Impact of dementia on 30-, 180-, and 365-day mortality during the first pandemic wave in older adults seen in spanish emergency departments diagnosed with or without COVID-19.

OBJECTIVES: To assess whether dementia is an independent predictor of death after a hospital emergency department (ED) visit by older adults with or without a COVID-19 diagnosis during the first pandemic wave. METHOD: We used data from the EDEN-Covid (Emergency Department and Elderly Needs during Covid) cohort formed by all patients ≥65 years seen in 52 Spanish EDs from March 30 to April 5, 2020. The association of prior history of dementia with mortality at 30, 180 and 365 d was evaluated in the overall sample and according to a COVID-19 or non COVID diagnosis. RESULTS: We included 9,770 patients aged 78.7 ± 8.3 years, 51.1% men, 1513 (15.5%) subjects with prior history of dementia and 3055 (31.3%) with COVID-19 diagnosis. 1399 patients (14.3%) died at 30 d, 2008 (20.6%) at 180 days and 2456 (25.1%) at 365 d. The adjusted Hazard Ratio (aHR) for age, sex, comorbidity, disability and diagnosis for death associated with dementia were 1.16 (95% CI 1.01-1.34) at 30 d; 1.15 at 180 d (95% CI 1.03-1.30) and 1.19 at 365 d (95% CI 1.07-1.32), p < .001. In patients with COVID-19, the aHR were 1.26 (95% CI: 1.04-1.52) at 30 days; 1.29 at 180 d (95% CI: 1.09-1.53) and 1.35 at 365 d (95% CI: 1.15-1.58). CONCLUSION: Dementia in older adults attending Spanish EDs during the first pandemic wave was independently associated with 30-, 180- and 365-day mortality. This impact was lower when adjusted for age, sex, comorbidity and disability, and was greater in patients diagnosed with COVID-19.

Immunophenotype profile by flow cytometry reveals different subtypes of extracellular vesicles in porcine seminal plasma.

BACKGROUND: Porcine seminal plasma (SP) is endowed with a heterogeneous population of extracellular vesicles (sEVs). This study evaluated the immunophenotypic profile by high-sensitivity flow cytometry of eight sEV subpopulations isolated according to their size (small [S-sEVs] and large [L-sEVs]) from four different SP sources, namely three ejaculate fractions (the first 10 mL of the sperm rich fraction [SRF-P1], the remaining SRF [SRF-P2], and the post-SRF [PSRF]) and entire ejaculate (EE). METHODS: Seminal EVs were isolated using a size exclusion chromatography-based protocol from six SP pools (five ejaculates/pool) of each SP source and characterized using complementary approaches including total protein (BCA™assay), particle size distribution (dynamic light scattering), morphology (transmission electron microscopy), and purity (albumin by Western blot). Expression of CD9, CD63, CD81, CD44 and HSP90ß was analyzed in all sEV subpopulations by high-sensitivity flow cytometry according to MIFlowCyt-EV guidelines, including an accurate calibration, controls, and discrimination by CFSE-labelling. RESULTS: Each sEV subpopulation exhibited a specific immunophenotypic profile. The percentage of sEVs positive for CD9, CD63, CD81 and HSP90ß differed between S- and L-sEVs (P < 0.0001). Specifically, the percentage of sEVs positive for CD9 and CD63 was higher and that for CD81 was lower in S- than L-sEVs in the four SP sources. However, the percentage of HSP90ß-positive sEVs was lower in S-sEVs than L-sEVs in the SRF-P1 and EE samples. The percentage of sEVs positive for CD9, CD63, and CD44 also differed among the four SP sources (P < 0.0001), being highest in PSRF samples. Notably, virtually all sEV subpopulations expressed CD44 (range: 88.04-98.50%). CONCLUSIONS: This study demonstrated the utility of high-sensitivity flow cytometry for sEV immunophenotyping, allowing the identification of distinct sEV subpopulations that may have different cellular origin, cargo, functions, and target cells.

Evaluation of the economic benefits, administration times, and patient preferences associated with the use of biotechnological drugs administered subcutaneously and intravenously in patients with cancer: a systematic review.

INTRODUCTION: Cancer imposes a high economic burden with medical care and medication costs. We evaluate the costs, the use of resources, the administration time, and the patient preferences associated with the use of biotechnological drugs in SC and IV presentations. METHODOLOGY: A systematic literature search was conducted in PubMed, Embase, and seven additional databases. The search was carried out in September 2021 and included only studies directly comparing SC and IV presentations. Evidence was synthesized narratively. RESULTS: 34 references were included, which only analyzed bortezomib, daratumumab, rituximab, and trastuzumab. Reduction in preparation costs of SC compared to IV presentations ranged from 6.6% to 50.1%, and in administration costs from 4.5% to 95.3%. SC administration of rituximab and trastuzumab resulted in less productivity loss. More than 68% of patients reported greater satisfaction with the SC route. A reduction of time in the infusion chair, lower costs of resources for preparation, and health personnel for the administration process were identified with SC administration. CONCLUSIONS: The use of SC daratumumab, rituximab, and trastuzumab in patients with cancer reduces direct and indirect costs and adverse events compared to IV use. Patients prefer the SC administration, perceiving more comfort, and less pain at the administration site.

Case report: Multisystem inflammatory syndrome in children associated with COVID-19, macrophage activation syndrome, and incomplete Kawasaki disease.

Background: Multisystem inflammatory syndrome in children (MIS-C), is a severe complication of coronavirus disease 2019 (COVID-19), characterized by persistent fever, systemic inflammatory response, and organ failure. MIS-C with a history of COVID-19 may share clinical features with other well-defined syndromes such as macrophage activation syndrome, Kawasaki disease, hemophagocytic syndrome and toxic shock syndrome. Case 1: An 11-year-old male with a history of hypothyroidism and precocious puberty with positive antibody test for COVID-19 was admitted for fever, poor general condition, severe respiratory distress, refractory shock, and multiple organ failure. His laboratory examination showed elevated inflammatory parameters, and bone marrow aspirate showed hemophagocytosis. Case 2: A 13-year-old male with a history of attention deficit hyperactivity disorder and cognitive delay presented clinical manifestations of Kawasaki disease, fever, conjunctival congestion, exanthema, and hyperemia in oral mucosa, tongue, and genitals, with refractory shock and multiple organ failure. Reverse transcriptase polymerase chain reaction (RT-PCR) and antibodies for COVID-19 were negative, inflammation parameters were elevated, and bone marrow aspirate showed hemophagocytosis. Patients required intensive care with invasive mechanical ventilation, vasopressor support, intravenous gamma globulin, systemic corticosteroids, low molecular weight heparin, antibiotics, and monoclonal antibodies and, patient 2 required renal replacement therapy. Conclusions: Multisystemic inflammatory syndrome in children can have atypical manifestations, and identifying them early is very important for the timely treatment and prognosis of patients.

Seminal Extracellular Vesicles and Their Involvement in Male (In)Fertility: A Systematic Review.

Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies specifically investigating such relationship. Embase, PubMed, and Scopus databases were searched up to 31 December 2022, primarily identifying a total of 1440 articles. After processing for screening and eligibility, 305 studies were selected as they focused on sEVs, and 42 of them were considered eligible because they included the word fertility or a related word such as infertility, subfertility, fertilization, and recurrent pregnancy loss in the title, objective(s), and/or keywords. Only nine of them met the inclusion criteria, namely (a) conducting experiments aimed at associating sEVs with fertility concerns and (b) isolating and adequately characterizing sEVs. Six studies were conducted on humans, two on laboratory animals, and one on livestock. The studies highlighted some sEV molecules, specifically proteins and small non-coding RNAs, that showed differences between fertile and subfertile or infertile males. The content of sEVs was also related to sperm fertilizing capacity, embryo development, and implantation. Bioinformatic analysis revealed that several of the highlighted sEV fertility-related proteins would be cross-linked to each other and involved in biological pathways related to (i) EV release and loading and (ii) plasma membrane organization.

Extracellular vesicles would be involved in the release and delivery of seminal TGF-ß isoforms in pigs.

Introduction: Pig seminal plasma (SP) is rich in active forms of all three isoforms (1-3) of transforming growth factor ß (TGF-ß), a chemokine modulatory of the immune environment in the female genital tract once semen is delivered during mating or artificial insemination (AI). The present study aimed to examine how TGF-ßs are secreted by the epithelium of the male reproductive tract and how they are transported in semen, emphasizing the interplay with seminal extracellular vesicles (sEVs). Methods: Source of TGF-ßs was examined by immunohistochemistry in testis, epididymis, and accessory sex glands, by immunocytochemistry in ejaculated spermatozoa, and by Luminex xMAP® technology in SP and sEVs retrieved from healthy, fertile male pigs used as breeders in AI programs. Results: All three TGF-ß isoforms were expressed in all reproductive tissues explored and would be released into ductal lumen either in soluble form or associated with sEVs. Ejaculated spermatozoa expressed all three TGF-ß isoforms, both inside and outside, probably the outer one associated with membrane-bound sEVs. The results confirmed that pig SP contains all three TGF-ß isoforms and demonstrated that a substantial portion of them is associated with sEVs. Discussion: Seminal EVs would be involved in the cellular secretion of the active forms of seminal TGF-ß isoforms and in their safe transport from the male to the female reproductive tract.

Loneliness, Depression, and Genetics in the Elderly: Prognostic Factors of a Worse Health Condition?

Loneliness is considered a prognostic factor for poorer health status in the elderly. It is proposed to analyze the role of loneliness in health status in terms of various factors. A total of 1747 individuals from the pilot survey of the Aging in Spain Longitudinal Study (ELES-PS) were reviewed. ELES is a cross-sectional study for collecting health variables, food habits, socioeconomic data, and cognitive and functional capacities, which was carried out on a Spanish representative sample of noninstitutionalized persons of 50 years of age or older. Moreover, since telomere shortening is associated with cellular senescence, 35 telomere-related SNPs and cognitive impairments were analyzed. The results characterize the "solos" as males of 50-60 years, who were overweight and had lower levels of hemoglobin and neutrophils. There is also an association between five SNPs related to telomere length and BDNF. A group of people with loneliness and depression was identified with poorer health and cognitive status, poorer perception of their quality of life, poorer quality of sleep, and lower physical activity. Therefore, it follows that telomeres and BDNF play a role as intermediaries between loneliness and depression and their relationship with a worse state of health.

New Advances in Biomedical Application of Polymeric Micelles.

In the last decade, nanomedicine has arisen as an emergent area of medicine, which studies nanometric systems, namely polymeric micelles (PMs), that increase the solubility and the stability of the encapsulated drugs. Furthermore, their application in dermal drug delivery is also relevant. PMs present unique characteristics because of their unique core-shell architecture. They are colloidal dispersions of amphiphilic compounds, which self-assemble in an aqueous medium, giving a structure-type core-shell, with a hydrophobic core (that can encapsulate hydrophobic drugs), and a hydrophilic shell, which works as a stabilizing agent. These features offer PMs adequate steric protection and determine their hydrophilicity, charge, length, and surface density properties. Furthermore, due to their small size, PMs can be absorbed by the intestinal mucosa with the drug, and they transport the drug in the bloodstream until the therapeutic target. Moreover, PMs improve the pharmacokinetic profile of the encapsulated drug, present high load capacity, and are synthesized by a reproducible, easy, and low-cost method. In silico approaches have been explored to improve the physicochemical properties of PMs. Based on this, a computer-aided strategy was developed and validated to enable the delivery of poorly soluble drugs and established critical physicochemical parameters to maximize drug loading, formulation stability, and tumor exposure. Poly(2-oxazoline) (POx)-based PMs display unprecedented high loading concerning water-insoluble drugs and over 60 drugs have been incorporated in POx PMs. Among various stimuli, pH and temperature are the most widely studied for enhanced drug release at the site of action. Researchers are focusing on dual (pH and temperature) responsive PMs for controlled and improved drug release at the site of action. These dual responsive systems are mainly evaluated for cancer therapy as certain malignancies can cause a slight increase in temperature and a decrease in the extracellular pH around the tumor site. This review is a compilation of updated therapeutic applications of PMs, such as PMs that are based on Pluronics®, micelleplexes and Pox-based PMs in several biomedical applications.

Towards Multimodal Equipment to Help in the Diagnosis of COVID-19 Using Machine Learning Algorithms.

COVID-19 occurs due to infection through respiratory droplets containing the SARS-CoV-2 virus, which are released when someone sneezes, coughs, or talks. The gold-standard exam to detect the virus is Real-Time Polymerase Chain Reaction (RT-PCR); however, this is an expensive test and may require up to 3 days after infection for a reliable result, and if there is high demand, the labs could be overwhelmed, which can cause significant delays in providing results. Biomedical data (oxygen saturation level-SpO2, body temperature, heart rate, and cough) are acquired from individuals and are used to help infer infection by COVID-19, using machine learning algorithms. The goal of this study is to introduce the Integrated Portable Medical Assistant (IPMA), which is a multimodal piece of equipment that can collect biomedical data, such as oxygen saturation level, body temperature, heart rate, and cough sound, and helps infer the diagnosis of COVID-19 through machine learning algorithms. The IPMA has the capacity to store the biomedical data for continuous studies and can be used to infer other respiratory diseases. Quadratic kernel-free non-linear Support Vector Machine (QSVM) and Decision Tree (DT) were applied on three datasets with data of cough, speech, body temperature, heart rate, and SpO2, obtaining an Accuracy rate (ACC) and Area Under the Curve (AUC) of approximately up to 88.0% and 0.85, respectively, as well as an ACC up to 99% and AUC = 0.94, respectively, for COVID-19 infection inference. When applied to the data acquired with the IMPA, these algorithms achieved 100% accuracy. Regarding the easiness of using the equipment, 36 volunteers reported that the IPMA has a high usability, according to results from two metrics used for evaluation: System Usability Scale (SUS) and Post Study System Usability Questionnaire (PSSUQ), with scores of 85.5 and 1.41, respectively. In light of the worldwide needs for smart equipment to help fight the COVID-19 pandemic, this new equipment may help with the screening of COVID-19 through data collected from biomedical signals and cough sounds, as well as the use of machine learning algorithms.

Polymeric Micelles: A Promising Pathway for Dermal Drug Delivery.

Nanotechnology is an area in great development and with application in the most varied fields of science, including cosmetic and pharmaceutical industries. Because conventional formulations for topical application are not always able to effectively penetrate the physical barrier that human skin exerts against factors and compounds of the external environment, polymeric micelles appear as alternative carriers for drugs and active ingredients delivery, also allowing ingredients with lower solubility and higher lipophilicity to be delivered. In fact, the augmented bioavailability of drugs, greater efficacy even at a lower dose, and selective drug delivery in specific organelles are very interesting advantages of the polymeric micelles usage in cutaneous application. As a consequence, they show a reduction in many of the local and systemic adverse effects, which might lead to an increase in patient compliance to the therapeutics, constituting a promising alternative to conventional topical formulations.

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

TPX-0131, a Potent CNS-penetrant, Next-generation Inhibitor of Wild-type ALK and ALK-resistant Mutations.

Since 2011, with the approval of crizotinib and subsequent approval of four additional targeted therapies, anaplastic lymphoma kinase (ALK) inhibitors have become important treatments for a subset of patients with lung cancer. Each generation of ALK inhibitor showed improvements in terms of central nervous system (CNS) penetration and potency against wild-type (WT) ALK, yet a key continued limitation is their susceptibility to resistance from ALK active-site mutations. The solvent front mutation (G1202R) and gatekeeper mutation (L1196M) are major resistance mechanisms to the first two generations of inhibitors while patients treated with the third-generation ALK inhibitor lorlatinib often experience progressive disease with multiple mutations on the same allele (mutations in cis, compound mutations). TPX-0131 is a compact macrocyclic molecule designed to fit within the ATP-binding boundary to inhibit ALK fusion proteins. In cellular assays, TPX-0131 was more potent than all five approved ALK inhibitors against WT ALK and many types of ALK resistance mutations, e.g., G1202R, L1196M, and compound mutations. In biochemical assays, TPX-0131 potently inhibited (IC50 <10 nmol/L) WT ALK and 26 ALK mutants (single and compound mutations). TPX-0131, but not lorlatinib, caused complete tumor regression in ALK (G1202R) and ALK compound mutation-dependent xenograft models. Following repeat oral administration of TPX-0131 to rats, brain levels of TPX-0131 were approximately 66% of those observed in plasma. Taken together, preclinical studies show that TPX-0131 is a CNS-penetrant, next-generation ALK inhibitor that has potency against WT ALK and a spectrum of acquired resistance mutations, especially the G1202R solvent front mutation and compound mutations, for which there are currently no effective therapies.

Clinical value of procalcitonin in critically ill patients infected by SARS-CoV-2.

Background Blood procalcitonin (PCT) levels usually increase during infectious diseases and might be helpful to differentiate bacterial from non-bacterial origin. COVID-19 patients could present co-infections at initial presentation in the Emergency Department and nosocomial infections during stay in the ICU. However, the published literature has not established whether PCT changes could aid in the diagnosis of infectious complication during the COVID-19 pandemic. Methods Retrospective, single-center, cohort study, including COVID-19 patients admitted between March and May 2020. The data were prospectively collected for department purposes; laboratory results were collected automatically at admission and during the whole patient admission. Results 56 patients were analyzed (female 32%, male 68%), 35 were admitted to ICU, and 21 received general ward care. 21 ICU patients underwent mechanical ventilation (88%), and 9 died during admission (26%). Non-survivors had higher initial blood PCT levels than survivors at ICU admission (p.

Targeting Oncogene mRNA Translation in B-Cell Malignancies with eFT226, a Potent and Selective Inhibitor of eIF4A.

The PI3K/AKT/mTOR pathway is often activated in lymphoma through alterations in PI3K, PTEN, and B-cell receptor signaling, leading to dysregulation of eIF4A (through its regulators, eIF4B, eIF4G, and PDCD4) and the eIF4F complex. Activation of eIF4F has a direct role in tumorigenesis due to increased synthesis of oncogenes that are dependent on enhanced eIF4A RNA helicase activity for translation. eFT226, which inhibits translation of specific mRNAs by promoting eIF4A1 binding to 5'-untranslated regions (UTR) containing polypurine and/or G-quadruplex recognition motifs, shows potent antiproliferative activity and significant in vivo efficacy against a panel of diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma models with ≤1 mg/kg/week intravenous administration. Evaluation of predictive markers of sensitivity or resistance has shown that activation of eIF4A, mediated by mTOR signaling, correlated with eFT226 sensitivity in in vivo xenograft models. Mutation of PTEN is associated with reduced apoptosis in vitro and diminished efficacy in vivo in response to eFT226. In models evaluated with PTEN loss, AKT was stimulated without a corresponding increase in mTOR activation. AKT activation leads to the degradation of PDCD4, which can alter eIF4F complex formation. The association of eFT226 activity with PTEN/PI3K/mTOR pathway regulation of mRNA translation provides a means to identify patient subsets during clinical development.

Assessment of an Assistive Control Approach Applied in an Active Knee Orthosis Plus Walker for Post-Stroke Gait Rehabilitation.

The goal of this study is the assessment of an assistive control approach applied to an active knee orthosis plus a walker for gait rehabilitation. The study evaluates post-stroke patients and healthy subjects (control group) in terms of kinematics, kinetics, and muscle activity. Muscle and gait information of interest were acquired from their lower limbs and trunk, and a comparison was conducted between patients and control group. Signals from plantar pressure, gait phase, and knee angle and torque were acquired during gait, which allowed us to verify that the stance control strategy proposed here was efficient at improving the patients' gaits (comparing their results to the control group), without the necessity of imposing a fixed knee trajectory. An innovative evaluation of trunk muscles related to the maintenance of dynamic postural equilibrium during gait assisted by our active knee orthosis plus walker was also conducted through inertial sensors. An increase in gait cycle (stance phase) was also observed when comparing the results of this study to our previous work. Regarding the kinematics, the maximum knee torque was lower for patients when compared to the control group, which implies that our orthosis did not demand from the patients a knee torque greater than that for healthy subjects. Through surface electromyography (sEMG) analysis, a significant reduction in trunk muscle activation and fatigability, before and during the use of our orthosis by patients, was also observed. This suggest that our orthosis, together with the assistive control approach proposed here, is promising and could be considered to complement post-stroke patient gait rehabilitation.

Association between Neutrophil-to-Lymphocyte Ratio with Abdominal Obesity and Healthy Eating Index in a Representative Older Spanish Population.

Poor diet quality and obesity, especially abdominal obesity, have been associated with systemic inflammation. The neutrophil-to-lymphocyte Ratio (NLR) is an available and inexpensive inflammation biomarker. The aim of the present study was to determine the association of dietary patterns and obesity with an inflammatory state. A group of 1747 Spanish noninstitutionalized older adults individuals were included, and a food-frequency questionnaire was applied. The Global Food Score (GFS) and Healthy Eating Index for Spanish population (SHEI) were calculated. Weight, height and waist (WC) and hip circumferences were measured, and BMI, waist-to-height ratio (WHtR), and waist-to-hip ratio (WHR) determined. In addition, body-fat percentage was measured by bioimpedance. NLR was calculated (NLR ≥ p80: 2.6; 2.8 and 2.4 as inflammatory status in the entire population, men and women, respectively). The men with inflammatory status presented significative higher values of WC, WHtR, WHR, and body-fat percentage (101.82 ± 10.34 cm, 0.61 ± 0.06, 0.98 ± 0.06, and 31.68 ± 5.94%, respectively) than those with better inflammatory status (100.18 ± 10.22 cm, 0.59 ± 0.06, 0.97 ± 0.07, and 30.31 ± 6.16%, respectively). Those males with worse inflammatory state had lower scores for protein foods (OR = 0.898 (0.812-0.993); p = 0.037). The women with NLR ≥ 2.4 had higher WHtR and WHR (0.62 ± 0.09 and 0.91 ± 0.09) than those with NLR < 2.4 (0.60 ± 0.08 and 0.90 ± 0.08). In multiple linear regression analysis, NLR was positively related with WHtR and negatively related with SHEI score (ß = 0.224 ± 0.094; R2 = 0.060; p < 0.05 and ß = -0.218 ± 0.101; R2 = 0.061; p < 0.05), adjusting by sex, age, marital status, education level, smoking, hours of sleeping and inflammatory diseases. In women, the higher the SHEI and GFS scores were and the better meeting the aims of cereal and vegetable servings, the less the odds of inflammatory status (OR = 0.970 (0.948-0.992); p = 0.008; OR = 0.963 (0.932-0.995); p = 0.024; OR = 0.818 (0.688-0.974); p = 0.024 and OR = 0.829 (0.730-0.942); p = 0.004, respectively). WHtR and quality of diet is related to the inflammation status in older adults regardless to the sex.

Spanish allele and haplotype database for 32 X-chromosome Insertion-Deletion polymorphisms.

X-chromosome markers have been proved to be decisive both complementing and solving kinship analysis, particularly when autosomal markers are not able to produce adequate likelihood ratios between different hypothesis. On the other hand, Pereira et al., (2012) have demonstrated that 32 Insertion/Deletion (InDel) markers located on the X-Chromosome have a very important power of discrimination in human populations, being a novel tool in the forensic and population fields. So, the aim of the present work was testing the forensic and population genetic efficiency of the 32 X-InDel polymorphisms in the Spanish population, and subsequently build an allele/haplotype frequencies database. To accomplish this objective, a total of 555 samples comprising male individuals from 13 Spanish regions were analysed for the above mentioned 32 X-InDels in two independent laboratories. A pairwise FST analysis was performed in order to understand if the studied Spanish sub-populations present significant differences among them, detecting possible population substructure. Also, linkage disequilibrium analyses were computed to investigate the presence of association between markers in the Spanish population. After Bonferroni correction, the absence of significant differences among the studied regions supports a global Spanish population database. Concerning LD, besides previously reported linked markers MID356-MID357 and MID3690-MID3719-MID2089, we also detected significant association between MID3703-MID3774, even after Bonferroni correction. Finally, after computing allele and haplotype frequencies, forensic efficiency parameters were calculated (PDmales = 99.999976 %; PDfemales = 99.99999999998 %). Mean exclusion chance values for duos were 0.999 and trios 0.99999. These results reinforce the suitability of the 32 X-InDels marker set both in identification and kinship studies.

Neuroanatomía funcional de la escala de coma de Glasgow / Functional neuroanatomy of the Glasgow coma scale

Introducción: La escala de coma de Glasgow (ECG) es una escala mundialmente reconocida para la clasificación de pacientes con trauma craneoencefálico de acuerdo a su compromiso neurológico. Esta escala evalúa la apertura ocular, la respuesta verbal y la respuesta motora. La neuroanatomía funcional representa un compromiso secuencial para el descenso en el puntaje de cada uno de estos ítems. El objetivo de esta revisión es describir la anatomía del sistema reticular activador ascendente (SRAA), la anatomía funcional del lenguaje, la anatomía del tallo cerebral y de las vías motoras que representan cada ítem evaluado por la ECG. Materiales y métodos: Se hizo una revisión narrativa bibliográfica de las principales vías para cada ítem de la ECG. Resultados: Las principales vías en relación con la apertura ocular se concentran en las vías del SRAA, las vías de la respuesta verbal incluyen las vías del lenguaje y las vías que provienen del putamen y del cerebelo que regulan la emisión del lenguaje, mientras que las vías que regulan la respuesta motora principalmente se relacionan con la vía piramidal, el sistema rubro-espinal y vestíbulo-espinal. Conclusiones: El descenso del puntaje en los tres ítems que evalúa la ECG se relacionan con vías específicas que predominan en los ganglios basales y en el tallo cerebral.

Introduction: The Glasgow Coma Scale (GCS) is a globally recognized scale for the classification of patients with traumatic brain injury according to their neurological impairment. This scale evaluates the ocular opening, the verbal response and the motor response. Functional neuroanatomy represents a sequential decrease in the score of each of these items. The objective of this review is to describe the anatomy of the ascending reticular activating system (ARAS), the functional anatomy of the language, and the anatomy of the brainstem and the motor pathways that represent each item evaluated by the GCS. Materials and methods: A narrative literature review of the main routes for each item of the scale was performed. Results: The main pathways in relation to the ocular opening are concentrated in the ARAS, the verbal response pathways include the language pathways and the connections that come from the putamen and the cerebellum that regulate the production of the language, while the pathways that regulate the motor response mainly relate to the pyramidal tract, the rubro-spinal and vestibulo-spinal systems. Conclusions: The decline of the score in the three items that evaluates the GCS is related to specific pathways that predominate in the basal ganglia and in the brainstem.

O paradoxo da institucionalização infantil: proteção ou risco? / The paradox of child institutionalization: protection or risk? / La paradoja de la institucionalización de niños: ¿protección o riesgo?

Desde meados do século XX, ganhou destaque o debate acerca dos efeitos da institucionalização de crianças. O abrigo adquire relação paradoxal entre proteção e risco, podendo ser facilitador ou dificultador para o desenvolvimento de crianças acolhidas. Assim, os objetivos do trabalho foram (1) analisar a produção científica sobre a institucionalização infantil, discutindo os benefícios e efeitos da institucionalização sobre o desenvolvimento de crianças e adolescentes; e (2) compreender como os artigos analisados identificam possíveis fatores de risco e de proteção. Como método, realizou-se uma revisão bibliográfica utilizando os descritores "abrigo"; "institucionalização infantil"; "fatores de risco e fatores de proteção"; "abrigamento prolongado"; "vínculo"; "apego"; "abrigo". Como resultado, 11 trabalhos foram selecionados. As produções analisadas apontaram que, embora o abrigo seja um local para acolhimento, assistência e proteção, deve-se estar atento aos fatores de risco e aos impactos negativos da institucionalização. Conclui-se que a institucionalização se faz necessária em alguns casos, devendo ocorrer com qualidade e responsabilidade junto às famílias e com o respaldo de políticas públicas.

Since the mid-twentieth century, the debate about the effects of children institutionalization has been on the spot. The institutional shelter has been getting into a paradoxical relationship between protection and risk and may be understood as either a facilitator or an impediment to children’s development. Thus, the objectives of this study are to (1) review scientific literature on child institutionalization, debating the benefits and effects of institutionalization on children’s and adolescents’ development; (2) understand how the articles analyzed identify possible risk and protection factors. Concerning methodology, we carried out a literature review using the descriptors "shelter"; "child institutionalization"; "risk factors and protective factors"; "prolonged shelter"; "bond"; "attachment"; "shelter". As a result, eleven articles were selected. Result analysis pointed out that although the shelter is a place for refuge, care and protection, one should be aware of the risk factors and the negative impact of institutionalization. It concludes that institutionalization is necessary in some cases, and it should occur with quality and responsibility together with the families and with the support of public policies.

Desde mediados del siglo XX, se hizo destacado el debate sobre los efectos de la institucionalización de los niños. El refugio adquiere una relación paradójica entre la protección y el riesgo, y puede ser un facilitador o un obstáculo para el desarrollo de los niños. Los objetivos del estudio fueron (1) revisar la literatura científica sobre la institucionalización de niños, la discusión de los beneficios y los efectos de la institucionalización en el desarrollo de los niños y adolescentes y (2) entender cómo los artículos analizados identifican posibles factores de riesgo y protección. Como método, se realizó una revisión de la literatura utilizando los descriptores "refugio"; "institucionalización de niños"; "factores de riesgo y factores de protección"; "refugio prolongado"; "vínculo"; "el apego", "la vivienda". Como resultado, fueron seleccionados once artículos. Las producciones analizadas señalaron que si bien el abrigo es un lugar de refugio, cuidado y protección, debe ser consciente de los factores de riesgo y el impacto negativo de la institucionalización. Se concluye que la institucionalización es necesaria en algunos casos, debe ocurrir con la calidad y la responsabilidad de las familias y con el apoyo de políticas públicas.