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BioRxiv : the Preprint Server For... Jun 2024Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial...
BACKGROUND
Oxidative stress is implicated in the pathogenesis and progression of abdominal aortic aneurysm (AAA). Antioxidant delivery as a therapeutic for AAA is of substantial interest although clinical translation of antioxidant therapy has met with significant challenges due to limitations in achieving sufficient antioxidant levels at the site of AAA. We posit that nanoparticle-based approaches hold promise to overcome challenges associated with systemic administration of antioxidants.
METHODS
We employed a peptide-based nanoplatform to overexpress a key modulator of oxidative stress, superoxide dismutase 2 (SOD2). The efficacy of systemic delivery of SOD2 mRNA as a nanotherapeutic agent was studied in two different murine AAA models. Unbiased mass spectrometry-enabled proteomics and high-dimensional bioinformatics were used to examine pathways modulated by SOD2 overexpression.
RESULTS
The murine SOD2 mRNA sequence was mixed with p5RHH, an amphipathic peptide capable of delivering nucleic acids to form self-assembled nanoparticles of ∼55 nm in diameter. We further demonstrated that the nanoparticle was stable and functional up to four weeks following self-assembly when coated with hyaluronic acid. Delivery of SOD2 mRNA mitigated the expansion of small AAA and largely prevented rupture. Mitigation of AAA was accompanied by enhanced SOD2 protein expression in aortic wall tissue. Concomitant suppression of nitric oxide, inducible nitric oxide synthase expression, and cell death was observed. Proteomic profiling of AAA tissues suggests that SOD2 overexpression augments levels of microRNAs that regulate vascular inflammation and cell apoptosis, inhibits platelet activation/aggregation, and downregulates mitogen-activated protein kinase signaling. Gene set enrichment analysis shows that SOD2 mRNA delivery is associated with activation of oxidative phosphorylation, lipid metabolism, respiratory electron transportation, and tricarboxylic acid cycle pathways.
CONCLUSIONS
These results confirm that SOD2 is key modulator of oxidative stress in AAA. This nanotherapeutic mRNA delivery approach may find translational application in the medical management of small AAA and the prevention of AAA rupture.
PubMed: 38948794
DOI: 10.1101/2024.06.17.599454 -
Sexuality Research & Social Policy :... Jun 2024Parents who do not feel responsible for parent-child sexual communication (PCSC) may be missing out on opportunities to engage in PCSC that has protective effects on...
INTRODUCTION
Parents who do not feel responsible for parent-child sexual communication (PCSC) may be missing out on opportunities to engage in PCSC that has protective effects on children's sexual well-being. Using the theory of planned behavior and feminist theory, we explore how parents' PCSC attitudes and demographics are associated with perceptions of who is responsible for PCSC.
METHODS
Using data collected in December 2019 through January 2020 from parents of 6-11-year-olds, we ran chi-square tests, ANOVAs, and logistic regressions to determine how parent PCSC attitudes and other parental factors are associated with parent perceptions of who is responsible for PCSC.
RESULTS
The majority of parents saw themselves and/or a co-parent as primarily responsible for PCSC about facts and values. Bivariately, parents with higher scores of perceived positive PCSC outcomes, subjective norms, and self-efficacy were more likely to believe that they were solely responsible or shared an equal responsibility for PCSC. Multivariately, mothers and genderqueer parents, parents with the same gender as their child, and parents whose co-parent was less involved in parenting were more likely to report being solely responsible for PCSC.
CONCLUSIONS
Most parents saw themselves or a partner as most responsible for PCSC; parent and child gender were the strongest determinants of parents' perceptions of PCSC responsibility.
POLICY IMPLICATIONS
These results suggest that it may be more effective for parent education to challenge and deconstruct traditional gender roles versus focusing on self-efficacy, norms, and perceived outcomes if we want to increase parents' perceived PCSC responsibility, especially within different-gender parent-child dyads.
PubMed: 38948363
DOI: 10.1007/s13178-023-00898-w -
Computational Psychiatry (Cambridge,... 2024Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their...
Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy , they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.
PubMed: 38948255
DOI: 10.5334/cpsy.109 -
Theranostics 2024: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment....
: Molecular imaging of microenvironment by hypoxia-activatable fluorescence probes has emerged as an attractive approach to tumor diagnosis and image-guided treatment. Difficulties remain in its translational applications due to hypoxia heterogeneity in tumor microenvironments, making it challenging to image hypoxia as a reliable proxy of tumor distribution. : We report a modularized theranostics platform to fluorescently visualize hypoxia via light-modulated signal compensation to overcome tumor heterogeneity, thereby serving as a diagnostic tool for image-guided surgical resection and photodynamic therapy. Specifically, the platform integrating dual modules of fluorescence indicator and photodynamic moderator using supramolecular host-guest self-assembly, which operates cooperatively as a cascaded "AND" logic gate. First, tumor enrichment and specific fluorescence turn-on in hypoxic regions were accessible via tumor receptors and cascaded microenvironment signals as simultaneous inputs of the "AND" gate. Second, image guidance by a lighted fluorescence module and light-mediated endogenous oxygen consumption of a photodynamic module as dual inputs of "AND" gate collaboratively enabled light-modulated signal compensation , indicating homogeneity of enhanced hypoxia-related fluorescence signals throughout a tumor. In and analyses, the biocompatible platform demonstrated several strengths including a capacity for dual tumor targeting to progressively facilitate specific fluorescence turn-on, selective signal compensation, imaging-time window extension conducive to precise normalized image-guided treatment, and the functionality of tumor glutathione depletion to improve photodynamic efficacy. The hypoxia-activatable, image-guided theranostic platform demonstrated excellent potential for overcoming hypoxia heterogeneity in tumors.
PubMed: 38948059
DOI: 10.7150/thno.95590 -
World Journal of Transplantation Jun 2024Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been...
BACKGROUND
Endoscopic management is the first-line therapy for post-liver-transplant anastomotic strictures. Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months, data on safety and duration for metal stents in this setting is scarce. Due to limited access to endoscopic retrograde cholangiopancreatography (ERCP) during the coronavirus disease 2019 pandemic in our centre, there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy. This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents.
AIM
To compare the safety and efficacy profile of different stenting durations using Kaffes stents.
METHODS
Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query. Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records. The main outcome was the incidence of complications when stents were left indwelling for 3 months 6 months. Stent efficacy was calculated rates of stricture recurrence between patients that had stenting courses for ≤ 120 d or > 120 d.
RESULTS
During the study period, a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course. In 33 ERCPs, the stent was removed or exchanged on a 3-month interval. No pancreatitis, perforations or deaths occurred. Minor post-ERCP complications were similar between the 3-month (abdominal pain and intraductal migration) and 6-month (abdominal pain, septic shower and embedded stent) groups - 6.1% 9.1% respectively, = 0.40. All strictures resolved at the end of the stenting course, but the stenting course was variable from 3 to 22 months. The recurrence rate for stenting courses lasting for up to 120 d was 71.4% and 21.4% for stenting courses of 121 d or over ( = 0.03). There were 28 patients that were treated with a single ERCP with Kaffes, 21 with removal after 120 d and 7 within 120 d. There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course (71.0% 10.0%, = 0.01).
CONCLUSION
Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.
PubMed: 38947975
DOI: 10.5500/wjt.v14.i2.91081 -
Frontiers in Psychology 2024Swearing, or the use of taboo language, has been repeatedly shown to induce hypoalgesia. While reliable hypoalgesic effects have been observed across studies, the... (Review)
Review
Swearing, or the use of taboo language, has been repeatedly shown to induce hypoalgesia. While reliable hypoalgesic effects have been observed across studies, the mechanisms by which swearing influences pain and the optimal dosage of swearing remain poorly understood. Plausible mechanistic rationale for swearing's impact on pain include sympathetic response, emotion, humor, distraction, aggression, state disinhibition, psychological flow, risky behavior, and self-confidence. It remains unknown how the intensity of the swear word, speech volume, frequency, or timing influences pain modulation. While the majority of evidence demonstrates the efficacy of swearing at attenuating acute pain responses, these studies have utilized healthy populations with controlled experiments in laboratory settings. Comparatively, less is known about how laboratory findings translate practically/clinically to diverse populations, various dosages, and different pain chronicities. A greater understanding of mechanistic underpinnings and practical implications are necessary to feasibly implement swearing as a therapeutic modality to combat pain. The purpose of the following mini-review is to provide an overview of the current evidence on swearing for the reduction of pain, speculate on plausible underlying mechanisms, and discuss the potential for optimization of swearing for real-world translation. Lastly, identifying knowledge gaps to aid in directing future research will be discussed.
PubMed: 38947907
DOI: 10.3389/fpsyg.2024.1416041 -
Patient Preference and Adherence 2024Psoriasis is a highly debilitating chronic inflammatory disease. Increased understanding of its pathophysiology has enabled development of targeted treatments such as...
PURPOSE
Psoriasis is a highly debilitating chronic inflammatory disease. Increased understanding of its pathophysiology has enabled development of targeted treatments such as biologics. Several medical treatments have been shown to be influenced by patients' experiences and expectations. However, only little is known about patients' experiences with and expectations towards biologics. Our objectives were to identify patients' treatment experiences and treatment expectations and assess their trajectories over the course of treatment with the IL-17A inhibitor secukinumab. Moreover, we aimed to document effects of psoriasis, factors that influence symptomatology, and prior treatment experiences.
PATIENTS AND METHODS
We conducted semi-structured interviews with = 24 patients with moderate-to-severe plaque psoriasis and employed a qualitative content analysis to derive thematic and evaluative codes. Findings were validated via peer debriefings with experienced dermatologists.
RESULTS
Patients reported burdensome physical and psychological psoriasis symptoms and identified factors that can improve or worsen symptomatology, including stress and self-efficacy. Prior treatment experiences were mostly negative. Past barriers to effective treatment included time constraints or limited access. Concerning secukinumab, patients initially expected complete to partial remission of symptoms and occurrence or absence of side effects. Closer inspection of expectations and experiences revealed three trajectories. For most patients, initial expectations were met and future expectations remained unchanged. For the other patients, however, the experience did not match their initial expectation. One group then adapted their future expectations according to their experience, while the other group did not.
CONCLUSION
To our knowledge, this is the first qualitative study to assess expectations towards treatment effectiveness and side effects, their trajectories, and interplay with experiences among psoriasis patients. Our findings highlight the value of further research on the subject in order to optimize care for psoriasis patients and to learn more about the trajectories and influence of treatment expectations in general.
PubMed: 38947870
DOI: 10.2147/PPA.S458643 -
Endoscopic Ultrasound 2024To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in...
Clinical efficacy of EUS-guided celiac plexus neurolysis EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.
BACKGROUND AND OBJECTIVE
To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer.
METHODS
We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups.
RESULTS
EUS-CPN and I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure.
CONCLUSIONS
Both EUS-CPN and EUS-I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.
PubMed: 38947749
DOI: 10.1097/eus.0000000000000048 -
Cureus May 2024Group care in child welfare and primary care settings has evolved, becoming a popular approach for maternal and infant health care. This study focuses on the...
BACKGROUND
Group care in child welfare and primary care settings has evolved, becoming a popular approach for maternal and infant health care. This study focuses on the perspectives of family medicine providers on group care visits for maternal and infant nutrition, a crucial aspect of primary healthcare. Hence, this study aimed to explore current practices and opinions regarding the efficacy of group care models in delivering nutrition education to mother-infant dyads.
METHODOLOGY
A quantitative, cross-sectional study was conducted among family physicians in Buraydah, Saudi Arabia, from June to August 2023. Participants were recruited using a randomized sampling method from primary healthcare centers. Data were collected through a well-structured, self-administered questionnaire. The total participant count was 60. Statistical analyses were conducted using descriptive and inferential methods.
RESULTS
The majority of participants were men (n=32, 53.3%), under 30 years of age (n=31, 51.7%), and had 0 to five years of experience in medical practice (n=32, 53.4%). A high weekly volume of infant and maternal clinic visits was reported (n=44, 73.3%) but predominantly conducted individual nutrition education sessions (n=60, 100%). A significant majority (n=41, 68.3%) expressed a positive potential for group care in nutrition education.
CONCLUSION
The study revealed a positive inclination among family medicine providers towards group care models for maternal and infant nutrition education. However, current practices largely involved one-on-one sessions, indicating a gap between the recognition and implementation of group care models. It underscores the need for enhanced integration of group care approaches into clinical practice, highlighting their perceived benefits in efficiency and comprehensiveness. Future steps include implementing group care programs addressing participant concerns and assessing their efficacy in educating mothers on infant nutrition.
PubMed: 38947639
DOI: 10.7759/cureus.61428 -
Heliyon Jun 2024Service-oriented organizational citizenship behavior refers to service workers' helping, cooperating, sharing, and donating actions that benefit others at a cost to...
Service-oriented organizational citizenship behavior refers to service workers' helping, cooperating, sharing, and donating actions that benefit others at a cost to themselves. Based on ethical climate theory, this research investigates whether corporations adopting environmental, social, and governance (ESG) management enhance service-oriented organizational citizenship behavior (SO OCB) among service employees. A total of 230 surveys were collected from call center workers in the insurance industry, and STATA 14.0 was used to analyze the 204 responses with useable data. The results show that employees' recognized ESG activities enable SO OCB through organizational commitment. Additionally, ESG activity recognition has a positive relationship with self-efficacy and empowerment, which helps service employees regulate external expectations. Thus, this finding is significant for call center workers experiencing emotional labor. Furthermore, the results suggest that firms can contribute to employees' SO OCB by practicing ESG activities. Firms should inform employees of their ESG management efforts as employees' recognition of an ethical climate can enhance their willingness to perform service-oriented behavior. Finally, ESG activity recognition can increase employees' organizational commitment, an important predictor of employee satisfaction and negative turnover rates.
PubMed: 38947470
DOI: 10.1016/j.heliyon.2024.e31999