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1.
RSC Adv ; 14(40): 29160-29167, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39285888

RESUMO

Transition metal dichalcogenides (TMDs) have attracted attention due to their broad-ranging physical properties. Their semiconducting characteristics make them attractive for nanotechnology applications. In particular, molybdenum disulfide (MoS2) and molybdenum diselenide (MoSe2) possess direct band gaps of 1.62 and 1.45 eV, respectively. Both monolayers are prone to oxidation in oxygen-rich environments. In this sense, we have studied the oxidation process in these 2D systems using first-principles calculations based on density functional theory. The stability of several oxidized structures under different growth conditions was analyzed via a formation-energy study, where the Janus oxidized phases are stable in oxygen-rich environments. The oxidation process is not random. Instead, it has a well-defined pattern, forming diagonal structures before reaching a complete monolayer. We have observed a systematic band-gap reduction as oxygen content increases, reaching 1.12 eV for MoSO and 0.83 eV for MoSeO, and a direct-to-indirect band-gap transition occurs at the early stages of oxidation. Our study is a step further towards designing new monolayers with engineered electronic properties and increasing reactivity towards molecules with a positive polarity on the O side of the monolayers.

2.
ACS Omega ; 9(33): 35718-35729, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39184510

RESUMO

In this work, we propose the construction of a two-dimensional system based on the stable phases previously reported for the 2D arsenic and phosphorus compounds, with hexagonal and orthorhombic symmetries. Therefore, we have modeled one hexagonal and three possible orthorhombic structures. To ensure the dynamical stability, we performed phonon spectra calculations for each system. We found that all phases are dynamically stable. To ensure the thermodynamic and mechanical stabilities, we have calculated cohesive energies and elastic constants. Our results show that the criteria for the stabilities are all fulfilled. For these stable structures, we computed the electronic and optical properties from first-principles studies based on density functional theory. The computation of electronic band gaps was performed by using the GW approximation to overcome the underestimation of the results obtained from standard DFT approaches. To study the optical properties, we have computed the dielectric function imaginary part within the BSE approach, which takes into account the excitonic effects and allows us to calculate the exciton binding energies of each system. The study was complemented by the computation of the absorption coefficient. From our calculations, it can be established that the 2D As-P systems are good candidates for several technological applications.

3.
ACS Omega ; 9(32): 35069-35079, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39157116

RESUMO

Oxide formation in superconducting TaN thin films is analyzed through experimental measurements and computational simulations. TaN was synthesized in an ultrahigh vacuum (UHV) system by reactive pulsed laser deposition and characterized in situ by X-ray photoelectron spectroscopy; it was also characterized ex situ by X-ray diffraction, transmission electron microscopy, and the four-point probe method. Despite being grown in an UHV chamber with a base pressure of 5 × 10-9 Torr, TaN contains a significant amount of oxygen (up to 20 at. %) attributed to residual gases containing O atoms. Several TaN1-x O x models, with different amounts of O atoms incorporated into N sites, were simulated using ab initio calculations to assess the feasibility of oxide formation. Thermodynamic stability analysis reveals that TaN1-x O x stability increases with oxygen addition, indicating that its incorporation is thermodynamically favorable. The oxygen-impurified TaN exhibits a face-centered cubic structure and is a superconductor (R = 0 Ω) at 2.99 K. The results discussed here highlight the importance of considering stable oxygen impurities when studying superconductivity in TaN films. The formation of TaN1-x O x regions in the compound may be key to understanding the variation in critical temperature reported in the literature.

4.
Cell Commun Signal ; 22(1): 377, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39061010

RESUMO

BACKGROUND: Tumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology. METHODS: Using single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line. We then used this model sensitivity to the EGFR inhibitor osimertinib across coexisting cell populations within the same tumor. Pathway-centered signaling dynamics associated with response to treatment and morphological characteristics of the MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated in MCPs less sensitive to treatment were then pharmacologically inhibited to identify target signaling proteins putatively implicated in promoting drug resistance. RESULTS: MCPs demonstrated highly heterogeneous sensitivities to osimertinib. Cell viability after treatment increased > 20% compared to the parental line in selected MCPs, whereas viability decreased by 75% in other MCPs. Reduced treatment response was detected in MCPs with higher proliferation rates, EGFR L858R expression, activation of EGFR binding partners and downstream signaling molecules, and expression of epithelial-to-mesenchymal transition markers. Levels of activation of EGFR binding partners and MCPs' proliferation rates were also associated with response to c-MET and IGFR inhibitors. CONCLUSIONS: MCPs represent a suitable model system to characterize heterogeneous biomolecular behaviors in preclinical studies and identify and functionally test biological mechanisms associated with resistance to targeted therapeutics.


Assuntos
Compostos de Anilina , Antineoplásicos , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Transdução de Sinais , Humanos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos/farmacologia , Receptores ErbB/metabolismo , Receptores ErbB/genética , Linhagem Celular Tumoral , Compostos de Anilina/farmacologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Acrilamidas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Indóis , Pirimidinas
5.
ACS Omega ; 9(26): 28903-28911, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38973937

RESUMO

The new generation of Li-ion batteries is based on integrating 2D materials into the electrodes to increase the energy density while reducing the charging time and size. The two-dimensional transition metal carbide or nitride (MXene) materials offer ideal electronic properties, such as metallic behavior, low energy barriers for Li-ion diffusion, and structural stability. This study focuses on Nb2C and Nb2CO2 MXenes, which have shown promising Li-storage capacity, especially the oxidized phase. By using density functional theory (DFT) and thermodynamic criteria, we studied the Li intercalation process in both MXenes. The results show that the Li intercalation process in the oxidized phase is more stable. Also, the Li diffusion barriers are 35 and 250 meV for the bare and oxidized phase, due to the strong interaction between Li ions and O functional groups. Nb2C and Nb2CO2 MXenes deliver a maximum gravimetric theoretical capacity of 275 and 233.26 mA h/g, respectively, with a stable performance.

6.
Beilstein J Nanotechnol ; 15: 808-816, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979525

RESUMO

Janus-type nanoparticles are important because of their ability to combine distinct properties and functionalities in a single particle, making them extremely versatile and valuable in various scientific, technological, and industrial applications. In this work, bimetallic silver-palladium Janus nanoparticles were obtained for the first time using the inert gas condensation technique. In order to achieve this, an original synthesis equipment built by Mantis Ltd. was modified by the inclusion of an additional magnetron in a second chamber, which allowed us to use two monometallic targets to sputter the two metals independently. With this arrangement, we could find appropriate settings at room temperature to promote the synthesis of bimetallic Janus nanoparticles. The structural properties of the resulting nanoparticles were investigated by transmission electron microscopy (TEM), and the chemical composition was analyzed by TEM energy dispersive spectroscopy (TEM-EDS), which, together with structural analysis, confirmed the presence of Janus-type nanostructures. Results of molecular dynamics and TEM simulations show that the differences between the crystalline structures of the Pd and Ag regions observed in the TEM micrographs can be explained by small mismatches in the orientations of the two regions of the particle. A density functional theory structural aims to understand the atomic arrangement at the interface of the Janus particle.

7.
J Clin Med ; 13(13)2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38999428

RESUMO

Introduction: Benign paroxysmal positional vertigo (BPPV) stands as the most common cause of peripheral vertigo. Its treatment with repositioning maneuvers on an examination table is highly effective. However, patients with back or neck problems, paraplegia, or other conditions face challenges with these maneuvers, potentially experiencing longer healing times and creating additional difficulties for physicians diagnosing and treating BPPV in everyday practice. The emergence of mechanical rotational chairs (MRCs) offers a more convenient alternative for performing these maneuvers. Objectives: The primary objective was to compare the effectiveness of maneuvers on the examination table with those on MRCs in BPPV patients diagnosed in the emergency room and randomly classified into one of the treatment options. The secondary objectives included a comparison of patient quality of life during BPPV episodes and after their resolution and an analysis of recurrences and associated risk factors. Methods: This was a cohort study on sixty-three patients diagnosed with BPPV in the emergency department. Patients were classified into two cohorts depending on diagnostic and treatment maneuvers (MRC or conventional repositioning maneuvers (CRMs)) and received weekly follow-ups until positioning maneuvers became negative. Subsequent follow-ups were conducted at 1 month, 3 months, and 6 months after the resolution of vertigo. Patients were classified into two groups based on their assigned treatment method. Results: Thirty-one patients were treated with CRMs and 32 with TRV. Mean age was 62.29 ± 17.67 years and the most affected canal was the PSC (96.8%). The mean number of required maneuvers was two, while 55.56% only required one maneuver until resolution. Recurrence was present in 26.98% of the patients during the 6-month follow-up. Comparing both cohorts, there were no statistically significant differences between treatments (TRV vs. CRM) regarding the number of maneuvers, number of recurrences, and days until remission of BPPV. Dizziness Handicap Inventory and Visual Analogue Scale values decreased considerably after BPPV resolution, with no statistically significant differences between the groups. Age was identified as a covariable in the number of maneuvers and days until BPPV resolution, showing that an increase in age implies a greater need of maneuvers. Conclusions: There was no difference between the means of treatment for BPPV in our population ot There was no difference between the groups of treatments for BPPV in our population. The quality of life of patients improved six months after the resolution of BPPV, regardless of the treatment applied.

8.
ACS Omega ; 9(23): 24721-24727, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38882092

RESUMO

Motivated by the experimental findings of Wolff et al., we investigated the TiN|FeCo multilayers at the atomic scale. Four different models were employed to investigate the interface, considering both Fe and Co surface terminations of the FeCo compounds. The interface formation energy formalism was employed to study the thermodynamic stability of these models. The results show that an interface mediated by Co atoms is most likely to appear in the experiment. Also, the Fe surface termination is more viable than a Co surface termination. The magnetic moments of Co at the interface are 1.48 µB/atom, which denotes a decay compared to bulk (1.76 µB/atom). Besides, Ti acquires a very small induced magnetization of -0.05 µB/atom. Our proposed atomistic model of the TiN|FeCo multilayer system fits perfectly with the structure obtained in experiments, and it is a step forward in the theoretical-experimental design of wear-resistant coatings with outstanding magnetic and mechanical properties.

9.
Br J Dermatol ; 191(4): 568-579, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-38820176

RESUMO

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a blistering disease caused by mutations in the gene encoding type VII collagen (C7). RDEB is associated with fibrosis, which is responsible for severe complications. The phenotypic variability observed in siblings with RDEB suggests that epigenetic modifications contribute to disease severity. Identifying epigenetic changes may help to uncover molecular mechanisms underlying RDEB pathogenesis and new therapeutic targets. OBJECTIVES: To investigate histone acetylation in RDEB skin and to explore histone deacetylase inhibitors (HDACi) as therapeutic molecules capable of counteracting fibrosis and disease progression in RDEB mice. METHODS: Acetylated histone levels were detected in human skin by immunofluorescence and in RDEB fibroblasts by enzyme-linked immunosorbent assay (ELISA). The effects of givinostat and valproic acid (VPA) on RDEB fibroblast fibrotic behaviour were assessed by a collagen-gel contraction assay, Western blot and immunocytofluorescence for α-smooth muscle actin, and ELISA for released transforming growth factor (TGF)-ß1. RNA sequencing was performed in HDACi- and vehicle-treated RDEB fibroblasts. VPA was systemically administered to RDEB mice and effects on overt phenotype were monitored. Fibrosis was investigated in the skin using histological and immunofluorescence analyses. Eye and tongue defects were examined microscopically. Mass spectrometry proteomics was performed on skin protein extracts from VPA-treated RDEB and control mice. RESULTS: Histone acetylation decreases in RDEB skin and primary fibroblasts. RDEB fibroblasts treated with HDACi lowered fibrotic traits, including contractility, TGF-ß1 release and proliferation. VPA administration to RDEB mice mitigated severe manifestations affecting the eyes and paws. These effects were associated with fibrosis inhibition. Proteomic analysis of mouse skin revealed that VPA almost normalized protein sets involved in protein synthesis and immune response, processes linked to the increased susceptibility to cancer and bacterial infections seen in people with RDEB. CONCLUSIONS: Dysregulated histone acetylation contributes to RDEB pathogenesis by facilitating the progression of fibrosis. Repurposing of HDACi could be considered for disease-modifying treatments in RDEB.


Recessive dystrophic epidermolysis bullosa (or 'RDEB') is a rare skin disease that affects fewer than 5,000 people in the USA. A similar number of people in Europe are affected. RDEB is caused by mutations in the gene that controls the production of a protein called 'type VII collagen' (or 'C7'). A shortage of C7 causes fragile skin that blisters. In severe forms of RDEB, wounds heal slowly and can even affect a person's life expectancy. Differences in the disease are common in people (even identical twins) with RDEB who have similar levels of C7. This suggests that how severe the disease is could be affected by molecular processes that control other genes. Understanding these processes may help us to find treatments for RDEB. This study was done in Italy, in collaboration with centres in Germany and Switzerland. We wanted to see whether a chemical modification called 'histone acetylation' (which influences gene activity) is different in RDEB and whether it can be targeted by a specific treatment. We found that histone acetylation is reduced in RDEB skin and in skin cells grown in the lab called 'fibroblasts'. When we increased histone acetylation in fibroblasts with two drugs called givinostat and valproic acid, the amount of scar tissue produced decreased. This is important because scar tissue can lead to severe symptoms. We carried out more experiments to study the effects of givinostat and valproic acid in mice with RDEB. We found that valproic acid reduces the severity of RDEB by decreasing the disease's harmful effects and reducing the amount of scar tissue. Our findings suggest that abnormal histone acetylation contributes to the scar tissue seen in RDEB. Our study shows that valproic acid could be useful in treating the scarring seen in RDEB and in reducing the effects of the disease. As this drug is used to treat other diseases, there could be potential for rapid repurposing of it for RDEB.


Assuntos
Colágeno Tipo VII , Progressão da Doença , Epidermólise Bolhosa Distrófica , Fibroblastos , Fibrose , Inibidores de Histona Desacetilases , Pele , Epidermólise Bolhosa Distrófica/tratamento farmacológico , Epidermólise Bolhosa Distrófica/patologia , Epidermólise Bolhosa Distrófica/genética , Animais , Humanos , Inibidores de Histona Desacetilases/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Colágeno Tipo VII/genética , Pele/patologia , Pele/efeitos dos fármacos , Camundongos , Ácido Valproico/farmacologia , Histonas/metabolismo , Acetilação/efeitos dos fármacos , Masculino , Feminino , Modelos Animais de Doenças , Fator de Crescimento Transformador beta1/metabolismo , Células Cultivadas , Criança , Carbamatos
10.
Eur Arch Otorhinolaryngol ; 281(6): 3253-3259, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38436756

RESUMO

PURPOSE: ChatGPT (Chat-Generative Pre-trained Transformer) has proven to be a powerful information tool on various topics, including healthcare. This system is based on information obtained on the Internet, but this information is not always reliable. Currently, few studies analyze the validity of these responses in rhinology. Our work aims to assess the quality and reliability of the information provided by AI regarding the main rhinological pathologies. METHODS: We asked to the default ChatGPT version (GPT-3.5) 65 questions about the most prevalent pathologies in rhinology. The focus was learning about the causes, risk factors, treatments, prognosis, and outcomes. We use the Discern questionnaire and a hexagonal radar schema to evaluate the quality of the information. We use Fleiss's kappa statistical analysis to determine the consistency of agreement between different observers. RESULTS: The overall evaluation of the Discern questionnaire resulted in a score of 4.05 (± 0.6). The results in the Reliability section are worse, with an average score of 3.18. (± 1.77). This score is affected by the responses to questions about the source of the information provided. The average score for the Quality section was 3.59 (± 1.18). Fleiss's Kappa shows substantial agreement, with a K of 0.69 (p < 0.001). CONCLUSION: The ChatGPT answers are accurate and reliable. It generates a simple and understandable description of the pathology for the patient's benefit. Our team considers that ChatGPT could be a useful tool to provide information under prior supervision by a health professional.


Assuntos
Otolaringologia , Humanos , Inquéritos e Questionários , Reprodutibilidade dos Testes , Internet , Doenças Nasais/diagnóstico
11.
Biochemistry ; 63(3): 251-263, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38243804

RESUMO

The 13 Hsp70 proteins in humans act on unique sets of substrates with diversity often being attributed to J-domain-containing protein (Hsp40 or JDP) cofactors. We were therefore surprised to find drastically different binding affinities for Hsp70-peptide substrates, leading us to probe substrate specificity among the 8 canonical Hsp70s from humans. We used peptide arrays to characterize Hsp70 binding and then mined these data using machine learning to develop an algorithm for isoform-specific prediction of Hsp70 binding sequences. The results of this algorithm revealed recognition patterns not predicted based on local sequence alignments. We then showed that none of the human isoforms can complement heat-shocked DnaK knockout Escherichia coli cells. However, chimeric Hsp70s consisting of the human nucleotide-binding domain and the substrate-binding domain of DnaK complement during heat shock, providing further evidence in vivo of the divergent function of the Hsp70 substrate-binding domains. We also demonstrated that the differences in heat shock complementation among the chimeras are not due to loss of DnaJ binding. Although we do not exclude JDPs as additional specificity factors, our data demonstrate substrate specificity among the Hsp70s, which has important implications for inhibitor development in cancer and neurodegeneration.


Assuntos
Proteínas de Escherichia coli , Proteínas de Choque Térmico , Humanos , Proteínas de Choque Térmico/metabolismo , Proteínas de Escherichia coli/química , Sítios de Ligação , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Peptídeos/metabolismo , Ligação Proteica
13.
Laryngoscope ; 134(5): 2405-2410, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38087849

RESUMO

OBJECTIVE: The objective of this study was to assess the clinical significance of the Bow and Lean Test (BLT) for the diagnosis of different variants of vertical canal Benign Paroxysmal Positional Vertigo (BPPV). BLT is commonly used for diagnoses of lateral semicircular canal (LSC) BPPV. However, vertical nystagmus in the BLT may indicate the presence of other variants such as PSC-BPPV. METHODS: 567 patients with vertical canal BPPV were recruited. Patients with anterior semicircular canal (ASC) or PSC-BPPV were weekly examined until the negativization of BPPV. Nystagmus characteristics during BLT were analyzed. RESULTS: Of 567 patients with vertical canal BPPV, 1.4% had ASC-BPPV. BLT was positive in 155 patients, showing patterns like down-beating nystagmus in bowing and no nystagmus in leaning (15.52% of patients), and down-beating in bowing and up-beating in leaning (6.17%), which was predominantly present in PSC-canalolithiasis. Statistically significant differences were observed in the direction of nystagmus provoked by BLT in PSC-BPPV subtypes. No significant differences were found in nystagmus latency or duration during BLT positions. Among BPPV subtypes, there was a significant difference in nystagmus duration and latency, especially between cupulolithiasis and other variants. BLT's sensitivity was 0.93 in bowing and 1 in a leaning position, while specificity was 0.93 and 0.82 respectively. CONCLUSION: Beyond the LSC, the BLT has expanded to other variants. However, study results differ likely due to variations in patient characteristics and test execution. Currently, no specific features for ASC have been found to differentiate it from PSC-BPPV limiting the test's use for this variant. LEVEL OF EVIDENCE: 3, according to Oxford Center for Evidence-Based Medicine Laryngoscope, 134:2405-2410, 2024.


Assuntos
Vertigem Posicional Paroxística Benigna , Nistagmo Patológico , Humanos , Vertigem Posicional Paroxística Benigna/diagnóstico , Canais Semicirculares , Nistagmo Patológico/diagnóstico , Meio Ambiente , Medicina Baseada em Evidências
14.
Nanoscale Adv ; 5(20): 5476-5486, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37822911

RESUMO

In the present work, we report on a theoretical-computational study of the growth mechanism of the TiO2-Graphene nanohybrid by atomic layer deposition. Hydroxyl groups (OH) are anchoring sites for interacting with the main ALD titanium precursors (Tetrakis (dimethylamino) Titanium, Titanium Tetrachloride, and Titanium Isopropoxide). Results demonstrate that the chemical nature of the precursor directly affects the reaction mechanism in each ALD growth step. Tetrakis(dimethylamino)titanium is the precursor that presents a higher affinity (lower energy barriers for the reaction) to hydroxylated graphene in the growth process. A complete reaction mechanism for each precursor was proposed. The differences between precursors were discussed through the non-covalent interactions index. Finally, the water molecules help reduce the energy barriers and consequently favor the formation of the TiO2-graphene nanohybrid.

15.
Brain Sci ; 13(6)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37371321

RESUMO

Alzheimer's disease (AD) is characterized by the buildup of plaques and tangles in the brain. Tangles are formed when the stabilizing protein, tau, becomes hyperphosphorylated and clumps together. There are limited treatments for AD; therefore, the exploration of new treatments is warranted. Previous research showed that plasma transfusion from young donor mice improved spatial memory and increased synaptic proteins in old transgenic APP/PS1 mice, suggesting a remediation of memory and synaptic function. In the current study, plasma was transfused from 2-3-month-old young wildtype mice (WT) to 8-month-old rTg4510 mice expressing human tau (Tau). One week after the transfusions, behavior and tau pathology were examined. We found that Tau mice injected with plasma had lower expression of phosphorylated tau (ptau) in the brain, accompanied by fewer tau tangles in the cortex and CA1 region of the hippocampus and smaller tau tangles in the cortex, when compared to Tau mice injected with saline. Despite no improvement in behavior, the decreased level of ptau and tangles open the door to future studies involving plasma transfusions.

16.
J Dev Orig Health Dis ; 14(4): 469-480, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37222148

RESUMO

Human health is strongly mediated by the gut microbiota ecosystem, which, in turn, depends not only on its state but also on its dynamics and how it responds to perturbations. Healthy microbiota ecosystems tend to be in criticality and antifragile dynamics corresponding to a maximum complexity configuration, which may be assessed with information and network theory analysis. Under this complex system perspective, we used a new analysis of published data to show that a children's population with an industrialized urban lifestyle from Mexico City exhibits informational and network characteristics similar to parasitized children from a rural indigenous population in the remote mountainous region of Guerrero, México. We propose then, that in this critical age for gut microbiota maturation, the industrialized urban lifestyle could be thought of as an external perturbation to the gut microbiota ecosystem, and we show that it produces a similar loss in criticality/antifragility as the one observed by internal perturbation due to parasitosis by the helminth A. lumbricoides. Finally, several general complexity-based guidelines to prevent or restore gut ecosystem antifragility are discussed.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Criança , População Rural , Estilo de Vida , México/epidemiologia
17.
Wellcome Open Res ; 8: 424, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-39219857

RESUMO

Tuberculosis (TB) caused 1.5 million deaths in 2020, making it the leading infectious killer after COVID-19. Bacille Calmette-Guerin (BCG) is the only licensed vaccine against TB but has sub-optimal efficacy against pulmonary TB and reduced effectiveness in regions close to the equator with high burden. Efforts to find novel vaccines are hampered due to the need for large-scale, prolonged, and costly clinical trials. Controlled human infection models (CHIMs) for TB may be used to accelerate vaccine development by ensuring only the most promising vaccine candidates are selected for phase 3 trials, but it is not currently possible to give participants Mycobacterium tuberculosis as a challenge agent. This study aims to replicate and refine an established BCG CHIM at the Liverpool School of Tropical Medicine. Participants will receive an intradermal injection with licensed BCG vaccine (Statens Serum Institut strain). In phase A, participants will undergo punch biopsy two weeks after administration, paired with minimally invasive methods of skin sampling (skin swab, microbiopsy, skin scrape). BCG detection by classical culture and molecular methods will be compared between these techniques and gold standard punch biopsy. Techniques meeting our pre-defined sensitivity and specificity criteria will be applied in Phase B to longitudinally assess intradermal BCG growth two, seven and fourteen days after administration. We will also measure compartmental immune responses in skin, blood and respiratory mucosa in Phase B. This feasibility study will transfer and refine an existing and safe model of BCG controlled human infection. Longitudinal BCG quantification has the potential to increase model sensitivity to detect vaccine and therapeutic responses. If successful, we aim to transfer the model to Malawi in future studies, a setting with endemic TB disease, to accelerate development of vaccines and therapeutics relevant for underserved populations who stand to benefit the most. Registration: ISRCTN: ISRCTN94098600 and ClinicalTrials.gov: NCT05820594.

18.
ACS Omega ; 7(38): 33884-33894, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36188272

RESUMO

Structural, electronic, and magnetic properties of two-dimensional Cr2N MXene under strain were studied. The uniaxial and biaxial strain was considered from -5 to 5%. Phonon dispersion was calculated; imaginary frequency was not found for both kinds of strain. Phonon density of states displays an interesting relation between strain and optical phonon gaps (OPGs), that it implies tunable thermal conductivity. When we apply biaxial tensile strain, the OPG increases; however, this is not appreciable under uniaxial strain. The electronic properties of the dynamically stable systems were investigated by calculating the band structure and electron localization function (ELF) along the (110) plane. The band structure showed a metallic behavior under compressive strain; nevertheless, under tensile strain, the system has a little indirect band gap of 0.16 eV. By analyzing, the ELF interactions between Cr-N are determined to be a weaker covalent bonding Cr2N under tensile strain. On the other hand, if the Cr atoms reduce or increase their self-distance, the magnetization alignment changes, also the magnetic anisotropy energy displays out-of-plane spin alignment. These properties extend the potential applications of Cr2N in the spintronic area as long as they can be grown on substrates with high lattice mismatch, conserving their magnetic properties.

19.
J Clin Med ; 11(14)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35887704

RESUMO

OBJECTIVES: The aim was to analyze and compare the compensatory process, vestibular dysfunction, postural control, and perceived disability in a population of patients with vestibular neuritis (VN). MATERIAL AND METHODS: This is a prospective and longitudinal study of 67 patients diagnosed with VN. Inclusion criteria were sudden onset of vertigo, unidirectional spontaneous horizontal nystagmus, and impairment in vestibular test. Exclusion criteria were imaging or clinical findings of any neurotologic disorder. All vestibular tests were performed; vHIT, vestibular evoked myogenic potentials (VEMPs), caloric test and computerized dynamic posturography (CDP), dizziness handicap inventory (DHI), and visual analogue scale (VAS) were also performed at every follow up. RESULTS: We observed a correlation between the composite score of CDP and baseline vestibular function elicited either by caloric test, VEMPs, or vHIT. There was a significant correlation between baseline vestibular function and first visit questionnaire scores. The main gain recovery for the horizontal canal was 0.1 ± 0.04 for the first three months. After that, the gain recovery significantly decreased. The presence of covert and overt saccades', latency and amplitude decreased, respectively, after the 6-month period, when compared to the baseline results. We also observed a decrease in the PR score from 3 months after the vestibular insult until the last follow up. We observed a significant decrease in DHI and VAS from the first visit until the last one. Those patients with an initial HC gain below 0.5 had significantly higher DHI and VAS scores at every follow up. CONCLUSIONS: There are different measurements that could become a complete measurement of the state of compensation, postural control, and disability of the patients. There is a time window in which the vestibular restoration could give us clinical insights regarding the management of VN patients.

20.
J Surg Res ; 278: 196-205, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35617785

RESUMO

INTRODUCTION: Research indicates that prophylactic mesh may help prevent incisional hernia after laparotomy, but best practice patterns in these situations are still evolving. Here, we compare the failure loads (FLs) and biomechanical stiffness (BMS) of 35 porcine abdominal wall laparotomy incisions reinforced with meshes of various widths and fixation distances using biomechanical testing. METHODS: In each specimen, a 10-cm incision was made and closed using continuous 1-0 Maxon suture. Specimens were randomized to mesh width (none, 2.5 cm, 3 cm, 4 cm, 6 cm, 8 cm) and tack separation (1.5 cm, 2 cm apart) and the meshes secured in an onlay fashion. Cyclic loads oscillating from 15 N to 140 N were applied to simulate abdominal wall stress, and the specimens subsequently loaded to failure. FLs (N) and BMS (N/mm) were comparatively analyzed. RESULTS: All specimens failed via suture pull-through. FLs and BMS were lowest in specimens with suture-only (421.43 N; 11.69 N/mm). FLs and BMS were significantly higher in 4-cm mesh specimens (567.51 N) than those with suture, 2.5-cm, and 3.0-cm mesh (all P < 0.05). FLs in specimens with a greater number of tacks were consistently higher in meshes of similar sizes, although these did not reach significance. CONCLUSIONS: A 4-cm mesh reenforcement was superior to suture-only and smaller meshes at preserving strength in laparotomy closure in a porcine model but larger meshes (6 cm, 8 cm) did not provide an additional benefit. Meshes with more fixation points may be advantageous, but additional data are needed to make definitive conclusions.


Assuntos
Parede Abdominal , Hérnia Ventral , Hérnia Incisional , Animais , Parede Abdominal/cirurgia , Hérnia Ventral/prevenção & controle , Hérnia Ventral/cirurgia , Hérnia Incisional/cirurgia , Laparotomia/efeitos adversos , Telas Cirúrgicas , Suturas , Suínos
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