CRISPR/Cas9-mediated multiplex gene editing of gamma and omega gliadins, paving the way for gliadin-free wheat.

Wheat is a staple cereal in the human diet. Despite its significance, an increasing percentage of the population suffers adverse reactions to wheat, which are triggered by wheat gluten, particularly the gliadin fractions. In this study, we employed CRISPR/Cas multiplexing to introduce targeted mutations into γ- and ω-gliadin genes of wheat, to produce lines deficient in one or both immunogenic gliadin fractions simultaneously. For this work, eight single guide RNAs (sgRNAs) were designed and combined into four plasmids to produce 59 modified wheat lines, of which 20 exhibited mutations in the target genes. Characterization of these lines through Sanger or NGS sequencing revealed a complex pattern of InDels, including deletions spanning multiple sgRNAs. The mutations were transmitted to the offspring, and the analysis of homozygous derived lines by RP-HPLC and monoclonal antibodies showed a 97.7% reduction in gluten content. Crossing these lines with other CRISPR/Cas lines deficient in the α-gliadins allowed multiple mutations to be combined. This work represents an important step forward in the use of CRISPR/Cas to develop gluten-free wheat.

Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Analysis of health inequities in transfers of admitted patients from an academic emergency department to partner community hospital.

BACKGROUND: Many academic medical centers (AMC) transfer patients who require admission but not tertiary care to partner community hospitals from their emergency departments (ED). These transfers alleviate ED boarding but may worsen existing healthcare disparities. We assessed whether disparities exist in the transfer of patients from one AMC ED to a community hospital General Medical Service. METHODS: We performed a retrospective cohort study on all patients screened for transfer between April 1 and December 31, 2021. During the screening process, the treating ED physician determines whether the patient meets standardized clinical criteria and a patient coordinator requests patient consent. We collected patient demographics data from the electronic health record and performed logistic regression at each stage of the transfer process to analyze how individual characteristics impact the odds of proceeding with transfer. RESULTS: 5558 patients were screened and 596 (11%) ultimately transferred. 1999 (36%) patients were Black or Hispanic, 698 (12%) had a preferred language other than English, and 956 (17%) were on Medicaid or uninsured. A greater proportion of Black and Hispanic patients were deemed eligible for interhospital transfer compared to White patients and a greater proportion of Hispanic patients completed transfer to the community hospital (p < 0.017 after Bonferroni correction). After accounting for other demographic variables, patients older than 50 (OR 1.21, 95% CI 1.04-1.40), with a preferred language other than English (OR 1.27, 95% CI 1.00-1.62), and from a priority neighborhood (OR 1.38, 95% CI 1.18-1.61) were more likely to be eligible for transfer, while patients who were male (OR 1.50, 95% CI 1.10-2.05) and younger than 50 (OR 1.85, 95% CI 1.20-2.78) were more likely to consent to transfer (p < 0.05). CONCLUSION: Health disparities exist in the screening process for our interfacility transfer program. Further investigation into why these disparities exist and mitigation strategies should be undertaken.

Code De-Escalation: Decreasing restraint use during agitation management in a community hospital emergency department.

INTRODUCTION: Restraint use in the emergency department (ED) can pose significant risks to patients and health care workers. We evaluate the effectiveness of Code De-escalation- a standardized, team-based approach for management and assessment of threatening behaviors- in reducing physical restraint use and workplace violence in a community ED. METHODS: A retrospective observational study of a pathway on physical restraint use among patients placed on an involuntary psychiatric hold in a community ED. This pathway includes a built-in step for the team members to systematically assess perceptions of threats from the patient behavior and threats perceived by the patient. Our primary outcome was the change in the rate of physical restraint use among patients on an involuntary psychiatric hold. Our secondary outcome was the change in the rate of workplace violence events involving all ED encounters. We evaluated our outcomes by comparing all encounters in a ten-month period before and after implementation, and compared our results to rates at neighboring community hospitals within the same hospital network. RESULTS: Pre intervention there were 434 ED encounters involving a psychiatric hold, post-intervention there were 535. We observed a significant decrease in physical restraint use, from 7.4% to 3.7% (ARR 0.028 [95% CI 0.002-0.055], p < 0.05). This was not seen at the control sites. CONCLUSIONS: A standardized de-escalation algorithm can be effective in helping ED's decrease their use of physical restraints in management of psychiatric patients experiencing agitation.

Practice as you Teach: Comparing Ordering Practices Between Shared and Physician-Only Visits in Academically Affiliated Community Emergency Departments.

BACKGROUND: Considerable variability exists in emergency physicians' (EPs) rates of resource utilization, which may cluster in distinct patterns. However, previous studies have focused on academic and tertiary care centers, and it is unclear whether similar patterns exist in community practice. OBJECTIVE: Our aim was to examine whether EPs practicing in community emergency departments (EDs) have practice patterns similar to those of academic EDs. Secondarily, we sought to investigate the effects of shared visits with advanced practice professionals and residents. METHODS: This was a retrospective study of two community EDs affiliated with an academic network. There were 62,860 visits among 50 EPs analyzed from October 1, 2018 through January 31, 2020 for rates of advanced imaging, admission, and shared visits. To classify practice patterns, we used a Gaussian Mixture Model (GMM), with groups and covariance determined by Bayesian Information Criteria. RESULTS: Our GMM revealed three groups. The largest had homogeneous patterns of resource use (n = 28; 50% were female; years of experience: 7; interquartile range [IQR] 2-11; advanced imaging: 28%; admission: 19%; shared: 34%), a small group with lower resource use (n = 4; 0% were female; years of experience: 6; IQR 4-10; advanced imaging: 28%; admission: 16%; shared: 8%), and a modest high-resource group (n = 18; 28% female; years of experience: 5; IQR 2-16; advanced imaging: 34%; admission: 23%; shared: 43%). Rates of shared visits had little direct correlation with imaging (r2 = 0.045) or admission (r2 = 0.093), and rates of imaging and admission were weakly correlated (r2 = 0.242). CONCLUSIONS: Our data suggest that community EPs may have multiple patterns of resource use, similar to those in academic EDs.

Antioxidant and Emulsifying Activity of the Exopolymer Produced by Bacillus licheniformis.

The exopolymer (ESPp) was obtained from Bacillus licheniformis IDN-EC, composed of a polyglutamic acid and polyglycerol phosphate chain O-substituted with αGal moieties (αGal/αGlcNH2 3:1 molar ratio) and with a 5000 Da molecular weight. The cytotoxicity activity of EPSp was determined by reducing the MTT (3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide) to formazan on HeLa cells. This EPS did not show cytotoxicity against the tested cell line. The ESPp presented great advantages as an antioxidant with free radical scavenging activities (1,1-diphenyl-2-picryl-hydrazyl radical (DPPH),hydroxyl radical (OH), and superoxide anion (O2-)) (65 ± 1.2%, 98.7 ± 1.9%, and 97 ± 1.7%), respectively. Moreover, EPSp increased the enzyme activity for catalase (CAT) and glutathione peroxidase (GSH-Px) in HeLa cells (CAT, 2.6 ± 0.24 U/mL; and GSH-Px, 0.75 ± 0.3 U/L). The presence of ESPp showed a significant protective effect against H2O2 in the cell line studied, showing great viability (91.8 ± 2.8, 89.9 ± 2.9, and 93.5 ± 3.6%). The EPSp presented good emulsifying activity, only for vegetable oils, olive oil (50 ± 2.1%) and sesame (72 ± 3%). Sesame was effective compared to commercials products, Triton X-100 (52.38 ± 1.6%), Tween 20 (14.29 ± 1.1%), and sodium dodecyl sulphate (SDS) (52.63 ± 1.6%). Furthermore, the EPS produced at 0.6 M has potential for environmental applications, such as the removal of hazardous materials by emulsification whilst resulting in positive health effects such as antioxidant activity and non-toxicity. EPSp is presented as a good exopolysaccharide for various applications.

LOX-1 in Cardiovascular Disease: A Comprehensive Molecular and Clinical Review.

LOX-1, ORL-1, or lectin-like oxidized low-density lipoprotein receptor 1 is a transmembrane glycoprotein that binds and internalizes ox-LDL in foam cells. LOX-1 is the main receptor for oxidized low-density lipoproteins (ox-LDL). The LDL comes from food intake and circulates through the bloodstream. LOX-1 belongs to scavenger receptors (SR), which are associated with various cardiovascular diseases. The most important and severe of these is the formation of atherosclerotic plaques in the intimal layer of the endothelium. These plaques can evolve into complicated thrombi with the participation of fibroblasts, activated platelets, apoptotic muscle cells, and macrophages transformed into foam cells. This process causes changes in vascular endothelial homeostasis, leading to partial or total obstruction in the lumen of blood vessels. This obstruction can result in oxygen deprivation to the heart. Recently, LOX-1 has been involved in other pathologies, such as obesity and diabetes mellitus. However, the development of atherosclerosis has been the most relevant due to its relationship with cerebrovascular accidents and heart attacks. In this review, we will summarize findings related to the physiologic and pathophysiological processes of LOX-1 to support the detection, diagnosis, and prevention of those diseases.

Implementation of a Novel Method for Processing Proteins from Acetic Acid Bacteria via Liquid Chromatography Coupled with Tandem Mass Spectrometry.

Acetic acid bacteria (AAB) and other members of the complex microbiotas, whose activity is essential for vinegar production, display biodiversity and richness that is difficult to study in depth due to their highly selective culture conditions. In recent years, liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has emerged as a powerful tool for rapidly identifying thousands of proteins present in microbial communities, offering broader precision and coverage. In this work, a novel method based on LC-MS/MS was established and developed from previous studies. This methodology was tested in three studies, enabling the characterization of three submerged acetification profiles using innovative raw materials (synthetic alcohol medium, fine wine, and craft beer) while working in a semicontinuous mode. The biodiversity of existing microorganisms was clarified, and both the predominant taxa (Komagataeibacter, Acetobacter, Gluconacetobacter, and Gluconobacter) and others never detected in these media (Asaia and Bombella, among others) were identified. The key functions and adaptive metabolic strategies were determined using comparative studies, mainly those related to cellular material biosynthesis, energy-associated pathways, and cellular detoxification processes. This study provides the groundwork for a highly reliable and reproducible method for the characterization of microbial profiles in the vinegar industry.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Derivation and Validation of a Brief Emergency Department-Based Prediction Tool for Posttraumatic Stress After Motor Vehicle Collision.

STUDY OBJECTIVE: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision. METHODS: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration. RESULTS: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort. CONCLUSION: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.

The association between day of arrival, time of arrival, daily volume and the rate of patients that "left without being seen".

INTRODUCTION: Patients' left without being seen (LWBS) rate is used as an emergency department (ED) quality indicator. Prior research has investigated characteristics of these patients, but there are minimal studies assessing the impact of departmental variables. We evaluate the LWBS rate at a granular level, looking at its relationship to day of week, hour of arrival and total patient volume. METHODS: Retrospective cohort analysis of 109,983 cases from a single academic center. We captured patient disposition, day of week and hour of day of arrival, and total daily volume. Chi-squared test was performed to determine the difference in LWBS rates based on arrival variables. We ran a polynomial regression for LWBS rates by decile of daily patient volume. RESULTS: The overall LWBS rate was 1.82% over 2 years. This varied significantly by day of week and hour of day (p < 0.001). Day of week rates ranged from 0.73% on Sunday to 2.45% on Wednesday. Hour of day rates ranged from 0.26% between 8 AM-9 AM, to 3.71% between 10 PM-11 PM. As total daily patient volume increased, LWBS rates gradually increased until the 70th percentile, followed by significant exponential growth afterwards. DISCUSSION: LWBS rates are not static measurements, and vary greatly depending on ED circumstances. Weekdays and evenings have significantly higher rates. Additionally, LWBS rates climb above 2% as daily registrations reach the 70th percentile, increasing exponentially at each subsequent decile. Understanding these effects will allow for more effective, targeted interventions to minimize this rate and improve throughput.

Machine Learning Methods for Predicting Patient-Level Emergency Department Workload.

BACKGROUND: Work Relative Value Units (wRVUs) are a component of many compensation models, and a proxy for the effort required to care for a patient. Accurate prediction of wRVUs generated per patient at triage could facilitate real-time load balancing between physicians and provide many practical operational and clinical benefits. OBJECTIVE: We examined whether deep-learning approaches could predict the wRVUs generated by a patient's visit using data commonly available at triage. METHODS: Adult patients presenting to an urban, academic emergency department from July 1, 2016-March 1, 2020 were included. Deidentified triage information included structured data (age, sex, vital signs, Emergency Severity Index score, language, race, standardized chief complaint) and unstructured data (free-text chief complaint) with wRVUs as outcome. Five models were examined: average wRVUs per chief complaint, linear regression, neural network and gradient-boosted tree on structured data, and neural network on unstructured textual data. Models were evaluated using mean absolute error. RESULTS: We analyzed 204,064 visits between July 1, 2016 and March 1, 2020. The median wRVUs were 3.80 (interquartile range 2.56-4.21), with significant effects of age, gender, and race. Models demonstrated lower error as complexity increased. Predictions using averages from chief complaints alone demonstrated a mean error of 2.17 predicted wRVUs per visit (95% confidence interval [CI] 2.07-2.27), the linear regression model: 1.00 wRVUs (95% CI 0.97-1.04), gradient-boosted tree: 0.85 wRVUs (95% CI 0.84-0.86), neural network with structured data: 0.86 wRVUs (95% CI 0.85-0.87), and neural network with unstructured data: 0.78 wRVUs (95% CI 0.76-0.80). CONCLUSIONS: Chief complaints are a poor predictor of the effort needed to evaluate a patient; however, deep-learning techniques show promise. These algorithms have the potential to provide many practical applications, including balancing workloads and compensation between emergency physicians, quantify crowding and mobilizing resources, and reducing bias in the triage process.

Outcomes for Patients Discharged to Involuntary Commitment for Substance Use Disorder Directly from the Hospital.

To evaluate the outcomes of patients discharged to involuntary commitment for substance use disorders directly from the hospital. We performed a retrospective chart review of 22 patients discharged to involuntary commitment for substance use disorder from the hospital between October 2016 and February 2020. We collected demographic data, details about each commitment episode, and healthcare utilization outcomes 1 year following involuntary commitment. Nearly all patients had a primary alcohol use disorder (91%) and had additional medical (82%) and psychiatric comorbidities (71%). One year following involuntary commitment, all patients had relapsed to substance use and had at least one emergency department visit while 78.6% had at least one admission. These findings suggest that patients discharged to involuntary commitment directly from the hospital universally relapsed and experienced significant medical morbidity during the first year following their release. This study adds to a growing literature recognizing the harms of involuntary commitment for substance use disorder.

Defining the Emergence of New Immunotherapy Approaches in Breast Cancer: Role of Myeloid-Derived Suppressor Cells.

Breast cancer (BC) continues to be the most diagnosed tumor in women and a very heterogeneous disease both inter- and intratumoral, mainly given by the variety of molecular profiles with different biological and clinical characteristics. Despite the advancements in early detection and therapeutic strategies, the survival rate is low in patients who develop metastatic disease. Therefore, it is mandatory to explore new approaches to achieve better responses. In this regard, immunotherapy arose as a promising alternative to conventional treatments due to its ability to modulate the immune system, which may play a dual role in this disease since the relationship between the immune system and BC cells depends on several factors: the tumor histology and size, as well as the involvement of lymph nodes, immune cells, and molecules that are part of the tumor microenvironment. Particularly, myeloid-derived suppressor cell (MDSC) expansion is one of the major immunosuppressive mechanisms used by breast tumors since it has been associated with worse clinical stage, metastatic burden, and poor efficacy of immunotherapies. This review focuses on the new immunotherapies in BC in the last five years. Additionally, the role of MDSC as a therapeutic target in breast cancer will be described.

Understanding the natural expansion of white mangrove (Laguncularia racemosa) in an ephemeral inlet based on geomorphological analysis and remote sensing data.

The interactions between local tides and river discharges are crucial in the processes related to the recruitment of mangrove propagules in estuarine systems. This investigation aimed to determine the causes of the recent natural recruitment and expansion of Laguncularia racemosa in mudflats within an ephemeral inlet in Mexico. We conducted a fluvial and coastal geomorphology assessment with spaceborne and UAV-based images. We deployed and recorded continuous data loggers in the estuarine system to assess water level and salinity. Depending on the available data, we used a combination of cloud-computing Google Earth Engine, UAV-Digital Surface Models, LiDAR, Google Earth images, and biophysical variables to monitor mangrove forests from 2005 to 2022. When the inlet is open, the estuarine system presents a full tidal range (∼1-1.5 m) with a strong salinity gradient (0-35 mS/cm), in contrast to the strong freshwater influence and minimal water level variability (<10 cm) that prevails for three months when the inlet is closed. Once the mouth of the river closes, there is considerable sediment accumulation, creating mudflat areas adjacent to the mangrove forests where Laguncularia racemosa propagules begin to establish under minimal water level variability and oligohaline conditions. After 16 years, the new forest expanded by 12.3 ha, presenting a very high density (10000 stems/ha), a considerable basal area (54-63 m2/ha), and a maximum canopy height of 15.8 m, which largely surpasses that of other semiarid Laguncularia racemosa forests within permanent open-inlet systems or even in ephemeral inlets with different hydrological conditions. Our study will help to understand the causes of natural Laguncularia racemosa recruitment in extremely dynamic systems.

Hypothermia following cold-water immersion treatment for exertional heat illness.

Cold-water immersion (CWI) is the gold standard therapy for exertional heat illness (EHS), and it is critical to perform CWI expeditiously when the core temperature exceeds 40°C; however, the treatment comes with risks, most notably hypothermia. Following a major marathon, three runners presented to our emergency department (ED) with symptomatic mild hypothermia requiring re-warming. Prior to developing hypothermia, all three were treated at the racecourse with CWI for EHS. During CWI, there are monitoring methods to determine appropriate cessation: continuous temperature measurement, regular temperature checks, using an equation to predict immersion time, and symptom observation. There is no consensus on the best system, but a monitoring method should be used to prevent over-cooling. This case series illustrates the importance of proper CWI execution in order to avoid harm.

Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study.

BACKGROUND: This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. METHODS: We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. RESULTS: Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. CONCLUSIONS: These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.