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Abstract Background Gastric adenomyoma is a rare benign tumor composed of glandular structures and smooth muscle fibers. While some classify gastric adenomyoma as a hamartoma, others view it as an abortive form of heterotopic pancreas. Despite its benign nature, there is a risk of malignant transformation. Predominantly found in the antrum, gastric adenomyoma affects all ages but is most common in adults aged 40–60 years. Symptoms are nonspecific, and its similarity to other lesions complicates diagnosis. This paper aims to provide a review of medical literature on gastric adenomyoma and its diagnosis and treatment methods, along with presenting an additional case report on the same topic. Case presentation We present the case of a 55-year-old Syrian man who experienced vomiting, weight loss, and chronic partial constipation. An obstructing mass in the pylorus was detected, and then an open surgery was performed to excise the lesion. A biopsy of the resected mass was obtained for histopathological examination. The final diagnosis of the lesion was pyloric-region adenomyoma with severe pyloric stenosis. After the successful surgery, the patient recovered without any recurrence or complications. Conclusions Several diagnostic approaches are available, including radiological studies, endoscopic examination, and fine needle aspiration guided by endoscopic ultrasonography. Treatment options involve endoscopic submucosal dissection and complete laparotomy resection. Further studies and thorough reviews are recommended to better understand the best clinical practices. Practitioners should consider gastric adenomyoma when encountering a mural gastric lesion.

Abstract Background Four out of five people living with osteoarthritis (OA) also suffer with at least one other long-term health condition. The complex interaction between OA and multiple long-term conditions (MLTCs) can result in difficulties with self-care, restricted mobility, pain, anxiety, depression and reduced quality of life. The aim of the MulTI-domain Self-management in Older People wiTh OstEoarthritis and Multi-Morbidities (TIPTOE) trial is to evaluate the clinical and cost-effectiveness of the Living Well self-management support intervention, co-designed with people living with OA, integrated into usual care, in comparison to usual care alone. Methods TIPTOE is a multi-centre, two-arm, individually randomised controlled trial where 824 individuals over 65 years old with knee and/or hip joint pain from their OA affected joint and at least one other long-term health condition will be randomised to receive either the Living Well Self-Management support intervention or usual care. Eligible participants can self-refer onto the trial via a website or be referred via NHS services across Wales and England. Those randomised to receive the Living Well support intervention will be offered up to six one-to-one coaching sessions with a TIPTOE-trained healthcare practitioner and a co-designed book. Participants will be encouraged to nominate a support person to assist them throughout the study. All participants will complete a series of self-reported outcome measures at baseline and 6- and 12-month follow-up. The primary outcome is symptoms and quality of life as assessed by the Musculoskeletal Health Questionnaire (MSK-HQ). Routine data will be used to evaluate health resource use. A mixed methods process evaluation will be conducted alongside the trial to inform future implementation should the TIPTOE intervention be found both clinically and cost-effective. An embedded ‘Study Within A Project’ (SWAP) will explore and address barriers to the inclusion of under-served patient groups (e.g. oldest old, low socioeconomic groups, ethnic groups). Discussion TIPTOE will evaluate the clinical and cost-effectiveness of a co-designed, living well personalised self-management support intervention for older individuals with knee and/or hip OA and MLTCs. The trial has been designed to maximise inclusivity and access. Trial registration ISRCTN 16024745 . Registered on October 16, 2023.

Montessori education is distinct for its implementation in 154 countries around the world. Lacking a Montessori trademark or comprehensive overseeing body, the expansion of the Montessori approach has often been diffuse and fragmented among competing organizations. The absence of centralized, accurate, and consistent accounting has made it difficult to document the scope, growth trends, and diverse populations of students served in Montessori schools. The primary objective of this study was to gather evidence to support a robust estimate of the number of Montessori schools worldwide. This estimate relies on national and regional organizations' broadest definitions of what constitutes a Montessori program. The study included two components: a survey of regional and national Montessori organizations and supplemental sources, including other published estimates and direct inquiries within key countries. Multiple sources allowed for triangulating data to reach a more confident estimate for the number of schools in each country and for synthesizing global perspectives on significant elements of Montessori fidelity worldwide. Through these sources, we document a total of 15,763 Montessori schools around the globe, roughly 9% of which are government funded. Countries with the largest number of Montessori schools are the United States, China, Thailand, Germany, Canada, and Tanzania; the United States, Thailand, the Netherlands, and India have the largest number of government-funded or public Montessori programs. Results of the fidelity analysis identified six practices that emerge consistently as central pillars of Montessori implementation.

Peanuts are recognized as one of the most common allergenic foods, known to induce severe Th2-mediated allergic reactions. The resulting global health concern has fostered the necessity to design innovative technologies capable of mitigating allergenicity. This study investigated the effect of an innovative thermomechanical process, “Intensification of Vaporization by Decompression to the Vacuum” (IVDV), on the protein content and immunogenicity of whole peanuts. Through animal studies using peanut allergy BALB/c mouse models, this research revealed a clear reduction in allergic symptoms once challenged with IVDV-treated peanut protein extract, compared to those receiving raw or deep-fried peanut protein extracts. Significant changes in immune response markers in animals were observed, including reduced levels of histamine, Th1/Th2 cytokines, and antibodies, thus confirming the efficacy of IVDV in mitigating allergenicity in peanuts. Saturated steam pressure was demonstrated to have a highly significant positive effect on the reduction of protein content in IVDV-treated samples through degradation, with a noteworthy reduction ranging from 42.3% to 89.2%. This pilot study embarked on a pioneering exploration into the ability of IVDV to offer a viable solution in reducing peanut allergenicity, opening new avenues for enhanced food safety and inclusivity. The ease of scalability of IVDV technology to an industrial level, along with its cost-efficiency, further enhance its appeal for widespread adoption.

In recent years, biographical studies of Maria Montessori have increasingly moved away presenting Montessori as a singular pedagogical genius, to considering Montessori as a movement builder immersed in a complicated, dense and changing international network of theorists, practitioners and policymakers. Scholars have highlighted the wide-ranging intellectual networks of feminists, doctors, anthropologists, philosophers, theosophists, Catholics, fascists and pacifists whose work Montessori was reading and actively engaging with, even after leaving academic research. In addition, new research presents how all of these thinkers were actively debating Montessori education, grappling with a wide range of pedagogical, theological and philosophical issues, and defying the representation of Montessori education as a single ideological monolith. Christine Quarfood, a professor of the History of Ideas at the University of Gothenburg, Sweden, makes a vital contribution to this conversation. Thanks to a translation from Swedish into English, Christine Quarfood’s 2017 study Montessoris pedagogiska imperium: kulturkritik och politik i mellankrigstidens Montessorirörelse (Dansk Band: 2017) is now available to English-speaking readers as The Montessori Movement in Interwar Europe: New Perspectives (Palgrave Macmillan: 2022).

The intricate interplay existing between gut microbiota and homeostasis extends to the realm of the brain, where emerging research underscores the significant impact of the microbiota on mood regulation and overall neurological well-being and vice-versa, with inflammation playing a pivotal role in mediating these complex interactions. This comprehensive review explores the complex interplay between inflammation, alterations in gut microbiota, and their impact on major depressive disorder (MDD). It provides a cohesive framework for the puzzle pieces of this triad, emphasizing recent advancements in understanding the gut microbiota and inflammatory states' contribution to the depressive features. Two directions of communication between the gut and the brain in depression are discussed, with inflammation serving as a potential modulator. Therapeutic implications were discussed as well, drawing insights from interventional studies on the effects of probiotics on gut bacterial composition and depressive symptoms. Ultimately, this review will attempt to provide a complete and valuable framework for future research and therapeutic interventions in MDD.

Objective: No standardised approach exists to provide advice after urgent suspected cancer (USC) referral when cancer is not found. This study aimed to assess preferences and acceptability of receiving advice after USC referral related to: 1) managing ongoing symptoms, 2) responding to early symptoms of other cancers, 3) cancer screening, 4) reducing risks of future cancer. Methods: 2,541 patients from two English NHS Trusts were mailed a survey 1–3 months after having no cancer found following urgent suspected gastrointestinal or head and neck cancer referral. Participants were asked about: willingness to receive advice; prospective acceptability; preferences related to mode, timing and who should provide advice; and previous advice receipt. Results: 406 patients responded (16.0%) with 397 in the final analyses. Few participants had previously received advice, yet most were willing to. Willingness varied by type of advice: fewer were willing to receive advice about early symptoms of other cancers (88.9%) than advice related to ongoing symptoms (94.3%). Acceptability was relatively high for all advice types. Reducing the risk of future cancer advice was more acceptable. Acceptability was lower in those from ethnic minority groups, and with lower levels of education. Most participants preferred to receive advice from a doctor; with results or soon after; either face to face or via the telephone. Conclusions: There is a potential unmet need for advice after USC referral when no cancer is found. Equitable intervention design should focus on increasing acceptability for people from ethnic minority groups and those with lower levels of education.

Alongside the immediate challenges of operating schools during the COVID-19 pandemic, over the past year, parents, students, and policymakers around the country have also debated equity and access to some of the country's most elite and segregated public schools. This qualitative case study examines how New York City activists conceptualized educational equity during the pandemic. Conceptually framed by Labaree's (1997) typology of the three competing purposes of education--democratic equality, social efficiency, and social mobility--we document different lessons learned from the pandemic by integration activists, who emphasized school integration for democratic equality; and meritocratic activists, who prioritized retaining the existing stratified system mainly to foster social mobility and social efficiency. Our findings highlight the challenge of sustaining a vision oriented around the public good amid powerful framings emphasizing the individual purposes of education.

Recently, there has been a growing interest in reducing waste to promote environmental sustainability, with particular focus on agricultural by-products, especially fruits and vegetables. Potato, a widely used crop across various industries, generates a significant amount of peel waste. This study aims to valorize potato peels using water bath extraction (WBE) and infrared-assisted extraction (IRAE), both with distilled water as the solvent, followed by assessments of antioxidant, antibacterial, and anti-sprouting activities. Optimization using response surface methodology identified optimal extraction conditions for WBE (90 °C for 70 min) and IRAE (80 °C for 10 min), with both methods yielding 3.5 mg GAE/g DM in polyphenol content. IRAE demonstrated superior energy efficiency and enhanced antioxidant activity. The extracts exhibited antibacterial properties against both Gram-positive (Listeria monocytogenes) and Gram-negative bacteria (Proteus sp. and Salmonella sp.), with inhibition zones ranging from 10 to 14 mm. Furthermore, the potato peels extract showed significant anti-sprouting effects at room temperature, reducing both the number and size of sprouts compared with the control. HPLC analysis showed the presence of different phenolic compounds such as rutin, catechin, caffeic acid, protocatechuic acid, chlorogenic acid, p-coumaric acid, and gallic acid in one or both extracts. These findings suggest that potato peels extract holds potential for applications in the food industry as a natural preservative due to its antioxidant properties, as well as a sprout suppressant. The antibacterial activity of the extracts suggests their potential as a natural preservative as well, offering protection against both Gram-positive and Gram-negative bacteria that may be present in food.

Therapy of BRAF-mutant melanoma with selective inhibitors of BRAF (BRAFi) and MEK (MEKi) represents a major clinical advance but acquired resistance to therapy has emerged as a key obstacle. To date, no clinical approaches successfully resensitize to BRAF/MEK inhibition. Here, we develop a therapeutic strategy for melanoma using bromosporine, a bromodomain inhibitor. Bromosporine (bromo) monotherapy produced significant anti-tumor effects against established melanoma cell lines and patient-derived xenografts (PDXs). Combinatorial therapy involving bromosporine and cobimetinib (bromo/cobi) showed synergistic anti-tumor effects in multiple BRAFi-resistant PDX models. The bromo/cobi combination was superior in vivo to standard BRAFi/MEKi therapy in the treatment-naive BRAF-mutant setting and to MEKi alone in the setting of immunotherapy-resistant NRAS- and NF1-mutant melanoma. RNA sequencing of xenografts treated with bromo/cobi revealed profound down-regulation of genes critical to cell division and mitotic progression. Bromo/cobi treatment resulted in marked DNA damage and cell-cycle arrest, resulting in induction of apoptosis. These studies introduce bromodomain inhibition, alone or combined with agents targeting the mitogen activated protein kinase pathway, as a rational therapeutic approach for melanoma refractory to standard targeted or immunotherapeutic approaches.

Discussions around the unethical use of emerging technology have become increasingly common in our society. Despite previous research acknowledging the importance of including societal-level discussions in engineering and technology undergraduate curricula, there is a lack of research around college students' understanding of and engagement with the ethics of new and emerging technology. In this qualitative study, we present the results from 17 interviews with students from a range of engineering and technology fields, describing how they reason as both designers and consumers of new technology. Our goal is to characterize students' patterns of reasoning about the ethics of new technology, and, in this paper, we describe how this reasoning is argued from multiple stakeholder perspectives (corporations, government, professionals, users and society). Our findings indicate privacy, security and balance of power as the most relevant ethical issues to respondents, and that participants consider several stakeholders in their reasoning, often shifting among multiple perspectives. Furthermore, interviewed students often concluded their reasoning by either resigning themselves to the pervasiveness of technology or by pushing the liability concerns to one stakeholder while diminishing the responsibility of others. In each case, respondents frequently avoided entering societal-level discussions related to ethical issues of emerging technology. Our results offer relevant insights that can facilitate further work related to the research and teaching of ethics to college students, as well as suggest areas for future research particularly building upon participants' feelings of resignation in relation to unethical use of new technology.

Purpose: Research on privileged parents, defined here as those with the economic, social, and educational resources to navigate school choice processes to their advantage, often depicts such parents as anxious about maintaining social mobility, leading them to "opportunity hoard" desirable or academically competitive schools in ways that exclude other families. In contrast, we identify a subset of privileged parents in urban settings that we term "happiness-oriented parents" who seek schools that prioritize their child's social-emotional happiness. Research Methods: Using a qualitative meta-analysis combining seven studies conducted by the authors in New York City; Hartford, Connecticut; and a small East Coast city between 2012 and 2021, we reanalyzed interview data from semistructured interviews with 106 privileged parents who have the ability to access and navigate a range of school choice options. Findings: We found a happiness orientation in a diverse group of privileged parents (40% identified as Black, Latinx, Asian American, or multiracial, and the remaining 60% were white). Although these parents were choosing a range of school options in different contexts and they identified different criteria as important to cultivating happiness, they consistently (1) centered happiness, (2) chose for social-emotional and noncompetitive academic factors, and (3) saw this choice as different from the norm. Implications: In identifying this repeated but understudied phenomenon, we consider that happiness-oriented parents' choices might affect a range of education policy changes and outcomes. In the case of our studies, we examine the potential of these parents as allies in school integration efforts.

Computing technology is reshaping the way in which professionals in the architecture, engineering, and construction industries conduct their business. The execution of construction tasks is changing from traditional 2D to 3D building information modeling (BIM)-based concepts. The use of BIM is expanded and enriched by the introduction of advanced computing technologies. At the same time, the demands for graduates in construction management with basic computing technology skills are on the rise. One of the challenges of construction management (CM) programs is how to incorporate computing knowledge so that future graduates can gain more experience with it during their undergraduate education. This paper presents a case study on this topic from an undergraduate construction management course at Purdue University. The in-class exercises and project required the use of computing technologies (e.g., quantity takeoff software, scheduling software, and Python programming) in this case study. The performance of students was evaluated before and after the project and the exercises. The findings showed the benefits of incorporating computing into a construction management curriculum as follows: (1) introducing the students to the efficiency and accuracy of computing technologies in CM; and (2) improving students' knowledge and skills in computing technologies and professional software applications. Based on students' feedback, short-term (one-class-long) programming training during the semester and more detailed instructions for a project are needed improvements in this course. The practice in this study provides insights for other instructors seeking to include more computing technologies into CM courses.

Sesame (Sesamum indicum L.) seed coat (SSC) is a by-product generated during the production of sesame paste, known as tahini. Research has demonstrated that this by-product is abundant in valuable nutritional compounds. Various extraction methods are employed to enhance the value of industrial waste by recovering its bioactive compounds. The study aims to optimize the extraction of polyphenols utilizing an infrared technique Ired-Irrad® (IR), in comparison to the water bath (WB) extraction. To optimize the extraction of polyphenols from SSC using both the IR and WB extraction methods, the study utilized Response Surface Methodology (RSM). Under optimal conditions, IR extraction resulted in an improved polyphenol yield, which was 20% higher than that obtained using WB extraction. Similarly, the antiradical activity, quantified as mg of Trolox equivalent per milliliter, increased from 0.58 mg TE/mL in the WB extract to 0.68 mg TE/mL in the IR extract. The phytochemical profile of the IR and WB extracts was examined through High-Performance Liquid Chromatography (HPLC). The major polyphenols identified in both extracts were the flavonoids rutin (3.87 mg/L in IR, 1.72 mg/L in WB) and catechin (3.05 mg/L in IR, 1.32 mg/L in WB). The IR extract revealed the highest yield of polyphenols among the majority of compounds, compared to WB. The lyophilized SSC extracts obtained through both the IR and WB methods demonstrated the most effective antibacterial activity against Listeria monocytogenes, with a minimal bactericidal concentration (MBC) value exceeding 100 mg/mL. However, minor antibacterial effects were detected against the Gram-negative strains, Salmonella Typhimurium and Escherichia coli O157:H7, for extracts obtained with both the IR and WB methods.

BackgroundDiabetes Mellitus, a global health challenge, affects 537 million individuals. Traditional management relies on periodic clinic visits, but technological advancements, including remote monitoring, offer transformative changes. Telemedicine enhances access, convenience, adherence, and glycemic control. Challenges include trust-building and limitations in face-to-face interactions. Integrating remote monitoring with in-person healthcare creates a hybrid approach. This study evaluates the impact on Type 2 Diabetes patients over 3 months.MethodsA retrospective case-control observational study. Inclusion criteria involved previous Type 2 Diabetes diagnosis and a minimum 3-month GluCare model period with two physical visits. Patients in the case group had in-clinic visits, bi-weekly app engagement, and monthly body weight readings. Control group had in-clinic visits only. Outcomes measured included HbA1c, lipid profile, CV risk, eGFR, urine Albumin/Creatinine Ratio, Uric Acid, and CRP.ResultsCase group showed significant HbA1c improvements (-2.19%), especially in higher baseline levels. Weight, BMI, LDL, total cholesterol, and CVD risk also improved. Controls showed smaller improvements. Higher digital interactions correlated with better outcomes. Patients with ≥11 interactions showed significant reductions in HbA1c (-2.38%) and weight (-6.00 kg).ConclusionThe GluCare.Health hybrid model demonstrates promising outcomes in Type 2 diabetes management. The integration of in-clinic consultations with continuous remote monitoring leads to substantial improvements in glycemic control and clinical parameters. The study highlights the importance of patient engagement in achieving positive outcomes, with higher digital interactions associated with greater reductions in HbA1c and weight. The hybrid approach proves more effective than digital-only interventions, emphasizing the need for comprehensive, end-to-end solutions in diabetes care.

The long history of Montessori education in India dates to 1915, and it was expanded through Maria and Mario Montessori's work in India between 1939 to 1946 and 1947 to 1949. The article characterizes a century of Montessori education in India as a series of "adapted, competing, and contested framings" with key disputes over Montessori education's intended purpose, audience, and how much it could be adapted. First, from 1915 to 1939, Montessori education was connected to the Indian independence movement as nation-building education, but it was eclipsed by a parallel rise of elite, private Montessori schools, a framing reinforced by Maria Montessori's insistence on fidelity to her method. Starting in the 1950s, other Indian educators adapted Montessori for poor children, an emphasis that continues today with government and foundation-funded schools. Finally, in the last thirty years, India's new middle class has driven demand for early childhood education, leading to branded Montessori franchises, some bearing little resemblance to Montessori's original pedagogy.

Abstract Introduction Breast magnetic resonance imaging (MRI) is increasingly being used for staging of patients with breast cancer due to its high sensitivity in detecting additional cancers (ACs). However, the clinical impact of diagnosing and treating these cancers remains unclear. Methods A retrospective study was undertaken of patients with newly diagnosed breast cancer who underwent staging MRI at The American University of Beirut Medical Centre (AUBMC) between 2012 and 2020. Pathology reports and breast MRI examinations were reviewed. Eighteen breast cancer patients with 19 pathology‐proven index cancers (ICs) and 19 pathology‐proven MRI‐detected ACs were included. Chi‐square and Fisher's exact tests for categorical variables and Wilcoxon signed rank test for numerical variables were used to compare ICs to ACs. Results The ICs consisted of four ductal carcinoma in situ (DCIS), 13 invasive ductal carcinomas (IDC), of which five with associated DCIS, and two invasive lobular carcinomas, (ILC) of which one with associated DCIS. ACs comprised 12 DCIS, five IDC, two with associated DCIS and two ILC, one with associated DCIS. Interval cancers were more frequently invasive whereas ACs were more frequently in situ (P = 0.021). ACs were more frequently nuclear grade 2 (P = 0.009). There was no statistically significant difference between ICs and ACs in lesion type (P = 0.062), shape (P = 0.073), initial enhancement (P = 1), delayed enhancement (P = 0.732), hormonal receptor profile (P = 0.68) and Ki67 (P = 0.388). Among ACs, ten (53%) were larger than 10 mm of which five (26%) were invasive cancers, and five (26%) were larger than the ICs. Conclusions ACs detected by breast MRI were more likely to be in situ and to show a nuclear grade 2. Although not reaching statistical significance, some ACs tend to be clinically significant by their type, size or nuclear grade. The impact on clinical management remains to be determined.

Cumin seeds are frequently utilized in herbal infusions and as flavoring agents in home cuisine. Nevertheless, studies have demonstrated that spices are frequently contaminated with pathogenic bacteria, including bacterial spores. The aim of this study was to assess the effectiveness of a new decontamination method called “Intensification of Vaporization by Decompression to the Vacuum” (IVDV) on intentionally contaminated Cuminum cyminum seeds. The study also examined the impact of this treatment on the color and oil profile of the treated samples. The untreated samples were inoculated with Escherichia coli (ATCC 25922) and Salmonella Typhimurium (ATCC 14028) and then subjected to IVDV treatment. Response surface methodology was employed to obtain safe, high-quality cumin seeds presenting a balance between microbial load, color, and oil profile. The optimal IVDV conditions were achieved at a pressure of 3.5 bar and a time of 133.45 s, resulting in typical 4 log reductions observed with 99.99% of Escherichia coli and Salmonella Typhimurium inactivation. The treated spices presented a mild color modification compared to the untreated ones, manifested by a darker shade (decreased L* value), reduced greenness (increased a* value), and heightened yellowness (increased b* value). The GC-MS analysis detected the existence of seven compounds in the treated cumin, with cuminaldehyde being the primary compound (83.79%). Furthermore, the use of IVDV treatment resulted in an increase in the total content of essential oils in some samples, whereby six monoterpenes were identified in the untreated sample compared to seven monoterpenes in IVDV-treated samples. This innovative technology demonstrated high efficacy in decontaminating C. cyminum seeds, improving the extractability of the essential oils while only slightly affecting the color.

BackgroundMost people living with dementia want to remain living in their own homes and are supported to do so by family carers. No interventions have consistently demonstrated improvements to people with dementia's life quality, functioning, or other indices of living as well as possible with dementia. We have co-produced, with health and social care professionals and family carers of people with dementia, a new intervention (NIDUS-family). To our knowledge, NIDUS-family is the first manualised intervention that can be tailored to personal goals of people living with dementia and their families and is delivered by facilitators without clinical training. The intervention utilizes components of behavioural management, carer support, psychoeducation, communication and coping skills training, enablement, and environmental adaptations, with modules selected to address dyads' selected goals. We will evaluate the effect of NIDUS-family and usual care on goal attainment, as measured by Goal Attainment Scaling (GAS) rated by family carers, compared to usual care alone at 12-month follow-up. We will also determine whether NIDUS-family and usual care is more cost-effective than usual care alone over 12 months.MethodsA randomised, two-arm, single-masked, multi-site clinical trial involving 297 people living with dementia-family carer dyads. Dyads will be randomised 2:1 to receive the NIDUS-family intervention with usual care (n = 199) or usual care alone (n = 98). The intervention group will be offered, over 1 year, via 6-8 video call or telephone sessions (or face to face if COVID-19 restrictions allow in the recruitment period) in the initial 6 months, followed by telephone follow-ups every 1-2 months to support implementation, with a trained facilitator.DiscussionIncreasing the time lived at home by people living with dementia is likely to benefit lives now and in the future. Our intervention, which we adapted to include remote delivery prior to trial commencement due to the COVID-19 pandemic, aims to address barriers to living as well and as independently as possible that distress people living with dementia, exacerbate family carer(s) stress, negatively affect relationships, lead to safety risks, and frequently precipitate avoidable moves to a care home.Trial registrationInternational Standard Randomised Controlled Trials Number ISRCTN11425138 . Registered on 7 October 2019.

Abstract Background HCV infection in hemodialysis units is a significant cause of morbidity and mortality. The risk of HCV infection among dialysis patients is higher compared to the general population due to high potential blood exposures in hemodialysis settings. This study aims to assess the national HCV seroprevalence in selected dialysis units and to determine the risk factors for acquiring HCV infection. Methods This cross-sectional study was conducted from 1 January to 31 March 2021. A total of 734 patients from 11 hemodialysis centers in Oman were included. Samples were tested simultaneously for HCV antibodies and HCV RNA. HCV genotyping was determined in all viremic patients. Demographic and hemodialysis center related data were gathered and their association with the positive HCV serology were explored using univariate and multivariate logistic regression analysis. Results Out of 800 patients selected from 11 dialysis units for the study, 734 patients (91.8%) were included. The overall seroprevalence of HCV infection among hemodialysis patients was 5.6%. (41/734). HCV RNA was detected in 31.7% (13/41) of seropositive hemodialysis patients. The most common genotype was subtype 1a, followed by subtype 3. Variables associated with high HCV prevalence were family history of HCV and duration of dialysis. Conclusion The prevalence of infection within hemodialysis patients in Oman has significantly decreased but remained higher than the general population. Continuous monitoring and follow-up, including periodic serosurvey and linkage to care and treatment are recommended. Additionally, practice audits are recommended for identifying gaps and ensuring sustainability of best practices and further improvement.

Abstract Whether sex differences exist in the cardiac remodeling related to aortic regurgitation (AR) is unclear. Cardiac magnetic resonance (CMR) is the current non-invasive reference standard for cardiac remodeling assessment and can evaluate tissue characteristics. This prospective cohort included patients with AR undergoing CMR between 2011 and 2020. We excluded patients with confounding causes of remodeling. We quantified left ventricular (LV) volume, mass, AR severity, replacement fibrosis by late Gadolinium enhancement (LGE), and extracellular expansion by extracellular volume fraction (ECV). We studied 280 patients (109 women), median age 59.5 (47.2, 68.6) years (P for age = 0.25 between sexes). Women had smaller absolute LV volume and mass than men across the spectrum of regurgitation volume (RVol) (P ≤ 0.01). In patients with ≥ moderate AR and with adjustment for body surface area, indexed LV end-diastolic volume and mass were not significantly different between sexes (all P > 0.5) but men had larger indexed LV end systolic volume and lower LV ejection fraction (P ≥ 0.01). Women were more likely to have NYHA class II or greater symptoms than men but underwent surgery at a similar rate. Prevalence and extent of LGE was not significantly different between sexes or across RVol. Increasing RVol was independently associated with increasing ECV in women, but not in men (adjusted P for interaction = 0.03). In conclusion, women had lower LV volumes and mass than men across AR severity but their ECV increased with higher regurgitant volume, while ECV did not change in men. Indexing to body surface area did not fully correct for the cardiac remodeling differences between men and women. Women were more likely to have symptoms but underwent surgery at a similar rate to men. Further research is needed to determine if differences in ECV would translate to differences in the course of AR and outcomes.

“Intensification of Vaporization by Decompression to the Vacuum” (IVDV) has initially emerged as a technology primarily employed for expanding and enhancing the texture of biological products. However, its recent applications have showcased significant promise in the realm of extracting bioactive molecules from various plant materials. In this context, optimization using response surface methodology was conducted to investigate the impact of IVDV pretreatment on the extractability of phenolic compounds from Eryngium creticum leaves and stems, as well as their biological activities. Using IVDV preceding the extraction led to higher total phenolic content (TPC) and enhanced antiradical activities in treated materials compared to untreated ones. The optimal processing conditions in terms of water content, steam pressure and treatment time were determined in order to maximize TPC (89.07 and 20.06 mg GAE/g DM in leaves and stems, respectively) and antiradical (DPPH) inhibition percentage (93.51% and 27.54% in leaves and stems, respectively). IVDV-treated extracts showed superior antioxidant, antibacterial and antibiofilm capacities compared to raw extracts. Using RP-UHPLC-PDA-MS, caffeic acid and rosmarinic acid were identified in IVDV-treated leaves. IVDV can be implemented as an innovative treatment applied prior to extraction to boost the recovery of biomolecules from plant matrices.

Education 4.0 uses digital technologies, innovative methodologies, and learning spaces to improve the quality of education. It reflects the changes brought about by the fourth industrial revolution and aims to develop skills relevant to current and future technology scenarios. The transformation of education to Education 4.0 presents challenges and opportunities, and requires the collaborative participation of industry, governments, universities, and society. This work aims to synthesize concepts of Education 4.0, and identify the innovative technologies, key competencies, learning approaches, trend topics, and how it is being applied in engineering education. A scoping review was conducted following the PRISMA statement. The Scopus and Web of Science databases were used in the review. Bibliometric tools in R Studio and VOSviewer software were employed to summarize the bibliometric data and analyze the results. Bibliometric analysis of the 528 selected documents revealed a significant growth in publications from 2017 to September 2023. Nearly half of the selected literature originated from conference proceedings, and 42.6% of the selected papers have not yet been cited. Moreover, five research clusters were identified from the select publications related to studying Education 4.0 in higher education, specifically engineering education: concept, competency-based learning, specific technologies applied to education, learning system, and competency-based learning. The use of Industry 4.0 technology, such as Artificial Intelligence, the Internet of Things, and Virtual Labs, combined with active learning teaching methodologies, such as gamification and blended learning, has been identified as points of convergence and trending research topics within Education 4.0.

Objective. To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis. Methods. PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: “congenital toxoplasmosis” or “gestational toxoplasmosis” and “diagnosis” and “blood,” “serum,” “amniotic fluid,” “placenta,” or “colostrum.” We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis. Results. Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity. Conclusion. Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges.

Background Up to 30% of children have constipation at some stage in their life. Although often short-lived, in one-third of children it progresses to chronic functional constipation, potentially with overflow incontinence. Optimal management strategies remain unclear. Objective To determine the most effective interventions, and combinations and sequences of interventions, for childhood chronic functional constipation, and understand how they can best be implemented. Methods Key stakeholders, comprising two parents of children with chronic functional constipation, two adults who experienced childhood chronic functional constipation and four health professional/continence experts, contributed throughout the research. We conducted pragmatic mixed-method reviews. For all reviews, included studies focused on any interventions/strategies, delivered in any setting, to improve any outcomes in children (0–18 years) with a clinical diagnosis of chronic functional constipation (excluding studies of diagnosis/assessment) included. Dual reviewers applied inclusion criteria and assessed risk of bias. One reviewer extracted data, checked by a second reviewer. Scoping review: We systematically searched electronic databases (including Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature) (January 2011 to March 2020) and grey literature, including studies (any design) reporting any intervention/strategy. Data were coded, tabulated and mapped. Research quality was not evaluated. Systematic reviews of the evidence of effectiveness: For each different intervention, we included existing systematic reviews judged to be low risk of bias (using the Risk of Bias Assessment Tool for Systematic Reviews), updating any meta-analyses with new randomised controlled trials. Where there was no existing low risk of bias systematic reviews, we included randomised controlled trials and other primary studies. The risk of bias was judged using design-specific tools. Evidence was synthesised narratively, and a process of considered judgement was used to judge certainty in the evidence as high, moderate, low, very low or insufficient evidence. Economic synthesis: Included studies (any design, English-language) detailed intervention-related costs. Studies were categorised as cost-consequence, cost-effectiveness, cost-utility or cost-benefit, and reporting quality evaluated using the consensus health economic criteria checklist. Systematic review of implementation factors: Included studies reported data relating to implementation barriers or facilitators. Using a best-fit framework synthesis approach, factors were synthesised around the consolidated framework for implementation research domains. Results Stakeholders prioritised outcomes, developed a model which informed evidence synthesis and identified evidence gaps. Scoping review 651 studies, including 190 randomised controlled trials and 236 primary studies, conservatively reported 48 interventions/intervention combinations. Effectiveness systematic reviews studies explored service delivery models (n = 15); interventions delivered by families/carers (n = 32), wider children’s workforce (n = 21), continence teams (n = 31) and specialist consultant-led teams (n = 42); complementary therapies (n = 15); and psychosocial interventions (n = 4). One intervention (probiotics) had moderate-quality evidence; all others had low to very-low-quality evidence. Thirty-one studies reported evidence relating to cost or resource use; data were insufficient to support generalisable conclusions. One hundred and six studies described implementation barriers and facilitators. Conclusions Management of childhood chronic functional constipation is complex. The available evidence remains limited, with small, poorly conducted and reported studies. Many evidence gaps were identified. Treatment recommendations within current clinical guidelines remain largely unchanged, but there is a need for research to move away from considering effectiveness of single interventions. Clinical care and future studies must consider the individual characteristics of children. Study registration This study is registered as PROSPERO CRD42019159008. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 128470) and is published in full in Health Technology Assessment; Vol. 28, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Between 5% and 30% of children experience constipation at some stage. In one-third of these children, this progresses to chronic functional constipation. Chronic functional constipation affects more children with additional needs. We aimed to find and bring together published information about treatments for chronic functional constipation, to help establish best treatments and treatment combinations. We did not cover assessment or diagnosis of chronic functional constipation. This project was guided by a ‘stakeholder group’, including parents of children with constipation, people who experienced constipation as children, and healthcare professionals/continence experts. We carried out a ‘scoping review’ and a series of ‘systematic reviews’. Our ‘scoping review’ provides an overall picture of research about treatments, with 651 studies describing 48 treatments. This helps identify important evidence gaps. ‘Systematic reviews’ are robust methods of bringing together and interpreting research evidence. Our stakeholder group decided to structure our systematic reviews to reflect who delivered the interventions. We brought together evidence about how well treatments worked when delivered by families/carers (32 studies), the wider children’s workforce (e.g. general practitioner, health visitor) (21 studies), continence teams (31 studies) or specialist consultant-led teams (42 studies). We also considered complementary therapies (15 studies) and behavioural strategies (4 studies). Care is affected by what is done and how it is done. We brought together evidence about different models of delivering care (15 studies), barriers and facilitators to implementation of treatments (106 studies) and costs (31 studies). Quality of evidence was mainly low to very low. Despite numerous studies, there was often insufficient information to support generalisable conclusions. Our findings generally agreed with current clinical guidelines. Management of childhood chronic functional constipation should be child-centred, multifaceted and adapted according to the individual child, their needs, the situation in which they live and the health-care setting in which they are looked after. Research is needed to address our identified evidence gaps. Scientific summary Background Chronic functional constipation (CFC) in childhood is common; it is estimated to affect 5–30% of school-aged children, becoming chronic in around one-third of cases. CFC has negative effects on quality of life (QoL) of children, families and carers, with increasing impact as the child gets older. Although rarely life-threatening, CFC is an unpleasant and distressing condition, associated with a wide range of complications, including physical discomfort, missed school, poor school performance, social isolation and reduced involvement in group activities. More than a third of children with CFC will present clinically with behavioural problems as a result of the constipation. The healthcare costs of childhood CFC are significant. Treatments are usually directed at symptom control since limited diagnostics mean no underlying cause is identified in more than 95% of cases, thus limiting ability to stratify treatments. There are a number of different interventions available for the management of CFC; however, the optimal strategy for combining and implementing interventions for individual circumstances remain unclear. National Institute for Health and Care Research (NIHR) commissioned this work to address the question: ‘What are the most effective interventions, and combinations and sequences of interventions, for childhood chronic functional constipation (CFC), and how can they best be implemented?’ Objectives Specific research questions (RQs) answered by this project were: RQ1: What is the current evidence relating to management strategies for childhood CFC? (Scoping review). RQ2: What are the most effective childhood CFC strategies and combinations of strategies in relation to outcomes of importance to stakeholders and/or cost to the patient/NHS? [Systematic review (SR) of evidence of effectiveness and cost effectiveness]. RQ3: What factors are associated with implementation success or failure of childhood CFC strategies and combinations of strategies for different subgroups? (SR of factors affecting implementation). RQ4: What are the evidence gaps in childhood CFC management strategies? Design We conducted a three-stage pragmatic mixed-method study. In stage 1, we completed a broad, comprehensive scoping review. In stage 2, we conducted focused SRs evaluating effectiveness, cost effectiveness and factors affecting implementation. In stage 3, we integrated findings, generating interactive evidence maps, exploring complementarity between our findings and published clinical guidelines, and identifying evidence gaps. Methods Patient and public involvement Stakeholder involvement was central to our project. We formed a stakeholder group (SG) from across the UK, comprising people with lived experience of childhood CFC, parents of children with CFC, healthcare professionals and representatives of relevant charities. We adhered to key principles for research co-production. The SG provided continuous project oversight and completed specific activities. These activities included development of an intervention taxonomy and logic model, agreement on outcomes for the review, identifying evidence gaps and reaching consensus on clinical implications. Scoping review Our scoping review was based on a systematic search of several electronic databases including medical literature analysis and retrieval system online (MEDLINE), excerpta medica database (EMBASE) and Cumulative Index to Nursing and Allied Health Literature (CINAHL; January 2011 to March 2020), as well as searches of grey literature, contacting experts and forward citation tracking. We included papers, regardless of study design, which investigated, reported or discussed any strategy, delivered in any setting, aimed at improving any outcomes in children (aged 0–18 years) with a clinical diagnosis of CFC. We did not include studies of assessment/diagnosis. We included studies involving children with or without additional needs but excluded those with a recognisable cause of constipation such as anorectal malformation, Hirschsprung’s disease, intestinal nerve abnormalities, metabolic or endocrine causes. Eligible abstracts and full texts were independently reviewed by two reviewers. Data were extracted by one reviewer and cross-checked by a second. Two reviewers independently applied descriptive codes to categorise the type of study, aim/focus of the study, outcomes, types of interventions/intervention combinations, and availability of data relating to effectiveness, economics or implementation factors. In keeping with scoping review methodology, we did not formally assess research quality. Data were summarised within an evidence gap map. Systematic reviews of evidence of effectiveness For our SRs of evidence of effectiveness, we considered all studies identified in the scoping review and ‘tagged’ them as studies of effectiveness. We included any studies investigating effectiveness of any intervention, or combination of interventions, aimed at improving outcomes in children with CFC. Informed by our stakeholders, we grouped studies according to whether the intervention was one that would be delivered by families/carers (‘Level 0’), the wider children’s workforce (e.g. general practitioner, health visitor) (‘Level 1’), continence teams (‘Level 2’) or specialist consultant-led teams (‘Level 3’). We also considered different models of service delivery, and complementary and psychosocial therapies. For each different intervention, we adopted a hierarchical, step-wise approach to inclusion of different study designs. If there was a comprehensive SR, judged to be low risk of bias (ROB) [using risk of bias assessment tool for systematic reviews (ROBIS) criteria, assessed by two independent reviewers], this was also included. Where we included a SR, we also included any randomised controlled trials (RCTs) published after the date of the search in the review. Where there was no SR, we included RCTs and other primary studies of intervention effectiveness. Data were extracted on study methods, participant characteristics, intervention characteristics [using template for intervention description and replication (TIDieR) framework], outcomes and key findings. ROB was judged using tools appropriate to the study design [e.g. Cochrane ROB tool for RCTs, critical appraisals skills programme (CASP) tools for cohort studies, Joanna Briggs Institute (JBI) tools for qualitative evidence, Ways of Evaluating Important and Relevant Data (WEIRD) tool for other study designs]. Relevant meta-analyses within included SRs were updated with any new RCTs following the methods reported in the SR. A narrative synthesis of evidence of effectiveness for each intervention, delivered within ‘level’ 0 to 3 was presented, with a process of considered judgement used to judge certainty in the evidence as high, moderate, low, very low or insufficient evidence. Economic evaluation For our SR of economic studies, we considered any economic evidence identified in our scoping review and conducted additional searching of electronic databases and citation tracking following best practice guidance. We included all types of study detailing costs related to interventions aimed at children with CFC that were published in English, regardless of study design. One reviewer extracted data, including details of economic evaluations, and these were checked by a second reviewer. Studies were categorised as cost-consequence, cost-effectiveness, cost-utility or cost-benefit and their quality evaluated using the consensus health economic criteria (CHEC) checklist, and data were brought together into a narrative synthesis. Systematic review of factors affecting implementation For our SR of factors affecting implementation, we included studies which were identified in the scoping review as explicitly reporting data relating to key participant variables, barriers, facilitators, equity factors and adherence. One reviewer systematically identified, extracted and coded [using the consolidated framework for implementation research (CFIR)] barriers and facilitators, and a second reviewer checked this. We used a best fit framework synthesis approach combining deductive and inductive thematic approaches to identify barriers and facilitators. Data were brought together in a narrative synthesis organised around the CFIR domains. Integration of findings Our integration of findings from the SRs was informed by decisions taken by our stakeholders, including development of a logic model. We explored agreements between our findings and recommendations within previously published guidelines. We brought our findings together within interactive evidence maps, and systematically identified evidence gaps. Results The scoping review included 651 studies, including 190 RCTs and 236 primary studies. Forty-eight interventions (or combinations of interventions) were reported. Studies were mainly conducted in high-income countries; no studies from low-income countries were identified. The most frequently reported interventions were delivered by carers, prior to healthcare professional involvement (22%); these were primarily lifestyle interventions focused on diet. The least frequently reported were psychosocial interventions (3%). Children were recruited from a variety of settings including hospitals, clinical outpatients, and other community settings. Interventions were generally delivered face to face either at home or within a variety of hospital settings such as the emergency department. Interventions were rarely delivered in education settings (e.g. school-based settings) (n = 5) or residential care/looked after population (n = 1) settings. The most frequently reported outcome measurement was defaecation frequency, which was reported in one-third of studies within the scoping review. School attendance or absenteeism was the least frequently reported outcome (n = 8 studies). Our SRs of effectiveness included 32 studies (including 2 SRs) which explored effectiveness of interventions delivered by families/carers (‘Level 0’); 21 studies (including 2 SRs) which explored effectiveness of interventions delivered by wider children’s workforce (‘Level 1’); 31 studies (including 1 SR) which explored effectiveness of interventions delivered by continence teams (‘Level 2’); 42 studies (no SRs) which explored effectiveness of interventions delivered by specialist consultant-led teams (‘Level 3’); 15 studies (no SRs) which explored effectiveness of different models of service delivery; 15 studies (2 SRs) which explored effectiveness of complementary therapies; and 4 studies (1 SR) which explored effectiveness of psychosocial interventions. Interventions for which there was some evidence of potential benefit included, within Level 0: a trial of cows’ milk-free diet, educational interventions for parents, selenium supplements. Within Level 1: laxatives, physical exercise focused on pelvic floor muscle, combined pharmacological, diet and behaviour programme. Within Level 2: combined oral and enema therapy, transanal irrigation, biofeedback (for children with abnormal defaecation dynamics), combined treatment programmes. Within Level 3: botulinum toxin, antegrade continence enema (ACE)/Malone antegrade continence enema (MACE), sacral modulation. Models of care delivery which may be beneficial included nurse-led clinics, an algorithm, or care pathway, used in primary care settings, specialist (Level 2) services and web-based information, following an appointment with a specialist. Complementary therapies for which there was some evidence of effectiveness included: connective tissue manipulation (CTM) for children with cerebral palsy (CP), and some herbal/traditional medicines. There was some evidence in favour of behavioural therapy. Interventions which evidence suggests may not be beneficial include, probiotics, additional dietary fibre, increased fluid intake and biofeedback (for children with normal defaecation dynamics). Evidence relating to probiotics was judged to be moderate quality, but for all other interventions was considered low to very low quality. There was insufficient evidence to support conclusions relating to several other interventions. We identified 31 studies which reported some evidence relating to cost or resource use, of which 20 were cost-of-illness studies. Fewer than 30% of the studies employed a formal economic evaluation study design. Most studies were poorly reported with limited details. Data included in this review were insufficient to support any generalisable conclusions relating to cost or resource use. One hundred and six studies described multiple barriers and facilitators across the five domains of the CFIR framework. The most commonly reported factors related to ‘successfulness’ of an intervention included; whether the intervention was adaptable, flexible and offered an advantage over an alternative solution; understanding the tension for change (i.e. why clinicians and families felt that the changes were needed now); the taboo nature of constipation and the reluctance of children, families, healthcare professionals and wider society to openly engage in discussion about constipation; a lack of understanding of what children and their families need; self-efficacy, coupled with individual knowledge and beliefs; and engagement of champions to support children. Research gaps were identified through evidence maps and stakeholder discussions. Key topics considered priorities for future research relate to recognition of CFC; information provision; diet; laxatives and combinations of laxatives; behavioural therapy and psychological support. Future research studies should address what works for which individual child, and when, including children with and without additional needs. Research to explore the optimal delivery of services, including identification of key components and features of effective teams and criteria for referring children from one ‘level’ to the next, is needed. Conclusions We conducted a comprehensive review of all evidence relating to interventions, and combinations of interventions, for children with CFC. The finding from our review are generally in agreement with the current guideline recommendations, where recommendations exist. A significant proportion of interventions for which we found evidence had not been addressed within current guidelines. This project has highlighted that research in this field often does not adhere to recognised standards for conduct and reporting or consider the complexities of interventions for CFC. We found no evidence which gave us high certainty in the findings; and we only had moderate certainty relating to one intervention (probiotics, with evidence demonstrating that probiotics may not have any beneficial – or harmful – effect). Our certainty about all other findings was low to very low or, in many cases, we judged that the evidence was insufficient to support any generalised conclusions. The current evidence base rarely measured outcomes deemed of highest priority to children and families, and many studies failed to describe the complex nature of the treatments that a child may be receiving. This limits the conclusions that can be made from the current evidence. Further, the limitations within the evidence base reduce confidence in recommendations and create a barrier to implementation of best practice, impairing progress in efforts to improve outcomes for this group of children. Our findings do not indicate that changes are necessarily needed to the treatment recommendations within current clinical guidelines. However, management of childhood CFC is complex, and there is no simple ‘one size fits all’ approach. Clinical care and future studies must consider the individual characteristics of each child with constipation, and the context – or environment – within which they live. Key goals of successful management of CFC should be early recognition of symptoms and delivery of interventions by families/carers, achieved by providing children and families/carers with effective education and support from members of the wider children’s workforce (primary care services). Development, evaluation and implementation of strategies to enhance the delivery of services focused on individualised care, combining lifestyle and behavioural strategies with laxatives are a priority. To avoid further research waste, it is essential that future research addresses the questions which are of the highest priority to key stakeholders and has the highest possible standards of conduct and reporting. Future research studies should address what works for which individual child, and when, including children with and without additional needs. Future research into any interventions for childhood CFC should take into account relevant evidence relating to the development and evaluation of complex interventions. Study registration This study is registered as PROSPERO CRD42019159008. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 128470) and is published in full in Health Technology Assessment; Vol. 28, No. 5. See the NIHR Funding and Awards website for further award information.