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1.
Diabetologia ; 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38951212

ABSTRACT

The increasing incidence of type 2 diabetes, which represents 90% of diabetes cases globally, is a major public health concern. Improved glucose management reduces the risk of vascular complications and mortality; however, only a small proportion of the type 2 diabetes population have blood glucose levels within the recommended treatment targets. In recent years, diabetes technologies have revolutionised the care of people with type 1 diabetes, and it is becoming increasingly evident that people with type 2 diabetes can also benefit from these advances. In this review, we describe the current knowledge regarding the role of technologies for people living with type 2 diabetes and the evidence supporting their use in clinical practice. We conclude that continuous glucose monitoring systems deliver glycaemic benefits for individuals with type 2 diabetes, whether treated with insulin or non-insulin therapy; further data are required to evaluate the role of these systems in those with prediabetes (defined as impaired glucose tolerance and/or impaired fasting glucose and/or HbA1c levels between 39 mmol/mol [5.7%] and 47 mmol/mol [6.4%]). The use of insulin pumps seems to be safe and effective in people with type 2 diabetes, especially in those with an HbA1c significantly above target. Initial results from studies exploring the impact of closed-loop systems in type 2 diabetes are promising. We discuss directions for future research to fully understand the potential benefits of integrating evidence-based technology into care for people living with type 2 diabetes and prediabetes.

2.
Chemistry ; : e202401810, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869382

ABSTRACT

The first Ficini reaction between ynamides and acrylates is reported herein. The reaction is catalyzed by B(C6F5)3 acting as a Lewis acid and is giving access to stable tri-substituted aminocyclobutenes in high yield. The resulting products can be hydrogenated and epimerized under basic conditions or in presence of a Lewis acid, providing two distinct trans- aminocyclobutane monoester stereoisomers in high yield and diastereoisomeric ratio (up to quantitative yield and >99:1 dr).

3.
Child Neuropsychol ; : 1-19, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38863216

ABSTRACT

Children and adolescents with neurodevelopmental disorders demonstrate extensive cognitive heterogeneity that is not adequately captured by traditional diagnostic systems, emphasizing the need for alternative assessment and classification techniques. Using a transdiagnostic approach, a retrospective cohort study of cognitive functioning was conducted using a large heterogenous sample (n = 1529) of children and adolescents 7 to 18 years of age with neurodevelopmental disorders. Measures of short-term memory, verbal ability, and reasoning were administered to participants with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), comorbid ADHD/ASD, and participants without neurodevelopmental disorders (non-NDD) using a 12-task, web-based neurocognitive testing battery. Unsupervised machine learning techniques were used to create a self-organizing map, an artificial neural network, in conjunction with k-means clustering to identify data-driven subgroups. The study aims were to: 1) identify cognitive profiles in the sample using a data-driven approach, and 2) determine their correspondence with traditional diagnostic statuses. Six clusters representing different cognitive profiles were identified, including participants with varying forms of cognitive impairment. Diagnostic status did not correspond with cluster-membership, providing evidence for the application of transdiagnostic approaches to understanding cognitive heterogeneity in children and adolescents with neurodevelopmental disorders. Additionally, the findings suggest that many typically developing participants may have undiagnosed learning difficulties, emphasizing the need for accessible cognitive assessment tools in school-based settings.

4.
J Diabetes Sci Technol ; : 19322968241250357, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38695387

ABSTRACT

Continuous glucose monitoring (CGM) has been shown to improve glycemic control and self-monitoring, as well as to reduce the risk of hypoglycemia. Integrated CGM (iCGM) FDA-cleared systems with published performance data are established nonadjunctive and accurate CGM tools that can directly inform decision-making in the treatment of diabetes (i.e., insulin dosing). Studies have assessed accuracy and safety data of CGMs that were eventually cleared for iCGM by the FDA and that informed the recommendation for their nonadjunctive use. Subsequent robust clinical trials and real-world studies demonstrated clinical effectiveness with improvements in a range of patient outcomes. In recent years, a number of non-iCGM-approved CGM devices have entered the market outside the United States worldwide. Some of these non-iCGM-approved CGM devices require additional user verification of blood glucose levels to be performed for making treatment decisions, termed adjunctive. Moreover, in many non-iCGM-approved CGM devices, accuracy studies published in peer-reviewed journals are scarce or have many limitations. Consequently, non-iCGM-approved CGM devices cannot be automatically perceived as having the same performance or quality standards than those approved for iCGM by the FDA. As a result, although these devices tend to cost less than iCGMs that carry FDA clearance and could therefore be attractive from the point of view of a health care payer, it must be emphasized that evaluation of costs should not be limited to the device (such as the usability preference that patients have for nonadjunctive sensors compared to adjunctive sensors) but to the wider value of the total benefit that the product provides to the patient.

5.
medRxiv ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38746387

ABSTRACT

Background: Vancomycin-resistant enterococcal (VRE) infections pose significant challenges in healthcare. Transmission dynamics of VRE are complex, often involving patient colonization and subsequent transmission through various healthcare-associated vectors. We utilized a whole genome sequencing (WGS) surveillance program at our institution to better understand the contribution of clinical and colonizing isolates to VRE transmission. Methods: We performed whole genome sequencing on 352 VRE clinical isolates collected over 34 months and 891 rectal screening isolates collected over a 9-month nested period, and used single nucleotide polymorphisms to assess relatedness. We then performed a geo-temporal transmission analysis considering both clinical and rectal screening isolates compared with clinical isolates alone, and calculated 30-day outcomes of patients. Results: VRE rectal carriage constituted 87.3% of VRE acquisition, with an average monthly acquisition rate of 7.6 per 1000 patient days. We identified 185 genetically related clusters containing 2-42 isolates and encompassing 69.6% of all isolates in the dataset. The inclusion of rectal swab isolates increased the detection of clinical isolate clusters (from 53% to 67%, P<0.01). Geo-temporal analysis identified hotspot locations of VRE transmission. Patients with clinical VRE isolates that were closely related to previously sampled rectal swab isolates experienced 30-day ICU admission (17.5%), hospital readmission (9.2%), and death (13.3%). Conclusions: Our findings describe the high burden of VRE transmission at our hospital and shed light on the importance of using WGS surveillance of both clinical and rectal screening isolates to better understand the transmission of this pathogen. This study highlights the potential utility of incorporating WGS surveillance of VRE into routine hospital practice for improving infection prevention and patient safety.

6.
Int J STD AIDS ; : 9564624241254874, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38756022

ABSTRACT

BACKGROUND: Recruitment in sexual health research is challenging. This study explores the potential of a Consent for Contact system (C4C) - generic consent for research contact - to improve participant recruitment and engagement in sexual health research. Our objectives were to understand patient and staff understanding of research, their views on a separate C4C system, and their preferences for its acceptability in a sexual health clinic setting. METHODS: A two-stage study was conducted at a large urban UK sexual health clinic from November 2021 to July 2022. Stage one involved a self-completed questionnaire administered to all patients and staff. In Stage 2, semi-structured interviews (SSIs) further explored patient concerns and preferences. Survey data were analysed using chi-square and Fisher's exact test and thematic analysis was applied to free-text responses and SSIs. RESULTS: A total of 205/300 patient (68%) and 41/280 staff questionnaires (15%) were completed. Motivations for research participation included altruism and personal interest. Statistically significant differences were found between patients' and staff members' concerns on confidentiality and anticipated feeling of pressure to participate. The majority of staff (n = 38, 93%) and half of patients (n = 100, 49%) supported implementation of a sexual health C4C system. Participants recognised the potential benefits of a sexual health C4C system, including enhanced privacy and increased research opportunities. Concerns were raised about stigma, terminology, and signing-up methods. CONCLUSION: This study found the C4C system has the potential to enhance participant recruitment and engagement in sexual health research, but implementation support is narrowly divided with concerns around privacy and sign-up processes. These insights call for a patient-centred design approach, emphasising clear communication and privacy. Future research should focus on implementing and evaluating a sexual health C4C system to further explore their effectiveness and acceptability in different contexts.

7.
Neurology ; 102(12): e209460, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38815233

ABSTRACT

BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) copathologies of ß-amyloid and tau are common in the Lewy body diseases (LBD), dementia with Lewy bodies (DLB) and Parkinson disease (PD), and target distinct hippocampal subfields compared with Lewy pathology, including subiculum and CA1. We investigated the hypothesis that AD copathologies impact the pattern of hippocampal subregion volume loss and cognitive function in LBD. METHODS: This was a cross-sectional and longitudinal, single-center, observational cohort study. Participants underwent neuropsychological testing and 3T-MRI with hippocampal segmentation using FreeSurferV7. PiB-PET and flortaucipir-PET imaging of comorbid ß-amyloid (A) and tau (T) were acquired. The association of functional cognition, ß-amyloid, and tau loads with hippocampal subregion volume was assessed. The contribution of subregion volumes to the relationship of AD-related deposits on functional cognition was examined with mediation analysis. The effects of AD-related deposits on the rate of subregion atrophy were evaluated with mixed-effects models. RESULTS: Of 103 participants (mean age: 70.3 years; 37.3% female), 52 had LBD with impaired cognition (LBD-I), 26 had normal cognition (LBD-N), and 25 were A- healthy controls (HCs). Volumes of hippocampal subregions prone to AD copathologies, including subiculum (F = 6.9, p = 0.002), presubiculum (F = 7.3, p = 0.001), and parasubiculum (F = 5.9, p = 0.004), were reduced in LBD-I compared with LBD-N and HC. Volume was preserved in CA2/3, Lewy pathology susceptible subregions. In LBD-I, reduced CA1, subiculum, and presubiculum volumes were associated with greater functional cognitive impairment (all p < 0.05). Compared with HC, subiculum volume was reduced in A+T+ but not A-T- participants (F = 2.62, p = 0.043). Reduced subiculum volume mediated the effect of amyloid on functional cognition (0.12, 95% CI: 0.005 to 0.26, p = 0.040). In 26 longitudinally-evaluated participants, baseline tau deposition was associated with faster CA1 (p = 0.021) and subiculum (p = 0.002) atrophy. DISCUSSION: In LBD, volume loss in hippocampal output subregions-particularly the subiculum-is associated with functional cognition and AD-related deposits. Tau deposition appears to accelerate subiculum and CA1 atrophy, whereas Aß does not. Subiculum volume may have value as a biomarker of AD copathology-mediated neurodegeneration and disease progression.


Subject(s)
Amyloid beta-Peptides , Hippocampus , Lewy Body Disease , Positron-Emission Tomography , tau Proteins , Humans , Lewy Body Disease/metabolism , Lewy Body Disease/diagnostic imaging , Lewy Body Disease/pathology , Female , Male , Aged , tau Proteins/metabolism , Hippocampus/diagnostic imaging , Hippocampus/pathology , Hippocampus/metabolism , Cross-Sectional Studies , Amyloid beta-Peptides/metabolism , Longitudinal Studies , Magnetic Resonance Imaging , Aged, 80 and over , Neuropsychological Tests , Cohort Studies , Alzheimer Disease/metabolism , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Middle Aged
8.
Chimia (Aarau) ; 78(4): 234-237, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38676616

ABSTRACT

Leveraging the unique reactivity profile of donor-acceptor aminocyclopropanes and cyclobutanes allows the preparation of complex nitrogen-substituted molecules. While most reports focus on donor-acceptor strained rings with two geminal carbonyl groups as acceptors, mono carbonyl acceptor systems, despite their synthetic relevance, have been considerably less studied. Herein we describe catalytic annulation reactions ofaminocyclopropane and aminocyclobutane monoesters employing silylium catalysis to activate these less reactive donor-acceptor systems.

9.
BMJ Open ; 14(4): e078808, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38631836

ABSTRACT

OBJECTIVES: Potentially harmful non-steroidal anti-inflammatory drugs (NSAIDs) utilisation persists at undesirable rates worldwide. The purpose of this paper is to review the literature on interventions to de-implement potentially harmful NSAIDs in healthcare settings and to suggest directions for future research. DESIGN: Scoping review. DATA SOURCES: PubMed, CINAHL, Embase, Cochrane Central and Google Scholar (1 January 2000 to 31 May 2022). STUDY SELECTION: Studies reporting on the effectiveness of interventions to systematically reduce potentially harmful NSAID utilisation in healthcare settings. DATA EXTRACTION: Using Covidence systematic review software, we extracted study and intervention characteristics, including the effectiveness of interventions in reducing NSAID utilisation. RESULTS: From 7818 articles initially identified, 68 were included in the review. Most studies took place in European countries (45.6%) or the USA (35.3%), with randomised controlled trial as the most common design (55.9%). Interventions were largely clinician-facing (76.2%) and delivered in primary care (60.2%) but were rarely (14.9%) guided by an implementation model, framework or theory. Academic detailing, clinical decision support or electronic medical record interventions, performance reports and pharmacist review were frequent approaches employed. NSAID use was most commonly classified as potentially harmful based on patients' age (55.8%), history of gastrointestinal disorders (47.1%), or history of kidney disease (38.2%). Only 7.4% of interventions focused on over-the-counter (OTC) NSAIDs in addition to prescription. The majority of studies (76.2%) reported a reduction in the utilisation of potentially harmful NSAIDs. Few studies (5.9%) evaluated pain or quality of life following NSAIDs discontinuation. CONCLUSION: Many varied interventions to de-implement potentially harmful NSAIDs have been applied in healthcare settings worldwide. Based on these findings and identified knowledge gaps, further efforts to comprehensively evaluate the effectiveness of interventions and the combination of intervention characteristics associated with effective de-implementation are needed. In addition, future work should be guided by de-implementation theory, focus on OTC NSAIDs and incorporate patient-focused strategies and outcomes, including the evaluation of unintended consequences of the intervention.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Quality of Life , Humans , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Pain/chemically induced , Europe
10.
Reproduction ; 167(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38593828

ABSTRACT

In brief: A ketogenic diet (KD) elevates blood ß-hydroxybutyrate to concentrations that are known to perturb the development, metabolism, histone acetylation and viability of preimplantation mouse embryos in culture. This study shows that a maternal KD changes available nutrient levels in the oviduct, leading to altered embryo development and epigenetic state in vivo. Abstract: A ketogenic diet elevates blood ß-hydroxybutyrate to concentrations that perturb the development, metabolism, histone acetylation (H3K27ac) and viability of preimplantation mouse embryos in vitro. However, whether a ketogenic diet alters ß-hydroxybutyrate concentrations within female reproductive fluid is unknown. This study aimed to quantify glucose and ß-hydroxybutyrate within mouse blood and oviduct fluid following standard diet and ketogenic diet consumption and to assess whether a maternal periconceptional ketogenic diet impacts in vivo embryo development and blastocyst H3K27ac. Female C57BL/6 × CBA mice were fed a standard or ketogenic diet (n = 24 each) for 24-27 days. Glucose and ß-hydroxybutyrate were quantified in blood via an electronic monitoring system and in oviduct fluid via ultramicrofluorescence. The developmental grade of flushed blastocysts was recorded, and blastocyst cell number and H3K27ac were assessed via immunofluorescence. A maternal ketogenic diet elevated ß-hydroxybutyrate in day 24 blood (P < 0.001) and oviduct fluid (P < 0.05) compared with a standard diet, whereas glucose was unchanged. A periconceptional ketogenic diet did not impact blastocyst cell number; however, it significantly delayed blastocyst development (P < 0.05) and reduced trophectoderm-specific H3K27ac (P < 0.05) compared with standard diet-derived embryos. Maternal ketogenic diet consumption is, therefore, associated with reproductive tract nutrient changes and altered embryonic development and epigenetics in vivo. Future studies to assess whether periconceptional/gestational ketogenic diet consumption impacts human preimplantation, fetal, and long-term offspring development and health are warranted.


Subject(s)
3-Hydroxybutyric Acid , Diet, Ketogenic , Embryonic Development , Histones , Mice, Inbred C57BL , Animals , Female , Histones/metabolism , Mice , Acetylation , 3-Hydroxybutyric Acid/blood , 3-Hydroxybutyric Acid/metabolism , Pregnancy , Blastocyst/metabolism , Mice, Inbred CBA , Oviducts/metabolism , Nutrients/metabolism , Maternal Nutritional Physiological Phenomena
11.
Lancet Oncol ; 25(5): 636-648, 2024 May.
Article in English | MEDLINE | ID: mdl-38621404

ABSTRACT

BACKGROUND: Patients with cancer are at greater risk of dying from COVID-19 than many other patient groups. However, how this risk evolved during the pandemic remains unclear. We aimed to determine, on the basis of the UK national pandemic protocol, how factors influencing hospital mortality from COVID-19 could differentially affect patients undergoing cancer treatment. We also examined changes in hospital mortality and escalation of care in patients on cancer treatment during the first 2 years of the COVID-19 pandemic in the UK. METHODS: We conducted a prospective cohort study of patients aged older than 19 years and admitted to 306 health-care facilities in the UK with confirmed SARS-CoV-2 infection, who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol (CCP) across the UK from April 23, 2020, to Feb 28, 2022; this analysis included all patients in the complete dataset when the study closed. The primary outcome was 30-day in-hospital mortality, comparing patients on cancer treatment and those without cancer. The study was approved by the South Central-Oxford C Research Ethics Committee in England (Ref: 13/SC/0149) and the Scotland A Research Ethics Committee (Ref 20/SS/0028), and is registered on the ISRCTN Registry (ISRCTN66726260). FINDINGS: 177 871 eligible adult patients either with no history of cancer (n=171 303) or on cancer treatment (n=6568) were enrolled; 93 205 (52·4%) were male, 84 418 (47·5%) were female, and in 248 (13·9%) sex or gender details were not specified or data were missing. Patients were followed up for a median of 13 (IQR 6-21) days. Of the 6568 patients receiving cancer treatment, 2080 (31·7%) died at 30 days, compared with 30 901 (18·0%) of 171 303 patients without cancer. Patients aged younger than 50 years on cancer treatment had the highest age-adjusted relative risk (hazard ratio [HR] 5·2 [95% CI 4·0-6·6], p<0·0001; vs 50-69 years 2·4 [2·2-2·6], p<0·0001; 70-79 years 1·8 [1·6-2·0], p<0·0001; and >80 years 1·5 [1·3-1·6], p<0·0001) but a lower absolute risk (51 [6·7%] of 763 patients <50 years died compared with 459 [30·2%] of 1522 patients aged >80 years). In-hospital mortality decreased for all patients during the pandemic but was higher for patients on cancer treatment than for those without cancer throughout the study period. INTERPRETATION: People with cancer have a higher risk of mortality from COVID-19 than those without cancer. Patients younger than 50 years with cancer treatment have the highest relative risk of death. Continued action is needed to mitigate the poor outcomes in patients with cancer, such as through optimising vaccination, long-acting passive immunisation, and early access to therapeutics. These findings underscore the importance of the ISARIC-WHO pandemic preparedness initiative. FUNDING: National Institute for Health Research and the Medical Research Council.


Subject(s)
COVID-19 , Hospital Mortality , Neoplasms , SARS-CoV-2 , Humans , COVID-19/mortality , COVID-19/epidemiology , Neoplasms/mortality , Neoplasms/therapy , Male , Female , Prospective Studies , Aged , Middle Aged , United Kingdom/epidemiology , Adult , Aged, 80 and over , Pandemics
12.
Acad Psychiatry ; 48(3): 244-248, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38570407

ABSTRACT

OBJECTIVE: Mental health treatment is often initiated in primary care settings, but many primary care providers (PCPs), residents, and medical students report discomfort in managing psychiatric conditions. This study evaluated the effect of an educational workshop that featured an evidence-based psychopharmacology clinical decision support tool (CDST) on trainee confidence and willingness to treat psychiatric conditions. METHODS: Participants completed pre- and post-workshop surveys. Nine months after the workshop, a subset of trainees participated in a focus group. RESULTS: Of the participants, 62.5% of the obstetrics-gynecology (OB-GYN) resident physicians (10/16) and 100% of the medical students (18/18) completed both pre- and post-surveys. Following the workshop, OB-GYN resident physicians reported significantly improved confidence in treating psychiatric disorders (p < 0.001), sense of having psychiatric support tools (p < 0.001), and knowledge of treating psychiatric disorders (p = 0.021). Medical students reported significantly improved confidence in treating psychiatric disorders (p < 0.001), willingness to devise treatment plans for psychiatric disorders (p = 0.024), sense of having psychiatric support tools (p < 0.001), knowledge of treating psychiatric disorders (p < 0.001), and comfort in presenting a psychiatric treatment plan to an attending (p = 0.003). Most focus group participants (93.75%; 15/16) reported that they continued to use the CDST, and it increased their confidence in formulating psychiatric treatment plans. CONCLUSIONS: These findings suggest that educational workshops that introduce high-quality psychopharmacology CDSTs may be an effective method for improving provider comfort in treating psychiatric disorders.


Subject(s)
Internship and Residency , Students, Medical , Humans , Students, Medical/psychology , Female , Primary Health Care , Male , Adult , Clinical Competence , Psychiatry/education , Obstetrics/education , Focus Groups , Gynecology/education , Attitude of Health Personnel , Psychopharmacology/education , Mental Disorders/therapy , Surveys and Questionnaires , Decision Support Systems, Clinical , Education
13.
Health Sci Rep ; 7(3): e1979, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38495896

ABSTRACT

Background and Aims: The United States of America and Sweden both contain a public and private component to their healthcare systems. While both countries spend a similar amount per capita on public healthcare expenditures, the United States spends significantly more in the private healthcare sector. Sweden has a social democratic model of health care, and given its identity as a welfare state, private health insurance providers have a small and nuanced role. Methods: This paper was completed after searches were queried for "Sweden," "United States," and variants of the words "insurance," "public," "private," "Medicare," "Medicaid," "public," and "costs." A preliminary search in May 2022, yielded 78 articles, of which 45 were ultimately considered relevant for this review. Inclusion criteria consisted of English language articles, topic relevance, and verification of MEDLINE-indexed journals. These searches were performed in PubMed, Google Scholar, Embase, and Cochrane. Summary findings of these searches are compiled in this review. Results: Sweden guarantees low-cost appropriate care to all citizens with equitable access; however, drawbacks of its system include high financial burden, lack of primary care infrastructure, as well as geographical and socioeconomic inequities. On the other hand, the United States' healthcare system is built around the private sector with public health insurance reserved only for the most vulnerable patient populations. Conclusion: Our goal is to provide an overview, compare the role of private health insurance in both countries, and highlight policies that have had beneficial effects in each nation. Possible solutions to the drawbacks of each nation's health insurance policies could be addressed by additional support to Sweden's vulnerable population by developing a program similar to the US' Medicare Advantage program. Conversely, the United States may benefit from increasing access to public health insurance, especially in instances where families face unemployment.

14.
Sci Rep ; 14(1): 3176, 2024 02 07.
Article in English | MEDLINE | ID: mdl-38326455

ABSTRACT

Hypoxic-ischemic encephalopathy (HIE) results from a lack of oxygen to the brain during the perinatal period. HIE can lead to mortality and various acute and long-term morbidities. Improved bedside monitoring methods are needed to identify biomarkers of brain health. Functional near-infrared spectroscopy (fNIRS) can assess resting-state functional connectivity (RSFC) at the bedside. We acquired resting-state fNIRS data from 21 neonates with HIE (postmenstrual age [PMA] = 39.96), in 19 neonates the scans were acquired post-therapeutic hypothermia (TH), and from 20 term-born healthy newborns (PMA = 39.93). Twelve HIE neonates also underwent resting-state functional magnetic resonance imaging (fMRI) post-TH. RSFC was calculated as correlation coefficients amongst the time courses for fNIRS and fMRI data, respectively. The fNIRS and fMRI RSFC maps were comparable. RSFC patterns were then measured with graph theory metrics and compared between HIE infants and healthy controls. HIE newborns showed significantly increased clustering coefficients, network efficiency and modularity compared to controls. Using a support vector machine algorithm, RSFC features demonstrated good performance in classifying the HIE and healthy newborns in separate groups. Our results indicate the utility of fNIRS-connectivity patterns as potential biomarkers for HIE and fNIRS as a new bedside tool for newborns with HIE.


Subject(s)
Hypothermia, Induced , Hypoxia-Ischemia, Brain , Humans , Infant, Newborn , Infant , Hypoxia-Ischemia, Brain/diagnostic imaging , Hypoxia-Ischemia, Brain/therapy , Spectroscopy, Near-Infrared/methods , Brain/diagnostic imaging , Magnetic Resonance Imaging , Hypothermia, Induced/methods , Biomarkers
15.
J Cancer ; 15(5): 1153-1168, 2024.
Article in English | MEDLINE | ID: mdl-38356706

ABSTRACT

We conducted a high-content screening (HCS) in neuroblastoma BE(2)-C cells to identify cell cycle regulators that control cell differentiation using a library of siRNAs against cell cycle-regulatory genes. We discovered that knocking down expression of cyclin dependent kinase inhibitor 3 (CDKN3) showed the most potent effect in inducing neurite outgrowth, the morphological cell differentiation marker of neuroblastoma cells. We then demonstrated that CDKN3 knockdown increased expression of neuroblastoma molecular differentiation markers, neuron specific enolase (NSE), ßIII-tubulin and growth associated protein 43 (GAP43). We further showed that CDKN3 knockdown reduced expression of cell proliferation markers Ki67 and proliferating cell nuclear antigen (PCNA), and reduced colony formation of neuroblastoma cells. More importantly, we observed a correlation of high tumor CDKN3 mRNA levels with poor patient survival in the investigation of public neuroblastoma patient datasets. In exploring the mechanisms that regulate CDKN3 expression, we found that multiple strong differentiation-inducing molecules, including miR-506-3p and retinoic acid, down-regulated CDKN3 expression. In addition, we found that N-Myc promoted CDKN3 expression at the transcriptional level by directly binding to the CDKN3 promoter. Furthermore, we found that CDKN3 and two additional differentiation-regulating cell cycle proteins identified in our HCS, CDC6 and CDK4, form an interactive network to promote expression of each other. In summary, we for the first time discovered the function of CDKN3 in regulating neuroblastoma cell differentiation and characterized the transcriptional regulation of CDKN3 expression by N-Myc in neuroblastoma cells. Our findings support that CDKN3 plays a role in modulating neuroblastoma cell differentiation and that overexpression of CDKN3 may contribute to neuroblastoma progression.

16.
Article in English | MEDLINE | ID: mdl-38375861

ABSTRACT

Background: The Omnipod® 5 Automated Insulin Delivery System was associated with favorable glycemic outcomes for people with type 1 diabetes (T1D) in two pivotal clinical trials. Real-world evidence is needed to explore effectiveness in nonstudy conditions. Methods: A retrospective analysis of the United States Omnipod 5 System users (aged ≥2 years) with T1D and sufficient data (≥90 days of data; ≥75% of days with ≥220 continuous glucose monitor readings/day) available in Insulet Corporation's device and person-reported datasets as of July 2023 was performed. Target glucose setting usage (i.e., 110-150 mg/dL in 10 mg/dL increments) was summarized and glycemic outcomes were examined. Subgroup analyses of those using the lowest average glucose target (110 mg/dL) and stratification by baseline characteristics (e.g., age, prior therapy, health insurance coverage) were conducted. Results: In total, 69,902 users were included. Multiple and higher glucose targets were more commonly used in younger age groups. Median percentage of time in range (TIR; 70-180 mg/dL) was 68.8%, 61.3%, and 53.6% for users with average glucose targets of 110, 120, and 130-150 mg/dL, respectively, with minimal time <70 mg/dL (all median <1.13%). Among those with an average glucose target of 110 mg/dL (n = 37,640), median TIR was 65.0% in children and adolescents (2-17 years) and 69.9% in adults (≥18 years). Subgroup analyses of users transitioning from Omnipod DASH or multiple daily injections and of Medicaid/Medicare users demonstrated favorable glycemic outcomes among these groups. Conclusion: These glycemic outcomes from a large and diverse sample of nearly 70,000 children and adults demonstrate effective use of the Omnipod 5 System under real-world conditions.

17.
JAMA Netw Open ; 7(2): e240456, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38411965

ABSTRACT

This cohort study investigates the association between T2* mapping of placental oxygenation and cortical and subcortical fetal brain volumes in typically developing fetuses scanned longitudinally in the third trimester.


Subject(s)
Placenta , Prenatal Care , Pregnancy , Female , Humans , Placenta/diagnostic imaging
18.
Diabetes Res Clin Pract ; 209: 111597, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38417535

ABSTRACT

AIMS: To evaluate real-world outcomes in people with Type 1 Diabetes (PwT1D) initiated on Omnipod DASH® Insulin Management System. METHODS: Anonymized clinical data were submitted to a secure web-based tool within the National Health Service network. Hemoglobin A1c (HbA1c), sensor-derived glucometrics, total daily dose of insulin (TDD), and patient-reported outcome changes between baseline and follow-up were assessed. Individuals were classified to "new-to-pump" (switched from multiple daily injections) and "established-on-pump" (switched from a tethered insulin pump) groups. RESULTS: 276 individuals from 11 centers [66.7 % female; 92 % White British; median age 41 years (IQR 20-50); diabetes duration 20 years (IQR 11-31); 49.3 % within "new-to-pump" group] were included. Baseline HbA1c was 8.0 ± 1.3 % (64 ± 14 mmol/mol). At follow-up [3 years (IQR 1.5-3.2)], HbA1c reduced by 0.3 % [(3 mmol/mol); p = 0.002] across the total population, 0.4 % [(5 mmol/mol); p = 0.001] in those "new-to-pump" and remained unchanged in those "established-on-pump". TDD decreased in the "new-to-pump" cohort (baseline:44.9 ± 21.0units vs follow-up:38.1 ± 15.4units, p = 0.002). Of those asked, 141/143 (98.6 %) stated Omnipod DASH had a positive impact on quality of life. CONCLUSIONS: Omnipod DASH was associated with improvements in HbA1c in PwT1D "new-to-pump" and maintained previous HbA1c levels in those "established-on-pump". User satisfaction in all groups and TDD reduction in those "new-to-pump" were reported.


Subject(s)
Diabetes Mellitus, Type 1 , Humans , Female , Adult , Male , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/therapeutic use , Glycated Hemoglobin , Quality of Life , State Medicine , Insulin/therapeutic use , Insulin Infusion Systems , Blood Glucose
20.
Article in English | MEDLINE | ID: mdl-38386544

ABSTRACT

Asphyxial cardiac arrest (ACA) survivors face lasting neurological disability from hypoxic ischemic brain injury. Sex differences in long-term outcomes after cardiac arrest (CA) are grossly understudied and underreported. We used rigorous targeted temperature management (TTM) to understand its influence on survival and lasting sex-specific neurological and neuropathological outcomes in a rodent ACA model. Adult male and female rats underwent either sham or 5-minute no-flow ACA with 18 hours TTM at either ∼37°C (normothermia) or ∼36°C (mild hypothermia). Survival, temperature, and body weight (BW) were recorded over the 14-day study duration. All rats underwent neurological deficit score (NDS) assessment on days 1-3 and day 14. Hippocampal pathology was assessed for cell death, degenerating neurons, and microglia on day 14. Although ACA females were less likely to achieve return of spontaneous circulation (ROSC), post-ROSC physiology and biochemical profiles were similar between sexes. ACA females had significantly greater 14-day survival, NDS, and BW recovery than ACA males at normothermia (56% vs. 29%). TTM at 36°C versus 37°C improved 14-day survival in males, producing similar survival in male (63%) versus female (50%). There were no sex or temperature effects on CA1 histopathology. We conclude that at normothermic conditions, sex differences favoring females were observed after ACA in survival, NDS, and BW recovery. We achieved a clinically relevant ACA model using TTM at 36°C to improve long-term survival. This model can be used to more fully characterize sex differences in long-term outcomes and test novel acute and chronic therapies.

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