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Clinical Rheumatology Jul 2024Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors...
Prior herpes zoster occurrence and high-dose corticosteroids increase herpes zoster risk in rheumatoid arthritis patients receiving janus kinase inhibitors in a retrospective and observational study.
Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5 months versus 33.5 months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.
PubMed: 38954278
DOI: 10.1007/s10067-024-07041-z -
Clinical Reviews in Allergy & Immunology Jul 2024Atopic dermatitis and psoriasis are common chronic inflammatory diseases of high incidence that share some clinical features, including symptoms of pruritus and pain,... (Review)
Review
Atopic dermatitis and psoriasis are common chronic inflammatory diseases of high incidence that share some clinical features, including symptoms of pruritus and pain, scaly lesions, and histologically, acanthosis and hyperkeratosis. Meanwhile, they are both commonly comorbid with metabolic disorders such as obesity and diabetes, indicating that both diseases may exist with significant metabolic disturbances. Metabolomics reveals that both atopic dermatitis and psoriasis have abnormalities in a variety of metabolites, including lipids, amino acids, and glucose. Meanwhile, recent studies have highlighted the importance of the microbiome and its metabolites in the pathogenesis of atopic dermatitis and psoriasis. Metabolic alterations and microbiome dysbiosis can also affect the immune, inflammatory, and epidermal barrier, thereby influencing the development of atopic dermatitis and psoriasis. Focusing on the metabolic and microbiome levels, this review is devoted to elaborating the similarities and differences between atopic dermatitis and psoriasis, thus providing insights into the intricate relationship between both conditions.
PubMed: 38954264
DOI: 10.1007/s12016-024-08995-3 -
Natural Products and Bioprospecting Jul 2024Alzheimer's disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula...
Alzheimer's disease (AD) is a complex neurodegenerative condition. 5α-epoxyalantolactone (5α-EAL), a eudesmane-type sesquiterpene isolated from the herb of Inula macrophylla, has various pharmacological effects. This work supposed to investigate the improved impact of 5α-EAL on cognitive impairment. 5α-EAL inhibited the generation of nitric oxide (NO) in BV-2 cells stimulated with lipopolysaccharide (LPS) with an EC of 6.2 μM. 5α-EAL significantly reduced the production of prostaglandin E2 (PGE) and tumor necrosis factor-α (TNF-α), while also inhibiting the production of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins. The ability of 5α-EAL to penetrate the blood-brain barrier (BBB) was confirmed via a parallel artificial membrane permeation assay. Scopolamine (SCOP)-induced AD mice model was employed to assess the improved impacts of 5α-EAL on cognitive impairment in vivo. After the mice were pretreated with 5α-EAL (10 and 30 mg/kg per day, i.p.) for 21 days, the behavioral experiments indicated that the administration of the 5α-EAL could alleviate the cognitive and memory impairments. 5α-EAL significantly reduced the AChE activity in the brain of SCOP-induced AD mice. In summary, these findings highlight the beneficial effects of the natural product 5α-EAL as a potential bioactive compound for attenuating cognitive deficits in AD due to its pharmacological profile.
PubMed: 38954263
DOI: 10.1007/s13659-024-00462-y -
Methods in Molecular Biology (Clifton,... 2024Lysosomes are membrane-enclosed organelles that digest intracellular material. They contain more than 50 different enzymes that can degrade a variety of macromolecules...
Lysosomes are membrane-enclosed organelles that digest intracellular material. They contain more than 50 different enzymes that can degrade a variety of macromolecules including nucleic acids, proteins, polysaccharides, and lipids. In addition to functioning within lysosomes, lysosomal enzymes are also secreted. Alterations in the levels and activities of lysosomal enzymes dysregulates lysosomes, which can lead to the intralysosomal accumulation of biological material and the development of lysosomal storage diseases (LSDs) in humans. Dictyostelium discoideum has a long history of being used to study the trafficking and functions of lysosomal enzymes. More recently, it has been used as a model system to study several LSDs. In this chapter, we outline the methods for assessing the activity of several lysosomal enzymes in D. discoideum (α-galactosidase, β-galactosidase, α-glucosidase, β-glucosidase, β-N-acetylglucosaminidase, α-mannosidase, cathepsin B, cathepsin D, cathepsin F, palmitoyl protein thioesterase 1, and tripeptidyl peptidase 1).
Topics: Dictyostelium; Lysosomes; Tripeptidyl-Peptidase 1; Enzyme Assays; Humans; beta-Galactosidase; Lysosomal Storage Diseases; Thiolester Hydrolases
PubMed: 38954197
DOI: 10.1007/978-1-0716-3894-1_4 -
Academic Psychiatry : the Journal of... Jul 2024As clinician educator tracks continue to gain popularity in graduate medical education, this report aims to fill a gap in the literature by providing a 14-year update on...
OBJECTIVE
As clinician educator tracks continue to gain popularity in graduate medical education, this report aims to fill a gap in the literature by providing a 14-year update on professional outcomes of participants in a psychiatry residency academic administrator, clinician educator (AACE) track and to compare these outcomes to non-track participants.
METHODS
An anonymous web-based survey querying professional achievements was distributed to all graduates of a psychiatry residency training program from 2009 to 2022. Outcomes of AACE track participants and non-track participants were compared.
RESULTS
Of 228 alumni contacted, 61% responded (n = 140). Eighty-seven percent of track participants responded (n = 74) while 41% of non-track participants responded (n = 45). Of track participants, 63% practice in academic settings with 57% having held administrative leadership roles, 49% educational leadership roles, and 39% national or regional leadership roles. Track graduates were academically engaged with 70% reporting at least one publication, 89% at least one presentation, and 93% attending at least one national meeting. In comparison, 31% of non-track participants practice in academic settings with 44% having held administrative, 29% educational, and 20% national or regional leadership roles. Thirty-nine percent have at least one publication, 75% at least one presentation, and 90% attended at least one national meeting. When compared to non-track participants, track participants were significantly more likely to have an academic affiliation and a higher number of publications and were more likely to hold national or regional leadership roles.
CONCLUSIONS
Track participants demonstrate longitudinal career success as clinician educators and academic administrators more so than non-track participants.
PubMed: 38954159
DOI: 10.1007/s40596-024-02004-7 -
Odontology Jul 2024This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in...
This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17β-estradiol (28 µg/kg/day) or placebo for 21 days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.
PubMed: 38954152
DOI: 10.1007/s10266-024-00964-8 -
Prevention Science : the Official... Jul 2024Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting...
Violence is a major public health problem globally, with the highest rates in low- and middle-income countries (LMICs) in the Americas and southern Africa. Parenting programmes in high-income countries can diminish risk for violence, by reducing risk factors such as child aggression and harsh parenting, and increasing protective factors such as child cognitive development and school readiness. However, there is critical need to identify low-cost programmes with replicable benefits that work in real-world LMICs contexts. A three-arm, randomised, single-blind trial evaluated effects of two low-cost, group-based parenting programmes recommended for LMICs (ACT: Raising Safe Kids; DBS: dialogic book-sharing) on child aggression (primary outcome), child development, parenting, maltreatment, and stress. Participants were 369 children with medium-high levels of aggression (mean age 3.1 years at baseline) in poor households. Interventions were implemented in city health and education services in southern Brazil. Maternal reports, filmed observations, child tasks, and hair cortisol were assessed at baseline, 1-month post-intervention, and 8-month follow-up. Intention-to-treat analyses compared each of ACT and DBS with a control group. Three hundred sixty-eight (99.7%) participants completed follow-up assessments 8 months after the interventions. There was no effect of ACT (standardised mean difference, SMD 0.11, 95% CI - 0.05, 0.27) or DBS (SMD 0.05, 95% CI - 0.11, 0.21) on the primary outcome of child aggression. ACT reduced harsh parenting behaviour post-intervention (SMD - 0.23; 95% CI - 0.46, - 0.01), but not at follow-up. DBS improved book-sharing practices at both time points (e.g., maternal sensitivity at follow-up SMD 0.33; 95% CI 0.08, 0.57). There were no benefits of either programme for other parenting, child development, or stress outcomes. Two parenting programmes in Brazil had small effects on parenting practices but did not reduce child aggression or several other important risk/protective factors for violence. Effective early interventions that reduce violence in real-world LMIC settings are highly desirable but may be challenging to achieve.
PubMed: 38954125
DOI: 10.1007/s11121-024-01698-3 -
Clinical Oral Investigations Jul 2024Studies exploring variations in peripheral muscle oxygenation and pressure pain thresholds (PPT) of masticatory muscles in individuals with Temporomandibular Disorders...
OBJECTIVES
Studies exploring variations in peripheral muscle oxygenation and pressure pain thresholds (PPT) of masticatory muscles in individuals with Temporomandibular Disorders (TMDs) are limited. The purpose of this study was to compare variations in peripheral oxygenation of the masseter muscle; PPT of the masseter and temporal muscles and correlate peripheral muscle oxygenation and PPT of the masseter muscle in individuals with different types of TMDs.
MATERIALS AND METHODS
Cross-sectional study involving 116 participants classified into three groups: muscle group (MG, n = 32), joint group (JG, n = 30) and muscle-joint group (MJG, n = 54). Individuals aged 26.97 ± 6.93, 68.97% female, 31,03% males were included. All participants were evaluated using the Diagnostic Criteria for Temporomandibular Disorders, Near-infrared spectroscopy (NIRS) for peripheral muscle oxygenation and pressure algometer for PPT.
RESULTS
There was no difference in masseter muscle oxygenation among groups. In the masseter muscle, a weakly positive correlation was observed between PPT and variation in tissue saturation index in the MG (rho = 0.365) and JG (rho = 0.317). In addition, the MJG expressed lower PPT (p = 0.004) than JG, demonstrating that MJG had more pain in this muscle.
CONCLUSIONS
MJG have lower PPT in the masseter muscle. Although the PPT is dependent on the type of TMDs, the correlation between PPT and oxygenation is weak. All TMDs groups evaluated (MG, JG, MJG) showed hemodynamic similarities of the masseter muscle.
CLINICAL RELEVANCE
Understanding pain thresholds and the hemodynamic behavior of the masticatory muscles contributes to a more assertive physiotherapeutic assessment in TMDs, serving as a basis for careful and individualized interventions.
Topics: Humans; Male; Temporomandibular Joint Disorders; Female; Cross-Sectional Studies; Adult; Pain Threshold; Pain Measurement; Masseter Muscle; Spectroscopy, Near-Infrared; Facial Pain; Oxygen; Temporal Muscle
PubMed: 38954100
DOI: 10.1007/s00784-024-05806-z -
Mikrochimica Acta Jul 2024A fluorescence probe based on molecularly imprinted polymers on red emissive biomass-derived carbon dots (r-BCDs@MIPs) was developed to detect tyramine in fermented meat...
Fabrication of fluorescence probe based on molecularly imprinted polymers on red emissive biomass-derived carbon dots coupled with smartphone readout for tyramine determination in fermented meat products.
A fluorescence probe based on molecularly imprinted polymers on red emissive biomass-derived carbon dots (r-BCDs@MIPs) was developed to detect tyramine in fermented meat products. The red emissive biomass-derived carbon dots (r-BCDs) were synthesized by the one-step solvothermal method using discarded passion fruit shells as raw materials. The fluorescence emission peak of r-BCDs was at 670 nm, and the relative quantum yield (QY) was about 2.44%. Molecularly imprinted sensing materials were prepared with r-BCDs as fluorescent centers for the detection of trace tyramine, which showed a good linear response in the concentration range of tyramine from 1 to 40 µg L. The linear correlation coefficient was 0.9837, and the limit of detection was 0.77 µg L. The method was successfully applied to the determination of tyramine in fermented meat products, and the recovery was 87.17-106.02%. The reliability of the results was verified through high-performance liquid chromatography (HPLC). Furthermore, we combined the r-BCDs@MIPs with smartphone-assisted signal readout to achieve real-time detection of tyramine in real samples. Considering its simplicity and convenience, the method could be used as a rapid and low-cost promising platform with broad application prospects for on-site detection of trace tyramine with smartphone-assisted signal readout.
Topics: Tyramine; Smartphone; Carbon; Quantum Dots; Meat Products; Fluorescent Dyes; Molecularly Imprinted Polymers; Limit of Detection; Spectrometry, Fluorescence; Biomass; Fermentation
PubMed: 38954059
DOI: 10.1007/s00604-024-06499-7 -
Cancer Immunology, Immunotherapy : CII Jul 2024In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and...
PURPOSE
In advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI) monotherapy is often preferred over intensive ICI treatment for frail patients and those with poor performance status (PS). Among those with poor PS, the additional effect of frailty on treatment selection and mortality is unknown.
METHODS
Patients in the veterans affairs national precision oncology program from 1/2019-12/2021 who received first-line ICI for advanced NSCLC were followed until death or study end 6/2022. Association of an electronic frailty index with treatment selection was examined using logistic regression stratified by PS. We also examined overall survival (OS) on intensive treatment using Cox regression stratified by PS. Intensive treatment was defined as concurrent use of platinum-doublet chemotherapy and/or dual checkpoint blockade and non-intensive as ICI monotherapy.
RESULTS
Of 1547 patients receiving any ICI, 66.2% were frail, 33.8% had poor PS (≥ 2), and 25.8% were both. Frail patients received less intensive treatment than non-frail patients in both PS subgroups (Good PS: odds ratio [OR] 0.67, 95% confidence interval [CI] 0.51 - 0.88; Poor PS: OR 0.69, 95% CI 0.44 - 1.10). Among 731 patients receiving intensive treatment, frailty was associated with lower OS for those with good PS (hazard ratio [HR] 1.53, 95% CI 1.2 - 1.96), but no association was observed with poor PS (HR 1.03, 95% CI 0.67 - 1.58).
CONCLUSION
Frail patients with both good and poor PS received less intensive treatment. However, frailty has a limited effect on survival among those with poor PS. These findings suggest that PS, not frailty, drives survival on intensive treatment.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Male; Female; Aged; Immunotherapy; Immune Checkpoint Inhibitors; Middle Aged; Frailty; Aged, 80 and over
PubMed: 38954019
DOI: 10.1007/s00262-024-03763-w