Stabilisation of Bromenium Ions in Macrocyclic Halogen Bond Complexes.

Halenium ions (X+) are highly reactive electron deficient species that are prevalent transient intermediates in halogenation reactions. The stabilisation of these species is especially challenging, with the most common approach to sequester reactivity through the formation of bis-pyridine (Py) complexes; [(Py)2X]+. Herein, we present the first example of a macrocyclic stabilisation effect for halenium species. Exploiting a series of bis-pyridine macrocycles, we demonstrate the first example of utilising the macrocyclic ligands to stabilise halenium species via the endotopic complexation of a bromenium cation, impressively facilitating the isolation of a bench stable 'Br+ NO3-' species. Solid state X-ray crystallographic structural comparison of macrocyclic Br(I) complexes with Ag(I) and Au(I) analogues provides insightful information concerning similarities and stark contrasts in halenium/metal cation coordination behaviors. Furthermore, the first chemical ligand exchange reactions of Br(I) complexes are reported between acyclic [(Py)2Br]+ species and a bis-pyridine macrocyclic donor ligand which importantly highlights a macrocycle effect for halenium cation stabilisation in the solution phase.

Rh sensitization in abortion care: where we've been and where we're going.

PURPOSE OF REVIEW: The purpose of this review is to summarize the historical context and recent literature that contribute to the debate about preventive strategies for Rhesus (Rh)-alloimmunization in abortion are. RECENT FINDINGS: Recent studies repeatedly demonstrate that the risk of Rh-alloimmunization in first trimester abortion care is very low. SUMMARY: Recent high-quality studies have demonstrated the physiologic presence of fetal red blood cells in maternal circulation even prior to abortion. Thus, establishing the low utility of Rh immunoglobulin prior to abortion before 12 weeks of gestation. There is yet to exist a consensus guideline that balances the desire to prevent a rare devastating outcome and the need to create practical guidelines based on evidence-based risk assessments.

Orbital masses as a rare presentation of Rosai-Dorfman disease: Clinicopathologic characterization of five cases.

Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis. Most cases present with marked, non-tender lymphadenopathy due to the proliferation of atypical histiocytes. A minority of cases involves extranodal sites and can present as bone lesions, skin rashes, pulmonary nodules, and rarely orbital masses. Orbital involvement in RDD is rare and may infrequently present as an isolated tumor mass without lymphadenopathy. This study aims to better characterize this uncommon presentation of this rare disease. Five cases of orbital RDD were identified from the last 18 years and the clinical characteristics of each case were compared with histopathological findings. Three men and two women ages 12-36 presented with complaints of eye swelling and/or vision changes. One patient had a history of neurofibromatosis type I and inflammatory pseudotumors while the other four had no signs of systemic disease or other sites of extranodal involvement at the time of presentation. Masses ranged in size from 1.0 cm to 3.5 cm and primarily involved the superior orbit. Resected lesions all displayed characteristic findings of admixed atypical histiocytes, lymphocytes, and plasma cells with a fibrotic background. Emperipolesis was seen in all cases. Immunostaining for S100 and CD68 was diffusely positive in the histiocyte population. Clinical follow-up was obtained for 4 of 5 patients: all four were disease-free at 1 to 15 years after resection. RDD should be considered in the differential for patients with orbital masses, even in the absence of lymphadenopathy or signs of systemic disease.

Dietary amino acids, macronutrients, vaginal birth, and breastfeeding are associated with the vaginal microbiome in early pregnancy.

The vaginal microbiome is a key player in the etiology of spontaneous preterm birth. This study aimed to illustrate maternal environmental factors associated with vaginal microbiota composition and function in pregnancy. Women in healthy pregnancy had vaginal microbial sampling from the posterior vaginal fornix performed at 16 weeks gestation. After shotgun metagenomic sequencing, heatmaps of relative abundance data were generated. Community state type (CST) was assigned, and alpha diversity was calculated. Demography, obstetric history, well-being, exercise, and diet using food frequency questionnaires were collected and compared against microbial parameters. A total of 119 pregnant participants had vaginal metagenomic sequencing performed. Factors with strongest association with beta diversity were dietary lysine (adj-R2 0.113, P = 0.002), valine (adj-R2 0.096, P = 0.004), leucine (adj-R2 0.086, P = 0.003), and phenylalanine (adj-R2 0.085, P = 0.005, Fig. 2D). Previous vaginal delivery and breastfeeding were associated with vaginal beta diversity (adj-R2 0.048, P = 0.003; adj-R2 0.045, P = 0.004), accounting for 8.5% of taxonomy variation on redundancy analysis. Dietary fat, starch, and maltose were positively correlated with alpha diversity (fat +0.002 SD/g, P = 0.025; starch +0.002 SD/g, P = 0.043; maltose +0.440 SD/g, P = 0.013), particularly in secretor-positive women. Functional signature was associated with CST, maternal smoking, and dietary phenylalanine, accounting for 8.9%-11% of the variation in vaginal microbiome functional signature. Dietary amino acids, previous vaginal delivery, and breastfeeding history were associated with vaginal beta diversity. Functional signature of the vaginal microbiome differed with community state type, smoking, dietary phenylalanine, and vitamin K. Increased alpha diversity correlated with dietary fat and starch. These data provide a novel snapshot into the associations between maternal environment, nutrition, and the vaginal microbiome. IMPORTANCE: This secondary analysis of the MicrobeMom randomized controlled trial reveals that dietary amino acids, macronutrients, previous vaginal birth, and breastfeeding have the strongest associations with vaginal taxonomy in early pregnancy. Function of the vaginal niche is associated mainly by species composition, but smoking, vitamin K, and phenylalanine also play a role. These associations provide an intriguing and novel insight into the association between host factors and diet on the vaginal microbiome in pregnancy and highlight the need for further investigation into the complex interactions between the diet, human gut, and vaginal microbiome.

Survey self-report of rheumatoid arthritis and treatments versus specialist clinician confirmation.

OBJECTIVE: To assess agreement between patient survey report and physician recorded arthritic conditions and medication use in order to validate population-based epidemiologic approaches to auto-immune arthritic conditions. METHODS: Rheumatologists in the U.S. Appalachian region recruited men 50 years or older with a confirmed rheumatoid arthritis (RA) diagnosis. For each participating patient, the treating specialist completed a brief chart abstraction that included rheumatic diagnosis and corresponding treatment. Patients participated in a telephone interview using the same questionnaire as applied in a larger random digit dial survey that queried arthritis diagnosis and treatment. We assessed patient-clinician agreement with the Prevalence Adjusted and Biased Adjusted Kappa (PABAK) statistic. RESULTS: We included 36 patient-clinician dyads in this analysis. All clinicians and patients concurred in the RA diagnosis (PABAK = 1). For concomitant systemic lupus and scleroderma, we observed generally concordant responses (PABAK 0.89 and 1, respectively). For medication use, for hydroxychloroquine or sulfasalazine was associated with the lowest PABAK (0.39), intermediate values for methotrexate and for the "other conventional synthetic DMARDs" category (0.67), and with the highest agreement PABAK value for the "biologic DMARD or JAK 2 inhibitor" category (0.89). CONCLUSION: Survey-based self-report of RA offers a useful approach in epidemiological investigation. This is particularly relevant to population-based approaches to autoimmune arthritis related to occupational and environmental factors.

A human model of Buruli ulcer: Provisional protocol for a Mycobacterium ulcerans controlled human infection study.

Critical knowledge gaps have impeded progress towards reducing the global burden of disease due to Mycobacterium ulcerans, the cause of the neglected tropical disease Buruli ulcer (BU). Development of a controlled human infection model of BU has been proposed as an experimental platform to explore host-pathogen interactions and evaluate tools for prevention, diagnosis, and treatment. We have previously introduced the use case for a new human model and identified M. ulcerans JKD8049 as a suitable challenge strain. Here, we present a provisional protocol for an initial study, for transparent peer review during the earliest stages of protocol development. Following simultaneous scientific peer review and community/stakeholder consultation of this provisional protocol, we aim to present a refined protocol for institutional review board (IRB) evaluation.

This paper describes a provisional clinical protocol for the pilot human challenge model of Mycobacterium ulcerans infection, which causes the skin disease 'Buruli ulcer' (BU). BU is typically painless and begins as a small area of redness or swelling, and is curable with antibiotics. If the diagnosis is delayed, it can result in large ulceration and disability. Side effects from antibiotics are common but rarely severe; nevertheless, preventative strategies, such as vaccination, are urgently needed. The overarching project, known as 'MuCHIM', aims to establish a safe and acceptable controlled human challenge model (CHIM) of this disease in healthy volunteers in Melbourne, Australia. This pilot protocol primarily aims to establish that it is safe and acceptable to participants, and secondarily to confirm successful establishment of infection and the infection rate amongst participants. We also aim to test less invasive diagnostic tests, assess immune responses to infection, to understand changes in the human microbiome during the trial, and explore microbiological characteristics of M. ulcerans infection. If this pilot is successful, we hope to test vaccines and other therapeutics using this model, which could blunt or reduce the rising incidence of this disease in Australia, while further informing vaccine development research.

Interactive effects of genetic liability and combat exposure on risk of alcohol use disorder among US service members.

BACKGROUND: An improved understanding of pathways to alcohol use disorder (AUD) among service members may inform efforts to reduce the substantial impact of AUD on this population. This study examined whether the relationship between a service-related risk factor (combat exposure) and later AUD varied based on individual differences in genetic liability to AUD. METHODS: The sample consisted of 1203 US Army soldiers of genetically determined European ancestry who provided survey and genomic data in the Army STARRS Pre/Post Deployment Study (PPDS; 2012-2014) and follow-up survey data in wave 1 of the STARRS Longitudinal Study (2016-2018). Logistic regression was used to estimate the conditional effect of combat exposure level (self-reported in PPDS) on odds of probable AUD diagnosis at follow-up, as a function of a soldier's polygenic risk score (PRS) for AUD. RESULTS: The direct effect of combat exposure on AUD risk was non-significant (AOR=1.12, 95 % CI=1.00-1.26, p=.051); however, a significant combat exposure x PRS interaction was observed (AOR=1.60, 95 % CI=1.03-2.46, p=.033). Higher combat exposure was more strongly associated with elevated AUD risk among soldiers with heightened genetic liability to AUD. CONCLUSIONS: The effect of combat exposure on AUD risk appeared to vary based on a service member's level of genetic risk for AUD. Continued investigation is warranted to determine whether PRS can help stratify AUD risk within stress-exposed groups such as combat-deployed soldiers. Such efforts might reveal opportunities to focus prevention efforts on smaller subgroups at the intersection of having both environmental exposures and genetic vulnerability to AUD.

B-cell Interleukin 1 Receptor 1 (IL1R1) modulates the female adipose tissue immune microenvironment during aging.

Myeloid cell production of interleukin-1ß (IL-1ß) drives inflammaging in visceral adipose tissue (vWAT) and contributes to the expansion of interleukin-1 receptor 1 (Il1r1) positive aged adipose B-cells (AABs). AABs promote metabolic dysfunction and inflammation under inflammatory challenges. However, it is unclear whether IL-1ß contributes to AAB-associated inflammation during aging. Using a B-cell specific knockout of Il1r1 (BKO mice), we characterized old vWAT in the absence of IL-1ß - B-cell signaling. In addition to sex-specific metabolic improvements in females, we identified a reduction in the proportion of B-cells and a sex-specific increase in the B1:B2 B-cell ratio in BKO vWAT. Using single cell RNA-sequencing of vWAT immune cells, we observed that BKO differentially affected inflammatory signaling in vWAT immune cells. These data suggest that IL-1ß - B-cell signaling supports the inflammatory response in multiple cell types and provides insight into the complex microenvironment in aged vWAT.

Transcatheter Aortic Valve Implantation by Valve Type in Women With Small Annuli: Results From the SMART Randomized Clinical Trial.

Importance: Historically, women with aortic stenosis have experienced worse outcomes and inadequate recognition compared to men, being both underdiagnosed and undertreated, while also facing underrepresentation in clinical trials. Objective: To determine whether women with small aortic annuli undergoing transcatheter aortic valve replacement have better clinical and hemodynamic outcomes with a self-expanding valve (SEV) or balloon-expandable valve (BEV). Design, Setting, Participants: The Small Annuli Randomized to Evolut or SAPIEN Trial (SMART) was a large-scale randomized clinical trial focusing on patients with small aortic annuli undergoing transcatheter aortic valve replacement, randomized to receive SEVs or BEVs and included 716 patients treated at 83 centers in Canada, Europe, Israel, and the US from April 2021 to October 2022. This prespecified secondary analysis reports clinical and hemodynamic findings for all 621 women enrolled in SMART. Data for this report were analyzed from February to April 2024. Interventions: Transcatheter aortic valve replacement with an SEV or a BEV. Main Outcomes and Measures: The composite coprimary clinical end point comprised death, disabling stroke, or heart failure-related rehospitalization. The coprimary valve function end point was the incidence of bioprosthetic valve dysfunction, both assessed through 12 months. Secondary end points included the incidence of moderate or severe prosthesis-patient mismatch. Results: A total of 621 women (mean [SD] age, 80.2 [6.2] years; 312 randomized to the SEV group and 309 to the BEV group) were included in the present analysis. At 12 months, there were no significant differences in the coprimary clinical end point between the SEV and BEV groups (9.4% vs 11.8%, absolute risk difference -2.3%; 95% CI -7.2 to 2.5, P = .35). However, SEV implantation was associated with less bioprosthetic valve dysfunction (8.4% vs 41.8%; absolute risk difference, -33.4%; 95% CI, -40.4 to -26.4; P < .001). SEV implantation resulted in lower aortic valve gradients and larger effective orifice areas at 30 days and 12 months and less mild or greater aortic regurgitation at 12 months compared to BEV implantation. Prosthesis-patient mismatch was significantly lower with SEVs, regardless of the definition used and adjustment for body mass index. Use of SEVs was associated with better quality of life outcomes as assessed by the Valve Academic Research Consortium-3 ordinal quality of life measure. Conclusions and Relevance: Among women with severe symptomatic aortic stenosis and small aortic annuli undergoing transcatheter aortic valve replacement, the use of SEVs, compared to BEVs, resulted in similar clinical outcomes and a markedly reduced incidence of bioprosthetic valve dysfunction through 12 months, including a lower risk of prosthesis-patient mismatch and better 12-month quality of life. Trial Registration: ClinicalTrials.gov Identifier: NCT04722250.

Enabling laboratory readiness and preparedness for the evaluation of suspected viral hemorrhagic fevers: development of a laboratory toolkit.

PURPOSE: Viral hemorrhagic fevers (VHFs), such as Ebola virus disease, Marburg virus disease, and Lassa fever, are associated with significant morbidity and mortality and the potential for person-to-person transmission. While most individuals in whom VHF is suspected will ultimately be diagnosed with a non-VHF illness, such patients may present to any United States healthcare facility (HCF) for initial evaluation; therefore, all HCFs must be prepared to evaluate and initiate care for suspect VHF patients, especially if they are acutely ill. Included within this evaluation is the ability to perform basic routine laboratory testing before VHF-specific diagnostic test results are available, as well as rapid malaria testing to assess for a common, dangerous "VHF mimic." OBJECTIVE: To improve laboratory preparedness and readiness in the initial care of suspect VHF patients who may present to acute care hospitals. DESIGN: Plan-Do-Study-Act quality improvement model. SETTING: Frontline healthcare facilities and their clinical laboratories. METHODS: We describe the development of a laboratory testing toolkit for a suspect VHF patient that can assist frontline HCFs in providing basic laboratory testing required for the care of these patients. RESULTS: The toolkit provides guidance on infection prevention and control, waste management, occupational health, laboratory test collection, processing, and resulting, in the context of suspect VHF patient evaluation. CONCLUSIONS: The toolkit is designed to be readily adapted by any frontline HCF in the US. With the guidance provided, facilities will be able to support safer initial evaluation of VHF suspects and ensure high-quality patient care.

Quasicrystal synthesis by shock compression.

Quasicrystals are of interest because of their unique nonperiodic structures and physical properties. Motivated by naturally occurring icosahedral AlCuFe- and decagonal AlNiFe-phases hosted in a shocked meteorite, different laboratories have undertaken a series of shock recovery experiments to understand their formation mechanism. Shock experiments generate a complex series of processes and conditions, including a near-instantaneous excursion to high pressure and high temperature, large shear stresses, local melting, rapid decompression, fast quenching and post-shock annealing. This highly dynamic scenario offers a very useful but imperfect tool for exploring the stability of novel alloys, such as quasicrystals. So far, all the shock-synthesized quasicrystals differ considerably in composition from any thermodynamically stable or metastable quasicrystals synthesized by metallurgical techniques at low pressure, leaving plenty of questions to be answered about their formation conditions and their nucleation and growth mechanisms occurring during shock experiments. In this Perspective, we summarize the previous studies of shock-synthesized quasicrystals and discuss the advantages and difficulties caused by the experimental complexity. We also propose a few directions for future experiments to better control the shock conditions and understand the properties of quasicrystals.

Validation of the prognostic index for spine metastasis (PRISM) for stratifying survival in patients treated with spinal stereotactic body radiation.

PURPOSE: The Prognostic Index for Spinal Metastasis (PRISM) is a scoring system derived from prospective data from a single institution that stratifies patients undergoing spine stereotactic radiosurgery (SSRS) for spinal metastases into subgroups by overall (OS). We sought to further demonstrate its generalizability by performing validation with a large dataset from a second high-volume institution, Mayo Clinic. METHODS AND MATERIALS: Eight hundred seventy-nine patients-424 from Mayo Clinic and 455 from MD Anderson Cancer Center (MDACC)-who received SSRS between 2007 and 2019 were identified. Patients were stratified by PRISM criteria, and overall survival (OS) for the PRISM groups for each cohort was compared using Kaplan-Meier estimations and univariate Cox proportional analyses. Model calibration and concordance indices (C-indices) were calculated for each cohort to assess the quality of the scoring system. RESULTS: Patient and tumor characteristics varied significantly between both cohorts including histology, sex, performance status, and number of organs involved (all P < 0.001). Median OS was 30.3 and 22.1 months for the Mayo and MDACC cohorts, respectively. Kaplan-Meier survival curves revealed robust separation between prognostic groups within both cohorts. The Mayo cohort showed median OS of 57.1, 37.0, 23.7, and 8.8 months for Groups 1, 2, 3, and 4, respectively. Univariate analysis revealed hazard ratios of 3.0 (95 % confidence interval [CI], 1.9-4.9), 5.2 (95 % CI, 3.2-8.3), and 12.9 (95 % CI, 7.8-21.4) for groups 2, 3 and 4, respectively all P < 0.001). The C-indices were 0.69 and 0.66 for the unstratified and stratified scores for the Mayo cohort, and 0.70 and 0.68 for the MDACC cohort, respectively. CONCLUSION: These data demonstrate robust validation of the PRISM score to stratify OS in patients treated with SSRS by a large external cohort, despite substantial differences among the cohorts. Overall, the PRISM scoring may help guide optimal treatment selection for patients with spine metastases.

Bivalent norovirus mRNA vaccine elicits cellular and humoral responses protecting human enteroids from GII.4 infection.

Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.

Quest for Orthologs in the Era of Biodiversity Genomics.

The era of biodiversity genomics is characterised by large-scale genome sequencing efforts that aim to represent each living taxon with an assembled genome. Generating knowledge from this wealth of data has not kept up with this pace. We here discuss major challenges to integrating these novel genomes into a comprehensive functional and evolutionary network spanning the tree of life. In summary, the expanding datasets create a need for scalable gene annotation methods. To trace gene function across species, new methods must seek to increase the resolution of ortholog analyses, e.g., by extending analyses to the protein domain level and by accounting for alternative splicing. Additionally, the scope of orthology prediction should be pushed beyond well-investigated proteomes. This demands the development of specialised methods for the identification of orthologs to short proteins and non-coding RNAs, and for the functional characterization of novel gene families. Furthermore, protein structures predicted by machine learning are now readily available, but this new information is yet to be integrated with orthology-based analyses. Finally, an increasing focus should be placed on making orthology assignments adhere to the FAIR principles. This fosters green bioinformatics by avoiding redundant computations and helps integrating diverse scientific communities sharing the need for comparative genetics and genomics information. It should also help with communicating orthology-related concepts in a format that is accessible to the public, to counteract existing misinformation about evolution.

Nodal T-cell lymphoma transdifferentiated from mantle cell lymphoma with Epstein-Barr virus infection.

INTRODUCTION: We report a case of mantle cell lymphoma (MCL) with apparent lineage switch to an EBV-positive T-cell lymphoma. Although lineage switch is a well-documented phenomenon in some hematolymphoid diseases, such as acute leukemias or histiocytic/dendritic cell neoplasms, lineage switch from mature B to T cell lymphoma is exceedingly rare. CASE PRESENTATION: A 55-year-old man with an established history of MCL presented to our institution. Peripheral blood flow cytometry was consistent with MCL. Biopsy of a lumbar vertebral fracture site demonstrated mantle cell lymphoma, EBV-associated, with large cells reminiscent of high-grade transformation (BCL1-positive). Two months later, a lymph node biopsy demonstrated an EBV-positive T-cell lymphoma without phenotypic evidence of B-cell lymphoma (BCL1-negative). Cytogenetic testing revealed CCND1::IGH fusion in all three specimens. IGH/IGK clonality testing revealed conserved monoclonal peaks in all three samples; TCR clonality testing revealed monoclonal peaks in the T cell lymphoma, only. NGS-based molecular genetic studies revealed shared mutations between the three samples, consistent with a clonal relationship suggesting evolution from mantle cell lymphoma to T cell lymphoma. CONCLUSIONS: This case demonstrates that lineage switch from mature B to mature T-cell phenotype is possible in certain settings. Whether lineage switch in this case was potentiated by EBV infection is unclear. The loss of BCL-1 expression in the T-cell lymphoma, despite conservation of the CCND1::IGH fusion, may be attributable to the downregulation of the IGH promoter as part of the shift from B to T-cell phenotype.

Organic Room Temperature Phosphorescence from BN-Substituted Xanthene Derivatives.

Emissive organic materials are predominantly fluorescent and there is significant interest in realizing and understanding examples that defy this paradigm and exhibit phosphorescence under ambient conditions. Organic room temperature phosphorescence (ORTP) offers the long-lived excited states and bathochromically-shifted emission maxima of phosphorescence without the use of potentially toxic and expensive transition metals. Most ORTP materials rely on well-studied structural motifs that include aryl carbonyls, sulfones, and heavy main group elements. We report the unexpected ORTP of a series of heavy atom-free BN-substituted xanthene derivatives. The creation of heteroatom-rich scaffolds, combined with stabilizing C-H···F interactions in the solid-state, resulted in oxygen-tolerant heavy atom-free organic phosphorescence without relying on the use of cryogenic temperatures, polymer matrices, or host-guest interactions. The observation of ORTP in these simple systems sets a blueprint for the further development of heavy atom-free organic phosphors.

Characterization of human placental fetal vessels in gestational diabetes mellitus.

Gestational diabetes mellitus is one of the most common complications during pregnancy. Its prevalence is rapidly increasing worldwide. Gestational diabetes mellitus is leading to an elevated risk for the development of endothelial dysfunction and cardiovascular diseases both in the mother and the child in later life. The underlying pathophysiological mechanisms are not well-understood. Therefore, we aimed to characterize the endothelial function in fetal placental vessels from mothers with gestational diabetes mellitus. In this study, we distinguished between insulin-treated and diet-controlled gestational diabetes mothers and compared them to a normoglycemic control group. The clinical data confirmed pre-conceptional overweight as a risk factor in women with insulin-treated gestational diabetes mellitus. The insulin-treated gestational diabetes group was also characterized by a recent family history of diabetes compared to mothers of the control or diet-controlled gestational diabetes group. Analyses of blood serum from umbilical cords suggested a reduced fetal insulin metabolism in the insulin-treated gestational diabetes group. Vascular function analysis in fetal placental vessels revealed an altered substance P-induced vasorelaxation in vessels from patients with insulin-dependent gestational diabetes. Inhibition of nitric oxide synthase affected only fetal vessel segments from the control group or diet-controlled gestational diabetes group, but not from insulin-dependent gestational diabetes. Finally, we found a significantly decreased substance P receptor (TACR1) mRNA expression in fetal vessel segments from patients with insulin-treated gestational diabetes. In conclusion, we provide evidence that different pathophysiological mechanisms might be responsible for the development of insulin-treated versus diet-controlled gestational diabetes. Only in fetal vessels from patients with insulin-treated gestational diabetes were we able to detect an endothelial dysfunction and a reduced fetal insulin conversion. This provides novel insights into the pathophysiology of the subtypes of gestational diabetes.

Physical health challenges faced by elders with severe mental illness: population-based retrospective cohort study.

BACKGROUND: Severe mental illness (SMI), which includes schizophrenia, schizoaffective disorder and bipolar disorder, has profound health impacts, even in the elderly. AIMS: To evaluate relative risk of hospital admission and length of hospital stay for physical illness in elders with SMI. METHOD: To construct a population-based retrospective cohort observed from April 2007 to March 2016, data from a case registry with full but de-identified electronic health records were retrieved for patients of the South London and Maudsley NHS Foundation Trust, the single secondary mental healthcare service provider in south-east London. We compared participants with SMI aged >60 years old with the general population of the same age and residing in the same areas through data linkage by age-, sex- and fiscal-year-standardised admission ratios (SARs) for primary diagnoses at hospital discharge. Furthermore, we compared the duration of hospital stay with an age-, sex- and cause-of-admission-matched random group by linear regression for major causes of admission. RESULTS: In total, records for 4175 older people with SMI were obtained, relating to 10 342 admission episodes, showing an overall SAR for all physical illnesses of 5.15 (95% CI: 5.05, 5.25). Among the top causes of admission, SARs ranged from 3.87 for circulatory system disorders (ICD-10 codes: I00-I99) to 6.99 for genitourinary system or urinary conditions (N00-N39). Specifically, the diagnostic group of 'symptoms, signs and findings, not elsewhere classified' (R00-R99) had an elevated SAR of 6.56 (95% CI: 6.22, 6.90). Elders with SMI also had significantly longer hospital stays than their counterparts in the general population, especially for digestive system illnesses (K00-K93), after adjusting for confounding. CONCLUSIONS: Poorer overall physical health and specific patterns were identified in elders with SMI.

Utility of the oxygenation index in management of congenital diaphragmatic hernia: a report from a Thai University Surgical Centre.

BACKGROUND: Oxygenation index (OI) is associated with severity of newborn pulmonary hypertension (PH) in congenital diaphragmatic hernia (CDH). Higher OI may indicate worst degree(s) of PH. OBJECTIVES: This study reports OI dynamic(s) over the first 72 h of life and its correlation with (1) perioperative morbidity and (2) CDH mortality. METHODS: Medical records of inborn CDH babies during 2002-2022 were examined. OI on Days (s) 1-3 and perioperative OI trends were recorded. Operation (primary vs patch repair) and survival rates (%) were studied. RESULTS: Fifty-five CDH newborns (54.5% male: 45.5% female)-mean birth GA 37.5 ± 2.7 wks. had a mean birth weight 2813 ± 684 g with prenatal diagnosis in 32.7% cases. 52/55 (94.5%) were intubated at birth and HFOV deployed in 29 (55.8%). Those requiring HFOV had higher OI on DOL1 (24.8 ± 17 vs 10.3 ± 11.5; p < 0.05), DOL 2 (26.3 ± 22.9 vs 6.7 ± 12.1; p < 0.05) and DOL 3 (21.9 ± 33.8 vs 5.5 ± 9.3; p = 0.04). Operation was undertaken in 36/55 (65.5%). Preoperative mortality group had significant higher OI on DOL 2 (42.1 ± 21.0 vs 14.9 ± 9.3; p = 0.04). CDH defects were-Type A N = 27 (75%), Type B N = 7 (19.4%) and Type C N = 2 (5.6%). Overall mortality was 40% (22/55). Statistically significant OI trends were recorded in non-survival vs. survival groups on DOL 1 (31.6 ± 16.8. vs 10.5 ± 9.0; p < 0.05, DOL 2 (38.1 ± 21.9 vs 6.3 ± 7.1; p < 0.05), and DOL 3 (38.8 ± 39.4; p = 0.012). CONCLUSIONS: OI dynamics are highly predictive for accurate monitoring of CDH cardiorespiratory physiology and crucially may guide ventilatory management as well as timing of surgery.