Quantifying Pain Location and Intensity with Multimodal Pain Body Diagrams.

To quantify an individual's subjective pain severity, standardized pain rating scales such as the numeric rating scale (NRS), visual analog scale (VAS), or McGill pain questionnaire (MPQ) are commonly used to assess pain on a numerical scale. However, these scales are often biased and fail to capture the complexity of pain experiences. In contrast, clinical practice often requires patients to report areas of pain by drawing on a body diagram, which is an effective but qualitative tool. The method presented here extracts quantifiable metrics from pain body diagrams (PBDs) which are validated against the NRS, VAS, and MPQ pain scales. By using a novel pressure-hue transformation on a digital tablet, different drawing pressures applied with a digital stylus can be represented as different hues on a PBD. This produces a visually intuitive diagram of hues ranging from green to blue to red, representing mild to moderate to most painful regions, respectively. To quantify each PBD, novel pain metrics were defined: (1) PBD mean intensity, which equals the sum of each pixel's hue value divided by the number of colored pixels, (2) PBD coverage, which equals the number of colored pixels divided by the total number of pixels on the body, and (3) PBD sum intensity, which equals the sum of all pixels' hue values. Using correlation and information theory analyses, these PBD metrics were shown to have high concordance with standardized pain metrics, including NRS, VAS and MPQ. In conclusion, PBDs can provide novel spatial and quantitative information that can be repeatedly measured and tracked over time to comprehensively characterize a participant's pain experience.

Order from chaos: a case report of a healthy live birth from a genetically "chaotic" embryo.

Objective: To report a case of a healthy, live birth resulting from a "chaotic" embryo (at least 6 chromosomal aneuploidies) after preimplantation genetic testing for aneuploidy (PGT-A). Design: Case report. Setting: University-affiliated fertility clinic. Patients: A same-sex couple with infertility due to failed donor intrauterine insemination and past implantation failure with in vitro fertilization (IVF)/intracytoplasmic sperm injection using donor sperm. Interventions: Frozen single embryo transfer of a "chaotic" embryo after genetic counseling and informed consent. Main Outcome Measures: Live birth of a healthy infant. Results: Controlled ovarian hyperstimulation and transvaginal oocyte retrieval in a 35-year-old female yielded 10 mature oocytes that underwent intracytoplasmic sperm injection with anonymous donor sperm and in vitro culture for 6 days. A single embryo underwent trophectoderm (TE) biopsy at the blastocyst stage and was cryopreserved. PGT-A revealed a "chaotic" test result. After genetic counseling and proper informed consent, a frozen single embryo transfer of this "chaotic" embryo resulted in a successful pregnancy and live birth of a healthy male infant. Conclusions: The reproductive potential of embryos with a "chaotic" TE biopsy result is unknown, but herein, we report a healthy, live birth from a "chaotic" embryo. We recommend that patients and providers faced with disposition decisions regarding "chaotic" embryos seek genetic counseling, consider rebiopsy, or consider transfer with informed consent.

Retrospective Evaluation of Intravenous Enoxaparin Administration in Feline Arterial Thromboembolism.

Induction of a hypocoagulable state is imperative in the treatment of feline arterial thromboembolism. Publications in human medicine report the use of enoxaparin intravenously in selected cases. The aim of our retrospective study was to report the regain of perfusion, short-term outcome, and complications of cats treated with a novel intravenous enoxaparin protocol (1 mg/kg bolus injection followed by 3 mg/kg/day continuous infusion) combined with oral clopidogrel administration. The secondary aim was to report the monitoring of enoxaparin with anti-Xa activity. There were 36 cats included. The probability of reaching limb reperfusion was significantly (p = 0.0148) higher with anti-Xa activity within or above the target range compared to results below the target range (19/21, 90% versus 11/20, 55%). The complications observed were acute kidney injury (15/36, 42%), hemorrhage (2/36, 6%), and neurological signs (6/36, 17%). The most common causes of death/euthanasia were cardiac instability, acute kidney injury, neurological abnormalities, and limb necrosis. The hospital discharge rate was 83% (10/12) for single limb and 29% (7/24) for dual limb thrombosis; the difference was significant (p = 0.0039). The median hospitalization time for the survivors was 119.5 (95-480) h. Our study supports the use of intravenous continuous rate infusion of enoxaparin in combination with oral clopidogrel for cats with aortic thromboembolism. We report similar discharge rates and lower hemorrhage rates than previously reported with thrombolytic treatment.

Gene-environment interaction analysis incorporating sex, cardiometabolic diseases, and multiple deprivation index reveals novel genetic associations with COVID-19 severity.

Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors (obesity and type 2 diabetes [T2D], tested jointly), and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome-wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the PGF gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non-genetic risk factors in an interaction testing approach for genetic discovery.

Regional biomechanical and failure properties of healthy human ascending aorta and root.

PURPOSE: Aortic dissection (AD) is a life-threatening event that occurs when the intimal entry tear propagates and separates inner from outer layers of the aorta. Diameter, the current criterion for aneurysm repair, is far from ideal and additional evidence to optimize clinical decision would be extremely beneficial. Biomechanical investigation of the regional failure properties of aortic tissue is essential to understand and proactively prevent AD. We previously studied biaxial mechanical properties of healthy human aorta. In this study, we investigated the regional failure properties of healthy human ascending aorta (AscAo) including sinuses of Valsalva (SOV), and sinotubular junction (STJ). RESULTS: A total of 430 intact tissue samples were harvested from 19 healthy donors whose hearts were excluded from heart transplantation. The donors had mean age of 51 ± 11.7 years and nearly equal gender distribution. Samples were excised from aortic regions and subregions at defined locations. Tissue strips were subjected to either biaxial or uniaxial failure testing. Wall thickness varied regionally being thickest at AscAo (2.08 ± 0.66 mm) and thinnest at SOV (1.46 ± 0.31 mm). Biaxial testing demonstrated hyperplastic behavior of aortic tissues. Posterior and lateral STJ subregions were found to be stiffer than anterior and medial subregions in both circumferential and longitudinal directions. Failure stresses were significantly higher in the circumferential than longitudinal directions in each subregion of AscAo, STJ, and SOV. Longitudinal failure stresses were significantly greater in AscAo than those in STJ or SOV. Longitudinal failure stresses in AscAo were much smaller anteriorly than posteriorly, and medially than laterally. CONCLUSIONS: The finding of weakest region at the sinotubular junction along the longitudinal direction corroborates clinical observations of that region being commonly involved as the initial site of intimal tear in aortic dissections. Failure stretch ratios correlated to elastic modulus at each region. Furthermore, strong correlation was seen between STJ failure stresses and elastic modulus at physiological pressure along both circumferential and longitudinal directions. Correlating in-vivo aortic elastic modulus based on in-vivo imaging with experimentally determined elastic modulus at physiological pressure and failure stresses may potentially provide valuable information regarding aortic wall strength. Better understanding of aortic biomechanics in normal physiologic and aneurysmal pathologic states may aid in determining risk factors for predicting dissection in patient-specific fashion.

Gene-Environment Interaction Analysis Incorporating Sex, Cardiometabolic Diseases, and Multiple Deprivation Index Reveals Novel Genetic Associations With COVID-19 Severity.

Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors [obesity and type 2 diabetes (T2D), tested jointly], and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome-wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the placental growth factor (PGF) gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non-genetic risk factors in an interaction testing approach for genetic discovery.

Transient hypogammaglobulinemia and severe atopic dermatitis: Open-label treatment with immunoglobulin in a case series.

BACKGROUND: We reported on six infants between 5 and 11 months old, with transient hypogammaglobulinemia of infancy and severe refractory atopic dermatitis, who were treated with open-label immunoglobulin (Ig) after conventional therapy failed. All six infants had an IgG level of <225 mg/dL, elevated eosinophil and IgE levels, and no urine or stool protein losses, but they did exhibit hypoalbuminemia. OBJECTIVE: To evaluate the utility of open-label immunoglobulin in infants with severe atopic dermatitis for whom conventional therapy failed. We reviewed the clinical utility of intravenous immunoglobulin in the treatment of severe atopic dermatitis, the most recent research in the field, and suggested mechanisms for its benefit. METHODS: The six infants were identified from a retrospective chart review at the University of California Los Angeles Allergy and Immunology outpatient pediatric clinic. RESULTS: All six patients were treated with 400 mg/kg/month of intravenous immunoglobulin and had normalization of their IgG and albumin levels, and all but one had clinically improved atopic dermatitis. CONCLUSION: Infants with severe atopic dermatitis who did not respond to conventional therapy avoidance may benefit from intravenous immunoglobulin therapy.

Spectral heterogeneity of PRODAN fluorescence in isotropic solvents revealed by multivariate photokinetic analysis.

This paper describes a multivariate analysis of the fluorescence emission of 6-propionyl-2-dimethylaminonaphthalene (PRODAN) in a series of isotropic solvents of differing polarity and hydrogen-bonding ability. Multivariate methods distill the essential features from spectral data matrices so that the structural details that are embedded within the data are revealed to the analyst. In the aprotic solvents investigated, the analysis reveals a pair of emission components that have emission maxima that scale with the orientational polarizability. In the alcohols, short-lived, polarity-independent blue bands tentatively attributed to neutral hydrogen-bonded solute-solvent complexes form and relax prior to emission from paired bands that have Stokes shifts that scale with the solvent hydrogen-bonding ability rather than the polarity. In water, the short-lived blue bands were not observed, but the shift in the paired bands did scale with the solvent hydrogen-bonding ability.