Redistribution of lamina-associated domains reshapes binding of pioneer factor FOXA2 in development of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus and the elderly, impacting 40% of individuals over 70. Regulation of heterochromatin at the nuclear lamina has been associated with aging and age-dependent metabolic changes. We previously showed that changes at the lamina in aged hepatocytes and laminopathy models lead to redistribution of lamina-associated domains (LADs), opening of repressed chromatin, and up-regulation of genes regulating lipid synthesis and storage, culminating in fatty liver. Here, we test the hypothesis that change in the expression of lamina-associated proteins and nuclear shape leads to redistribution of LADs, followed by altered binding of pioneer factor FOXA2 and by up-regulation of lipid synthesis and storage, culminating in steatosis in younger NAFLD patients (aged 21-51). Changes in nuclear morphology alter LAD partitioning and reduced lamin B1 signal correlate with increased FOXA2 binding before severe steatosis in young mice placed on a western diet. Nuclear shape is also changed in younger NAFLD patients. LADs are redistrubted and lamin B1 signal decreases similarly in mild and severe steatosis. In contrast, FOXA2 binding is similar in normal and NAFLD patients with moderate steatosis and is repositioned only in NAFLD patients with more severe lipid accumulation. Hence, changes at the nuclear lamina reshape FOXA2 binding with progression of the disease. Our results suggest a role for nuclear lamina in etiology of NAFLD, irrespective of aging, with potential for improved stratification of patients and novel treatments aimed at restoring nuclear lamina function.

Predictive factors influencing internal rotation following reverse total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is increasingly used as a treatment modality for various pathologies. The purpose of this review is to identify preoperative risk factors associated with loss of internal rotation (IR) after RTSA. METHODS: A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Ovid MEDLINE, Ovid Embase, and Scopus were queried. The inclusion criteria were as follows: articles in English language, minimum 1-year follow-up postoperatively, study published after 2012, a minimum of 10 patients in a series, RTSA surgery for any indication, and explicitly reported IR. The exclusion criteria were as follows: articles whose full text was unavailable or that were unable to be translated to English language, a follow-up of less than 1 year, case reports or series of less than 10 cases, review articles, studies in which tendon transfers were performed at the time of surgery, procedures that were not RTSA, and studies in which the range of motion in IR was not reported. RESULTS: The search yielded 3792 titles, and 1497 duplicate records were removed before screening. Ultimately, 16 studies met the inclusion criteria with a total of 5124 patients who underwent RTSA. Three studies found that poor preoperative functional IR served as a significant risk factor for poor postoperative IR. Eight studies addressed the impact of subscapularis, with 4 reporting no difference in IR based on subscapularis repair and 4 reporting significant improvements with subscapularis repair. Among studies with sufficient power, BMI was found to be inversely correlated with degree of IR after RTSA. Preoperative opioid use was found to negatively affect IR. Other studies showed that glenoid retroversion, component lateralization, and individualized component positioning affected postoperative IR. CONCLUSIONS: This study found that preoperative IR, individualized implant version, preoperative opioid use, increased body mass index and increased glenoid lateralization were all found to have a significant impact on IR after RTSA. Studies that analyzed the impact of subscapularis repair reported conflicting results.

The Fate of Unresurfaced Patellae in Contemporary Total Knee Arthroplasty: Early to Midterm Results.

BACKGROUND: Leaving the patella unresurfaced in total knee arthroplasty (TKA) has increased significantly over the past decade in the United States, likely due to modern patella-friendly implants, complications with resurfacing, and the knowledge that historical studies were scientifically confounded. This study evaluated revision-free survivorship out to 8.5 years in a cohort of contemporary primary TKAs with patella-friendly femoral components and unresurfaced patellae. METHODS: A total of 1,053 consecutive primary TKAs with unresurfaced patellae were retrospectively reviewed. A selective patellar nonresurfacing protocol was used for all cases. Kaplan-Meier survivorship estimates were calculated based on patellar revision and the latest follow-up. An aggressive lateral patellar facetectomy was performed in 78% (823 of 1,053) of cases. The cohort was 62% women and 43% American Society of Anesthesiologists physical status classification I or II with a mean age and body mass index of 65 years (range, 35 to 94) and 35 kg/m2 (range, 18 to 65), respectively. RESULTS: A total of 4 (0.4%, 4 of 1,053) unresurfaced patellae were revised. Three were resurfaced as part of other procedures: 2 for global instability and one for aseptic loosening at a mean of 1.6 years; and one patella was resurfaced by an outside surgeon for unexplained pain. The all-cause revision-free survivorship estimate specifically related to the patella was 98.9% (95% confidence interval, 98 to 100) out to 8.5 years. No significant difference in survivorship was related to patellae with or without a lateral patellar facetectomy (99.5 versus 98.1%, P ≥ .191); however, 3 of 4 patellar revisions occurred in TKAs without a lateral patellar facetectomy (P = .035). CONCLUSIONS: The results of this study demonstrate excellent revision-free survivorship related to unresurfaced patellae, particularly when a lateral facetectomy was performed. These early to midterm results using modern patella-friendly femoral components are promising and comparable to resurfaced patellae in the literature. LEVEL OF EVIDENCE: IV.

Predictors of Plastic Surgery Applicant Success: An Analysis of the Texas STAR Database.

INTRODUCTION: Integrated plastic surgery residency is one of the most competitive medical specialties. Although previous studies have surveyed integrated plastic surgery residency program directors regarding desired applicant characteristics, there is a paucity of literature assessing detailed application characteristics and reported match outcomes from applicants in recent application cycles. This study examines application characteristics associated with matching into integrated plastic surgery residency from 2017 to 2023. METHODS: The authors accessed the Texas Seeking Transparency in Application to Residency database, which contains survey information from graduating medical students nationwide regarding residency application characteristics and specialties/programs to which applications were submitted. Characteristics of matched versus unmatched applicants between 2017 and 2023 were compared using χ 2 and 2-sided, independent t tests. Univariate logistic regression models were used to assess predictors of a successful match. RESULTS: A total of 381 integrated plastic surgery residency applicants responded to the Texas Seeking Transparency in Application to Residency survey from 2017 to 2023. Mean United States Medical Licensing Exam Step 2 CK scores; the number of away rotations, interview offers, and honored clerkships; and Alpha Omega Alpha membership rate were significantly associated with and predictive of matching. Preference signaling of programs was associated with an increased interview offer rate. CONCLUSIONS: Higher board examination scores, increasing numbers of honored clerkships, away rotations, and Alpha Omega Alpha membership were identified as statistically significant predictors of matching into integrated plastic surgery residency. Prospective applicants should use this information to help guide their efforts in these areas that appear to be associated with a successful transition to residency.

Loneliness and sense of community are not two sides of the same coin: Identifying different determinants using the 2019 Nova Scotia Quality of Life data.

The purpose of this study was to explore the relative importance of lifestyle factors and living conditions when predicting loneliness and sense of community (SOC) in a representative sample of 12,871 participants from Nova Scotia collected in 2019. Using multiple regression and measures of relative importance based on the Lindeman, Merenda and Gold (lmg) method, we identified which variables are most important to predicting measures of loneliness and SOC. Twenty-two predictors accounted for 46% of the variance in SOC and the top 10 predictors accounted for 36% of the variance: satisfaction with quality of the natural environment in the neighborhood (ri = 0.09), life satisfaction (ri = 0.05), number of neighbors one can rely on (ri = 0.05), confidence in institutions (ri = 0.05), feeling better off due to government policy or programming (ri = 0.04), feeling safe walking in neighborhood after dark (ri = 0.03), mental health (ri = 0.02), number of friends one can rely on (ri = 0.02), volunteering (ri = 0.02), and perceptions of time adequacy (ri = 0.02). Only six of these variables were also the top predictors of loneliness. These results show that both community- and individual-level variables are substantial predictors of social well-being. The effect sizes differ between models, which suggests that there may be important predictors of loneliness that we have not accounted for. This study may inform community-level programming and policy that seeks to promote social well-being for individuals and their communities.

Benchmarking of protein interaction databases for integration with manually reconstructed signalling network models.

Protein interaction databases are critical resources for network bioinformatics and integrating molecular experimental data. Interaction databases may also enable construction of predictive computational models of biological networks, although their fidelity for this purpose is not clear. Here, we benchmark protein interaction databases X2K, Reactome, Pathway Commons, Omnipath and Signor for their ability to recover manually curated edges from three logic-based network models of cardiac hypertrophy, mechano-signalling and fibrosis. Pathway Commons performed best at recovering interactions from manually reconstructed hypertrophy (137 of 193 interactions, 71%), mechano-signalling (85 of 125 interactions, 68%) and fibroblast networks (98 of 142 interactions, 69%). While protein interaction databases successfully recovered central, well-conserved pathways, they performed worse at recovering tissue-specific and transcriptional regulation. This highlights a knowledge gap where manual curation is critical. Finally, we tested the ability of Signor and Pathway Commons to identify new edges that improve model predictions, revealing important roles of protein kinase C autophosphorylation and Ca2+ /calmodulin-dependent protein kinase II phosphorylation of CREB in cardiomyocyte hypertrophy. This study provides a platform for benchmarking protein interaction databases for their utility in network model construction, as well as providing new insights into cardiac hypertrophy signalling. KEY POINTS: Protein interaction databases are used to recover signalling interactions from previously developed network models. The five protein interaction databases benchmarked recovered well-conserved pathways, but did poorly at recovering tissue-specific pathways and transcriptional regulation, indicating the importance of manual curation. We identify new signalling interactions not previously used in the network models, including a role for Ca2+ /calmodulin-dependent protein kinase II phosphorylation of CREB in cardiomyocyte hypertrophy.

Identifying patterns of neurocognitive dysfunction through direct comparison of children with leukemia, central nervous system tumors, and sickle cell disease.

PURPOSE: To quantify and compare the magnitude and type of neurocognitive dysfunction in at-risk children with central nervous system (CNS) tumors, acute lymphoblastic leukemia (ALL), and sickle cell disease (SCD) using a common instrument and metric to directly compare these groups with each other. METHODS: Fifty-three participants between the ages of 7 and 12 years (n = 27 ALL, n = 11 CNS tumor, n = 15 SCD) were enrolled and assessed using the NIH Toolbox Cognition Battery (NIHTCB). Participants with ALL or CNS tumor were 0-18 months posttherapy, while participants with SCD possessed the SS or Sß0 genotype, took hydroxyurea, and had no known history of stroke. RESULTS: Independent sample t-tests showed that participants with ALL and CNS tumor experienced greatest deficits in processing speed (ALL d = -0.96; CNS tumor d = -1.2) and inhibitory control and attention (ALL d = -0.53; CNS tumor d = -0.97) when compared with NIHTCB normative data. Participants with SCD experienced deficits in cognitive flexibility only (d = -0.53). Episodic memory was relatively spared in all groups (d = -0.03 to -0.32). There were no significant differences in function when groups were compared directly with each other by analysis of variance. CONCLUSIONS: Use of a common metric to quantify the magnitude and type of neurocognitive dysfunction across at-risk groups of participants by disease shows that participants perform below age-expected norms in multiple domains and experience dysfunction differently than one another. This approach highlights patterns of dysfunction that can inform disease- and domain-specific interventions.

Associations of potential ADRD plasma biomarkers in cognitively normal volunteers.

INTRODUCTION: This study examined the relationships between 13 novel blood-plasma biomarkers and dementia-related demographic and health factors in a cohort of 237 cognitively normal research volunteers whose average age was ≈82 years and who were 63% female. METHODS: We regressed each biomarker on selected covariates to explore the associations between the biomarkers and selected factors to assess whether they may contribute to biomarker values. Post hoc sensitivity analyses were done with updated data and consistent variable sets for robustness and batch effects. RESULTS: Biomarker concentrations were largely not associated with demographics or health conditions, but some expected associations (e.g., apolipoprotein E [APOE] status with amyloid beta [Aß]42/Aß40) were observed. Post hoc results remained similar to those of the main analysis. DISCUSSION: The absence of strong associations between the biomarkers with age, gender, or medical conditions suggests that changes in these biomarkers, when observed, may be attributable to neuropathological changes. HIGHLIGHTS: Among N = 237 cognitively normal adults, we studied candidate Alzheimer's disease and related dementia (ADRD) plasma biomarkers. Biomarkers were largely not associated with demographic or health factors. Apolipoprotein E (APOE) status was associated with amyloid beta (Aß)42/Aß40 ratio. These results support hypotheses that plasma biomarkers are informative for ADRD.

Qualitative study exploring general dental practitioners' views of MIH and its management in the UK and Australia.

BACKGROUND: Molar-incisor hypomineralisation (MIH) is a prevalent condition, and how it is managed varies greatly between professional groups. AIM: To explore, and compare, the UK and Australian general dental practitioners' management of MIH in children. DESIGN: Face-to-face (remote) semistructured interviews were undertaken, using country-specific topic guides. Participants were purposively sampled and recruited through national conferences and research networks (eviDent Foundation and Northern Dental Practice Based Research Network). Interviews (from each country) were audio-recorded, transcribed verbatim and independently analysed using thematic analysis. RESULTS: Two major themes arose from the UK interviews: (i) decision-making complexities and understanding of treatment options and (ii) need for specialist input. The main Australian themes were (i) multidisciplinary approach to management supporting decision-making complexities and (ii) economic implications for care. Several difficulties, such as financial implications, multidisciplinary care and clinical decision-making, were identified as barriers to effectively managing MIH by GDPs in primary care. CONCLUSION: There are similarities and differences in the knowledge and management of MIH amongst UK and Australian nonspecialists. The different healthcare systems played a significant role in shaping how GDPs manage MIH with barriers relating to affordability, multidisciplinary care and clinical decision-making.

Subfascial/Intramuscular Dual-Plane Gluteal Implantation and Supplemental Fat Grafting: A Novel Technique for Buttock Augmentation.

BACKGROUND: Much debate exists within the current literature as to which plane is safest and most effective for gluteal implant buttock augmentation. A novel subfascial/intramuscular (SF/IM) dual-plane technique appears to combine the benefits of each plane. OBJECTIVES: The aim of this study was to describe our experience with SF/IM plane gluteal implantation, and to discuss its indications, efficacy, and safety, and offer recommendations on its proper use. METHODS: A retrospective chart review was conducted of 175 consecutive cases of gluteal augmentation with solid silicone implants in the SF/IM pocket, with and without supplemental autologous fat transfer. Outcomes from all patients were analyzed to determine the rate of complication and need for surgical revision. RESULTS: In 175 cases of bilateral buttock augmentation with gluteal implantation using the SF/IM pocket, the most common complication was infection. This complication was seen in 13 cases (7.43%), 7 (4%) of which were superficial and did not require surgical intervention. Other complications included dehiscence, seroma, capsular contracture, and implant migration. CONCLUSIONS: The SF/IM gluteal implantation, in combination with liposculpture and autologous fat transfer into the overlaying subcutaneous space, allows for a durable cosmetic augmentation of the buttocks in patients lacking sufficient volume for augmentation with fat transfer alone. This technique was found to have complication rates similar to those of other established augmentation techniques, as well the cosmetic advantages of a large, stable pocket with thick, soft tissue coverage of the inferior pole.

Whole-genome and transcriptome analysis enhances precision cancer treatment options.

BACKGROUND: Recent advances are enabling delivery of precision genomic medicine to cancer clinics. While the majority of approaches profile panels of selected genes or hotspot regions, comprehensive data provided by whole-genome and transcriptome sequencing and analysis (WGTA) present an opportunity to align a much larger proportion of patients to therapies. PATIENTS AND METHODS: Samples from 570 patients with advanced or metastatic cancer of diverse types enrolled in the Personalized OncoGenomics (POG) program underwent WGTA. DNA-based data, including mutations, copy number and mutation signatures, were combined with RNA-based data, including gene expression and fusions, to generate comprehensive WGTA profiles. A multidisciplinary molecular tumour board used WGTA profiles to identify and prioritize clinically actionable alterations and inform therapy. Patient responses to WGTA-informed therapies were collected. RESULTS: Clinically actionable targets were identified for 83% of patients, of which 37% of patients received WGTA-informed treatments. RNA expression data were particularly informative, contributing to 67% of WGTA-informed treatments; 25% of treatments were informed by RNA expression alone. Of a total 248 WGTA-informed treatments, 46% resulted in clinical benefit. RNA expression data were comparable to DNA-based mutation and copy number data in aligning to clinically beneficial treatments. Genome signatures also guided therapeutics including platinum, poly-ADP ribose polymerase inhibitors and immunotherapies. Patients accessed WGTA-informed treatments through clinical trials (19%), off-label use (35%) and as standard therapies (46%) including those which would not otherwise have been the next choice of therapy, demonstrating the utility of genomic information to direct use of chemotherapies as well as targeted therapies. CONCLUSIONS: Integrating RNA expression and genome data illuminated treatment options that resulted in 46% of treated patients experiencing positive clinical benefit, supporting the use of comprehensive WGTA profiling in clinical cancer care.

Dysregulated expression of the alternatively spliced variant mRNAs of the mu opioid receptor gene, OPRM1, in the medial prefrontal cortex of male human heroin abusers and heroin self-administering male rats.

Heroin, a mu agonist, acts through the mu opioid receptor. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, creating an array of splice variants that are conserved from rodent to humans. Increasing evidence suggests that these OPRM1 splice variants are pharmacologically important in mediating various actions of mu opioids, including analgesia, tolerance, physical dependence, rewarding behavior, as well as addiction. In the present study, we examine expression of the OPRM1 splice variant mRNAs in the medial prefrontal cortex (mPFC), one of the major brain regions involved in decision-making and drug-seeking behaviors, of male human heroin abusers and male rats that developed stable heroin-seeking behavior using an intravenous heroin self-administration (SA) model. The results show similar expression profiles among multiple OPRM1 splice variants in both human control subjects and saline control rats, illustrating conservation of OPRM1 alternative splicing from rodent to humans. Moreover, the expressions of several OPRM1 splice variant mRNAs were dysregulated in the postmortem mPFCs from heroin abusers compared to the control subjects. Similar patterns were observed in the rat heroin SA model. These findings suggest potential roles of the OPRM1 splice variants in heroin addiction that could be mechanistically explored using the rat heroin SA model.

Ancient DNA confirmation of lepromatous leprosy in a skeleton with concurrent osteosarcoma, excavated from the leprosarium of St. Mary Magdalen in Winchester, Hants., UK.

To establish a biological profile and disease aetiologies for one of four burials recovered during a Time Team dig at the St. Mary Magdalen leprosarium, Winchester, UK in AD 2000. Osteological techniques were applied to estimate age at death, biological sex, stature and pathology. Visual assessment of the material was supplemented by radiographic examination. Evidence for leprosy DNA was sought using ancient DNA (aDNA) analysis. The remains are those of a male individual excavated from a west-east aligned grave. The skeleton shows signs of two pathologies. Remodelling of the rhino-maxillary area and degenerative changes to small bones of the feet and reactive bone on the distal lower limbs suggest a multibacillary form of leprosy, whereas the right tibia and fibula show the presence of a primary neoplasm identified as an osteosarcoma. The aDNA study confirmed presence of Mycobacterium leprae in several skeletal elements, and the strain was genotyped to the 3I lineage, one of two main SNP types present in mediaeval Britain and ancestral to extant strains in America. This is a rare documentation of leprosy in association with a primary neoplasm.

Progression of infection and detection of Pseudoloma neurophilia in zebrafish Danio rerio Hamilton by PCR and histology.

Pseudoloma neurophilia is a critical threat to the zebrafish (Danio rerio) model, as it is the most common infectious agent found in research facilities. In this study, our objectives were two-fold: (1) compare the application of diagnostic tools for P. neurophilia and (2) track the progression of infection using PCR and histology. The first experiment showed that whole-body analysis by qPCR (WB-qPCR) can be a standardized process, providing a streamlined diagnostic protocol, without the need for extraction of specific tissues. Evaluating the course of infection in experimentally infected fish, we showed key dynamics in infection. Starting with a low dose exposure of 8000 spores/fish, the prevalence remained low until 92 days post-exposure (dpe), followed by a 30%-40% prevalence by histology or 40%-90% by PCR until the end of the experiment at 334 dpe. WB-qPCR positively detected infection in more fish than histology throughout the study, as WB-qPCR detected the parasite as early as 4 dpe, whereas it was undetected by histology until 92 dpe. We also added a second slide for histologic analyses, showing an increase in detection rate from 24% to 26% when we combined all data from our experiments, but this increase was not statistically significant.

Dominant Power and the Concept of Caste: Implications for Dentistry and Oral Health Inequality.

This paper explores the issues of caste and casteism in the U.S. as described by Pulitzer Prize winning journalist Isabel Wilkerson in her 2020 book "Caste: The Origin of Our Discontents". Wilkerson argues that a caste system not only exists in the U.S. but operates as a hidden force affecting social inequality. The paper draws on Wilkerson's work to explore caste as an analytical concept. It begins by defining caste and casteism in contrast with racism, the eight pillars of a caste system, the consequences of casteism, and the psychological drivers of casteism. The paper then applies to concept of caste to understanding power, dentistry, and oral health inequality. The paper concludes by emphasizing that the concept of caste and its relationship to oral health inequality must be understood it if we want to create real social change.

Two alternative methods for the retrieval of somatic cell populations from the mouse ovary.

Many modern techniques employed to uncover the molecular fundamentals underlying biological processes require dissociated cells as their starting point/substrate. Investigations into ovarian endocrinology or folliculogenesis, therefore, necessitate robust protocols for dissociating the ovary into its constituent cell populations. While in the mouse, methods to obtain individual, mature follicles are well-established, the separation and isolation of single cells of all types from early mouse follicles, including somatic cells, has been more challenging. Herein we present two methods for the isolation of somatic cells in the ovary. These methods are suitable for a range of applications relating to the study of folliculogenesis and mouse ovarian development. First, an enzymatic dissociation utilising collagenase and a temporary, primary cell culture step using neonatal mouse ovaries which yields large quantities of granulosa cells from primordial, activating, and primary follicles. Second, a rapid papain dissociation resulting in a high viability single cell suspension of ovarian somatic cells in less than an hour, which can be applied from embryonic to adult ovarian samples. Collectively these protocols can be applied to a broad array of investigations with unique advantages and benefits pertaining to both.

Higher severe acute respiratory syndrome coronavirus 2 infection rate in pregnant patients.

BACKGROUND: During the early months of the coronavirus disease 2019 pandemic, risks associated with severe acute respiratory syndrome coronavirus 2 in pregnancy were uncertain. Pregnant patients can serve as a model for the success of clinical and public health responses during public health emergencies as they are typically in frequent contact with the medical system. Population-based estimates of severe acute respiratory syndrome coronavirus 2 infections in pregnancy are unknown because of incomplete ascertainment of pregnancy status or inclusion of only single centers or hospitalized cases. Whether pregnant women were protected by the public health response or through their interactions with obstetrical providers in the early months of pandemic is not clearly understood. OBJECTIVE: This study aimed to estimate the severe acute respiratory syndrome coronavirus 2 infection rate in pregnancy and to examine the disparities by race and ethnicity and English language proficiency in Washington State. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection diagnosed between March 1, 2020, and June 30, 2020 were identified within 35 hospitals and clinics, capturing 61% of annual deliveries in Washington State. Infection rates in pregnancy were estimated overall and by Washington State Accountable Community of Health region and cross-sectionally compared with severe acute respiratory syndrome coronavirus 2 infection rates in similarly aged adults in Washington State. Race and ethnicity and language used for medical care of pregnant patients were compared with recent data from Washington State. RESULTS: A total of 240 pregnant patients with severe acute respiratory syndrome coronavirus 2 infections were identified during the study period with 70.7% from minority racial and ethnic groups. The principal findings in our study were as follows: (1) the severe acute respiratory syndrome coronavirus 2 infection rate was 13.9 per 1000 deliveries in pregnant patients (95% confidence interval, 8.3-23.2) compared with 7.3 per 1000 (95% confidence interval, 7.2-7.4) in adults aged 20 to 39 years in Washington State (rate ratio, 1.7; 95% confidence interval, 1.3-2.3); (2) the severe acute respiratory syndrome coronavirus 2 infection rate reduced to 11.3 per 1000 deliveries (95% confidence interval, 6.3-20.3) when excluding 45 cases of severe acute respiratory syndrome coronavirus disease 2 detected through asymptomatic screening (rate ratio, 1.3; 95% confidence interval, 0.96-1.9); (3) the proportion of pregnant patients in non-White racial and ethnic groups with severe acute respiratory syndrome coronavirus disease 2 infection was 2- to 4-fold higher than the race and ethnicity distribution of women in Washington State who delivered live births in 2018; and (4) the proportion of pregnant patients with severe acute respiratory syndrome coronavirus 2 infection receiving medical care in a non-English language was higher than estimates of pregnant patients receiving care with limited English proficiency in Washington State (30.4% vs 7.6%). CONCLUSION: The severe acute respiratory syndrome coronavirus 2 infection rate in pregnant people was 70% higher than similarly aged adults in Washington State, which could not be completely explained by universal screening at delivery. Pregnant patients from nearly all racial and ethnic minority groups and patients receiving medical care in a non-English language were overrepresented. Pregnant women were not protected from severe acute respiratory syndrome coronavirus 2 infection in the early months of the pandemic. Moreover, the greatest burden of infections occurred in nearly all racial and ethnic minority groups. These data coupled with a broader recognition that pregnancy is a risk factor for severe illness and maternal mortality strongly suggested that pregnant people should be broadly prioritized for coronavirus disease 2019 vaccine allocation in the United States similar to some states.

Disease severity, pregnancy outcomes, and maternal deaths among pregnant patients with severe acute respiratory syndrome coronavirus 2 infection in Washington State.

BACKGROUND: Evidence is accumulating that coronavirus disease 2019 increases the risk of hospitalization and mechanical ventilation in pregnant patients and for preterm delivery. However, the impact on maternal mortality and whether morbidity is differentially affected by disease severity at delivery and trimester of infection are unknown. OBJECTIVE: This study aimed to describe disease severity and outcomes of severe acute respiratory syndrome coronavirus 2 infections in pregnancy across the Washington State, including pregnancy complications and outcomes, hospitalization, and case fatality. STUDY DESIGN: Pregnant patients with a polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 1, 2020, and June 30, 2020, were identified in a multicenter retrospective cohort study from 35 sites in Washington State. Sites captured 61% of annual state deliveries. Case-fatality rates in pregnancy were compared with coronavirus disease 2019 fatality rates in similarly aged adults in Washington State using rate ratios and rate differences. Maternal and neonatal outcomes were compared by trimester of infection and disease severity at the time of delivery. RESULTS: The principal study findings were as follows: (1) among 240 pregnant patients in Washington State with severe acute respiratory syndrome coronavirus 2 infections, 1 in 11 developed severe or critical disease, 1 in 10 were hospitalized for coronavirus disease 2019, and 1 in 80 died; (2) the coronavirus disease 2019-associated hospitalization rate was 3.5-fold higher than in similarly aged adults in Washington State (10.0% vs 2.8%; rate ratio, 3.5; 95% confidence interval, 2.3-5.3); (3) pregnant patients hospitalized for a respiratory concern were more likely to have a comorbidity or underlying conditions including asthma, hypertension, type 2 diabetes mellitus, autoimmune disease, and class III obesity; (4) 3 maternal deaths (1.3%) were attributed to coronavirus disease 2019 for a maternal mortality rate of 1250 of 100,000 pregnancies (95% confidence interval, 257-3653); (5) the coronavirus disease 2019 case fatality in pregnancy was a significant 13.6-fold (95% confidence interval, 2.7-43.6) higher in pregnant patients than in similarly aged individuals in Washington State with an absolute difference in mortality rate of 1.2% (95% confidence interval, -0.3 to 2.6); and (6) preterm birth was significantly higher among women with severe or critical coronavirus disease 2019 at delivery than for women who had recovered from coronavirus disease 2019 (45.4% severe or critical coronavirus disease 2019 vs 5.2% mild coronavirus disease 2019; P<.001). CONCLUSION: Coronavirus disease 2019 hospitalization and case-fatality rates in pregnant patients were significantly higher than in similarly aged adults in Washington State. These data indicate that pregnant patients are at risk of severe or critical disease and mortality compared to nonpregnant adults, and also at risk for preterm birth.

In Pursuit of the "Perforator" in the Perforator Skin Flap.

Another congress of the World Society for Reconstructive Microsurgery (WSRM) this past year in Bologna was magnificent not just for the presentation of so many keynote lectures by the giants of our field nor the novel and innovative ideas shown by those who will someday follow in those footsteps, but by making all of us realize how many capable microsurgeons there are now practically everywhere in this world, doing incredibly important surgical management of challenges that previously were unmet and resulted in sheer devastation for so many of our patients. How much we are the same in our goals, aspirations, and abilities could not be overlooked, but it is amazing how much we also want to learn more together-each relying on the other. To do so, we must not forget our origins as we appropriately plan for the future. All this we philosophized in our WSRM panel on lower extremity reconstruction, while emphasizing on the surface the perforator flap that at the least today has caught everyone's attention. In this overview to follow, we once again tell two stories, starting with the beginnings of the concept of flaps in showing how the nomenclature has evolved over time according to our various surgical manipulations. Often overlooked, though, is a parallel timeline by the anatomists who have better elucidated the circulation to these flaps, where it will become obvious that often long ago the existence of perforators was recognized by them long before known by the surgeons. At least today, these two paths have at least temporarily intersected. Our pursuit of the "perforator" in the perforator skin flap has come full circle, following the course of the history of the flap itself-a pursuit of excellence.

Broadening the spectrum of fluorescent protein tools for use in the encapsulated human fungal pathogen Cryptococcus neoformans.

Green fluorescent protein (GFP) and its counterparts are modern molecular biology research tools indispensable in many experimental systems. Within fungi, researchers studying Saccharomyces cerevisiae and other model ascomycetes have access to a wide variety of fluorescent proteins. Unfortunately, many of these tools have not crossed the phylum divide into the Basidiomycota, where only GFP S65T, Venus, Ds-Red, and mCherry are currently available. To address this, we searched the literature for potential candidates to be expressed in the human fungal pathogen Cryptococcus neoformans and identified a suite of eight more modern fluorescent proteins that span the visible spectrum. A single copy of each fluorophore was heterologously expressed in Safe Haven 1 and their fluorescence intensities compared in this encapsulated yeast. mTurquoise2, mTFP1, Clover, mNeonGreen, mRuby3, and Citrine were highly visible under the microscope, whereas Superfolder GFP and mMaroon1 were not. Expressed fluorophores did not impact growth or virulence as demonstrated by an in vitro spotting assay and murine inhalation model, respectively.