Does cognitive dysfunction correlate with dizziness severity in patients with vestibular migraine?

OBJECTIVE: To characterize the relationship between dizziness severity and cognitive dysfunction in vestibular migraine (VM) patients. METHODS: Dizziness Handicap Inventory (DHI) and Cognitive Failures Questionnaire (CFQ) scores were compared pre- and post-treatment in a cohort of definite VM patients who underwent evaluation in a multidisciplinary clinic from 2016 to 2020. RESULTS: 44 patients were included. DHI reduction of 11.96 (SD 11.49) (p < 0.001) from an initial mean of 58.36 (22.05) and CFQ reduction of 4.57 (12.20) (p = 0.017) from an initial mean of 47.66 (19.12) were demonstrated. Both pre- and post-treatment DHI scores correlated with pre- and post-treatment CFQ scores (r = 0.537, p < 0.001 and r = 0.667, p < 0.001, respectively). Change in DHI score correlated with change in CFQ score (r = 0.351, p = 0.019). CONCLUSIONS: Cognitive dysfunction in VM patients is correlated with dizziness severity. The DHI may fail to thoroughly assess cognitive dysfunction in VM patients. Additionally, multidisciplinary treatment of VM reduces both dizziness severity and cognitive dysfunction.

Development and internal validation of a humeral torsion prediction model in professional baseball pitchers.

BACKGROUND: Humeral torsion (HT) has been linked to pitching arm injury risk after controlling for shoulder range of motion. Currently measuring HT uses expensive equipment, which inhibits clinical assessment. Developing an HT predictive model can aid clinical baseball arm injury risk examination. Therefore, the purpose of this study was to develop and internally validate an HT prediction model using standard clinical tests and measures in professional baseball pitchers. METHODS: An 11-year (2009-2019) prospective professional baseball cohort was used for this study. Participants were included if they were able to participate in all practices and competitions and were under a Minor League Baseball contract. Preseason shoulder range of motion (external rotation [ER], internal rotation [IR], horizontal adduction [HA]) and HT were collected each season. Player age, arm dominance, arm injury history, and continent of origin were also collected. Examiners were blinded to arm dominance. An a priori power analysis determined that 244 players were needed for accurate prediction models. Missing data was low (<3%); thus, a complete case analysis was performed. Model development followed the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) recommendations. Regression models with restricted cubic splines were performed. Following primary model development, bootstrapping with 2000 iterations were performed to reduce overfitting and assess optimism shrinkage. Prediction model performance was assessed through root mean square error (RMSE), R2, and calibration slope with 95% confidence intervals (CIs). Sensitivity analyses included dominant and nondominant HT. RESULTS: A total of 407 professional pitchers (age: 23.2 [standard deviation 2.4] years, left-handed: 17%; arm history prevalence: 21%) participated. Predictors with the highest influence within the model include IR (0.4, 95% CI 0.3, 0.5; P < .001), ER (-0.3, 95% CI -0.4, -0.2; P < .001), HA (0.3, 95% CI 0.2, 0.4; P < .001), and arm dominance (right-handed: -1.9, 95% CI -3.6, -0.1; P = .034). Final model RMSE was 12, R2 was 0.41, and calibration was 1.00 (95% CI 0.94, 1.06). Sensitivity analyses demonstrated similar model performance. CONCLUSIONS: Every 3° of IR explained 1° of HT. Every 3° of ER explained 1° less of HT, and every 7° of HA explained 1° of HT. Right-handers had 2° less HT. Models demonstrated good predictive performance. This predictive model can be used by clinicians to infer HT using standard clinical test and measures. These data can be used to enhance professional baseball arm injury examination.

The Association Between Curvature and Rupture in a Murine Model of Abdominal Aortic Aneurysm and Dissection.

BACKGROUND: Mouse models of abdominal aortic aneurysm (AAA) and dissection have proven to be invaluable in the advancement of diagnostics and therapeutics by providing a platform to decipher response variables that are elusive in human populations. One such model involves systemic Angiotensin II (Ang-II) infusion into low density-lipoprotein receptor-deficient (LDLr-/-) mice leading to intramural thrombus formation, inflammation, matrix degradation, dilation, and dissection. Despite its effectiveness, considerable experimental variability has been observed in AAAs taken from our Ang-II infused LDLr-/- mice (n=12) with obvious dissection occurring in 3 samples, outer bulge radii ranging from 0.73 to 2.12 mm, burst pressures ranging from 155 to 540 mmHg, and rupture location occurring 0.05 to 2.53 mm from the peak bulge location. OBJECTIVE: We hypothesized that surface curvature, a fundamental measure of shape, could serve as a useful predictor of AAA failure at supra-physiological inflation pressures. METHODS: To test this hypothesis, we fit well-known biquadratic surface patches to 360° micro-mechanical test data and used Spearman's rank correlation (rho) to identify relationships between failure metrics and curvature indices. RESULTS: We found the strongest associations between burst pressure and the maximum value of the first principal curvature (rho=-0.591, p-val=0.061), the maximum value of Mean curvature (rho=-0.545, p-val=0.087), and local values of Mean curvature at the burst location (rho=-0.864, p-val=0.001) with only the latter significant after Bonferroni correction. Additionally, the surface profile at failure was predominantly convex and hyperbolic (saddle-shaped) as indicated by a negative sign in the Gaussian curvature. Findings reiterate the importance of shape in experimental models of AAA.

In-situ calibration of laser/galvo scanning system using dimensional reference artefacts.

Laser powder bed fusion systems use a high-power laser, steered by two galvanometer (galvo) mirrors to scan a pattern on metal powder layers. Part geometric tolerances depend on the positioning accuracy of the laser/galvo system. This paper describes an in-situ calibration technique utilizing a camera coaxially aligned with the laser imaging a dimensional reference artefact. The laser positions are determined from the images captured by the camera while scanning the artefact. The measurement uncertainty is estimated using simulations. The in-situ calibration results are compared with the results obtained from the typical 'mark and measure' galvo calibration method.

Rates of asymptomatic respiratory virus infection across age groups.

Respiratory viral infections are a leading cause of disease worldwide. A variety of respiratory viruses produce infections in humans with effects ranging from asymptomatic to life-treathening. Standard surveillance systems typically only target severe infections (ED outpatients, hospitalisations, deaths) and fail to track asymptomatic or mild infections. Here we performed a large-scale community study across multiple age groups to assess the pathogenicity of 18 respiratory viruses. We enrolled 214 individuals at multiple New York City locations and tested weekly for respiratory viral pathogens, irrespective of symptom status, from fall 2016 to spring 2018. We combined these test results with participant-provided daily records of cold and flu symptoms and used this information to characterise symptom severity by virus and age category. Asymptomatic infection rates exceeded 70% for most viruses, excepting influenza and human metapneumovirus, which produced significantly more severe outcomes. Symptoms were negatively associated with infection frequency, with children displaying the lowest score among age groups. Upper respiratory manifestations were most common for all viruses, whereas systemic effects were less typical. These findings indicate a high burden of asymptomatic respiratory virus infection exists in the general population.

How Genomics Is Personalizing the Management of Dyslipidemia and Cardiovascular Disease Prevention.

PURPOSE OF THE REVIEW: To summarize advances in genomic medicine and anticipated future directions to improve cardiovascular risk reduction. RECENT FINDINGS: Mendelian randomization and genome-wide association studies have given significant insights into the role of genetics in dyslipidemia and cardiovascular disease (CVD), with over 160 gene loci found to be associated with coronary artery disease to date. This has enabled the creation of genetic risk scores that have demonstrated improved risk prediction when added to clinical markers of CVD risk. Incorporation of genomic data into clinical patient care is on the horizon. Genomic medicine is expected to offer improved risk assessment, determination of targeted treatment strategies, and improved detection of lipid disorders causal to CVD development.

The future of n-3 polyunsaturated fatty acid therapy.

PURPOSE OF REVIEW: This article focuses on the potential role by which a complex mixture of omega-3 fatty acids (OM3-FAs) may beneficially modify cardiovascular risk by modifying the cholesterol composition of atherogenic lipoproteins. This hypothesis is being tested in the STRENGTH trial, which is enrolling 13 000 patients on statins at high cardiovascular risk with hypertriglyceridemia and low HDL cholesterol (HDL-C) treated with an OM3-carboxylic acid. RECENT FINDINGS: Complex mixtures of OM3-FAs containing predominately eicosapentanoic acid and docosahexanoic acid in combination with statins lowers non-HDL by reducing triglyceride-rich lipoprotein cholesterol (TRL-C) while shifting small LDL cholesterol (LDL-C) to large LDL-C. Recent genomic and epidemiological studies have implicated TRL-C and small LDL-C as causal for cardiovascular disease. Therefore OM3-FAs containing both eicosapentanoic acid and docosahexanoic acid in combination with statins may beneficially modify the high residual risk for patients with hypertriglyceridemia and low HDL-C. SUMMARY: Although outcome trials are underway, subgroup analyses of data from previous randomized controlled trials are suggestive of a reduction in coronary artery disease and atherosclerotic cardiovascular disease event rates with triglyceride and TRL-C lowering therapies, particularly if accompanied by low HDL-C. Although the limitations of such data are acknowledged, clinicians must make treatment decisions while awaiting more definitive results from well-designed large-scale randomized controlled trials.

A fire history derived from Pinus resinosa Ait. for the Islands of Eastern Lac La Croix, Minnesota, USA.

We reconstructed fire occurrence near a fur-trade era canoe travel corridor (used ca. 1780-1802) in the Quetico-Superior region west of Lake Superior to explore the possibility of human influence on pre-fire suppression rates of fire occurrence. Our research objectives were to (1) examine the spatial and temporal patterns of fire in the study area, (2) test fires' strength of association with regional drought, and (3) assess whether reconstructed fire frequencies could be explained by observed rates of lightning fire ignition over the modern period of record. We developed a 420-year fire history for the eastern portion of Lac La Croix in the Boundary Waters Canoe Area Wilderness (BWCAW). Seventy-one fire-scarred samples were collected from remnant Pinus resinosa Ait. (red pine) stumps and logs from thirteen distinct island and three mainland forest stands. Collectively these samples contained records of 255 individual fire scars representing 79 fire events from 1636 to 1933 (study area mean fire intervals [MFI] 3.8 yr). Reconstructed fires were spatially and temporally asynchronous and not strongly associated with regional drought (P > 0.05). When compared to the conservative, tree-ring reconstructed estimate of historical fire occurrence and modern lightning-caused fires (1929-2012), a noticeable change in the distribution and frequency of fires within the study area was evident with only two lightning-ignited island fires since 1934 in the study area. Our results suggest a high likelihood that indigenous land use contributed to surface fire ignitions within our study area and highlights the importance of examining the potential effects of past indigenous land use when determining modern approaches to fire and wilderness management in fire-adapted ecosystems.

Preseason shoulder range of motion screening as a predictor of injury among youth and adolescent baseball pitchers.

BACKGROUND: Approximately 6 million youngsters play organized baseball yearly, and injuries are common. Defining of risk factors for injuries in the throwing shoulder has largely been confined to the professional thrower. Unfortunately, these risk factors apply to only 1% of pitchers at risk for injury. Risk factors for injury in youth pitchers have received far less attention than those in more mature professional pitchers. Development of such an understanding would help clarify injury prevention efforts for the other 99% of pitchers actively participating in competitive baseball. This study intended to determine the ability of range of motion (ROM) measures to predict arm injuries in baseball pitchers aged 8 to 18 years. METHODS: Supine passive shoulder ROM was assessed in 115 pitchers with a digital inclinometer. Two trials of ROM were measured before the season. Arm injuries were prospectively tracked. Receiver operating characteristic curves were used to identify athletes who were at high risk for injury. Statistical significance was set a priori (α = .05). RESULTS: There were 33 injured and 82 uninjured pitchers. Side-to-side differences of horizontal adduction >15° and internal rotation >13° may discriminate between those adolescent pitchers at 4 and 6 times greater risk of injury, respectively. CONCLUSION: Preseason ROM differences were able to identify those adolescents at high risk for injury during the season. It appears that the risk profile for adolescent pitchers includes horizontal adduction differences that differ from the established prospective profile in adult pitchers.

Cadaveric and Computed Tomography Analysis of the Anterior Ethmoidal Artery Flap.

BACKGROUND: The anterior ethmoidal artery (AEA) flap has been successful in repairing anterior nasal septal perforations and has been presumed to be axially based on AEA branches coursing through or around the cribriform plate (CP). However, limited evidence supports the flap's axial supply. The purposes of this cadaveric and computed tomography (CT) study were to assess the arterial anatomy from the CP to the septum, and to determine AEA flap length to predict ideal flap base width. METHODS: Ten fresh latex-injected cadavers were utilized for endoscopic dissection to identify arteries traversing the CPs on each side. First, arterial trajectories along the dorsal septum were recorded. Measurements were then made bilaterally along the septum from the middle turbinate (MT) axilla to the nasal branch of the AEA (NBAEA) traversing the CP. Additionally, 100 sinus CTs were reviewed to measure AEA flap lengths bilaterally. RESULTS: From 10 cadavers, 20 sides were utilized for measurements. In all cadavers, the AEA septal branches coursed diagonally or horizontally along the dorsal septum, and never directly vertically. The mean distance from the MT axilla to the NBAEA was 1.24 ± 1.93 cm (range = 1-1.5 cm). Based on CTs, the mean AEA flap length was 6.40 ± 0.60 cm. CONCLUSIONS: Based on the non-vertical courses of AEA septal branches, the AEA flap is more likely a random transposition flap than an axial flap. Average AEA flap length ranged from 6.0 to 7.0 cm. Assuming 3:1 length:width ratios, AEA flap base widths should be about 2.0-2.3 cm. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2100-2104, 2024.

Comparison between a deep-learning and a pixel-based approach for the automated quantification of HIV target cells in foreskin tissue.

The availability of target cells expressing the HIV receptors CD4 and CCR5 in genital tissue is a critical determinant of HIV susceptibility during sexual transmission. Quantification of immune cells in genital tissue is therefore an important outcome for studies on HIV susceptibility and prevention. Immunofluorescence microscopy allows for precise visualization of immune cells in mucosal tissues; however, this technique is limited in clinical studies by the lack of an accurate, unbiased, high-throughput image analysis method. Current pixel-based thresholding methods for cell counting struggle in tissue regions with high cell density and autofluorescence, both of which are common features in genital tissue. We describe a deep-learning approach using the publicly available StarDist method to count cells in immunofluorescence microscopy images of foreskin stained for nuclei, CD3, CD4, and CCR5. The accuracy of the model was comparable to manual counting (gold standard) and surpassed the capability of a previously described pixel-based cell counting method. We show that the performance of our deep-learning model is robust in tissue regions with high cell density and high autofluorescence. Moreover, we show that this deep-learning analysis method is both easy to implement and to adapt for the identification of other cell types in genital mucosal tissue.

The Role of Humeral Torsion on Glenohumeral Rotation in Injured Baseball Players.

Background: Differences in rotational range of motion (ROM) compared to humeral retrotorsion (HRT)-corrected rotational ROM exist in healthy baseball athletes, but it is unclear whether these differences exist in a pathological population. Purpose/Hypothesis: The purpose of this study was to determine if there are disparities between objectively measured differences in ROM and HRT-corrected deficits in injured baseball players. It was hypothesized that disparities would exist between (1) the side-to-side difference in glenohumeral external rotation (GER) and the HRT-corrected glenohumeral external rotation deficit (GERD) and (2) the side-to-side difference in glenohumeral internal rotation (GIR) and the HRT-corrected glenohumeral internal rotation deficit (GIRD). Study Design: Cross-sectional study; Level of evidence, 3. Methods: Data from 172 baseball players with shoulder or elbow injuries (45 shoulder, 127 elbow) were reviewed in July 2023. GER and GIR were measured on the injured and noninjured sides of all players, and diagnostic ultrasound was used to measure HRT. Dependent t tests were run to compare the side-to side differences in GER and GIR with the HRT-corrected GERD and GIRD, respectively. Results: In the players with a shoulder injury, there was a significant disparity between the side-to-side difference in GER and the HRT-corrected GERD (2°± 14° vs -13°± 15°, respectively) and between the side-to-side difference in GIR and the HRT-corrected GIRD (-14°± 8° vs 2°± 9°, respectively) (P < .001 for both). Similarly, players with an elbow injury had significant disparities between the side-to-side difference in GER and the HRT-corrected GERD (6°± 9° vs -10°± 9°, respectively) and between the side-to-side difference in GIR and the HRT-corrected GIRD (-12°± 8° vs 4°± 10°, respectively) (P < .001 for both). Conclusion: The results supported our hypothesis that there were disparities between objectively measured differences in GER and GIR compared with the HRT-corrected GERD and GIRD in injured baseball players. Consideration must be given to osseous adaptations that occur at the glenohumeral joint when evaluating and treating this population.

A narrative review of little league shoulder: proximal humeral physis widening is only one piece of the puzzle, it is time to consider posterior glenoid dysplasia.

Baseball athletes across all levels of play are at an increased risk for upper extremity injury due to the supraphysiologic demands on the shoulder and elbow during overhead throwing. Little league baseball players present with a unique subset of injuries that can affect the growth plate, commonly at the shoulder or the elbow. Ascertaining a diagnosis and plan of care for little league shoulder (LLS) historically focuses on the proximal humeral physis in skeletally immature throwing athletes presenting with shoulder pain. However, while not a current standard of care, posterior glenoid dysplasia is often present in youth baseball athletes presenting with LLS, warranting a shift in the way clinicians evaluate for and treat the youth baseball athlete's pathologic shoulder. Therefore, purpose of this narrative review is 2-fold: first, to describe the current standard of care as it relates to a diagnosis of LLS, and second, to critically describe a comprehensive evaluation process for youth throwing athletes with shoulder pain that includes screening for evidence of posterior glenoid dysplasia. This paper summarizes the current state of the available evidence for anatomic considerations of LLS in the baseball athletes throwing shoulder. Additionally, we provide a framework for clinical evaluation using a multidisciplinary approach to evaluate the entire kinetic chain of the youth baseball athlete presenting with LLS and posterior glenoid dysplasia. A case study is presented to describe common presentations, clinical and objective examinations, and a plan of care from time of evaluation to return to throwing.

The epigenetic landscape of oral squamous cell carcinoma.

BACKGROUND: There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs. METHODS: DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival. RESULTS: Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series. CONCLUSION: Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.

The heparin-binding protein interactome in pancreatic diseases.

BACKGROUND: The cellular microenvironment plays an important role in the regulation of homoeostasis and is a source of potential biomarkers and drug targets. In a genome-wide analysis the extracellular proteins that bind to heparin (HBPs) have been shown to form highly modular and interconnected extracellular protein regulatory networks. Using a systems biology approach, we have investigated the role of HBP networks in the normal pancreas and pancreatic digestive diseases. METHODS: Lists of mRNAs encoding for HBPs associated with the normal pancreas (NP), acute pancreatitis (AP), chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) were obtained using public databases and publications. Networks of the putative protein interactomes derived from mRNA expression data of HBPs were built and analysed using cluster analysis, gene ontology term enrichment and canonical pathways analysis. RESULTS: The extracellular heparin-binding putative protein interactomes in the pancreas were better connected than their non heparin-binding counterparts, having higher clustering coefficients in the normal pancreas (0.273), acute pancreatitis (0.457), chronic pancreatitis (0.329) and pancreatic ductal adenocarcinoma (0.269). 'Hepatic Fibrosis/Hepatic Stellate Cell Activation' appears to be a significant canonical pathway in pancreatic homoeostasis in health and disease with a large number of important HBPs. CONCLUSIONS: Our analyses clearly demonstrate that HBPs form disease-specific and highly connected networks that can be explored for potential biomarkers and as collective drug targets via the modification of heparin binding properties.

In situ visualization of aortic dissection propagation in notched rabbit aorta using synchrotron X-ray tomography.

Aortic dissection is a complex, intramural, and dynamic condition involving multiple mechanisms, hence, difficult to observe. In the present study, a controlled in vitro aortic dissection was performed using tension-inflation tests on notched rabbit aortic segments. The mechanical test was combined with conventional (cCT) and synchrotron (sCT) computed tomography for in situ imaging of the macro- and micro-structural morphological changes of the aortic wall during dissection. We demonstrate that the morphology of the notch and the aorta can be quantified in situ at different steps of the aortic dissection, and that the notch geometry correlates with the critical pressure. The phenomena prior to propagation of the notch are also described, for instance the presence of a bulge at the tip of the notch is identified, deforming the remaining wall. Finally, our method allows us to visualize for the first time the propagation of an aortic dissection in real-time with a resolution that has never previously been reached. STATEMENT OF SIGNIFICANCE: With the present study, we investigated the factors leading to the propagation of aortic dissection by reproducing this mechanical process in notched rabbit aortas. Synchrotron CT provided the first visualisation in real-time of an aortic dissection propagation with a resolution that has never previously been reached. The morphology of the intimal tear and aorta was quantified at different steps of the aortic dissection, demonstrating that the early notch geometry correlates with the critical pressure. This quantification is crucial for the development of better criteria identifying patients at risk. Phenomena prior to tear propagation were also described, such as the presence of a bulge at the tip of the notch, deforming the remaining wall.

Soluble E-cadherin: A marker of genital epithelial disruption.

PROBLEM: The genital epithelial barrier is a crucial first line of defence against HIV, and epithelial disruption may enhance HIV susceptibility. Assessment of genital epithelial integrity requires biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. The purpose of this study was to evaluate soluble E-cadherin (sE-cad) as a marker of genital epithelial disruption. METHOD OF STUDY: Using in vitro models of endocervical and foreskin epithelial cells, we assessed changes in sE-cad, IL-6, IL-1ß, and IL-1α levels following mechanical disruption. We also assessed changes in sE-cad levels in vivo in cervicovaginal secretions after epithelial disruption by endocervical cytobrush sampling in Canadian women, and assessed the relationship between levels of sE-cad in coronal sulcus swabs to membrane-bound E-cadherin in the overlying foreskin tissue in Ugandan men. RESULTS: sE-cad levels immediately increased after in vitro epithelial physical disruption with the degree of elevation dependent on the extent of disruption, as did levels of IL-1ß and IL-1α; this was followed by a delayed increase in IL-6 levels. In vivo results confirmed that sE-cad levels in cervicovaginal secretions were elevated 6 h after cytobrush sampling when compared to baseline. Furthermore, levels of sE-cad in the prepuce were inversely correlated with the amount of membrane-bound E-cadherin of overlying tissue. CONCLUSION: Our results validate the use of sE-cad as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.

Effect of Adjunctive Dexmedetomidine in the Treatment of Alcohol Withdrawal Compared to Benzodiazepine Symptom-Triggered Therapy in Critically Ill Patients: The EvADE Study.

OBJECTIVE: This study evaluated the safety and efficacy of adjunctive dexmedetomidine for alcohol withdrawal syndrome (AWS) treatment compared to symptom-triggered benzodiazepine therapy. METHODS: This single-center, retrospective, cohort study evaluated patients admitted to an intensive care unit (ICU) with AWS. Patients were divided into 2 groups: adjunctive dexmedetomidine or symptom-triggered therapy (control). Primary outcome was change in Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) score. Secondary outcomes assessed cumulative ICU benzodiazepine requirement and ICU/hospital length of stay (LOS). Safety outcomes evaluated incidence of adverse events, new onset seizures, and intubation. Propensity matching was performed to minimize differences between study groups. RESULTS: Overall, 147 patients were included, 56 in the dexmedetomidine group and 91 in the control group. Patient demographics were similar, however baseline CIWA-Ar score was statistically higher in the dexmedetomidine group. Following propensity matching, 55 patients were included in each group. No significant difference was noted for change in CIWA-Ar score (median, IQR) [3.8 (-0.4-12.3) dexmedetomidine vs. 5.4 (1.4-12.9) control, p = 0.223]. Secondary endpoints revealed increased benzodiazepine requirements (p = 0.001), prolonged ICU LOS (p = 0.050), and more frequent use of physical restraints (p = 0.001) in the dexmedetomidine group. While not statistically significant, the development of new onset seizures (p = 0.775) and intubation (p = 0.294) occurred more frequently in the dexmedetomidine group. CONCLUSION: The addition of dexmedetomidine to symptom-triggered benzodiazepines for AWS did not produce a significant change in CIWA-Ar scores from baseline compared to symptom-triggered therapy alone. The increased rate of new onset seizures and intubation warrant further investigation into the safety of dexmedetomidine in AWS.

Quantitative Immunofluorescent Imaging of Immune Cells in Mucosal Tissues.

Understanding the interplay between commensals, pathogens, and immune cells in the skin and mucosal tissues is critical to improve prevention and treatment of a myriad of diseases. While high-parameter flow cytometry is the current gold standard for immune cell characterization in blood, it is less suitable for mucosal tissues, where structural and spatial information is lost during tissue disaggregation. Immunofluorescence overcomes this limitation, serving as an excellent alternative for studying immune cells in mucosal tissues. However, the use of immunofluorescent microscopy for analyzing clinical samples is hampered by a lack of high-throughput quantitative analysis techniques. In this chapter, we describe methods for sectioning, staining, and imaging whole sections of human foreskin tissue. We also describe methods to automate immune cell quantification from immunofluorescent images, including image preprocessing and methods to quantify both circular and irregularly shaped immune cells using open-source software.