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2.
Front Oncol ; 14: 1428182, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015503

RESUMO

Introduction: While Immune checkpoint inhibition (ICI) therapy shows significant efficacy in metastatic melanoma, only about 50% respond, lacking reliable predictive methods. We introduce a panel of six proteins aimed at predicting response to ICI therapy. Methods: Evaluating previously reported proteins in two untreated melanoma cohorts, we used a published predictive model (EaSIeR score) to identify potential proteins distinguishing responders and non-responders. Results: Six proteins initially identified in the ICI cohort correlated with predicted response in the untreated cohort. Additionally, three proteins correlated with patient survival, both at the protein, and at the transcript levels, in an independent immunotherapy treated cohort. Discussion: Our study identifies predictive biomarkers across three melanoma cohorts, suggesting their use in therapeutic decision-making.

3.
J Pharm Pharmacol ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016304

RESUMO

OBJECTIVES: This study aims to evaluate the effects of Croton grewioides essential oil (CGEO) and anethole on follicle survival, growth, and oxidative stress in cultured bovine ovarian tissues. METHODS: Ovarian tissues were cultured for 6 days in a medium supplemented with different concentrations (1, 10, 100, or 1000 µg mL-1) of CGEO or anethole and then, follicular survival and growth, collagen content, and stromal cell density in ovarian tissues cultured in vitro were evaluated by histology. The mRNA levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase 1 (GPX1), peroxirredoxin 6 (PRDX6), and nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated by real-time PCR. The activity of SOD, CAT, glutathione peroxidase (GPx), and thiol concentrations were investigated. KEY FINDINGS: Ovarian tissues cultured with 1 µg mL-1 CGEO or anethole had a higher percentage of healthy follicles than those cultured in a control medium (P < .05). The 1 µg mL-1 CGEO also increased the number of stromal cells, collagen fibers, and thiol levels. Anethole (1 µg mL-1) increased CAT activity and reduced that of GPx. The activity of SOD was reduced by CGEO. In contrast, 1 µg mL-1 anethole reduced mRNA for CAT, PRDX1, and NRF2 (P < .05). In addition, 1 µg mL-1 CGEO reduced mRNA for CAT, PRDX6, and GPx1 (P < .05). CONCLUSIONS: The presence of 1 µg mL-1 anethole or CGEO in a culture medium promotes follicle survival and regulates oxidative stress and the expression of mRNA and activity of antioxidant enzymes in cultured bovine ovarian tissues.

4.
Vopr Virusol ; 69(2): 175-186, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38843023

RESUMO

INTRODUCTION: The COVID-19 pandemic caused by SARS-CoV-2 has created serious health problems worldwide. The most effective way to prevent the occurrence of new epidemic outbreaks is vaccination. One of the modern and effective approaches to vaccine development is the use of virus-like particles (VLPs). The aim of the study is to develop a technology for production of VLP based on recombinant SARS-CoV-2 proteins (E, M, N and S) in insect cells. MATERIALS AND METHODS: Synthetic genes encoding coronavirus proteins E, M, N and S were used. VLP with various surface proteins of strains similar to the Wuhan virus, Delta, Alpha and Omicron were developed and cloned into the pFastBac plasmid. The proteins were synthesized in the baculovirus expression system and assembled into VLP in the portable Trichoplusia ni cell. The presence of insertion in the baculovirus genome was determined by PCR. ELISA and immunoblotting were used to study the antigenic activity of VLP. VLP purification was performed by ultracentrifugation using 20% sucrose. Morphology was assessed using electron microscopy and dynamic light scattering. RESULTS: VLPs consisting of recombinant SARS-CoV-2 proteins (S, M, E and N) were obtained and characterized. The specific binding of antigenic determinants in synthesized VLPs with antibodies to SARS-CoV-2 proteins has been demonstrated. The immunogenic properties of VLPs have been studied. CONCLUSION: The production and purification of recombinant VLPs consisting of full-length SARS-CoV-2 proteins with a universal set of surface antigens have been developed and optimized. Self-assembling particles that mimic the coronavirus virion induce a specific immune response against SARS-CoV-2.


Assuntos
Baculoviridae , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinas de Partículas Semelhantes a Vírus , Animais , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/metabolismo , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Humanos , COVID-19/virologia , COVID-19/imunologia , Baculoviridae/genética , Baculoviridae/metabolismo , Vacinas contra COVID-19/imunologia , Anticorpos Antivirais/imunologia , Proteínas M de Coronavírus/genética , Proteínas M de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/imunologia , Fosfoproteínas
5.
Am J Ophthalmol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942228

RESUMO

PURPOSE: Pan-retinal photocoagulation (PRP) is the mainstay of treatment for proliferative diabetic retinopathy (PDR), reducing the risk of severe vision loss. Pain poses a potential obstacle to effective laser delivery and patient compliance. Therefore, implementing pain relief strategies can enhance both treatment efficacy and patient comfort. DESIGN: A systematic review and meta-analysis. METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines. The PubMed, Embase and Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that enrolled patients undergoing PRP due to DR and compared analgesics or non-steroidal anti-inflammatory drugs (NSAID) to placebo. Pain was evaluated with the visual analogue scale. The version 2 of the Cochrane Collaboration's Risk of Bias in Randomized Controlled Trials tool and its version for crossover trials were used to assess the risk of bias. The Grading of Recommendations, Assessment, Development, and Evaluation tool was used to measure the certainty of evidence. RESULTS: A total of 13 studies were included, comprising 1404 eyes from RCTs, nine of which were crossover. Patients who were administered analgesia reported a significantly lower pain sensitivity compared to those who received placebo (Standardized mean difference [SMD] -0.38; 95% confidence interval [CI] -0.58, -0.17; P<0.01; I2=69%). Subgroup analysis of systemic administration of analgesics/NSAIDs (metamizole, Entonox, acetaminophen, ibuprofen, caffeine, mefenamic acid, intramuscular ketorolac tromethamine, and potassium diclofenac) also showed a statistically significant reduction in pain when compared to placebo (SMD -0.28; 95% CI -0.50, -0.07; P<0.01; I2=43%). Exclusive eye drops administration (ketorolac tromethamine 0.5% and sodium diclofenac 0.1%) also showed a significant difference in pain sensitivity (SMD -0.46; 95% CI -0.88, -0.05; I2=83%), however with a more significant heterogeneity. CONCLUSION: The results of this meta-analysis including over 1000 patients demonstrated that the use of analgesics significantly reduced pain sensitivity during PRP, and systemic analgesia is potentially better than topical administration when compared to placebo.

6.
Eur J Gen Pract ; 30(1): 2357780, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38832626

RESUMO

BACKGROUND: Worldwide, there are concerns about declining mental health of children and young people (CYP). OBJECTIVES: To examine trends in GP consultation rates for psychosocial problems and the impact of the COVID-19 pandemic. METHODS: We performed a population-based cohort study using electronic GP records of CYP (0-24 years) living in the Rotterdam metropolitan area between 2016 and 2021. We calculated monthly consultation rates for psychosocial problems, stratified by age group and sex. We used negative binomial models to model the pre-COVID-19 trend, and estimate expected rates post-COVID-19 onset. We modelled the effect of COVID-19 infection rate and school closure on consultation rates per sex and age group. RESULTS: The cohort increased from 64801 to 92093 CYP between January 2016 and December 2021. Median age was 12.5 years and 49.3% was female. Monthly consultation rates increased from 2,443 to 4,542 consultations per 100,000 patient months over the six years. This trend (RR 1.009, 95%CI 1.008-1.011) started well before the COVID-19 pandemic. Consultation rates of adolescent girls and young women increased most strongly. Between March and May 2020, there was a temporary reduction in consultation rates, whereupon these returned to expected levels. COVID-19 infection rate and school closures showed small but significant associations with consultation rates for psychosocial problems but this did not affect the overall trend. Although consultation rates for psychosocial problems increased, this increment was stable over the entire study period. CONCLUSION: The COVID-19 pandemic did not significantly increase consultation rates for psychosocial problems in CYP. The consultation rates increased, especially in adolescent girls and young women.


CYP' consultation rates for psychosocial problems within general practice almost doubled between 2016 and 2021 in the Rotterdam metropolitan area, the Netherlands.This increase was steady over time and was not affected by the COVID-19 pandemic.Consultation rates in general practice for psychosocial problems increased most strongly in adolescent girls and young women.


Assuntos
COVID-19 , Encaminhamento e Consulta , Humanos , Feminino , Adolescente , COVID-19/epidemiologia , Criança , Masculino , Países Baixos/epidemiologia , Pré-Escolar , Lactente , Adulto Jovem , Encaminhamento e Consulta/estatística & dados numéricos , Estudos de Coortes , Transtornos Mentais/epidemiologia , Recém-Nascido , Medicina Geral/estatística & dados numéricos
7.
BMJ Mil Health ; 170(3): 212-215, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777366

RESUMO

OBJECTIVE: The selection process to the British Army's Brigade of Gurkhas is rigorous, demanding and competitive. The ethos of recruitment to the Gurkhas is grounded in an overarching tenant: that selection is free, fair and transparent. The aim of this study was to retrospectively review reasons for potential recruits (PRs) to be deemed medically unsuitable or deferred suitability on medical grounds for selection to the Brigade of Gurkhas. METHODS: A retrospective review was conducted by extracted data from published post-exercise reports for the past four years to ascertain numbers of PRs deemed medically fit, medically unsuitable or deferred suitability on medical grounds. The International Classification of Disease version 11 (ICD-11) codes were retrospectively assigned to code medical reasons for non-progression. Rates of medical non-progression were compared by year. RESULTS: A total of 3154 PRs were analysed between 2018 and 2021. There was no significant difference between PRs deemed medically fit and those deemed medically suitable or deferred on medical grounds over the study period (p=0.351). There was a significant difference in the ratio of PRs deferred on medical grounds and those deemed medically unsuitable over the study period (p<0.05). CONCLUSION: Selection to the Gurkhas is extremely competitive. These data demonstrate that, overall, reasons for medical deferral or unsuitability have remained constant despite the impact of a global pandemic. These data reinforce the central tenant of Gurkha selection; that it continues to be free, fair, and transparent.


Assuntos
Militares , Humanos , Estudos Retrospectivos , Militares/estatística & dados numéricos , Masculino , Estudos de Coortes , Reino Unido , Seleção de Pessoal/métodos , Seleção de Pessoal/estatística & dados numéricos , Saúde Ocupacional/estatística & dados numéricos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Feminino , Índia/epidemiologia , Adulto
8.
Eur Rev Med Pharmacol Sci ; 28(8): 3036-3040, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38708461

RESUMO

OBJECTIVE: The primary aim of this study was to explore the involvement of cervical discopathy in the development of non-cyclic mastalgia by employing cervical magnetic resonance imaging (MRI). PATIENTS AND METHODS: A total of 407 patients were included in the study. Individualized management plans were developed for each patient. Pathological findings in MRI results were assessed by specialists in physical therapy and neurosurgery, and appropriate treatment was administered. Visual assessments of patients were conducted. The Analog Scale (VAS) scoring system was used at the initial presentation, and patients were evaluated at 1 and 3 months following the treatment. RESULTS: In the MRI examinations of the patients included in the study, simultaneous cervical disc protrusion was observed in 29% (n: 124) of those with annular bulging. Comparing the VAS scores of patients before treatment, at the 1st and at the 3rd month showed a significant decrease in mastalgia pain (p < 0.001). CONCLUSIONS: The diagnosis of cervical discopathy holds significant importance in the treatment of mastalgia patients. Therefore, clinicians should keep the cervical spine in mind as a potential contributing factor to mastalgia.


Assuntos
Vértebras Cervicais , Imageamento por Ressonância Magnética , Mastodinia , Humanos , Feminino , Vértebras Cervicais/diagnóstico por imagem , Pessoa de Meia-Idade , Masculino , Adulto , Mastodinia/diagnóstico , Medição da Dor , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/diagnóstico , Idoso
9.
J Magn Reson ; 363: 107703, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38781770

RESUMO

Experimental confirmation of the manifestations of new spin exchange paradigm in EPR spectra of 14N nitroxide radical solutions is presented. It was shown that in the region of relatively low concentrations of radicals, the two side components of the spectrum have a mixed shape (the sum of the absorptive line and dispersive line). The dispersion contributions in these two lines have opposite signs. As the concentration of radicals increases, the contribution of dispersion passes through an extremum and in the region of maximum contribution of dispersion, the contribution of absorption to these two lines changes sign. In the region of high concentrations of radicals, when one homogeneously broadened line is practically observed, it turns out that these side components have resonant frequencies that do not coincide with the frequency of the center of gravity of the spectrum.

10.
J Am Med Dir Assoc ; : 105031, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38772527

RESUMO

With increased focus on antimicrobial stewardship in post-acute, long-term care (PALTC) settings, optimization of diagnostic testing is essential. Molecular diagnostics are currently being offered and used for the diagnosis of urinary tract infections (UTIs) in community and PALTC settings. Yet, no studies to date explore the role of rapid diagnostics such as polymerase chain reaction and other molecular methods in the stewardship efforts of PALTC settings, specifically compared with standard testing with urinalysis and culture with antimicrobial susceptibility testing. This article outlines a framework of diagnostic stewardship to critically evaluate the use of molecular diagnostics for the diagnosis of UTIs in PALTC and the impact on patient outcomes and antimicrobial stewardship. The authors suggest a 5-step process for evaluating the role of novel diagnostics in the PALTC setting. Understanding the shortcomings of newer diagnostic tests may identify needs for further investigation before their widespread use.

11.
J Neurol ; 271(7): 4551-4565, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38717611

RESUMO

OBJECTIVE: We assessed the psychometric properties, established normative data for the German Multifactorial Memory Questionnaire (MMQ), and analyzed its association with neuropsychiatric factors across the life span to provide a validated metamemory assessment for a German-speaking population. METHODS: The three MMQ scales (memory satisfaction, self-rated ability, and strategy application) were translated into German, considering cultural, linguistic, and conceptual aspects. To validate the MMQ and assess associations with neuropsychiatric factors, the Complainer Profile Identification, Geriatric Depression Scale, Beck Anxiety Inventory, Pittsburgh Sleep Quality Index, and Short-Form-Health Survey were applied in an online study in 336 healthy participants with follow-up after 8 months. RESULTS: Psychometric evaluation of the German MMQ showed normal distribution of all scales and good to excellent validity, internal consistency, and retest reliability. We provide percentiles and normative data for z-score conversion. Importantly, even subclinically elevated scores in depressiveness and anxiety were associated with decreased memory satisfaction and self-rated ability. Furthermore, although the influence of age on the German MMQ scales was minimal, effects of neuropsychiatric factors such as sleep quality, anxiety, and depressiveness on MMQ Satisfaction and Ability varied across the life span. CONCLUSIONS: Our study provides a validated German translation of the MMQ with normative data and reliability measures, including reliable change scores. We show the impact of neuropsychiatric factors on the MMQ scales across the life span and emphasize the relevance of a multifactorial approach to metamemory as a measure of individualized everyday functionality and the importance of including neuropsychiatric factors into both research and clinical assessments of metamemory.


Assuntos
Psicometria , Humanos , Masculino , Feminino , Psicometria/normas , Pessoa de Meia-Idade , Idoso , Adulto , Alemanha , Reprodutibilidade dos Testes , Adulto Jovem , Idoso de 80 Anos ou mais , Metacognição/fisiologia , Inquéritos e Questionários/normas , Adolescente , Ansiedade/diagnóstico , Ansiedade/fisiopatologia , Transtornos da Memória/diagnóstico , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Testes Neuropsicológicos/normas
12.
BMJ Mil Health ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38604756

RESUMO

INTRODUCTION: Measuring cortisol during military training offers insights into physiological responses to stress. We attempted precisely timed, cortisol awakening response (CAR) and pre-sleep cortisol (PSC), and diurnal slope (peak morning minus evening cortisol), during a British Army exercise. We aimed to understand cortisol dynamics and evaluate the feasibility of CAR and PSC in this environment. METHOD: Setting: high-intensity, 10-day infantry exercise. Participants: regular infantry soldiers exercising (EX, n=25) or headquarters-based (HQ, n=6). Participants undertook PSC and WAKE and WAKE+30 min samples after 1-2 days, 5-6 days and 9-10 days. Wrist-worn GENEActiv accelerometers were used to assess sleep duration in EX only. Samples taken ±15 min from prespecified time points were deemed adherent. Validated questionnaires were used to measure resilience and perceived stress. Cortisol and cortisone were measured simultaneously by liquid chromatography tandem mass spectrometry. RESULTS: From adherent participants' samples, CAR was positive and tended to decrease as the exercise progressed. From all available data, HQ demonstrated greater diurnal slope than EX (F=7.68, p=0.02), reflecting higher morning cortisol (F=4.72, p=0.038) and lower PSC (p=0.04). No differences were seen in cortisol:cortisone ratio. 26.1% of CAR samples were adherent, with moderately strong associations between adherence and stress (r=0.41, p=0.009) but no association between adherence and day of exercise (χ2=0.27, p=0.8), sleep duration (r=-0.112, p=0.43) or resilience (r=-0.79, p=0.75). Test-retest reliability ratings for CAR were Cronbach's α of 0.48, -11.7 and 0.34 for the beginning, middle and end of the exercise, respectively. CONCLUSIONS: We observed a reduction in morning cortisol and decreased diurnal slope during a high-intensity military exercise, compared with the HQ comparator cohort in whom diurnal slope was preserved. A carefully timed CAR was not feasible in this setting.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38641965

RESUMO

AIM: To evaluate the implementation of a mixed virtual and in-person brief intervention for young people, aged 12-25 years, presenting to a large urban mental health service in crisis with suicidal ideation and/or self-harm. METHODS: A pragmatic, real-world evaluation was conducted on the Youth Brief Intervention Service between June 2021 (inception) and October 2022. Service users were offered four sessions over an approximate one-month period. Sessions focused on distress tolerance, safety plans and support systems. Implementation outcomes related to service uptake, retention, fidelity of the model and service user experience. Effectiveness outcomes were measured pre-post and included mental health-related hospital service utilization (primary outcome), functioning, mental health status, self-harm, suicidal ideation and quality of life. RESULTS: Of the 136 young people referred to the Youth Brief Intervention Service, 99 were accepted with 17 disengaging before the first session. Eighty percent of people who commenced, completed the package of care. Young persons' and parent/carers experience of service was high (97% and 88%, respectively). Mental health-related emergency department presentations and inpatient days decreased from 3 months pre-intake to 3 months post-intake (42 vs. 7 presentations, X2 = 25.3, p < .001; 11 vs. 0 inpatient days, X2 = 9.1, p = .01). There were significant improvements in mental health status, days engaging in self-harm, general health and functioning and quality of life. CONCLUSIONS: The Youth Brief Intervention Service is feasible, acceptable, subjectively beneficial and coincided with less mental health-related emergency department presentations and inpatient days, and improved mental health status and behaviour.

14.
Phys Rev Lett ; 132(15): 152501, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38683002

RESUMO

We report the first mass measurement of the proton-halo candidate ^{22}Al performed with the low energy beam ion trap facility's 9.4 T Penning trap mass spectrometer at facility for rare isotope beams. This measurement completes the mass information for the lightest remaining proton-dripline nucleus achievable with Penning traps. ^{22}Al has been the subject of recent interest regarding a possible halo structure from the observation of an exceptionally large isospin asymmetry [J. Lee et al., Large isospin asymmetry in Si22/O22 Mirror Gamow-Teller transitions reveals the halo structure of ^{22}Al, Phys. Rev. Lett. 125, 192503 (2020).PRLTAO0031-900710.1103/PhysRevLett.125.192503]. The measured mass excess value of ME=18 092.5(3) keV, corresponding to an exceptionally small proton separation energy of S_{p}=100.4(8) keV, is compatible with the suggested halo structure. Our result agrees well with predictions from sd-shell USD Hamiltonians. While USD Hamiltonians predict deformation in the ^{22}Al ground state with minimal 1s_{1/2} occupation in the proton shell, a particle-plus-rotor model in the continuum suggests that a proton halo could form at large quadrupole deformation. These results emphasize the need for a charge radius measurement to conclusively determine the halo nature.

15.
BMJ Mil Health ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38688679

RESUMO

INTRODUCTION: ECG changes are associated with regular long-term intensive exercise due to electrical manifestations of increased vagal tone, increased ventricular wall thickness and enlarged chamber size. The aim of this study was to further understand the relationship of athletic ECG changes and athletic performance in an athletic population. METHODS: A retrospective cohort study was performed in 195 Nepali civilian males undergoing selection to the Gurkhas. V̇O2max (maximal oxygen consumption) was estimated from a 1.5-mile run time using Cooper's formula and correlated with athletic ECG adaptations. Variables were explored with univariable and multivariable linear regression. RESULTS: The median number of athletic changes on ECG was 2 (IQR 1-2). There was no significant correlation (p=0.46) between the number of ECG adaptations and the degree of cardiovascular fitness by estimated V̇O2max (estV̇O2max). We found a negligible but significant correlation between the presence of inferior T wave inversion (TWI) and estV̇O2max (R2=0.03, p=0.02). The multivariable-fitted regression model was: estV̇O2max~Intercept+presence of RVH (right ventricular hypertrophy) voltage criteria+absence of sinus arrhythmia+T wave axis+inferior TWI. The overall regression was statistically significant: R2=0.10, F(df=4, df=189)=[5.4], p=0.0004). All variables in the multivariable model significantly predicted estV̇O2max (p<0.04). CONCLUSION: ECG changes of athleticism negligibly predict and differentiate athletic performance in our athletic population. The most predictive ECG markers being voltage criteria for left ventricular hypertrophy and RVH. Markers of increased vagal tone were not predictive. TWI, being a marker for disease, was also a marker for athletic performance in this cohort. The number of athletic ECG adaptations did not predict increased athletic performance.

16.
Sci Total Environ ; 932: 172589, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657803

RESUMO

Emerging contaminants are a growing concern for scientists and public authorities. The group of per-polyfluoroalkyl substances (PFAS), known as 'forever chemicals', in complex environmental liquid and solid matrices was analysed in this study. The development of global analytical methods based on combustion ion chromatography (CIC) is expected to provide accurate picture of the overall PFAS contamination level via the determination of extractable organic fluorine (EOF) and adsorbable organic fluorine (AOF). The obtained results may be put into perspective with other methods such as targeted analyses (LC-MS/MS). The impact of pH, the presence of dissolved organic carbon and suspended particles on AOF measurements were explored. The effectiveness of the washing step to remove adsorbed inorganic fluorine (IF) has been proven for samples containing up to 8 mgF.L-1. CIC-based methods showed good repeatability and reproducibility for the complex matrices studied. Environmental applications of these methods have been tested. AOF and EOF analyses could explain between 1 % and 23 % and 0.1 % to 2 % of total organic fluorine (TOF), respectively. The sum of PFAS compounds expressed as fluorine could explain from 0.2 % to 11 % and from 0.003 % to 5 % for AOF and EOF, respectively. These results also suggest that some fluorinated compounds are not adsorbed or extractable and/or lost by volatilisation during the application of AOF and EOF analytical procedure. These findings highlight that AOF and EOF are not entirely efficient as proxy to assess "total PFAS" for assessing environmental contamination by PFAS. However, these methods could still be applied to gain a better understanding of the sources and fate of PFAS in the environment.

17.
Virol J ; 21(1): 81, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589896

RESUMO

Orthobunyavirus oropouche ense virus (OROV), the causative agent of Oropouche fever, is widely dispersed in Brazil and South America, causing sporadic outbreaks. Due to the similarity of initial clinical symptoms caused by OROV with other arboviruses found in overlapping geographical areas, differential diagnosis is challenging. As for most neglected tropical diseases, there is a shortage of reagents for diagnosing and studying OROV pathogenesis. We therefore developed and characterized mouse monoclonal antibodies and, one of them recognizes the OROV nucleocapsid in indirect immunofluorescent (IFA) and immunohistochemistry (IHC) assays. Considering that it is the first monoclonal antibody produced for detecting OROV infections, we believe that it will be useful not only for diagnostic purposes but also for performing serological surveys and epidemiological surveillance on the dispersion and prevalence of OROV in Brazil and South America.


Assuntos
Infecções por Bunyaviridae , Orthobunyavirus , Animais , Camundongos , Anticorpos Monoclonais , Infecções por Bunyaviridae/diagnóstico , Brasil/epidemiologia
18.
Dig Dis Sci ; 69(6): 2165-2174, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38594435

RESUMO

BACKGROUND: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn's disease (CD) in clinical and biochemical remission. AIMS: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. METHODS: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. RESULTS: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. CONCLUSION: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT03172377.


Assuntos
Adalimumab , Doença de Crohn , Humanos , Adalimumab/administração & dosagem , Adalimumab/uso terapêutico , Adalimumab/efeitos adversos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/diagnóstico , Feminino , Masculino , Adulto , Esquema de Medicação , Resultado do Tratamento , Pessoa de Meia-Idade , Indução de Remissão
19.
Eur J Pain ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572961

RESUMO

BACKGROUND: Radiating leg pain is common in patients with low back pain (LBP). In this study, we aimed to determine the prevalence and incidence of LBP with radiating leg pain in Dutch general practice, and to describe the prescribed medications and requested imaging diagnostics. METHODS: The Rijnmond Primary Care Database containing over 500,000 primary care patients was used to select patients ≥18 years with LBP with radiating leg pain between 2013 and 2021. Data on patient characteristics, LBP episodes, prescribed medication and requested imaging in the first 3 months of an episode was extracted. Descriptive statistics were used to present patient characteristics and diagnostic/therapeutic interventions. RESULTS: A total of 27,695 patients were included. The total number of LBP with radiating leg pain episodes in these patients was 36,268. In 2021, the incidence and prevalence were 19.1 and 25.7 per 1000 patient years, respectively. In 60% of patients, the episode duration was shorter than 1 month. In 62% of the episodes, patients visited the general practitioner (GP) one to two times. In 59% of the episodes, at least one medication was prescribed, non-steroidal anti-inflammatory drugs (NSAIDs) being the most common one (45%). In approximately 11% of the episodes, additional diagnostic imaging was requested. CONCLUSION: LBP with radiating leg pain is common in Dutch general practice patients. About 2/3rd were prescribed pain medications. Dutch request few to none diagnostic imaging for these patients which is in line with clinical practice guidelines. SIGNIFICANCE: In this new study, we have gained insights into the incidence and prevalence of LBP with radiating leg pain in Dutch general practice. Both remained fairly stable over the study period of 9 years (2013-2021). Overall, the care burden regarding seeking contact with the GPs and the requested diagnostics seem not to be that high. In 62% of the care episodes, there were one or two consultations with the GP, and in 11% of the episodes a diagnostic imaging was requested. Pain medications frequently prescribed (i.e. 2/3rd of the episodes), with NSAIDs being the most common ones.

20.
Work ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457171

RESUMO

BACKGROUND: Recent research indicates that as men age, their tendency to ruminate about work decreases, while ruminating remains high in women, which poses an increased risk for impaired health among older women. OBJECTIVE: This study explored gender differences/similarities in the process of unwinding from work in men and women aged between 56-65 years. METHODS: Semi-structured qualitative interviews were conducted online with eight men and eight women, recruited from a UK leading organization that provides health care solutions between May and June 2022. Participants were asked about their job role and responsibilities, their leisure time activities, how they unwind post work, and their experiences of thinking about work related thoughts outside of work. Transcripts were analyzed using an inductive analysis. RESULTS: Three superordinate themes were identified that underpinned their ability to unwind: 'Work style', 'Creating work-life balance' and 'Switching off from one's responsibilities'. Women reported a more perfectionist approach, they set high standards for themselves, were worried about making mistakes, and demonstrated, if in a supervisory role, a more nurturing and holistic approach to their colleagues/subordinates, while men, were more focused on task completion. Most women, but not men, also described difficulties in psychologically switching off from work, and stated they could only truly relax outside the home, when they are away from household activities. CONCLUSION: The study provides nuanced insights into the experiences of unwinding from work, and the findings suggest the need for person-centric approaches in developing interventions to help workers over 56 years to psychologically disengage from work.

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