Aagaardkarlsson3368
Orofacial pain disorders involving trigeminal sensory neurons disproportionately affect women and can be modulated by hormones, especially estrogen (E2). Proinflammatory mediators, like serotonin (5HT), can act on sensory neurons expressing the transient receptor potential vanilloid 1 (TRPV1) ion channel, resulting in peripheral sensitization. We previously reported peripheral 5HT evokes greater pain behaviors in the hindpaw of female rats during proestrus and estrus, stages when E2 fluctuates. It is unknown if this interaction is comparable in the trigeminal system. We hypothesized that E2 exacerbates 5HT-evoked nocifensive pain behaviors and pain signaling in female trigeminal sensory neurons. We report 5HT-evoked nocifensive behaviors are significantly higher during estrus and proestrus, which is attenuated by blocking the 5HT2A receptor. The comparable dose of 5HT was not nociceptive in males unless capsaicin was also administered. When administered with capsaicin, a lower dose of 5HT evoked trigeminal pain behaviors in females during proestrus. Further, basal 5HT content in the vibrissal pad was higher in cycling females compared to males. Ex vivo, E2 enhanced 5HT-potentiated CGRP release from trigeminal neurons, which was not significantly reduced by blocking the 5HT2A receptor. Our data indicates that estrogen fluctuation influences the pronociceptive effects of 5HT on trigeminal sensory neurons.
To report the efficacy of intravitreal injection (IVI) of brolucizumab for recalcitrant diabetic macular edema (DME) in a real-world setting.
This was a single-center, prospective uncontrolled non-randomized case series. Three eyes with recalcitrant DME, who have received a minimum of ten intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, underwent IVI brolucizumab and were followed-up for minimum of 16 weeks. Patients underwent best-corrected visual acuity (BCVA) testing, ophthalmic examination, and optical coherence tomography at baseline and all the scheduled follow-up visits (Weeks 4, 8, 12, and 16). All three patients demonstrated notable improvement in BCVA and reduction in the fluid on SD-OCT lasting up to week 12. At week 16, all three eyes maintained the visual acuity gains. However, early increase in fluid was noted in all the three cases, for which second dose of IVI brolucizumab was planned. No ocular or systemic adverse events were noted in any of the cases.
In this real-world case series, treatment with IVI brolucizumab exhibited excellent visual acuity outcomes lasting up to 16 weeks for the treatment of recalcitrant DME. learn more Single dose IVI brolucizumab achieves good anatomical improvement based on SD-OCT persisting up to 12 weeks, followed by early recurrence of fluid at week 16. The results did not show any ocular or systemic safety concerns for IVI brolucizumab.
In this real-world case series, treatment with IVI brolucizumab exhibited excellent visual acuity outcomes lasting up to 16 weeks for the treatment of recalcitrant DME. Single dose IVI brolucizumab achieves good anatomical improvement based on SD-OCT persisting up to 12 weeks, followed by early recurrence of fluid at week 16. The results did not show any ocular or systemic safety concerns for IVI brolucizumab.Clinical studies with time to event endpoints typically report the median follow-up (i.e., censoring) time for the subjects in the trial, alongside the median time to event. The reason for this is to provide information about the opportunity for subjects in the study to experience the event of interest (Betensky, 2015 [1]). The median follow-up time is often calculated from the Kaplan-Meier estimate for time to censoring. In most clinical studies, the censoring time is a composite measure, defined as the minimum of time to drop-out from the study and time to administrative end of study. The time to drop-out component may or may not be observed; it is observed only if drop-out occurs before the event and the end of the study. However, the time to end of study is observed for each subject, as it is the time from entry to the study to the calendar date that is administratively set as the end of the study. It is known even for subjects who have the event prior to the end of the study. This decomposition of the censoring time into a time that is itself potentially censored and a time that is fully observed raises the interesting question of whether estimation of the censoring distribution could be improved through a decoupling of these times. We demonstrate in simulations that consideration of censoring in this way yields reduced variability under some circumstances and should be used in practice. We illustrate these concepts through application to a meningioma study.
Adults with profound intellectual and multiple disabilities (PIMD) have problems to be actively involved in essential life activities that affect their health. The aim of this study was to explore the utility of goal attainment scaling (GAS) in evaluating an intervention for adults with PIMD, and to describe how the GAS goals were set according to the International Classification of Functioning, Disability and Health (ICF) domains of body function as well as activity and participation.
As part of an aquatic intervention (Structured water dance), 28 adults with PIMD received GAS goals which were adapted to their individual needs and which the intervention could affect.
Twenty of the goals were formulated within the ICF Activity/Participation domain and eight within the Body Functions domains. On average, participants improved by 1.25 levels on the five-level GAS scales.
GAS can be a useful tool for setting and evaluating individualized and meaningful goals, in body functions as well as in activity and participation, related to a healthpromoting activity for adults with PIMD.
GAS can be a useful tool for setting and evaluating individualized and meaningful goals, in body functions as well as in activity and participation, related to a healthpromoting activity for adults with PIMD.
The purpose of this study is to investigate the influence of perceived security, perceived privacy, and satisfaction on Facebook user continuance intention. In addition, the serial multiple mediating effects of trust and satisfaction on the relationship between continuance intention and Facebook determinants are explored. This study also investigates the moderating role of Facebook addiction on the relationship between satisfaction and continuance intention.
To achieve the study aims, an online survey was conducted among university undergraduate students. Data were collected from 450 voluntary participants. The statistical analysis was performed using SPSS and PROCESS macro models.
The study results confirm that perceived privacy and satisfaction have significant impacts on Facebook continuance intention. The path analysis results confirm the full mediating roles of trust and satisfaction in the relationship between perceived security and continuance intention. Furthermore, the moderating role of Facebo moderating effects of Facebook addiction on the relationship between satisfaction and continuance intention are also examined. The study results make important contributions to Facebook continuance intention research and advance scholarship into aspects of undergraduate students' continuance intention in the context of Facebook.
This research integrated perceived privacy, perceived security, and trust with an Information System (IS) success model. This is the first study to investigate the serial mediating effects of trust and satisfaction on the determinants of Facebook continuance intention. The moderating effects of Facebook addiction on the relationship between satisfaction and continuance intention are also examined. The study results make important contributions to Facebook continuance intention research and advance scholarship into aspects of undergraduate students' continuance intention in the context of Facebook.We previously demonstrated that angiopoietin-like protein 8 (ANGPTL8) forms ANGPTL3/8 and ANGPTL4/8 complexes that increase with feeding to direct fatty acids (FA) toward adipose tissue through differential modulation of lipoprotein lipase (LPL) activity. Each complex correlated inversely with high density lipoprotein cholesterol (HDL) in control subjects. We thus investigated ANGPTL3/8 and ANGPTL4/8 levels in type 2 diabetes patients, who can present with decreased HDL. While ANGPTL3/8 levels in type 2 diabetes patients were similar to those previously observed in normal controls, ANGPTL4/8 levels were roughly twice as high as those in control subjects. Concentrations of ANGPTL3/8 and ANGPTL4/8 in type 2 diabetes patients were inversely correlated with HDL, with the correlation being significant for ANGPTL4/8. We therefore measured the ability of the various ANGPTL proteins and complexes to inhibit endothelial lipase (EL), the enzyme which hydrolyzes phospholipids (PL) in HDL. While confirming ANGPTL3 as an EL inhibitor, we found that ANGPTL4 was a more potent EL inhibitor than ANGPTL3. Interestingly, we observed that while ANGPTL3/8 had increased EL-inhibitory activity compared to ANGPTL3 alone, ANGPTL4/8 exhibited decreased potency in inhibiting EL compared to ANGPTL4 alone. Together, these results show for the first time that ANGPTL4 is a more potent EL inhibitor than ANGPTL3 and suggest a possible reason for why ANGPTL4/8 levels are correlated inversely with HDL.Novel therapeutics for the treatment of leishmaniasis are of interest as the disease not only is becoming more prevalent, but drug resistance is increasing in certain regions of the world. Reported here is the use of Bi3+-doped strontium aluminum oxyfluoride phosphors and protease inhibitors to test in vitro inhibitory activity against cultured promastigote Leishmania tarentolae and effects on L. tarentolae secreted acid phosphatase (SAP) activity. Cell viability did not significantly decrease in the presence of 50 μM anti-perovskite compounds, implying limited cytotoxicity. Yet SAP activity did increase in the cell free preparations with time in the presence of strontium compounds. Of interest was the observation that cell free SAP activity did not increase in the presence of protease inhibitors with or without added strontium compounds. Since secreted proteases may play a role in the maturation of Leishmania SAP and thus be involved with parasite-host infection establishment, this is in further need of evaluation. Nitric oxide production on day 4 post-addition of the strontium compounds was evaluated and showed an approximately 50% decrease in NO production in the presence of two test compounds relative to DMSO control cells. This is the first report of anti-perovskite compound inhibition of NO production by Leishmania.The manufacturing sector is critical in the realization of the economic pillar of the Kenyan Vision 2030. Over the last decade, the sector has experienced declining growth, mainly attributed to the agro-processing industry's poor financial performance. The Kenyan government has initiated stringent financial reforms across agro-based sectors, including coffee processing firms, to improve performance and increase farmers' returns. However, limited studies have investigated the impacts of working capital management (WCM) on small-scale coffee wet mills' financial performance. We assessed the effect of working capital management on financial performance in small-scale coffee wet mills. We collected the data from 41 small-scale coffee wet mills in Embu County, Eastern Kenya. We adopted a multivariate regression analysis approach on panel data (2014-2018) to analyze working capital management's impact on small-scale coffee wet mills' financial performance. Our findings showed that the current ratio and average payment period negatively affected the return on small-scale coffee wet mills' assets.
