Search

Background: Shift workers are at an increased risk of developing sleep disorders. The standard therapy recommended for sleep disorders is cognitive behavioural therapy for insomnia (CBT-I). Many of its interventions are based on a regular sleep and wake rhythm, which is difficult to apply for shift workers. We have therefore developed a new therapy manual specifically for shift workers (CBT-I-S), which should be more applicable to their needs. In particular, all interventions that require regularity have been removed, and instead, interventions that address factors that proved to be relevant to sleep in our preliminary study have been integrated. We now want to test this manual for its effectiveness. Methods: A randomised controlled trial with N = 142 will be conducted to compare two conditions: the newly developed therapy manual will be carried out in the experimental group, while cognitive behavioural therapy for insomnia will be employed in the standard group. Both treatments will be conducted online via MS Teams in a group setting with seven sessions each. Data will be collected at three measurement points (pre, post, 6-month follow-up) and analysed using linear mixed models. The study will investigate whether the two treatments have led to significant improvements in total sleep time, sleep onset latency, subjective sleep quality and daytime sleepiness in shift workers. It will also examine whether the new therapy manual is superior to standard therapy in shift workers and whether these effects are stable. Discussion: We assume that interventions designed to address depressive mood, anxiety, worry, rumination, dysfunctional thought patterns and attitudes towards sleep will also improve sleep. If this is indeed the case, these interventions could replace previous ones that require regularity. This could significantly improve the treatment of insomnia in shift workers. Trial registration: German Clinical Trials Registry DRKS DRKS00032086. Registered on August 16, 2023. [ABSTRACT FROM AUTHOR]

Abstract Background Shift workers are at an increased risk of developing sleep disorders. The standard therapy recommended for sleep disorders is cognitive behavioural therapy for insomnia (CBT-I). Many of its interventions are based on a regular sleep and wake rhythm, which is difficult to apply for shift workers. We have therefore developed a new therapy manual specifically for shift workers (CBT-I-S), which should be more applicable to their needs. In particular, all interventions that require regularity have been removed, and instead, interventions that address factors that proved to be relevant to sleep in our preliminary study have been integrated. We now want to test this manual for its effectiveness. Methods A randomised controlled trial with N = 142 will be conducted to compare two conditions: the newly developed therapy manual will be carried out in the experimental group, while cognitive behavioural therapy for insomnia will be employed in the standard group. Both treatments will be conducted online via MS Teams in a group setting with seven sessions each. Data will be collected at three measurement points (pre, post, 6-month follow-up) and analysed using linear mixed models. The study will investigate whether the two treatments have led to significant improvements in total sleep time, sleep onset latency, subjective sleep quality and daytime sleepiness in shift workers. It will also examine whether the new therapy manual is superior to standard therapy in shift workers and whether these effects are stable. Discussion We assume that interventions designed to address depressive mood, anxiety, worry, rumination, dysfunctional thought patterns and attitudes towards sleep will also improve sleep. If this is indeed the case, these interventions could replace previous ones that require regularity. This could significantly improve the treatment of insomnia in shift workers. Trial registration German Clinical Trials Registry DRKS DRKS00032086 . Registered on August 16, 2023.

Despite the surge in efficacy studies, the relative effectiveness of any two math interventions is largely unknown and replications are rare. To ensure that students benefit from high-quality learning experiences, the current conceptual replication of Wang and Woodworth, a randomized control trial, evaluated the relative impacts of two computer programs used in a school district as supplements to students' regular education math instruction, DreamBox Learning and Zearn Math. For 115 students in kindergarten and first grade, data were collected before and after an 11-week implementation period. Measures of effect size, but not null hypothesis statistical tests, suggested that participants in the DreamBox condition had higher test scores on posttest numeracy and geometry (Hedges g =.32 and.14). There was also a statistically significant group by pretest interaction, evidence of "Matthew Effects" for numeracy. Although some support for adopting DreamBox as a supplemental method for improving math competencies of students in early elementary school was provided, more research is needed as the true effect may be smaller than what the present study reports. The study's implications are discussed. [ABSTRACT FROM AUTHOR]

Reiki is a philosophy and healing technique that directs the use of vital energy (ki) for energy rebalance, as well as healing, in a holistic sense, of physical, emotional, mental, and spiritual processes. The practice is part of the integrative and complementary practices recognized by the World Health Organization. This study aimed to evaluate the Reiki effects on people's life quality perception, by using the World Health Organization Quality of Life-BREF (WHOQOL-BREF). We analyzed the answers of 144 individuals, and the data were categorized in quartiles according to the number of Reiki sessions attended. The results of each question and dimension of the questionnaire were analyzed by Student's t test (individual questions) and analysis of variance (dimensions). We observed significant improvement in the perception of physical pain, need for medical treatment, meaning of life, physical environment, availability of money, availability of information, locomotion, work capacity, access to health, place of residence, and transportation facilities. Reiki sessions have improved people's quality of life perception in many aspects, proving its therapeutic efficacy in a broader approach to health promotion. [ABSTRACT FROM AUTHOR]

A vast majority of elementary students struggle with the core, pre-algebraic concept of mathematical equivalence. The Improving Children's Understanding of Equivalence (ICUE) intervention integrates four research-based strategies to improve outcomes for second grade students: (1) introducing the equal sign before arithmetic, (2) nontraditional arithmetic practice, (3) concreteness fading exercises, and (4) comparison and explanation. In a large-scale randomized control trial in California public schools, 132 second grade teachers were randomly assigned to either use the ICUE intervention or an active control consisting of nontraditional arithmetic practice alone. Using data from 121 teachers in the analytic sample, the study found that students in the intervention group outperformed students in the active control on proximal and transfer measures of equivalence with no observable tradeoffs in computational fluency. The findings suggest that the ICUE intervention helps students construct a robust understanding of mathematical equivalence, a critical precursor to success in algebra. [ABSTRACT FROM AUTHOR]

Adaptive learning systems personalize instruction to students' individual learning needs and abilities. Such systems have shown positive impacts on learning. Many schools in the United States have adopted adaptive learning systems, and the rate of adoption in China is accelerating, reaching almost 2 million unique users for one product alone in the past 3 years. Given such rapid adoption in China, it is useful to examine the efficacy of adaptive learning within that country's educational system. This study aimed to compare the learning impacts of individualized adaptive learning courseware to two common instructional approaches in China: large-group and small-group classroom instruction. This paper describes the results of two efficacy studies of one of China's first adaptive learning systems, Squirrel AI Learning. One study compares classroom-based individualized adaptive learning instruction to large-group instruction, and another to small-group instruction. Chinese eighth-grade students from two provinces randomly assigned to use Squirrel AI Learning showed greater gains on a mathematics test than those randomly assigned to whole-class or small-group instruction led by expert teachers. Findings provide a basis for further research into the selection, use, and impact of adaptive learning systems in Chinese education. [ABSTRACT FROM AUTHOR]

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies. [ABSTRACT FROM AUTHOR]

Copyright of China Surfactant Detergent & Cosmetics (1001-1803) is the property of China Surfactant Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Detergent & Cosmetics is the property of Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

User measurement bias during subcutaneous tumor measurement is a source of variation in preclinical in vivo studies. We investigated whether this user variability could impact efficacy study outcomes, in the form of the false negative result rate when comparing treated and control groups. Two tumor measurement methods were compared; calipers which rely on manual measurement, and an automatic 3D and thermal imaging device. Tumor growth curve data were used to create an in silico efficacy study with control and treated groups. Before applying user variability, treatment group tumor volumes were statistically different to the control group. Utilizing data collected from 15 different users across 9 in vivo studies, user measurement variability was computed for both methods and simulation was used to investigate its impact on the in silico study outcome. User variability produced a false negative result in 0.7% to 18.5% of simulated studies when using calipers, depending on treatment efficacy. When using an imaging device with lower user variability this was reduced to 0.0% to 2.6%, demonstrating that user variability impacts study outcomes and the ability to detect treatment effect. Reducing variability in efficacy studies can increase confidence in efficacy study outcomes without altering group sizes. By using a measurement device with lower user variability, the chance of missing a therapeutic effect can be reduced and time and resources spent pursuing false results could be saved. This improvement in data quality is of particular interest in discovery and dosing studies, where being able to detect small differences between groups is crucial. [ABSTRACT FROM AUTHOR]

A long‐standing university‐community partnership used a longitudinal randomized control trial to implement and evaluate two couple relationship education (CRE) curricula, ELEVATE and Couples Connecting Mindfully (CCM), among an economically and racially diverse population of adult couples. Married and non‐married couples (n = 929 couples) completed baseline surveys and were randomly assigned to either one of the two program groups or to the control group by implementation site. Follow‐up surveys were collected at 2 months, 6 months, and 1 year after baseline. Using an intent‐to‐treat approach, growth curve modeling comparisons of trajectories indicated program effects at 1 year post‐baseline in key outcome areas. Both the ELEVATE and the CCM group reported significant gains in couple relationship skills, couple quality, and family harmony over time compared to the control group that experienced either no change or declines. Further, the ELEVATE group also demonstrated positive program effects on measures of mental health and sleep quality. An assessment of the central premise of CRE indicated that the immediate post‐program improvements in couple relationship skills predicted later couple quality for both program groups. This study indicates that both ELEVATE and CCM can be considered evidence‐based CRE programs for use with a broad population of couples. [ABSTRACT FROM AUTHOR]

Background: The increasing need for speech therapy due to our ageing population raises the demand on therapeutical resources. To meet this demand, innovative delivery of speech training is required. eHealth applications may provide a solution, as intensified and prolonged training is only possible and affordable in patients' home environment. Aims: This study explores the effects on speech intelligibility of game‐based speech training that provides automatic feedback on loudness, pitch and pronunciation. Additionally, we investigate how satisfied patients are with the game‐based speech training and how they experience the automatic feedback. Furthermore, patients' preferences for game‐based speech training compared with face‐to‐face training are explored. Methods and Procedures: Eight adult dysarthric speakers with Parkinson's disease (PD) completed a 4‐week game‐based speech training in their home environment. For each speaker, 24 speech utterances were audio recorded 4 weeks before (T1), immediately before (T2) and immediately after (T3) the training. All speech samples were rated on speech intelligibility by 10 untrained listeners, by comparing them with the corresponding utterances realized by a healthy speaker. Changes over time were analysed using a linear mixed‐effects analysis. Patient satisfaction with the game and the automatic feedback was assessed using a questionnaire. The preferences of patients were collected using a paired comparisons procedure in which the patients were asked whether they would prefer game‐based or face‐to‐face speech training in four hypothetical scenarios with different hypothesized levels of speech improvement. Outcomes and Results: While there was no significant difference in speech intelligibility ratings between T1 and T2, we did find one between T2 and T3. At T3, speech intelligibility was rated higher than at T2, indicating positive effects of the game‐based speech training. Patients generally seemed satisfied with the game as average ratings were above 7 on a 10‐point rating scale. Generally, patients agreed with the automatic feedback and could use it to positively change the way they spoke. Patients prefer the training that provides the highest hypothetical improvement, and thus do not prefer face‐to‐face above game‐based therapy. Conclusions and Implications: The results of this study suggest that dysarthric speakers due to PD see game‐based speech therapy as a valid alternative for face‐to‐face therapy and that it leads to an average improvement in speech intelligibility. For an optimal effect and user satisfaction it should preferably not be used in isolation but in combination with face‐to‐face training. In this manner, the strengths of both therapeutic deliveries can be harnessed. WHAT THIS PAPER ADDS: What is already known on this subject: Dysarthric speech in patients with PD is known to benefit from intensified and long‐term speech therapy. The increasing need for speech therapy due to our ageing population raises the demand on therapeutical resources making highly frequent and long‐term therapy difficult. eHealth provides the opportunity to intensify and prolong speech training in patients' home environment. A drill‐and‐practice method was employed and investigated in a web‐based speech application, indicating positive effects on speech intelligibility. However, participants indicated a lack of variation in exercises making the training less enjoyable. Other research showed that serious games can increase enjoyment during training. What this paper adds to existing knowledge: The results of this study show that it is possible to develop a serious game that can be successfully used for speech training by patients with dysarthria due to PD. Comparing speech intelligibility ratings before and after training, we observed significant improvements in speech intelligibility ratings. Patients generally agree with the automatic feedback and can use it to positively change the way they speak. Average ratings were above 7 on a 10‐point scale, indicating that patients are satisfied with the game. Patients prefer the type of training (game based or face to face) that provides the highest hypothetical improvement. What are the potential or actual clinical implications of this work?: The results of this study suggest that game‐based speech training can improve speech intelligibility in patients. This indicates that it can be considered a suitable approach in the treatment of patients with dysarthria due to PD. Patients do not prefer game‐based training above face‐to‐face training in all scenarios. For that reason, for every patient one should carefully consider how to optimally combine game‐based and face‐to‐face training. [ABSTRACT FROM AUTHOR]

The best practices of agile software development have had a significant positive impact on the quality of software and time‐to‐delivery. As a result, many leading software companies employ some form of agile software development practices. Some of the most important best practices of agile software development, which have received significant attention in recent years, are automated unit testing (AUT) and test‐driven development (TDD). Both of these practices work in conjunction to provide numerous benefits. AUT leads to reduced time to test, discover bugs, fix bugs, and implement new features; wider and measurable test coverage; reproducibility, reusability, consistency, and reliability of tests; improved accuracy, regression testing, parallel testing, faster feedback cycle, reduced cost, and higher team morale. The benefits of TDD include flexible and adaptive program design, cleaner interfaces, higher code quality, maintainability, extensibility, reliability, detailed evolving specification, reduced time on bug fixes and feature implementation, reliable refactoring, and code changes, reduced cost, reduced development time, and increased programmer productivity. Unfortunately, students in introductory programming courses are generally not introduced to AUT and TDD. This leads to the development of bad programming habits and practices which become harder to change later on. By introducing the students earlier to these industry‐standard best practices, not only the motivation and interest of students in this area can be increased but also their academic success and job marketability can be enhanced. This paper presents the detailed design and efficacy study of an introductory C++ programming course designed using the principles of AUT and TDD. The paper presents the pedagogical techniques employed to build industry‐proven agile software development practices in the students. As part of the paper, all the course material including the source code for the labs and the automated unit tests are being made available to encourage people to incorporate these best practices into their curricula. [ABSTRACT FROM AUTHOR]

(1) Background: The oral vaccination of free-roaming dogs against rabies has been developed as a promising complementary tool for mass dog vaccination. However, no oral rabies vaccine has provided efficacy data in dogs according to international standards. (2) Methods: To test the immunogenicity and efficacy of the third-generation oral rabies virus vaccine strain, SPBN GASGAS, in domestic dogs, dogs were offered an egg-flavoured bait containing 3.0 mL of the vaccine (107.5 FFU/mL) or a placebo egg-flavoured bait. Subsequently, these 25 vaccinated and 10 control animals were challenged approximately 6 months later with a dog rabies virus isolate. Blood samples were collected at different time points postvaccination and examined by ELISA and RFFIT. (3) Results: All but 1 of the 25 vaccinated dogs survived the challenge infection; meanwhile, all 10 control dogs succumbed to rabies. The serology results showed that all 25 vaccinated dogs seroconverted in ELISA (>40% PB); meanwhile, only 13 of the 25 vaccinated dogs tested seropositive ≥ 0.5 IU/mL) in RFFIT. (4) Conclusions: The SPBN GASGAS rabies virus vaccine meets the efficacy requirements for live oral rabies vaccines as laid down by the European Pharmacopoeia and the WOAH Terrestrial Manual. SPBN GASGAS already fulfilled the safety requirements for oral rabies vaccines targeted at dogs. Hence, the egg-flavoured bait containing SPBN GASGAS is the first oral vaccine bait that complies with WOAH recommendations for the intended use of oral vaccination of free-roaming dogs against rabies.

Currently, bacterial conjunctivitis is managed by multiple antibiotic eye-drop solution, which is highly inefficient due to low ocular bioavailability and frequent dosing. Therapeutic soft contact lenses can be used to sustain the release of ocular drugs. However, the conventional soaking method (economic and widely used) showed low drug uptake and high burst release, and the optophysical properties of the contact lens were altered for clinical application. In this paper, novel ofloxacin-loaded niosomes were developed to increase the drug loading capacity of contact lenses while also sustaining ocular drug delivery. Ofloxacin-loaded niosomes were prepared by the thin film hydration technique with three levels of cholesterol. The niosome-laden contact lenses (OFL-Nio-L) led to improved optophysical properties (swelling, transmittance, oxygen permeability) and lysozyme adherence compared to the conventional soaked contact lens (CV-OFL-L). The in vitro drug release data of CV-OFL-L showed high burst release, while OFL-Nio-L lenses showed sustained release up to 48–96 h. In a rabbit tear fluid model, the OFL-Nio-100-L lens showed a high drug concentration at all-time points compared to the CV-OFL-L and eye-drop solution. The efficacy study in the rabbit model showed improved healing effect with OFL-Nio-100-L lens compared to frequent eye-drop therapy. In conclusion, the paper demonstrated the successful application of niosomes to deliver ofloxacin using contact lens without affecting the critical lens properties to substitute eye-drop therapy. [ABSTRACT FROM AUTHOR]

Safe and effective rotavirus vaccines (RVs) are needed to reduce the enormous public health burden of rotavirus illness in developing countries. Vaccination is critical for effective control of rotavirus infection since it cannot be prevented with improvements in water and sanitation. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) has completed several groundbreaking RV trials (Phase I-Phase IV). The safety, immunogenicity, efficacy, and effectiveness of different RVs were evaluated among both urban and rural populations. In this study, we present the results, policy implications, and lessons learned for successful implementation of these trials as well as future directions for rotavirus vaccination in Bangladesh. [ABSTRACT FROM AUTHOR]

The efficacy of an eye cream containing polypeptides to reduce dark circles under eyes was studied. According to the relevant standards and methods, the internal control test (pH test), safety test and in vivo efficacy evaluation test were carried out to verify the performance of the eye cream in reducing dark circles. Thirty volunteers with obvious dark circles around their eyes were selected to use the eye cream for two months. The results show that the eye cream can pass the internal control index test and has no irritation to the eyes.The changes in skin moisture content of cuticle were analyzed, and the difference of ITA was measured by skin color probe. Visualized image analysis on the dark circles around the left and right eyes, as well as the subjective evaluation made by the volunteers, were operated. The conclusions are drawn that, the eye cream containing polypeptides has a good efficacy in reducing dark circles without any adverse reactions. [ABSTRACT FROM AUTHOR]

[Display omitted] • A modified emulsiosonication method was developed for combinatorial FR-NLC. • Prolonged-release of drugs from linogel obeyed non-Fickian Higuchi kinetics model. • Linogel exhibited enhanced permeation via alteration in tight junction of skin. • Improved drug deposition was recorded after dermal application of linogel. • In vitro efficacy study showed greater efficacy of linogel against skin cancer. In the present study, combinatorial nanostructured lipid carrier gel of 5-fluorouracil and resveratrol was formulated, optimized and characterized to enhance permeation in between epidermis and dermis layers of the skin to obtain a synergistic effect against skin cancer. After extensive trials, a newly modified emulsiosonication method was developed and additionally, for the first time, stability studies were done in the beginning to optimize formulation technique, which exhibited two major benefits simultaneously; first, it provided best-optimized technique for preparation of combinatorial lipid-nanosystem, and secondly, it also demonstrated a detailed report card of durability of formulations. In vitro release study showed a significantly improved, slow and prolonged release of drugs from the optimized lipid-nanosystem (*** p < 0.05), which followed non-Fickian Higuchi kinetics. Besides, mechanism of skin permeation enhancement study, dermatokinetic assessment, and depth analysis of optimized formulation on skin exhibited improved permeation and well distribution of drugs up to the dermis layer of skin. Moreover, combinatorial linogel possessed significantly greater efficacy (** p < 0.01) on the A431 cell line, as compared to the conventional formulation. Thus, findings revealed that modified method of preparation for dual drug-loaded lipid-nanosystem lead to the production of a stable formulation that also improved the retention of both 5-fluorouracil and resveratrol in between the epidermis and dermis region of skin thereby helping in the management and treatment of skin cancer. [ABSTRACT FROM AUTHOR]

To manage glaucoma, timolol is currently delivered via eye drop solution in high doses due to poor ocular bioavailability. The silicone contact lenses can be used to control the release of timolol by conventional soaking technology without changing or altering the swelling and optical transmittance of the contact lens. However, the soaking method showed limitations of low timolol uptake and high-burst release. In this research work, we have investigated the influence of microemulsion on timolol loading from the soaking solution and its ability to control the drug release kinetics. The contact lenses were soaked in the timolol-microemulsion soaking solution (TB-ME-SM) and compared with the timolol-soaking solution (TB-SM) without microemulsion. The loading of timolol laden-microemulsion in the contact lenses did not alter the swelling and transmittance properties. The two fold improvement in the timolol loading was noted from the TB-ME-SM soaking solution in comparison to TB-SM solution. The flux report showed improvement in the release rate profiles of TB-ME-SM lenses (up to 48–96 h) in comparison to TB-SM lenses (up to 24–36 h). The rabbit tear fluid data of TB-ME-SM lenses showed improvement in the timolol retention time in comparison to TB-SM lenses and eye drop solution. The efficacy study in the rabbit model showed a peak and valley profile with eye drop therapy, while TB-ME-SM-2 contact lenses showed prolong reduction in intra ocular pressure for 96 h. The study demonstrates the potential of microemulsion to improve the uptake of timolol and control release kinetics without altering the swelling and transmittance of the contact lens. [ABSTRACT FROM AUTHOR]

Objective: To compare the results of treatment with antianginal drug nicorandil in patients with stable coronary artery disease according to the results of the observational study (OS) «NIKEA» and randomized controlled trial (RCT) «IONA». Methods: «NIKEA » observational program included 590 patients with stable angina pectoris. Subgroups in the OS were formed based on the adherence to nicorandil use. Adherence was assessed during follow-up direct questioning. «IONA » RCT included 5126 patients with stable angina pectoris. Results: Follow-up period and mean age of patients were equal in OS and RCT. In OS the group of adherent to nicorandil use patients had fewer males, life-saving drugs were administered significantly more often than in RCT, comorbidities (arterial hypertension, peripheral atherosclerosis and diabetes mellitus) were more pronounced. Angina pectoris class III was diagnosed in 32% of the OS patients vs 11% of the RCT patients, and class I – in 4.4% and 26%, respectively (р

Background: Many tumors are refractory to immune checkpoint inhibitors, but their combination with cytotoxics is expected to improve sensitivity. Understanding how and when cytotoxics best re-stimulate tumor immunity could help overcome resistance to immune checkpoint inhibitors. Methods: studies were performed in C57BL/6 mice grafted with immune-refractory LL/2 lung cancer model. A longitudinal immunomonitoring study on tumor, spleen, and blood after multiple treatments including Cisplatin, Pemetrexed, and anti-VEGF, either alone or in combination, was performed, spanning a period of up to 21 days, to determine the optimal time window during which immune checkpoint inhibitors should be added. Finally, an efficacy study was conducted comparing the antiproliferative performance of various schedules of anti-VEGF, Pemetrexed-Cisplatin doublet, plus anti-PD-1 (i.e., immunomonitoring-guided scheduling, concurrent dosing or a random sequence), as well as single agent anti-PD1. In vivo studies were performed in C57BL/6 mice grafted with immune-refractory LL/2 lung cancer model. A longitudinal immunomonitoring study on tumor, spleen, and blood after multiple treatments including Cisplatin, Pemetrexed, and anti-VEGF, either alone or in combination, was performed, spanning a period of up to 21 days, to determine the optimal time window during which immune checkpoint inhibitors should be added. Finally, an efficacy study was conducted comparing the antiproliferative performance of various schedules of anti-VEGF, Pemetrexed-Cisplatin doublet, plus anti-PD-1 (i.e., immunomonitoring-guided scheduling, concurrent dosing or a random sequence), as well as single agent anti-PD1. Results: Anti-VEGF and cytotoxic agents show time-dependent immunomodulatory effects, suggesting that sequencing is a critical feature when combining these agents with immune checkpoint inhibitors. An efficacy study confirmed that sequencing treatments further enhance antiproliferative effects in lung cancer models compared to concurrent dosing and partly reverse the resistance to cytotoxics and anti-PD1.Conclusions: Anti-VEGF and cytotoxic agents show time-dependent immunomodulatory effects, suggesting that sequencing is a critical feature when combining these agents with immune checkpoint inhibitors. An efficacy study confirmed that sequencing treatments further enhance antiproliferative effects in lung cancer models compared to concurrent dosing and partly reverse the resistance to cytotoxics and anti-PD1., Competing Interests: All authors declared that there are no conflicts of interest., (© The Author(s) 2024.)

Objectives: We assessed the efficacy of a 3-week primary or salvage caspofungin regimen in patients with chronic obstructive pulmonary disease (COPD) and concomitant proven or suspected invasive pulmonary aspergillosis (IPA)., Methods: Forty-four patients were treated with an initial loading caspofungin dose of 70 mg, followed by a daily dose of 50 mg for 20 days. The main efficacy endpoint was clinical effectiveness. Secondary endpoints included the clinical efficacy of caspofungin after 1 week, therapeutic efficacy based on the European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, the sensitivity of different Aspergillus strains to caspofungin in vitro , and the safety of caspofungin., Results: An assessment of 42 patients in the intention-to-treat group revealed efficacy rates of 33.33% within 1 week and 38.10% within 3 weeks. According to the EORTC/MSG criteria, the treatment success rate was 38.10%. The success rate of first-line treatment was 54.76%, whereas salvage treatment had a success rate of 45.24%. No adverse events were reported among the participants., Conclusions: Caspofungin is effective and safe as an initial or salvage treatment for patients with IPA and COPD.

Human embryonic stem cell (hESC)-derived midbrain dopaminergic (mDA) cell transplantation is a promising therapeutic strategy for Parkinson's disease (PD). Here, we present the derivation of high-purity mDA progenitors from clinical-grade hESCs on a large scale under rigorous good manufacturing practice (GMP) conditions. We also assessed the toxicity, biodistribution, and tumorigenicity of these cells in immunodeficient rats in good laboratory practice (GLP)-compliant facilities. Various doses of mDA progenitors were transplanted into hemi-parkinsonian rats, and a significant dose-dependent behavioral improvement was observed with a minimal effective dose range of 5,000-10,000 mDA progenitor cells. These results provided insights into determining a low cell dosage (3.15 million cells) for human clinical trials. Based on these results, approval for a phase 1/2a clinical trial for PD cell therapy was obtained from the Ministry of Food and Drug Safety in Korea, and a clinical trial for treating patients with PD has commenced., Competing Interests: Declaration of interests D.-W.K. is a chief technology officer of S. Biomedics Co., Ltd. J.H.E., M.-Y.J., H.-J.H., S.K.C., S.T.N., K.-S.J., D.-H.K., C.-Y.P., and M.S.C. are currently employed at S. Biomedics Co., Ltd. We have patents related to this work. 1. Title: method for inducing differentiation of stem cells into dopaminergic neural precursor cells, patent number: 102392133(KR), 11655450(US), 07152050(JP), and 2020202273(AU). 2. Title: efficient and universal method for neural differentiation of human pluripotent stem cells, patent number: 101168053(KR), 08551783(US), 05756019(JP), and 02502987(EP)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Copyright of Detergent & Cosmetics is the property of Detergent & Cosmetics Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Currently, conjunctivitis is treated using ofloxacin eye drop solution, which shows low bioavailability and patient non-compliance. Ofloxacin loaded contact lens can be used to overcome the issues related to eye drop solutions (i.e. low bioavailability and frequent instillation). However, the conventional soaking method shows poor ofloxacin uptake and significantly affect the swelling and optical properties of the contact lenses. The current research investigates the effect of microemulsion on the ofloxacin uptake and its effect on the physical properties of the contact lens along with ofloxacin-release kinetics. In comparison to the conventional soaking method (Of-SM, ofloxacin-packaging solution), the ofloxacin loaded microemulsion-soaked contact lenses (Of-ME) showed improved drug uptake and physical properties of the contact lenses. The in vitro release data of Of-ME contact lenses showed 72–120 h release profile, while Of-SM contact lenses showed 24–60 h. The in vivo drug release data in the tear fluid (New Zealand rabbit's eye) showed high ofloxacin retention in comparison to the eye drop solution. The efficacy study in the rabbit model showed equivalent healing effect with the Of-ME contact lens in comparison to the frequent high dose eye drop therapy. Thus, the study demonstrates the application of microemulsion system to improve the ofloxacin loading capacity in the contact lens along with improvement in the physical properties to treat conjunctivitis. [ABSTRACT FROM AUTHOR]

Purpose The basic aim of the present study was to analyze the results of implant failures in two different implant populations, and how these results may vary depending on how the data are compiled and analyzed. Materials and Methods: Two groups of consecutively treated patients were included who had been provided with either one single implant in a partially edentulous upper jaw (1881 patients) or four to eight implants in an edentulous upper jaw (2031 patients/12 454 implants). The risk of implant failure in the two groups separately and in combination was statistically compared by using uni‐ and multivariable analyses. Results: The two groups showed significant differences in inclusion, surgical treatment protocols, and the risk of implant failures (P <.05). Overall, 25‐year patient‐level cumulative survival rates (CSRs) were 75.8% and 96.3% for edentulous and single implant treatment, respectively. "Dental condition" was the variable associated with the greatest risk of implant failure (HR 6.00; edentulous). Only one variable was significantly associated with the risk of implant failure in all tested groups ("time after surgery"; a decreased risk was observed over time), and more variables were statistically associated with implant failures in the edentulous group than in the single implant group. Conclusions: Edentulous patients present a significantly and substantially higher risk of implant failures than patients provided with a single implant. When patients with different clinical conditions are pooled into the same group, patients with the most common condition in the total group have greatest impact on the result of the total group. Based on the present observations, risk patterns for a certain oral condition are not necessarily comparable with the implant treatment received by other patients, and the external validity may be limited in small, homogeneous groups of patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate hypocholesterolemic and hypoglycemic potential of citrus peel extract and powder using rodent experimental modeling. Methods: Considering the fact, rat feeding trial was carried out for a period of 56 d to access the prophylaxis of citrus peel flavonoids by employing normal (study I), hyperglycemic (study II) and hypercholesterolemic (study III) rats. Each study was further divided into three groups to ensure the provision of selected diets, i.e., control, functional and nutraceutical diets. Each study was further divided into three groups to ensure the provision of selected diets, i.e., control, functional and nutraceutical diets. Results: Declining trend for total cholesterol was observed in all studies with maximum reduction (8.55%) in rat group fed on nutraceutical diet in study III. Likewise, levels of low density lipoproteins and triglycerides reduced 11.39% and 7.89% respectively in hypercholesterolemic rats. Moreover, nutraceutical diet alleviated the sera glucose level by 8.96% in study II. Conclusions: Conclusively, inclusion of citrus peel bioflavonoids in dietary therapies is a promising strategy to modulate lipidemic and glycemic attributes without imparting any deleterious effect on hematological parameters.

The purpose of this study was to verify the efficacy of a single intra-articular (i.a.) injection of a hyaluronic acid-chitlac (HY-CTL) enriched with two low dosages of triamcinolone acetonide (TA, 2.0 mg/mL and 4.5 mg/mL), in comparison with HY-CTL alone, with a clinical control (TA 40 mg/mL) and with saline solution (NaCl) in an in vivo osteoarthritis (OA) model. Seven days after chemical induction of OA, 80 Sprague Dawley male rats were grouped into five arms (n = 16) and received a single i.a. injection of: 40 mg/mL TA, HY-CTL alone, HY-CTL with 2.0 mg/mL TA (RV2), HY-CTL with 4.5 mg/mL TA (RV4.5) and 0.9% NaCl. Pain sensitivity and Catwalk were performed at baseline and at 7, 14 and 21 days after the i.a. treatments. The histopathology of the joint, meniscus and synovial reaction, type II collagen expression and aggrecan expression were assessed 21 days after treatments. RV4.5 improved the local pain sensitivity in comparison with TA and NaCl. RV4.5 and TA exerted similar beneficial effects in all gait parameters. Histopathological analyses, measured by Osteoarthritis Research Society International (OARSI) and Kumar scores and by immunohistochemistry, evidenced that RV4.5 and TA reduced OA features in the same manner and showed a stronger type II collagen and aggrecan expression; both treatments reduced synovitis, as measured by Krenn score and, at the meniscus level, RV4.5 improved degenerative signs as evaluated by Pauli score. TA or RV4.5 treatments limited the local articular cartilage deterioration in knee OA with an improvement of the physical structure of articular cartilage, gait parameters, the sensitivity to local pain and a reduction of the synovial inflammation.

Background Opioid-induced constipation (OIC) has become more common in the intensive care unit (ICU) due to increased opioid utilization. Traditional laxatives often prove ineffective against OIC, leading to the increased utilization of naloxegol. However, further research is needed to confirm naloxegol's effectiveness and safety in critical care. This study aimed to explore the safety and efficacy of this intervention in critically ill OIC patients. Methods A single-center retrospective study was conducted on 353 patients who received one or more doses of naloxegol from January 1, 2019, to June 30, 2020, for OIC at a tertiary care center. The primary endpoint of this study was to evaluate serious adverse events such as reduced analgesic effect, gastrointestinal perforation, seizure, acute myocardial infarction (AMI), or ventricular arrhythmias using Naranjo Scale in critically ill patients. The secondary goal was to assess the efficacy of naloxegol, measured by the time of the first bowel movement. Results The average duration of naloxegol use was three days, with the first bowel movement occurring at an average of 11.3 hours. Furthermore, 59.8% of individuals had their first bowel movement within 20 hours of receiving naloxegol. There was a low level of causality between naloxegol use and adverse events such as gastrointestinal perforation, seizures, AMI, cardiovascular mortality, stroke, and ventricular arrhythmia. Additionally, reduction in analgesia showed no strong relationship with naloxegol use indicated by the Naranjo Scale assessment. Conclusion Naloxegol showed promising safety and efficacy profiles in treating OIC amongst critically ill patients, though our findings require further validation through prospective studies. This research paves the way for further investigation into naloxegol's role in OIC management, emphasizing the necessity of personalized treatment strategies in critical care settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rizwan et al.)

Background Limited numbers of large effectiveness studies on routine dental implant treatment are available in the literature. Purpose To report retro-prospective data on prevalence of early implant failures in a large number of routine patients/operations at 1 referral clinic. Materials and methods A total of 2848 patients were consecutively provided with 9582 implants with an anodized surface (Nobel Biocare AB) during 3448 implant operations between 2003 and 2011. All patients were invited to a follow-up program and early implant failures up to first annual examination were consecutively identified. A logistic multivariate data analysis was performed to identify possible factors with an association to early implant failures. Results A total of 43, 73, and 81 implant operations were denoted as early failures depending on when cut-off time was defined, using: abutment connection, prosthesis placement, or at first year of follow-up, respectively. Five factors showed significant association to 'early implant failures,' where the highest risk for a failure was associated to 'surgeon' (hazard ratio [HR] 5.13), followed by 'not prosthetic treatment at the referral clinic' (HR 2.71). When all 5 significant factors were present, the risk for an early failure after an operation was 7.0%, and the risk decreased to 0.1% when none/lowest risk factors were present. Conclusions The role of the surgeons/dentists involved in the rehabilitation of the implant patients and numbers of placed implants (degree of tooth loss) showed the strongest associations to early implant failures in the present clinic. Also increased bone resorption was associated to increased risk for implant failure. [ABSTRACT FROM AUTHOR]

Background Little knowledge is available on implant treatment in large effectiveness studies in routine practice. Purpose To report retro-prospective data on prevalence of peri-implantitis surgery and late implant failures in a large number of routine patients at 1 referral clinic. Materials and methods Altogether 9582 implants with an anodized surface (Nobel Biocare AB) were consecutively placed between 2003 and 2011 and followed-up to end of 2015. All peri-implantitis operations and late implant failures were consecutively identified. A logistic multivariate data analysis was performed to identify association between the complications and different clinical factors. Furthermore, data on prevalence on risk for inflammation and bone loss at implants ('peri-implantitis') and surgery related to peri-implantitis was collected for another reference group of about 10 000 implant patients during 3 consecutive years (2013-2015). Results Cumulative survival rates for implant operations without peri-implantitis surgery or implant failures were calculated to 96.4% (95% CI: 97.3-95.4) and 95.0% (95% CI: 96.0-94.1) after 10 years, respectively. Risk for 'peri-implantitis surgery' showed a significant association ( P < .05) to number of placed implants (hazard ratio [HR] 1.40; 95% CI: 1.24-1.59). Three factors showed significant association to risk for 'late implant failures,' where 'treatment in lower jaw' had the highest risk; HR 2.03. 'Overall implant failures' were associated to 4 significant factors where 'surgeon' (HR 2.50) showed highest impact on risk. 'Numbers of implants' and 'bone resorption' at surgery were the 2 significant factors that were consistent for all the time periods of failures during follow-up (early/late/total). On an average 7.4% of examined patients in the reference group were denoted with highest risk group ('peri-implantitis') of which on an average 12.7% of these patients had surgery related to peri-implantitis. Conclusions 'The dentist' involved in the surgical and prosthetic rehabilitation of the implant patients, 'number of implants' and degree of 'bone resorption' seem to have most impact on overall implant complications and failures in the present patient group. [ABSTRACT FROM AUTHOR]

Objective To investigate hypocholesterolemic and hypoglycemic potential of citrus peel extract and powder using rodent experimental modeling. Methods Considering the fact, rat feeding trial was carried out for a period of 56 d to access the prophylaxis of citrus peel flavonoids by employing normal (study I), hyperglycemic (study II) and hypercholesterolemic (study III) rats. Each study was further divided into three groups to ensure the provision of selected diets, i.e. , control, functional and nutraceutical diets. Each study was further divided into three groups to ensure the provision of selected diets, i.e. , control, functional and nutraceutical diets. Results Declining trend for total cholesterol was observed in all studies with maximum reduction (8.55%) in rat group fed on nutraceutical diet in study III. Likewise, levels of low density lipoproteins and triglycerides reduced 11.39% and 7.89% respectively in hypercholesterolemic rats. Moreover, nutraceutical diet alleviated the sera glucose level by 8.96% in study II. Conclusions Conclusively, inclusion of citrus peel bioflavonoids in dietary therapies is a promising strategy to modulate lipidemic and glycemic attributes without imparting any deleterious effect on hematological parameters. [ABSTRACT FROM AUTHOR]