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1.
Int J Cancer ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995124

ABSTRACT

Epstein-Barr virus (EBV) is an oncogenic virus associated with various malignancies, including classical Hodgkin lymphoma (cHL). Despite its known association, the specific role of humoral immune response to EBV remains poorly characterized in cHL. To address this, we conducted a study using a custom protein microarray to measure the antibody responses in cHL patients and matched healthy controls recruited from an East-Asian hospital-based case-control study. We identified 16 IgG antibodies significantly elevated in EBV-positive cHL compared with controls, defining an "East-Asian antibody signature of EBV-positive cHL." We evaluated responses against these 16 antibodies in a distinct European population, leveraging data from our previous European cHL case-control study from the UK, Denmark, and Sweden. A subset of antibodies (14/16, 87.5%) from the "East-Asian antibody signature of EBV-positive cHL" exhibited significant associations with cHL in the European population. Conversely, we assessed the "European antibody signature of EBV-positive cHL" identified in our prior study which consisted of 18 EBV antibodies (2 IgA, 16 IgG), in the East-Asian population. A subset of these antibodies (15/18, 83.3%) maintained significant associations with cHL in the East-Asian population. This cross-comparison of antibody signatures underscores the robust generalizability of EBV antibodies across populations. Five anti-EBV IgG antibodies (LMP-1, TK, BALF2, BDLF3, and BBLF1), found in both population-specific antibody signatures, represent a "core signature of EBV-positive cHL." Our findings suggest that the antibody responses targeting these core EBV proteins reflect a specific EBV gene expression pattern, serving as potential biomarkers for EBV-positive cHL independent of population-specific factors.

2.
J Am Chem Soc ; 146(28): 18927-18937, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38968420

ABSTRACT

Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter involved in many physiological processes that are integral to proper cellular functioning. Due to its profound anti-inflammatory and antioxidant properties, H2S plays important roles in preventing inflammatory skin disorders and improving wound healing. Transdermal H2S delivery is a therapeutically viable option for the management of such disorders. However, current small-molecule H2S donors are not optimally suited for transdermal delivery and typically generate electrophilic byproducts that may lead to undesired toxicity. Here, we demonstrate that H2S release from metal-organic frameworks (MOFs) bearing coordinatively unsaturated metal centers is a promising alternative for controlled transdermal delivery of H2S. Gas sorption measurements and powder X-ray diffraction (PXRD) studies of 11 MOFs support that the Mg-based framework Mg2(dobdc) (dobdc4- = 2,5-dioxidobenzene-1,4-dicarboxylate) is uniquely well-suited for transdermal H2S delivery due to its strong yet reversible binding of H2S, high capacity (14.7 mmol/g at 1 bar and 25 °C), and lack of toxicity. In addition, Rietveld refinement of synchrotron PXRD data from H2S-dosed Mg2(dobdc) supports that the high H2S capacity of this framework arises due to the presence of three distinct binding sites. Last, we demonstrate that transdermal delivery of H2S from Mg2(dobdc) is sustained over a 24 h period through porcine skin. Not only is this significantly longer than sodium sulfide but this represents the first example of controlled transdermal delivery of pure H2S gas. Overall, H2S-loaded Mg2(dobdc) is an easily accessible, solid-state source of H2S, enabling safe storage and transdermal delivery of this therapeutically relevant gas.


Subject(s)
Administration, Cutaneous , Hydrogen Sulfide , Metal-Organic Frameworks , Hydrogen Sulfide/chemistry , Hydrogen Sulfide/administration & dosage , Metal-Organic Frameworks/chemistry , Animals , Swine , Skin/metabolism
3.
ERJ Open Res ; 10(4)2024 Jul.
Article in English | MEDLINE | ID: mdl-39010888

ABSTRACT

Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown. Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease (i.e., asthma, COPD or bronchiectasis) were compared to the non-airways group. Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group. Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge.

4.
Chemistry ; : e202402163, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949770

ABSTRACT

Gases are essential for various applications relevant to human health, including in medicine, biomedical imaging, and pharmaceutical synthesis. However, gases are significantly more challenging to safely handle than liquids and solids. Herein, we review the use of porous materials, such as metal-organic frameworks (MOFs), zeolites, and silicas, to adsorb medicinally relevant gases and facilitate their handling as solids. Specific topics include the use of MOFs and zeolites to deliver H2S for therapeutic applications, 129Xe for magnetic resonance imaging, O2 for the treatment of cancer and hypoxia, and various gases for use in organic synthesis. This Perspective aims to bring together the organic, inorganic, medicinal, and materials chemistry communities to inspire the design of next-generation porous materials for the storage and delivery of medicinally relevant gases.

5.
Nat Struct Mol Biol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951624

ABSTRACT

During formation of the transcription-competent open complex (RPo) by bacterial RNA polymerases (RNAPs), transient intermediates pile up before overcoming a rate-limiting step. Structural descriptions of these interconversions in real time are unavailable. To address this gap, here we use time-resolved cryogenic electron microscopy (cryo-EM) to capture four intermediates populated 120 ms or 500 ms after mixing Escherichia coli σ70-RNAP and the λPR promoter. Cryo-EM snapshots revealed that the upstream edge of the transcription bubble unpairs rapidly, followed by stepwise insertion of two conserved nontemplate strand (nt-strand) bases into RNAP pockets. As the nt-strand 'read-out' extends, the RNAP clamp closes, expelling an inhibitory σ70 domain from the active-site cleft. The template strand is fully unpaired by 120 ms but remains dynamic, indicating that yet unknown conformational changes complete RPo formation in subsequent steps. Given that these events likely describe DNA opening at many bacterial promoters, this study provides insights into how DNA sequence regulates steps of RPo formation.

6.
PLOS Glob Public Health ; 4(7): e0003451, 2024.
Article in English | MEDLINE | ID: mdl-38990937

ABSTRACT

Voluntary National Reviews are the formal mechanism for countries to report on progress and share lessons learned on SDG implementation. We assessed the Voluntary National Reviews submitted by countries in the WHO Eastern Mediterranean Region to note the reported progress on Sustainable Development Goal (SDG) implementation, the review preparation process and how health is positioned and framed to identify priorities for accelerating progress on the health-related SDGs. We extracted quantitative and qualitative data from 26 Voluntary National Reviews from 18 countries submitted during the period 2016 to January 2022. We focused on three areas: SDG implementation, the review preparation process and the positioning of health in the reviews. Three assessors conducted the data extraction based on the agreed framework according to their language of expertise (Arabic, English and French). One assessor supervised the whole process for consistency. If there was a doubt in interpretation, it was discussed and agreed among the assessors. Countries have established a mechanism for SDG implementation under high-level leadership, engaged in multistakeholder consultations, aligned and mainstreamed SDGs to national plans, and created a monitoring and review mechanism. Countries reported use of national participatory approach for the report preparation. The prioritization of both health and well-being (SDG3) and economic growth (SDG8) in the reports is unique compared to other regional and global assessments. Health was often framed around disease and health care provision without linkages to societal inequities and structural challenges. The reports indicated good progress in SDG implementation. Addressing upstream issues and the determinants of health requires the health sector to take a more strategic approach in advocating for health and well-being. Further research is needed to demonstrate how to address synergies and trade-offs of policy choices and identify the co-benefits of addressing health in the context of fiscal instability and widening inequities in the region.

7.
J Natl Cancer Inst ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954841

ABSTRACT

BACKGROUND: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents. METHODS: We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population. FINDINGS: We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively). INTERPRETATION: Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma.

8.
Angew Chem Int Ed Engl ; : e202408423, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946592

ABSTRACT

The hydrostannylation of white phosphorus (P4) allows this crucial industrial precursor to be easily transformed into useful P1 products via direct, 'one pot' (or even catalytic) procedures. However, a thorough mechanistic understanding of this transformation has remained elusive, hindering attempts to use this rare example of successful, direct P4 functionalization as a model for further reaction development. Here, we provide a deep and generalizable mechanistic picture for P4 hydrostannylation by combining DFT calculations with in situ31P NMR reaction monitoring and kinetic trapping of previously unobservable reaction intermediates using bulky tin hydrides. The results offer important insights into both how this reaction proceeds and why it is successful and provide implicit guidelines for future research in the field of P4 activation.

10.
Cognition ; 251: 105885, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39024843

ABSTRACT

Current theories propose that mental effort is invested only when the anticipated benefits, such as rewards, outweigh the associated costs, like task difficulty. Yet, it remains unclear whether this motivational and mitigating aspect of reward processing is reflected in the evaluation of reward/difficulty cues as such, and to what extent it depends on task experience. In a pre-registered experiment (N = 84), we used the affect misattribution procedure (AMP) to gauge affective evaluations of nonword cues predicting reward and task difficulty levels. Contrary to previous studies, the AMP was administered at the outset, after cue instructions, and after the cues were used in a random dot motion (RDM) task. Compared to baseline, cues predicting a larger reward were evaluated more positively after RDM task experience, and most importantly, already after cue instructions, with no difference between the two phases. This evaluative effect manifested in increased performance after larger reward cues in the RDM task. Our results suggest that AMP effects may generally capture performance expectations which are independent of task experience. Importantly, these instructed expectations of reward and difficulty play a crucial role in the evaluation and subsequent investment of mental effort.

11.
Sci Justice ; 64(4): 347-359, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39025560

ABSTRACT

It is now well established that decision making can be susceptible to cognitive bias in a broad range of fields, with forensic science being no exception. Previously published research has revealed a bias blind spot in forensic science where examiners do not recognise bias within their own domain. A survey of 101 forensic anthropology practitioners (n = 52) and students (n = 38) was undertaken to assess their level of awareness of cognitive bias and investigate their attitudes towards cognitive bias within forensic anthropology. The results revealed that the forensic anthropology community (∼90%) had a high level of awareness of cognitive bias. Overall ∼89% expressed concerns about cognitive bias in the broad discipline of forensic science, their own domain of forensic anthropology, and in the evaluative judgments they made in reconstruction activities, identifying a significant reduction in the bias blind spot. However, more than half of the participants believed that bias can be reduced by sheer force of will, and there was a lack of consensus about implementing blinding procedures or context management. These findings highlight the need to investigate empirically the feasibility of proposed mitigating strategies within the workflow of forensic anthropologists and their capabilities for increasing the transparency in decision making.


Subject(s)
Attitude , Forensic Anthropology , Humans , Forensic Anthropology/methods , Surveys and Questionnaires , Male , Female , Bias , Cognition , Decision Making , Adult
12.
PLOS Glob Public Health ; 4(7): e0002838, 2024.
Article in English | MEDLINE | ID: mdl-39024230

ABSTRACT

BACKGROUND: Country submission of Voluntary National Reviews is the formal mechanism to report on progress of the Sustainable Development Goals (SDGs). Despite strong political commitment to strong information systems, large data gaps exist in the Eastern Mediterranean Region. METHODS: This study aims to review reports submitted by countries in the region to assess the comprehensiveness of reporting on the health-reported SDG targets and indicators. We conducted a content analysis of reports submitted between 2016 and 2021 of 18 countries of the region. The review focused on progress on the SDGs by assessing i) the reporting on the 50 health-related targets and indicators ii) data availability using the WHO reporting framework, and iii) data availability based on source of information. Spreadsheets were developed and used to extract data and facilitate content analysis. RESULTS: All reports confirmed that SDG monitoring and reporting mechanisms have been established, however, only 11 reported on all 17 SDGs and 8 explicitly mentioned country specific 2030 targets. Many reports identified data availability as a key challenge to SDG monitoring; for the health SDG, data availability ranged from 48% to 93% among the five countries reporting this figure. Comprehensiveness of reporting varied by type of indicator (maternal, child and infant mortality were the most common) and by country income level (greater reporting by high income countries). CONCLUSIONS: Significant work remains to enhance information systems across the region to monitor progress and guide actions to achieve the health-related SDGs. Strengthening health information systems regulatory frameworks, data collection capacities including strengthening civil registration and vital statistics and population-based surveys are key steps to enhancing access to quality data which in turn can contribute to achieving the health-related SDGs.

13.
Res Sq ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39011095

ABSTRACT

Type 2 and type 1 diabetes (T2D, T1D) exhibit sex differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), hormone secretion, and bioenergetics. In nondiabetic (ND) donors, sex differences in islet cells gene accessibility and expression predominantly involved sex chromosomes. Islets from T2D donors exhibited similar sex differences in sex chromosomes differentially expressed genes (DEGs), but also exhibited sex differences in autosomal genes. Comparing ß cells from T2D vs. ND donors, gene enrichment of female ß cells showed suppression in mitochondrial respiration, while male ß cells exhibited suppressed insulin secretion. Thus, although sex differences in gene accessibility and expression of ND ß cells predominantly affect sex chromosomes, the transition to T2D reveals sex differences in autosomes highlighting mitochondrial failure in females.

14.
Brain Behav Immun ; 121: 56-69, 2024 Jul 21.
Article in English | MEDLINE | ID: mdl-39043341

ABSTRACT

Alzheimer's Disease (AD) is a neurodegenerative disease characterized by profound memory impairments, synaptic loss, neuroinflammation, and hallmark pathological markers. High-fat diet (HFD) consumption increases the risk of developing AD even after controlling for metabolic syndrome, pointing to a role of the diet itself in increasing risk. In AD, the complement system, an arm of the immune system which normally tags redundant or damaged synapses for pruning, becomes pathologically overactivated leading to tagging of healthy synapses. While the unhealthy diet to AD link is strong, the underlying mechanisms are not well understood in part due to confounding variables associated with long-term HFD which can independently influence the brain. Therefore, we experimented with a short-term diet regimen to isolate the diet's impact on brain function without causing obesity. This project investigated the effect of short-term HFD on 1) memory, 2) neuroinflammation including complement, 3) AD pathology markers, 4) synaptic markers, and 5) in vitro microglial synaptic phagocytosis in the 3xTg-AD mouse model. Following the consumption of either standard chow or HFD, 3xTg-AD and non-Tg mice were tested for memory impairments. In a separate cohort of mice, levels of hippocampal inflammatory markers, complement proteins, AD pathology markers, and synaptic markers were measured. For the last set of experiments, BV2 microglial phagocytosis of synapses was evaluated. Synaptoneurosomes isolated from the hippocampus of 3xTg-AD mice fed chow or HFD were incubated with equal numbers of BV2 microglia. The number of BV2 microglia that phagocytosed synaptoneurosomes was tracked over time with a live-cell imaging assay. Finally, we incubated BV2 microglia with a complement receptor inhibitor (NIF) and repeated the assay. Behavioral analysis showed 3xTg-AD mice had significantly impaired long-term contextual and cued fear memory compared to non-Tg mice that was further impaired by HFD. HFD significantly increased inflammatory markers and complement expression while decreasing synaptic marker expression only in 3xTg-AD mice, without altering AD pathology markers. Synaptoneurosomes from HFD-fed 3xTg-AD mice were phagocytosed at a significantly higher rate than those from chow-fed mice, suggesting the synapses were altered by HFD. The complement receptor inhibitor blocked this effect in a dose-dependent manner, demonstrating the HFD-mediated increase in phagocytosis was complement dependent. This study indicates HFD consumption increases neuroinflammation and over-activates the complement cascade in 3xTg-AD mice, resulting in poorer memory. The in vitro data point to complement as a potential mechanistic culprit and therapeutic target underlying HFD's influence in increasing cognitive vulnerability to AD.

15.
Optom Vis Sci ; 101(6): 290-297, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38856650

ABSTRACT

SIGNIFICANCE: There is a lack of research from high-income countries with various health care and funding systems regarding barriers and facilitators in low vision services (LVS) access. Furthermore, very few studies on LVS provision have used claims data. PURPOSE: This study aimed to investigate which patient characteristics predict receiving multidisciplinary LVS (MLVS) in the Netherlands, a high-income country, based on health care claims data. METHODS: Data from a Dutch national health insurance claims database (2015 to 2018) of patients with eye diseases causing potentially severe visual impairment were retrieved. Patients received MLVS (n = 8766) and/or ophthalmic treatment in 2018 (reference, n = 565,496). MLVS is provided by professionals from various clinical backgrounds, including nonprofit low vision optometry. Patient characteristics (sociodemographic, clinical, contextual, general health care utilization) were assessed as potential predictors using a multivariable logistic regression model, which was internally validated with bootstrapping. RESULTS: Predictors for receiving MLVS included prescription of low vision aids (odds ratio [OR], 8.76; 95% confidence interval [CI], 7.99 to 9.61), having multiple ophthalmic diagnoses (OR, 3.49; 95% CI, 3.30 to 3.70), receiving occupational therapy (OR, 2.32; 95% CI, 2.15 to 2.51), mental comorbidity (OR, 1.17; 95% CI, 1.10 to 1.23), comorbid hearing disorder (OR, 1.98; 95% CI, 1.86 to 2.11), and receiving treatment in both a general hospital and a specialized ophthalmic center (OR, 1.23; 95% CI, 1.10 to 1.37), or by a general practitioner (OR, 1.23; 95% CI, 1.18 to 1.29). Characteristics associated with lower odds included older age (OR, 0.30; 95% CI, 0.28 to 0.32), having a low social economic status (OR, 0.91; 95% CI, 0.86 to 0.97), physical comorbidity (OR, 0.87; 95% CI, 0.82 to 0.92), and greater distance to an MLVS (OR, 0.95; 95% CI, 0.92 to 0.98). The area under the curve of the model was 0.75 (95% CI, 0.75 to 0.76; optimism = 0.0008). CONCLUSIONS: Various sociodemographic, clinical, and contextual patient characteristics, as well as factors related to patients' general health care utilization, were found to influence MLVS receipt as barriers or facilitators. Eye care practitioners should have attention for socioeconomically disadvantaged older patients when considering MLVS referral.


Subject(s)
Big Data , Vision, Low , Humans , Male , Female , Vision, Low/epidemiology , Middle Aged , Aged , Netherlands/epidemiology , Adult , Optometry/statistics & numerical data , Insurance Claim Review , Adolescent , Young Adult , Patient Acceptance of Health Care/statistics & numerical data , Eye Diseases/therapy , Eye Diseases/epidemiology , Health Services Accessibility/statistics & numerical data , Child
16.
ChemSusChem ; : e202401057, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38874542

ABSTRACT

Efficient fluorination reactions are key in the late-stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)-H fluorinations using Selectfluor® - one of the most popular fluorination agents - allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H-TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H-TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3x higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H-TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)-H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.

17.
Plast Reconstr Surg ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38857439

ABSTRACT

BACKGROUND: Breast augmentation with implants is one of the most performed aesthetic surgical procedures performed worldwide. We describe this new option for breast implant secondary procedures, the intra pectoralis major pocket, as a feasible and reproducible surgical technique. METHODS: A retrospective chart review was conducted on all patients who underwent revision augmentation or mastopexy augmentation procedure between 2005 and 2022 by the senior author. The intramuscular pocket is dissected between the pectoral muscle fascicles where almost is not bleeding. RESULTS: Patients were followed for an average of 21.5 months. A total of 319 patients underwent revisionary breast augmentation/mastopexies performed by the senior author. Indications for reoperation were based both on specific patient dissatisfaction with their original surgery and surgeon's physical examination and assessment. In 196 cases we performed the intramuscular pocket. None of the intramuscular had capsular contracture or animation deformity in the follow up period. CONCLUSIONS: The intramuscular technique is a valuable and safe technique for secondary breast augmentation.

18.
BMJ Neurol Open ; 6(1): e000737, 2024.
Article in English | MEDLINE | ID: mdl-38835539

ABSTRACT

Introduction: Cases of nitrous oxide (N2O)-induced myeloneuropathy are increasing at UK hospitals. At our centre, a dedicated ambulatory care pathway, endorsed nationally, was established to treat and monitor patients with N2O-myeloneuropathy in 2021 and refined through three audit cycles. We analysed the outcomes of patients on this pathway to better understand factors associated with non-engagement. Alongside, a novel approach using WhatsApp for questionnaire delivery was trialled in an attempt to improve engagement with treatment. Methods: Patients on the N2O ambulatory care pathway were identified from MDT meeting lists from 9 September 2022 to 25 April 2023. Clinical data were collected via electronic clinical records, including the most recent neurological examination and reason for discharge from the pathway. Patients identified from MDT lists from 27 January 2023 to 14 March 2023 were approached to participate in weekly 12-item surveys, delivered via WhatsApp. This was approved as a service development project with approval for WhatsApp use given by the chief clinical information officer. Results: 35/56 (62.5%) patients were discharged from ambulatory care due to non-attendance and 17/56 (30.4%) completed their treatment course. The median time from initial presentation to discharge was 49 days. 24/40 (60.0%) of patients with a final neurological examination documented had a residual deficit, with objective sensory deficits most common. 12 patients were approached to receive weekly questionnaires via WhatsApp. 5/8 who expressed interest returned a consent form. All participants were withdrawn due to non-response or participant choice. 1/5 returned more than two surveys. Conclusion: Despite poor participation in surveys delivered via WhatsApp, novel approaches are needed to improve engagement with patients on the N2O ambulatory care pathway.

19.
Chem Sci ; 15(24): 9104-9111, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38903236

ABSTRACT

N-Triflylphosphoramides (NTPAs) represent an important catalyst class in asymmetric catalysis due to their multiple hydrogen bond acceptor sites and acidity, which is increased by several orders of magnitude compared to conventional chiral phosphoric acids (CPAs). Thus, NTPAs allow for several challenging transformations, which are not accessible with CPAs. However, detailed evidence on their hydrogen bonding situation, complex structures and aggregation is still lacking. Therefore, this study covers the hydrogen bonding behavior and structural features of binary NTPA/imine complexes compared to their CPA counterparts. Deviating from the single-well potential hydrogen bonds commonly observed in CPA/imine complexes, the NTPA/imine complexes exhibit a tautomeric equilibrium between two proton positions. Low-temperature NMR at 180 K supported by computer simulations indicates a OHN hydrogen bond between the phosphoramide oxygen and the imine, instead of the mostly proposed NHN H-bond. Furthermore, this study finds no evidence for the existence of dimeric NTPA/NTPA/imine complexes as previously suggested for CPA systems, both synthetically and through NMR studies.

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