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2.
J Phys Chem Lett ; 15(26): 6826-6834, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38916593

RESUMEN

Resonance Raman spectroscopy can provide insights into complex reaction mechanisms by selectively enhancing the signals of specific molecular species. In this work, we demonstrate that, by changing the excitation wavelength, Raman bands of different intermediates in the methanol-to-hydrocarbons reactions can be identified. We show in particular how UV excitation enhances signals from short-chain olefins and cyclopentadienyl cations during the induction period, while visible excitation better detects later-stage aromatics. However, visible excitation is prone to fluorescence that can obscure Raman signals, and hence, we show how fast fluorescence rejection techniques like Kerr gating are necessary for extracting useful information from visible excitation measurements.

3.
Curr Protoc ; 4(6): e1030, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38923763

RESUMEN

Functional characterization of enzymes/proteins requires determination of the binding affinity of small molecules or other biomolecules with the target proteins. Several available techniques, such as proteomics and drug discovery strategies, require a precise and high-throughput assay for rapid and reliable screening of potential candidates for further testing. Surface plasmon resonance (SPR), a well-established label-free technique, directly measures biomolecular affinities. SPR assays require immobilization of one interacting component (ligand) on a conductive metal (mostly gold or silver) and a continuous flow of solution containing potential binding partner (analyte) across the surface. The SPR phenomenon occurs when polarized light excites the electrons at the interface of the metal and the dielectric medium to generate electromagnetic waves that propagate parallel to the surface. Changes in the refractive index due to interaction between the ligand and analyte are measured by detecting the reflected light, providing real-time data on kinetics and specificity. A prominent use of SPR is identifying compounds in crude plant extracts that bind to specific molecules. Procedures that utilize SPR are becoming increasingly applicable outside the laboratory setting, and SPR imaging and localized SPR (LSPR) are cheaper and more portable alternative for in situ detection of plant or mammalian pathogens and drug discovery studies. LSPR, in particular, has the advantage of direct attachment to test tissues in live-plant studies. Here, we describe three protocols utilizing SPR-based assays for precise analysis of protein-ligand interactions. © 2024 Wiley Periodicals LLC. Basic Protocol 1: SPR comparison of binding affinities of viral reverse transcriptase polymorphisms Basic Protocol 2: SPR screening of crude plant extract for protein-binding agents Basic Protocol 3: Localized SPR-based antigen detection using antibody-conjugated gold nanoparticles.


Asunto(s)
Resonancia por Plasmón de Superficie , Resonancia por Plasmón de Superficie/métodos , Ligandos , Unión Proteica , Proteínas/química , Proteínas/metabolismo , Oro/química
4.
Adv Biochem Eng Biotechnol ; 187: 1-35, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38273207

RESUMEN

Rapid detection of protein and small-molecule analytes is a valuable technique across multiple disciplines, but most in vitro testing of biological or environmental samples requires long, laborious processes and trained personnel in laboratory settings, leading to long wait times for results and high expenses. Fusion of recognition with reporter elements has been introduced to detection methods such as enzyme-linked immunoassays (ELISA), with enzyme-conjugated secondary antibodies removing one of the many incubation and wash steps. Chimeric protein switch biosensors go further and provide a platform for homogenous mix-and-read assays where long wash and incubation steps are eradicated from the process. Chimeric protein switch biosensors consist of an enzyme switch (the reporter) coupled to a recognition element, where binding of the analyte results in switching the activity of the reporter enzyme on or off. Several chimeric protein switch biosensors have successfully been developed for analytes ranging from small molecule drugs to large protein biomarkers. There are two main formats of chimeric protein switch biosensor developed, one-component and multi-component, and these formats exhibit unique advantages and disadvantages. Genetically fusing a recognition protein to the enzyme switch has many advantages in the production and performance of the biosensor. A range of immune and synthetic binding proteins have been developed as alternatives to antibodies, including antibody mimetics or antibody fragments. These are mainly small, easily manipulated proteins and can be genetically fused to a reporter for recombinant expression or manipulated to allow chemical fusion. Here, aspects of chimeric protein switch biosensors will be reviewed with a comparison of different classes of recognition elements and switching mechanisms.


Asunto(s)
Técnicas Biosensibles , Proteínas Recombinantes de Fusión , Técnicas Biosensibles/métodos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/química , Humanos
5.
Sens Diagn ; 3(1): 104-111, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38249540

RESUMEN

Concentration-therapeutic efficacy relationships have been observed for several therapeutic monoclonal antibodies (TmAb), where low circulating levels can result in ineffective treatment and high concentrations can cause adverse reactions. Rapid therapeutic drug monitoring (TDM) of TmAb drugs would provide the opportunity to adjust an individual patient's dosing regimen to improve treatment results. However, TDM for immunotherapies is currently limited to centralised testing methods with long sample-collection to result timeframes. Here, we show four point-of-care (PoC) TmAb biosensors by combining anti-idiotypic Affimer proteins and NanoBiT split luciferase technology at a molecular level to provide a platform for rapid quantification (<10 minutes) for four clinically relevant TmAb (rituximab, adalimumab, ipilimumab and trastuzumab). The rituximab sensor performed best with 4 pM limit of detection (LoD) and a quantifiable range between 8 pM-2 nM with neglectable matrix effects in serum up to 1%. After dilution of serum samples, the resulting quantifiable range for all four sensors falls within the clinically relevant range and compares favourably with the sensitivity and/or time-to-result of current ELISA standards. Further development of these sensors into a PoC test may improve treatment outcome and quality of life for patients receiving immunotherapy.

6.
J Chem Theory Comput ; 20(2): 513-531, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38157404

RESUMEN

Vibrational spectroscopy is an omnipresent spectroscopic technique to characterize functional nanostructured materials such as zeolites, metal-organic frameworks (MOFs), and metal-halide perovskites (MHPs). The resulting experimental spectra are usually complex, with both low-frequency framework modes and high-frequency functional group vibrations. Therefore, theoretically calculated spectra are often an essential element to elucidate the vibrational fingerprint. In principle, there are two possible approaches to calculate vibrational spectra: (i) a static approach that approximates the potential energy surface (PES) as a set of independent harmonic oscillators and (ii) a dynamic approach that explicitly samples the PES around equilibrium by integrating Newton's equations of motions. The dynamic approach considers anharmonic and temperature effects and provides a more genuine representation of materials at true operating conditions; however, such simulations come at a substantially increased computational cost. This is certainly true when forces and energy evaluations are performed at the quantum mechanical level. Molecular dynamics (MD) techniques have become more established within the field of computational chemistry. Yet, for the prediction of infrared (IR) and Raman spectra of nanostructured materials, their usage has been less explored and remain restricted to some isolated successes. Therefore, it is currently not a priori clear which methodology should be used to accurately predict vibrational spectra for a given system. A comprehensive comparative study between various theoretical methods and experimental spectra for a broad set of nanostructured materials is so far lacking. To fill this gap, we herein present a concise overview on which methodology is suited to accurately predict vibrational spectra for a broad range of nanostructured materials and formulate a series of theoretical guidelines to this purpose. To this end, four different case studies are considered, each treating a particular material aspect, namely breathing in flexible MOFs, characterization of defects in the rigid MOF UiO-66, anharmonic vibrations in the metal-halide perovskite CsPbBr3, and guest adsorption on the pores of the zeolite H-SSZ-13. For all four materials, in their guest- and defect-free state and at sufficiently low temperatures, both the static and dynamic approach yield qualitatively similar spectra in agreement with experimental results. When the temperature is increased, the harmonic approximation starts to fail for CsPbBr3 due to the presence of anharmonic phonon modes. Also, the spectroscopic fingerprints of defects and guest species are insufficiently well predicted by a simple harmonic model. Both phenomena flatten the potential energy surface (PES), which facilitates the transitions between metastable states, necessitating dynamic sampling. On the basis of the four case studies treated in this Review, we can propose the following theoretical guidelines to simulate accurate vibrational spectra of functional solid-state materials: (i) For nanostructured crystalline framework materials at low temperature, insights into the lattice dynamics can be obtained using a static approach relying on a few points on the PES and an independent set of harmonic oscillators. (ii) When the material is evaluated at higher temperatures or when additional complexity enters the system, e.g., strong anharmonicity, defects, or guest species, the harmonic regime breaks down and dynamic sampling is required for a correct prediction of the phonon spectrum. These guidelines and their illustrations for prototype material classes can help experimental and theoretical researchers to enhance the knowledge obtained from a lattice dynamics study.

7.
EClinicalMedicine ; 65: 102275, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38106553

RESUMEN

Background: Hypertension is a leading cause of morbidity and mortality worldwide, yet a substantial proportion of cases are undiagnosed. Understanding the scale of undiagnosed hypertension and identifying groups most at risk is important to inform approaches to detection. Methods: In this cross-sectional cohort study, we used data from the 2015 to 2019 Health Survey for England, an annual, cross-sectional, nationally representative survey. The survey follows a multi-stage stratified probability sampling design, involving a random sample of primary sampling units based on postcode sectors, followed by a random sample of postal addresses within these units. Within each selected household, all adults (aged ≥16 years) and up to four children, were eligible for participation. For the current study, individuals aged 16 years and over who were not pregnant and had valid blood pressure data were included in the analysis. The primary outcome was undiagnosed hypertension, defined by a measured blood pressure of 140/90 mmHg or above but no history of diagnosis. Age-adjusted prevalence of undiagnosed hypertension was estimated across sociodemographic and health-related characteristics, including ethnicity, region, rural-urban classification, relationship status, highest educational qualification, National Statistics Socio-Economic Classification (NS-SEC), Body Mass Index (BMI), self-reported general health, and smoking status. To assess the independent association between undiagnosed hypertension and each characteristic, we fitted a logistic regression model adjusted for sociodemographic factors. Findings: The sample included 21,476 individuals, of whom 55.8% were female and 89.3% reported a White ethnic background. An estimated 30.7% (95% confidence interval 29.0-32.4) of men with hypertension and 27.6% (26.1-29.1) of women with hypertension were undiagnosed. Younger age, lower BMI, and better self-reported general health were associated with an increased likelihood of hypertension being undiagnosed for men and women. Living in rural areas and in regions outside of London and the East of England were also associated with an increased likelihood of hypertension being undiagnosed for men, as were being married or in a civil partnership and having higher educational qualifications for women. Interpretation: Hypertension is commonly undiagnosed, and some of the groups that are at the lowest risk of hypertension are the most likely to be undiagnosed. Given the high lifetime risk of hypertension and its strong links with morbidity and mortality, our findings suggest a need for greater awareness of the potential for undiagnosed hypertension, including among those typically considered 'low risk'. Further research is needed to assess the impact of extending hypertension screening to lower-risk groups. Funding: None.

8.
Crim Behav Ment Health ; 33(6): 415-427, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37914961

RESUMEN

BACKGROUND: While there is empirical evidence to support associations between psychopathy scale ratings and offending or deviant behaviours, suggested as support for a unified theory of crime, evidence to date has been mainly from countries with high economic ratings and Western philosophies. In countries with a wide range of cultural groups and languages and a complex history of colonisation and apartheid, such scale ratings and correlations may differ. AIMS: To explore the psychometric properties of the Youth Psychopathic Traits Inventory-Short Version (YPI-S) and its applicability and relationship to deviant and actual or potential criminal behaviour among young adults in South Africa. METHODS: 18- to 20-year-olds from poor socio-economic backgrounds were recruited by a fieldworker with an existing relationship with community-based youth centres. Consenting participants completed the Deviant Behaviour Variety Scale, reflecting criminal or similar behaviours in the 12 months prior to rating and the YPI-S. Reliability measurements, principal factor analysis, Spearman's Rho correlations, chi square and multiple regression were used to explore performance of the YPI-S in this sample and relationship of YPI-S scores to deviancy. RESULTS: Of the 213 participants recruited, 176 completed all data points and were entered into analyses. The YPI-S was found to have generally good psychometric properties; however, in factor analysis, while items mapped well into an emotional subscale and quite well into an interpersonal scale, as in the original, behavioural items did not. Emotional, interpersonal and total YPI-S scores were significantly associated with reported deviant behaviour scores. CONCLUSION: The findings of this study suggest value in using the YPI-S with young people in South Africa to help identify those vulnerable to committing criminal acts. Among these disadvantaged young people, however, caution should be used in interpreting scores on its behavioural dimension. It is interesting that the emotional dimension, which incorporates perhaps the most personal features such as 'callous and unemotional traits' (albeit probably better considered as difficulty in recognising emotions in others), seemed most robust, suggesting that there may be core problems in a pathway to crime-or theory of crime-that transcend culture. This possibility, likely to be remediable through personal interventions, would benefit from further investigation.


Asunto(s)
Trastorno de Personalidad Antisocial , Adulto Joven , Humanos , Adolescente , Trastorno de Personalidad Antisocial/diagnóstico , Trastorno de Personalidad Antisocial/psicología , Psicometría , Sudáfrica , Reproducibilidad de los Resultados , Inventario de Personalidad
9.
BMC Pregnancy Childbirth ; 23(1): 782, 2023 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-37950165

RESUMEN

BACKGROUND: Social support during pregnancy can alleviate emotional and physical pressures, improving the well-being of mother and child. Understanding women's lived experiences and perceptions of social support during pregnancy is imperative to better support women. This systematic review explores and synthesises the qualitative research on women's experiences of social support during pregnancy. METHODS: Databases PubMed, CINAHL, MEDLINE, APA PsycInfo and Scopus were searched with no year limit. Eligible studies included pregnant women or women who were up to one year postpartum and were assessed on their experiences of social support during pregnancy. The data were synthesised using the thematic synthesis approach. RESULTS: Fourteen studies were included with data from 571 participating women across ten countries; two studies used focus groups, and 12 used interviews to collect their data. Four main themes were developed ('a variety of emotional support', 'tangible and intangible instrumental support', 'traditional rituals and spiritual support', and 'the all-encompassing natal home'), and six sub-themes ('female network connections', 'care and affection from the husband', 'dissatisfaction with relationships', 'financial support from the husband and family', 'practical support from family and friends', 'health information support'). CONCLUSIONS: This systematic review sheds light on women's experiences of social support during pregnancy. The results indicate a broad variety of emotional support experienced and valued by pregnant women from different sources. Additionally, women expressed satisfaction and dissatisfaction with tangible and intangible support forms. It was also highlighted that spirituality played an essential role in reducing stress and offering coping mechanisms for some, whereas spirituality increased stress levels for others.


Asunto(s)
Mujeres Embarazadas , Apoyo Social , Niño , Femenino , Embarazo , Humanos , Mujeres Embarazadas/psicología , Periodo Posparto , Madres/psicología , Investigación Cualitativa
10.
Angew Chem Int Ed Engl ; 62(45): e202312645, 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37723118

RESUMEN

CO2 hydrogenation to methanol has the potential to serve as a sustainable route to a wide variety of hydrocarbons, fuels and plastics in the quest for net zero. Synergistic Pd/In2 O3 (Palldium on Indium Oxide) catalysts show high CO2 conversion and methanol selectivity, enhancing methanol yield. The identity of the optimal active site for this reaction is unclear, either as a Pd-In alloy, proximate metals, or distinct sites. In this work, we demonstrate that metal-efficient Pd/In2 O3 species dispersed on Al2 O3 can match the performance of pure Pd/In2 O3 systems. Further, we follow the evolution of both Pd and In sites, and surface species, under operando reaction conditions using X-ray Absorption Spectroscpy (XAS) and infrared (IR) spectroscopy. In doing so, we can determine both the nature of the active sites and the influence on the catalytic mechanism.

11.
Biosens Bioelectron ; 237: 115488, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37419072

RESUMEN

Therapeutic monoclonal antibodies (TmAb) have emerged as effective treatments for a number of cancers and autoimmune diseases. However, large interpatient disparities in the pharmacokinetics of TmAb treatment requires close therapeutic drug monitoring (TDM) to optimise dosage for individual patients. Here we demonstrate an approach for achieving rapid, sensitive quantification of two monoclonal antibody therapies using a previously described enzyme switch sensor platform. The enzyme switch sensor consists of a ß-lactamase - ß-lactamase inhibitor protein (BLA-BLIP) complex with two anti-idiotype binding proteins (Affimer proteins) as recognition elements. The BLA-BLIP sensor was engineered to detect two TmAbs (trastuzumab and ipilimumab) by developing constructs incorporating novel synthetic binding reagents to each of these mAbs. Trastuzumab and ipilimumab were successfully monitored with sub nM sensitivity in up to 1% serum, thus covering the relevant therapeutic range. Despite the modular design, the BLA-BLIP sensor was unsuccessful in detecting two further TmAbs (rituximab and adalimumab), an explanation for which was explored. In conclusion, the BLA-BLIP sensors provide a rapid biosensor for TDM of trastuzumab and ipilimumab with the potential to improve therapy. The sensitivity of this platform alongside its rapid action would be suitable for bedside monitoring in a point-of-care (PoC) setting.


Asunto(s)
Técnicas Biosensibles , Monitoreo de Drogas , Humanos , Ipilimumab , Anticuerpos Monoclonales/uso terapéutico , Trastuzumab/uso terapéutico , Inmunoterapia
12.
Chem Soc Rev ; 52(11): 3599-3626, 2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37171037

RESUMEN

Carbohydrate diversity is foundational in the molecular literacy that regulates cellular function and communication. Consequently, delineating and leveraging this structure-function interplay continues to be a core research objective in the development of candidates for biomedical diagnostics. A totemic example is the ubiquity of 2-deoxy-2-[18F]-fluoro-D-glucose (2-[18F]-FDG) as a radiotracer for positron emission tomography (PET), in which metabolic trapping is harnessed. Building on this clinical success, more complex sugars with unique selectivities are gaining momentum in molecular recognition and personalised medicine: this reflects the opportunities that carbohydrate-specific targeting affords in a broader sense. In this Tutorial Review, key milestones in the development of 2-[18F]-FDG and related glycan-based radiotracers for PET are described, with their diagnostic functions, to assist in navigating this rapidly expanding field of interdisciplinary research.


Asunto(s)
Fluorodesoxiglucosa F18 , Radiofármacos , Radiofármacos/metabolismo , Tomografía de Emisión de Positrones/métodos , Carbohidratos , Glucosa
14.
Cancers (Basel) ; 15(3)2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36765816

RESUMEN

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30-40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood-brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.

15.
Health Promot J Austr ; 34(2): 294-302, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36625407

RESUMEN

ISSUE ADDRESSED: Speech-language pathologists (SLPs) may provide indirect services focusing on the promotion of rich communication environments in early childhood education centres. Evaluating children's outcomes following SLP-led professional development in early childhood education centres is challenging. The aim of this scoping review was to identify how child outcomes were measured in studies exploring SLP professional development in early childhood education. METHODS: A systematic search of seven databases was conducted to identify studies that included the provision of an indirect SLP service and measurement of child outcomes. Twelve studies were identified that met all inclusion criteria for the scoping review. Information about the research design, professional development training provided and child outcome measures collected were all extracted from the identified studies. RESULTS: Half of the identified studies relied on the direct assessment of child language and seven studies utilised video-recording of interactions between educators and child/ren in their care. CONCLUSIONS: Evaluating child outcomes following SLP professional development in early childhood education centres is not only challenging but also expensive. Considerations for the allocation of suitable resources to evaluate indirect services are discussed. SO WHAT?: SLPs may need to demonstrate the impact of indirect services focusing on health promotion through the evaluation of child outcomes. The findings of this investigation outline the challenges identifying appropriate tools to capture the outcomes of children.


Asunto(s)
Comunicación , Intervención Educativa Precoz , Niño , Preescolar , Humanos
16.
Front Behav Neurosci ; 16: 947396, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36187381

RESUMEN

Dreams may contribute to psychological adaptation by aiding in mood regulation. One way it could be achieved is through a desensitization process whereby negative events are replayed within the dream under lower conditions of negative emotionality. Evidence of this theory is supported by the tendency of dreamers to evaluate their emotions felt in their dreams more positively compared to an independent judge (i.e., positivity bias). Additionally, it has been observed that while dream emotions are typically more negative than pre-sleep emotions, morning emotions are more positive, suggesting that emotional regulation occurs overnight and may help improve mood in the morning. The present study aimed to examine the relationships between pre-sleep, dream, and morning mood and the potential desensitization function of remembered dreams as indicated by their effects on morning mood and stress. Methodology: Participants (N = 188; Mean age = 19.2, SD = 3.0) recorded their dreams (N = 345 dreams) and self-reported their stress and mood at bedtime, during their dream retrospectively, and upon waking. A judge also evaluated the subjects' dream moods. Subjects' positivity bias was defined as the difference between the subjects and the judge's evaluation of the positive emotions in the dream. Results: A MANOVA revealed that subjects perceived a higher level of positive emotions in their dreams compared to a judge. Multi-group path analysis revealed that some relationships between pre-sleep, dream, and morning emotions and stress differed in positive and negative dream nights. In both groups, the strongest predictors of morning mood and stress were pre-sleep mood and stress, respectively. The second strongest predictor of positive morning mood was the subjects' dream positivity bias. Conclusion: Results provide some support for the association of dreaming in mood regulation attributable to REM sleep. They also highlight that pathways implicated in mood regulation may be distinct from stress regulation.

17.
Front Psychiatry ; 13: 770380, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35308880

RESUMEN

Several studies have highlighted associations between adverse life events and the dysphoric character of dream experiences. This degree of continuity between waking-life and dream content seems partly attributed to the emotional and personal attachment linked to the incorporated waking experiences. Numerous changes in the processing of emotion-related stimuli are also reported across different human developmental stages. Therefore, we were interested in testing whether age would modulate the impact of recent troubling experiences on dream characteristics. Two hundred sixty participants, evenly distributed in five developmental stages, matched for gender and their exposure to a troubling experience, were selected from a large sample collected for a previous normative study of dreams of Canadians. Participants completed a dream questionnaire from which independent judges subsequently scored the dreams. We observed no interactions between the experience of troubling events and age. However, individuals who experienced a recent troubling event reported a higher frequency of nightmares and their dreams were more emotionally negative. Participants who experienced a moderately severe troubling event were also more likely to experience a dream whose maximal threat severity was of moderate intensity. Adolescents and young adults had dreams with a higher level of oneiric threats compared to older adults (>40 years old). Young adults also reported a higher frequency of nightmares compared to older adults. Our findings have implications for modern dream theories. They also suggest that dysphoric dreams might serve as potential proxies of mental health status and developmental stages. Future studies are now needed to explore the implications of these findings for psychological adaptation.

18.
J Org Chem ; 87(7): 4603-4616, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35302774

RESUMEN

A modular approach to prepare tri- and tetracyclic carbazoles by a sequential [3 + 2]heteroannulation is described. First, optimization of Pd-catalyzed Buchwald-Hartwig amination followed by C/N-arylation in a one-pot process is established. Second, mechanistic analyses identified the origins of chemo- and regioselective sequential control of both bond-forming steps. Finally, the substrate scope is demonstrated by the preparation of a range of tri- and tetracyclic carbazoles, including expedient access to several natural products and anti-cancer agents.


Asunto(s)
Carbazoles , Paladio , Aminación , Catálisis
19.
Child Abuse Negl ; 124: 105459, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35007971

RESUMEN

BACKGROUND: Adverse Childhood Experiences (ACEs) have been associated with a greater risk of later criminal offending. However, existing research in this area has been primarily conducted in Western developed countries and cross-cultural studies are rare. OBJECTIVES: This study examined the relationship between ACEs and criminal behaviors in young adults living in 10 countries located across five continents, after accounting for sex, age, and cross-national differences. PARTICIPANTS AND SETTING: In total, 3797 young adults aged between 18 and 20 years (M = 18.97; DP = 0.81) were assessed locally in community settings within the 10 countries. METHOD: The ACE Questionnaire was used to assess maltreatment and household dysfunction during childhood and a subset of questions derived from the Deviant Behavior Variety Scale (DBVS) was used to determine past-year criminal variety pertaining to 10 acts considered crime across participating countries. RESULTS: Physical and sexual abuse, physical neglect, and household substance abuse were related to criminal variety, globally, and independently across sexes and countries ranked differently in the United Nations Human Development Index (HDI). In addition, three out of five experiences of household dysfunction were related to criminal variety, but subsequent analyses indicate that some forms of household dysfunction only hold statistical significance among males or females, or in countries ranking lower in the HDI. CONCLUSIONS: This research strengthens the finding that there are cross-cultural mechanisms perpetuating the cycle of violence. It also indicates that forms of household dysfunction have an impact on criminal behavior that is shaped by gender and the country's levels of social well-being.


Asunto(s)
Experiencias Adversas de la Infancia , Maltrato a los Niños , Criminales , Delitos Sexuales , Adolescente , Adulto , Niño , Conducta Criminal , Femenino , Humanos , Masculino , Violencia , Adulto Joven
20.
Int J Speech Lang Pathol ; 24(4): 395-406, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-34651529

RESUMEN

Purpose: Brain tumour and leukaemia represent the most common childhood cancers and can result in communication and swallowing difficulties. The purpose of this study was to survey health professionals and consumers regarding the management of communication and swallowing difficulties in children with brain tumour or leukaemia (CBTL).Method: In this study participants completed a survey focussing on (1) communication and swallowing assessment and intervention, (2) multidisciplinary team (MDT) practices and (3) risk factors. Quantitative data were reported using descriptive statistics. Qualitative data were analysed using NVivo12 Qualitative Data Analysis Software.Result: Twenty-four participants were included (22 health professionals; two consumers). Most participants (≥80%) agreed that comprehensive and regular communication and swallowing assessments improved outcomes. Communication and swallowing interventions were reported to improve outcomes by 96% of participants. MDT care was considered essential in improving outcomes. Speech-language pathologists were the primary health professional identified in communication management; additional multidisciplinary health professionals were highlighted in swallowing management. Risk factors were identified across three categories: cancer-related, treatment-related and child-factors.Conclusion: This study collates the expertise and experience of multidisciplinary health professionals and consumers which can be used to guide assessment and intervention for communication and swallowing in CBTL. It also provides perspectives on MDT care and consideration of patient values and risk factors.


Asunto(s)
Neoplasias Encefálicas , Trastornos de Deglución , Leucemia , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Comunicación , Deglución , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Personal de Salud , Humanos , Leucemia/complicaciones
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