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1.
JMIR Nurs ; 7: e54561, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363595

RESUMO

BACKGROUND: Health care is highly complex and can be both emotionally and physically challenging. This can lead health care workers to develop compassion fatigue and burnout (BO), which can negatively affect their well-being and patient care. Higher levels of resilience can potentially prevent compassion fatigue and BO. Strategies that enhance resilience include gratitude, exercise, and mindfulness. OBJECTIVE: The purpose of this study was to determine if a 3-week daily resiliency practice, prompted via a gratitude, exercise, and mindfulness smartphone app, impacted the professional quality of life, physical activity, and happiness level of health care workers in a newborn intensive care unit setting. METHODS: In total, 65 participants from a level III newborn intensive care unit at a regional hospital in the western United States completed this study. The Professional Quality of Life Scale, Physical Activity Vital Sign, and Subjective Happiness Score instruments were used to evaluate the effects of the mobile health (mHealth) intervention. Further, 2-tailed dependent paired t tests were used to evaluate participant pre- and postintervention instrument scores. Multiple imputation was used to predict scores of participants who practiced an intervention but did not complete the 3 instruments post intervention. RESULTS: Dependent t tests using the original data showed that participants, as a whole, significantly improved in BO (t35=2.30, P=.03), secondary trauma stress (STS; t35=2.11, P=.04), and happiness (t35=-3.72, P<.001) scores. Compassion satisfaction (CS; t35=-1.94, P=.06) and exercise (t35=-1.71, P=.10) were trending toward, but did not reach, significance. Using the original data, only the gratitude intervention group experienced significant improvements (CS, BO, and happiness), likely due to the higher number of participants in this group. Analysis using imputed data showed that participants, as a whole, had significant improvements in all areas: CS (t64=-4.08, P<.001), BO (t64=3.39, P=.001), STS (t64=4.08, P<.001), exercise (t64=-3.19, P=.002), and happiness (t64=-3.99, P<.001). Looking at the intervention groups separately using imputed data, the gratitude group had significant improvements in CS, BO, STS, and happiness; the exercise group had significant improvements in STS and exercise; and the mindfulness group had significant improvements in CS and happiness. CONCLUSIONS: Phone app delivery of resilience-enhancing interventions is a potentially effective intervention model for health care workers. Potential barriers to mHealth strategies are the technical issues that can occur with this type of intervention. Additional longitudinal and experimental studies with larger sample sizes need to be completed to better evaluate this modality.

2.
Plants (Basel) ; 13(2)2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38256757

RESUMO

Atmospheric carbon dioxide (CO2) concentrations are increasing and may exceed 800 ppm by 2100. This is increasing global mean temperatures and the frequency and severity of heatwaves. Recently, we showed for the first time that the combination of short-term warming and elevated carbon dioxide (eCO2) caused extreme upward bending (i.e., hyponasty) of leaflets and leaf stems (petioles) in tomato (Solanum lycopersicum), which reduced growth. Here, we examined additional species to test the hypotheses that warming + eCO2-induced hyponasty is restricted to compound-leaved species, and/or limited to the Solanaceae. A 2 × 2 factorial experiment with two temperatures, near-optimal and supra-optimal, and two CO2 concentrations, ambient and elevated (400, 800 ppm), was imposed on similarly aged plants for 7-10 days, after which final petiole angles were measured. Within Solanaceae, compound-leaf, but not simple-leaf, species displayed increased hyponasty with the combination of warming + eCO2 relative to warming or eCO2 alone. In non-solanaceous species, hyponasty, leaf-cupping, and changes in leaf pigmentation as a result of warming + eCO2 were variable across species.

3.
Infant Ment Health J ; 45(1): 11-21, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38140832

RESUMO

Mothers of infants born extremely preterm requiring prolonged medical intervention in the Neonatal Intensive Care Unit (NICU) are at high risk of developing stress. Parent-administered infant massage is a well-established, safe intervention for preterm infants with many developmental benefits, but the published literature has mostly examined its impact on infants and parents through self-reported or observational measures of stress. The aim of this study was to measure salivary cortisol, a biomarker for stress, in extremely preterm infants and their mothers immediately pre and post parent-administered infant massage in order to detect potential changes in physiologic stress. Twenty-two mother-infant dyads completed massage education with a physical or occupational therapist. All dyads provided salivary cortisol samples via buccal swab immediately pre- and post-massage at the second session. Of mothers determined to be "cortisol responders" (15/22), salivary cortisol levels were lower after massage (pre-minus post-level: -26.47 ng/dL, [CI = -4.40, -48.53], p = .016, paired t-test). Our primary findings include a clinically significant decrease (as measured by percent change) in maternal cortisol levels immediately post parent-administered massage, indicating decreased physiological stress. Integration of infant massage into NICU clinical practice may support maternal mental health, but further powered studies are necessary to confirm findings.


Las madres de infantes nacidos extremadamente prematuros en la Unidad de Cuidado Intensivo Neonatal (NICU) se encentran bajo alto riesgo de desarrollar estrés. El masaje que una madre le da al infante es una intervención segura, bien establecida, para infantes prematuros, con muchos beneficios de desarrollo, aunque la información publicada disponible ha examinado por la mayor parte el impacto del masaje en los infantes y progenitores por medio de medidas de estrés auto reportadas o de observación. El propósito de este estudio fue medir el cortisol salival, un biomarcador de estrés, en infantes extremadamente prematuros y sus madres inmediatamente antes y después del masaje que la madre le da, para detectar posibles cambios en el estrés fisiológico. Veintidós díadas madre-infante completaron 2 sesiones educativas de masaje con un terapeuta físico u ocupacional. Todas las díadas aportaron muestras de cortisol salival por medio de hisopado bucal inmediatamente antes y después del masaje en la segunda sesión. Los niveles de cortisol en infantes no fueron suficientes para el análisis. De las madres a quienes se les determinó haber dado "respuesta de cortisol" (15/22), los niveles de cortisol salival fueron más bajos después del masaje (nivel antes menos nivel después: −26.47 ng/dL, [CI = −4.40, −48.53]. p = .016, prueba-t pareada). Entre nuestros resultados primarios se incluye una baja clínicamente significativa (tal como fue medida por el cambio porcentual) en los niveles de cortisol materno inmediatamente después del masaje. Estos resultados sugieren que el masaje dado por la madre a infantes prematuros pudiera reducir el cortisol materno, un marcador fisiológico de estrés.


Assuntos
Hidrocortisona , Lactente Extremamente Prematuro , Lactente , Feminino , Recém-Nascido , Humanos , Pais/psicologia , Mães/psicologia , Unidades de Terapia Intensiva Neonatal , Massagem/métodos
4.
Front Pharmacol ; 14: 1221905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818189

RESUMO

Background: Although many acute exacerbations of COPD (AECOPD) are triggered by non-bacterial causes, they are often treated with antibiotics. Preliminary research suggests that the Chinese herbal medicine "Shufeng Jiedu" (SFJD), may improve recovery and therefore reduce antibiotic use in patients with AECOPD. Aims: To assess the feasibility of conducting a randomised placebo-controlled clinical trial of SFJD for AECOPD in UK primary care. Methods: GPs opportunistically recruited patients experiencing an AECOPD. Participants were randomised 1:1 to usual care plus SFJD or placebo for 14 days. Participants, GPs and research nurses were blinded to treatment allocation. GPs could prescribe immediate, delayed or no antibiotics, with delayed prescribing encouraged where appropriate. Participants were asked to complete a participant diary, including EXACT-PRO and CAT™ questionnaires for up to 4 weeks. Outcomes included recruitment rate and other measures of study feasibility described using only descriptive statistics and with no formal comparisons between groups. We also conducted qualitative interviews with recruited and non-recruited COPD patients and clinicians, analysed using framework analysis. Results: Over 6 months, 19 participants (6 SFJD, 13 placebo) were recruited. Sixteen (84%) participants returned diaries or provided a diary by recall. Overall, 1.3 participants were recruited per 1,000 patients on the COPD register per month open. Median duration of treatment was 9.8 days in the intervention group vs 13.3 days in the placebo group. The main reason for discontinuation in both groups was perceived side-effects. in both groups. Point estimates for both the EXACT-PRO and CAT™ outcomes suggested possible small benefits of SFJD. Most patients and clinicians were happy to try SFJD as an alternative to antibiotics for AECOPD. Recruitment was lower than expected because of the short recruitment period, the lower incidence of AECOPD during the COVID-19 pandemic, patients starting antibiotics from "rescue packs" before seeing their GP, and workforce challenges in primary care. Conclusion: Recruitment was impaired by the COVID-19 pandemic. Nevertheless, we were able to demonstrate the feasibility of recruiting and randomising participants and identified approaches to address recruitment challenges such as including the trial medication in COPD patients' "rescue packs" and delegating recruitment to a central trials team. Clinical Trial Registration: Identifier, ISRCTN26614726.

5.
Transl Vis Sci Technol ; 12(9): 20, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37750746

RESUMO

Purpose: To evaluate the efficacy of topical losartan after blast injury-simulating irregular phototherapeutic keratectomy (PTK) in rabbits. Methods: Twelve NZW rabbits underwent 100 pulse 6.5 mm diameter PTK over a metal screen to generate severe surface irregularity and inhibit epithelial basement membrane regeneration. Corneas were treated with 0.8 mg/mL losartan in balanced salt solution (BSS) or BSS 50 µL six times per day for six weeks after PTK. All corneas had slit lamp photography, with and without 1% fluorescein at two, four, and six weeks after PTK, and were analyzed using immunohistochemistry for the myofibroblast marker α-smooth muscle actin (α-SMA), keratocyte marker keratocan, mesenchymal cell marker vimentin, transforming growth factor (TGF)-ß1, and collagen type IV. Results: Topical 0.8 mg/mL losartan six times a day significantly decreased anterior stromal α-SMA intensity units compared to BSS at six weeks after anterior stromal irregularity-inducing screened PTK (P = 0.009). Central corneal opacity, however, was not significantly different between the two groups. Keratocan, vimentin, TGF-ß1, or collagen type IV levels in the anterior stroma were not significantly different between the two groups. Conclusions: Topical losartan effectively decreased myofibroblast generation after surface blast simulation irregular PTK. However, these results suggest initial masking-smoothing PTK, along with adjuvant topical losartan therapy, may be needed to decrease corneal stromal opacity after traumatic injuries that produce severe surface irregularity. Translational Relevance: Topical losartan decreased scar-producing stromal myofibroblasts after irregular PTK over a metal screen but early smoothing of irregularity would also likely be needed to significantly decrease corneal opacity.


Assuntos
Opacidade da Córnea , Losartan , Coelhos , Animais , Losartan/farmacologia , Miofibroblastos , Vimentina , Colágeno Tipo IV , Opacidade da Córnea/tratamento farmacológico
6.
Environ Res ; 234: 116524, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37390952

RESUMO

The study investigated water treatment sludge (WTS) as a phosphorus (P) adsorbent and examined the release of organic matter during the P adsorption process. Previous studies indicated that WTS is an effective adsorbent for P but also releases organic matter, which may affect the organoleptic properties of treated water, but no study has characterised organic release and conducted an in-depth study on its behaviours. This study characterised the organic release during the P adsorption process from four different WTS samples. This study also offers results from a 60-day column experiment that indicate that WTS columns effectively removed the majority of P from the 2 mg/L feed solution. The total organic carbon (TOC) release was gradually reduced from 24.9 mg/L on day 1 to stable levels of 4.4 mg/L to 4.1 mg/L from day 22 onwards. After 60 days, when the organic matter was nearly exhausted, WTS columns were still effective in P adsorption from the solution. In addition, the thermal treatment of WTS at different temperatures was investigated to reduce TOC release and increase P adsorption. The results showed that thermal treatment not only minimized TOC release but also enhanced the P adsorption capacity of the sludge. In a 24-h batch experiment, WTS treated at 600 °C showed the highest P adsorption (1.7 mg/g) with negligible TOC release when compared to sludge treated at 500 °C WTS (1.2 mg/g), 700 °C WTS (1.5 mg/g) and dried WTS (0.75 mg/g). However, the release of inorganic compounds slightly increased after thermal treatment. Future studies could focus on determining whether the thermal processing of WTS which can enhance the WTS's adsorption to emerging pollutants like per- and poly-fluoroalkyl substances and other contaminants. The findings of this study could influence the management practices of water authorities and contribute to the water sector's sustainability objectives.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Esgotos , Poluentes Químicos da Água/análise , Adsorção , Fósforo , Purificação da Água/métodos
7.
Pilot Feasibility Stud ; 8(1): 262, 2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36536462

RESUMO

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a major reason for consultations in primary care, hospital admissions, deterioration in function, and mortality. Despite the majority of exacerbations not being caused by bacteria, as many as 70% of patients who present in UK primary care with AECOPD are prescribed antibiotics as part of standard care. However, finding effective non-antibiotic treatments for COPD exacerbations is a priority to reduce antibiotic use. The Chinese herbal medicine Shufeng Jiedu® (SFJD) has the potential to reduce treatment failure and duration of hospital stay. This study aims to determine the feasibility of conducting a fully powered randomised, double blind, placebo-controlled clinical trial on SFJD for AECOPD in UK primary care. METHODS: This study is a phase III, two-arm individually double blind, randomised, placebo-controlled feasibility trial with nested qualitative study, coordinated by the Southampton Clinical Trial Unit (SCTU). Patients aged ≥ 40 years, with a current AECOPD, presenting with increased sputum purulence/volume, or breathlessness, and for whom the GP is considering use of antibiotics, will be eligible to participate. We aim to recruit seven eligible participants per month and randomise them to receive either the patent Chinese herbal medicine SFJD capsules or placebo for 14 consecutive days and to follow-up for 12 weeks. The primary outcomes include the feasibility of recruitment, study retention, and the percentage of diary completion. DISCUSSION: If this trial demonstrates the feasibility of recruitment, delivery, and follow-up, we will seek funding for a fully powered placebo-controlled trial of SFJD for the treatment of AECOPD in primary care. TRIAL REGISTRATION: This trial is registered via ISRCTN on 1 July 2021, identifier: ISRCTN26614726.

8.
J Geriatr Oncol ; 13(8): 1103-1110, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35973916

RESUMO

INTRODUCTION: Specialized palliative care (SPC) is beneficial towards end of life because of its holistic approach to improve quality of life and comfort of patients and their families. Few studies have described how patient age, sex, comorbidities, and socioeconomic status (SES) are associated with SPC use in nonselective populations who die of cancer. This study aimed to evaluate the use of SPC in the year preceding death by all Norwegian individuals with a recent cancer diagnosis who died of cancer. MATERIALS AND METHODS: From nationwide registries, we identified patients with a recent (<5 years) cancer diagnosis who died during 2010-2014. Using binary logistic regression models, we estimated the probability of receiving hospital-based SPC during the last year of life according to individual (age, sex, comorbidity), cancer (stage, type, and months since diagnosis), and SES (e.g., living alone, household income, and education) characteristics. RESULTS: The analytical sample contained 45,521 patients with a median age at death of 75 years; 46% were women. The probability of receiving hospital-based SPC in the total cohort was 0.43 (95% confidence interval [CI] 0.42-0.43). Use of SPC was higher if patients were younger, female, had limited comorbidity, metastatic disease, had one the following cancer types: colorectal, pancreatic, bladder, kidney, or gastric, were diagnosed more than six months before death, and had higher SES. Adjusted model results suggested that the probability of using SPC in the last year of life for patients aged 80-89 years was 0.31 (95% CI 0.30-0.32), compared to a probability of 0.63 (95% CI 0.61-0.65) for patients aged 50-59 years. For patients ≥90 years, the probability was 0.16 (95% CI 0.15-0.18). DISCUSSION: Less hospital-based SPC use among older patients, males, and those with lower SES indicates possible under-treatment in these groups. Future studies should be designed to determine the underlying reasons for these observed differences.


Assuntos
Neoplasias , Cuidados Paliativos , Masculino , Humanos , Feminino , Idoso , Qualidade de Vida , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias/diagnóstico , Sistema de Registros , Estudos de Coortes
9.
Support Care Cancer ; 30(4): 3131-3140, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34877613

RESUMO

PURPOSE: The purpose of this study is to investigate changes over time in quality of life (QoL) in incurable lung cancer patients and the impact of determinants like molecular alterations (MA). METHODS: In a prospective, longitudinal, multicentric study, we assessed QoL, symptom burden, psychological distress, unmet needs, and prognostic understanding of patients diagnosed with incurable lung cancer at the time of the diagnosis (T0) and after 3 (T1), 6 (T2) and 12 months (T3) using validated questionnaires like FACT-L, National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT), PHQ-4, SCNS-SF-34, and SEIQoL. RESULTS: Two hundred seventeen patients were enrolled, 22 (10%) with reported MA. QoL scores improved over time, with a significant trend for DT, PHQ-4, and SCNS-SF-34. Significant determinants for stable or improving scores over time were survival > 6 months, performance status at the time of diagnosis, and presence of MA. Patients with MA showed better QoL scores (FACT-L at T1 104.4 vs 86.3; at T2 107.5 vs 90.0; at T3 100.9 vs 92.8) and lower psychological distress (NCCN DT at T1 3.3 vs 5; at T2 2.7 vs 4.5; at T3 3.7 vs 4.5; PHQ-4 at T1 2.3 vs 4.1; at T2 1.7 vs 3.6; at T3 2.2 vs 3.6), but also a worsening of the scores at 1 year and a higher percentage of inaccurate prognostic understanding (27 vs 17%) compared to patients without MA. CONCLUSION: Patients with tumors harboring MA are at risk of QoL deterioration during the course of the disease. Physicians should adapt their communication strategies in order to maintain or improve QoL.


Assuntos
Neoplasias Pulmonares , Qualidade de Vida , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Estudos Prospectivos , Qualidade de Vida/psicologia , Inquéritos e Questionários
11.
Schizophr Res ; 243: 372-382, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34187732

RESUMO

Deficits in early auditory information processing contribute to cognitive and psychosocial disability; this has prompted development of interventions that target low-level auditory processing, which may alleviate these disabilities. The frequency following response (FFR) is a constellation of event-related potential and frequency characteristics that reflect the processing of acoustic stimuli at the level of the brainstem and ascending portions of the auditory pathway. While FFR is a promising candidate biomarker of response to auditory-based cognitive training interventions, the psychometric properties of FFR in schizophrenia patients have not been studied. Here we assessed the psychometric reliability and magnitude of group differences across 18 different FFR parameters to determine which of these parameters demonstrate adequate internal consistency. Electroencephalography from 40 schizophrenia patients and 40 nonpsychiatric comparison subjects was recorded during rapid presentation of an auditory speech stimulus (6000 trials). Patients showed normal response amplitudes but longer latencies for most FFR peaks and lower signal-to-noise ratios (SNRs) than healthy subjects. Analysis of amplitude and latency estimates of peaks, however, indicated a need for a substantial increase in task length to obtain internal consistency estimates above 0.80. In contrast, excellent internal consistency (>0.95) was shown for FFR sustained responses. Only SNR scores reflecting the FFR sustained response yielded significant group differences and excellent internal consistency, suggesting that this measure is a viable candidate for use in clinical treatment studies. The present study highlights the use of internal consistency estimates to select FFR characteristics for use in future intervention studies interested in individual differences among patients.


Assuntos
Esquizofrenia , Percepção da Fala , Estimulação Acústica , Biomarcadores , Cognição , Eletroencefalografia , Humanos , Reprodutibilidade dos Testes , Esquizofrenia/terapia , Percepção da Fala/fisiologia
12.
Psychiatry Res ; 305: 114239, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34673326

RESUMO

Neurophysiological biomarkers of auditory processing show promise predicting outcomes following auditory-based targeted cognitive training (TCT) in schizophrenia, but the viability of the frequency following response (FFR) as a biomarker has yet to be examined, despite its ecological and face validity for auditory-based interventions. FFR is an event-related potential (ERP) that reflects early auditory processing. We predicted that schizophrenia patients would show acute- and longer-term FFR malleability in the context of TCT. Patients were randomized to either TCT (n = 30) or treatment as usual (TAU; n = 22), and electroencephalography was recorded during rapid presentation of an auditory speech stimulus before treatment, after one hour of training, and after 30 h of training. Whereas patients in the TCT group did not show changes in FFR after training, amplitude reductions were observed in the TAU. FFR was positively associated with performance on a measure of single word-in-noise perception in the TCT group, and with a measure of sentence-in-noise perception in both groups. Psychometric reliability analyses of FFR scores indicated high internal consistency but low one-hour and 12-week test-rest reliability. These findings support the dissociation between measures of speech discriminability along the hierarchy of cortical and subcortical early auditory information processing in schizophrenia.


Assuntos
Transtornos Cognitivos , Esquizofrenia , Percepção da Fala , Estimulação Acústica , Percepção Auditiva/fisiologia , Biomarcadores , Cognição , Transtornos Cognitivos/complicações , Eletroencefalografia , Humanos , Reprodutibilidade dos Testes , Esquizofrenia/complicações , Esquizofrenia/terapia , Percepção da Fala/fisiologia
13.
Respiration ; 100(12): 1165-1173, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34384085

RESUMO

BACKGROUND: Lung-sparing cytoreductive surgery by extended pleurectomy and decortication (EPD) in combination with hyperthermic intrathoracic chemoperfusion (HITOC) forms a promising treatment strategy for malignant pleural mesothelioma and recurrent pleural thymic malignancies. OBJECTIVES: The objective of this study was to scrutinize the surgical procedure and perioperative patient management with emphasis on perioperative morbidity and local tumor control. METHODS: In 2014, a standardized EPD and HITOC procedure was implemented at the Thoraxklinik Heidelberg. This retrospective analysis included clinical data of consecutive patients with pleural mesothelioma and pleural metastasized malignancies treated by EPD and HITOC. The surgical procedure, perioperative management, lung function data, and progression-free survival (PFS) were analyzed. RESULTS: In the time range between April 2, 2014 and July 2018, 76 patients with pleural malignancies have been treated with EPD and HITOC, and were analyzed retrospectively. It included 61 patients with pleural mesothelioma and 15 patients with pleural metastases of thymic malignancies (12), non-small cell lung cancer (1), colorectal carcinoma (1), and sarcoma (1). Perioperative morbidity following EPD and HITOC treatments represented 23.7% of overall malignancies, while 30- and 90-day mortality were 0 and 1.3%, respectively. Median PFS lasted 18.4 months for mesothelioma and 72.2 months for thymic malignancies. CONCLUSION: Combining EPD with HITOC can be performed in patients with either pleural mesothelioma or pleural metastases resulting in low perioperative morbidity and mortality as well as remarkable local tumor control.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Hipertermia Induzida , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurais , Cirurgia Torácica , Neoplasias do Timo , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Neoplasias Pulmonares/terapia , Mesotelioma/cirurgia , Recidiva Local de Neoplasia , Neoplasias Pleurais/cirurgia , Estudos Retrospectivos , Neoplasias do Timo/patologia , Resultado do Tratamento
14.
J Med Chem ; 64(9): 5905-5930, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33904304

RESUMO

There is an urgent need for new treatments for visceral leishmaniasis (VL), a parasitic infection which impacts heavily large areas of East Africa, Asia, and South America. We previously reported on the discovery of GSK3494245/DDD01305143 (1) as a preclinical candidate for VL and, herein, we report on the medicinal chemistry program that led to its identification. A hit from a phenotypic screen was optimized to give a compound with in vivo efficacy, which was hampered by poor solubility and genotoxicity. The work on the original scaffold failed to lead to developable compounds, so an extensive scaffold-hopping exercise involving medicinal chemistry design, in silico profiling, and subsequent synthesis was utilized, leading to the preclinical candidate. The compound was shown to act via proteasome inhibition, and we report on the modeling of different scaffolds into a cryo-EM structure and the impact this has on our understanding of the series' structure-activity relationships.


Assuntos
Desenho de Fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/química , Proteínas de Protozoários/metabolismo , Animais , Antiprotozoários/química , Antiprotozoários/metabolismo , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Sítios de Ligação , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Meia-Vida , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/metabolismo , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Camundongos , Simulação de Dinâmica Molecular , Complexo de Endopeptidases do Proteassoma/química , Inibidores de Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Inibidores de Proteassoma/uso terapêutico , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo , Proteínas de Protozoários/química , Piridinas/química , Piridinas/metabolismo , Piridinas/farmacologia , Piridinas/uso terapêutico , Solubilidade , Relação Estrutura-Atividade
15.
Oncologist ; 26(6): e1058-e1065, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33687742

RESUMO

BACKGROUND: Although current guidelines advocate early integration of palliative care, symptom burden and palliative care needs of patients at diagnosis of incurable cancer and along the disease trajectory are understudied. MATERIAL AND METHODS: We assessed distress, symptom burden, quality of life, and supportive care needs in patients with newly diagnosed incurable cancer in a prospective longitudinal observational multicenter study. Patients were evaluated using validated self-report measures (National Comprehensive Cancer Network Distress Thermometer [DT], Functional Assessment of Cancer Therapy [FACT], Schedule for the Evaluation of Individual Quality of Life [SEIQoL-Q], Patients Health Questionnaire-4 [PHQ-4], modified Supportive Care Needs Survey [SCNS-SF-34]) at baseline (T0) and at 3 (T1), 6 (T2), and 12 months (T3) follow-up. RESULTS: From October 2014 to October 2016, 500 patients (219 women, 281 men; mean age 64.2 years) were recruited at 20 study sites in Germany following diagnosis of incurable metastatic, locally advanced, or recurrent lung (217), gastrointestinal (156), head and neck (55), gynecological (57), and skin (15) cancer. Patients reported significant distress (DT score ≥ 5) after diagnosis, which significantly decreased over time (T0: 67.2%, T1: 51.7%, T2: 47.9%, T3: 48.7%). The spectrum of reported symptoms was broad, with considerable variety between and within the cancer groups. Anxiety and depressiveness were most prevalent early in the disease course (T0: 30.8%, T1: 20.1%, T2: 14.7%, T3: 16.9%). The number of patients reporting unmet supportive care needs decreased over time (T0: 71.8 %, T1: 61.6%, T2: 58.1%, T3: 55.3%). CONCLUSION: Our study confirms a variable and mostly high symptom burden at the time of diagnosis of incurable cancer, suggesting early screening by using standardized tools and underlining the usefulness of early palliative care. IMPLICATIONS FOR PRACTICE: A better understanding of symptom burden and palliative care needs of patients with newly diagnosed incurable cancer may guide clinical practice and help to improve the quality of palliative care services. The results of this study provide important information for establishing palliative care programs and related guidelines. Distress, symptom burden, and the need for support vary and are often high at the time of diagnosis. These findings underscore the need for implementation of symptom screening as well as early palliative care services, starting at the time of diagnosis of incurable cancer and tailored according to patients' needs.


Assuntos
Neoplasias , Cuidados Paliativos , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/terapia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
16.
J Nutr ; 151(4): 902-910, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33561256

RESUMO

BACKGROUND: Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. OBJECTIVES: We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. METHODS: Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-α concentrations, gut microbiota, and liver TNF-α and fatty acid synthase (Fasn) mRNA concentrations were assessed. RESULTS: F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P < 0.001) independent of impact on weight, whereas no difference was found between Ath + FV and CON groups in these 2 pathologic markers. Furthermore, F&V supplementation prevented Ath diet-induced dyslipidemia (high concentrations of serum TG and VLDL cholesterol and lower concentrations of HDL cholesterol), reduced serum TNF-α concentration (by 21.5%), suppressed mRNA expression of liver TNF-α and Fasn, and ameliorated Ath-induced gut microbiota dysbiosis. CONCLUSIONS: Our results indicate that consuming a large quantity and variety of F&Vs causally attenuates diet-induced atherosclerosis and hepatic steatosis in mice. These effects of F&Vs are associated with, and may be mediated through, improved atherogenic dyslipidemia, alleviated gut dysbiosis, and suppressed inflammation.


Assuntos
Aterosclerose/dietoterapia , Aterosclerose/prevenção & controle , Frutas , Receptores de LDL/deficiência , Verduras , Animais , Aterosclerose/etiologia , Dieta Aterogênica/efeitos adversos , Suplementos Nutricionais , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Fatores de Risco de Doenças Cardíacas , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Receptores de LDL/genética , Fator de Necrose Tumoral alfa/sangue , Aumento de Peso
17.
BMJ Open Sport Exerc Med ; 7(1): e000935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500785

RESUMO

PURPOSE: To determine whether supplementation with turmeric or curcumin extract effects pain and physical function in individuals with knee osteoarthritis (OA). Second, we investigated the therapeutic response (pain and function) of turmeric compared with non-steroidal anti-inflammatory drugs (NSAIDs). METHODS: A search was conducted in MEDLINE, Embase, CINAHL and Cochrane Review. Inclusion criteria included randomised controlled trials reporting pain and physical function in humans with knee OA comparing turmeric therapy with NSAIDs or no therapy. Two reviewers screened 5273 abstracts. Risk of bias and quality were assessed via Cochrane Collaboration tool and CONSORT (Consolidated Standards of Reporting Trials) 2010, respectively. RESULTS: Ten studies were included in the final analysis. Eight had high methodological quality and two were categorised as good with a mean CONSORT quality score of 21.1. Nine studies had adequate sequence generation and six had adequate allocation concealment. Participants and outcome assessors were blinded in eight studies. Three of the studies compared turmeric therapy to NSAIDs. All 10 studies showed improvement in pain and function from baseline with turmeric therapy (p≤0.05). In three studies comparing turmeric to NSAIDs, there were no differences in outcome scores (p>0.05). In all studies there were no significant adverse events in the turmeric therapy group. CONCLUSION: Compared with placebo, there appears to be a benefit of turmeric on knee OA pain and function. Based on a small number of studies the effects are similar to that of NSAIDs. Variables such as optimal dosing, frequency and formulation remain unclear at this time.

18.
Schizophr Res ; 228: 280-287, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33493776

RESUMO

BACKGROUND: Schizophrenia patients show widespread deficits in neurocognitive, clinical, and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are robust translational biomarkers associated with schizophrenia and associated with cognitive dysfunction, negative symptom severity, and psychosocial disability. Although these biomarkers are conceptually linked as measures of early auditory information processing, it is unclear whether MMN and gamma-band ASSR account for shared vs. non-shared variance in cognitive, clinical, and psychosocial functioning. METHODS: Multiple regression analyses with MMN, gamma-band ASSR, and clinical measures were performed in large cohorts of schizophrenia outpatients (N = 428) and healthy comparison subjects (N = 283). RESULTS: Reduced MMN (d = 0.67), gamma-band ASSR (d = -0.40), and lower cognitive function were confirmed in schizophrenia patients. Regression analyses revealed that reduced MMN amplitude showed unique associations with lower verbal learning and negative symptoms, reduced gamma-band ASSR showed a unique association with working memory deficits, and both reduced MMN amplitude and reduced gamma-band ASSR showed an association with daily functioning impairment in schizophrenia patients. CONCLUSION: MMN and ASSR measures are non-redundant and complementary measures of early auditory information processing that are associated with important domains of functioning. Studies are needed to clarify the neural substrates of MMN and gamma-band ASSR to improve our understanding of the pathophysiology of schizophrenia and accelerate their use in the development of novel therapeutic interventions.


Assuntos
Esquizofrenia , Estimulação Acústica , Percepção Auditiva , Cognição , Eletroencefalografia , Potenciais Evocados Auditivos , Humanos , Memória de Curto Prazo , Esquizofrenia/complicações
19.
J Psychiatr Res ; 132: 174-181, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33126011

RESUMO

OBJECTIVE: Wisdom has gained increasing interest among researchers as a personality trait relevant to well-being and mental health. We previously reported development of a new 24-item San Diego Wisdom Scale (SD-WISE), with good to excellent psychometric properties, comprised of six subscales: pro-social behaviors, emotional regulation, self-reflection (insight), tolerance for divergent values (acceptance of uncertainty), decisiveness, and social advising. There is controversy about whether spirituality is a marker of wisdom. The present cross-sectional study sought to address that question by developing a new SD-WISE subscale of spirituality and examining its associations with various relevant measures. METHODS: Data were collected from a national-level sample of 1,786 community-dwelling adults age 20-82 years, as part of an Amazon M-Turk cohort. Participants completed the 24-item SD-WISE along with several subscales of a commonly used Brief Multidimensional Measure of Religiousness/Spirituality, along with validated scales for well-being, resilience, happiness, depression, anxiety, loneliness, and social network. RESULTS: Using latent variable models, we developed a Spirituality subscale, which demonstrated acceptable psychometric properties including a unidimensional factor structure and good reliability. Spirituality correlated positively with age and was higher in women than in men. The expanded 28-item, 7-subscale SD-WISE total score (called the Jeste-Thomas Wisdom Index or JTWI) demonstrated acceptable psychometric properties. The Spirituality subscale was positively correlated with good mental health and well-being, and negatively correlated with poor mental health. However, compared to other components of wisdom, the Spirituality factor showed weaker (i.e., small-to-medium vs. medium-to-large) association with the SD-WISE higher-order Wisdom factor (JTWI). CONCLUSION: Similar to other components as well as overall wisdom, spirituality is significantly associated with better mental health and well-being, and may add to the predictive utility of the total wisdom score. Spirituality is, however, a weaker contributor to overall wisdom than components like pro-social behaviors and emotional regulation. Longitudinal studies of larger and more diverse samples are needed to explore mediation effects of these constructs on well-being and health.


Assuntos
Solidão , Espiritualidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
20.
Chemistry ; 26(29): 6652-6661, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32159249

RESUMO

The preparation of an entirely supramolecular, multichromophoric azaborondipyrromethene (ABDP)/zinc tetraphenylporphyrin (ZnTPP)/exfoliated graphene (GR) nanoensemble was accomplished. The ABDP derivative bears glycol chains for enhancing solubility and a pyridine functionality for allowing coordination with ZnTPP. The ABDP/ZnTPP/GR nanoensemble was characterized in terms of morphology and composition by using complementary microscopy imaging, thermogravimetric analysis, Raman as well as steady-state and time-resolved absorption and emission spectroscopy. The photophysical and electrochemical assessment of ABDP/ZnTPP/GR as well as the binding properties of the ABDP/ZnTPP complex, employed as a reference, are presented. Energy and electron transfer events were observed in ABDP/ZnTPP upon photoexcitation. However, in the case of ABDP/ZnTPP/GR, the graphene-induced aggregation of the chromophores alters their electronic interactions, enhancing the energy/electron transfer process between them.

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