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1.
Endocr Connect ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38838713

ABSTRACT

Prader Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with a birth incidence of approximately 1 in 10,000-30,000. Management of people with PWS requires a multi-disciplinary approach, ideally through a multi-disciplinary team (MDT) clinic with community support. Hypotonia, poor feeding and faltering growth are characteristic features in the neonatal period, followed by hyperphagia and risk of rapid weight gain later in childhood. Children and adolescents (CA) with PWS usually display developmental delay and mild learning disability, and can develop endocrinopathies, scoliosis, respiratory difficulties (both central and obstructive sleep apnoea), challenging behaviours, skin picking, and mental health issues especially into adulthood. This consensus statement is intended to be a reference document for clinicians managing children and adolescents (up to 18 years of age) with PWS. It considers the bio-psycho-social domains of diagnosis, clinical assessment, and management in the paediatric setting as well as during and after transition to adult services. The guidance has been developed from information gathered from peer-reviewed scientific reports and from the expertise of a range of experienced clinicians in the United Kingdom and Ireland involved in the care of patients with PWS.

2.
J Clin Neurosci ; 124: 142-143, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38705026

ABSTRACT

Corticosteroids are a potential treatment to combat Complex Regional Pain Syndrome, however the adverse effect profile far outweighs the benefits of using them. Avascular necrosis and Osteonecrosis are among well defined adverse effects. Postmenopausal women are especially affected by corticosteroids due to loss of estrogen. Diabetics are an interesting study as their pain perception is altered due to either high cortisol levels or the development of peripheral neuropathy.


Subject(s)
Prednisolone , Reflex Sympathetic Dystrophy , Humans , Reflex Sympathetic Dystrophy/drug therapy , Prednisolone/therapeutic use , Prednisolone/administration & dosage , Female
3.
J Pharm Bioallied Sci ; 16(Suppl 1): S886-S888, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38595393

ABSTRACT

Background: Dental implant surgery has become a widely accepted method for replacing missing teeth. However, the success of dental implant procedures can be influenced by various factors, including the quality of preoperative planning and assessment. Cone beam computed tomography (CBCT) imaging provides valuable insights into a patient's oral anatomy, but accurately predicting implant success remains a challenge. Materials and Methods: In this randomized controlled trial (RCT), a cohort of 150 patients requiring dental implants was randomly divided into two groups: an artificial intelligence (AI)-assisted group and a traditional assessment group. Preoperative CBCT images of all patients were acquired and processed. The AI-assisted group utilized a machine learning model trained on historical data to assess implant success probability based on CBCT images, while the traditional assessment group relied on conventional methods and clinician expertise. Key parameters such as bone density, bone quality, and anatomical features were considered in the AI model. Results: After the completion of the study, the AI-assisted group demonstrated a significantly higher implant success rate, with 92% of implants successfully integrating into the bone compared to 78% in the traditional assessment group. The AI model showed an accuracy of 87% in predicting implant success, whereas traditional assessment methods achieved an accuracy of 71%. Additionally, the AI-assisted group had a lower rate of complications and required fewer postoperative interventions compared to the traditional assessment group. Conclusion: The AI-assisted approach significantly improved implant success rates and reduced complications, underscoring the importance of incorporating AI into the dental implant planning process.

4.
bioRxiv ; 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38496569

ABSTRACT

Colorectal cancer has been linked to chronic colitis and red meat consumption, which can increase colonic iron and heme. Heme oxygenase-1 ( Hmox1 ) metabolizes heme and releases ferrous iron, but its role in colonic tumorigenesis is not well-described. Recent studies suggest that ferroptosis, the iron-dependent form of cell death, protects against colonic tumorigenesis. Ferroptosis culminates in excessive lipid peroxidation that is constrained by the antioxidative glutathione pathway. We observed increased mucosal markers of ferroptosis and glutathione metabolism in the setting of murine and human colitis, as well as murine colonic neoplasia. We obtained similar results in murine and human colonic epithelial organoids exposed to heme and the ferroptosis activator erastin, especially induction of Hmox1 . RNA sequencing of colonic organoids from mice with deletion of intestinal epithelial Hmox1 (Hmox1 ΔIEC ) revealed increased ferroptosis and activated glutathione metabolism after heme exposure. In a colitis-associated cancer model we observed significantly fewer and smaller tumors in Hmox1 ΔIEC mice compared to littermate controls. Transcriptional profiling of Hmox1 ΔIEC tumors and tumor organoids revealed increased ferroptosis and oxidative stress markers in tumor epithelial cells. In total, our findings reveal ferroptosis as an important colitis-associated cancer signature pathway, and Hmox1 as a key regulator in the tumor microenvironment.

5.
ACS Omega ; 9(10): 11377-11387, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38496957

ABSTRACT

Catalysts with active, selective, and reusable features are desirable for sustainable development. The present investigation involved the synthesis and characterization of bear-surfaced ultrasmall Pd particles (<1 nm) loaded onto the surface of magnetic nanoparticles (8-10 nm). The amount of Pd loading onto the surface of magnetite is recorded as 2.8 wt %. The characterization process covered the utilization of scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), transmission electron microscopy (TEM), inductively coupled plasma (ICP), and X-ray photoelectron spectroscopy (XPS) methods. The Pd@Fe3O4 catalyst has shown remarkable efficacy in the hydrogenation of quinoline, resulting in the production of >99% N-ring hydrogenated (py-THQ) product. Additionally, the catalyst facilitated the conversion of nitroarenes into their corresponding aniline derivatives, where hydrogen was achieved by H2O molecules with the aid of tetrahydroxydiboron (THDB) as an equilibrium supportive at 80 °C in 1 h. The high efficiency of a transfer hydrogenation catalyst is closely related to the metal-support synergistic effect. The broader scope of functional group tolerance is evaluated. The potential mechanism underlying the hydrogenation process has been elucidated through the utilization of isotopic labeling investigations. The application of the heterocyclic compound hydrogenation reaction is extended to formulate the medicinally important tubular polymerization inhibitor drug synthesis. The investigation of the recyclability of Pd@Fe3O4 has been conducted.

6.
Chem Rec ; 24(4): e202300352, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38501854

ABSTRACT

Recently, carbon neutrality has been promoted as a potentially practical solution to global CO2 emissions and increasing energy-consumption challenges. Many attempts have been made to remove CO2 from the environment to address climate change and rising sea levels owing to anthropogenic CO2 emissions. Herein, membrane technology is proposed as a suitable solution for carbon neutrality. This review aims to comprehensively evaluate the currently available scientific research on membranes for carbon capture, focusing on innovative microporous material membranes used for CO2 separation and considering their material, chemical, and physical characteristics and permeability factors. Membranes from such materials comprise metal-organic frameworks, zeolites, silica, porous organic frameworks, and microporous polymers. The critical obstacles related to membrane design, growth, and CO2 capture and usage processes are summarized to establish novel membranes and strategies and accelerate their scaleup.

7.
Chem Asian J ; : e202301007, 2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38311592

ABSTRACT

Reducing CO2 emissions is an urgent global priority. In this context, several mitigation strategies, including CO2 tax and stringent legislation, have been adopted to halt the deterioration of the natural environment. Also, carbon recycling procedures undoubtedly help reduce net emissions into the atmosphere, enhancing sustainability. Utilizing Earth's abundant CO2 to produce high-potential green chemicals and light fuels opens new avenues for the chemical industry. In this context, many attempts have been devoted to converting CO2 as a feedstock into various value-added chemicals, such as CH4 , lower methanol, light olefins, gasoline, and higher hydrocarbons, for numerous applications involving various catalytic reactions. Although several CO2 -conversion methods have been used, including electrochemical, photochemical, and biological approaches, the hydrogenation method allows the reaction to be tuned to produce the targeted compound without significantly altering infrastructure. This review discusses the numerous hydrogenation routes and their challenges, such as catalyst design, operation, and the combined art of structure-activity relationships for the various product formations.

8.
Langmuir ; 40(10): 5040-5059, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38419155

ABSTRACT

Polluted water has become a concern for the scientific community as it causes many severe threats to living beings. Detection or removal of contaminants present in wastewater and attaining purity of water that can be used for various purposes are a primary responsibility. Different treatment methods have already been used for the purification of sewage. There is a need for low-cost, highly selective, and reusable materials that can efficiently remove pollutants or purify contaminated water. In this regard, MOFs have shown significant potential for applications such as supercapacitors, drug delivery, gas storage, pollutant adsorption, etc. The outstanding structural diversity, substantial surface areas, and adjustable pore sizes of MOFs make them superior candidates for wastewater treatment. This Review provides an overview of the interaction science and engineering (kinetic and thermodynamic aspects with interactions) underpinning MOFs for water purification. First, fundamental strategies for the synthesis methods of MOFs, different categories, and their applicability in wastewater treatment are summarized, followed by a detailed explanation of various interaction mechanisms. Finally, current challenges and future outlooks for research on MOF materials toward the adsorption of hazardous components are discussed. A new avenue for modifying their structural characteristics for the adsorption and separation of hazardous materials, which will undoubtedly direct future work, is also summarized.

9.
Chem Asian J ; 19(8): e202400045, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38375590

ABSTRACT

In the realm of material science, carbon materials, especially olive-derived carbon (ODC), have become vital due to their sustainability and diverse properties. This review examines the sustainable extraction and use of ODC, a carbohydrate-rich by-product of olive biomass. We focus on innovative preparation techniques like pyrolysis, which are crucial forenhancing ODC's microstructure and surface properties. Variables such as activating agents, impregnation ratios, and pyrolysis conditions significantly influence these properties. ODC's high specific surface area renders it invaluable for applications in energy storage (batteries and supercapacitors) and environmental sectors (water purification, hydrogen storage). Its versatility and accessibility underscore its potential for broad industrial use, makingit as a key element in sustainable development. This review provides a detailed analysis of ODC preparation methodologies, its various applications, and its role in advancing sustainable energy solutions. We highlight the novelty of ODC research and its impact on future studies, establishing this review as a crucial resource for researchers and practitioners in sustainable carbon materials. As global focus shifts towards eco-friendly solutions, ODC emerges as a critical component in shaping a sustainable, innovation-driven future.

10.
J Neurooncol ; 166(1): 51-57, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38224403

ABSTRACT

PURPOSE: Craniopharyngiomas can be aggressive leading to significant complications and morbidity. It is not clear whether there are any predictive factors for incidence or outcomes. Our aim was therefore to record the incidence, presentation, characteristics and progression of paediatric craniopharyngiomas in the West of Scotland. METHOD: Retrospective case note review for children diagnosed with paediatric craniopharyngiomas at the Royal Hospital for Children Glasgow, from 1995 to 2021 was conducted. All analyses were conducted using GraphPad Prism 9.4.0. RESULTS: Of 21 patients diagnosed with craniopharyngiomas, the most common presenting symptoms were headaches (17/21, 81%); visual impairment (13/21, 62%); vomiting (9/21, 43%) and growth failure (7/21, 33%). Seventeen (81%) patients underwent hydrocephalus and/or resection surgery within 3 months of diagnosis, usually within the first 2 weeks (13/21, 62%). Subtotal resection surgeries were performed in 71% of patients, and median time between subsequent resection surgeries for tumour recurrence was 4 years (0,11). BMI SDS increased at 5 year follow-up (p = 0.021) with 43% being obese (BMI > + 2SD). More patients acquired hypopituitarism post-operatively (14/16, 88%) compared to pre-operatively (4/15, 27%). A greater incidence of craniopharyngiomas were reported in more affluent areas (10/21, 48%) (SIMD score 8-10) compared to more deprived areas (6/10, 29%) (SIMD score 1-3). Five patients (24%) died with a median time between diagnosis and death of 9 years (6,13). CONCLUSION: Over 25 years the management of craniopharyngioma has changed substantially. Co-morbidities such as obesity are difficult to manage post-operatively and mortality risk can be up to 25% according to our cohort.


Subject(s)
Craniopharyngioma , Pituitary Neoplasms , Child , Humans , Craniopharyngioma/complications , Craniopharyngioma/epidemiology , Craniopharyngioma/surgery , Treatment Outcome , Retrospective Studies , Pituitary Neoplasms/complications , Pituitary Neoplasms/epidemiology , Pituitary Neoplasms/surgery , Neoplasm Recurrence, Local/surgery , Postoperative Complications/etiology
11.
Chem Rec ; 24(1): e202300216, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37651034

ABSTRACT

In recent years, the rapid growth in renewable energy applications has created a significant demand for efficient energy storage solutions on a large scale. Among the various options, rechargeable zinc-air batteries (ZABs) have emerged as an appealing choice in green energy storage technology due to their higher energy density, sustainability, and cost-effectiveness. Regarding this fact, a spotlight is shaded on air electrode for constructing high-performance ZABs. Cobalt oxide-based electrocatalysts on the air electrode have gained significant attention due to their extraordinary features. Particularly, exploration and integration of bifunctional behavior for energy storage has remarkably promoted both ORR and OER to facilitate the overall performance of the battery. The plot of this review is forwarded towards in-depth analysis of the latest advancements in electrocatalysts that are based on cobalt oxide and possess bifunctional properties along with an introduction of the fundamental aspects of ZABs, Additionally, the topic entails an examination of the morphological variations and mechanistic details mentioning about the synthesis processes. Finally, a direction is provided for future research endeavors through addressing the challenges and prospects in the advancement of next-generation bifunctional electrocatalysts to empower high-performing ZABs with bifunctional cobalt oxide.

12.
Obesity (Silver Spring) ; 32(2): 252-261, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37919617

ABSTRACT

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.


Subject(s)
Prader-Willi Syndrome , Humans , Child, Preschool , Prader-Willi Syndrome/drug therapy , Prader-Willi Syndrome/complications , Diazoxide/pharmacology , Diazoxide/therapeutic use , Hyperphagia/complications , Body Composition , Insulin/therapeutic use
13.
J Bronchology Interv Pulmonol ; 31(1): 63-69, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37246305

ABSTRACT

BACKGROUND: Benign airway stenosis (BAS) represents a significant burden on patients, providers, and healthcare systems. Spray cryotherapy (SCT) has been proposed as an adjunctive treatment to reduce BAS recurrence. We sought to examine safety and practice variations of the latest SCT system when used for BAS. METHODS: We conducted a retrospective multicenter cohort study in seven academic institutions within the Interventional Pulmonary Outcomes Group. All patients who underwent at least one SCT session with a diagnosis of BAS at the time of procedure at these institutions were included. Demographics, procedure characteristics, and adverse events were captured through each center's procedural database and electronic health record. RESULTS: A total of 102 patients underwent 165 procedures involving SCT from 2013 to 2022. The most frequent etiology of BAS was iatrogenic (n = 36, 35%). In most cases, SCT was used prior to other standard BAS interventions (n = 125; 75%). The most frequent SCT actuation time per cycle was five seconds. Pneumothorax complicated four procedures, requiring tube thoracostomy in two. Significant post-SCT hypoxemia was noted in one case, with recovery by case conclusion and no long-term effects. There were no instances of air embolism, hemodynamic compromise, or procedural or in-hospital mortality. CONCLUSION: SCT as an adjunctive treatment for BAS was associated with a low rate of complications in this retrospective multicenter cohort study. SCT-related procedural aspects varied widely in examined cases, including actuation duration, number of actuations, and timing of actuations relative to other interventions.


Subject(s)
Cryosurgery , Cryotherapy , Humans , Retrospective Studies , Cohort Studies , Constriction, Pathologic/etiology , Cryotherapy/adverse effects , Cryosurgery/adverse effects
14.
Shock ; 61(1): 4-18, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37752080

ABSTRACT

ABSTRACT: Sepsis remains a major challenge that necessitates improved approaches to enhance patient outcomes. This study explored the potential of machine learning (ML) techniques to bridge the gap between clinical data and gene expression information to better predict and understand sepsis. We discuss the application of ML algorithms, including neural networks, deep learning, and ensemble methods, to address key evidence gaps and overcome the challenges in sepsis research. The lack of a clear definition of sepsis is highlighted as a major hurdle, but ML models offer a workaround by focusing on endpoint prediction. We emphasize the significance of gene transcript information and its use in ML models to provide insights into sepsis pathophysiology and biomarker identification. Temporal analysis and integration of gene expression data further enhance the accuracy and predictive capabilities of ML models for sepsis. Although challenges such as interpretability and bias exist, ML research offers exciting prospects for addressing critical clinical problems, improving sepsis management, and advancing precision medicine approaches. Collaborative efforts between clinicians and data scientists are essential for the successful implementation and translation of ML models into clinical practice. Machine learning has the potential to revolutionize our understanding of sepsis and significantly improve patient outcomes. Further research and collaboration between clinicians and data scientists are needed to fully understand the potential of ML in sepsis management.


Subject(s)
Physicians , Sepsis , Humans , Sepsis/genetics , Algorithms , Machine Learning , Gene Expression
15.
Nanoscale ; 16(2): 868-878, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38099850

ABSTRACT

The rational construction of free-standing and flexible electrodes for application in electrochemical energy storage devices and next-generation supercapacitors is an emerging research focus. Herein, we prepared a redox-active ferrocene dicarboxylic acid (Fc)-based nickel metal-organic framework (MOF) on electrospun carbon nanofibers (NiFc-MOF@CNFs) via an in situ approach. This in situ approach avoided the aggregation of the MOF. The NiFc-MOF@CNF flexible electrode showed a high redox-active behavior owing to the presence of ferrocene and flexible carbon nanofibers, which led to unique properties, including high flexibility and lightweight. Furthermore, the prepared electrode was utilized in a supercapacitors (SC) without the use of any binder, which achieved a specific capacity of 460 C g-1 at 1 A g-1 with an excellent cyclic retention of 82.2% after 25 000 cycles and a good rate capability. A flexible asymmetric supercapacitor device was assembled, which delivered a high energy density of 56.25 W h kg-1 and a long-lasting cycling performance. Also, the prepared electrode could be used as a freestanding electrode in flexible devices at different bending angles. The obtained cyclic voltammetry curves showed negligible changes, indicating the high stability and good flexibility of the electrode. Thus, the use of the in situ strategy can lead to the uniform growth of redox-active MOFs or other porous materials on CNFs.

16.
Chem Asian J ; : e202301012, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38100493

ABSTRACT

To combat with energy crisis considering clean energy, oxygen evolution reaction (OER) is crucial to implement electrolytic hydrogen fuel production in real life. Here, straightforward chemical synthesis pathways are followed to prepare cobalt tetraoxide nanoparticles (Co3 O4 NPs) in an alkaline OER process using poly[(2-methacryloyloxy)ethyl]trimethylammonium chloride (Co3 O4 NPs@PMTC) as support to prevent aggregation. In material characterization, the X-ray diffraction (XRD) pattern confirms the crystallinity of the synthesized Co3 O4 NPs@PMTC, and Raman spectroscopy indicates that the Co3 O4 NPs contain cubic close-packed oxides. The morphological analysis reveals the wrinkle-like disruption which is distributed evenly owing to the folded nanosheet arrays. Energy-dispersive X-ray spectroscopy indicates the presence of a significant number of cobalt atoms in the Co3 O4 NPs, and elemental mapping analysis demonstrates the composition of the NPs. At a current density of 10 mA cm-2 , oxygen is emitted at 1.67 V delivering an overpotential of 440 mV. This unique structure of Co3 O4 NPs@PMTC provides beneficial functions that are responsible for a large number of active sites and the rapid release of oxygen gas with long-term stability. Through kinetic study, we found a Tafel slope of 48.9 mV dec-1 which proves the catalytic behavior of Co3 O4 NPs@PMTC is promising toward the OER process.

17.
J Mater Chem B ; 11(45): 10929-10940, 2023 11 22.
Article in English | MEDLINE | ID: mdl-37937634

ABSTRACT

Tuberculosis (TB) remains one of the most infectious pathogens with the highest human mortality and morbidity. Biofilm formation during Mycobacterium tuberculosis (Mtb) infection is responsible for bacterial growth, communication, and, most essentially, increased resistance/tolerance to antibiotics leading to higher bacterial persistence. Thus, biofilm growth is presently considered a key virulence factor in the case of chronic disease. Metal-Organic Frameworks (MOFs) have recently emerged as a highly efficient system to improve existing antibiotics' therapeutic efficacy and reduce adverse effects. In this regard, we have synthesized Cu-MOF (IITI-3) using a solvothermal approach. IITI-3 was well characterized by various spectroscopic techniques. Herein, IITI-3 was first encapsulated with isoniazid (INH) to form INH@IITI-3 with 10 wt% loading within 1 hour. INH@IITI-3 was well characterized by PXRD, TGA, FTIR, and BET surface area analysis. Furthermore, the drug release kinetics studies of INH@IITI-3 have been performed at pH 5.8 and 7.4 to mimic the small intestine and blood pH, respectively. The results show that drug release follows first-order kinetics. Furthermore, the antimycobacterial activity of INH@IITI-3 demonstrated significant bacterial killing and altered the structural morphology of the bacteria. Moreover, INH@IITI-3 was able to inhibit the mycobacterial biofilm formation upon treatment and showed less cytotoxicity toward the murine RAW264.7 macrophages. Thus, this work significantly opens up new possibilities for the applications of INH@IITI-3 in biofilm infections in Mtb and further contributes to TB therapeutics.


Subject(s)
Metal-Organic Frameworks , Mycobacterium tuberculosis , Tuberculosis , Humans , Animals , Mice , Isoniazid/chemistry , Antitubercular Agents/chemistry , Metal-Organic Frameworks/pharmacology , Metal-Organic Frameworks/therapeutic use , Tuberculosis/drug therapy , Tuberculosis/microbiology
18.
Front Endocrinol (Lausanne) ; 14: 1231043, 2023.
Article in English | MEDLINE | ID: mdl-38027197

ABSTRACT

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.


Subject(s)
Congenital Hyperinsulinism , Child , Infant , Humans , Child, Preschool , Consensus , Congenital Hyperinsulinism/diagnosis , Congenital Hyperinsulinism/genetics , Congenital Hyperinsulinism/therapy , Pancreatectomy , United Kingdom
19.
Proc Natl Acad Sci U S A ; 120(45): e2306476120, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37906644

ABSTRACT

The IL-1 Family member IL-38 has been characterized primarily as an antiinflammatory cytokine in human and mouse models of systemic diseases. Here, we examined the role of IL-38 in the murine small intestine (SI). Immunostaining of SI revealed that IL-38 expression partially confines to intestinal stem cells. Cultures of intestinal organoids reveal IL-38 functions as a growth factor by increasing organoid size via inducing WNT3a. In contrast, organoids from IL-38-deficient mice develop more slowly. This reduction in size is likely due to the downregulation of intestinal stemness markers (i.e., Fzd5, Ephb2, and Olfm4) expression compared with wild-type organoids. The IL-38 binding to IL-1R6 and IL-1R9 is still a matter of debate. Therefore, to analyze the molecular mechanisms of IL-38 signaling, we also examined organoids from IL-1R9-deficient mice. Unexpectedly, these organoids, although significantly smaller than wild type, respond to IL-38, suggesting that IL-1R9 is not involved in IL-38 signaling in the stem cell crypt. Nevertheless, silencing of IL-1R6 disabled the organoid response to the growth property of IL-38, thus suggesting IL-1R6 as the main receptor used by IL-38 in the crypt compartment. In organoids from wild-type mice, IL-38 stimulation induced low concentrations of IL-1ß which contribute to organoid growth. However, high concentrations of IL-1ß have detrimental effects on the cultures that were prevented by treatment with recombinant IL-38. Overall, our data demonstrate an important regulatory function of IL-38 as a growth factor, and as an antiinflammatory molecule in the SI, maintaining homeostasis.


Subject(s)
Intestinal Mucosa , Wnt Signaling Pathway , Animals , Mice , Homeostasis , Intercellular Signaling Peptides and Proteins/metabolism , Interleukins/metabolism , Intestinal Mucosa/metabolism , Organoids/metabolism , Stem Cells/metabolism
20.
Inorg Chem ; 62(42): 17083-17092, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37820058

ABSTRACT

A highly conductive and rationally constructed metal-organic framework (MOF)-derived metal phosphide with a carbonaceous nanostructure is a meticulous architecture toward the development of electrode materials for energy storage devices. Herein, we report a facile strategy to design and construct a new three-dimensional (3D) Cu-MOF via a solvent diffusion method at ambient temperature, which was authenticated by a single-crystal X-ray diffraction study, revealing a novel topology of (2,4,7)-connected three-nodal net named smm4. Nevertheless, the poor conductivity of pristine MOFs is a major bottleneck hindering their capacitance. To overcome this, we demonstrated an MOF-derived Cu3P/Cu@NC heterostructure via low-temperature phosphorization of Cu-MOF. The electronic and ionic diffusion kinetics in Cu3P/Cu@NC were improved due to the synergistic effects of the heterostructure. The as-prepared Cu3P/Cu@NC heterostructure electrode delivers a specific capacity of 540 C g-1 at 1 A g-1 with outstanding rate performance (190 C g-1 at 20 A g-1) and cycle stability (91% capacity retention after 10,000 cycles). Moreover, the assembled asymmetric solid-state supercapacitor (ASC) achieved a high energy density/power density of 45.5 Wh kg-1/7.98 kW kg-1 with a wide operating voltage (1.6 V). Long-term stable capacity retention (87.2%) was accomplished after 5000 cycles. These robust electrochemical performances suggest that the Cu3P/Cu@NC heterostructure is a suitable electrode material for supercapacitor applications.

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