Hypoxic pulmonary vasoconstriction is heterogeneously distributed in the prone dog

Hypoxic pulmonary vasoconstriction (HPV) is thought to protect gas exchange by decreasing perfusion to hypoxic regions. However, with global hypoxia, non-uniformity in HPV may cause over-perfusion to some regions, leading to high-altitude pulmonary edema. To quantify the spatial distribution of HPV and regional PO2 (PRO2) among small lung regions (approximately 2.0 cm3), five prone beagles (approximately 8.3 kg) were anesthetized and ventilated (PEEP approximately 2 cm H2O) with an F1O2 of 0.21, then 0.50, 0.18, 0.15, and 0.12 in random order. Regional blood perfusion (Q), ventilation (VA) and calculated PRO2 were obtained using iv infusion of 15 microm and inhalation of 1 microm fluorescent microspheres. Lung pieces were clustered by their relative blood flow response to each F1O2. Clusters were shown to be spatially grouped within animals and across animals. Lung piece resistance increased as PRO2 decreased to 60-70 mmHg but dropped at PRO2's < 60mmHg. Regional ventilation changed little with hypoxia. HPV varied more in strength of response, rather than PRO2 response threshold. In initially homogeneous VA/Q lungs, we conclude that HPV response is heterogeneous and spatially clustered.     

Dissolution rates of carbonated hydroxyapatite in hydrochloric acid.

Osteoclasts have been shown to dissolve efficiently and effectively the mineral phase of bone by locally controlling the environment surrounding the cell. Although this mineral phase has been identified and well characterized as carbonated hydroxyapatite, there is little understanding of the factors that affect the dissolution properties of this mineral phase. Mimicking the mechanism by which osteoclasts dissolve the mineral phase of bone may provide insight into methods for the decalcification of atherosclerotic mineral deposits in the vascular system. Accordingly, a detailed characterization of the effects of various chemical and mechanical parameters on the dissolution of carbonated hydroxyapatite mineral was investigated in this study. Increases in the mineral dissolution rate (2-10 times) were associated with increases in dissolving solution [H+], osmolality, temperature, and flow rate. Mineral dissolution rate increases (5-8 times) were associated with greater surface area of the mineral and mechanical agitation of the dissolving solution.     

Machine Learning Predicts the Fall Risk of Total Hip Arthroplasty Patients Based on Wearable Sensor Instrumented Performance Tests

BackgroundThe prevalence of falls affects the wellbeing of aging adults and places an economic burden on the healthcare system. Integration of wearable sensors into existing fall risk assessment tools enables objective data collection that describes the functional ability of patients. In this study, supervised machine learning was applied to sensor-derived metrics to predict the fall risk of patients following total hip arthroplasty.MethodsAt preoperative, 2-week, and 6-week postoperative appointments, patients (n = 72) were instrumented with sensors while they performed the timed-up-and-go walking test. Preoperative and 2-week postoperative data were used to form the feature sets and 6-week total times were used as labels. Support vector machine and linear discriminant analysis classifier models were developed and tested on various combinations of feature sets and feature reduction schemes. Using a 10-fold leave-some-subjects-out testing scheme, the accuracy, sensitivity, specificity, and area under the receiver-operator curve (AUC) were evaluated for all models.ResultsA high performance model (accuracy = 0.87, sensitivity = 0.97, specificity = 0.46, AUC = 0.82) was obtained with a support vector machine classifier using sensor-derived metrics from only the preoperative appointment. An overall improved performance (accuracy = 0.90, sensitivity = 0.93, specificity = 0.59, AUC = 0.88) was achieved with a linear discriminant analysis classifier when 2-week postoperative data were added to the preoperative data.ConclusionThe high accuracy of the fall risk prediction models is valuable for patients, clinicians, and the healthcare system. High-risk patients can implement preventative measures and low-risk patients can be directed to enhanced recovery care programs.     

Assessment of Informal Caregiver Assistance and Strain With Total Hip and Knee Arthroplasty

BackgroundThe purpose of our study is to assess which patient-related and caregiver-related factors are predictive of caregiver strain and assistance when caring for total hip and knee arthroplasty (THA and TKA) patients within 2 weeks after surgery.MethodsWe conducted a prospective study of caregivers of participants enrolled in 2 randomized trials. Caregivers provided demographics and completed the Caregiver Strain Index and Caregiver Assistance Scale pre-surgery and post-surgery. We performed backwards stepwise regression with mixed-effects negative binomial models to investigate predictors of caregiver strain and assistance for THA and TKA caregivers.ResultsThree hundred six caregiver/patient pairs were included. Our models of caregiver strain found Caregiver Assistance Scale scores and patient age to be predictive for all caregivers. We also found caregiver gender and smoking status to be predictive for THA caregivers and caregiver age to be predictive for TKA caregivers. Our models of assistance provided by caregivers found time (post-surgery vs pre-surgery) was predictive for all caregivers. We also found patient body mass index, and patient and caregiver gender to be predictive for THA caregivers, and patient and caregiver employment status and caregiver education level to be predictive for TKA caregivers.ConclusionOur study identifies patient-related and caregiver-related factors which are associated with caregiver strain and assistance when caring for arthroplasty patients. As this is the first study to assess assistance provided by caregivers, it is important for future research to validate our results and to further explore whether patient-reported outcomes may also be related to assistance and strain.     

STAG2 as a prognostic biomarker in low-grade non-muscle invasive bladder cancer

ObjectiveImprovements to bladder cancer risk stratification guidelines are needed to better tailor post-operative surveillance and adjuvant therapy to individual patients. We previously identified STAG2 as a commonly mutated tumor suppressor gene in bladder cancer and an independent predictor of progression in NMIBC. Here we test the value of combining STAG2 immunostaining with other risk stratification biomarkers in NMIBC, and as an individual biomarker in MIBC.Materials and MethodsSTAG2 immunohistochemistry was performed on a progressor-enriched cohort of tumors from 297 patients with NMIBC, and on tumors from 406 patients with MIBC from Aarhus University Hospital in Denmark. Survival analysis was performed using Kaplan-Meier survival analysis, the log rank test, and Cox proportional hazards models.ResultsSTAG2-negative low-grade NMIBC tumors were 2.5 times less likely to progress to muscle invasion than STAG2-positive low-grade NMIBC tumors (Log-rank test, P = 0.008). In a composite group of patients with AUA intermediate and high-risk NMIBC tumors, STAG2-negative tumors were less likely to progress (Log-rank test, P = 0.02). In contrast to NMIBC, we show that STAG2 is not useful as a prognostic biomarker in MIBC.ConclusionsSTAG2 immunostaining can be used to subdivide low-grade NMIBC tumors into two groups with substantially different risks of disease progression. Furthermore, STAG2 immunostaining may be useful to enhance NMIBC risk stratification guidelines, though larger cohorts are needed to solidify this conclusion in individual risk groups. STAG2 is not useful as a biomarker in MIBC. Further study of the use of STAG2 immunostaining as a biomarker for predicting the clinical behavior in NMIBC is warranted.     

Thyroid health status of ammonium perchlorate workers: a cross-sectional occupational health study

Since pharmaceutical exposures to perchlorate are known to suppress thyroid function in patients with hyperthyroidism, a study of employees at a perchlorate manufacturing plant was conducted to assess whether occupational exposure to perchlorate suppresses thyroid function. Exposure to perchlorate was assessed by measurement of ambient air concentrations of total and respirable perchlorate particles, and systemic absorption was assessed by measurement of urinary perchlorate excretion. Airborne exposures ranged from 0.004 to 167 mg total particulate perchlorate per day. Urinary perchlorate measurements demonstrated that exposure to the airborne particulate perchlorate resulted in systemic absorption. Workers were grouped into four exposure categories with mean absorbed perchlorate dosages of 1, 4, 11 and 34 mg perchlorate per day. Thyroid function was assessed by measurement of serum thyroid-stimulating hormone, free thyroxine index, thyroxine, triiodothyronine, thyroid hormone binding ratio, thyroid peroxidase antibodies, and by clinical examination. No differences in thyroid-function parameters were found between the four groups of workers across approximately three orders of magnitude of exposure and of dose. Thus human thyroid function was not affected by these levels of absorbed perchlorate. In addition, no clinical evidence of thyroid abnormalities was found in any exposure group. The blood-cell counts were normal in all groups, indicating no evidence of hematotoxicity in this exposure range. The absence of evidence of an effect on thyroid function or blood cells from occupational airborne perchlorate exposure at a mean absorption of 34 mg/day demonstrates a no-observed-adverse-effect-level (NOAEL) that can assist in the evaluation of human health risks from environmental perchlorate contamination.     

Influence of traumatic grief on suicidal ideation among young adults

OBJECTIVE: The purpose of this study was to examine the influence of traumatic grief on suicidal ideation. METHOD: The Beck-Kovacs Scale for Suicidal Ideation was administered to 76 young adult friends of suicide victims. RESULTS: Traumatic grief was associated with a 5.08 times greater likelihood of suicidal ideation, after control for depression. Comorbid traumatic grief and depression were not associated with a greater likelihood of suicidal ideation. CONCLUSIONS: Syndromal traumatic grief heightens vulnerability to suicidal ideation.