Digital Spatial Profiling Identifies Distinct Molecular Signatures of Vascular Lesions in Pulmonary Arterial Hypertension.

RATIONALE: Idiopathic Pulmonary Arterial Hypertension (IPAH) is characterized by extensive pulmonary vascular remodeling due to plexiform and obliterative lesions, media hypertrophy, inflammatory cell infiltration, and alterations of the adventitia. OBJECTIVE: Test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles, which collectively are different from control pulmonary arteries. METHODS: We used digital spatial transcriptomics to profile the genome-wide differential transcriptomic signature of key pathological lesions (plexiform, obliterative, intima+media hypertrophy, and adventitia) in IPAH lungs (n= 11) and compared these data to the intima+media and adventitia of control pulmonary artery (n=5). RESULTS: We detected 8273 transcripts in the IPAH lesions and control lung pulmonary arteries. Plexiform lesions and IPAH adventitia exhibited the greatest number of differentially expressed genes when compared with intima-media hypertrophy and obliterative lesions. Plexiform lesions in IPAH showed enrichment for (i) genes associated with TGFß-signaling and (ii) mutated genes affecting the extracellular matrix and endothelial-mesenchymal transformation. Plexiform lesions and IPAH adventitia showed upregulation of genes involved in immune and interferon signaling, coagulation, and complement pathways. Cellular deconvolution indicated variability in the number of vascular and inflammatory cells between IPAH lesions, which underlies the differential transcript profiling. CONCLUSIONS: IPAH lesions express unique molecular transcript profiles enriched for pathways involving pathogenetic pathways, including genetic disease drivers, innate and acquired immunity, hypoxia sensing, and angiogenesis signaling. These data provide a rich molecular-structural framework in IPAH vascular lesions that inform novel biomarkers and therapeutic targets in this highly morbid disease.

De novo variants in FRYL are associated with developmental delay, intellectual disability, and dysmorphic features.

FRY-like transcription coactivator (FRYL) belongs to a Furry protein family that is evolutionarily conserved from yeast to humans. The functions of FRYL in mammals are largely unknown, and variants in FRYL have not previously been associated with a Mendelian disease. Here, we report fourteen individuals with heterozygous variants in FRYL who present with developmental delay, intellectual disability, dysmorphic features, and other congenital anomalies in multiple systems. The variants are confirmed de novo in all individuals except one. Human genetic data suggest that FRYL is intolerant to loss of function (LoF). We find that the fly FRYL ortholog, furry (fry), is expressed in multiple tissues, including the central nervous system where it is present in neurons but not in glia. Homozygous fry LoF mutation is lethal at various developmental stages, and loss of fry in mutant clones causes defects in wings and compound eyes. We next modeled four out of the five missense variants found in affected individuals using fry knockin alleles. One variant behaves as a severe LoF variant, whereas two others behave as partial LoF variants. One variant does not cause any observable defect in flies, and the corresponding human variant is not confirmed to be de novo, suggesting that this is a variant of uncertain significance. In summary, our findings support that fry is required for proper development in flies and that the LoF variants in FRYL cause a dominant disorder with developmental and neurological symptoms due to haploinsufficiency.

A scoping review of human health co-benefits of forest-based climate change mitigation in Europe.

Climate change is a pressing global challenge with profound implications for human health. Forest-based climate change mitigation strategies, such as afforestation, reforestation, and sustainable forest management, offer promising solutions to mitigate climate change and simultaneously yield substantial co-benefits for human health. The objective of this scoping review was to examine research trends related to the interdisciplinary nexus between forests as carbon sinks and human health co-benefits. We developed a conceptual framework model, supporting the inclusion of exposure pathways, such as recreational opportunities or aesthetic experiences, in the co-benefit context. We used a scoping review methodology to identify the proportion of European research on forest-based mitigation strategies that acknowledge the interconnection between mitigation strategies and human impacts. We also aimed to assess whether synergies and trade-offs between forest-based carbon sink capacity and human co-benefits has been analysed and quantified. From the initial 4,062 records retrieved, 349 reports analysed European forest management principles and factors related to climate change mitigation capacity. Of those, 97 studies acknowledged human co-benefits and 13 studies quantified the impacts on exposure pathways or health co-benefits and were included for full review. Our analysis demonstrates that there is potential for synergies related to optimising carbon sink capacity together with human co-benefits, but there is currently a lack of holistic research approaches assessing these interrelationships. We suggest enhanced interdisciplinary efforts, using for example multideterminant modelling approaches, to advance evidence and understanding of the forest and health nexus in the context of climate change mitigation.

Endoscopic 5-Aminolevulinic Acid-Induced Fluorescence-Guided Intraparenchymal Brain Tumor Resection-Can the Endoscope Detect More Fluorescence Than the Microscope?

OBJECTIVES: Using a laboratory-based optical setup, we show that 5-aminolevulinic acid (5ALA) fluorescence is better detected using the endoscope than the microscope. Furthermore, we present our case series of fully endoscopic 5ALA-guided resection of intraparenchymal tumors. METHODS: A Zeiss Pentero microscope was compared with the Karl Storz Hopkins endoscope. The spectra and intensity of each blue light source were measured. Quantitative fluorescence detection thresholds were measured using a spectrometer. Subjective fluorescence detection thresholds were measured by 6 blinded neuro-oncology surgeons. Clinical data were prospectively collected for all consecutive cases of fully endoscopic 5ALA-guided resection of intraparenchymal tumors between 2012 and 2023. RESULTS: The intensity of blue light on the sample was greater for the endoscope than the microscope at working distances less than 20 mm. The quantitative fluorescence detection thresholds were lower for the endoscope than the microscope at both 30-/10-mm working distances. Fluorescence detection threshold was 0.65%-0.80% relative 4-dicyanomethylene-2-methyl-6-p-dimethylaminostyryl-4H-pyranthe concentration (3.20 × 10-7 to 3.94 × 10-7mol/dm-3) for the microscope, 0.40%-0.55% relative concentrations (1.97 × 10-7 to 2.71 × 10-7mol/dm-3) for the endoscope at 30 mm, and 0.15%-0.30% relative concentrations (7.40 × 10-8 to 1.48 × 10-7mol/dm-3) for the endoscope at 10 mm. In total, 49 5ALA endoscope-assisted brain tumor resections were carried out on 45 patients (mean age = 41 years, male = 28). Greater than 95% resection was achieved in 80% of cases and gross total resection in 42%. Gross total resection was achieved in 100% of tumors in noneloquent locations. There was 1 new neurologic deficit. CONCLUSIONS: The endoscope provides enhanced visualization/detection of 5ALA-induced fluorescence compared with the microscope. 5ALA endoscopic-assisted resection of intraparenchymal tumors is safe and feasible.

Incidence and Risk Factors for ICU-Associated Delirium in the Alert Geriatric Trauma Population.

BACKGROUND: This study analyzed the overall incidence of delirium, comorbid conditions, injury patterns, and pharmacological risk factors for the development of delirium in an alert, geriatric trauma population. METHODS: IRB-approved, prospective, consecutive cohort series at two Southeastern Level 1 trauma centers from June 11 to August 15, 2023. Delirium was assessed using the Confusion Assessment Method (CAM) score. Comorbidities and medications were detailed from electronic medical records. Inclusion criteria: age ≥55, GCS ≥14, and ICU admission for trauma. Patients on a ventilator were excluded. Data was analyzed using SPSS version 28 (Armonk, NY: IBM Corp). RESULTS: In total, 196 patients met inclusion criteria. Incidences of delirium for Hospital 1 (n = 103) and Hospital 2 (n = 93) were 15.5% and 12.9%, respectively, with an overall incidence of 14.3% and with no statistical differences between hospitals (P = .599). CAD, CKD, dementia, stroke history, and depression were statistically significant risk factors for developing delirium during ICU admission. Inpatient SSRI/SNRIs, epinephrine/norepinephrine, and lorazepam were significant risk factors. Injury patterns, operative intervention, and use of lidocaine infusions and gabapentin were not statistically significant in delirium development. Using binary linear regression (BLR) analysis, independent risk factors for delirium were dementia, any stage CKD, home SSRI/SRNI prescription, any spine injury and cerebrovascular disease, or injury. DISCUSSION: Comorbidities of CAD, CHF, CKD, and depression, and these medications: home lorazepam and ICU epinephrine/norepinephrine statistically are more common in patients developing delirium. Dementia, CKD, home SSRI/SRNI and stroke/cerebrovascular disease/injury, and spine injuries are independent predictors by BLR.

The feasibility and acceptability of an app-based intervention with brief behavioural support (APPROACH) to promote brisk walking in people diagnosed with breast, prostate and colorectal cancer in the UK.

INTRODUCTION: Increased moderate to vigorous physical activity (MVPA) can improve clinical and psychosocial outcomes for people living with and beyond cancer (LWBC). This study aimed to assess the feasibility and acceptability of trial procedures in a pilot randomised controlled trial (RCT) of a theory-driven app-based intervention with behavioural support focused on promoting brisk walking (a form of MVPA) in people LWBC (APPROACH). METHODS: Participants diagnosed with breast, prostate or colorectal cancer were recruited from a single UK hospital site. Assessments at baseline and 3 months included online questionnaires, device-measured brisk walking (activPAL accelerometer) and self-reported weight and height. Participants were randomised to intervention or control (care as usual). The intervention comprised a non-cancer-specific app to promote brisk walking (National Health Service 'Active 10') augmented with print information about habit formation, a walking planner and two behavioural support telephone calls. Feasibility and acceptability of trial procedures were explored. Initial estimates for physical activity informed a power calculation for a phase III RCT. A preliminary health economics analysis was conducted. RESULTS: Of those medically eligible, 369/577 (64%) were willing to answer further eligibility questions and 90/148 (61%) of those eligible were enrolled. Feasibility outcomes, including retention (97%), assessment completion rates (>86%) and app download rates in the intervention group (96%), suggest that the trial procedures are acceptable and that the intervention is feasible. The phase III RCT will require 472 participants to be randomised. As expected, the preliminary health economic analyses indicate a high level of uncertainty around the cost-effectiveness of the intervention. CONCLUSIONS: This pilot study demonstrates that a large trial of the brisk walking intervention with behavioural support is both feasible and acceptable to people LWBC. The results support progression onto a confirmatory phase III trial to determine the efficacy and cost-effectiveness of the intervention.

Proteome-scale tissue mapping using mass spectrometry based on label-free and multiplexed workflows.

Multiplexed bimolecular profiling of tissue microenvironment, or spatial omics, can provide deep insight into cellular compositions and interactions in both normal and diseased tissues. Proteome-scale tissue mapping, which aims to unbiasedly visualize all the proteins in whole tissue section or region of interest, has attracted significant interest because it holds great potential to directly reveal diagnostic biomarkers and therapeutic targets. While many approaches are available, however, proteome mapping still exhibits significant technical challenges in both protein coverage and analytical throughput. Since many of these existing challenges are associated with mass spectrometry-based protein identification and quantification, we performed a detailed benchmarking study of three protein quantification methods for spatial proteome mapping, including label-free, TMT-MS2, and TMT-MS3. Our study indicates label-free method provided the deepest coverages of ~3500 proteins at a spatial resolution of 50 µm and the largest quantification dynamic range, while TMT-MS2 method holds great benefit in mapping throughput at >125 pixels per day. The evaluation also indicates both label-free and TMT-MS2 provide robust protein quantifications in terms of identifying differentially abundant proteins and spatially co-variable clusters. In the study of pancreatic islet microenvironment, we demonstrated deep proteome mapping not only enables to identify protein markers specific to different cell types, but more importantly, it also reveals unknown or hidden protein patterns by spatial co-expression analysis.

Digital spatial profiling identifies molecular changes involved in development of colitis-associated colorectal cancer.

Objective: Chronic colonic inflammation seen in inflammatory bowel disease (IBD) is a risk factor for colorectal cancer (CRC). Colitis-associated cancers (CAC) are molecularly different from sporadic CRC. This study aimed to evaluate spatially defined molecular changes associated with neoplastic progression to identify mechanisms of action and potential biomarkers for prognostication. Design: IBD patients who had undergone colectomy for treatment of their IBD or dysplasia were identified from an institutional database. Formalin-fixed paraffin embedded samples from areas of normal, inflamed, dysplastic and adenocarcinoma tissue were identified for digital spatial profiling using the Nanostring GeoMx™ Cancer Transcriptome Atlas. RNA expression and quantification of 1812 genes was measured and analysed in a spatial context to compare differences in gene expression. Results: Sixteen patients were included, nine patients had CAC, two had dysplasia only and five had colitis only. Significant, step-wise differences in gene expression were seen between tissue types, mainly involving progressive over-expression of collagen genes associated with stromal remodelling. Similarly, MYC over-expression was associated with neoplastic progression. Comparison of normal and inflamed tissue from patients who progressed to those who did not also showed significant differences in immune-related genes, including under-expression of thte chemokines CCL18, CCL25 and IL-R7, as well as CD3, CD6 and lysozyme. The known oncogene CD24 was significantly overexpressed. Conclusion: Both tissue types and patient groups are molecularly distinguishable on the basis of their gene expression patterns. Further prospective work is necessary to confirm these differences and establish their clinical significance and potential utility as biomarkers.

Systematic review of social determinants of childhood immunisation in low- and middle-income countries and equity impact analysis of childhood vaccination coverage in Nigeria.

BACKGROUND: Nigeria has a high proportion of the world's underimmunised children. We estimated the inequities in childhood immunisation coverage associated with socioeconomic, geographic, maternal, child, and healthcare characteristics among children aged 12-23 months in Nigeria using a social determinants of health perspective. METHODS: We conducted a systematic review to identify the social determinants of childhood immunisation associated with inequities in vaccination coverage among low- and middle-income countries. Using the 2018 Nigeria Demographic and Health Survey (DHS), we conducted multiple logistic regression to estimate the association between basic childhood vaccination coverage (1-dose BCG, 3-dose DTP-HepB-Hib (diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type B), 3-dose polio, and 1-dose measles) and socioeconomic, geographic, maternal, child, and healthcare characteristics in Nigeria. RESULTS: From the systematic review, we identified the key determinants of immunisation to be household wealth, religion, and ethnicity for socioeconomic characteristics; region and place of residence for geographic characteristics; maternal age at birth, maternal education, and household head status for maternal characteristics; sex of child and birth order for child characteristics; and antenatal care and birth setting for healthcare characteristics. Based of the 2018 Nigeria DHS analysis of 6,059 children aged 12-23 months, we estimated that basic vaccination coverage was 31% (95% CI: 29-33) among children aged 12-23 months, whilst 19% (95% CI:18-21) of them were zero-dose children who had received none of the basic vaccines. After controlling for background characteristics, there was a significant increase in the odds of basic vaccination by household wealth (AOR: 3.21 (2.06, 5.00), p < 0.001) for the wealthiest quintile compared to the poorest quintile, antenatal care of four or more antenatal care visits compared to no antenatal care (AOR: 2.87 (2.21, 3.72), p < 0.001), delivery in a health facility compared to home births (AOR 1.32 (1.08, 1.61), p = 0.006), relatively older maternal age of 35-49 years compared to 15-19 years (AOR: 2.25 (1.46, 3.49), p < 0.001), and maternal education of secondary or higher education compared to no formal education (AOR: 1.79 (1.39, 2.31), p < 0.001). Children of Fulani ethnicity in comparison to children of Igbo ethnicity had lower odds of receiving basic vaccinations (AOR: 0.51 (0.26, 0.97), p = 0.039). CONCLUSIONS: Basic vaccination coverage is below target levels for all groups. Children from the poorest households, of Fulani ethnicity, who were born in home settings, and with young mothers with no formal education nor antenatal care, were associated with lower odds of basic vaccination in Nigeria. We recommend a proportionate universalism approach for addressing the immunisation barriers in the National Programme on Immunization of Nigeria.

Spatial top-down proteomics for the functional characterization of human kidney.

Background: The Human Proteome Project has credibly detected nearly 93% of the roughly 20,000 proteins which are predicted by the human genome. However, the proteome is enigmatic, where alterations in amino acid sequences from polymorphisms and alternative splicing, errors in translation, and post-translational modifications result in a proteome depth estimated at several million unique proteoforms. Recently mass spectrometry has been demonstrated in several landmark efforts mapping the human proteoform landscape in bulk analyses. Herein, we developed an integrated workflow for characterizing proteoforms from human tissue in a spatially resolved manner by coupling laser capture microdissection, nanoliter-scale sample preparation, and mass spectrometry imaging. Results: Using healthy human kidney sections as the case study, we focused our analyses on the major functional tissue units including glomeruli, tubules, and medullary rays. After laser capture microdissection, these isolated functional tissue units were processed with microPOTS (microdroplet processing in one-pot for trace samples) for sensitive top-down proteomics measurement. This provided a quantitative database of 616 proteoforms that was further leveraged as a library for mass spectrometry imaging with near-cellular spatial resolution over the entire section. Notably, several mitochondrial proteoforms were found to be differentially abundant between glomeruli and convoluted tubules, and further spatial contextualization was provided by mass spectrometry imaging confirming unique differences identified by microPOTS, and further expanding the field-of-view for unique distributions such as enhanced abundance of a truncated form (1-74) of ubiquitin within cortical regions. Conclusions: We developed an integrated workflow to directly identify proteoforms and reveal their spatial distributions. Where of the 20 differentially abundant proteoforms identified as discriminate between tubules and glomeruli by microPOTS, the vast majority of tubular proteoforms were of mitochondrial origin (8 of 10) where discriminate proteoforms in glomeruli were primarily hemoglobin subunits (9 of 10). These trends were also identified within ion images demonstrating spatially resolved characterization of proteoforms that has the potential to reshape discovery-based proteomics because the proteoforms are the ultimate effector of cellular functions. Applications of this technology have the potential to unravel etiology and pathophysiology of disease states, informing on biologically active proteoforms, which remodel the proteomic landscape in chronic and acute disorders.

Queering food security research: A critical analysis of 2SLGBTQ+ People's experiences of food insecurity in Toronto during the COVID-19 pandemic.

INTRODUCTION: Household food insecurity (HFI), stress, isolation, and discrimination are major determinants of health that disproportionately affect 2SLGBTQ + people. The COVID-19 pandemic potentially exacerbated these inequities. This study investigates HFI rates among 2SLGBTQ + adults living in diverse household conditions during the pandemic and explores the idea that heteronormative conceptions of the "household" may affect measurement of HFI. METHODS: Cross-sectional survey responses were collected from 437 self-identified 2SLGBTQ + people from Toronto, Canada between March and July 2021. The survey measured HFI, sexual/gender identities, socio-demographic factors, household composition, and psycho-social stress/distress. Multinomial logistic regression was used to assess variation in odds of marginal, moderate, and severe HFI in relation to sexual/gender identities, household composition, psycho-social distress, and socio-demographic covariates. RESULTS: Forty-two percent of respondents reported some level of HFI, with severe HFI higher among respondents who were bisexual, transgender/gender diverse, and/or assigned-female-at-birth. Living alone was associated with decreased odds of reporting marginal HFI but increased odds of moderate or severe HFI compared to living with a partner, family, or roommates; living with children was associated with decreased odds of both marginal and severe HFI. One indicator of psycho-social distress (perceived discrimination) was associated with higher odds of all levels of HFI, while the other (isolation) was associated with decreased odds of marginal HFI. CONCLUSION: These findings highlight the high prevalence of HFI linked with discrimination among 2SLGBTQ + individuals during the pandemic. The complicated results regarding household composition and social isolation may suggest a need to revise definitions of the household when measuring, monitoring, and seeking to mitigate HFI in 2SLGBTQ + communities.

Immunohistochemistry screening for TP53 mutation in myeloid neoplasms in AZF-fixed bone marrow biopsies.

TP53 mutational status in myeloid neoplasms is prognostic and in acute myeloid leukaemia (AML) may lead to alternative induction therapy; therefore, rapid assessment is necessary for precision treatment. Assessment of multiple prognostic genes by next generation sequencing in AML is standard of care, but the turn-around time often cannot support rapid clinical decision making. Studies in haematological neoplasms suggest p53 immunohistochemistry (IHC) correlates with TP53 mutational status, but they have used variable criteria to define TP53 overexpression. p53 IHC was performed and interpreted on AZF-fixed, acid decalcified bone marrow biopsies on 47 cases of clonal myeloid neoplasms with TP53 mutations between 2016 and 2019 and 16 control samples. Results were scored by manual and digital analysis. Most TP53-mutated cases (81%) overexpressed p53 by digital analysis and manual analysis gave similar results. Among the nine TP53-mutated IHC-negative cases, seven (78%) were truncating mutations and two (22%) were single-hit missense mutations. Using a digital cut-off of at least 3% ≥1+ positive nuclei, the sensitivity and specificity are 81% and 100%; cases with loss-of-function mutations were more likely to be negative. In this cohort, p53 immunopositivity correlated with TP53 mutational status, especially missense mutations, with excellent specificity. Truncating TP53 mutations explain most IHC-negative cases, impacting the sensitivity. We demonstrate that p53 IHC can screen for TP53 mutations allowing quicker treatment decisions for most patients. However, not all patients will be identified, so molecular studies are required. Furthermore, cut-offs for positivity vary in the literature, consequently laboratories should independently validate their processes before adopting p53 IHC for clinical use. p53 IHC performs well to screen for TP53 mutations in AZF-fixed bone marrow. Performance in our setting differs from the literature, which shows variability of pre-analytic factors and cut-offs used to screen for TP53 mutations. Each laboratory should validate p53 IHC to screen for TP53 mutations in their unique setting.

Nutritional care pathways in cancer patients with malignant bowel obstruction: A retrospective multi-centre study.

INTRODUCTION: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO. METHODS: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression. RESULTS: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups. CONCLUSION: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life.

A Flexible and Efficient Approach to Missing Transverse Momentum Reconstruction.

Missing transverse momentum is a crucial observable for physics at hadron colliders, being the only constraint on the kinematics of "invisible" objects such as neutrinos and hypothetical dark matter particles. Computing missing transverse momentum at the highest possible precision, particularly in experiments at the energy frontier, can be a challenging procedure due to ambiguities in the distribution of energy and momentum between many reconstructed particle candidates. This paper describes a novel solution for efficiently encoding information required for the computation of missing transverse momentum given arbitrary selection criteria for the constituent reconstructed objects. Pileup suppression using information from both the calorimeter and the inner detector is an integral component of the reconstruction procedure. Energy calibration and systematic variations are naturally supported. Following this strategy, the ATLAS Collaboration has been able to optimise the use of missing transverse momentum in diverse analyses throughout Runs 2 and 3 of the Large Hadron Collider and for future analyses.

Asian-White disparities in obstetric anal sphincter injury: a systematic review and meta-analysis.

OBJECTIVE: Obstetrical anal sphincter injury describes a severe injury to the perineum and perianal muscles after birth. Obstetrical anal sphincter injury occurs in approximately 4.4% of vaginal births in the United States; however, racial and ethnic inequities in the incidence of obstetrical anal sphincter injury have been shown in several high-income countries. Specifically, an increased risk of obstetrical anal sphincter injury in individuals who identify as Asian vs those who identify as White has been documented among residents of the United States, Australia, Canada, Western Europe, and the Scandinavian countries. The high rates of obstetrical anal sphincter injury among the Asian diaspora in these countries are higher than obstetrical anal sphincter injury rates reported among Asian populations residing in Asia. A systematic review and meta-analysis of studies in high-income, non-Asian countries was conducted to further evaluate this relationship. DATA SOURCES: MEDLINE, Ovid, Embase, EmCare, and the Cochrane databases were searched from inception to March 2023 for original research studies. STUDY ELIGIBILITY CRITERIA: Observational studies using keywords and controlled vocabulary terms related to race, ethnicity and obstetrical anal sphincter injury. All observational studies, including cross-sectional, case-control, and cohort were included. 2 reviewers followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Meta-analysis of Observational Studies in Epidemiology recommendations. METHODS: Meta-analysis was performed using RevMan (version 5.4; Cochrane Collaboration, London, United Kingdom) for dichotomous data using the random effects model and the odds ratios as effect measures with 95% confidence intervals. Subgroup analysis was performed among Asian subgroups. The risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal tools. Meta-regression was used to determine sources of between-study heterogeneity. Results: A total of 27 studies conducted in 7 countries met the inclusion criteria encompassing 2,337,803 individuals. The pooled incidence of obstetrical anal sphincter injury was higher among Asian individuals than White individuals (pooled odds ratio, 1.64; 95% confidence interval, 1.48-1.80). Subgroup analyses showed that obstetrical anal sphincter injury rates were highest among South Asians and among population-based vs hospital-based studies. Meta-regression showed that moderate heterogeneity remained even after accounting for differences in studies by types of Asian subgroups included, study year, mode of delivery included, and study setting. Conclusion: Obstetrical anal sphincter injury is more frequent among Asian versus white birthing individuals in multiple high-income, non-Asian countries. Qualitative and quantitative research to elucidate underlying causal mechanisms responsible for this relationship are warranted.

Cluster-Enhanced Nanopore Sensing of Ovarian Cancer Marker Peptides in Urine.

The development of novel methodologies that can detect biomarkers from cancer or other diseases is both a challenge and a need for clinical applications. This partly motivates efforts related to nanopore-based peptide sensing. Recent work has focused on the use of gold nanoparticles for selective detection of cysteine-containing peptides. Specifically, tiopronin-capped gold nanoparticles, trapped in the cis-side of a wild-type α-hemolysin nanopore, provide a suitable anchor for the attachment of cysteine-containing peptides. It was recently shown that the attachment of these peptides onto a nanoparticle yields unique current signatures that can be used to identify the peptide. In this article, we apply this technique to the detection of ovarian cancer marker peptides ranging in length from 8 to 23 amino acid residues. It is found that sequence variability complicates the detection of low-molecular-weight peptides (<10 amino acid residues), but higher-molecular-weight peptides yield complex, high-frequency current fluctuations. These fluctuations are characterized with chi-squared and autocorrelation analyses that yield significantly improved selectivity when compared to traditional open-pore analysis. We demonstrate that the technique is capable of detecting the only two cysteine-containing peptides from LRG-1, an emerging protein biomarker, that are uniquely present in the urine of ovarian cancer patients. We further demonstrate the detection of one of these LRG-1 peptides spiked into a sample of human female urine.

Droplet-based optical trapping for cell separation in mock forensic samples.

Optical tweezers have a wide range of uses for mechanical manipulation of objects in the microscopic range. This includes both living and static cells in a variety of biomedical and research applications. Single-focus optical tweezers, formed by focusing a laser beam through a high numerical aperture immersion objective, create a significant force, which enables controlled transport of a variety of different cell types and morphologies in three dimensions. Optical tweezers have been previously reported to capture and separate spermatozoa from a reconstituted simulated postcoital sample. We report herein the development of a simplified, more efficient cell transfer protocol that can separate and isolate both spermatozoa as well as leukocytes, with similar efficiencies as those previously reported. The new cell transfer method was used to separate sperm cells from a reconstituted mixture of spermatozoa and vaginal epithelial cells, with complete STR profiles developed from 50 cells with little evidence of contribution from the female contributor to the mixture. This modified protocol was then used to separate 21 samples of enriched leukocytes, with trapped cells ranging from 5 to 22 cells. Complete STR profiles were developed from as few as 10 leukocytes. Thus, with minimal sample preparation and a short trapping time, this method has the potential to provide an alternative to traditional differential extraction methods for separation of sperm:nonsperm mixtures while also providing versatility for separation of cells with differing morphologies.

Partner Exclusion from Childbirth During COVID-19 in Canada: Implications for Theory and Policy.

We explore partner exclusion from perinatal care in Canada during the COVID-19 pandemic. Participants' narratives show that pregnant couples frame partner presence as a [human] right that was denied, and articulated this as denial of the "right to experience" and the "right to care." These restrictions deprived birth partners and families of an experience that is important to them, and represent a repudiation of the resurgence of birth as a social event which entails valued forms of care. We show that the medical establishment's commitment to partner presence during perinatal care is weak, although caring masculinity is normative.

Comprehensive Assessment of Nutrition and Dietary Influences in Hypermobile Ehlers-Danlos Syndrome-A Cross-sectional Study.

INTRODUCTION: Disorders of gut-brain interaction (DGBI) are common in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder (hEDS/HSD). Food is a known trigger for DGBI symptoms, which often leads to dietary alterations and, increasingly, nutrition support. We aimed to explore dietary behaviors and influencing factors in patients with hEDS/HSD. METHODS: In a cross-sectional study, patients with hEDS/HSD were recruited from Ehlers-Danlos Support UK (nontertiary) and tertiary neurogastroenterology clinics to complete questionnaires characterizing the following: dietary behaviors, nutrition support, DGBI (Rome IV), gastrointestinal symptoms, anxiety, depression, avoidant restrictive food intake disorder (ARFID), mast cell activation syndrome, postural tachycardia syndrome (PoTS), and quality of life. We used stepwise logistic regression to ascertain which factors were associated with dietary behaviors and nutrition support. RESULTS: Of 680 participants (95% female, median age 39 years), 62.1% altered their diet in the last year and 62.3% regularly skipped meals. Altered diet was associated with the following: reflux symptoms ( P < 0.001), functional dyspepsia ( P = 0.008), reported mast cell activation syndrome ( P < 0.001), and a positive screen for ARFID, specifically fear of eating and low interest ( P < 0.001). Approximately 31.7% of those who altered their diet required nutrition support. The strongest predictor of requiring nutrition support was a positive screen for ARFID, specifically fear of eating (OR: 4.97, 95% CI: 2.09-11.8, P < 0.001). DISCUSSION: Altered diet is very common in the patients with hEDS/HSD we studied and influenced by functional dyspepsia, reflux symptoms, and ARFID. Those with ARFID have a 4-fold increased risk of requiring nutrition support, and therefore, it is paramount that psychological support is offered in parallel with dietary support in the management of DGBI in hEDS/HSD.