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1.
PLoS One ; 19(7): e0306539, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959274

RESUMO

In the wake of the mental health crisis in children and adolescents, the coordination of education and mental health services has become a global priority. However, differing terminologies and classifications across sectors, hinder effective comparison. The classification in education focuses mainly on outputs like qualifications or throughputs like teaching programs. This proof-of-concept study tested the applicability of a standard classification of health services, the Description and Evaluation of Services and DirectoriEs (DESDE), to evaluate education services for mental health users in the context of Spain and The Netherlands. It was conducted alongside the PECUNIA project, that sought to develop methods for the assessment of mental health costs and outcomes in different sectors. The study followed an ontoterminology approach involving: 1) identification of services from a predefined list of 46 resource-use items, 2) disambiguation of identified services with the DESDE, and classifying them as accurate, ambiguous, vague or confuse; and 3) external validation by an expert panel. The analysis was conducted at the level of type of resource, target population and care provision. From the initial list, only ten of the resources could be categorized as services using DESDE, and not activities, interventions or professionals. Only four of them (8,65%) were accurate across all disambiguation categories. Experts were unaware of terminology problems in classification of service provision in the education sector. Classifications and glossaries can clarify service naming, description and costing allowing comparative effectiveness analysis and facilitating cross-sectoral planning. This should be grounded in common methodologies, tools, and units of analysis.


Assuntos
Serviços de Saúde Mental , Terminologia como Assunto , Humanos , Espanha , Adolescente , Países Baixos , Criança , Saúde Mental , Transtornos Mentais/terapia , Transtornos Mentais/classificação , Transtornos Mentais/diagnóstico
2.
Dalton Trans ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967417

RESUMO

In this work we report the synthesis, structural characterization and magnetic properties of a family of butterfly complexes {Cr2Ln2} with Ln = Tb (4), Ho (5), Er (6), Tm (7) and Yb (8), extending the family of previously reported isostructural compounds with Gd (1), Dy (2) and Y (3). As in 1 and 2, an anti-ferromagnetic Cr(III)-Ln(III) exchange interaction is found. For oblate ions 4 and 5, SMM behavior with a purely Orbach relaxation mechanism is observed with thermal barriers of 38 cm-1 (4) and 32 cm-1 (5). Complex 4 displays hysteresis opening up to 2.4 K with loss of magnetization at zero field. The prolate complex ions 6 and 7 are field-induced SMM's with dominant Orbach, direct and QTM relaxation mechanisms. Compound 8 did not show SMM properties.

4.
Eur Urol Focus ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38839508

RESUMO

BACKGROUND AND OBJECTIVE: Several minimally invasive treatments have been developed to treat benign prostatic obstruction (BPO) via a transurethral approach, with a non-negligible risk of complications such as urethral stricture and external sphincter damage. Our aim was to present the Gozzi surgical technique for suprapubic transvesical adenoma resection of the prostate (STAR-P) for BPO and to assess its safety, feasibility, and outcomes. METHODS: We conducted a retrospective analysis of 44 consecutive patients who underwent STAR-P for BPO. All the procedures were performed in a single private hospital by one surgeon from 2020 to 2022. An innovative resectoscope designed by the surgeon was subsequently produced by Tontarra Medizintechnik (Wurmlingen, Germany) with a 42.06 Fr external sheath that allows the use of loops of three different sizes. The instrument is inserted into the bladder via suprapubic access, which ensures greater freedom of movement without compromising the external sphincter. Clinical data were retrospectively collected. Preoperative and intraoperative variables, postoperative complications, and functional outcomes of the STAR-P procedure were assessed. A descriptive statistical analysis was performed. KEY FINDINGS AND LIMITATIONS: No intraoperative complications were observed. Two patients (4.5%) experienced urinary urgency symptoms after catheter removal that resolved within 90 d. Median times were 105 min for surgery overall and 65 min for resection. All patients showed an improvement in voiding quality. CONCLUSIONS AND CLINICAL IMPLICATIONS: STAR-P is a safe, feasible, and cost-effective procedure that spares the bulbomembranous and penile urethra and the external urethral sphincter, and should be discussed with patients as a possible option for treatment of BPO. PATIENT SUMMARY: We describe a new, safe, and feasible technique for surgical treatment of urinary obstruction caused by a large prostate. Keyhole surgery is performed through the lower abdomen, which means that the urethra below the prostate is not damaged. Only a small scar of 2-3 cm in the lower abdomen is evident at the end of the healing process.

5.
Dalton Trans ; 53(24): 10303-10317, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38832753

RESUMO

We present the synthesis of two new novel tetradentate ligands based on 1,3,4-oxadiazole, 2-(2-pyridyl)-5-[N,N-bis(2-pyridylmethyl)aminomethyl]-1,3,4-oxadiazole (LTetraPy-ODA) and 2-(2-phenyl)-5-[N,N-bis(2-pyridylmethyl)aminomethyl]-1,3,4-oxadiazole (LTetraPh-ODA). The ligands were used to prepare six mononuclear complexes [FeII(LTetraPy-ODA)(NCE)] (C1-C3) and [FeII(LTetraPh-ODA)(NCE)] (C4-C6) where E = S, Se or BH3. In addition, the ligand LTetraPy-ODA was employed in the synthesis of a new di-nuclear complex [FeII2(LTetraPh)](ClO4)4·1 CH3NO2·1.5 H2O (C7). Characterization of all complexes was carried out using single-crystal X-ray crystallography, elemental analysis, and infrared spectroscopy. Magnetic susceptibility measurements, performed in the temperature range of 2-300 K using a SQUID magnetometer, revealed spin crossover behaviour exclusively in the mononuclear complexes C3 and C6, in which two monodentate NCBH3- co-ligands coordinate. The presence of the lattice solvent was found to be crucial to the spin transition property, with complex C3 exhibiting a switching temperature (T1/2) of approximately 165 K and C6 approximately 194 K. The other four mononuclear complexes C1, C2, C4, C5, as well as the dinuclear complex C7 are locked in the high spin state over the measured temperature range. Density Functional Theory (DFT) calculations were performed on complexes C1-C6 to rationalise the observed magnetic behaviour, demonstrating the significant effect of the NCS-, NCSe- and NCBH3- co-ligands ligands on the spin-crossover behaviour of the [FeII(L)(NCE)] complexes.

7.
Int J Infect Dis ; : 107132, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942168

RESUMO

OBJECTIVE: The 2022 mpox epidemic reached a peak in Belgium and the rest of Europe in July 2022, after which it unexpectedly subsided. This study investigates epidemiological, behavioral, and immunological factors behind the waning of the epidemic in Belgium. METHODS: We investigated temporal evolutions in the characteristics and behavior of mpox patients using national surveillance data and data from a prospective registry of mpox patients in the Institute of Tropical Medicine (Antwerp). We studied behavioral changes in the population at risk using a survey among HIV-pre-exposure prophylaxis (PrEP) users. We determined the seroprevalence of anti-orthopoxvirus antibodies among HIV-PrEP users across four time points in 2022. RESULTS: Mpox patients diagnosed at the end of the epidemic had less sexual risk behavior compared to those diagnosed earlier: they engaged less in sex at mass events, had fewer sexual partners and were less likely to belong to the sexual network's central group. Among HIV-PrEP users there were no notable changes in sexual behavior. Anti-orthopoxvirus seroprevalence did not notably increase before the start of national vaccination campaigns. CONCLUSION: The observed changes in group immunity and behavior in the population at greater risk of exposure to mpox seem unable to explain the waning of the mpox epidemic. A change in the profile of mpox patients might have contributed to the decline in cases.

8.
Transl Psychiatry ; 14(1): 200, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714646

RESUMO

Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias-an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.


Assuntos
Antidepressivos , Azóis , Transtorno Depressivo Maior , Emoções , Isoindóis , Compostos Organosselênicos , Humanos , Feminino , Masculino , Compostos Organosselênicos/farmacologia , Método Duplo-Cego , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Antidepressivos/uso terapêutico , Antidepressivos/farmacologia , Pessoa de Meia-Idade , Emoções/efeitos dos fármacos , Azóis/farmacologia , Espectroscopia de Ressonância Magnética , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/metabolismo , Giro do Cíngulo/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem
9.
Nat Commun ; 15(1): 4224, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38762522

RESUMO

Waning antibody responses after COVID-19 vaccination combined with the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness. As a countermeasure, bivalent mRNA-based booster vaccines encoding the ancestral spike protein in combination with that of Omicron BA.1 or BA.5 were introduced. Since then, different BA.2-descendent lineages have become dominant, such as XBB.1.5, JN.1, or EG.5.1. Here, we report post-hoc analyses of data from the SWITCH-ON study, assessing how different COVID-19 priming regimens affect the immunogenicity of bivalent booster vaccinations and breakthrough infections (NCT05471440). BA.1 and BA.5 bivalent vaccines boosted neutralizing antibodies and T-cells up to 3 months after boost; however, cross-neutralization of XBB.1.5 was poor. Interestingly, different combinations of prime-boost regimens induced divergent responses: participants primed with Ad26.COV2.S developed lower binding antibody levels after bivalent boost while neutralization and T-cell responses were similar to mRNA-based primed participants. In contrast, the breadth of neutralization was higher in mRNA-primed and bivalent BA.5 boosted participants. Combined, our data further support the current use of monovalent vaccines based on circulating strains when vaccinating risk groups, as recently recommended by the WHO. We emphasize the importance of the continuous assessment of immune responses targeting circulating variants to guide future COVID-19 vaccination policies.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Imunogenicidade da Vacina , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , SARS-CoV-2/imunologia , SARS-CoV-2/genética , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Linfócitos T/imunologia , Vacinação
10.
J Psychosom Res ; 181: 111668, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38640771

RESUMO

OBJECTIVE: In this study, we examined the extent to which parents and their children with a chronic condition communicate their stress to one another and whether stress communication is associated with different forms of dyadic coping. METHODS: In a sample of 239 parent-child dyads, self-reported stress communication and different forms of perceived dyadic coping (i.e., emotion-oriented, problem-oriented, and negative dyadic coping) were assessed using a cross-sectional design. RESULTS: We first found that children's stress communication was positively associated with more positive (r = 0.28, p < .001) and less negative dyadic coping responses by children (r = -0.22, p < .001). Children's stress communication was also associated with more positive (r = 0.52, r = 0.45, p's < 0.001), and less negative dyadic coping responses by parents (r = -0.19, p < .001). Using dyadic data of children with a chronic condition and their parents, we found that more stress communication of children was associated with healthier coping responses of both children (perceived emotion-oriented dyadic coping: ß = 0.23, p < .001) and parents (perceived emotion-oriented dyadic coping: ß = 0.33, p < .001; perceived problem-oriented dyadic coping: ß = 0.22, p < .001). CONCLUSION: This underscores the importance of communication and adaptive coping strategies of parents and children in the context of a child's chronic condition. These findings may help us find ways to support children and their parents to optimally communicate about and deal with their stress.


Assuntos
Adaptação Psicológica , Relações Pais-Filho , Estresse Psicológico , Humanos , Masculino , Feminino , Criança , Doença Crônica/psicologia , Estudos Transversais , Estresse Psicológico/psicologia , Adulto , Pais/psicologia , Emoções , Comunicação , Adolescente
11.
J Endocrinol Invest ; 47(6): 1361-1371, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38630213

RESUMO

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.


Assuntos
Obesidade , Sobrepeso , Humanos , Obesidade/terapia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/terapia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Itália/epidemiologia , Comorbidade , Terapia Comportamental/métodos , Terapia Comportamental/normas , Guias de Prática Clínica como Assunto/normas , Gerenciamento Clínico , Cirurgia Bariátrica/métodos
13.
Euro Surveill ; 29(17)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38666400

RESUMO

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.


Assuntos
Surtos de Doenças , Homossexualidade Masculina , Humanos , Masculino , Países Baixos/epidemiologia , Estudos Soroepidemiológicos , Estudos Transversais , Homossexualidade Masculina/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Vacínia/epidemiologia , Anticorpos Antivirais/sangue , Vacinação/estatística & dados numéricos , Adulto Jovem , Modelos Teóricos , Ensaio de Imunoadsorção Enzimática , Imunoglobulina G/sangue
14.
Obes Surg ; 34(5): 1395-1404, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38472706

RESUMO

INTRODUCTION: Knowing how metabolic and bariatric surgery (MBS) is indicated in different countries is essential information for the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). AIM: To analyze the indications for MBS recommended by each of the national societies that comprise the IFSO and how MBS is financed in their countries. METHODS: All IFSO societies were asked to fill out a survey asking whether they have, and which are their national guidelines, and if MBS is covered by their public health service. RESULTS: Sixty-three out of the 72 IFSO national societies answered the form (87.5%). Among them, 74.6% have some kind of guidelines regarding indications for MBS. Twenty-two percent are still based on the US National Institute of Health (NIH) 1991 recommendations, 43.5% possess guidelines midway the 1991s and ASMBS/IFSO 2022 ones, and 34% have already adopted the latest ASMBS/IFSO 2022 guidelines. MBS was financially covered in 65% of the countries. CONCLUSIONS: Most of the IFSO member societies have MBS guidelines. While more than a third of them have already shifted to the most updated ASMBS/IFSO 2022 ones, another significant number of countries are still following the NIH 1991 guidelines or even do not have any at all. Besides, there is a significant number of countries in which surgical treatment is not yet financially covered. More effort is needed to standardize indications worldwide and to influence insurers and health policymakers to increase the coverage of MBS.


Assuntos
Cirurgia Bariátrica , Doenças Metabólicas , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Obesidade/cirurgia , Doenças Metabólicas/cirurgia , Sociedades Médicas
15.
Viruses ; 16(3)2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38543804

RESUMO

Pathogenic lagoviruses (Rabbit hemorrhagic disease virus, RHDV) are widely spread across the world and are used in Australia and New Zealand to control populations of feral European rabbits. The spread of the non-pathogenic lagoviruses, e.g., rabbit calicivirus (RCV), is less well studied as the infection results in no clinical signs. Nonetheless, RCV has important implications for the spread of RHDV and rabbit biocontrol as it can provide varying levels of cross-protection against fatal infection with pathogenic lagoviruses. In Chile, where European rabbits are also an introduced species, myxoma virus was used for localised biocontrol of rabbits in the 1950s. To date, there have been no studies investigating the presence of lagoviruses in the Chilean feral rabbit population. In this study, liver and duodenum rabbit samples from central Chile were tested for the presence of lagoviruses and positive samples were subject to whole RNA sequencing and subsequent data analysis. Phylogenetic analysis revealed a novel RCV variant in duodenal samples that likely originated from European RCVs. Sequencing analysis also detected the presence of a rabbit astrovirus in one of the lagovirus-positive samples.


Assuntos
Infecções por Caliciviridae , Vírus da Doença Hemorrágica de Coelhos , Lagovirus , Animais , Coelhos , Filogenia , Chile , Infecções por Caliciviridae/epidemiologia , Vírus da Doença Hemorrágica de Coelhos/genética
16.
Chem Sci ; 15(8): 2755-2762, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38404386

RESUMO

Chromophores face applicability limitations due to their natural tendency to aggregate, with a subsequent deactivation of their emission features. Hence, there has been a fast development of aggregation induced emission (AIE) emitters, in which non-radiative motional deactivation is inhibited. However, a fine control of their colloidal properties governing the emitting performance is fundamental for their application in thin film optoelectronics. In addition, ion-based lighting devices, such as light emitting electrochemical cells (LECs), requires the design of ionic AIE emitters, whose structure allows (i) an easy ion polarizability to assist charge injection and (ii) a reversible electrochemical behavior. To date, these fundamental questions have not been addressed. Herein, the hydrophilic/hydrophobic balance of a family of cationic tetraphenyl ethene (TPE) derivatives is finely tuned by chemical design. The hydrophilic yet repulsive effect of pyridinium-based cationic moieties is balanced with hydrophobic variables (long alkyl chains or counterion chemistry), leading to (i) a control between monomeric/aggregate state ruling photoluminescence, (ii) redox behavior, and (iii) enhanced ion conductivity in thin films. This resulted in a LEC enhancement with the first ionic AIE emitters, reaching values of 0.19 lm W-1 at ca. 50 cd m-2. Overall, this design rule will be key to advance ionic active species for optoelectronics.

17.
ACS Photonics ; 11(2): 714-722, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38405393

RESUMO

Surface-enhanced spectroscopy techniques are the method-of-choice to characterize adsorbed intermediates occurring during electrochemical reactions, which are crucial in realizing a green and sustainable future. Characterizing species with low coverage or short lifetimes has so far been limited by low signal enhancement. Recently, single-band metasurface-driven surface-enhanced infrared absorption spectroscopy (SEIRAS) has been pioneered as a promising technology to monitor a single vibrational mode during electrochemical CO oxidation. However, electrochemical reactions are complex, and their understanding requires the simultaneous monitoring of multiple adsorbed species in situ, hampering the adoption of nanostructured electrodes in spectro-electrochemistry. Here, we develop a multi-band nanophotonic-electrochemical platform that simultaneously monitors in situ multiple adsorbed species emerging during cyclic voltammetry scans by leveraging the high resolution offered by the reproducible nanostructuring of the working electrode. Specifically, we studied the electrochemical reduction of CO2 on a Pt surface and used two separately tuned metasurface arrays to monitor two adsorption configurations of CO with vibrational bands at ∼2030 and ∼1840 cm-1. Our platform provides a ∼40-fold enhancement in the detection of characteristic absorption signals compared to conventional broadband electrochemically roughened platinum films. A straightforward methodology is outlined starting with baselining our system in a CO-saturated environment and clearly detecting both configurations of adsorption. In contrast, during the electrochemical reduction of CO2 on platinum in K2CO3, CO adsorbed in a bridged configuration could not be detected. We anticipate that our technology will guide researchers in developing similar sensing platforms to simultaneously detect multiple challenging intermediates, with low surface coverage or short lifetimes.

18.
J Proteome Res ; 23(3): 1049-1061, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38372774

RESUMO

Elucidating antibody-antigen complexes at the atomic level is of utmost interest for understanding immune responses and designing better therapies. Cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for mapping protein-protein interactions, suggesting valuable structural insights. However, the use of XL-MS studies to enable epitope/paratope mapping of antibody-antigen complexes is still limited up to now. XL-MS data can be used to drive integrative modeling of antibody-antigen complexes, where cross-links information serves as distance restraints for the precise determination of binding interfaces. In this approach, XL-MS data are employed to identify connections between binding interfaces of the antibody and the antigen, thus informing molecular modeling. Current literature provides minimal input about the impact of XL-MS data on the integrative modeling of antibody-antigen complexes. Here, we applied XL-MS to retrieve information about binding interfaces of three antibody-antigen complexes. We leveraged XL-MS data to perform integrative modeling using HADDOCK (active-passive residues and distance restraints strategies) and AlphaLink2. We then compared these three approaches with initial predictions of investigated antibody-antigen complexes by AlphaFold Multimer. This work emphasizes the importance of cross-linking data in resolving conformational dynamics of antibody-antigen complexes, ultimately enhancing the design of better protein therapeutics and vaccines.


Assuntos
Complexo Antígeno-Anticorpo , Espectrometria de Massas , Mapeamento de Epitopos
19.
Toxicol In Vitro ; 96: 105783, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38278458

RESUMO

Arsenic compounds are common environmental toxicants worldwide and particularly enriched in the Northeast and the Southwestern United States, the Alps, and Bangladesh. Exposure to arsenic is linked with various detrimental health outcomes, including cancer, cognitive decline, and kidney damage. Our group has previously shown that arsenic trioxide alters T cell cytokine production. In the current study, we demonstrate that exposure to arsenic compounds alters B cell function in an in vitro influenza model. Human peripheral blood mononuclear cells (PBMCs) were isolated from blood and cultured with arsenic trioxide (As3O2) and subsequently challenged with Influenza A virus. B cells showed decreased expression of CD267, surface IgG and CD80 when treated with As3O2. Taken together, the data suggest that As3O2 affects the activation and surface antibody expression of human peripheral B cells. Overall, this suggests that As3O2 exposure could cause impaired humoral immunity.


Assuntos
Arsenicais , Orthomyxoviridae , Humanos , Trióxido de Arsênio/toxicidade , Leucócitos Mononucleares , Linfócitos B
20.
Anal Bioanal Chem ; 416(4): 925-944, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38214704

RESUMO

Lipids are a diverse class of molecules involved in many biological functions including cell signaling or cell membrane assembly. Owing to this relevance, LC-MS/MS-based lipidomics emerged as a major field in modern analytical chemistry. Here, we thoroughly characterized the influence of MS and LC settings - of a Q Exactive HF operated in Full MS/data-dependent MS2 TOP N acquisition mode - in order to optimize the semi-quantification of polar lipids. Optimization of MS-source settings improved the signal intensity by factor 3 compared to default settings. Polar lipids were separated on an ACQUITY Premier CSH C18 reversed-phase column (100 × 2.1 mm, 1.7 µm, 130 Å) during an elution window of 28 min, leading to a sufficient number of both data points across the chromatographic peaks, as well as MS2 spectra. Analysis was carried out in positive and negative ionization mode enabling the detection of a broader spectrum of lipids and to support the structural characterization of lipids. Optimal sample preparation of biological samples was achieved by liquid-liquid extraction using MeOH/MTBE resulting in an excellent extraction recovery > 85% with an intra-day and inter-day variability < 15%. The optimized method was applied on the investigation of changes in the phospholipid pattern in plasma from human subjects supplemented with n3-PUFA (20:5 and 22:6). The strongest increase was observed for lipids bearing 20:5, while 22:4 bearing lipids were lowered. Specifically, LPC 20:5_0:0 and PC 16:0_20:5 were found to be strongest elevated, while PE 18:0_22:4 and PC 18:2_18:2 were decreased by n3-PUFA supplementation. These results were confirmed by targeted LC-MS/MS using commercially available phospholipids as standards.


Assuntos
Lipidômica , Fosfolipídeos , Humanos , Fosfolipídeos/análise , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massa com Cromatografia Líquida , Cromatografia Líquida de Alta Pressão
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