Miracle-dz/UniFAR-FTUs huggingface dataset:
A Longitudinal Study of Functional Status and Correlates Following Coronary Artery Bypass Graft Surgery in Women

BackgroundThere is limited information available to help women gauge their functional status following coronary artery bypass graft surgery. ObjectiveThis article describes changes in functional status and the influence of comorbidity, household composition, fatigue, and surgical pain on functional status in women during the first 6 weeks at home following coronary artery bypass surgery. MethodA single-group longitudinal design was used for this research. Women were interviewed in person before hospital discharge and by telephone at 2, 4, and 6 weeks after discharge. Functional status was assessed by (a) the Inventory of Functional Status in the Elderly and subscales of the Sickness Impact Profile; (b) comorbid conditions by simple tally; and (c) fatigue and surgical pain by the Energy/Fatigue and Pain Severity subscales of the MOS Patient Assessment Questionnaire. ResultsWomen experienced significant gains in functional status over 6 weeks, particularly between 2 and 4 weeks. They engaged most frequently in personal care and low-level household activities during the study period, and most reported improvement in their overall functional status. None of the women were completely recovered or had regained baseline functional status by 6 weeks. The women experienced significant decreases in fatigue and surgical pain, but continued to experience both at 6 weeks. Fatigue and surgical pain were significantly correlated at all time periods. DiscussionInformation about recovery following coronary artery bypass graft, and particularly the finding that recovery is incomplete by 6 weeks, should be incorporated into discharge planning and follow-up for this patient population.
Subcutaneous bioavailability of therapeutic antibodies as a function  of FcRn binding affinity in mice

The neonatal Fc receptor (FcRn) plays an important and well-known role in immunoglobulin G (IgG) catabolism; however, its role in the disposition of IgG after subcutaneous (SC) administration, including bioavailability, is relatively unknown. To examine the potential effect of FcRn on IgG SC bioavailability, we engineered three anti-amyloid β monoclonal antibody (mAb) reverse chimeric mouse IgG2a (mIgG2a) Fc variants (I253A.H435A, N434H and N434Y) with different binding affinities to mouse FcRn (mFcRn) and compared their SC bioavailability to that of the wild-type (WT) mAb in mice. Our results indicated that the SC bioavailability of mIgG2a was affected by mFcRn-binding affinity. Variant I253A.H435A, which did not bind to mFcRn at either pH 6.0 or pH 7.4, had the lowest bioavailability (41.8%). Variant N434Y, which had the greatest increase in binding affinity at both pH 6.0 and pH 7.4, had comparable bioavailability to the WT antibody (86.1% vs. 76.3%), whereas Variant N434H, which had modestly increased binding affinity at pH 6.0 to mFcRn and affinity comparable to the WT antibody at pH 7.4, had the highest bioavailability (94.7%). A semi-mechanism-based pharmacokinetic model, which described well the observed data with the WT antibody and variant I253A.H435A, is consistent with the hypothesis that the decreased bioavailability of variant I253A.H435A was due to loss of the FcRn-mediated protection from catabolism at the absorption site. Together, these data demonstrate that FcRn plays an important role in SC bioavailability of therapeutic IgG antibodies.
Effects of lipopolysaccharide, multiwalled carbon nantoubes, and the combination on lung alveolar epithelial cells

Multiwalled carbon nanotubes (MWCNT) have been shown to induce lung fibrosis in animal models, however the underlying molecular factors/mechanisms are still unclear. In this study, we investigated the effects of lipopolysaccharide (LPS), MWCNT, and the combination of LPS and MWCNT on the expression of matrix metalloproteinase‐9 and metalloproteinase‐12 (MMP‐9, MMP‐12), collagen 3A1 (Col3A1), and transforming growth factor beta (TGFβ) in alveolar epithelial A549 cells. MMPs are proteinases that degrade extracellular matrix and play a role in lung fibrosis. A549 cells were exposed to LPS (1 ng/mL), MWCNT (20 μg/mL), and the combination and analyzed for paracellular permeability, TGFβ, Col3A1, MMP‐9, MMP‐12, NF‐κB activation, and cell migration by real‐time PCR and immunofluorescence. LPS, the combination of LPS and MWCNT, and MWCNT only at the highest tested dose induced blue dextran extravasation. LPS and MWCNT increased the expression of TGFβ and its downstream target gene Col3A, and MMP‐9 and MMP‐12 mRNA. MWCNT potently induced cell migration toward wound healing, whereas LPS slightly induced cell migration. Both, LPS and MWCNT, induced NF‐κB nuclear translocation. Our results indicate that MWCNT activated alveolar epithelial cells to promote fibrogenesis, and that LPS differentially primes molecular factors involved in lung remodeling. These findings suggest a role of alveolar epithelial cells in fibrogenesis and also may aid in the design and development of tests for screening of fibrogenic agents. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 445–455, 2017.
Anatomic relations of the Marshall vein: importance for catheterization of the coronary sinus in ablation procedures.

AIMS Our objective was to study the anatomic relations of the human left atrial oblique vein (Marshall vein), particularly of its ostium opening into the coronary sinus, in order to guide ablation procedures related to that vein. METHODS AND RESULTS The study was carried out in 23 heart-specimens (mean weight 446 +/- 204 g) of individuals whose mean ages were 43 +/- 21 years, 20 males. The coronary sinus was opened longitudinally, exposing the ostium of the tributary veins; the Vieussens valve was looked for, as well as its relationship to the left atrial oblique vein. The diameters of the left atrial oblique vein and the coronary sinus ostia were measured and the distance between them was determined. The left atrial oblique vein could be identified in 20 (87%) of the hearts, while the Vieussens valve was present in 17 (74%) of the specimens (in 16 of which the left atrial oblique vein was identified). In such condition, the vein was adjacent to the Vieussens valve and proximally positioned relative to the coronary sinus ostium in most of them (14/16 cases). The mean diameters of the left atrial oblique vein and of the coronary sinus ostia were, respectively, 1.23 +/- 0.38 and 8.22 +/- 1.88 mm. The mean distance between both ostia was 30.9 +/- 10.2 mm. CONCLUSION When present, the left atrial oblique vein can be easily recognized, adjacent to the Vieussens valve. The mean distance between the coronary sinus opening and left atrial oblique vein ostium was around 30 mm, independently of the heart weight and the presence of cardiomegaly.
Blastoid Variant Mantle Cell Lymphoma with Complex Karyotype Including 11 q Duplication 11 q

We describe a case of blastoid mantle cell lymphoma with a complex karyotype. The blastoid variant is a rare type of non-Hodgkin lymphoma exhibiting an aggressive clinical course. Mantle cell lymphoma is a distinct entity of mature B-cell neoplasms genetically characterized by the presence of t(11;14). In the present case, conventional analysis revealed structural abnormalities of chromosomes 2, 4, 6, 10, 13, and 19, along with 3 additional marker chromosomes. The derivative 1 chromosome determined in the case was a result of t(1p;11q). Our interesting finding was the presence of a different translocation between 11q and chromosome 1 in addition to t(11;14). Thus, the resulting 11q duplication was believed to additionally increase the enhanced expression of cyclin D1 gene, which is responsible in the pathogenesis of the disease. Fluorescence in situ hybridization method by the t(11;14) probe revealed clonal numerical abnormalities of chromosomes 11 and 14 in some cells. The detection of multiple abnormalities explains the bad prognosis in the present case. On the basis of our findings, we can easily conclude that results of cytogenetic analyses of similar mantle cell lymphoma patients would provide clues about new responsible gene regions and disease prognosis. In conclusion, it has been suggested that the presence of multiple chromosomal aberrations in addition to the specific t(11;14) may have a negative impact on clinical course and survival rate.
Recanalization of totally occluded iliac and adjacent venous segments.

PURPOSE The purpose of this study was to report our experience with percutaneous recanalization of totally occluded iliac veins and inferior vena cava. MATERIAL AND METHODS Recanalization of the iliac vein was performed in 38 limbs. In nine limbs, recanalization of the inferior vena cava was also necessary (two with filter). In 28 of 38 limbs, the stent was extended below the groin crease into the common femoral vein segment. Large-caliber (14 or 16 mm for iliac vein) flexible self-expanding stents were used. Stents were routinely extended for a short distance into the inferior vena cava to forestall development of iliocaval stenosis. Intravascular ultrasound scan was a valuable tool in the procedure. The median length of the recanalized segment was long (22 cm), and multiple stents (median, n = 3) were necessary in most patients. Forty-five percent of the patients had coagulation abnormalities. RESULTS No morbidity or mortality was seen. Actuarial primary, primary assisted, and secondary patency rates of the stents at 24 months were 49%, 62%, and 76%, respectively. Median pain level decreased significantly (level 4 to level 0; P <.0001) after stent placement, and more than two thirds of the patients became totally pain free after the procedure. Swelling also improved significantly, and a third of the patients became totally free of any swelling after stent placement. Sixty-six percent of cases with stasis ulcers/dermatitis (n = 14) were resolved (actuarial, 1 year), although uncorrected reflux persisted in many of these limbs. CONCLUSION Percutaneous recanalization of the occluded iliac vein with stent placement appears to be successful in the short term, with good patency, significant symptom resolution, and minimal morbidity.
Pharmacokinetic Study of Ferumoxytol: A New Iron Replacement Therapy in Normal Subjects and Hemodialysis Patients

Background: Currently available intravenous iron preparations are not ideal, either because of safety concerns or dose limitations. We investigated the safety and pharmacokinetics of ferumoxytol, a new iron replacement therapy, in normal subjects and hemodialysis patients. Methods: In a randomized, double-blind, ascending-dose study in normal volunteers (n = 41), 6 subjects received placebo, and 8 subjects each received ferumoxytol, at 1, 2 or 4 mg iron/kg, injected at 60 mg iron/min. The remaining subjects received 4 mg iron/kg at injection rates of 90 (n = 3), 180 (n = 3) or 1,800 mg iron/min (n = 5). In the second, open-label, ascending-dose study, 20 hemodialysis patients received 125 or 250 mg of iron over 5 min. Results: In normal subjects, the blood half-life of ferumoxytol increased with increasing dose from 9.3 to 14.5 h (p < 0.05) but not with increasing rate of injection. The drug half-life in hemodialysis patients was similar to normal subjects. Ferumoxytol was not removed with hemodialysis. Serum iron (p < 0.001), transferrin saturation (p < 0.001) and ferritin increased in both populations. No serious adverse events were attributable to ferumoxytol. Conclusion: Ferumoxytol was well tolerated in this study. Its pharmacokinetic properties and simplicity of administration suggest that it will be an attractive form of iron replacement therapy.
Chinese nasopharyngeal carcinoma patients treated with radiotherapy

Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China. Prominent acute side effects of radiotherapy create problems in daily living and working that can generate considerable financial difficulties. A better adjustment to a diagnosis of NPC appears to be associated with an improved rate of recovery, a better quality of life (QoL), a quicker return to work, and normal functioning. Patient satisfaction with physician consultation and the way information is provided in particular may have significant bearing on QoL. The current study reports on short‐term QoL after radiotherapy in NPC patients as a function of satisfaction with the information provided.
Characterization of the hyperpolarization-activated current, I(f), in ventricular myocytes from human failing heart.

BACKGROUND Disease-associated electrophysiological alterations may contribute to the increased predisposition to arrhythmias of the hypertrophied or failing myocardium. An I(f)-like current is expressed in rat left ventricular myocytes (LVMs), its amplitude being linearly related to the severity of cardiac hypertrophy. Here, we report the occurrence and electrophysiological properties of I(f) in human LVMs. METHODS AND RESULTS LVMs were isolated from hearts of three male patients undergoing cardiac transplantation for terminal heart failure due to ischemic dilated cardiomyopathy. The patch-clamp technique was used to record I(f), ie, a barium-insensitive, cesium-sensitive, time-dependent increasing inward current elicited on hyperpolarization. Membrane capacitance was 244 +/- 27 pF (n = 25). I(f) occurred in all cells tested; its density measured at -120 mV was 2.1 +/- 0.3 pA/pF. Activation curves of I(f) (n = 24) were fitted by a Boltzmann function; the threshold was -55 mV; midpoint, -70.9 +/- 2.1 mV; slope, -5.4 +/- 0.3 mV; and maximal specific conductance, 19.6 +/- 2.5 pS/pF. I(f) blockade by extracellular cesium was voltage dependent. Reducing extracellular potassium concentration from 25 to 5.4 mmol/L caused a shift of the reversal potential from -12.7 +/- 0.5 to -24.8 +/- 2.1 mV and a 64% decrease of current conductance. CONCLUSIONS I(f) is present in human LVMs. Its electrophysiological characteristics resemble those previously described in hypertrophied rat LVMs and suggest that I(f) could be an arrhythmogenic mechanism in patients with severe heart failure.
Attributions and behaviours of parents abused as children: a mediational analysis of the intergenerational continuity of child maltreatment (Part II).

BACKGROUND This study extends previous research (Dixon, Browne, & Hamilton-Giachritsis, 2004) by exploring the mediational properties of parenting styles and their relation to risk factors in the intergenerational cycle of child maltreatment. Families with newborns where at least one of the parents was physically and/or sexually abused as a child (AP families) were compared, in terms of parents' attributions and behaviour, to families where the parents had no childhood history of victimization (NAP families). METHODS Information was collected from 4351 families (135 AP families) by community nurses as part of the 'health visiting' service. The same health visitor visited each family twice at home when the child was 4 to 6 weeks and 3 to 5 months of age, to assess behavioural indicators of positive parenting. RESULTS Within 13 months after birth, 9 (6.7%) AP families were referred for maltreating their own child in comparison to 18 (.4%) NAP families. Assessments found a significantly higher number of risk factors and measures indicating poor parenting for AP families. Mediational analysis found that intergenerational continuity of child maltreatment was explained to a larger extent (62% of the total effect) by the presence of poor parenting styles together with the three significant risk factors (parenting under 21 years, history of mental illness or depression, residing with a violent adult). The three risk factors alone were less explanatory (53% of the total effect). CONCLUSION This study provides an explanation for why a minority of parents abused in childhood go on to maltreat their own infant, evidencing poor parenting styles and mediating risk factors. Hence, prevention may be enhanced in AP families by the promotion of 'positive parenting' in addition to providing additional support to young parents, tackling mental illness/depression and domestic violence problems.
Antioxidative stress effect of phosphoserine dimers is mediated via activation of the Nrf2 signaling pathway.

SCOPE Phosphoserine-containing peptides have been shown to exert antioxidative stress effects, by lowering lipid peroxidation, increasing intracellular glutathione, and increasing the expression of antioxidant enzymes in human intestinal epithelial cells. However, the role of phosphoserine residues in antioxidative stress activity, and their mechanism of action, remains unknown. METHODS AND RESULTS The antioxidative stress activity of phosphoserine and phosphoserine peptides was examined using an in vitro model of hydrogen peroxide (H2 O2 )-induced oxidative stress in Caco-2 cells. Phosphoserine dimers (2PS) reduced IL-8 secretion in H2 O2 -treated Caco-2 cells, and reduced H2 O2 -induced expression of genes involved in inflammation and generation of reactive oxygen species (ROS), including chemokine (C-C motif) ligand 5 (CCL5), lactoperoxidase (LPO), myeloperoxidase (MPO), neutrophil cytosolic factor 1/2 (NCF1/2), and nitric oxide synthase 2A (NOS2), and upregulated metallothionein 3 (MT3), peroxiredoxin 3 (PRDX3), and surfactant, pulmonary-associated protein D (SFTPD), which are involved in protection against oxidative stress and activation of the Nrf2 signaling pathway. At the protein level, 2PS reduced H2 O2 -induced phosphorylation of the ERK1/2 and JNK MAPKs, and increased Nrf2 expression. Moreover, the ability of 2PS to reduce H2 O2 -induced IL-8 secretion, a marker of inflammation and oxidative stress, was abrogated in Nrf2 knockdown cells. CONCLUSION These results suggest that 2PS reduce H2 O2 -induced oxidative stress via the Nrf2 signaling pathway, and reveal a potential mechanism for the antioxidative stress activity of phosphoserine-containing peptides.
The Associations of Plant Protein Intake With All-Cause Mortality in CKD.

BACKGROUND Plant protein intake is associated with lower production of uremic toxins and lower serum phosphorus levels. Therefore, at a given total protein intake, a higher proportion of dietary protein from plant sources might be associated with lower mortality in chronic kidney disease. STUDY DESIGN Observational study. SETTINGS & PARTICIPANTS 14,866 NHANES III participants 20 years or older without missing data for plant and animal protein intake and mortality. PREDICTORS Plant protein to total protein ratio and total plant protein intake. Patients were stratified by estimated glomerular filtration rate (eGFR)<60 or ≥60mL/min/1.73m(2). OUTCOMES All-cause mortality. MEASUREMENTS Plant and total protein intakes were estimated from 24-hour dietary recalls. Mortality was ascertained by probabilistic linkage with National Death Index records through December 31, 2000. RESULTS Mean values for plant protein intake and plant protein to total protein ratio were 24.6±13.2 (SD) g/d and 33.0% ± 14.0%, respectively. The prevalence of eGFRs<60mL/min/1.73m(2) was 4.9%. There were 2,163 deaths over an average follow-up of 8.4 years. Adjusted for demographics, smoking, alcohol use, comorbid conditions, body mass index, calorie and total protein intake, and physical inactivity, each 33% increase in plant protein to total protein ratio was not associated with mortality (HR, 0.88; 95% CI, 0.74-1.04) in the eGFR≥60mL/min/1.73m(2) subpopulation, but was associated with lower mortality risk (HR, 0.77; 95% CI, 0.61-0.96) in the eGFR<60mL/min/1.73m(2) subpopulation. In sensitivity analyses, results were similar in those with eGFR<60mL/min/1.73m(2) defined by serum cystatin C level. LIMITATIONS Whether results are related to plant protein itself or to other factors associated with more plant-based diets is difficult to establish. CONCLUSIONS A diet with a higher proportion of protein from plant sources is associated with lower mortality in those with eGFR<60mL/min/1.73m(2). Future studies are warranted to determine the causal role of plant protein intake in reducing mortality in those with eGFR<60mL/min/1.73m(2).
Patches and fences: probing for plasma membrane domains

SUMMARY Cell plasma membranes appear to be composed of domains, patches whose composition and function differ from the average for an entire membrane surface. Proteins and lipids may be segregated into domains by different mechanisms. Some of these mechanisms are discussed, followed by a summary of the evidence for membrane domains obtained in my laboratory. This evidence is largely based on measurements of the lateral diffusion of membrane proteins and lipids. Recent new approaches to the interpretation of lateral diffusion measurements, consideration of so-called fractal or long time-tails promise to give new insights into the stability and lifetime of membrane domains.
Does it Matter if we get it Right? Impact of Appropriateness of Empiric Antimicrobial Therapy Among Surgical Patients

ABSTRACT Previous studies have shown conflicting evidence regarding the impact of inappropriate, initial antibiotic therapy. The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy for the treatment of infection among surgical patients. We hypothesized that inappropriate empiric antimicrobial therapy would predict increased mortality risk compared with appropriate therapy. This was a retrospective analysis of a prospectively maintained database of all surgical patients admitted to a tertiary care center from 1996 to 2007 and treated for sepsis. “Appropriate” empiric antibiotic treatment was determined by sensitivity testing. Demographics and comorbidities, infection sites, infection organisms, and outcomes were compared between inappropriately and appropriately treated groups. Multivariable log-binomial regression was performed. There were 2,855 patients (7,158 infectious episodes) identified by culture analysis as either appropriately or inappropriately treated. Three hundred seventeen (15%) inappropriately treated infectious episodes resulted in death compared with 718 (14%) of the appropriately treated infectious episodes. After adjusting for statistically significant variables, inappropriately treated episodes of infection were not found to be associated with an increased risk for mortality compared with appropriately treated episodes of infection (relative risk, 1.0; 95% confidence interval, 0.99 – 1.02; P = 0.36). Our study observed no difference in mortality between appropriately and inappropriately treated infections within a surgical population.