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Mental disorders account for a large and increasing health burden worldwide. Characterizing the spectrum of mental disorders and trends over time in adolescents should influence education policies and support preventative strategies at schools. Retrospective study of all hospitalizations in Spain in adolescents 11-18-years old, including mental disorders as diagnosis using the Spanish National Registry of Hospital Discharges. Information was retrieved from 2000 to 2021. During the 22-year study period there were 2,015,589 hospitalizations in adolescents in Spain, of which 118,609 (5.9%) had mental disorders. The rate of psychiatric diagnoses significantly increased from 3.9% in 2000 to 9.5% in 2021. Females accounted for 55.1% of admissions. Mean age at admission declined from 17 to 15 years-old from 2000 to 2021. Mean hospital stay was 10.6 days. Mean in-hospital mortality was 0.24%. By rate order, diagnoses were: substance use disorders (SUD) (40%) > eating disorders (15%) > anxiety/posttraumatic stress disorder (PTSD) (13%) > attention deficit hyperactivity disorder (ADHD) (9%) > major depression (8%) > schizophrenia/psychosis (6%) > autism spectrum disorder (ASD) (6%) > sleep disorder (3%) > suicidal behavior (2%) > sexual disorders (1%). A significant gender dichotomy was noticed, with female predominance for internalizing disorders (i.e., anxiety, depression, suicidal behavior and eating disorders) whereas externalizing disorders (i.e., SUD, ADHD, ASD, schizophrenia and other psychoses) predominated in males. Suicidal behavior and male sex were independent predictors of in-hospital death in multivariate analysis. After the first year of the COVID-19 pandemic, hospitalizations due to mental disorders in adolescents increased by 51% in 2021. There is a growing crisis of mental health among adolescents in Spain. Although the COVID-19 pandemic has unveiled the high rate and severity of psychiatric disorders among youth, a steadily increase has occurred since the beginning of the millennium. Primary preventative strategies should be adapted to distinct and more prevalent mental disorders in adolescents.
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BACKGROUND: Suicide ranks as a leading cause of premature death among adolescents globally. Understanding the trends and key determinants of suicidal behavior in youth are critical for implementing educational policies and supporting preventive strategies in schools. METHODS: This retrospective study examined all hospitalizations due to suicidal behavior in children and adolescents aged 11 to 18 years in Spain, using data from the Spanish National Registry of Hospital Discharges spanning 2000 to 2021. RESULTS: Over the 22-year study period, there were 2,015,589 hospitalizations among adolescents in Spain, with 118,609 (5.9 %) cases involving mental disorders. There were 2855 admissions with suicidal behavior, constituting 2.4 % of the hospitalizations among youth with mental disorders. Girls represented 73.4 % of all hospitalizations, with a median age of 16 years. Admissions for suicidal behavior saw a four-fold increase during the last decade (p < 0.001). The in-hospital mortality rate for adolescents with suicidal behavior doubled that of those hospitalized for other mental disorders. During the first year of the COVID-19 pandemic, admissions of adolescents with suicidal behavior decreased, only to surge by 2.5-fold during 2021. CONCLUSION: Hospital admissions for suicidal behavior among adolescents have risen in Spain over the last two decades. Girls represented 73.4 % of these admissions, yet in-hospital mortality was more frequent in boys.
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Infections caused by carbapenem-resistant Acinetobacter baumannii are a global threat causing a high number of fatal infections. This microorganism can also easily acquire antibiotic resistance determinants, making the treatment of infections a big challenge, and has the ability to persist in the hospital environment under a wide range of conditions. The objective of this work was to study the molecular epidemiology and genetic characteristics of two blaOXA24/40Acinetobacter baumannii outbreaks (2009 and 2020-21) at a tertiary hospital in Northern Spain. Thirty-six isolates were investigated and genotypically screened by Whole Genome Sequencing to analyse the resistome and virulome. Isolates were resistant to carbapenems, aminoglycosides and fluoroquinolones. Multi-Locus Sequence Typing analysis identified that Outbreak 1 was mainly produced by isolates belonging to ST3Pas/ST106Oxf (IC3) containing blaOXA24/40, blaOXA71 and blaADC119. Outbreak 2 isolates were exclusively ST2Pas/ST801Oxf (IC2) blaOXA24/40, blaOXA66 and blaADC30, the same genotype seen in two isolates from 2009. Virulome analysis showed that IC2 isolates contained genes for capsular polysaccharide KL32 and lipooligosacharide OCL5. A 8.9 Kb plasmid encoding the blaOXA24/40 gene was common in all isolates. The persistance over time of a virulent IC2 clone highlights the need of active surveillance to control its spread.
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Acinetobacter baumannii , Proteínas de Bactérias , Tipagem de Sequências Multilocus , Proteínas de Bactérias/genética , Centros de Atenção Terciária , Acinetobacter baumannii/genética , Espanha/epidemiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Genômica , beta-Lactamases/genéticaRESUMO
The extent of the influence that molecular curvature plays on the self-assembly of supramolecular polymers remains an open question in the field. We began addressing this fundamental question with the introduction of "carpyridines", which are saddle-shaped monomers that can associate with one another through π-π interactions and in which the rotational and translational movements are restricted. The topography displayed by the monomers led, previously, to the assembly of highly ordered 2D materials even in the absence of strong directional interactions such as hydrogen bonding. Here, we introduce a simple strategy to gain control over the dimensionality of the formed structures yielding classical unidimensional polymers. These have been characterized using well-established protocols allowing us to determine and confirm the self-assembly mechanism of both fibers and sheets. The calculated interaction energies are significantly higher than expected for flexible self-assembling units lacking classical "strong" non-covalent interactions. The versatility of this supramolecular unit to assemble into either supramolecular fibers or 2D sheets with strong association energies highlights remarkably well the potential and importance of molecular shape for the design of supramolecular materials and the applications thereof.
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Sexually transmitted infections (STIs) have become the second in the global rating of infectious diseases after respiratory infections. Globally, over 1 million, new STI is diagnosed every day. Although four conditions are the most representative and of obligatory declaration (gonorrhea, syphilis, chlamydia, and human immunodeficiency virus [HIV]), there are many other prevalent STI, including trichomona, herpes simplex, papillomavirus, and viral hepatitis. Herein, we perform a narrative and retrospective review, analyzing information from public databases from distinct Spanish government institutions. STI significantly declined in Spain during 2020 as a result of lockdown and social isolation measures dictated in response to the COVID-19 pandemic. After releasing restrictions, a major STI rebound occurred in 2021. Increases were 49% for gonorrhea, 45% for HIV, 39% for chlamydia, and 32% for syphilis. Based on nationwide statistics, we build a narrative review of the recent STI surge after COVID-19. In summary, we propose a holistic approach to confront the current re-emergence of STI. On one hand, new innovative medical advances must be implemented, including new rapid tests, novel vaccines, pre-exposure prophylaxis beyond HIV, and long-acting antivirals. On the other hand, information to citizens needs to be reformulated with interventions aimed to build a healthier society, alike it has been undertaken with tobacco, alcohol, diet, and lifestyle. STI determines important sexual, reproductive, and maternal-child health consequences. To promote human well-being or flourishing, the education of adolescents and young adults should be aligned with human ecology. Therefore, it is urgent to address new approaches in sexual health that represent a clear benefit for individual persons and society. In this way, favoring a cultural evolution aimed to delay the age of first sexual intercourse and the avoidance of multiple sex partners should be prioritized.
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COVID-19 , Gonorreia , Infecções por HIV , Infecções Sexualmente Transmissíveis , Sífilis , Adolescente , Humanos , Masculino , Adulto Jovem , Controle de Doenças Transmissíveis , COVID-19/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , HIV , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Pandemias , Infecções Sexualmente Transmissíveis/epidemiologia , Sífilis/diagnóstico , Sífilis/epidemiologia , FemininoRESUMO
The increasing rates of antimicrobial resistance among carbapenem-resistant Acinetobacter baumannii in the Middle East and North Africa are one of the major concerns for healthcare settings. We characterised the first A. baumannii isolate harbouring five ß-lactamases identified in Egypt. The isolate Ale25 was obtained from an ICU patient of a hospital from Alexandria. The isolate was phenotypically and genotypically screened for carbapenemase genes. The isolate was resistant to carbapenems, aminoglycosides, fluoroquinolones and cefiderocol. Whole-Genome Sequencing identified five ß-lactamase genes, blaNDM-1, blaOXA-23, blaOXA-64, blaPER-7 and blaADC-57, together with other antibiotic resistance genes, conferring resistance to sulfonamides, macrolides, tetracyclines, rifamycin and chloramphenicol. Virulome analysis showed the presence of genes involved in adhesion and biofilm production, type II and VI secretion systems, exotoxins, etc. Multi-Locus Sequence Typing analysis identified the isolate as Sequence Types 113Pas and 2246Oxf, belonging to International Clone 7. Sequencing experiments revealed the presence of four plasmids of 2.7, 22.3, 70.4 and 240.8 Kb. All the ß-lactamase genes were located in the chromosome, except the blaPER-7, gene which was found within the plasmid of 240.8 Kb. This study highlights the threat of the emergence and dissemination of these types of isolates.
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Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Acinetobacter baumannii/genética , Tipagem de Sequências Multilocus , Egito , Testes de Sensibilidade Microbiana , Infecções por Acinetobacter/tratamento farmacológico , beta-Lactamases/genética , Proteínas de Bactérias/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Two-dimensional (2D) materials are a key target for many applications in the modern day. Self-assembly is one approach that can bring us closer to this goal, which usually relies upon strong, directional interactions instead of covalent bonds. Control over less directional forces is more challenging and usually does not result in as well-defined materials. Explicitly incorporating topography into the design as a guiding effect to enhance the interacting forces can help to form highly ordered structures. Herein, we show the process of shape-assisted self-assembly to be consistent across a range of derivatives that highlights the restriction of rotational motion and is verified using a diverse combination of solid state analyses. A molecular curvature governed angle distribution nurtures monomers into loose columns that then arrange to form 2D structures with long-range order observed in both crystalline and soft materials. These features strengthen the idea that shape becomes an important design principle leading towards precise molecular self-assembly and the inception of new materials.
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Carbapenem resistant Acinetobacter baumannii is a major global concern, especially in countries of the Middle East and North Africa, where the antibiotic resistance rates are on the rise. The aim of this study was to study the genomic characteristics and antimicrobial susceptibility profile of thirty-six multidrug resistant A. baumannii clinical isolates obtained in hospitals from Alexandria, Egypt. Antibiotic resistance rates were estimated by determination of Minimum Inhibitory Concentrations. Carbapenemase genes, other antibiotic resistance genes and virulence factors were then screened by the use of Whole Genome Sequencing. Isolates were also subjected to Multi Locus Sequence Typing (MLST) using the Pasteur Scheme and to core genome MLST to study their clonal relatedness. In addition, plasmid analysis was performed by the use of a commercial kit and S1- Pulsed Field Gel Electrophoresis, and Hybridization experiments with DIG-labeled DNA probes for bla NDM-1, blaPER-7 and bla GES-like were performed to locate these genes. The majority of isolates were resistant to ß-lactams (including carbapenems), fluoroquinolones, aminoglycosides and trimethoprim; and some showed resistance to cefiderocol and minocycline. We identified 8 different bla OXA-51-like variants including bla OXA-51, bla OXA-64, bla OXA-65, bla OXA-66, bla OXA-68, bla OXA-91, bla OXA-94 and bla OXA-336; bla OXA-23, bla NDM-1, bla PER-7, bla GES-like and bla ADC-like and other antibiotic resistance genes, some of these genes were within transposons or class 1 integrons. Multiple virulence factors responsible for adherence, biofilm production, type II and type VI secretion systems, exotoxins, exoenzymes, immune modulation and iron uptake were observed and 34 out of 36 isolates showed motility. Thirty-five out of 36 isolates clustered with International Clones 2, 4, 5, 7, 8 and 9; and 9 STs were identified including ST570, ST2, ST600, ST15, ST113, ST613, ST85, ST158, ST164. Plasmids ranging in size from 1.7 to 70 kb were found; bla NDM-1 and blaPER-7 genes were located in the chromosome and bla GES-like genes were simultaneously located in the chromosome and in a plasmid of 70kb. In conclusion, this study revealed a wide spectrum of antibiotic resistance genes and a variety of lineages among A. baumannii isolated in hospitals from Alexandria, and highlights the importance of investigating the molecular epidemiology to control the spread of multi-drug resistant isolates.
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Acinetobacter baumannii , Tipagem de Sequências Multilocus , Egito , Antibacterianos/farmacologia , beta-Lactamases/genética , Fatores de Virulência/genética , Testes de Sensibilidade MicrobianaRESUMO
Multidrug resistant Acinetobacter baumannii is one of the most important nosocomial pathogens worldwide. During the last decades it has become a major threat for healthcare settings due to the high antibiotic resistance rates among these isolates. Many resistance determinants are coded by conjugative or mobilizable plasmids, facilitating their dissemination. The majority of plasmids harbored by Acinetobacter species are less than 20 Kb, however, high molecular weight elements are the most clinically relevant since they usually contain antibiotic resistance genes. The aim of this work was to describe, classify and determine the genetic content of plasmids harbored by carbapem resistant A. baumannii isolates belonging to predominant clonal lineages circulating in hospitals from Alexandria, Egypt. The isolates were subjected to S1-Pulsed Field Gel Electrophoresis experiments to identify high molecular weight plasmids. To further analyze the plasmid content and the genetic localization of the antibiotic resistance genes, isolates were sequenced by Illumina Miseq and MinION Mk1C and a hybrid assembly was performed using Unicycler v0.5.0. Plasmids were detected with MOBsuite 3.0.3 and Copla.py v.1.0 and mapped using the online software Proksee.ca. Replicase genes were further analyzed through a BLAST against the Acinetobacter Plasmid Typing database. Eleven plasmids ranging in size from 4.9 to 205.6 Kb were characterized and mapped. All isolates contained plasmids, and, in many cases, more than two elements were identified. Antimicrobial resistance genes such as bla OXA-23, bla GES-like, aph(3')-VI and qacEΔ1 were found in likely conjugative large plasmids; while virulence determinants such as septicolysin or TonB-dependent receptors were identified in plasmids of small size. Some of these resistance determinants were, in turn, located within transposons and class 1 integrons. Among the identified plasmids, the majority encoded proteins belonging to the Rep_3 family, but replicases of the RepPriCT_1 (Aci6) family were also identified. Plasmids are of high interest as antibiotic resistance control tools, since they may be used as genetic markers for antibiotic resistance and virulence, and also as targets for the development of compounds that can inhibit transfer processes.
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Acinetobacter baumannii , Egito , Plasmídeos , Hospitais , Antibacterianos , Células Clonais , CarbapenêmicosRESUMO
Introduction: Hydatidiform mole is a type of gestational trophoblastic disease that results from the abnormal fertilization of an oocyte and causes nonspecific symptoms such as amenorrhea, metrorrhagia, and enlarged uterus. Although rare, its most characteristic symptoms include hyperemesis, early-onset pre-eclampsia, anemia, and respiratory distress. Case presentation: A 47-year-old Moroccan woman consulted the emergency department of the Hospital Clínico Universitario in Valladolid (Spain) after a month of persistent coughing and emesis. The patient reported epigastralgia and amenorrhoea for two months, as well as scant vaginal bleeding two days prior to consultation. Taking into account that the patient tested positive for pregnancy, that a heterogeneous intrauterine mass measuring 124x120mm was observed on transvaginal ultrasound, that no abnormal findings were reported on Doppler ultrasound, and that her serum ßhCG levels reached a value of 772.110 mIU/mL, a diagnosis of hydatidiform mole was suspected. Once informed about the possible therapeutic options, the patient decided to undergo a total hysterectomy, as she stated that she had already fulfilled her desire to be a mother. After the procedure, the patient's clinical condition improved, and the pathology report of the mass confirmed the diagnosis of partial hydatidiform mole. Conclusion: Early diagnosis of hydatidiform mole is paramount in order to provide adequate treatment and improve the prognosis of these patients. Therefore, despite its low incidence and non-specific clinical manifestations, it should be considered as a differential diagnosis for first-trimester metrorrhagia.
Introducción. La mola hidatiforme es un tipo de enfermedad trofoblástica gestacional que se presenta como resultado de la fertilización anormal de un ovocito y que ocasiona síntomas inespecíficos como amenorrea, metrorragia y aumento del tamaño del útero. Aunque infrecuentes, sus síntomas más característicos incluyen hiperémesis, preeclampsia de inicio temprano, anemia y distrés respiratorio. Presentación del caso. Mujer marroquí de 47 años que consultó al servicio de urgencias del Hospital Clínico Universitario de Valladolid debido a que había presentado tos y vómitos por un mes. La paciente refirió haber sufrido epigastralgia y amenorrea por dos meses, así como escaso sangrado vaginal en los últimos dos días. Teniendo en cuenta que la paciente dio positivo en una prueba de embarazo, que en la ecografía transvaginal se observó una masa intrauterina heterogénea de 124x120mm, que no se reportaron hallazgos anormales en la ecografía Doppler y que sus niveles séricos de ßhCG alcanzaron un valor de 772.110 mUI/mL, se sospechó un diagnóstico de mola hidatiforme. Una vez informada sobre las posibles alternativas terapéuticas, la paciente decidió someterse a una histerectomía total, pues refirió que ya había cumplido su deseo de ser madre. Luego de realizar procedimiento, la condición clínica de la paciente mejoró; además, el informe de patología de la masa permitió confirmar el diagnóstico de mola hidatiforme parcial. Conclusiones. El diagnóstico temprano de la mola hidatiforme es de gran importancia para ofrecer un tratamiento adecuado y, de esta forma, mejorar el pronóstico de estas pacientes. Por tanto, a pesar de su baja incidencia y sus manifestaciones clínicas inespecíficas, se debe considerar como diagnóstico diferencial de las metrorragias del primer trimestre.
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There are many different types of gallbladder diseases, mainly resulting from inflammation. The long-term presence of an insult to the gallbladder leads to chronic inflammation, which is a nidus for complications such as Mirizzi syndrome and gallbladder cancer, both of which can become mimics of one another. Preoperative diagnosis of either gallbladder cancer or Mirizzi syndrome is often difficult, leading to late diagnosis and complicating the patient's treatment course. We report a case of a 65-year-old male who presented with abdominal pain and significant weight loss, with no physical evidence of jaundice and normal liver function. This was initially diagnosed as acute cholecystitis and Mirizzi syndrome before being diagnosed as gallbladder adenocarcinoma on final histology.
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Self-assembly and molecular recognition are critical processes both in life and material sciences. They usually depend on strong, directional non-covalent interactions to gain specificity and to make long-range organization possible. Most supramolecular constructs are also at least partially governed by topography, whose role is hard to disentangle. This makes it nearly impossible to discern the potential of shape and motion in the creation of complexity. Here, we demonstrate that long-range order in supramolecular constructs can be assisted by the topography of the individual units even in the absence of highly directional interactions. Molecular units of remarkable simplicity self-assemble in solution to give single-molecule thin two-dimensional supramolecular polymers of defined boundaries. This dramatic example spotlights the critical function that topography can have in molecular assembly and paves the path to rationally designed systems of increasing sophistication.
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Until 2020, only Belgium, Luxembourg, Switzerland, and the Netherlands admitted, under differentiated legal coverage, requests for euthanasia and / or assisted suicide in patients with non-terminal illnesses, and for reasons of intractable and unbearable suffering. Since March 2021 this is also possible in Spain. The objective of this work is to review the existing studies and characteristics of the practice of euthanasia and assisted suicide (ESA) in people with mental disorders (TM) and / or dementia (D) and see if the legal requirements essential in ESA applications in these patients are to be met. The hypothesis is that compliance with these requirements is especially difficult in patients with TM-D, either because of the characteristics of the disease itself, or because of the recognized legal security failures. Likewise, there may be sources of fraud not actually prosecuted by the State, either due to the complicity of society and / or due to the necessary cooperation of Medicine. As a result of this review, we raise criticaethical-deontological considerations about the approval of ESA for patients with TM-D, and its errors and consequences, to the reflection of the readers. We propose as an alternative to ESA the so-called â³palliative psychiatryâ³, which aims at improving the quality of life of patients and their families by facing the problems associated with severe persistent mental illness -potentially fatal- through the prevention and relief of suffering.
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Eutanásia , Transtornos Mentais , Suicídio Assistido , Humanos , Países Baixos , Qualidade de VidaRESUMO
Because cancer is the second leading cause of death globally, investigation of new photosensitizers for photodynamic therapy is highly desirable. In this work, different peripherally substituted subphthalocyanines (SubPcs) with either a benzocrown moiety (CE-) or a tyrosine methyl ester (Tyr-) as the axial ligand have been prepared. Target SubPcs showed high ΦΔ values, >0.50 in EtOH. Both CE- and Tyr- moieties increased substantially the hydrophilicity of the compounds (log P = 1.79-2.63, n-octanol/PBS). Uptake to cells, subcellular localization, and monitoring of the progression of cell death over time are described. Improved spectroscopic behavior of the CE- series in cell culture medium resulted in higher photodynamic activity versus that of the Tyr- series. In particular, the peripherally triethylsulfanyl SubPc-CE exhibited extraordinarily low EC50 values of 2.3 and 4.4 nM after light activation and high TC50 values of 14.49 and 5.25 µM (i.e., dark toxicity without activation) on SK-MEL-28 and HeLa cells, respectively, which rank it among the best photosensitizers ever.
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Isoindóis/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Humanos , Isoindóis/química , Fármacos Fotossensibilizantes/química , Relação Estrutura-AtividadeRESUMO
Antimicrobial resistance is one of the biggest threats to global health as current antibiotics are becoming useless against resistant infectious pathogens. Consequently, new antimicrobial strategies are urgently required. Drug delivery systems represent a potential solution to improve current antibiotic properties and reverse resistance mechanisms. Among different drug delivery systems, solid lipid nanoparticles represent a highly interesting option as they offer many advantages for nontoxic targeted drug delivery. Several publications have demonstrated the capacity of SLNs to significantly improve antibiotic characteristics increasing treatment efficiency. In this review article, antibiotic-loaded solid lipid nanoparticle-related works are analyzed to summarize all information associated with applying these new formulations to tackle the antibiotic resistance problem. The main antimicrobial resistance mechanisms and relevant solid lipid nanoparticle characteristics are presented to later discuss the potential of these nanoparticles to improve current antibiotic treatment characteristics and overcome antimicrobial resistance mechanisms. Moreover, solid lipid nanoparticles also offer new possibilities for other antimicrobial agents that cannot be administrated as free drugs. The advantages and disadvantages of these new formulations are also discussed in this review. Finally, given the progress of the studies carried out to date, future directions are discussed.
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The amyloid precursor protein (APP) is a type I transmembrane protein with unknown physiological function but potential impact in neurodegeneration. The current study demonstrates that APP signals to the nucleus causing the generation of aggregates consisting of its adapter protein FE65, the histone acetyltransferase TIP60 and the tumour suppressor proteins p53 and PML. APP C-terminal (APP-CT50) complexes co-localize and co-precipitate with p53 and PML. The PML nuclear body generation is induced and fusion occurs over time depending on APP signalling and STED imaging revealed active gene expression within the complex. We further show that the nuclear aggregates of APP-CT50 fragments together with PML and FE65 are present in the aged human brain but not in cerebral organoids differentiated from iPS cells. Notably, human Alzheimer's disease brains reveal a highly significant reduction of these nuclear aggregates in areas with high plaque load compared to plaque-free areas of the same individual. Based on these results we conclude that APP-CT50 signalling to the nucleus takes place in the aged human brain and is involved in the pathophysiology of AD.
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Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Hipocampo/patologia , Proteína da Leucemia Promielocítica/metabolismo , Núcleo Celular/metabolismo , Células HEK293 , Hipocampo/metabolismo , Humanos , Organoides , Placa Amiloide/metabolismo , Placa Amiloide/patologiaRESUMO
The objective of this study was the phenotypic and genotypic characterization of a carbapenem resistant Acinetobacter baumannii (CRAB) isolate. The isolate, recovered in Northern Spain in 2019, was identified by MALDI-TOF to the species level. Antimicrobial susceptibility testing was performed using the Phoenix BD NMIC-502 Panel, E-test, and broth microdilution methods. The presence of a metallo-ß-lactamase (MBL) was verified by PCR and immunochromatographic assays. The genetic location of the MBL was confirmed using S1-pulsed-field gel electrophoresis (S1-PFGE) followed by Southern blot hybridization. Whole genome sequencing (WGS) was completed using the Miseq and MinION platforms, followed by core-genome MLST (cgMLST) and seven-locus MLST analysis. The CRAB was assigned ST85 (Pasteur scheme) and ST957 (Oxford scheme) representing international clone (IC) 9 and harbored the intrinsic ß-lactamase OXA-94 with ISAba1 upstream of it, and the MBL bla NDM-6. Hybridization experiments revealed that the bla NDM-6 was encoded on the chromosome. Using WGS the bla NDM-6 environment could be identified arranged in the following order: ISAba14, aphA6, ISAba125, bla NDM-6, ble MBL, trpF, dsbC, cutA, and ISAba14. Downstream, a 10,462 bp duplication was identified, including a second copy of bla NDM-6 in the following genetic composition: ISAba125, bla NDM-6, ble MBL, trpF, dsbC, cutA, and ISAba14. To our knowledge, this is the first description of bla NDM-6 in A. baumannii. The MBL was present in two copies in the chromosome in a new genetic environment associated with IS elements highlighting the contribution of mobile genetic elements in the dissemination of this gene.
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Using a combination of short- and long-read DNA sequencing, we have investigated the location of antibiotic resistance genes and characterized mobile genetic elements (MGEs) in three clinical multi-drug resistant Acinetobacter baumannii. The isolates, collected in Bolivia, clustered separately with three different international clonal lineages. We found a diverse array of transposons, plasmids and resistance islands related to different insertion sequence (IS) elements, which were located in both the chromosome and in plasmids, which conferred resistance to multiple antimicrobials, including carbapenems. Carbapenem resistance might be caused by a Tn2008 carrying the bla OXA-23 gene. Some plasmids were shared between the isolates. Larger plasmids were less conserved than smaller ones and they shared some homologous regions, while others were more diverse, suggesting that these big plasmids are more plastic than the smaller ones. The genetic basis of antimicrobial resistance in Bolivia has not been deeply studied until now, and the mobilome of these A. baumannii isolates, combined with their multi-drug resistant phenotype, mirror the transfer and prevalence of MGEs contributing to the spread of antibiotic resistance worldwide and require special attention. These findings could be useful to understand the antimicrobial resistance genetics of A. baumannii in Bolivia and the difficulty in tackling these infections.