Abstract Background Plaque psoriasis (PsO) requires long‐term treatment for symptom control and remission; thus, a long‐term pharmacological intervention is necessary. Treatment persistence reflects ...long‐term therapeutic effectiveness and tolerance. Objectives This study investigates drug persistence and compares treatment discontinuation rates across biologic agents and apremilast used by PsO patients in Finland and Sweden. Methods This retrospective register‐based cohort study included bio‐naïve patients (≥18 years) with moderate‐to‐severe PsO, who initiated treatment with abatacept, adalimumab, brodalumab, certolizumab pegol, etanercept, golimumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab, ustekinumab or apremilast during 2008–2020 in Finland or Sweden. The main analysis evaluated persistence (based on duration of continuous treatment) and compared rates of treatment discontinuation using guselkumab as reference drug, during 2018–2020 in Finland. Treatment discontinuation was assessed by survival analysis of the time to first drug discontinuation, including switching to other study drugs. Due to limited sample size ( n < 20), certain biologics (abatacept, brodalumab, certolizumab pegol, etanercept, golimumab, risankizumab and tildrakizumab) were excluded from the persistence analysis. Results In Finland, 709 patients fulfilled the inclusion criteria during 2018–2020 for the main analysis. The highest persistence was observed for guselkumab and ustekinumab with 90 and 85% of treated patients, respectively, continuing treatment for ≥1 year. Comparable results were observed in the expanded cohort analysis (index starting in 2008; 2745 bio‐naïve patients in Finland and 10,970 in Sweden). Furthermore, patients treated with guselkumab in Finland showed lower treatment discontinuation rates compared to other study drugs. Conclusion Guselkumab and ustekinumab demonstrated high persistence as measured by continued treatment for at least 1 year. Furthermore, these treatments demonstrated lower rates of discontinuation compared to other study drugs included in the analysis. Understanding the balance between efficacy and feasibility in treatment decisions is crucial, as feasibility may impact persistency outcomes and potentially increase persistency rates.
Objectives
The objectives of this study were to investigate the occurrence, types and severity of malocclusions in children with speech sound disorder (SSD) persisting after 6 years of age, and to ...compare these findings to a control group of children with typical speech development (TSD).
Methods
In total, 105 children were included: 61 with SSD and motor speech involvement (mean age 8:5 ± 2:8 years; range 6:0–16:7 years, 14 girls and 47 boys) and 44 children with TSD (mean age 8:8 ± 1:6; range 6:0–12:2 years, 19 girls and 25 boys). Extra-oral and intra-oral examinations were performed by an orthodontist. The severity of malocclusion was scored using the IOTN-DHC Index.
Results
There were differences between the SSD and TSD groups with regard to the prevalence, type, and severity of malocclusions; 61% of the children in the SSD group had a malocclusion, as compared to 29% in the TSD group. In addition, the malocclusions in the SSD group were rated as more severe. Functional posterior crossbite and habitual lateral and/or anterior shift appeared more frequently in the SSD group. Class III malocclusion, anterior open bite and scissors bite were found only in the SSD group.
Conclusion
Children with SSD and motor speech involvement are more likely to have a higher prevalence of and more severe malocclusions than children with TSD.
Extraoral vertical ramus osteotomy (EVRO) is used in orthognathic surgery for the treatment of mandibular deformities. Originally, EVRO required postoperative intermaxillary fixation (IMF). EVRO has ...been developed using rigid fixation, omitting postoperative IMF. We examined retrospectively the long-term stability and postoperative complications for patients with mandibular deformities who underwent EVRO with internal rigid fixation. Patients who were treated with EVRO for a mandibular deformity in the period 2008–2017 at the Clinic of Oral and Maxillofacial Surgery, Mölndal, Sweden were included (N = 26). Overjet and overbite were calculated digitally and cephalometric analyses were performed preoperatively, and at three days, six months, and 18 months postoperatively. There was a general setback of the mandible, decreased gonial angle and reduced degree of skeletal opening. Excellent dental and vertical skeletal stabilities were seen up to 18 months postoperatively, although relapse was seen sagitally up to six months postoperatively. Since the overjet did not show any significant change over time, the sagittal skeletal changes have been attributed to dental compensation. There was no permanent damage to the facial nerve and 5.8% neurosensory damage to the inferior alveolar nerve was observed.
Highlights • For treatment of inflammation-reactive astrocytes the extracellular concentration of IL-1β is kept at a low level. • For treatment of inflammation-reactive astrocytes the μ-opioid ...receptor Gs protein is inhibited and Gi/0 protein is stimulated. • For treatment of inflammation-reactive astrocytes the Na+ /K+ -ATPase activity is increased. • For treatment of inflammation-reactive astrocytes the actin filaments will thereby be restored.
Abstract Despite their abundance and their enormous significance for various ecological processes, endocrine systems of microcrustaceans have been poorly investigated. Here, we used a highly ...sensitive radioimmunoassay (RIA) to determine free and conjugated ecdysteroid levels in whole-body extracts of adult Daphnia magna during a complete molt cycle. Ecdysteroid levels were predominated by free ecdysteroids. Starting from basal levels in the postmolt stage the concentration of free ecdysteroids increased sharply in the early premolt stage, followed by a sharp decline back to basal levels just prior to ecdysis. Polar and apolar ecdysteroid conjugates were found in rather low amounts with little variation during the molt cycle. Only small amounts of ecdysteroids were found in newly deposited eggs of D. magna , which suggest a sparing investment of maternal ecdysteroids into the eggs for early embryogenesis. As in whole-body extracts, free ecdysteroids were the predominant ecdysteroids found in eggs of D. magna , together with small amounts of polar and intermediary amounts of apolar conjugates. Hence, the pathways leading to polar and apolar ecdysteroid conjugates appear to be of minor importance in D. magna . Analyses of the immunodetectable peak in free ecdysteroids by liquid chromatography–mass spectrometry (LC–MS) revealed that molting is induced most probably by an increased level of 20-hydroxyecdysone. Microcrustaceans of the genus Daphnia are key components in freshwater food webs. Examination of the functional role of ecdysteroids in controlling developmental processes might help to understand the performance of the herbivorous grazer in its environment, in particular with regard to the adverse effects of environmental xenobiotics acting as endocrine disrupters.
In order to imitate the in vivo situation with constituents from the blood-brain barrier, astrocytes from newborn rat cerebral cortex were co-cultured with adult rat brain microvascular endothelial ...cells. These astrocytes exhibited a morphologically differentiated appearance with long processes. 5-HT, synthetic mu-, delta- or kappa-opioid agonists, and the endogenous opioids endomorphin-1, beta-endorphin, and dynorphin induced higher Ca(2+) amplitudes and/or more Ca(2+) transients in these cells than in astrocytes in monoculture, as a sign of more developed signal transduction systems. Furthermore, stimulation of the co-cultured astrocytes with 5-HT generated a pronounced increase in intracellular Ca(2+) release in the presence of the inflammatory or pain mediating activators substance P, calcitonin gene-related peptide (CGRP), lipopolysaccharide (LPS), or leptin. These Ca(2+) responses were restored by opioids so that the delta- and kappa-opioid receptor agonists reduced the number of Ca(2+) transients elicited after incubation in substance P+CGRP or leptin, while the mu- and delta-opioid receptor agonists attenuated the Ca(2+) amplitudes elicited in the presence of LPS or leptin. In LPS treated co-cultured astrocytes the mu-opioid receptor antagonist naloxone attenuated not only the endomorphin-1, but also the 5-HT evoked Ca(2+) transients. These results suggest that opioids, especially mu-opioid agonists, play a role in the control of neuroinflammatory activity in astrocytes and that naloxone, in addition to its interaction with mu-opioid receptors, also may act through some binding site on astrocytes, other than the classical opioid receptor.
We investigated the influence of juvenile hormones (JH) on the composition of cuticular hydrocarbons (CHCs) and the division of labor in colonies of the African ant Myrmicaria eumenoides. CHCs have ...long been implicated in nestmate recognition in social insect colonies. In M. eumenoides, the CHC profiles also vary with the task performed from brood-tender-type to forager type. The endocrine factors regulating the task allocation as well as the intracolonial recognition cues are not well understood, but JHs are prime candidates. Only JH III was identified in the hemolymph of M. eumenoides workers. Foragers had significantly higher JH III titers than brood tenders. The application of exogenous JH III and a JH analogue (methoprene) to M. eumenoides workers did not result in an observable acceleration of task change in our study. However, longevity of the focus workers, and thus the observational period, was reduced by the applications. Changes from a brood-tender-type to a forager-type CHC profile were accelerated by the application of JH III and methoprene, resulting in brood-tending workers that displayed forager-type CHC profiles. We present the first data supporting that recognition cues of an eusocial Hymenopteran are influenced by JH III, which could thus play a major role in the regulation of the dynamic nature of social insect colonies. JH III is connected to at least two key processes: the acceleration of CHC changes and the more long-term modulation of task shifting. Moreover, this indicates that changes in CHC recognition cues do not trigger task allocation in social insect colonies.
Abstract The aim of this study was to investigate whether nicotine acetylcholine receptors (nAChRs) are expressed in a more pronounced way in astrocytes co-cultured with microvascular endothelial ...cells from adult rat brain, compared with monocultured astrocytes, as a sign of a more developed signal transduction system. Also investigated was whether nicotine plays a role in the control of neuroinflammatory reactivity in astrocytes. Ca2+ imaging experiments were performed using cells loaded with the Ca2+ indicator Fura-2/AM. Co-cultured astrocytes responded to lower concentrations of nicotine than did monocultured astrocytes, indicating that they are more sensitive to nicotine. Co-cultured astrocytes also expressed a higher selectivity for α7nAChR and α4/β2 subunits and evoked higher Ca2+ transients compared with monocultured astrocytes. The Ca2+ transients referred to are activators of Ca2+ -induced Ca2+ release from intracellular stores, both IP3 and ryanodine, triggered by influx through receptor channels. The nicotine-induced Ca2+ transients were attenuated after incubation with the inflammatory mediator lipopolysaccharide (LPS), but were not attenuated after incubation with the pain-transmitting peptides substance P and calcitonin-gene-related peptide, nor with the infection and inflammation stress mediator, leptin. Furthermore, LPS-induced release of interleukin-1β (IL-1β) measured by enzyme-linked immunosorbent assay (ELISA) was more pronounced in co-cultured versus monocultured astrocytes. Incubation with both LPS and IL-1β further attenuated nicotine-induced Ca2+ response. We also found that LPS and IL-1β induced rearrangement of the F-actin filaments, as measured with an Alexa488-conjugated phalloidin probe. The rearrangements consisted of increases in ring formations and a more dispersed appearance of the filaments. These results indicate that there is a connection between a dysfunction of nicotine Ca2+ signaling in inflammatory reactive astrocytes and upregulation of IL-1β and the rearrangements of actin filaments in the cells.
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