in either a unique or partially overlapping manner with the different clinical features and test scores. Protein-protein interaction network analysis of the identified genes reveals that while some of these genes are members of already identified protein networks others are not. These findings indicate that genetic risk factors for PD differentially affect the phenotypic presentation and that genes associated with PD risk are also differentially associated with individual disease phenotypic characteristics at baseline. These findings raise the intriguing possibility that different SNPs/gene effects impact discrete phenotypic characteristics. Furthermore, they support the hypothesis that different gene and protein-protein interaction networks that underlie PD risk, the PD phenotype, and the neurodegenerative process leading to the disease phenotype, and point to the significance of the genetic background on disease phenotype.

Reducing acetylated tau is neuroprotective in brain injury.

Traumatic brain injury (TBI) is the largest non-genetic, non-aging related risk factor for Alzheimer's disease (AD). We report here that TBI induces tau acetylation (ac-tau) at sites acetylated also in human AD brain. This is mediated by S-nitrosylated-GAPDH, which simultaneously inactivates Sirtuin1 deacetylase and activates p300/CBP acetyltransferase, increasing neuronal ac-tau. Subsequent tau mislocalization causes neurodegeneration and neurobehavioral impairment, and ac-tau accumulates in the blood. Blocking GAPDH S-nitrosylation, inhibiting p300/CBP, or stimulating Sirtuin1 all protect mice from neurodegeneration, neurobehavioral impairment, and blood and brain accumulation of ac-tau after TBI. Ac-tau is thus a therapeutic target and potential blood biomarker of TBI that may represent pathologic convergence between TBI and AD. Increased ac-tau in human AD brain is further augmented in AD patients with history of TBI, and patients receiving the p300/CBP inhibitors salsalate or diflunisal exhibit decreased incidence of AD and clinically diagnosed TBI.