Expanding the coverage of spatial proteomics: a machine learning approach.

MOTIVATION: Multiplexed protein imaging methods use a chosen set of markers and provide valuable information about complex tissue structure and cellular heterogeneity. However, the number of markers that can be measured in the same tissue sample is inherently limited. RESULTS: In this paper, we present an efficient method to choose a minimal predictive subset of markers that for the first time allows the prediction of full images for a much larger set of markers. We demonstrate that our approach also outperforms previous methods for predicting cell-level protein composition. Most importantly, we demonstrate that our approach can be used to select a marker set that enables prediction of a much larger set than could be measured concurrently. AVAILABILITY AND IMPLEMENTATION: All code and intermediate results are available in a Reproducible Research Archive at https://github.com/murphygroup/CODEXPanelOptimization.

Comparative genomics sheds new light on the convergent evolution of infrared vision in snakes.

Infrared vision is a highly specialized sensory system that evolved independently in three clades of snakes. Apparently, convergent evolution occurred in the transient receptor potential ankyrin 1 (TRPA1) proteins of infrared-sensing snakes. However, this gene can only explain how infrared signals are received, and not the transduction and processing of those signals. We sequenced the genome of Xenopeltis unicolor, a key outgroup species of pythons, and performed a genome-wide analysis of convergence between two clades of infrared-sensing snakes. Our results revealed pervasive molecular adaptation in pathways associated with neural development and other functions, with parallel selection on loci associated with trigeminal nerve structural organization. In addition, we found evidence of convergent amino acid substitutions in a set of genes, including TRPA1 and TRPM2. The analysis also identified convergent accelerated evolution in non-coding elements near 12 genes involved in facial nerve structural organization and optic nerve development. Thus, convergent evolution occurred across multiple dimensions of infrared vision in vipers and pythons, as well as amino acid substitutions, non-coding elements, genes and functions. These changes enabled independent groups of snakes to develop and use infrared vision.

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

BACKGROUND AND PURPOSE: Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS: INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS: Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION: Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

How state firework restrictions affect the incidence of paediatric firework injuries in the USA.

OBJECTIVES: State laws dictate firework access in the USA, and the association between state laws and paediatric firework injuries has not been investigated. We hypothesise that states with fewer firework restrictions will have a higher incidence of paediatric firework injuries. METHODS: A retrospective review (2012-2020) of paediatric patients who sustained a fireworks-related injury was conducted using the Pediatric Health Information System. Inclusion criteria were age less than 18 years and International Classification of Diseases code for fireworks-related injury. States were classified as 'unrestrictive' or 'restrictive' based on permitted fireworks. Case number, demographics and injury severity were evaluated. A negative binomial regression was used to evaluate independent variables predictive of firework injuries, with the dependent variable being the number of injuries. Independent variables that were predictive of number of injuries were subsequently evaluated with a Mann-Whitney test to determine the significance of the differences between 'unrestrictive' and 'restrictive' states. RESULTS: During the study period, 2299 fireworks-related injuries were reported. Mean age was 9.2±4.8 years (range 0-17). Most injuries, based on raw numbers, were in 'unrestrictive' states (72.6%). When normalised measures were used for comparison, based on paediatric state population, there was a statistically significant difference with a higher percentage of injuries in unrestricted states (p=0.002). The mean number of cases per million pediatric-aged individuals was higher in the 'unrestrictive' states versus the 'restrictive' states (p=0.003). CONCLUSIONS: States with fewer firework restrictions had a higher incidence of fireworks-related injuries in children. Restricting fireworks may protect children from fireworks-related injuries.

Community cervical cancer screening and precancer risk in women living with HIV in Jos Nigeria.

BACKGROUND: High HIV prevalence, and lack of organized screening for the indigent population receiving care and treatment within HIV clinics in low-resource settings increases cervical cancer incidence. We sought to determine predictors of cervical precancer in women living with HIV and receiving cervical cancer screening in Jos, Nigeria. METHODS: A cross-sectional study of women living with HIV and receiving care and treatment in adult HIV/AIDS clinics in Jos-Metropolis, Nigeria between June 2020 and April 2023. Ethical approvals were obtained from the ethics committee in Jos, Nigeria and Northwestern University IRB, USA. Informed consent was obtained from eligible participants, and data on socio-demographics, cancer risk factors, and cytology reports were collected. The outcome variables were cervical precancer lesions. The independent variables were prior Pap smear status, socio-demographics, income, educational, and other reproductive health factors. Descriptive statistics was done to obtain means ± sd, frequencies, and percentages for the variables. Univariate and bivariate analyses were done to determine predictors of cervical dysplasia. Analyses were performed using R software. RESULTS: Of 957 women screened, 570 were living with HIV and 566 women had cytology report and were included in the final analysis. The mean age was 45.08 ± 8.89 years and 81.6% had no prior evidence of Pap test (under-screened). Prevalence of cervical dysplasia was 24% (mild and severe dysplasia were 12.9% and 11.1%, respectively). Age above 45 years (aOR = 3.48, p = 0.009), postmenopausal status (aOR = 7.69, p = 0.000), and women with no history of prior IUCD use (aOR = 5.94, p = 0.0001), were predictors for severe dysplasia. Women who had history of STI (aOR = 0.17, p = 0.000), prior use of IUCD (aOR = 0.32, p = 0.004), prior use of condom (aOR = 2.50, p = 0.003) and had co-morbidities (aOR = 0.46, p = 0.009) were more likely to have had a Pap test in the past. CONCLUSIONS: The majority of indigent women receiving care at HIV clinics had their first Pap test screening, and lack of organized screening among older and post-menopausal women with HIV, puts women at a higher risk of developing severe cervical precancer lesions.

Intraoperative Radiation Exposure in Adolescent Idiopathic and Neuromuscular Scoliosis.

BACKGROUND: Intraoperative imaging is often used to aid pedicle screw placement during scoliosis operations. Higher rates of cancer and death have been observed in orthopaedic surgeons and radiation technologists, including a fourfold higher rate of breast cancer in female orthopaedic surgeons. The purpose of this study was to evaluate variability in intraoperative radiation during spinal fusions for both adolescent idiopathic scoliosis (AIS) and neuromuscular scoliosis (NMS). METHODS: A retrospective review of posterior spinal fusion and segmental spinal instrumentation for scoliosis performed by pediatric orthopaedic surgeons from 2017 to 2019 at a single institution was performed. Inclusion criteria included: a diagnosis of AIS or NMS and patients between 8 and 18 years of age. Exclusion criteria included: revision surgery, use of intraoperative navigation, and patients younger than 10 at the time of scoliosis onset within the AIS cohort. Data collected included: preoperative curve, body mass index (BMI), number of levels fused, number of Ponte osteotomies, and fluoroscopy time. One-way analysis of variance tests, Bonferroni post hoc tests, independent t tests, and Pearson correlations were utilized with significance determined at the 95% confidence level ( a = 0.05). RESULTS: A total of 148 patients were included in the study. The average fluoroscopy time was 143 ± 67 seconds. Patients with NMS had higher average fluoroscopy times (193 ± 75 s) compared with patients with AIS (129 ± 58 s, P < 0.001). In patients with AIS, fluoroscopy time correlated to the patient's preoperative curve ( r = 0.182, P = 0.050). Patients with AIS with fewer than 12 levels fused had significantly less radiation exposure than those with 12 or more levels fused ( P = 0.01). When controlling for the number of levels fused, patients with AIS with higher BMIs had significantly greater fluoroscopy times ( P = 0.001). In patients with NMS, fluoroscopy time negatively correlated with BMI ( r = -0.459, P = 0.009) and positively correlated with a preoperative curve ( r = 0.475, P = 0.007). CONCLUSION: Fluoroscopy times vary greatly during adolescent spinal fusions for scoliosis. Longer fluoroscopy times are correlated with: NMS diagnosis, larger preoperative curve, BMI, and number of levels fused. Surgeons' knowledge of factors affecting fluoroscopy time will increase awareness and may be the first step in decreasing intraoperative radiation risks. LEVEL OF EVIDENCE: Level III; Therapeutic-a retrospective study.

The Prevalence of Hip Dysplasia on Radiographs for Adolescent Idiopathic Scoliosis.

BACKGROUND: During radiographic assessment of adolescent idiopathic scoliosis (AIS), upright images frequently capture the hip. The purpose of this study was to assess the prevalence of radiographic hip dysplasia on postero-anterior (PA) scoliosis radiographs, as defined as a lateral center edge angle (LCEA) ≤25 degrees. METHODS: All patients with upright PA scoliosis radiographs over a one-year study period at a single tertiary academic medical center (2020 to 2021) were included in the study. Radiographs containing the hip joints were annotated by 3 reviewers for left and right LCEA, and triradiate cartilage (TRC) status. Inter-rater reliability was determined among the 3 reviewers. RESULTS: Two hundred fifty patients {500 hips, 75.6% female, median age 14 [interquartile range (IQR)=3]} had PA scoliosis radiographs that captured the hip, which qualified for analysis. Seventy-four hips (14.8%) demonstrated evidence of dysplasia (LCEA ≤25 deg) in 55/250 patients (22%). The median LCEA was significantly lower in the dysplastic hip cohort (23.9 deg, IQR=4.8 deg), compared with those without dysplasia (33 deg IQR=7.3 deg; P =0.001). A higher percentage of dysplastic hip patients were female than male (72.7% vs. 27.3%). Patients with bilateral dysplasia had a similar LCEA ( 22.9 deg) [to those with unilateral dysplasia (22.9 deg left, 23.9 deg right, P =0.689)]. CONCLUSIONS: In a cohort of 250 AIS patients, 22% demonstrated evidence of hip dysplasia, as defined as an LCEA ≤2 degrees. The dysplastic patients were more likely to be female. Screening for hip symptomatology in AIS patients may be of benefit, considering the frequency of radiographic hip dysplasia in this population. LEVEL OF EVIDENCE: III. Type of Evidence: diagnostic.

Markers of periodontal disease and risk of stroke: INTERSTROKE case-control study.

BACKGROUND: Periodontal disease may be an important modifiable risk factor for stroke. AIMS: To determine the contribution of markers of periodontal disease to stroke risk globally, within subpopulations, and by stroke subtypes. METHODS: INTERSTROKE is the largest international case-control study of risk factors for first acute stroke. All participants were asked a standardised set of questions about the presence or absence of painful teeth, painful gums or lost teeth, as markers of periodontal disease, within the previous year. The total number of reported variables was calculated per participant. Multivariable conditional logistic regression examined the association of these variables with acute stroke. RESULTS: In 26901 participants, across 32 countries, there was a significant multivariable association between lost teeth and stroke (OR 1.11, 95 % CI 1.01 - 1.22), but not painful teeth (OR 1.00, 95 % CI 0.91-1.10) or painful gums (OR 1.01, 95 % CI 0.89 - 1.14). When these symptoms were considered together there was a graded increased odds of stroke, with the largest magnitude of association seen if a patient reported all three of painful teeth, painful gums and lost teeth (OR 1.34, 95 % CI 1.00 - 1.79). CONCLUSIONS: Our findings suggest that features of severe periodontal disease are a risk factor for acute stroke. Periodontal disease should be considered as a potentially modifiable risk factor for stroke.

3DCellComposer - A Versatile Pipeline Utilizing 2D Cell Segmentation Methods for 3D Cell Segmentation.

Background: Cell segmentation is crucial in bioimage informatics, as its accuracy directly impacts conclusions drawn from cellular analyses. While many approaches to 2D cell segmentation have been described, 3D cell segmentation has received much less attention. 3D segmentation faces significant challenges, including limited training data availability due to the difficulty of the task for human annotators, and inherent three-dimensional complexity. As a result, existing 3D cell segmentation methods often lack broad applicability across different imaging modalities. Results: To address this, we developed a generalizable approach for using 2D cell segmentation methods to produce accurate 3D cell segmentations. We implemented this approach in 3DCellComposer, a versatile, open-source package that allows users to choose any existing 2D segmentation model appropriate for their tissue or cell type(s) without requiring any additional training. Importantly, we have enhanced our open source CellSegmentationEvaluator quality evaluation tool to support 3D images. It provides metrics that allow selection of the best approach for a given imaging source and modality, without the need for human annotations to assess performance. Using these metrics, we demonstrated that our approach produced high-quality 3D segmentations of tissue images, and that it could outperform an existing 3D segmentation method on the cell culture images with which it was trained. Conclusions: 3DCellComposer, when paired with well-trained 2D segmentation models, provides an important alternative to acquiring human-annotated 3D images for new sample types or imaging modalities and then training 3D segmentation models using them. It is expected to be of significant value for large scale projects such as the Human BioMolecular Atlas Program.

Learning Morphological, Spatial, and Dynamic Models of Cellular Components.

In this chapter, we describe protocols for using the CellOrganizer software on the Jupyter Notebook platform to analyze and model cell and organelle shape and spatial arrangement. CellOrganizer is an open-source system for using microscope images to learn statistical models of the structure of cell components and how those components are organized relative to each other. Such models capture the statistical variation in the organization of cellular components by jointly modeling the distributions of their number, shape, and spatial distributions. These models can be created for different cell types or conditions and compared to reflect differences in their spatial organizations. The models are also generative, in that they can be used to synthesize new cell instances reflecting what a model learned and to provide well-structured cell geometries that can be used for biochemical simulations.

Unilateral renal cortical necrosis.

A 51-year-old woman presented to her local emergency department with acute onset right-sided flank pain and nausea. Her blood results on admission were largely unremarkable aside from leucocytosis and neutrophilia. Two days after admission, she developed the following: stage 3 AKI with oliguria, anaemia, thrombocytopenia, and acute derangement of liver function tests. A computed tomography of the kidney ureter bladder demonstrated a right-sided 4 mm obstructing vesicoureteric junction stone with associated hydronephrosis and hydroureter. She was transferred to a tertiary care centre; gram negative sepsis was confirmed with a Proteus on blood culture and laboratory findings were in keeping with DIC. She was treated with Tazobactam/Piperacillin and intravenous fluids. In addition, further imaging showed improving right-sided hydronephrosis and left renal cortical necrosis. The aetiology of this presentation was sepsis complicated by disseminated intravascular coagulation. The coagulopathy likely contributed to the unilateral renal cortical necrosis. Cortical necrosis usually affects both kidneys, and is typically a complication of sepsis, shock, or obstetrical trauma. To our knowledge, there are only 2 reported cases of unilateral renal cortical necrosis and contralateral hydronephrosis with renal colic and septic shock. Potential pathogenetic mechanisms are discussed.

Virtual Patient/Family Communication in the Acute Care Setting.

Patient and family-centered care strategies see patients and families as valuable healthcare team members and are therefore treated as essential clinical partners to achieve safe, high-quality care. Traditionally, hospitals have relied on physical presence as the primary strategy for including families in shared decision-making. During COVID-19, widespread visitor restrictions removed this primary strategy. Hospitals rapidly deployed virtual communication tools to address the challenges visitor restrictions created. The rapid deployment produced benefits and unintended consequences, especially for the healthcare providers. Through a series of qualitative interviews with family members and healthcare providers, consistent themes were identified and mapped to the sociotechnical model. This project identified barriers to adoption and proposed corresponding success criteria. Although the project focused on implementing virtual communication in the context of the COVID-19 pandemic, virtual communication strategies can likely support family-centered care goals outside of the pandemic context.

CT pulmonary arteriogram diagnosis of macroscopic fat embolism to the lung.

Pulmonary fat embolism (PFE) is a recognised complication of long bone fractures. The majority of cases represent microscopic embolism and are not detectable at CT pulmonary arteriography (CTPA). CT can be used to detect macroscopic fat based on Hounsfield attenuation. This case describes a case of macroscopic fat embolism to the pulmonary arteries which was confidently diagnosed at CTPA. Distinction from thromboembolism is important as treatment is supportive and may avoid risks of anticoagulation.

Effect of Cold vs Temperate Conditions on Physical Performance During Extended Mountain Warfare Training at Moderate Altitude.

INTRODUCTION: The purpose of this study was to investigate the effect of environmental conditions on body composition, upper body power, and lower body power throughout a ∼4-week military mountain training exercise. We hypothesized that countermovement jump and ballistic push-up performance would decrease as a result of extended mountain field training and that winter (cold) conditions would result in greater decrements compared to fall (temperate) conditions. We also expected to observe a strong positive correlation between changes in performance and changes in skeletal muscle mass. Finally, we expected acute changes in performance upon altitude exposure. MATERIALS AND METHODS: A total of 111 U.S. Infantry Marines (110 M; 1 F) provided written informed consent to participate in this study according to a protocol approved by the Naval Health Research Center. There were 54 participants in the fall cohort and 57 in the winter cohort. Maximum effort countermovement jump and ballistic push-up performance were assessed at different timepoints: (1) baseline at the sea level, (2) before training at ∼2100 m, (3) midpoint of training at ∼2100 m, (4) end of training at ∼2100 m, and (5) after 3 to 4 weeks of recovery at the sea level. The fall cohort trained at moderate temperatures (average day/night, 20°C/3°C), whereas the winter cohort trained under snowy winter conditions (7°C/-14°C). RESULTS: The results suggested that seasonal conditions did not significantly affect changes in body composition or physical performance. Furthermore, no acute effects of altitude on physical performance were detected. Training exercise did, however, cause performance decrements in countermovement jump height, countermovement jump peak power, and ballistic push-up height. Repeated measure correlation analyses suggested that there was a weak positive correlation between the decrease in skeletal muscle mass and the decrease in countermovement jump peak power throughout the training. CONCLUSIONS: The results of our study suggest that explosive movements are negatively affected by extended military training, seemingly independent of environmental training conditions or temperature. Planning and execution of military training should account for the likelihood that warfighter physical power will decline and may not return to pretraining levels within the month following the training event. It may also be advised to consider targeted exercises to aid in recovery of muscular strength and power. Future work should consider additional factors that likely influenced the decrease in physical performance that occurs during extended military training, such as nutrition, sleep, and psychological and cognitive stresses.

Image-based discrimination of the early stages of mesenchymal stem cell differentiation.

Mesenchymal stem cells (MSCs) are self-renewing, multipotent cells, which can be used in cellular and tissue therapeutics. MSCs cell number can be expanded in vitro, but premature differentiation results in reduced cell number and compromised therapeutic efficacies. Current techniques fail to discriminate the "stem-like" population from early stages (12 h) of differentiated MSC population. Here, we imaged nuclear structure and actin architecture using immunofluorescence and used deep learning-based computer vision technology to discriminate the early stages (6-12 h) of MSC differentiation. Convolutional neural network models trained by nucleus and actin images have high accuracy in reporting MSC differentiation; nuclear images alone can identify early stages of differentiation. Concurrently, we show that chromatin fluidity and heterochromatin levels or localization change during early MSC differentiation. This study quantifies changes in cell architecture during early MSC differentiation and describes a novel image-based diagnostic tool that could be widely used in MSC culture, expansion and utilization.

How comprehensive is our comprehensive geriatric assessment in clinical practice? An Irish perspective.

PURPOSE: Comprehensive geriatric assessment (CGA) is the cornerstone of high-quality care for older adults. There is no current gold standard to guide what should be included as the baseline measure for CGAs. We examined what metrics are being captured in CGA baseline assessments completed by community based integrated care teams in Ireland. METHODS: CGA's care pathways in Ireland are usually initiated with a written document that establish patients baseline in various assessment areas. These documents were the focus of this study. We completed a cross-sectional study of the components captured in CGA baseline assessments completed in a community setting. We contacted operational leads in each of the community health organisations in Ireland and requested a copy of their current initial baseline screening document for CGA. RESULTS: We reviewed 16 individual CGA baseline documents for analysis in this study. Common assessment areas in all documents included frailty (with the Rockwood Clinical frailty scale used in 94%, n = 15), cognition (4AT-56% of CGAs, MMSE-25%, MOCA-25%, AMTS-19%, AD8-19%, Addenbrookes-13%, 6CIT-13%, mini cog-6%), mobility (100%, n = 16), falls (100%, n = 16), continence (100% n = 16), nutrition (100% n = 16). Mood (94%, n = 15), pain (44%, n = 7), bone health (63%, n = 10), sleep (62%, n = 10) and skin integrity (56%, n = 9). Formal functional assessment was completed in 94% (n = 15) of CGAs with the Barthel index being the tool most used 81% (n = 13). Half of the CGAs included a section describing carer strain (50%, n = 8). The majority of CGAs included a patient centred question which was some variation of 'what matters most to me' (75% n = 11). 87.5% of assessments included a care plan summary (n = 14). CONCLUSIONS: This report highlights that the core tenets of CGA are being assessed across different community based initial CGA screening instruments. There was significant variability in the discussion of challenging topics such as carer strain and social well-being. Our results should prompt a discussion about whether a minimum dataset should be developed for inclusion in nationwide initial baseline CGA document, aiming to improve standardisation of assessments, which will impact areas highlighted for intervention and ultimately guide population health policy.

Inpatient Costs of Treating Patients With COVID-19.

Importance: With more than 6.2 million hospitalizations due to COVID-19 in the US, recognition of the average hospital costs to provide inpatient care during the pandemic is necessary to understanding the national medical resource use and improving public health readiness and related policies. Objective: To examine the mean cost to provide inpatient care to treat COVID-19 and how it varied through the pandemic waves and by important sociodemographic patient characteristics. Design, Setting, and Participants: This cross-sectional study used inpatient-level data from March 1, 2020, to March 31, 2022, extracted from a repository of clinical, administrative, and financial information covering 97% of academic medical centers across the US. Main Outcomes and Measures: Cost to produce care for each stay was calculated using direct hospital costs to provide care adjusted for geographic differences in labor costs using area wage indices. Results: The sample included 1 333 404 stays with a primary or secondary COVID-19 diagnosis from 841 hospitals. The cohort included 692 550 (52%) men, with mean (SD) age of 59.2 (17.5) years. The adjusted mean cost of an inpatient stay was $11 275 (95% CI, $11 252-$11 297) overall, increasing from $10 394 (95% CI, $10 228-$10 559) at the end of March 2020 to $13 072 (95% CI, $12 528-$13 617) by the end of March 2022. Patients with specific comorbidities had significantly higher mean costs than their counterparts: those with obesity incurred an additional $2924 in inpatient stay costs, and those with coagulation deficiency incurred an additional $3017 in inpatient stay costs. Stays during which the patient required extracorporeal membrane oxygenation (ECMO) had an adjusted mean cost of $36 484 (95% CI, $34 685-$38 284). Conclusions and Relevance: In this cross-sectional study, an adjusted mean hospital cost to provide care for patients with COVID-19 increased more than 5 times the rate of medical inflation overall. This appeared to be explained partly by changes in the use of ECMO, which increased over time.

West Nile Virus-Induced Expression of Senescent Gene Lgals3bp Regulates Microglial Phenotype within Cerebral Cortex.

Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Using spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phenotypes. Our results show that WNV-activated microglia share transcriptional signatures with aged microglia, including upregulation of genes involved in interferon response and inflammation. Lgals3bp was broadly expressed in the CNS and robustly upregulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations without differences in virologic control or survival. These data indicate that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neuroinflammation-related cognitive decline in aging and post-viral infections.

"Monitoring Postoperative Weight Changes Following Reduction Mammoplasty in Adolescents".

BACKGROUND: Macromastia can limit women's ability to exercise. Reduction mammoplasty has been reported to subjectively improve exercise capability and stimulate weight loss. Considering the lack of published quantitative data, we sought to examine change in weight and body mass index (BMI) in adolescent women following reduction mammoplasty. METHODS: Retrospective chart review was performed of patients under 21 years of age that underwent reduction mammoplasty at our institution from 2015 through 2019. RESULTS: Fifty-six patients with follow-up weight measurements were included in analysis. Median follow-up time of our sample was 46.0 months. Only 22 (39.3%) experienced a decrease in BMI at final follow-up compared to baseline. Patients classified as healthy weight preoperatively (BMI 18.5-24.9kg/m) experienced a significant increase in BMI at 2-year, 3-year, 5-year, and final postoperative follow-up compared to baseline. Patients classified as overweight (25.0-29.99kg/m) or obese (≥30kg/m) did not experience significant BMI change at final postoperative follow-up. CONCLUSIONS: BMI and weight trended upwards postoperatively regardless of BMI classification. Reduction mammoplasty alone is not sufficient to stimulate weight loss. Healthy lifestyle changes should be encouraged to help prevent weight gain in adolescent women following reduction mammoplasty.

Shaping the tripartite symbiosis: are termite microbiome functions directed by the environmentally acquired fungal cultivar?

Microbiome assembly critically impacts the ability of hosts to access beneficial symbiont functions. Fungus-farming termites have co-evolved with a fungal cultivar as a primary food source and complex gut microbiomes, which collectively perform complementary degradation of plant biomass. A large subset of the bacterial community residing within termite guts are inherited (vertically transmitted) from parental colonies, while the fungal symbiont is, in most termite species, acquired from the environment (horizontally transmitted). It has remained unknown how the gut microbiota sustains incipient colonies prior to the acquisition of the fungal cultivar, and how, if at all, bacterial contributions are modulated by fungus garden establishment. Here, we test the latter by determining the composition and predicted functions of the gut microbiome using metabarcoding and shotgun metagenomics, respectively. We focus our functional predictions on bacterial carbohydrate-active enzyme and nitrogen cycling genes and verify compositional patterns of the former through enzyme activity assays. Our findings reveal that the vast majority of microbial functions are encoded in the inherited microbiome, and that the establishment of fungal gardens incurs only minor modulations of predicted bacterial capacities for carbohydrate and nitrogen metabolism. While we cannot rule out that other symbiont functions are gained post-fungus garden establishment, our findings suggest that fungus-farming termite hosts are equipped with a near-complete set of gut microbiome functions at the earliest stages of colony life. This inherited, incipient bacterial microbiome likely contributes to the high extent of functional specificity and coevolution observed between termite hosts, gut microbiomes, and the fungal cultivar.