Novel Measurement of the Neutron Magnetic Form Factor from A=3 Mirror Nuclei.

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6

A preliminary investigation of longitudinal associations between ethnic-racial identity and critical consciousness among Black and Latinx youth.

OBJECTIVES: In order for parents, educators, and communities to support racially/ethnically minoritized youth to resist and heal from White supremacy, it is important to examine how youths' beliefs about their ethnic-racial identity (ERI) and critical consciousness (CC) around racism inform one another. Despite this need, limited empirical research examines whether these processes are related across adolescence. METHOD: The present two-wave longitudinal study investigates whether ERI content (i.e., centrality, private regard) and CC (i.e., critical social analysis, interpersonal antiracism actions) are associated with one another among Black and Latinx youth N = 233; young women (55.6%); young men (44.4%); M = 14.96 years old, SD = 1.46. RESULTS: Autoregressive cross-lagged panel models suggested that youths' centrality at W1 was positively and significantly associated with a critical social analysis at W2, and critical social analysis at W1 was positively and significantly associated with private regard at W2 for both groups. Involvement in interpersonal antiracism actions at W1 was positively and significantly associated with private regard at W2 for both groups. Group differences existed in the link between centrality at W1 and interpersonal antiracism actions at W2. CONCLUSION: Results indicate that ERI and CC may be viable entry points into stimulating youths' capacity to challenge racism, although there is promise in activating antiracism action to further stimulate ERI development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

"I can't provide what my child needs": Early feeding experiences of caregivers of children with craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) is a congenital condition that can be associated with feeding challenges in infants. As part of the larger 'Craniofacial microsomia: Accelerating Research and Education (CARE)' program, this study described caregivers' early feeding experiences. DESIGN AND MATERIALS: US-based caregivers of 34 children with CFM participated in remote narrative interviews. Two authors completed inductive thematic analysis in an iterative process until consensus was reached. RESULTS: Caregivers' narratives outlined the inherent challenges of feeding an infant with special healthcare needs. The first theme 'Navigating Challenges and Managing Expectations' describes the distress participants experienced when they were unable to breastfeed and the negative emotional effect of switching to formula. The second theme 'Making Adaptations' outlines the methods participants tried, including breast pumps and feeding tubes. The third theme 'Accessing Support' describes participants' interactions with healthcare providers and challenges accessing feeding support. The final theme 'Growing from Adversity' recounts participants' relief once their child established a feeding pattern and the personal growth gained from their experiences. CONCLUSIONS: Caregivers reported several feeding related challenges associated with CFM, many of which negatively affected their wellbeing. Negative consequences were particularly pronounced in cases where caregivers' feeding experiences differed from their expectations. Participants identified challenges in accessing reliable feeding information and support. Despite difficult experiences, caregivers cited some positive outcomes, including increased confidence and resilience. PRACTICE IMPLICATIONS: Holistic feeding information and support for families affected by CFM should be inclusive of several feeding methods to improve care delivery, child health, and the caregiver experience.

Validation of Patient-Reported Outcomes in Patients With Nonmetastatic Breast Cancer Receiving Comprehensive Nodal Irradiation in the RadComp Trial.

PURPOSE: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.

The impact of cytotoxic therapy on the risk of progression and death in clonal cytopenia(s) of undetermined significance.

Clonal cytopenia of undetermined significance (CCUS) is defined by a myeloid driver mutation in the context of otherwise unexplained cytopenia. CCUS has an inherent risk of progressing to myeloid neoplasm. However, it is unknown how exposure to previous cytotoxic therapy may impact the risk of progression and survival. We stratified CCUS patients by prior exposure to DNA-damaging therapy. Of 151 patients, 46 (30%) had received cytotoxic therapy and were classified as therapy-related CCUS (t-CCUS), whereas 105 (70%) had de novo CCUS. A lower proportion of t-CCUS had hypercellular marrows (17.8% vs. 44.8%, P=0.002) but had higher median bone marrow blast percentages. After a median follow up of 2.2 years, t-CCUS had significantly shorter PFS (1.8 vs. 6.3 years, HR 2.1, P=0.007) and median OS (3.6 years vs. not reached, HR 2.3, P=0.007) compared to CCUS. Univariable and multivariable time-to-event analyses showed that exposure to cytotoxic therapy independently accounted for inferior PFS and OS. Despite the similarities in clinical presentation between CCUS and t-CCUS, we show that exposure to prior cytotoxic therapies was an independent risk-factor for inferior outcomes. This suggests that t-CCUS represents a unique clinical entity that needs more stringent monitoring or earlier intervention strategies.

Micro-RNA profiles of pathology and resilience in posterior cingulate cortex of cognitively intact elders.

The posterior cingulate cortex (PCC) is a key hub of the default mode network underlying autobiographical memory retrieval, which falters early in the progression of Alzheimer's disease (AD). We recently performed RNA sequencing of post-mortem PCC tissue samples from 26 elderly Rush Religious Orders Study participants who came to autopsy with an ante-mortem diagnosis of no cognitive impairment but who collectively displayed a range of Braak I-IV neurofibrillary tangle stages. Notably, cognitively unimpaired subjects displaying high Braak stages may represent cognitive resilience to AD pathology. Transcriptomic data revealed elevated synaptic and ATP-related gene expression in Braak Stages III/IV compared with Stages I/II, suggesting these pathways may be related to PCC resilience. We also mined expression profiles for small non-coding micro-RNAs (miRNAs), which regulate mRNA stability and may represent an underexplored potential mechanism of resilience through the fine-tuning of gene expression within complex cellular networks. Twelve miRNAs were identified as differentially expressed between Braak Stages I/II and III/IV. However, the extent to which the levels of all identified miRNAs were associated with subject demographics, neuropsychological test performance and/or neuropathological diagnostic criteria within this cohort was not explored. Here, we report that a total of 667 miRNAs are significantly associated (rho > 0.38, P < 0.05) with subject variables. There were significant positive correlations between miRNA expression levels and age, perceptual orientation and perceptual speed. By contrast, higher miRNA levels correlated negatively with semantic and episodic memory. Higher expression of 15 miRNAs associated with lower Braak Stages I-II and 47 miRNAs were associated with higher Braak Stages III-IV, suggesting additional mechanistic influences of PCC miRNA expression with resilience. Pathway analysis showed enrichment for miRNAs operating in pathways related to lysine degradation and fatty acid synthesis and metabolism. Finally, we demonstrated that the 12 resilience-related miRNAs differentially expressed in Braak Stages I/II versus Braak Stages III/IV were predicted to regulate mRNAs related to amyloid processing, tau and inflammation. In summary, we demonstrate a dynamic state wherein differential PCC miRNA levels are associated with cognitive performance and post-mortem neuropathological AD diagnostic criteria in cognitively intact elders. We posit these relationships may inform miRNA transcriptional alterations within the PCC relevant to potential early protective (resilience) or pathogenic (pre-clinical or prodromal) responses to disease pathogenesis and thus may be therapeutic targets.

Extracellular mixed histones are neurotoxic and modulate select neuroimmune responses of glial cells.

Although histone proteins are widely known for their intranuclear functions where they organize DNA, all five histone types can also be released into the extracellular space from damaged cells. Extracellular histones can interact with pattern recognition receptors of peripheral immune cells, including toll-like receptor 4 (TLR4), causing pro-inflammatory activation, which indicates they may act as damage-associated molecular patterns (DAMPs) in peripheral tissues. Very limited information is available about functions of extracellular histones in the central nervous system (CNS). To address this knowledge gap, we applied mixed histones (MH) to cultured cells modeling neurons, microglia, and astrocytes. Microglia are the professional CNS immunocytes, while astrocytes are the main support cells for neurons. Both these cell types are critical for neuroimmune responses and their dysregulated activity contributes to neurodegenerative diseases. We measured effects of extracellular MH on cell viability and select neuroimmune functions of microglia and astrocytes. MH were toxic to cultured primary murine neurons and also reduced viability of NSC-34 murine and SH-SY5Y human neuron-like cells in TLR4-dependent manner. MH did not affect the viability of resting or immune-stimulated BV-2 murine microglia or U118 MG human astrocytic cells. When applied to BV-2 cells, MH enhanced secretion of the potential neurotoxin glutamate, but did not modulate the release of nitric oxide (NO), tumor necrosis factor-α (TNF), C-X-C motif chemokine ligand 10 (CXCL10), or the overall cytotoxicity of lipopolysaccharide (LPS)- and/or interferon (IFN)-γ-stimulated BV-2 microglial cells towards NSC-34 neuron-like cells. We demonstrated, for the first time, that MH downregulated phagocytic activity of LPS-stimulated BV-2 microglia. However, MH also exhibited protective effect by ameliorating the cytotoxicity of LPS-stimulated U118 MG astrocytic cells towards SH-SY5Y neuron-like cells. Our data demonstrate extracellular MH could both damage neurons and alter neuroimmune functions of glial cells. These actions of MH could be targeted for treatment of neurodegenerative diseases.

Five-Year Outcomes from a Prospective Study on the Safety and Efficacy of Phasix-ST Mesh Use at the Hiatus During Paraesophageal Hernia Repair.

INTRODUCTION: Laparoscopic paraesophageal hernia (PEH) repair has a high hernia recurrence rate. The aim of this study was to assess the 5-year hernia recurrence rate after PEH repair using a combination of bioresorbable mesh and advanced surgical techniques to address tension as needed in a prospective group of patients. METHODS: In 2016 a prospective database was established for 50 patients undergoing primary, elective PEH repair with a new bioresorbable mesh (Phasix-ST). Intra-operatively, tension was addressed with Collis gastroplasty and / or diaphragm relaxing incisions as needed. All 50 patients from the initial study were tracked and asked to return for objective follow-up. Recurrence was considered present for any hernia > 2 cm in size. RESULTS: Objective follow-up was obtained in 27 of the original 50 patients (54%) at a median of 5.25 years after their PEH repair. Prior to the 5-year follow-up, 5 patients had a known recurrent hernia. Objective evaluation at 5 years identified an additional 3 recurrences, for a total recurrence rate of 25% (8/32 patients). The hernia recurrence rate in patients with a Collis gastroplasty was significantly lower compared to those without a Collis (7% vs 54%, p=0.008). Two patients underwent re-operation for hernia recurrence. No patient had a mesh infection or mesh erosion. CONCLUSION: The combination of Phasix-ST mesh and tension reducing techniques during PEH repair led to a 25% hernia recurrence rate at 5 years. The addition of a Collis gastroplasty led to significantly fewer hernia recurrences and is indicative of the potential for esophageal shortening in many patients with a PEH. The long-term safety and efficacy of Phasix-ST mesh in combination with surgical technique for PEH repair is confirmed.

Does Ileus Represent the Forgotten End Organ Failure in Critical Illness?

PURPOSE OF REVIEW: This review evaluates the current literature on ileus, impaired gastrointestinal transit (IGT), and acute gastrointestinal injury (AGI) and its impact on multiple organ dysfunction syndrome. RECENT FINDINGS: Ileus is often under recognized in critically ill patients and is associated with significant morbidity and is potentially a marker of disease severity as seen in other organs like kidneys (ATN).

Maternal Metabolic Status and Orofacial Cleft Risk: A Case-Control Study in Thailand.

OBJECTIVES: Metabolic syndrome (MetS) has been suggested to play a role in congenital defects. This study investigated the association of MetS and its components with orofacial clefts (OFCs). METHODS: We conducted a case-control study in Northeast Thailand. Ninety-four cases with cleft lip, with or without cleft palate, were frequency matched with 94 controls on the infant's age and mother's education. We administered a mother's health questionnaire and collected anthropometric measurements and blood samples. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed among infants without a family history of OFCs, mothers who were not currently breastfeeding, and mothers who were >6 months postpartum. RESULTS: When compared to mothers of normal weight, the OR associated with OFCs were 2.44 (95% CI, 1.04-5.76, P = .04) in overweight mothers, and 3.30 (95% CI, 1.14-9.57, P = .03) in obese mothers. Low HDL-C raised the risk of OFCs 2.95 times (95% CI, 1.41-6.14, P = .004) compared to normal HDL-C levels. Mothers with 4 or 5 features of MetS were 2.77 times as likely to have the affected child than those who did not (95% CI, 0.43-17.76), but this difference was not statistically significant (P = .28). Subgroup analyses showed similar results, uncovering an additional significant association between underweight mothers and OFCs. CONCLUSIONS: The results indicate a robust association between underweight and overweight/obese maternal body mass index and increased OFC risk. Additionally, low HDL-C in mothers is linked to an elevated risk of OFCs. Further research is needed to evaluate if promoting strategies to maintain optimal body weight and enhance HDL-C levels in reproductive-age and pregnant women icould contribute to a reduction of the risk of OFCs in their progeny.

Leveraging inter-individual transcriptional correlation structure to infer discrete signaling mechanisms across metabolic tissues.

Inter-organ communication is a vital process to maintain physiologic homeostasis, and its dysregulation contributes to many human diseases. Given that circulating bioactive factors are stable in serum, occur naturally, and are easily assayed from blood, they present obvious focal molecules for therapeutic intervention and biomarker development. Recently, studies have shown that secreted proteins mediating inter-tissue signaling could be identified by 'brute force' surveys of all genes within RNA-sequencing measures across tissues within a population. Expanding on this intuition, we reasoned that parallel strategies could be used to understand how individual genes mediate signaling across metabolic tissues through correlative analyses of gene variation between individuals. Thus, comparison of quantitative levels of gene expression relationships between organs in a population could aid in understanding cross-organ signaling. Here, we surveyed gene-gene correlation structure across 18 metabolic tissues in 310 human individuals and 7 tissues in 103 diverse strains of mice fed a normal chow or high-fat/high-sucrose (HFHS) diet. Variation of genes such as FGF21, ADIPOQ, GCG, and IL6 showed enrichments which recapitulate experimental observations. Further, similar analyses were applied to explore both within-tissue signaling mechanisms (liver PCSK9) and genes encoding enzymes producing metabolites (adipose PNPLA2), where inter-individual correlation structure aligned with known roles for these critical metabolic pathways. Examination of sex hormone receptor correlations in mice highlighted the difference of tissue-specific variation in relationships with metabolic traits. We refer to this resource as gene-derived correlations across tissues (GD-CAT) where all tools and data are built into a web portal enabling users to perform these analyses without a single line of code (gdcat.org). This resource enables querying of any gene in any tissue to find correlated patterns of genes, cell types, pathways, and network architectures across metabolic organs.

Pro-neuroinflammatory and neurotoxic potential of extracellular histones H1 and H3.

Histones organize DNA within cellular nuclei, but they can be released from damaged cells. In peripheral tissues extracellular histones act as damage-associated molecular patterns (DAMPs) inducing pro-inflammatory activation of immune cells. Limited studies have considered DAMP-like activity of histones in the central nervous system (CNS); therefore, we studied the effects of extracellular histones on microglia, the CNS immunocytes, and on neuronal cells. Both the linker histone H1 and the core histone H3 induced pro-inflammatory activation of microglia-like cells by upregulating their secretion of NO and cytokines, including interferon-γ-inducible protein 10 (IP-10) and tumor necrosis factor-α (TNF). The selective inhibitors MMG-11 and TAK-242 were used to demonstrate involvement of toll-like receptors (TLR) 2 and 4, respectively, in H1-induced NO secretion by BV-2 microglia. H1, but not H3, downregulated the phagocytic activity of BV-2 microglia. H1 was also directly toxic to all neuronal cell types studied. We conclude that H1, and to a lesser extent H3, when released extracellularly, have the potential to act as a CNS DAMPs. Inhibition of the DAMP-like effects of extracellular histones on microglia and their neurotoxic activity represents a potential strategy for combating neurodegenerative diseases that are characterized by the adverse activation of microglia and neuronal death.

A Delphi Method for Development of a Barrett's Esophagus Question Prompt List as a Communication Tool for Optimal Patient-physician Communication.

BACKGROUND METHODS: The question prompt list content was derived through a modified Delphi process consisting of 3 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of Barrett's esophagus" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" Questions were reviewed and categorized into themes. In round 2, experts rated questions on a 5-point Likert scale. In round 3, experts rerated questions modified or reduced after the previous rounds. Only questions rated as "essential" or "important" were included in Barrett's esophagus question prompt list (BE-QPL). To improve usability, questions were reduced to minimize redundancy and simplified to use language at an eighth-grade level (Fig. 1). RESULTS: Twenty-one esophageal medical and surgical experts participated in both rounds (91% males; median age 52 years). The expert panel comprised of 33% esophagologists, 24% foregut surgeons, and 24% advanced endoscopists, with a median of 15 years in clinical practice. Most (81%), worked in an academic tertiary referral hospital. In this 3-round Delphi technique, 220 questions were proposed in round 1, 122 (55.5%) were accepted into the BE-QPL and reduced down to 76 questions (round 2), and 67 questions (round 3). These 67 questions reached a Flesch Reading Ease of 68.8, interpreted as easily understood by 13 to 15 years olds. CONCLUSIONS: With multidisciplinary input, we have developed a physician-derived BE-QPL to optimize patient-physician communication. Future directions will seek patient feedback to distill the questions further to a smaller number and then assess their usability.

Intrauterine Device Placement Success for Adolescents and Young Adults at Community-Based Reproductive Health Clinics.

BACKGROUND: Despite the endorsement of intrauterine device (IUD) use in adolescents and young adults (AYAs) by leading professional organizations and demonstrated acceptance and desirability by AYAs, clinicians may worry about the procedural difficulty of IUD device placement in younger patients. OBJECTIVE: The aim of this study was to evaluate the clinical outcomes of first-attempt IUD placement in an AYA population by vaginal delivery (VD) history. STUDY DESIGN: We performed a retrospective cohort study of patients under 25 years old at reproductive health clinics with an IUD placement attempt between January 1 and August 31, 2017. We abstracted sociodemographic characteristics, pregnancy history, and procedural characteristics including complications. Bivariate analyses compared successful first-attempt IUD placement by VD history. We also assessed the frequency of secondary clinical outcomes including ancillary measures used, provider type, symptoms reported during the procedure, and complications. RESULTS: We included 1325 participants (median age = 21.3 years), including 42 (3.2%) with a previous VD. Nearly all IUD placements were successful on the first attempt (n = 1301, 98.2%) and performed by advanced practice clinicians (n = 1314, 99.2%). First-attempt IUD placement success was similar in those participants with and without VD (P > .999). Ancillary measures other than nonsteroidal anti-inflammatory drugs were used infrequently (n = 16, 3.6%). Among participants with an unsuccessful placement, 66.7% returned, and all had a successful IUD placement on the second attempt. Documented complications within 6 months of placement were rare (n = 29) and mostly comprised expulsions (n = 27, 93.1%). CONCLUSION: IUD placement success among AYAs at community-based reproductive health clinics is high and is not associated with a history of VD.

Developmental Trajectories of Parental Self-Efficacy as Children Transition to Adolescence in Nine Countries: Latent Growth Curve Analyses.

Little is known about the developmental trajectories of parental self-efficacy as children transition into adolescence. This study examined parental self-efficacy among mothers and fathers over 3 1/2 years representing this transition, and whether the level and developmental trajectory of parental self-efficacy varied by cultural group. Data were drawn from three waves of the Parenting Across Cultures (PAC) project, a large-scale longitudinal, cross-cultural study, and included 1178 mothers and 1041 fathers of children who averaged 9.72 years of age at T1 (51.2% girls). Parents were from nine countries (12 ethnic/cultural groups), which were categorized into those with a predominant collectivistic (i.e., China, Kenya, Philippines, Thailand, Colombia, and Jordan) or individualistic (i.e., Italy, Sweden, and USA) cultural orientation based on Hofstede's Individualism Index (Hofstede Insights, 2021). Latent growth curve analyses supported the hypothesis that parental self-efficacy would decline as children transition into adolescence only for parents from more individualistic countries; parental self-efficacy increased over the same years among parents from more collectivistic countries. Secondary exploratory analyses showed that some demographic characteristics predicted the level and trajectory of parental self-efficacy differently for parents in more individualistic and more collectivistic countries. Results suggest that declines in parental self-efficacy documented in previous research are culturally influenced.

National survey sampling exercise on current practice in channelled local anaesthetic biopsy in suspected head and neck cancer.

OBJECTIVE: Out-patient channelled endoscopic local anaesthetic biopsy reduces the time to diagnosis and wider use may improve cancer pathway times. This study aimed to assess the practice of ENT surgeons using channelled local anaesthetic biopsy. METHOD: A survey was distributed nationally, containing questions about out-patient local anaesthetic biopsy. RESULTS: In total, 58 responses were returned; only 12 per cent of respondents (n = 7) used general anaesthetic biopsy. The advantages of local anaesthetic biopsy were: the avoidance of general anaesthetic for patients with poor performance scores (95 per cent, n = 55) and faster cancer pathway times (91 per cent, n = 53). Disadvantages were: clinics running late (29 per cent, n = 17) and complications (24 per cent, n = 14). The main barrier to using local anaesthetic was access to channelled flexible endoscopy (38 per cent, n = 22), with 43 per cent (n = 25) reporting they were not using out-patient channelled endoscopes but would be interested in using them. CONCLUSION: Surgeons are interested in using channelled endoscopic local anaesthetic biopsy, but they are limited by access to equipment. Increased use of channelled endoscopes may improve national cancer pathway times and avoid challenging general anaesthetics.

Lipid biology of plasmalogen-derived halolipids: Signature molecules of myeloperoxidase and eosinophil peroxidase activity.

Myeloperoxidase and eosinophil peroxidase exert their antimicrobial functions through the oxidative actions of their hypohalous acid products. Plasmalogen phospholipids are particularly susceptible to oxidation of their vinyl ether functional group by hypohalous acids. This produces a family of halogenated lipid products with pro-inflammatory roles and potential biomarker utility. The initial product of plasmalogen oxidation by HOCl is 2-chlorofatty aldehyde, which has been shown to play a key role at the blood-endothelium interface. In vitro and in vivo studies indicate increased endothelial barrier permeability, neutrophil chemotaxis, neutrophil and platelet adherence to endothelium, and promotion of erythrocyte lysis as some of its effects. These effects may be due to protein modification by 2-chlorofatty aldehyde. 2-Chlorofatty aldehyde is metabolized by host dehydrogenases to 2-chlorofatty acid. While it is less chemically reactive, 2-chlorofatty acid has partial overlap of pro-inflammatory effects with 2-chlorofatty aldehyde and unique actions such as induction of neutrophil extracellular trap formation. The stability of 2-chlorofatty acid in plasma also makes it well-suited as a biomarker of HOCl generation, and its plasma levels may be predictive of disease outcomes. 2-Bromofatty aldehydes and acids are produced analogously from HOBr reaction with plasmalogens. Their functions have yet to be well-elucidated, though similarities with chlorolipids have been observed, and increased reactivity with proteins is expected through enhanced electrophilicity of the alpha carbon. Altogether, these halogenated lipids represent underexplored mediators of diseases involving excess hypohalous acid production.

Resistance analysis following sotrovimab treatment in participants with COVID-19 during the phase III COMET-ICE study.

Aim: Sotrovimab is an engineered human monoclonal antibody that binds a conserved region of the SARS-CoV-2 spike protein. The COMET-ICE phase III study evaluated sotrovimab for treatment of mild to moderate COVID-19 in nonhospitalized participants with ≥1 risk factor for severe disease progression. Materials & methods: We evaluated the presence of circulating SARS-CoV-2 variants of concern or interest (VOCs/VOIs) and characterized the presence of baseline, post-baseline and emergent amino acid substitutions detected in the epitope of sotrovimab in SARS-CoV-2. Results: None of the sotrovimab-treated participants with baseline epitope substitutions, and 1 of 48 sotrovimab-treated participants with post-baseline epitope substitutions, met the primary clinical endpoint for progression. Conclusion: Overall, progression was not associated with identified VOC/VOI or the presence of epitope substitutions in sotrovimab-treated participants.

Analysis of the genetics of the SARS-CoV-2 virus from participants in a clinical study for treatment of COVID-19 In a large clinical study, the ability of the monoclonal antibody sotrovimab to treat patients with mild to moderate COVID-19 was looked at. This paper focuses on the genetics of the SARS-CoV-2 viruses from participants in this clinical study. Overall, most participants in the study were infected with the original 'wild type' variant of SARS-CoV-2. We also looked for changes in the virus at the positions on the viral spike protein where sotrovimab binds. In participants treated with sotrovimab, changes in the virus at the site where sotrovimab binds on the viral surface protein were not associated with negative outcomes in participants. Clinical Trial Registration: NCT04545060 (ClinicalTrials.gov).