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Ni-Mn-Ga based alloys are widely studied due to their potential for practical applications, making use of their martensitic transformations. However, hysteresis is a long-standing drawback that reduces the chance of transferring these alloys from the laboratory to industry. In this work, we studied a Cr-doped Ni2.15Mn0.70Cr0.15Ga alloy. We arrived at this composition by integrating data obtained from the previous phase and hysteresis diagrams taken from the literature. The compound presents a magnetostructural transition at room temperature, with a ferromagnetic martensite phase, and moderate thermal hysteresis of approximately 4 K. The magnetocaloric and ferromagnetic shape memory effects were explored, showing a reversible entropy change of approximately 9 Jkg-1K-1 under 0–5 T field change, and a cyclical magnetic-field-induced deformation close to 0.81% under 0–9 T, an advance towards high reversibility for this family alloys.

This chapter reviews the adaption of theories of social cognition to interventions for problematic alcohol use. Social cognitive theories focus on thoughts and feelings individuals have about themselves or others, and there is an established and successful tradition of applying these theories to intervention. We provide a brief primer of key theories, describe how each one has been applied to intervention, and review key findings. We consider both long-standing applications of social cognitive theories (e.g., Social Cognitive Theory) and emergent applications (e.g., Self-Affirmation Theory). We close by discussing implications across theories and suggesting future directions.

Objectives: The aim of this study was to identify the risk factors associated with early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. Methods: This is an analysis of the postcardiotomy extracorporeal membrane oxygenation registry, a retrospective multicenter cohort study including 781 patients aged more than 18 years who required venoarterial extracorporeal membrane oxygenation for cardiopulmonary failure after cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. Results: After a mean venoarterial extracorporeal membrane oxygenation therapy of 6.9 ± 6.2 days, hospital and 1–year mortality were 64.4% and 67.2%, respectively. Hospital mortality after venoarterial extracorporeal membrane oxygenation therapy for more than 7 days was 60.5% (P = 0.105). Centers that had treated more than 50 patients with postcardiotomy venoarterial extracorporeal membrane oxygenation had a significantly lower hospital mortality than lower–volume centers (60.7% vs 70.7%, adjusted odds ratio, 0.58; 95% confidence interval, 0.41–0.82). The postcardiotomy extracorporeal membrane oxygenation score was derived by assigning a weighted integer to each independent pre–venoarterial extracorporeal membrane oxygenation predictors of hospital mortality as follows: female gender (1 point), advanced age (60–69 years, 2 points; ≥70 years, 4 points), prior cardiac surgery (1 point), arterial lactate 6.0 mmol/L or greater before venoarterial extracorporeal membrane oxygenation (2 points), aortic arch surgery (4 points), and preoperative stroke/unconsciousness (5 points). The hospital mortality rates according to the postcardiotomy extracorporeal membrane oxygenation score was 0 point, 45.6%; 1 point, 40.5%; 2 points, 51.1%; 3 points, 57.8%; 4 points, 70.7%; 5 points, 68.3%; 6 points, 77.5%; and 7 points or more, 89.7% (P < 0.0001). Conclusions: Age, female gender, prior cardiac surgery, preoperative acute neurologic events, aortic arch surgery, and increased arterial lactate were associated with increased risk of early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. Center experience with postcardiotomy venoarterial extracorporeal membrane oxygenation may contribute to improved results. PC-ECMO Study Group Collaborators of the PC-ECMO Study Group: Kristiina Pälve, MD, PhD, Vesa Anttila, MD, PhD, MD, Thomas Fux, MD, PhD, Gilles Amr, MD, Nikolaos Kalampokas, MD, Artur Lichtenberg, MD, Anders Jeppsson, MD, PhD, Marco Gabrielli, MD, Daniel Reichart, MD, Sidney Chocron, MD, PhD, Mariafrancesca Fiorentino, MD, Ugolino Livi, MD, Ivan Netuka, MD, Dieter De Keyzer, MD, Krister Mogianos, MD, Zein El Dean, MRCS, LLM, Angelo M. Dell’Aquila, MD, Nicla Settembre, MD, PhD, and Stefano Rosato, MSc.

Development of cell therapies and bioengineering approaches has rapidly progressed over the past decade. This chapter will explore the opportunities and emerging challenges of stem cell–based therapies and regenerative medicine. Stem cells and regenerative medicine are part of an ongoing process of study, research, and application. The recent years have witnessed major achievements and results. The overall increased interest in stem cell is due to their specific biological nature and their potential that has allowed a better understanding of aging and degenerative diseases. The plasticity is the most important feature in stem cell–based therapy. The conventional definition describes stem cells as undifferentiated progenitor cells that under specific biomolecular stimuli via the differentiation pathway can produce different cell phenotypes. The “stemness” per se indicates the capacity of stem cells self-renewal ab libitum, an almost incessantly capability of self-proliferation. According to a broad acceptance, scientists have categorized the stem cells based on their differentiation potential as totipotent, pluripotent, multipotent, oligopotent, and unipotent. In this brief chapter, authors aimed to classify the great variety of stem cells, including the induced pluripotent stem cells (iPSs), to describe the mesenchymal stem cells (MSCs) from different tissues, to highlight the incredible uniqueness of MSC constructs among different phenotypes, and to trigger the readers' interest toward these strategic cell types with some useful insights to medical aspects.

Background: There is uncertainty whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) should be used in older patients with cardiopulmonary failure after cardiac surgery. Methods: This was a retrospective multicenter study of 781 patients who required postcardiotomy VA-ECMO for cardiopulmonary failure after adult cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. A parallel systematic review with meta-analysis of the literature was performed. Results: The hospital mortality in the overall Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation (PC-ECMO) series was 64.4%. A total of 255 patients were 70 years old or older (32.7%), and their hospital mortality was significantly higher than in younger patients (76.1% vs 58.7%; adjusted odds ratio, 2.199; 95% confidence interval [CI], 1.536 to 3.149). Arterial lactate level greater than 6 mmol/L before starting VA-ECMO was the only predictor of hospital mortality among patients 70 years old or older in univariate analysis (82.6% vs 70.4%; P = 0.029). Meta-analysis of current and previous studies showed that early mortality after postcardiotomy VA-ECMO was significantly higher in patients aged 70 years or older compared with younger patients (odds ratio, 2.09; 95% CI, 1.59 to 2.75; 5 studies including 1547 patients; I², 5.9%). The pooled early mortality rate among patients aged 70 years or older was 78.8% (95% CI, 74.1 to 83.5; 6 studies including 617 patients; I², 41.8%). Two studies reported 1-year mortality (including hospital mortality) of 79.9% and 75.6%, respectively, in patients 70 years old or older. Conclusions: Advanced age should not be considered a contraindication for postcardiotomy VA-ECMO. However, in view of the high risk of early mortality, meaningful scrutiny is needed before using VA-ECMO after cardiac surgery in older patients.

Background: The evidence of the benefits of using venoarterial extracorporeal membrane oxygenation (VA-ECMO) after coronary artery bypass grafting (CABG) is scarce. Methods: We analyzed the outcomes of patients who received VA-ECMO therapy due to cardiac or respiratory failure after isolated CABG in 12 centers between 2005 and 2016. Patients treated preoperatively with ECMO were excluded from this study. Results: VA-ECMO was employed in 148 patients after CABG for median of 5.0 days (mean, 6.4, SD 5.6 days). In-hospital mortality was 64.2%. Pooled in-hospital mortality was 65.9% without significant heterogeneity between the centers (I2 8.6%). The proportion of VA-ECMO in each center did not affect in-hospital mortality (p = 0.861). No patients underwent heart transplantation and six patients received a left ventricular assist device. Logistic regression showed that creatinine clearance (p = 0.004, OR 0.98, 95% CI 0.97–0.99), pulmonary disease (p = 0.018, OR 4.42, 95% CI 1.29–15.15) and pre-VA-ECMO blood lactate (p = 0.015, OR 1.10, 95% CI 1.02–1.18) were independent baseline predictors of in-hospital mortality. One-, 2-, and 3-year survival was 31.0%, 27.9%, and 26.1%, respectively. Conclusions: One third of patients with need for VA-ECMO after CABG survive to discharge. In view of the burden of resources associated with VA-ECMO treatment and the limited number of patients surviving to discharge, further studies are needed to identify patients who may benefit the most from this treatment.

Publisher Summary Prostate cancer is one of the most common malignancies in Western men, and risk factors include age, race, inherited genes, and environmental factors, such as diet. Although the precise molecular mechanisms underlying carcinogenesis and progression are currently unknown, histological studies indicate a multistage developmental progression. The existence of premalignant lesions has been demonstrated in the prostate based on shared histological and molecular features with adenocarcinoma, as well as prevalence and severity. Prostate cancer arises from the accumulation of genetic and epigenetic alterations. Cytogenetic analyses have demonstrated the prevalence of chromsomal aberrations associated with prostate tumorigenesis and many genes that map to deleted or amplified regions have been investigated for their roles in disease progression. In recent years, genome-wide profiling of prostate tumors has led to the identification of a number of biomarkers and pathways that are altered in prostate cancer, some of which may be potential molecular targets for therapy. Despite the advancing knowledge of genes altered in prostate adenocarcinoma, the precise molecular pathways, their combinatorial relation, and the ordering of events utilized in the development of preneoplastic lesions and adenocarcinoma are still being refined. To elucidate mechanisms and to begin to test new therapies and preventative strategies for human prostate cancer, a number of groups have been developing novel animal models of prostate cancer. These models will help to define many aspects of the molecular and cellular pathogenesis of prostate cancer, such as the role of inflammation, angiogenesis, and stromal-epithelial interactions. This chapter highlights the recent advances in the understanding of the molecular pathology of prostatic adenocarcinoma and the latest developments in mouse prostate cancer models.

Plasma Lp[a] levels and apo[a] isoform distribution among lipoproteins isolated by density gradient ultracentrifugation were studied in subjects with one-band or two-band apo[a] phenotypes as assessed by gradient gel electrophoresis before and after an oral fat load. There were no significant differences in the ultracentrifugal profile between fasting plasma and postprandial plasma that was freed of triglyceride-rich particles (TRP). One-band phenotypes exhibited a single symmetrical peak in the density gradient, whereas two-band phenotypes exhibited a multi-modal distribution. Low molecular weight apo[a] isoforms were preferentially associated with low density Lp[a] whereas high molecular weight apo[a] isoforms were found with high density Lp[a] particles. Feeding a high fat meal caused no significant increase in the total plasma level of Lp[a]. However, the isolated TRP contained the apoB-100-apo[a] complex in a quantity that represented only about 1% of its total amount in the fasting plasma. In all cases the apo[a] isoforms present in TRP were also present in the fasting plasma; however, in the two-band apo[a] phenotypes the ratio of the slow over the fast migrating band was in all cases about eightfold higher in TRP than in the fasting plasma. These observations indicate that postprandially a small percentage of apoB-100-apo[a] associates with TRP and suggest that this complex may derive from de novo synthesis rather than from a pre-existing Lp[a] plasma pool. The liver would be the source of the complex due to the presence in the latter of apoB-100.

We previously described a family of rhesus monkeys in which three out of six members had a spontaneous hypercholesterolemia related to a decrease in number of low density lipoprotein receptors (LDL-R) (Scanu et al. 1988. J. Lipid Res. 29: 1671-1681). During the current work an additional female normocholesterolemic offspring was generated from the mating of the original dam and sire. Moreover, from the breeding of one of the affected male offspring with six unrelated normocholesterolemic female monkeys, eight offspring were generated of which three were hypercholesterolemic on a cholesterol-free diet and exhibited the same degree of LDL-R deficiency as shown by studies in skin fibroblast cultures. All of the animals studied had levels of plasma lipoprotein[a] protein ranging between 1.0 mg/dl and 57.5 mg/dl that were only weakly correlated with total plasma cholesterol, LDL cholesterol, and apoB. LDL-R deficiency correlated with plasma LDL but not Lp[a]. A 7 week fat challenge (16.5% lard, 0.64% cholesterol) that raised the plasma LDL levels markedly had no effect on plasma Lp[a]. Animals with the single band apo[a] phenotype moving on SDS-PAGE faster than apoB-100 exhibited a tendency for high plasma Lp[a] levels which, however, varied widely. Wide variations in Lp[a] levels were also noted with the other apo[a] phenotypes. Taken together our results demonstrate a successful transmission to second generation animals of the LDL-R deficiency phenotype and provide evidence that this phenotype correlates well with plasma LDL levels but not Lp[a]. Our data also suggest that the apo[a] gene is only partially involved in the regulation of the plasma Lp[a] levels.

Lymphangioleiomyomatosis (LAM), a rare multisystem disease affecting women, is characterized by cystic lung disease and abdominal tumors (e.g., angiomyolipomas (AMLs) and lymphangioleiomyomas). Proliferation of abnormal smooth muscle-like cells (LAM cells) is observed throughout the lung, along axial lymphatics in the thorax and abdomen, and in AMLs. Patients can present with progressive dyspnea, recurrent pneumothoraces, hemoptysis, chylous pleural effusions, and/or ascites. Diagnosis may be made by lung biopsy or by clinical and roentgenographic data. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC), an autosomal dominant disorder with variable penetrance caused by mutations in the tumor suppressor genes TSC1 and/or TSC2. LAM cells from sporadic LAM patients contain TSC mutations. TSC1 encodes hamartin, a protein with a role in cell adhesion; TSC2 encodes tuberin, a protein involved in cell-cycle progression and control of cell growth and proliferation, in part, through its regulation of mammalian target of rapamycin (mTOR). The natural course of LAM is highly variable. Therapy includes hormonal manipulations, bronchodilators, supplemental oxygen, and lung transplantation. Clinical trials are under way to study the effects of rapamycin, an inhibitor of mTOR.

Publisher Summary This chapter describes the detailed method for analyzing telomere lengths in archival tissue sections using fluorescence in situ hybridization (FISH) protocol. The method was developed to allow high-resolution telomere length assessment in human formalin-fixed and paraffin-embedded (FFPE) tissue sections, thus making the vast resources of archival tissues available for telomere length analysis. Validation of the method showed that intensity of the fluorescent telomeric (TEL-FISH) signals is linearly related to telomere length as determined independently via Southern blot analysis of telomeric restriction fragments. Unlike Southern analysis, TEL-FISH can be performed on very small, fixed specimens. Providing single-cell resolution completely avoids the confounding effects of cell-type heterogeneity typically present in clinical specimens. It is important to note that because TEL-FISH can be combined with standard immunofluorescence and tissue architecture is maintained, direct comparisons among different regions or specific cell types are easily accomplished. Further information regarding regions of interest can be obtained by performing standard hematoxylin and eosin staining following examination of the TEL-FISH slides by fluorescence microscopy. As the telomeric signal intensity is directly related to telomere length, quantitation is possible via standard image analysis techniques.

A family of rhesus monkeys comprising a sire, a dam, and four male offspring were fed a cholesterol-free Purina Chow diet for several months. The sire, 431-J, and two of the offspring, B-8204 and B-8806, had persistent plasma cholesterol levels in the range of 100-130 mg/dl, whereas the dam, 766-I, and the two other offspring, B-1000 and B-7643, exhibited a marked hypercholesterolemia in the 250-300 mg/dl range associated with an elevation of plasma LDL and apoB. When fed for 12 weeks a diet containing 12.5% lard and 0.25% cholesterol, sire, dam, B-1000 and B-7643 exhibited a marked hypercholesterolemia (500-800 mg/dl range), whereas B-8204 and B-8806 developed only a modest hypercholesterolemia (200-250 mg/dl). All animals were Lp[a]+. Skin fibroblasts from each animal and from control cells were grown in 10% fetal calf serum, transferred to 10% lipoprotein-deficient serum for 48 hr, and then incubated at 4 degrees C or 37 degrees C with 125I-labeled Lp[a]-free LDL. The fibroblasts from dam and offspring B-1000 and B-7643 bound and internalized 125I-labeled LDL less efficiently than control cells. Mathematical analyses of the 4 degrees C binding data indicated that there were no significant differences in LDL binding affinity between test and control cells suggesting that cells from the animals with a spontaneous hypercholesterolemia had a decreased number of LDL receptors. This conclusion was supported by the results of ligand and immunoblot analyses carried out on cell lysates separated by gradient gel electrophoresis. We conclude that a genetically determined LDL receptor deficiency was responsible, in part, for the spontaneous hypercholesterolemia observed in three out of the six family members and that this deficiency accounted for the hyperresponsiveness to a dietary fat and cholesterol challenge by the dam and the two offspring, B-1000 and B-7643. The hyperresponsiveness noted in the sire that had no evidence for LDL-receptor deficiency illustrates that factors other than the LDL receptor were responsible for the hypercholesterolemia attending the fat challenge.