Practical Advice on Measuring and Applying Light for Laboratory Mammals.

Light is recognized as an important component of the environment for laboratory animals. It supports vision, sets the phase of circadian clocks, and drives wide-ranging adjustments in physiological and behavioral state. Manipulating light is meanwhile a key experimental approach in the fields of vision science and chronobiology. Nevertheless, until recently, there has been no consensus on methods for quantifying light as experienced by laboratory animals. Widely adopted practices employ metrics such as illuminance (units = lux) that are designed to quantify light as experienced by human observers. These weight energy across the spectrum according to a spectral sensitivity profile for human vision that is not widely replicated for non-human species. Recently, a Consensus View was published that proposes methods of light measurement and standardization that take account of these species-specific differences in wavelength sensitivity. Here, we draw upon the contents of that consensus to provide simplified advice on light measurement in laboratory mammal experimentation and husbandry and quantitative guidance on what constitutes appropriate lighting for both visual and circadian function.

Novel inhibition of central carbon metabolism pathways by Rac and Cdc42 inhibitor MBQ-167 and paclitaxel.

Triple negative breast cancer (TNBC) represents a therapeutic challenge where standard chemotherapy is limited to paclitaxel. MBQ-167, a clinical stage small molecule inhibitor that targets Rac and Cdc42, inhibits tumor growth and metastasis in mouse models of TNBC. Herein, we investigated the efficacy of MBQ-167 in combination with paclitaxel in TNBC pre-clinical models, as a prelude to safety trials of this combination in advanced breast cancer patients. Individual MBQ-167 or combination therapy with paclitaxel was more effective at reducing TNBC cell viability and increasing apoptosis compared to paclitaxel alone. In orthotopic mouse models of human TNBC (MDA-MB-231 and MDA-MB-468), individual MBQ-167, paclitaxel, or the combination reduced mammary tumor growth with similar efficacy, with no apparent liver toxicity. However, paclitaxel single agent treatment significantly increased lung metastasis, while MBQ-167, single or combined, reduced lung metastasis. In the syngeneic 4T1/BALB/c model, combined MBQ-167 and paclitaxel decreased established lung metastases by ~80%. To determine the molecular basis for the improved efficacy of the combined treatment on metastasis, 4T1 tumor extracts from BALB/c mice treated with MBQ-167, paclitaxel, or the combination were subjected to transcriptomic analysis. Gene set enrichment identified specific downregulation of central carbon metabolic pathways by the combination of MBQ-167 and Paclitaxel but not individual compounds. Biochemical validation, by immunoblotting and metabolic Seahorse analysis, shows that combined MBQ-167 and paclitaxel reduces glycolysis. This study provides a strong rationale for the clinical testing of MBQ-167 in combination with paclitaxel as a potential therapeutic for TNBC and identifies a unique mechanism of action.

Profiles of alcohol intoxication and their associated risks in young adults' natural settings: A multilevel latent profile analysis applied to daily transdermal alcohol concentration data.

OBJECTIVE: Transdermal alcohol concentration (TAC) sensors capture aspects of drinking events that self-reports cannot. The multidimensional nature of TAC data allows novel classification of drinking days and identification of associated behavioral and contextual risks. We used multilevel latent profile analysis (MLPA) to create day-level profiles of TAC features and test their associations with (a) daily behaviors and contexts and (b) risk for alcohol use disorders at baseline. METHOD: Two hundred twenty-two regularly heavy-drinking young adults (Mage = 22.3) completed the Alcohol Use Disorders Identification Test (AUDIT) at baseline and then responded to mobile phone surveys and wore TAC sensors for six consecutive days. MLPA identified day-level profiles using four TAC features (peak, rise rate, fall rate, and duration). TAC profiles were tested as correlates of daily drinking behaviors, contexts, and baseline AUDIT. RESULTS: Four profiles emerged: (a) high-fast (8.5% of days), (b) moderate-fast (12.8%), (c) low-slow (20.4%), and (d) little-to-no drinking days (58.2%). Profiles differed in the odds of risky drinking behaviors and contexts. The highest risk occurred on high-fast days, followed by moderate-fast, low-slow, and little-to-no drinking days. Higher baseline AUDIT predicted higher odds of high-fast and moderate-fast days. CONCLUSIONS: Days with high and fast intoxication are reflective of high-risk drinking behaviors and were most frequent among those at risk for alcohol use disorders. TAC research using MLPA may offer novel and important insights to intervention efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predicting Postoperative Satisfaction with Breasts: How Important is the Preoperative BREAST-Q Score?

BACKGROUND: The role that preoperative Satisfaction with Breast plays in a patient's postoperative course after postmastectomy breast reconstruction (PMBR) is not understood. The aim of this study is to understand the impact of the preoperative score on postoperative outcome as an independent variable. METHODS: We examined patients who underwent PMBR between 2017 and 2021 and who completed the BREAST-Q Satisfaction with Breasts at 1 year postoperatively. Two multiple linear regression models (Model 1 with the preoperative Satisfaction with Breasts score and Model 2 without the preoperative score), likelihood ratio tests, simple t-statistics, and sample patient dataset to predict the 1 year score were performed. Multiple imputation was used to account for missing preoperative scores. RESULTS: Overall, 2324 patients were included. Model 1 showed that the preoperative score is significantly associated with the postoperative score (ß = 0.09, 95% confidence interval 0.04-0.14; p < 0.001). Comparing Model 1 and Model 2 demonstrated that including preoperative Satisfaction with Breasts in a regression significantly improves model fit (test statistic = 10.04; p = 0.0021). Using the absolute value of the t-statistics as a measure of variable importance in linear regression, the importance of the preoperative score was quantified as 3.39-more important than neoadjuvant radiation, mastectomy weight, body mass index, bilateral prophylactic mastectomy, and race, but less than adjuvant radiation, reconstruction type, and psychiatric diagnoses. CONCLUSION: Preoperative Satisfaction with Breasts scores are an important independent predictor of postoperative satisfaction after PMBR. Just as vital sign and work-up are carefully documented before surgery, preoperative scores should be collected to pre-emptively gauge patients' satisfaction and optimize postoperative outcomes.

In vivo multi-contrast depth-resolved choroidal imaging of a mouse using polarization-diversity optical coherence tomography.

The results of depth-resolved multi-contrast in vivo mouse choroidal imaging using a polarization-diversity optical coherence tomography (PD-OCT) system are presented. A selectively chosen depth of focus that was fine-tuned with a sensorless adaptive optics technique and a simple segmentation based on the degree of polarization uniformity signal visualizes the detailed features of a mouse choroid from the OCT angiography images. A comprehensive image analysis of the choroid revealed the distinctive pathological characteristics of the laser-induced choroidal neovascularization mouse.

Ocean-colour anomalies quantified by the human eye.

Phytoplankton turn seawater green when their concentration increases. This allows us to monitor them using ocean colour. However, as the spectral properties of phytoplankton and their relationship with other coloured substances in seawater vary, subtle differences (anomalies) in ocean colour occur that can cause large errors in estimates of phytoplankton abundance. Identifying and understanding these anomalies is required to interpret ocean-colour data properly, but not all scientists have access to, or can afford, the in-situ instrumentation needed to do this. We show that practical, low-cost tools developed in the 19th century (a Secchi disk and Forel-Ule colour scale) can be used to quantify a colour anomaly in the Weddell Sea. Our findings imply that ocean-colour anomalies can be identified using affordable methods. Furthermore, records collected over the last century may contain clues on how ocean ecosystems have changed with climate.

Achieving Enteral Autonomy in Children with Intestinal Failure Following Inpatient Admission: A Case Series.

We describe cases of intestinal failure wherein inpatient admission was critical toward enteral autonomy. We performed a retrospective chart review of 6 children with long-term parenteral nutrition dependence who were weaned from parenteral nutrition following admission. Admissions included feeding and medication titration, interdisciplinary care, and home parenteral nutrition team consultation.

Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States.

BACKGROUND: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. METHODS: We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. RESULTS: Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). CONCLUSIONS: After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.

Indication and efficacy of injection laryngoplasty for laryngeal clefts - A retrospective cohort study.

PURPOSE: Laryngeal cleft (LC) is an anatomical defect of the larynx, where there is a gap (or cleft) between the arytenoids. Milder types can be treated with injection laryngoplasty (IL), involving injection with a filler, resulting in a decreased depth of the cleft and thereby reducing tracheal penetration or aspiration. The effect, however, is temporary. The aim of this study was to investigate the possible indications and the efficacy of IL for LC. METHODS: Patients who underwent IL for LC between March 2018 and June 2023 were retrospectively evaluated. The following parameters were studied: incidence of LC symptoms and objective swallowing evaluations before and after IL, the duration of possible symptom improvement, complications, and the number of subsequent suture repairs. RESULTS: Eighty-five patients were included. Before IL, 81 (96 %) patients had symptoms of aspiration during feeding, compared to 41 (54 %) patients after IL (p ≤ 0.001). In 42 (49 %) patients, temporary symptom relief occurred, in 22 (26 %) patients symptoms persisted, in 16 (19 %) patients symptoms decreased permanently. Mild complications such as cough and desaturations in the direct postoperative period occurred. CONCLUSION: This study shows a statistically significant decrease in the number of parents/caretakers reporting swallowing symptoms after injection laryngoplasty, and a decrease in the average percentage of parents/caretakers reporting various other symptoms. Based on our results, injection laryngoplasty can be recommended as a diagnostic tool in the treatment of laryngeal cleft. Furthermore, it can be used as bridge therapy (i.e. until patients outgrow their symptoms, or until suture repair).

Acousto-optic-based time domain electric field sensor for magnetic resonance imaging applications.

An acousto-optic (AO)-based electric field sensor is presented for time domain measurement under magnetic resonance imaging (MRI). A fully MR-compatible sensor is designed and fabricated using a phase-shifted fiber Bragg grating mechanically coupled to a piezoelectric transducer. Mechanical resonance of the piezoelectric transducer is matched to the operating frequencies of commonly used MRI systems to increase the sensitivity of the sensor. Sensitivity of the sensor is measured as 1.27 mV/V/m, with a minimum detectable electric field of 4.4 mV/m/√/Hz. Directivity of the sensor is measured with a 18 dB orthogonal component rejection. The dynamic range of the sensor is calculated as 117 dB/Hz, which allows the measurement of electric fields up to 3.2 kV/m. In MRI studies, the AO sensor was able detect local hot spots around a reference implant accurately with high signal-to-noise ratio. AO sensor exhibited similar or better performance when compared with commercially available MRI compatible electric field sensors. Furthermore, the small size of the sensor with the flexible fiber optic link could allow in situ measurements of electric fields during critical interventional procedures such as pacemaker lead or deep brain stimulator placement as an MRI dosimeter during diagnostic scans.

A cross-cohort analysis of dental plaque microbiome in early childhood caries.

Early childhood caries (ECC) is a multifactorial disease with a microbiome playing a significant role in caries progression. Understanding changes at the microbiome level in ECC is required to develop diagnostic and preventive strategies. In our study, we combined data from small independent cohorts to compare microbiome composition using a unified pipeline and applied a batch correction to avoid the pitfalls of batch effects. Our meta-analysis identified common biomarker species between different studies. We identified the best machine learning method for the classification of ECC versus caries-free samples and compared the performance of this method using a leave-one-dataset-out approach. Our random forest model was found to be generalizable when used in combination with other studies. While our results highlight the potential microbial species involved in ECC and disease classification, we also mentioned the limitations that can serve as a guide for future researchers to design and use appropriate tools for such analyses.

Development and initial validation of a disease-specific instrument to measure health-related quality of life in hypersensitivity pneumonitis.

Rationale and objective: Disease-specific health-related quality of life (HRQOL) instruments enable us to capture domains that are most relevant to specific patient populations and are useful when a more individualised approach to patient assessment is desired. In this study, we assessed the validity and reliability of the first instrument specifically developed to measure HRQOL in hypersensitivity pneumonitis (HP). Methods: A 39-item HP-HRQOL instrument and several anchors were collected from a cohort of patients with HP. Exploratory factor analysis and item reduction were utilised to construct a shortened version of the instrument. Several validity and reliability analyses were conducted on this version of the HP-HRQOL. Measurements and main results: 59 patients with HP completed the study. The revised HP-HRQOL instrument comprises 15 items composing two factors (domains): 1) impacts on daily life; and 2) mental wellbeing. Internal consistency reliability was strong for Factor 1 (Cronbach's α=0.94, 95% CI 0.92-0.96) and Factor 2 (Cronbach's α=0.89, 95% CI 0.85-0.94). Test-retest reliability was strong (ICC 0.94, 95% CI 0.89-0.97). The HP-HRQOL strongly correlated with other validated patient-reported outcome measures and moderately correlated with % predicted forced vital capacity. The HP-HRQOL distinguished between those with different severities of HP as determined by lung function and supplemental oxygen use. Conclusions: The HP-HRQOL, the first patient-reported outcome instrument specific to adults with HP, possesses strong validity and reliability characteristics for measuring disease-specific HRQOL and distinguishes among patients with different severities of disease.

Soft tissue aneurysmal bone cyst presenting as an enlarging neck mass: Case report and review of the head and neck literature.

Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.

Age-specific colorectal cancer incidence trends in Canada, 1971-2021.

INTRODUCTION: Colorectal cancer (CRC) incidence among adults younger than 50 years has increased in recent decades, leading to some advocating for lowering the age to start CRC screening. Here, we estimate age-specific trends in CRC incidence in Canada and changes in risk by birth cohort. METHODS: CRC incidence data from 1971 to 2021 by province, sex, and five-year age group (35-64) were obtained from the National Cancer Incidence Reporting System and the Canadian Cancer Registry. Annual percent changes in age-specific or age-adjusted incidence rates were analyzed with joinpoint regression. Birth cohort effect was estimated with age-period-cohort models and reported as cohort incidence rate ratios (IRRs) with respect to the 1947-51 cohort. RESULTS: CRC incidence has increased among all age groups under 50 years, with the largest relative increases occurring in the youngest age group (35-39 years). Males and females had similar incidence trends, though males under age 50 had larger increases than females. The birth cohort analysis showed that males born since 1966 have a significantly higher risk than those born at any other time. CONCLUSIONS: These results up to 2021 confirm and update reports that CRC incidence is increasing among adults under age 50 in Canada and that the youngest birth cohorts carry the highest risk. Future studies should assess the effectiveness of CRC screening in younger populations.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS). OBJECTIVE: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis was conducted of all RCC BM patients treated with SRS from January 1, 2010 to March 31, 2021. INTERVENTION: SRS for RCC BMs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Next-generation sequencing was performed to identify gene alterations more prevalent in BM patients. Clinical factors and genes altered in ≥10% of samples were assessed per patient using Cox proportional hazards models and per individual BM using clustered competing risks regression with competing risk of death. RESULTS AND LIMITATIONS: Ninety-one RCC BM patients underwent SRS to 212 BMs, with a median follow-up of 38.8 mo for patients who survived. The median intracranial progression-free survival and OS were 7.8 (interquartile range [IQR] 5.7-11) and 21 (IQR 16-32) mo, respectively. Durable local control of 83% was achieved at 12 mo after SRS, and 59% of lesions initially meeting the radiographic criteria for progression at 3-mo evaluation would be considered to represent pseudoprogression at 6-mo evaluation. A comparison of genomic alterations at both the gene and the pathway level for BM+ patients compared with BM- patients revealed phosphoinositide 3-kinase (PI3K) pathway alterations to be more prevalent in BM+ patients (43% vs 16%, p = 0.001, q = 0.01), with the majority being PTEN alterations (17% vs 2.7%, p = 0.003, q = 0.041). CONCLUSIONS: To our knowledge, this is the largest study investigating genomic profiles of RCC BMs and the only such study with annotated intracranial outcomes. SRS provides durable in-field local control of BMs. Recognizing post-SRS pseudoprogression is crucial to ensure appropriate management. The incidence of PI3K pathway alterations is more prevalent in BM+ patients than in BM- patients and warrants further investigation in a prospective setting. PATIENT SUMMARY: We examined the outcomes of radiotherapy for the treatment of brain metastases in kidney cancer patients at a single large referral center. We found that radiation provides good control of brain tumors, and certain genetic mutations may be found more commonly in patients with brain metastasis.

Understanding the physical literacy development of 8- to 12-year-old children living with chronic medical conditions: A comprehensive, mixed methods inquiry.

BACKGROUND: Physical literacy is a concept used to describe the combined physical, affective and cognitive capacities facilitating an active lifestyle. Physical activity participation is essential for children living with chronic medical conditions, but knowledge of physical literacy among this group is scarce. METHODS: An explanatory, sequential mixed methods design was used to comprehensively describe the physical literacies of children with chronic medical conditions (CMCs). Participants were recruited from paediatric cardiology, respirology/cystic fibrosis, neurology, haematology and endocrinology outpatient clinics. All participants completed the Canadian Assessment of Physical Literacy (2nd Edition), and those with higher and lower scores were invited to a semi-structured interview. A deductive-inductive thematic analysis was applied using Margaret Whitehead's conceptualization of physical literacy. RESULTS: Using normative strata, 80.0% of the 99 children assessed (mean age = 9.97 ± 1.3 years, 48% girls) were considered beginning or progressing in their overall physical literacy (mean score = 56.5 ± 13.8/100). Meanwhile, physical literacy informed participants' approach to new, active experiences and may have contributed to a strong sense of self. There was a significant difference between endocrinology and haematology patients on total physical literacy score (p = 0.03) but not domain scores. Participants scored high on motivation/confidence (mean = 22.9 ± 5.0/30) but obtained low physical competence (mean = 11.8 ± 5.6/30) and daily behaviour scores (n = 72, mean = 15.5 ± 7.1/30). Main themes represent salient experiences of children with CMCs within the domains of physical literacy, including their need to evaluate active contexts, self-regulate activity intensity and manage physical limitations. CONCLUSIONS: Children with CMCs can achieve recommended levels of physical literacy without meeting normative standards for physical competence. Participants would benefit from a physical literacy intervention that targets the development of bodily self-regulation skills and risk evaluation in active settings.