Search Results for: Studio REDUCE-IT e appropriatezza prescrittiva degli acidi grassi omega-3

Stroke, Ahead of Print. BACKGROUND:Stroke often results in significant impairments across various domains, including movement, language, cognition, and mood. Neurostimulants have been proposed as potential therapeutic interventions to enhance recovery in these areas.METHODS:This narrative literature review examines clinical trials investigating the efficacy of neurostimulants in poststroke recovery. It evaluates outcomes related to aphasia, motor deficits, cognition, fatigue, and depression.RESULTS:The qualitative analysis included 34 trials testing the following neurostimulants: methylphenidate (n=6), amphetamines (n=8), memantine (n=2), modafinil (n=2), levodopa (n=14), amantadine (n=1), bromocriptine (n=3), and ropinirole (n=1). Of the 34 studies, 31 were randomized, placebo-controlled (double-blind, n=27; single-blind, n=2; unblinded n=2), 2 were randomized and not placebo-controlled, and 1 was not randomized. Study design was either multiarm (n=23), crossover (n=10), or used subjects as their own control (n=1). Mean sample size was 49.4 (5–593).CONCLUSIONS:Current evidence suggests that memantine may be effective for aphasia, although few phase III trials exist, whereas bromocriptine and amphetamines lack sufficient evidence for long-term recovery of aphasia. Levodopa may improve motor aphasias but has not shown long-term benefits for motor recovery. Similarly, ropinirole has not been shown to improve poststroke motor outcomes. Methylphenidate has limited efficacy for cognitive improvement but may enhance poststroke functionality and mood. Modafinil may help with poststroke fatigue. In conclusion, there are promising results of positive effects of neurostimulants with few side effects, though studies are limited by heterogeneous designs and small sample sizes. Neurostimulant efficacy must be assessed in conjunction with specific rehabilitation modalities as part of larger, well-designed studies to best understand their effects on impairment.

Introduction
In the UK, the number of ethnically diverse older adults (OA) is growing. These individuals suffer complex health issues that are made worse by socioeconomic status, acculturation experiences and language barriers. Additionally, this varied group is the least active and a highly sedentary subgroup in the general population, which poses serious health concerns. Various interventions have been implemented with OAs to reduce their sedentary behaviour (SB) and enhance their physical activity (PA). However, there is still limited research that implements stakeholders’ perceptions in translating the interventions into real-life settings, particularly for ethnically diverse OAs. Therefore, the current study aims to explore stakeholders’ perceptions of the transferability of a 12-week home space intervention for ethnically diverse sedentary OAs, that is, aimed at reducing their SB and increasing their PA.

Methods
Exploratory qualitative research using in-depth interviews (IDIs) and a purposive sampling technique will be employed to recruit stakeholders. Before conducting the IDIs, the primary researcher (NAAM) will discuss the findings of the 12-week home space intervention study for ethnically diverse OAs to explain the intervention, and then the interview will revolve around the transferability of the intervention to transfer the intervention into real-world practice into the stakeholder contexts. A diverse group of stakeholders from Swansea, Wales, UK, representing a range of roles including health promotion professionals, programme leads, service providers, policymakers and researchers will be included. The qualitative data obtained will be analysed using reflexive thematic analysis.

Ethics and dissemination
Stakeholders will be required to provide written informed consent prior to initiation of the study. Ethical approval for this study has been obtained from the College of Engineering Research Ethics Committee (320249732903), Swansea University. The study’s results will be shared with the scientific community through a peer-reviewed journal publication and with study participants through seminars and workshops.

Introduction
The use of teleneuropsychology or neuropsychological remote assessment increased during and after the COVID-19 pandemic in 2020. Teleneuropsychology facilitates remote assessment for populations that do not have access to neuropsychological services as well as individuals who are vulnerable or have physical restrictions that would otherwise make it difficult for individuals to receive appropriate care. However, there are many instruments that are not validated or lack normative data for the overall population. Therefore, this study aims to develop normative data for a neuropsychological battery administered on telehealth with commonly used tools to identify cognitive performance in older adults.

Methods and analysis
The following study will use a previously informatics-generated list of participants who have a lower risk of developing Alzheimer’s disease and other related dementias. Participants will complete screening surveys related to cognitive and health status. They will also complete questionnaires related to sociodemographic information, depression, functionality and social determinants of health. Participants will undergo a teleneuropsychological battery examination via remote assessment. We estimate recruiting 500 participants to establish normative data.

Ethics and dissemination
The current protocol is approved by the University of Florida’s Institutional Review Board. Results will be analysed and disseminated in a research paper once sample number goals are completed.

Objective
Developmental language disorder (DLD) is a common communication disorder that impacts children’s ability to learn, comprehend and use language effectively, yet it remains under-researched, particularly in the Arab countries. This scoping review aims to provide a comprehensive narrative summary on the epidemiology of DLD among children aged ≤10 years in the Arab countries.

Design
A scoping review.

Data sources
PubMed, Scopus and Web of Science.

Eligibility criteria
We included studies that reported on the prevalence or risk factors of DLD in children aged ≤10 years from any Arab country. Only peer-reviewed publications were considered, and the study populations were required to consist of children without underlying medical conditions known to contribute to language or speech delay.

Data extraction and synthesis
Two reviewers independently performed abstract and full-text screening and extracted relevant data. The risk factors identified as linked to DLD were grouped into maternal and perinatal factors, factors related to children and family and environmental factors.

Results
From 4832 citations, 17 were deemed eligible and included in this review. The reviewed studies were conducted in only seven Arab countries, with the majority from Egypt (eight studies, 47.1%) and Saudi Arabia (four studies, 23.5%). The reported prevalence of DLD ranged from 3.2% in Egyptian children aged 3–6 years to 25.6% in Saudi Arabian children aged 1–5 years. Among the identified risk factors for DLD were sex, low birth weight, a history of speech and language delay in the family, parental socioeconomic status, perinatal complications, larger family size and early screen exposure.

Conclusion
The reported prevalence of DLD varied across the seven Arab countries. Strategies to address the preventable underlying DLD-associated risk factors are required. There is a clear gap in evidence related to the burden of DLD among children in most of the 22 Arab countries, which warrants further research.

Objectives
Organ procurement coordinators (OPCs) play a pivotal role in navigating end-of-life and second-birth narratives by securing familial consent for solid organ donation. Given the low rates of cadaveric organ donation in Türkiye and worldwide, OPCs are essential in advocating for and facilitating these donations. This study explores the reasons for refusal that OPCs have encountered during the familial consent process.

Design
We gathered the data through semistructured interviews with 30 OPCs. Thematic analysis was used to identify and analyse key themes, with a specific focus on cultural, religious, spiritual and folkloric barriers contributing to the low rates of cadaveric organ donation in Türkiye.

Setting
Hospitals and organ transplant centres operating under the jurisdiction of the Ankara Regional Coordination Centre in Türkiye.

Participants
Participants were recruited using a purposeful random sampling strategy to enhance credibility and reduce bias. Eligible informants included OPCs with at least 2 years of experience in the role. Among the 30 participants, 18 were based in central organ transplant centres associated with Training and Research Hospitals in Ankara, and 12 were from peripheral city hospitals.

Results
Coordinators identified five main barriers that hinder their ability to secure familial consent for cadaveric organ donation: (1) religion, (2) concerns about the wishes of the deceased, (3) desire to choose recipients, (4) familial dynamics and (5) folklore. Each category was further contextualised through subcategories derived from the frequency and nuances of recurring themes.

Conclusion
OPCs face significant challenges in promoting cadaveric organ donations due to cultural barriers. Their experiences underscore the need for culturally competent approaches in organ donation campaigns and the importance of supporting coordinators in their roles. Enhanced cultural understanding and targeted interventions could improve cadaveric organ donation rates.

Introduction
The ARFID InitiativE Sweden (ARIES) investigates the genetic and environmental factors contributing to avoidant/restrictive food intake disorder (ARFID) in children and adolescents aged 6–14 years. ARIES will establish a national biobank and research registry. It aims to provide data for immediate research and track ARFID outcomes and clarify genetic links between ARFID and other conditions and analyse the gut microbiome to guide nutrition interventions.

Methods and analysis
The study will involve 1500 Swedish children and adolescents with ARFID and a control group of 500 Swedish children and adolescents without ARFID. Parents/guardians and their children will complete online questionnaires assessing ARFID and other eating disorder (ED) pathology, co-occurring conditions, quality of life and parental stress and ED pathology. All participants will provide a saliva sample for comprehensive genetic analyses. Additionally, a subset of participants will provide a stool sample to investigate the gut microbiome in ARFID.

Ethics and dissemination
ARIES was approved by the Swedish Ethical Review Authority (Dnr 2023-04638). All participants will give assent and their parents will complete informed consent. Data will be made available by the authors on reasonable request. Findings will be published in scientific journals and shared with the public and stakeholders in accessible ways, for example, via social media.

Introduction
Neonatal sepsis is a key contributor to neonatal mortality worldwide, and low- and middle-income countries (LMIC) are disproportionately affected. With antimicrobial resistance challenging effective treatment of neonatal sepsis, it is increasingly urgent to improve infection prevention and control (IPC) in LMIC neonatal units (NNU) and reduce transmission of infections. One pathway to improvement which merits further exploration is the collaboration with families to build an IPC intervention.
Families are constantly present on neonatal units, and much of the hands-on care for their newborns is given by them. For IPC to be effective, families must adhere to IPC standards within the NNU, but furthermore, any IPC intervention implemented must be feasible and acceptable for families as well as the hospital staff as this will increase uptake and effectiveness of the intervention. This scoping review aims to provide an overview of parental involvement in infection prevention and control in low- and middle-income setting neonatal units.

Methods and analysis
This protocol was developed in line with the Joanna Briggs Institute recommendations. Searches will be carried out on six databases (Medline, CINAHL, Global Health, EMBASE, Web of Science and Global Index Medicus), and reference searching will be carried out on included studies. The search will be carried out from 2000 to present (end date 28/02/2024), and included languages will be English, French, Spanish and Portuguese. Screening and data extraction will be performed independently by two reviewers, with a third reviewer to resolve conflicts. Results will be reported by narrative synthesis of each sub-question in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Ethics and dissemination
This study will be carried out using already published data exclusively and therefore does not require further ethical approval. Results will be disseminated through peer-reviewed publications and conference presentations and through engagement with peers and relevant stakeholders.

Trial registration number
Registered with Open Science Framework – https://osf.io/snc7a/?view_only=8ffc39d837594b4388c7394a838c3a9e

Objectives
To explore patient, carer and clinician experiences of the QbTest and its impact on patient outcomes for attention deficit hyperactivity disorder (ADHD) diagnosis and medication management.

Design
Mixed-methods systematic review.

Data sources
MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and WHO ICTRP (from inception to September 2024).

Study selection
Primary studies, of any design, that evaluated any version of the QbTest (QbMini

Introduction
Around 70% of people with psychosis experience auditory verbal hallucinations (AVHs), which can cause distress and impair the social functioning of the individual. AVATAR therapy works by facilitating a ‘face-to-face’ dialogue between the person and a digital representation (avatar) of their persecutory voice. Although there is cumulative evidence of this way of working with voices, enhancing the therapeutic focus on improved confidence and sense of control of the voices in social situations represents a promising way to boost generalisation of therapy gains into social contexts. We aim to enhance AVATAR therapy by incorporating immersive Virtual Reality (VR) social environments aiming to help the person to deal better with their voices in daily situations.

Methods and analysis
A randomised controlled feasibility trial will be conducted. 40 patients aged 18 or above who are at early stages of psychosis (first episode of psychosis in the last five years) and report distressing and interfering voices will be recruited. Participants will be randomised to receive either a novel, enhanced version of AVATAR therapy (AVATAR_VRSocial) in addition to usual care or usual care alone. Assessor-blinded assessments will be conducted at baseline, 3 months (post-intervention) and 6 months (follow­-up). Key therapeutic targets of AVATAR_VRSocial will be those established by the previous evidence of this approach (ie, power and control, self-esteem and future focus), while introducing exposure and management of distressing voices during social interactions. Analyses will focus on feasibility outcomes (recruitment, retention and completion rates) and preliminary estimates of intervention effects. Qualitative interviews will be carried out with participants allocated to AVATAR_VRSocial to gain a comprehensive understanding of participants’ views on the acceptability of the intervention and research procedures. Thematic analysis of the qualitative interviews will assess the acceptability of the intervention, trial procedures and the new VR technology and software involved.

Ethics and dissemination
The study has received ethical approval from the Ethics Commission at the Faculty of Psychology (Ruhr-Universität Bochum), and there is an independent Trial Steering Committee and Lived Experience Advisory Panel also supporting it. Findings will be disseminated through peer­-reviewed publications, conference presentations and science dissemination events.

Trial registration number
ISRCTN35980117.

Stroke, Ahead of Print. BACKGROUND:Branch atherosclerosis disease (BAD) is prone to early neurological deterioration (END). The purpose of this study was to assess the efficacy and safety of argatroban plus dual antiplatelet therapy (DAPT) for preventing END in high-risk branch atherosclerosis disease patients.METHODS:This multicenter, open-label, blinded end point, randomized controlled trial including branch atherosclerosis disease patients with mild stroke (National Institutes of Health Stroke Scale score ≤5) was conducted at 4 centers in China from May 18, 2021 to February 8, 2023. Within 48 hours after symptom onset, patients were randomly assigned to receive argatroban plus DAPT or DAPT alone in a 1:1 ratio. The primary end points were the incidence of END (National Institutes of Health Stroke Scale score increase ≥2) within 7 days and excellent functional outcome (modified Rankin Scale score of 0 to 1) at 90 days.RESULTS:A total of 111 patients were randomized, with 11 excluded for specific reasons, resulting in 100 patients included in the modified intention-to-treat population. Among the 100 patients, 49 received argatroban plus DAPT and 51 received DAPT alone, 63 (63.0%) were men, and the median age was 64 (range, 55–74) years. END occurred in 20.4% (10/49) of the argatroban plus DAPT group and 47.1% (24/51) of the DAPT group (risk difference, 26.7% [95% CI, 14.1–39.2]; risk ratio, 2.31 [95% CI, 1.49–3.58];P=0.006). At the 90-day follow-up, 87.8% (43/49) in the argatroban plus DAPT group and 68.6% (35/51) in the DAPT group achieved an excellent functional outcome (risk difference, −19.1% [95% CI, −30.3 to −8.0]; risk ratio, 0.78 [95% CI, 0.67–0.91];P=0.025). There was 1 minor hemorrhage in each group.CONCLUSIONS:Argatroban plus DAPT is a safe and effective strategy to reduce END occurrence and improve 90-day functional outcome in high-risk branch atherosclerosis disease patients.REGISTRATION:URL:https://www.chictr.org.cn; Unique Identifier: ChiCTR21000 46487.

Stroke, Ahead of Print. BACKGROUND:Neuronal pyroptosis is involved in neuronal cell death and neurological damage after cerebral ischemia-reperfusion. 14,15-Epoxyeicosatrienoic acid (14,15-EET) can reduce neuronal loss induced by cerebral ischemia-reperfusion by regulating mitochondrial biological processes. However, it remains unclear how 14,15-EET regulates mitochondrial homeostasis, inhibits neuronal pyroptosis, and promotes neurological functional recovery after cerebral ischemia-reperfusion.METHODS:Mice with middle cerebral artery occlusion and reperfusion were used as an animal model to study the cerebral ischemia-reperfusion disease. The neurological function of mice was performed at 1, 3, and 5 days to test the therapeutic effects of 14,15-EET. Transmission electron microscope imaging and Nissl staining were used to analyze neuronal morphological structure, mitophagy, and neuronal pyroptosis. Western blot and transcriptome were used to detect the levels of mitophagy and neuronal pyroptosis signaling pathway–related molecules. HT22 cells were used in in vitro studies to detect the mechanism by which 14,15-EET reduces neuronal pyroptosis after oxygen-glucose deprivation/reoxygenation treatment.RESULTS:14,15-EET treatment reduced cerebral infarct volumes and improved neurological functional recovery in mice after cerebral ischemia-reperfusion. 14,15-EET treatment maintained the morphological structure of neurons in the ischemic penumbra area as well as the dendritic spine density in mice after cerebral ischemia-reperfusion. The upregulation of NLRP1 (NOD-like receptor thermal protein domain associated protein 1), IL (interleukin)-1β, caspase-1, and GSDMD (gasdermin D) induced by cerebral ischemia-reperfusion was inhibited, and the expression of mitophagy proteins Parkin and LC3B was increased by 14,15-EET treatment. Transcriptome profiling found that 14,15-EET exerts a neuroprotection role in promoting neural function recovery by activating the WNT (wingless-type MMTV integration site family) signaling pathway. We found that 14,15-EET upregulated the WNT pathway proteins such as WNT1, WNT3A, β-catenin, and p-GSK-3β (phosphorylation of glycogen synthase kinase 3β) in vivo and in vitro. The WNT signaling pathway inhibitor XAV-939 reduced the expression of mitophagy protein Parkin and upregulated the expression of caspase-1 and GSDMD in HT22 cells with oxygen-glucose deprivation/reoxygenation and 14,15-EET treatment.CONCLUSIONS:14,15-EET regulates mitochondrial homeostasis to inhibit neuronal pyroptosis, thereby promoting the recovery of neurological function in mice after cerebral ischemia-reperfusion. These results provide new ideas for maintaining mitochondrial homeostasis and inhibiting neuronal pyroptosis after cerebral ischemia-reperfusion.

Circulation, Ahead of Print. The growing morbidity, mortality, and health care costs related to heart failure (HF) underscore the urgent need to prioritize its primary prevention. Whereas a risk-based approach for HF prevention remains in its infancy, several key opportunities exist to actualize this paradigm in clinical practice. First, the 2022 American Heart Association/American College of Cardiology/Heart Failure Society of America HF guidelines provided recommendations, for the first time, on the clinical utility of multivariable risk equations to estimate risk of incident HF. Second, the American Heart Association recently developed the PREVENT (Predicting Risk of Cardiovascular Disease Events) equations, which not only enable prediction of incident HF separately, but also include HF in the prediction of total cardiovascular disease. Third, the predominant phenotype of HF risk has emerged as the cardiovascular-kidney-metabolic syndrome. Fourth, the emergence of novel therapies that prevent incident HF (eg, sodium-glucose cotransporter-2 inhibitors) and target multiple cardiovascular-kidney-metabolic axes demonstrate growing potential for risk-based interventions. Whereas the concept of risk-based prevention has been established for decades, it has only been operationalized for atherosclerotic cardiovascular disease prevention to date. Translating these opportunities into a conceptual framework of risk-based primary prevention of HF requires implementation of PREVENT-HF (Predicting Risk of Cardiovascular Disease Events–Heart Failure) equations, targeted use of cardiac biomarkers (eg, natriuretic peptides) and echocardiography for risk reclassification and earlier detection of pre-HF, and definition of therapy-specific risk thresholds that incorporate net benefit and cost-effectiveness. This scientific statement reviews the current evidence for accurate risk prediction, defines strategies for equitable prevention, and proposes potential strategies for the successful implementation of risk-based primary prevention of HF.

Structural variations (SVs) have significant effects on the microbial phenotypes. The underlying mechanism of functional changes caused by gut microbial SVs in the development of ulcerative colitis (UC) need further investigation.

Introduction
Postdischarge suicide risk among psychiatric patients is a great concern. Gamified interventions have demonstrated promise in reducing the risk. This study aims to reduce postdischarge suicide risk through a mHealth intervention that engages and supports patients through gamified features. Built on our previous research, this study will develop, optimise and evaluate a gamified intervention under the Multi-phase Optimization Strategy (MOST) framework in implementation science.

Methods and analysis
This study will be conducted at the Shenzhen Kangning Hospital. Following the MOST framework, we will develop the gamified mHealth app (Tailored Evidence-based Enhancements in Mental Health (TEEM)) with four intervention components in the selection phase. In the optimisation phase, a factorial design randomised controlled trial (RCT) will be conducted to identify the optimised configuration. A total of 320 patients with mental disorders will be recruited and randomised into 16 groups to receive TEEM with different combinations of intervention components, with follow-ups scheduled at 1 week, 1 month, 2 months and 3 months after discharge. In the confirmation phase, we will assess the optimised TEEM through a standard RCT, comparing it to usual care. An additional 320 patients with mental disorders will be recruited for this phase, and the follow-up schedule is the same as in the optimisation phase. Psychiatric patients and family members, clinical and community mental health service providers will be recruited as the community team to help develop and evaluate the TEEM. Quantitative data will be analysed using the intention-to-treat approach and generalised estimating equations, and qualitative data will be coded and categorised to identify key themes.

Ethics/dissemination
The Ethics Committee Review Board of Shenzhen Kangning Hospital has approved this study. All participants will provide written informed consent prior to enrolment. The findings will be disseminated through peer-reviewed scientific journals and conference presentations, and a report will be submitted to the National Natural Science Foundation of China and the mental health authorities in the Shenzhen Municipal Health Commission.

Trial registration number
ClinicalTrials.gov, ID: NCT06358339

Objectives
The purpose of this study was to identify which, and to what extent, demographic and operational factors are indicative of likelihood for a new call handler or paramedic to remain in role within the first two years of employment at an ambulance trust using data held in the trust’s bespoke data warehouse.

Design
The study uses a retrospective observational cohort design using routinely collected data.

Setting
One ambulance trust focused on a large, predominantly urban area in the UK.

Participants
The study used the data of all employees of the trust who started employment as call handlers (869) or paramedics (1672) between 1 January 2018 and 31 July 2023.

Primary and secondary outcome measures
‘Time-to-event’ analysis of ‘likelihood to remain in post within the first two years of employment’ as call handlers or paramedics via accelerated failure time regression.

Results
Several factors showed a significant contribution to the likelihood of remaining in post within an ambulance National Health Service Trust. Among the findings, short-term sick leave in the first two years of employment was associated with increased retention for paramedics (0.040, 95% CI 0.030, 0.060). In addition, female call handlers were found to have increased retention (0.29, 95% CI 0.043, 0.54), and paramedic retention increased with time outside of ‘job cycle time’ (JCT) activities (ie, activities other than responding to calls) (0.097, 95% CI 0.057, 0.14).

Conclusions
This study presents a method for extracting new insights from routinely collected operational data, identifying common drivers and specific predictors for retention among the ambulance NHS workforce. It emphasises the importance of workforce-centred retention strategies, highlighting the need for non-JCT time, which in turn would allow paramedics to have time to reflect and recuperate to avoid burnout and attrition. The study also suggests that a lack of sick leave might indicate a lack of trust and self-care culture, potentially leading to paramedic staff attrition. Our approach to retention analytics provides a new mechanism for trusts to monitor and respond to their attrition risks in a timely, proactive fashion.

Introduction
Prolonged grief disorder (PGD) represents a substantial public health issue, especially in oncology settings where it affects up to 30% of bereaved carers. Current best-practice treatments are lengthy, and up to 50% of participants have persistent PGD. Building on encouraging recent research with psychedelic-assisted therapies, the Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief (PARTING) trial is the first study to consider psilocybin-assisted psychotherapy as a potential treatment for prolonged grief.

Methods and analysis
PARTING is an open-label pilot trial of psilocybin-assisted psychotherapy for approximately 15 people with cancer-related PGD. It aims to investigate feasibility, safety, acceptability, participant experience and participant-reported therapeutic effects. Over a 5-week intervention period, participants will undergo three preparation sessions before receiving a psychoactive (25 mg) dose of psilocybin alongside non-directive supportive guidance, followed by four integration sessions. All sessions will be delivered by a psychologist and either a nurse or Indigenous Therapist. An artificial intelligence-assisted tool will be used to create an artwork of participants’ psychedelic experience.
Outcomes will be investigated over a 12-month follow-up period. Feasibility will be assessed through recruitment/retention rates and completion of follow-up assessments. Safety will be evaluated via adverse events over 12 months and the comparison of physiological measures (vital signs, biochemistry, haematology, ECG) recorded during screening and 1 day after the psilocybin dose. Qualitative thematic analysis of semistructured interviews with participants and trial therapists will assess acceptability and the therapeutic potential of the treatment. Diagnostic clinical interviews for PGD and quantitative participant-reported measures of therapeutic effects are also being collected. Participant-reported measures include grief severity, depression, anxiety, grief avoidance, psychological flexibility, connectedness, and quality of life.

Ethics and dissemination
Ethics approval has been obtained from QIMR Berghofer Medical Research Institute Human Research Ethics Committee (P3801). Dissemination of results will occur via conference presentations, peer-reviewed publications and media.

Trial registration number
Australian New Zealand Clinical Trials Registry (ACTRN12623000827639).