pinecone/core-2020-05-10-deduplication huggingface dataset:
Predictors of medication-related problems among medicaid patients participating in a pharmacist-provided telephonic medication therapy management program

STUDY OBJECTIVE:

To identify predictors of medication-related problems (MRPs) among Medicaid patients participating in a telephonic medication therapy management (MTM) program.
DESIGN:

Retrospective analysis of data from patients enrolled in a previously published study.
DATA SOURCES:

Two Medicaid administrative claims file databases (for health care utilization and prescription dispensing information) and one pharmacy organization file for MTM program information.
PATIENTS:

Seven hundred twelve adult Medicaid patients who participated in a statewide pharmacist-provided telephone-based MTM program and who received an initial medication therapy review.
MEASUREMENTS AND MAIN RESULTS:

The primary dependent variable was the number of MRPs detected during the initial medication therapy review. Secondary dependent variables were the detection of one or more MRPs related to indication, effectiveness, safety, and adherence. Predictor variables were selected a priori that, from the literature and our own practice experiences, were hypothesized as being potentially associated with MRPs: demographics, comorbidities, medication use, and health care utilization. Bivariate analyses were performed, and multivariable models were constructed. All predictor variables with significant associations (defined a priori as p<0.1) with the median number of MRPs detected were then entered into a three-block multiple linear regression model. The overall model was significant (p<0.001, R(2)  = 0.064). Significant predictors of any MRPs (p<0.05) were total number of medications, obesity, dyslipidemia, and one or more emergency department visits in the past 3 months. For indication-related MRPs, the model was significant (p<0.001, R(2)  = 0.049), and predictors included female sex, obesity, dyslipidemia, and total number of medications (p<0.05). For effectiveness-related MRPs, the model was significant (p<0.001, R(2)  = 0.054), and predictors included bone disease and dyslipidemia (p<0.05). For safety-related MRPs, the model was significant (p<0.001, R(2)  = 0.046), and dyslipidemia was a predictor (p<0.05). No significant predictors of adherence-related MRPs were identified.
CONCLUSION:

This analysis supports the relative importance of number of medications as a predictor of MRPs in the Medicaid population and identifies other predictors. However, given the models' low R(2) values, these findings indicate that other unknown factors are clearly important and that criteria commonly used for determining MTM eligibility may be inadequate in identifying appropriate patients for MTM in a Medicaid population
Cellular inhibitor of apoptosis-2 is a critical regulator of apoptosis in airway epithelial cells treated with asthma-related inflammatory cytokines

Aberrant apoptosis of airway epithelial cells (AECs) is a disease contributing feature in the airways of asthmatics. The proinflammatory cytokines tumor necrosis factor α (TNFα) and interferon γ (IFNγ) are increased in asthma and have been shown to contribute to apoptosis at the airways. In the present study, we investigated the role of the inhibitor of apoptosis protein (IAP) family in primary AECs exposed to TNFα and IFNγ. IAPs are potent regulators of caspase activity elicited by the intrinsic and extrinsic apoptosis pathways. However, while caspase‐mediated apoptosis was observed in AECs exposed to doxorubicin, it was not observed after cytokine treatment. Instead, AECs exhibited proapoptotic changes evidenced by an increased Bax:Bcl2 transcript ratio and partial processing of procaspase‐3. Examination by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) and Western analysis showed that proapoptotic changes were associated with a time‐ and dose‐dependent induction of cellular IAP‐2 (cIAP2), potentiated primarily by IFNγ. The abundance of the IAP antagonists X‐linked IAP‐associated factor 1 (XAF1) and second mitochondria‐derived activator of caspases did not change, although a moderate nuclear redistribution was observed for XAF1, which was also observed for cIAP2. Small interfering RNA (siRNA)‐mediated depletion of cIAP2 from AECs leads to caspase‐3 activation and poly (ADP‐ribose) polymerase cleavage, but this required extended cytokine exposure to produce a concomitant decrease in cIAP1 and Bcl2. These results indicate that AECs possess endogenous mechanisms making them highly resistant to apoptosis due to asthma‐related inflammatory cytokines, and the activity of cIAP2 plays an important role in this protection.Eugene Roscioli, Rhys Hamon, Richard E. Ruffin, Susan Lester, and Peter Zalewsk
Effects of long-term head-down-tilt bed rest and different training regimes on the coagulation system of healthy men

Immobility plus preexisting chronic disease or acute trauma can activate the coagulation system, thus increasing the risk for thromboembolic events. The effects of long-term bed-rest immobility and microgravity on the coagulation system of healthy persons (e.g., during crewed Mars missions) have not yet been studied. The main objective of the second Berlin BedRest Study (BBR2-2) "Coagulation Part" was to investigate adaptations of the hemostatic system during long-term bed rest (60 days) under simulated microgravity (6° head-down-tilt [6°HDT]) and after mobilization in three different volunteer groups (randomly assigned to CTR= inactive control group; RE= resistive exercise only group; and RVE= resistive exercise with whole-body vibration group). In 24 males (aged 21-45 years), before, during, and after long-term bed rest, key parameters of coagulation were measured from venous blood samples: D-dimer (DD), thrombin-antithrombin III complex (TAT), and prothrombin fragment F1 + 2 (PT-F1 + 2). Additionally, modified rotational thrombelastometry (ROTEM (®) ) analysis was performed. Times of exploratory analyses were as follows: baseline data collection 2 days before bed rest (BDC-2); eight different days of 6°HDT bed rest (HDT1-HDT60), and two different days after reambulation (R + 3 and R + 6). We found significant changes in DD, TAT, and PT-F1 + 2 over the total time course, but no consistent effect of physical interventions (RE, RVE) on these parameters. Notably, no parameter reached levels indicative of intravascular thrombin formation. All ROTEM® parameters remained within the normal range and no pathological traces were found. Sixty days of 6°HDT bed rest are not associated with pronounced activation of the coagulation system indicative of intravascular thrombus formation in healthy volunteers independent of the training type during the bed rest
Concurrent muscle and bone deterioration in a murine model of cancer cachexia

Cachexia is defined as an excessive, involuntary loss of fat and lean tissue. We tested the validity of the Lewis lung carcinoma (LLC) as a model of cancer cachexia and examined its effect on the two major lean tissue components, skeletal muscle and bone. LLC cells (0.75 × 106) were injected into the left thigh of C57BL/6 mice. Control mice received an equal volume injection of growth media. Tumors were observed in all LLC-injected animals 21 and 25 days post inoculation. LLC-injected animals showed significant reductions in fat and lean mass despite having the same average daily caloric intake as media-treated mice. Global bone mineral density (BMD) had fallen by 5% and 6% in the LLC animals at 21 and 25 days, respectively, compared to a BMD increase of 5% in the 25-day media-treated animals. Extensor digitorum longus (EDL) muscles (isolated from the noninjected hindlimb) showed earlier and quantitatively greater losses in mass, physiological cross-sectional area (pCSA), and tetanic force compared to soleus muscles from the same hindlimb. By the 25th day post-LLC inoculation, EDL force/pCSA was reduced by 19% versus media treatment. This loss in specific force was not trivial as it accounted for about one-third of the reduction in EDL absolute force at this time point. Muscle strips dissected from the diaphragm of LLC mice also exhibited significant reductions in force/pCSA at day 25. We conclude that LLC is a valid model of cachexia that induces rapid losses in global BMD and in limb and respiratory muscle function
Multiple mechanisms underlying rectification in retinal cyclic nucleotide-gated (CNGA1) channels

In cyclic nucleotide-gated (CNGA1) channels, in the presence of symmetrical ionic conditions, current-voltage (I-V) relationship depends, in a complex way, on the radius of permeating ion. It has been suggested that both the pore and S4 helix contribute to the observed rectification. In the present manuscript, using tail and gating current measurements from homotetrameric CNGA1 channels expressed in Xenopus oocytes, we clarify and quantify the role of the pore and of the S4 helix. We show that in symmetrical Rb(+) and Cs(+) single-channel current rectification dominates macroscopic currents while voltage-dependent gating becomes larger in symmetrical ethylammonium and dimethylammonium, where the open probability strongly depends on voltage. Isochronal tail currents analysis in dimethylammonium shows that at least two voltage-dependent transitions underlie the observed rectification. Only the first voltage-dependent transition is sensible to mutation of charge residues in the S4 helix. Moreover, analysis of tail and gating currents indicates that the number of elementary charges per channel moving across the membrane is less than 2, when they are about 12 in K(+) channels. These results indicate the existence of distinct mechanisms underlying rectification in CNG channels. A restricted motion of the S4 helix together with an inefficient coupling to the channel gate render CNGA1 channels poorly sensitive to voltage in the presence of physiological Na(+) and K(+)
Cardiac power integral: a new method for monitoring cardiovascular performance

Cardiac power (PWR) is the continuous product of flow and pressure in the
proximal aorta. Our aim was to validate the PWR integral as a marker of left
ventricular energy transfer to the aorta, by comparing it to stroke work (SW)
under multiple different loading and contractility conditions in subjects without
obstructions in the left ventricular outflow tract. Six pigs were under general
anesthesia equipped with transit time flow probes on their proximal
aortas and Millar micromanometer catheters in their descending aortas to
measure PWR, and Leycom conductance catheters in their left ventricles to
measure SW. The PWR integral was calculated as the time integral of PWR
per cardiac cycle. SW was calculated as the area encompassed by the pressure–
volume loop (PV loop). The relationship between the PWR integral and SW
was tested during extensive mechanical and pharmacological interventions that
affected the loading conditions and myocardial contractility. The PWR integral
displayed a strong correlation with SW in all pigs (R2 > 0.95, P < 0.05)
under all conditions, using a linear model. Regression analysis and Bland Altman
plots also demonstrated a stable relationship. A mixed linear analysis
indicated that the slope of the SW-to-PWR-integral relationship was similar
among all six animals, whereas loading and contractility conditions tended to
affect the slope. The PWR integral followed SW and appeared to be a promising
parameter for monitoring the energy transferred from the left ventricle to
the aorta. This conclusion motivates further studies to determine whether the
PWR integral can be evaluated using less invasive methods, such as echocardiography
combined with a radial artery catheter.(c) 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
Mechanical correlates of dyspnea in bronchial asthma.

We hypothesized that dyspnea and its descriptors, that is, chest tightness, inspiratory effort, unrewarded inspiration, and expiratory difficulty in asthma reflect different mechanisms of airflow obstruction and their perception varies with the severity of bronchoconstriction. Eighty-three asthmatics were studied before and after inhalation of methacholine doses decreasing the 1-sec forced expiratory volume by ~15\% (mild bronchoconstriction) and ~25\% (moderate bronchoconstriction). Symptoms were examined as a function of changes in lung mechanics. Dyspnea increased with the severity of obstruction, mostly because of inspiratory effort and chest tightness. At mild bronchoconstriction, multivariate analysis showed that dyspnea was related to the increase in inspiratory resistance at 5 Hz (R 5) (r (2) = 0.10, P = 0.004), chest tightness to the decrease in maximal flow at 40\% of control forced vital capacity, and the increase in R 5 at full lung inflation (r (2) = 0.15, P = 0.006), inspiratory effort to the temporal variability in R 5-19 (r (2) = 0.13, P = 0.003), and unrewarded inspiration to the recovery of R 5 after deep breath (r (2) = 0.07, P = 0.01). At moderate bronchoconstriction, multivariate analysis showed that dyspnea and inspiratory effort were related to the increase in temporal variability in inspiratory reactance at 5 Hz (X 5) (r (2) = 0.12, P = 0.04 and r (2) = 0.18, P < 0.001, respectively), and unrewarded inspiration to the decrease in X 5 at maximum lung inflation (r (2) = 0.07, P = 0.04). We conclude that symptom perception is partly explained by indexes of airway narrowing and loss of bronchodilatation with deep breath at low levels of bronchoconstriction, but by markers of ventilation heterogeneity and lung volume recruitment when bronchoconstriction becomes more severe
Decreased stability of erythroblastic islands in integrin β3-deficient mice

Erythroblasts proliferate and differentiate in hematopoietic organs within erythroblastic islands (EI) composed of erythropoietic progenitor cells attached to a central macrophage. This cellular interaction crucially involves the erythroid intercellular adhesion molecule-4 (ICAM-4) and αv integrin. Because integrins are biologically active as α/β heterodimers, we asked whether β3 could be a heterodimerization partner of αv integrin in EIs. To this end we compared stress erythropoiesis driven by two different mechanisms, namely that of integrin β3-deficient (β3−/−) mice that exhibit impaired hemostasis due to platelet dysfunction with that of systemically erythropoietin-overexpressing (tg6) mice. While compared to the respective wild type (wt) controls β3−/− mice had much less erythropoietic stimulation than tg6 mice β3−/− blood contained more erythrocytes of a lower maturity stage. Unexpectedly, membranes of peripheral erythrocytes from β3−/− mice (but not those from either wt control or from tg6 mice) contained calnexin, a chaperone that is normally completely lost during terminal differentiation of reticulocytes prior to their release into the circulation. In contrast to erythropoietin-overexpressing mice, the erythropoietic subpopulations representing orthochromatic erythroblasts and premature reticulocytes as well as the number of cells per EI were reduced in β3−/− bone marrow. In conclusion, absence of integrin β3 impairs adhesion of the latest erythroid developmental stage to the central macrophage of EIs resulting in preterm release of abnormally immature erythrocytes into the circulation
Acute impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in humans.

Contains fulltext :
                  138396.pdf (publisher's version ) (Open Access)Retrograde shear rate (SR) in the brachial artery (BA) is associated with endothelial dysfunction; a precursor to atherosclerosis. The BA does not typically manifest clinical atherosclerosis, whereas the superficial femoral artery (SFA) is more prone to developing plaque. Examine whether the impact of incremental levels of retrograde SR differs between atherosclerosis-prone (i.e., SFA) and -resistant vessels (i.e., BA) in healthy men. Thirteen healthy young men reported three times to the laboratory. We examined BA flow-mediated dilation (FMD) before and after 30-min exposure to cuff inflation around the forearm at 0, 30, and 60 mmHg, to manipulate retrograde SR. Subsequently, the 30-min intervention was repeated in the SFA, using the same cuff pressure as in the forearm. Order of testing (vessel and intervention) was randomized among subjects. We found a dose-dependent increase in retrograde SR with 30 and 60 mmHg cuff inflation, which was present in both the BA and SFA (all P < 0.05). BA and SFA FMD decreased after the 30-min intervention ("time": P = 0.012), and this was dependent on cuff pressure ("cuff x time": P = 0.024). A significant decrease in FMD was observed after 60 mmHg only and this change was similarly present in both arteries ("time x artery": P = 0.227). Moreover, the BA and SFA demonstrate a similar relationship between changes in retrograde SR and FMD (r = 0.498 and 0.475, respectively). Our study demonstrates that acute exposure to an increase in retrograde shear leads to comparable decreases in FMD in atherosclerotic-prone and -resistant conduit arteries in humans
Effects of ATP7A overexpression in mice on copper transport and metabolism in lactation and gestation

Placentae and mammary epithelial cells are unusual in robustly expressing two copper &quot;pumps&quot;, ATP7A and B, raising the question of their individual roles in these tissues in pregnancy and lactation. Confocal microscopic evidence locates ATP7A to the fetal side of syncytiotrophoblasts, suggesting a role in pumping Cu towards the fetus; and to the basolateral (blood) side of lactating mammary epithelial cells, suggesting a role in recycling Cu to the blood. We tested these concepts in wild-type C57BL6 mice and their transgenic counterparts that expressed hATP7A at levels 10-20&times; those of endogenous mAtp7a. In lactation, overexpression of ATP7A reduced the Cu concentrations of the mammary gland and milk ~50%. Rates of transfer of tracer (64)Cu to the suckling pups were similarly reduced over 30-48 h, as was the total Cu in 10-day -old pups. During the early and middle periods of gestation, the transgenic litters had higher Cu concentrations than the wild-type, placental Cu showing the reverse trend; but this difference was lost by the first postnatal day. The transgenic mice expressed ATP7A in some hepatocytes, so we investigated the possibility that metalation of ceruloplasmin (Cp) might be enhanced. Rates of (64)Cu incorporation into Cp, oxidase activity, and ratios of holo to apoceruloplasmin were unchanged. We conclude that in the lactating mammary gland, the role of ATP7A is to return Cu to the blood, while in the placenta it mediates Cu delivery to the fetus and is the rate-limiting step for fetal Cu nutrition during most of gestation in mice
Manipulation of arterial stiffness, wave reflections, and retrograde shear rate in the femoral artery using lower limb external compression.

Contains fulltext :
                  125640.pdf (publisher's version ) (Open Access)Exposure of the arterial wall to retrograde shear acutely leads to endothelial dysfunction and chronically contributes to a proatherogenic vascular phenotype. Arterial stiffness and increased pressure from wave reflections are known arbiters of blood flow in the systemic circulation and each related to atherosclerosis. Using distal external compression of the calf to increase upstream retrograde shear in the superficial femoral artery (SFA), we examined the hypothesis that changes in retrograde shear are correlated with changes in SFA stiffness and pressure from wave reflections. For this purpose, a pneumatic cuff was applied to the calf and inflated to 0, 35, and 70 mmHg (5 min compression, randomized order, separated by 5 min) in 16 healthy young men (23 +/- 1 years of age). Doppler ultrasound and wave intensity analysis was used to measure SFA retrograde shear rate, reflected pressure wave intensity (negative area [NA]), elastic modulus (Ep), and a single-point pulse wave velocity (PWV) during acute cuff inflation. Cuff inflation resulted in stepwise increases in retrograde shear rate (P < 0.05 for main effect). There were also significant cuff pressure-dependent increases in NA, Ep, and PWV across conditions (P < 0.05 for main effects). Change in NA, but not Ep or PWV, was associated with change in retrograde shear rate across conditions (P < 0.05). In conclusion, external compression of the calf increases retrograde shear, arterial stiffness, and pressure from wave reflection in the upstream SFA in a dose-dependent manner. Wave reflection intensity, but not arterial stiffness, is correlated with changes in peripheral retrograde shear with this hemodynamic manipulation.1 juli 201
From morphological heterogeneity at alveolar level to the overall mechanical lung behavior: an in vivo microscopic imaging study.

In six male anesthetized, tracheotomized, and mechanically ventilated rabbits, we imaged subpleural alveoli under microscopic view (60×) through a "pleural window" obtained by stripping the endothoracic fascia and leaving the parietal pleura intact. Three different imaging scale levels were identified for the analysis on increasing stepwise local distending pressure (P ld) up to 16.5 cmH2O: alveoli, alveolar cluster, and whole image field. Alveolar profiles were manually traced, clusters of alveoli of similar size were identified through a contiguity-constrained hierarchical agglomerative clustering analysis and alveolar surface density (ASD) was estimated as the percentage of air on the whole image field. Alveolar area distributions were remarkably right-skewed and showed an increase in median value with a large topology-independent heterogeneity on increasing P ld. Modeling of alveolar area distributions on increasing P ld led to hypothesize that absolute alveolar compliance (change in surface area over change in P ld) increases fairly linearly with increasing initial alveolar size, the corollary of this assumption being a constant specific compliance. Clusters were reciprocally interweaved due to their highly variable complex shapes. ASD was found to increase with a small coefficient of variation (CV <25\%) with increasing P ld. The CV of lung volume at each transpulmonary pressure was further decreased (about 6\%). The results of the study suggest that the considerable heterogeneity of alveolar size and of the corresponding alveolar mechanical behavior are homogenously distributed, resulting in a substantially homogenous mechanical behavior of lung units and whole organ