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BACKGROUND: In September 2015, the four-component, protein-based meningococcal serogroup B vaccine (4CMenB; Bexsero) became available for private purchase in Spain. METHODS: We conducted a nationwide matched case-control study to assess the effectiveness of 4CMenB in preventing invasive meningococcal disease in children. The study included all laboratory-confirmed cases of invasive meningococcal disease in children younger than 60 months of age between October 5, 2015, and October 6, 2019, in Spain. Each case patient was matched with four controls according to date of birth and province. 4CMenB vaccination status of the case patients and controls was compared with the use of multivariate conditional logistic regression. RESULTS: We compared 306 case patients (243 [79.4%] with serogroup B disease) with 1224 controls. A total of 35 case patients (11.4%) and 298 controls (24.3%) had received at least one dose of 4CMenB. The effectiveness of complete vaccination with 4CMenB (defined as receipt of at least 2 doses, administered in accordance with the manufacturer's recommendations) was 76% (95% confidence interval [CI], 57 to 87) against invasive meningococcal disease caused by any serogroup, and partial vaccination was 54% (95% CI, 18 to 74) effective. Complete vaccination resulted in an effectiveness of 71% (95% CI, 45 to 85) against meningococcal serogroup B disease. Vaccine effectiveness with at least one dose of 4CMenB was 64% (95% CI, 41 to 78) against serogroup B disease and 82% (95% CI, 21 to 96) against non-serogroup B disease. With the use of the genetic Meningococcal Antigen Typing System, serogroup B strains that were expected to be covered by 4CMenB were detected in 44 case patients, none of whom had been vaccinated. CONCLUSIONS: Complete vaccination with 4CMenB was found to be effective in preventing invasive disease by serogroup B and non-serogroup B meningococci in children younger than 5 years of age.
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Infecciones Meningocócicas , Vacunas Meningococicas , Neisseria meningitidis Serogrupo B , Niño , Humanos , Lactante , Estudios de Casos y Controles , Infecciones Meningocócicas/microbiología , Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/uso terapéutico , Neisseria meningitidis , EspañaRESUMEN
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that belong to the neuromuscular cholinergic system, their main function is to hydrolyze the neurotransmitter acetylcholine (ACh), through their hydrolysis these enzymes regulate the neuronal and neuromuscular cholinergic system. They have recently attracted considerable attention due to the discovery of new enzymatic and nonenzymatic functions. These discoveries have aroused the interest of numerous scientists, consolidating the relevance of this group of enzymes. Recent investigations have revealed a positive correlation between several risk factors for metabolic syndrome (MetS) and the expression of cholinesterases (ChE's), which underscore the impact of high ChE's activity on the pro-inflammatory state associated with MetS. In addition, the excessive hydrolysis of ACh and other choline esters (succinylcholine, propionylcholine, butyrylcholine, etc.) by both ChE's results in the overproduction of fatty acid precursor metabolites, which facilitate the synthesis of very low-density lipoproteins and triacylglycerols. Participation in these processes may represent the link between ChE's and metabolic disorders. However, further scientific research is required to fully elucidate the involvement of ChE's in metabolic diseases. This review aims to collect recent research studies that contribute to understanding the association between the cholinergic system and metabolic diseases.
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Acetilcolina , Acetilcolinesterasa , Butirilcolinesterasa , Humanos , Butirilcolinesterasa/metabolismo , Acetilcolinesterasa/metabolismo , Acetilcolina/metabolismo , Animales , Enfermedades Metabólicas/enzimología , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/enzimologíaRESUMEN
BACKGROUND: Although universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population. METHODS: The landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City. RESULTS: From August 2019 to April 2023, 137 patients underwent genetic testing. The median age at diagnosis was 60 years (range 36-85), 58.4 % were women, and 38.7 % were metastatic at diagnosis. The frequency of germline PVs was 16 % (n = 22): ATM 36.4 % (n = 8), CDKN2A/p16INK4A 27.3 % (n = 6), BRCA2 9.1 % (n = 2), PALB2 9.1 % (n = 2), CHEK2 9.1 % (n = 2), TP53 4.5 % (n = 1), and NF1 4.5 % (n = 1). Additionally, 2 carriers of monoallelic germline variants in MUTYH were identified. No significant differences were observed between carriers and non-carriers in terms of family history of pancreatic cancer. CONCLUSIONS: We identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.
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The Case A 47-year-old woman with a history of drug-resistant epilepsy during childhood presented to the emergency department with sudden dyspnea and chest pain. Upon admission, her oxygen saturation was 88%. A chest CT scan revealed pulmonary cystic lesions consistent with lymphangioleiomyomatosis and a right spontaneous pneumothorax, which resolved with the placement of a chest tube. Physical examination revealed a hypopigmented macule on the skin of the lumbar region, facial angiofibromas, and periungual fibromas. An abdominal MRI documented multiple bilateral renal tumors that were hypointense on T2-weighted imaging and showed a black boundary artifact, suggestive of fat-poor angiomyolipomas (AMLs). Subsequent percutaneous biopsy of the largest renal tumor confirmed the diagnosis of angiomyolipoma (positive for HMB-45 on immunohistochemistry). The brain MRI revealed subependymal nodules. The pulmonary function tests showed a mild obstructive pattern. Germline genetic testing confirmed the suspected diagnosis, and the patient started oral systemic treatment with everolimus (Afinitor) 10 mg once daily, along with dexamethasone rinses for prophylaxis.
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Neoplasias Renales , Inhibidores mTOR , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Inhibidores mTOR/uso terapéutico , Everolimus/uso terapéutico , Angiomiolipoma/tratamiento farmacológico , Angiomiolipoma/genética , Angiomiolipoma/patología , Síndromes Neoplásicos Hereditarios/tratamiento farmacológico , Síndromes Neoplásicos Hereditarios/genética , Serina-Treonina Quinasas TORRESUMEN
The elongation of metallic nanoparticles (NPs) embedded in a dielectric matrix after irradiation with swift heavy ions is a phenomenon that has been known for several years. However, the precise mechanism behind this deformation process is still not fully understood, primarily due to the dearth of information during intermediate stages of deformation. In this study, we report the continuation of our previous work [Peña-Rodríguez et al., Sci. Rep. 7(1), 922 (2017)], exploiting the strong dependence of the localized surface plasmon resonance on the aspect ratio of elongated metal NPs to study the elongation kinetics in situ. In situ optical absorption spectra were measured using a polarizing beam splitter to separate the longitudinal and transverse plasmon modes of the anisotropic NPs. Then, the detailed geometrical and compositional parameters were determined from a fit of these spectra. The use of linearly polarized light allowed for a more accurate analysis of the elongation kinetics, particularly useful in the first stages, where longitudinal and transverse modes overlap.
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Schizophrenia (SZ) is a serious mental disorder that is typically treated with antipsychotic medication. Treatment-resistant schizophrenia (TRS) is the condition where symptoms remain after pharmacological intervention, resulting in long-lasting functional and social impairments. As the identification and treatment of a TRS patient requires previous failed treatments, early mechanisms of detection are needed in order to quicken the access to effective therapy, as well as improve treatment adherence. In this study, we aim to find a microRNA (miRNA) signature for TRS, as well as to shed some light on the molecular pathways potentially involved in this severe condition. To do this, we compared the blood miRNAs of schizophrenia patients that respond to medication and TRS patients, thus obtaining a 16-miRNA TRS profile. Then, we assessed the ability of this signature to separate responders and TRS patients using hierarchical clustering, observing that most of them are grouped correctly (~70% accuracy). We also conducted a network, pathway analysis, and bibliography search to spot molecular pathways potentially altered in TRS. We found that the response to stress seems to be a key factor in TRS and that proteins p53, SIRT1, MDM2, and TRIM28 could be the potential mediators of such responses. Finally, we suggest a molecular pathway potentially regulated by the miRNAs of the TRS profile.
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Antipsicóticos , MicroARNs , Esquizofrenia , Humanos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Esquizofrenia/diagnóstico , MicroARNs/genética , MicroARNs/uso terapéutico , Esquizofrenia Resistente al Tratamiento , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Resistencia a Medicamentos/genéticaRESUMEN
The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.
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Trastorno Depresivo Mayor , Factor II del Crecimiento Similar a la Insulina , Humanos , Ratas , Animales , Ratones , Factor II del Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , Trastorno Depresivo Mayor/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/metabolismo , Anhedonia , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Proteína 2 de Unión a Factor de Crecimiento Similar a la InsulinaRESUMEN
The brain extracellular matrix (ECM) is involved in crucial processes of neural support, neuronal and synaptic plasticity, extrasynaptic transmission, and neurotransmission. ECM is a tridimensional fibrillary meshwork composed of macromolecules that determine its bioactivity and give it unique characteristics. The characterization of the brain ECM is critical to understand its dynamic in SZ. Thus, a comparative study was developed with 71 patients with schizophrenia (SZ) and 70 healthy controls. Plasma of participants was analysed by label-free liquid chromatography-tandem mass spectrometry, and the results were validated using the classical western blot method. Lastly, immunostaining of post-mortem human brain tissue was performed to analyse the distribution of the brain ECM proteins by confocal microscopy. The analysis identified four proteins: fibronectin, lumican, nidogen-1, and secreted protein acidic and rich in cysteine (SPARC) as components of the brain ECM. Statistical significance was found for fibronectin (P = 0.0166), SPARC (P = 0.0003), lumican (P = 0.0012), and nidogen-1 (P < 0.0001) that were decreased in the SZ group. Fluorescence imaging of prefrontal cortex (PFC) sections revealed a lower expression of ECM proteins in SZ. Our study proposes a pathophysiological dysregulation of proteins of the brain ECM, whose abnormal composition leads to a progressive neuronal impairment and consequently to neurodegenerative processes due to lack of neurophysiological support and dysregulation of neuronal homeostasis. Moreover, the brain ECM and its components are potential pharmacological targets to develop new therapeutic approaches to treat SZ.
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Fibronectinas , Esquizofrenia , Encéfalo/metabolismo , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Humanos , Lumican/metabolismo , Osteonectina/metabolismo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismoRESUMEN
OBJECTIVE: Describe the prevalence of breast cancer (BC)- associated germline pathogenic variants (PVs) among Mexican patients with triple-negative BC (TNBC). MATERIALS AND METHODS: The spectrum of PVs identified among patients with TNBC who were enrolled in a prospective registry and underwent genetic testing was analyzed. RESULTS: Of 387 patients with invasive TNBC and a median age at diagnosis of 39 years (range 21-72), 113 (29%) were carriers of PVs in BC-susceptibility genes: BRCA1 (79%), BRCA2 (15%), and other (6%: ATM, BRIP1, PALB2, PTEN, RAD51C, and TP53). PV carriers were younger at BC diagnosis (37 vs. 40 years, p=0.004) than non-carriers. CONCLUSION: A large proportion of TNBC in Mexican patients is associated with germline PVs, the vast majority in BRCA. The incremental yield of PVs in other BC-susceptibility genes was modest, and a stepwise approach starting with BRCA testing may be justified if it is more cost-effective than multigene panel testing.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Células Germinativas , Humanos , Persona de Mediana Edad , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/genética , Adulto JovenRESUMEN
Insulin-like growth factor 2 (IGF-2) and IGF binding protein 7 (IGFBP-7) have been related to schizophrenia (SZ) due to their implication in neurodevelopment. The purpose of this study was to assess whether the alterations in IGF-2 and IGFBP-7 in SZ patients are intrinsically related to the psychiatric disorder itself or are a secondary phenomenon due to antipsychotic treatment. In order to test this hypothesis, we measured plasma IGF-2 and IGFBP-7 in drug-naïve first episode (FE) and multiple episodes or chronic (ME) SZ Caucasian patients who have been following treatment for years. A total of 55 SZ patients (FE = 15, ME = 40) and 45 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the Self-Assessment Anhedonia Scale (SAAS) were employed to check schizophrenic symptomatology and anhedonia, respectively. Plasma IGF-2 and IGFBP-7 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The FE SZ patients had much lower IGF-2, but not IGFBP-7, than controls. Moreover, both IGF-2 and IGFBP-7 significantly increased after atypical antipsychotic treatment (aripiprazole, olanzapine, or risperidone) in these patients. On the other hand, chronic patients showed higher levels of both proteins when compared to controls. Our study suggests that circulatory IGF-2 and IGFBP-7 increase after antipsychotic treatment, regardless of long-term conditions and being lower in drug-naïve FE patients.
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Antipsicóticos , Esquizofrenia , Anhedonia , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Esquizofrenia/metabolismoRESUMEN
The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText-NT-3 and Co-IP NEText-TrkC. Computational modelling of protein-peptide docking by CABS-dock provided a medium-high accuracy model for NT-3-NEText (4.6935 Å) and TrkC-NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia.
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Simulación del Acoplamiento Molecular , Neurotrofina 3/química , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/química , Receptor trkC/química , Esquizofrenia/etiología , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Estructura Secundaria de Proteína , Receptor trkC/genética , Receptor trkC/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismoRESUMEN
In high-yielding dairy cattle, severe postpartum negative energy balance is often associated with metabolic and infectious disorders that negatively affect production, fertility, and welfare. Mobilization of adipose tissue associated with negative energy balance is reflected through an increased level of nonesterified fatty acids (NEFA) in the blood plasma. Earlier, identification of negative energy balance through detection of increased blood plasma NEFA concentration required laborious and stressful blood sampling. More recently, attempts have been made to predict blood NEFA concentration from milk samples. In this study, we aimed to develop and validate a model to predict blood plasma NEFA concentration using the milk mid-infrared (MIR) spectra that are routinely measured in the context of milk recording. To this end, blood plasma and milk samples were collected in wk 2, 3, and 20 postpartum for 192 lactations in 3 herds. The blood plasma samples were taken in the morning, and representative milk samples were collected during the morning and evening milk sessions on the same day. To predict plasma NEFA concentration from the milk MIR spectra, partial least squares regression models were trained on part of the observations from the first herd. The models were then thoroughly validated on all other observations of the first herd and on the observations of the 2 independent herds to explore their robustness and wide applicability. The final model could accurately predict blood plasma NEFA concentrations <0.6 mmol/L with a root mean square error of prediction of <0.143 mmol/L. However, for blood plasma with >1.2 mmol/L NEFA, the model clearly underestimated the true level. Additionally, we found that morning blood plasma NEFA levels were predicted with significantly higher accuracy using MIR spectra of evening milk samples compared with MIR spectra of morning samples, with root mean square error of prediction values of, respectively, 0.182 and 0.197 mmol/L, and R2 values of 0.613 and 0.502. These results suggest a time delay between variations in blood plasma NEFA and related milk biomarkers. Based on the MIR spectra of evening milk samples, cows at risk for negative energy status, indicated by detrimental morning blood plasma NEFA levels (>0.6 mmol/L), could be identified with a sensitivity and specificity of, respectively, 0.831 and 0.800. As this model can be applied to millions of historical and future milk MIR spectra, it opens an opportunity for regular metabolic screening and improved resilience phenotyping.
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Ácidos Grasos no Esterificados/sangre , Leche/química , Espectrofotometría Infrarroja/veterinaria , Ácido 3-Hidroxibutírico/sangre , Animales , Bovinos , Pruebas Diagnósticas de Rutina , Metabolismo Energético , Ácidos Grasos no Esterificados/química , Femenino , Fertilidad , Humanos , Lactancia , Periodo Posparto , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
Work-related musculoskeletal disorders are a major concern globally affecting societies, companies, and individuals. To address this, a new sensor-based system is presented: the Smart Workwear System, aimed at facilitating preventive measures by supporting risk assessments, work design, and work technique training. The system has a module-based platform that enables flexibility of sensor-type utilization, depending on the specific application. A module of the Smart Workwear System that utilizes haptic feedback for work technique training is further presented and evaluated in simulated mail sorting on sixteen novice participants for its potential to reduce adverse arm movements and postures in repetitive manual handling. Upper-arm postures were recorded, using an inertial measurement unit (IMU), perceived pain/discomfort with the Borg CR10-scale, and user experience with a semi-structured interview. This study shows that the use of haptic feedback for work technique training has the potential to significantly reduce the time in adverse upper-arm postures after short periods of training. The haptic feedback was experienced positive and usable by the participants and was effective in supporting learning of how to improve postures and movements. It is concluded that this type of sensorized system, using haptic feedback training, is promising for the future, especially when organizations are introducing newly employed staff, when teaching ergonomics to employees in physically demanding jobs, and when performing ergonomics interventions.
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Ergonomía , Enfermedades Musculoesqueléticas , Dispositivos Electrónicos Vestibles , Retroalimentación , Humanos , Enfermedades Musculoesqueléticas/prevención & control , PosturaRESUMEN
Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 µM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 µM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.
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Antiprotozoarios/química , Antiprotozoarios/farmacología , Péptidos de Penetración Celular/química , Ciclobutanos/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diseño de Fármacos , Células HeLa , Humanos , Modelos Moleculares , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Análisis Espectral , Relación Estructura-ActividadRESUMEN
This report describes the direct fabrication of interim implant-supported crowns in a single clinical session by applying a preheated composite resin to a clear silicone matrix made by diagnostic waxing. This technique facilitates the fabrication of custom interim restorations with appropriate soft-tissue molding and enables an inexpensive, predictable, functional, and esthetic outcome after implant surgery.
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Implantes Dentales , Prótesis Dental de Soporte Implantado , Resinas Compuestas , Coronas , Estética DentalRESUMEN
The interactions between prokaryotes and eukaryotes are abundant in nature. These microorganisms also interact in the human body. Fungal-bacteria interactions are present in many diseases. In this study, we evaluated the microbial interaction of Fusarium falciforme and Staphylococcus aureus developing mixed biofilm in vitro. When both microorganisms grew up together the mixed biofilm biomass decreased than F. falciforme monobiofilm biomass. S. aureus was able to interact and form aggregates over the mycelium and conidia surface of F. falciforme. Our results suggest that S. aureus could bind to colloidal chitin. On another hand, the supernatants from S. aureus biofilm and S. aureus-F. falciforme presented an antifungal effect over F. falciforme biofilm formation. Finally we found that the pH had an inhibitory effect over fungal biofilm formation. We concluded that S. aureus can affect the F. falciforme growth negatively in mixed biofilm involving factors like pH, supernatants compounds, anchor to chitin, and bacterial viability.
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Biopelículas/crecimiento & desarrollo , Ojo/microbiología , Fusarium/crecimiento & desarrollo , Interacciones Microbianas/fisiología , Staphylococcus aureus/fisiología , Ácido Acético , Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Biomasa , Quitina , Fusarium/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Ácido Láctico , Viabilidad Microbiana/efectos de los fármacos , Micelio , Esporas FúngicasRESUMEN
In an effort to explore novel ligand scaffolds for stable and inert lanthanide complexation in magnetic resonance imaging contrast agent research, three chiral ligands containing a highly rigid (1S,2S)-1,2-cyclobutanediamine spacer and different number of acetate and picolinate groups were efficiently synthesized. Potentiometric studies show comparable thermodynamic stability for the Gd3+ complexes formed with either the octadentate (L3)4- bearing two acetate or two picolinate groups or the heptadentate (L2)4- analogue bearing one picolinate and three acetate groups (log KGdL = 17.41 and 18.00 for [Gd(L2)]- and [Gd(L3)]-, respectively). In contrast, their dissociation kinetics is revealed to be very different: the monohydrated [Gd(L3)]- is considerably more labile, as a result of the significant kinetic activity of the protonated picolinate function, as compared to the bishydrated [Gd(L2)]-. This constitutes an uncommon example in which lowering ligand denticity results in a remarkable increase in kinetic inertness. Another interesting observation is that the rigid ligand backbone induces an unusually strong contribution of the spontaneous dissociation to the overall decomplexation process. Thanks to the presence of two inner-sphere water molecules, [Gd(L2)]- is endowed with high relaxivity (r1 = 7.9 mM-1 s-1 at 20 MHz, 25 °C), which is retained in the presence of large excess of endogenous anions, excluding ternary complex formation. The water exchange rate is similar for [Gd(L3)]- and [Gd(L2)]-, while it is 1 order of magnitude higher for the trishydrated tetraacetate analogue [Gd(L1)]- (kex298 = 8.1, 10, and 127 × 106 s-1, respectively). A structural analysis via density functional theory calculations suggests that the large bite angle imposed by the rigid (1S,2S)-1,2-cyclobutanediamine spacer could allow the design of ligands based on this scaffold with suitable properties for the coordination of larger metal ions with biomedical applications.
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Preventive healthcare has attracted much attention recently. Improving people's lifestyles and promoting a healthy diet and wellbeing are important, but the importance of work-related diseases should not be undermined. Musculoskeletal disorders (MSDs) are among the most common work-related health problems. Ergonomists already assess MSD risk factors and suggest changes in workplaces. However, existing methods are mainly based on visual observations, which have a relatively low reliability and cover only part of the workday. These suggestions concern the overall workplace and the organization of work, but rarely includes individuals' work techniques. In this work, we propose a precise and pervasive ergonomic platform for continuous risk assessment. The system collects data from wearable sensors, which are synchronized and processed by a mobile computing layer, from which exposure statistics and risk assessments may be drawn, and finally, are stored at the server layer for further analyses at both individual and group levels. The platform also enables continuous feedback to the worker to support behavioral changes. The deployed cloud platform in Amazon Web Services instances showed sufficient system flexibility to affordably fulfill requirements of small to medium enterprises, while it is expandable for larger corporations. The system usability scale of 76.6 indicates an acceptable grade of usability.
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Técnicas Biosensibles , Enfermedades Musculoesqueléticas/fisiopatología , Dispositivos Electrónicos Vestibles , Ergonomía/métodos , Humanos , Enfermedades Profesionales/fisiopatologíaRESUMEN
Surface motility and biofilm formation are behaviours which enable bacteria to infect their hosts and are controlled by different chemical signals. In the plant symbiotic alpha-proteobacterium Sinorhizobium meliloti, the lack of long-chain fatty acyl-coenzyme A synthetase activity (FadD) leads to increased surface motility, defects in biofilm development and impaired root colonization. In this study, analyses of lipid extracts and volatiles revealed that a fadD mutant accumulates 2-tridecanone (2-TDC), a methylketone (MK) known as a natural insecticide. Application of pure 2-TDC to the wild-type strain phenocopies the free-living and symbiotic behaviours of the fadD mutant. Structural features of the MK determine its ability to promote S. meliloti surface translocation, which is mainly mediated by a flagella-independent motility. Transcriptomic analyses showed that 2-TDC induces differential expression of iron uptake, redox and stress-related genes. Interestingly, this MK also influences surface motility and impairs biofilm formation in plant and animal pathogenic bacteria. Moreover, 2-TDC not only hampers alfalfa nodulation but also the development of tomato bacterial speck disease. This work assigns a new role to 2-TDC as an infochemical that affects important bacterial traits and hampers plant-bacteria interactions by interfering with microbial colonization of plant tissues.
Asunto(s)
Proteínas Bacterianas/metabolismo , Cetonas/metabolismo , Cetonas/farmacología , Medicago sativa/microbiología , Sinorhizobium meliloti/efectos de los fármacos , Sinorhizobium meliloti/metabolismo , Proteínas Bacterianas/genética , Biopelículas/efectos de los fármacos , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Mutación , Fenotipo , Sinorhizobium meliloti/genética , SimbiosisRESUMEN
Ectodermal dysplasia is a heterogeneous genetic condition affecting 1.6 to 22 per 100000 people. Oral manifestations associated with this condition include hyperdontia, hypodontia, microdontia, and conical teeth. Traditional treatment consists of a combination of orthodontic and rehabilitation therapies. The initial treatment stage uses removable prostheses and interim crowns for long periods, thus increasing risks for developing secondary caries. This clinical report describes the use of direct composite resin bonding with preheated compactable resins applied to vacuum-formed trays filled with clear silicone. This restorative treatment provides predictable, inexpensive, minimally invasive, functional, and esthetic recovery before orthodontic treatment.