bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Autoimmune Myasthenia Gravis in a Health Maintenance Organization in Buenos Aires, Argentina
Authors: Bettini Mariela , Chaves Marcelo , Cristiano Edgardo , Pagotto Vanina , Perez Lucia , Giunta Diego , Rugiero Marcelo
Published: June 2017

Background: Different epidemiological studies, especially in Europe, have estimated the incidence density of myasthenia gravis (MG) to range between 1.7 and 21.3/1,000,000/person-year; however, data from regions such as Latin America are scarce. This study is aimed at estimating the incidence and prevalence of acquired MG in Buenos Aires, Argentina. Methods: The study population comprised of affiliates of the Italian Hospital Medical Care Program, a prepaid health maintenance organization located in Buenos Aires. The evaluation method for case detection included a retrospective search from January 1, 2006, through December 31, 2012. Results: Of the 60 cases identified, 36 (60%) were females. The median age at diagnosis was 69 years (IQR 51.5-79). The mean age at diagnosis was 63.3 years (SD ±20). A total of 28 patients (46.7%) had generalized MG and 32 had ocular MG (53.3%). Thirty five patients (58.3%) had acetylcholine receptor antibodies and 2 (3.3%) had muscle-specific receptor tyrosine kinase antibodies. The crude incidence density (ID) of MG was 61.33 per 1,000,000 person-years (95% CI 47.62-79.99). The adjusted ID for the Argentinean population was 38.8 per 1,000,000 person-years (95% CI 27.09-50.51) and for the Buenos Aires population was 47.49 (95% CI 34.73-60.25). Conclusions: The results obtained are similar to those published for other geographical areas.
Atherosclerosis and the Hydrogen Sulfide Signaling Pathway – Therapeutic Approaches to Disease Prevention
Authors: Wang Zhi-Jun , Wu Jian , Guo Wei , Zhu Yi-Zhun
Published: June 2017

Hydrogen sulfide (H2S) is now admitted as a third gasotransmitter together with nitric oxide (NO) and carbon monoxide (CO), albeit it was originally considered as a foul and poisonous gas. Endogenous H2S production in mammalian cells is counting on the three enzymes acting on cysteine. Involvement of H2S in various physiological and pathological processes has been extensively studied in the last fifteen years. Mounting evidence suggests that H2S is able to protect against atherosclerosis development and progression. Exogenous H2S supplement has salutary effects on atherogenesis, and reduction of the endogenous H2S level accelerates atherosclerosis. The anti-atherosclerotic mechanisms of H2S have been descried in different aspects, including endothelium preservation, antioxidative action, anti-inflammatory responses, vasorelaxation, regulation of ion channels, etc. However, further investigation is still needed to help us gain more insights into the fundamental underlying mechanisms, and that will allow us to design better therapeutic applications of H2S in the treatment of atherosclerosis.
Surgical Management of Patients with Neuroendocrine Neoplasms of the Appendix: Appendectomy or More
Authors: Pawa Nikhil , Clift Ashley K. , Osmani Helai , Drymousis Panagiotis , Cichocki Andrzej , Flora Rashpal , Goldin Robert , Patsouras Dimitrios , Baird Alan , Malczewska Anna , Kinross James , Faiz Omar , Antoniou Anthony , Wasan Harpreet , Kaltsas Gregory A. , Darzi Ara , Cwikla Jaroslaw B. , Frilling Andrea
Published: June 2017

Background: Appendiceal neuroendocrine neoplasms (ANEN) are mostly indolent tumours treated effectively with simple appendectomy. However, controversy exists regarding the necessity of oncologic right hemicolectomy (RH) in patients with histologic features suggestive of more aggressive disease. We assess the effects of current guidelines in selecting the surgical strategy (appendectomy or RH) for the management of ANEN. Methods/Aims: This is a retrospective review of all ANEN cases treated over a 14-year period at 3 referral centres and their management according to consensus guidelines of the European and the North American Neuroendocrine Tumor Societies (ENETS and NANETS, respectively). The operation performed, the tumour stage and grade, the extent of residual disease, and the follow-up outcomes were evaluated. Results: Of 14,850 patients who had appendectomies, 215 (1.45%) had histologically confirmed ANEN. Four patients had synchronous non-ANEN malignancies. One hundred and ninety-three patients had index appendectomy. Seventeen patients (7.9%) had lymph node metastases within the mesoappendix. Forty-nine patients underwent RH after appendectomy. The percentages of 30-day morbidity and mortality after RH were 2 and 0%, respectively. Twelve patients (24.5%) receiving completion RH were found to have lymph node metastases. Two patients had liver metastases, both of them synchronous. The median follow-up was 38.5 months (range 1-143). No patient developed disease recurrence. Five- and 10-year overall survival for all patients with ANEN as the only malignancy was both 99.05%. Conclusions: The current guidelines appear effective in identifying ANEN patients at risk of harbouring nodal disease, but they question the oncological relevance of ANEN lymph node metastases. RH might present an overtreatment for a number of patients with ANEN.
Lys 42/43/44 and Arg 12 of thrombin-activable fibrinolysis inhibitor comprise a thrombomodulin exosite essential for its antifibrinolytic potential
Authors: Wu Chengliang , Stafford Alan , Fredenburgh James , Weitz Jeffrey , Gils Ann , Declerck Paul , Kim Paul
Published: June 2017

The thrombin-thrombomodulin (TM) complex activates thrombin-activable fibrinolysis inhibitor (TAFI) more efficiently than thrombin alone. The exosite on TAFI required for its TM-dependent activation by thrombin has not been identified. Based on previous work by us and others, we generated TAFI variants with one or more of residues Lys 42, Lys 43, Lys 44 and Arg 12 within the activation peptide mutated to alanine. Mutation of one, two, or three Lys residues or the Arg residue alone decreased the catalytic efficiency of TAFI activation by thrombin-TM by 2.4-, 3.2-, 4.7-, and 15.0-fold, respectively, and increased the TAFI concentrations required for half-maximal prolongation of clot lysis times (K1/2) by 3-, 4,- 15-, and 24-fold, respectively. Mutation of all four residues decreased the catalytic efficiency of TAFI activation by 45.0-fold, increased the K1/2 by 130-fold, and abolished antifibrinolytic activity in a clot lysis assay at physiologic levels of TAFI. Similar trends in the antifibrinolytic activity of the TAFI variants were observed when plasma clots were formed using HUVECs as the source of TM. When thrombin was used as the activator, mutation of all four residues reduced the rate of activation by 1.1-fold compared with wild-type TAFI, suggesting that these mutations only impacted activation kinetics in the presence of TM. Surface plasmon resonance data suggest that mutation of the four residues abrogates TM binding with or without thrombin. Therefore, Lys 42, Lys 43, Lys 44 and Arg 12 are critical for the interaction of TAFI with the thrombin-TM complex, which modulates its antifibrinolytic potential.
New paradigms in venous thromboprophylaxis of medically ill patients
Authors: Spyropoulos Alex C. , Raskob Gary E.
Published: June 2017

Acutelly-ill hospitalised medical patients are at risk of venous thromboembolism (VTE), both in-hospital and in the immediate post-discharge period, and mortality from VTE is thought to be particularly high in this patient population. However, despite previous mandates from international antithrombotic guidelines such as those of the American College of Chest Physicians (ACCP) for the “universal” use of thromboprophylaxis in hospitalised medical patients, global audits suggest that implementation of thromboprophylaxis continues to be challenging because of the perceived higher risk of bleeding and lower risk of VTE than that reported in clinical trials. Recent population-based studies also reveal that a “universal” hospital-only thromboprophylactic strategy does not reduce the community burden of VTE from this population, which may constitute nearly one quarter of the attributable risk of VTE. Lastly, four large randomised placebo-controlled trials of extended thromboprophylaxis have failed to show a definitive net clinical benefit in hospitalised medical patients. Recent large-scale efforts in deriving and validating scored VTE and bleed risk assessment models (RAMs) have been completed in the medically-ill population. In addition, an elevated D-dimer as a new biomarker to identify at-VTE risk medically ill patients has also undergone prospective evaluation. This paper will review current concepts of VTE and bleed risk in hospitalised medical patients, both in the hospital as well as the post-hospital discharge period, and will discuss new paradigms of thromboprophylaxis in this population using an individualised, patient-centered approach.
TNFR2 Stimulation Promotes Mitochondrial Fusion via Stat3- and NF-kB–Dependent Activation of OPA1 Expression
Authors: Nan Jinliang , Hu Hengxun , Sun Yong , Zhu Lianlian , Wang Yingchao , Zhong Zhiwei , Zhao Jing , Zhang Na , Wang Ya , Wang Yaping , Ye Jian , Zhang Ling , Hu Xinyang , Zhu Wei , Wang Jian’an
Published: June 2017

Rationale:

Mitochondria are important cellular organelles and play essential roles in maintaining cell structure and function. Emerging evidence indicates that in addition to having proinflammatory and proapoptotic effects, TNFα (tumor necrosis factor α) can, under certain circumstances, promote improvements in mitochondrial integrity and function, phenomena that can be ascribed to the existence of TNFR2 (TNFα receptor 2).

Objective:

The present study aimed to investigate whether and how TNFR2 activation mediates the effects of TNFα on mitochondria.

Methods and Results:

Freshly isolated neonatal mouse cardiac myocytes treated with shRNA targeting TNFR1 were used to study the effects of TNFR2 activation on mitochondrial function. Neonatal mouse cardiac myocytes exhibited increases in mitochondrial fusion, a change that was associated with increases in mitochondrial membrane potential, intracellular ATP levels, and oxygen consumption capacity. Importantly, TNFR2 activation–induced increases in OPA1 (optic atrophy 1) protein expression were responsible for the above enhancements, and these changes could be attenuated using siRNA targeting OPA1. Moreover, both Stat3 and RelA bound to the promoter region of OPA1 and their interactions synergistically upregulated OPA1 expression at the transcriptional level. Stat3 acetylation at lysine 370 or lysine 383 played a key role in the ability of Stat3 to form a supercomplex with RelA. Meanwhile, p300 modulated Stat3 acetylation in HEK293T (human embryonic kidney 293T) cells, and p300-mediated Stat3/RelA interactions played an indispensable role in OPA1 upregulation. Finally, TNFR2 activation exerted beneficial effects on OPA1 expression in an in vivo transverse aortic constriction model, whereby TNFR1-knockout mice exhibited better outcomes than in mice with both TNFR1 and TNFR2 knocked out.

Conclusions:

TNFR2 activation protects cardiac myocytes against stress by upregulating OPA1 expression. This process was facilitated by p300-mediated Stat3 acetylation and Stat3/RelA interactions, leading to improvements in mitochondrial morphology and function.
Platelets Express Activated P2Y
12
Receptor in Patients With Diabetes Mellitus
Authors: Hu Liang , Chang Lin , Zhang Yan , Zhai Lili , Zhang Shenghui , Qi Zhiyong , Yan Hongmei , Yan Yan , Luo Xinping , Zhang Si , Wang Yiping , Kunapuli Satya P. , Ye Hongying , Ding Zhongren
Published: June 2017

Background:

Platelets from patients with diabetes mellitus are hyperactive. Hyperactivated platelets may contribute to cardiovascular complications and inadequate responses to antiplatelet agents in the setting of diabetes mellitus. However, the underlying mechanism of hyperactivated platelets is not completely understood.

Methods:

We measured P2Y
12
expression on platelets from patients with type 2 diabetes mellitus and on platelets from rats with diabetes mellitus. We also assayed platelet P2Y
12
activation by measuring cAMP and VASP phosphorylation. The antiplatelet and antithrombotic effects of AR-C78511 and cangrelor were compared in rats. Finally, we explored the role of the nuclear factor-κB pathway in regulating P2Y
12
receptor expression in megakaryocytes.

Results

Platelet P2Y
12
levels are 4-fold higher in patients with type 2 diabetes mellitus compared with healthy subjects. P2Y
12
expression correlates with ADP-induced platelet aggregation (r=0.89,
P
<0.01). P2Y
12
in platelets from patients with diabetes mellitus is constitutively activated. Although both AR-C78511, a potent P2Y
12
inverse agonist, and cangrelor have similar antiplatelet efficacy on platelets from healthy subjects, AR-C78511 exhibits more powerful antiplatelet effects on diabetic platelets than cangrelor (aggregation ratio 36±3% versus 49±5%, respectively,
P
<0.05). Using a FeCl
3
-injury mesenteric arteriole thrombosis model in rats and an arteriovenous shunt thrombosis model in rats, we found that the inverse agonist AR-C78511 has greater antithrombotic effects on GK rats with diabetes mellitus than cangrelor (thrombus weight 4.9±0.3 mg versus 8.3±0.4 mg, respectively,
P
<0.01). We also found that a pathway involving high glucose-reactive oxygen species-nuclear factor-κB increases platelet P2Y
12
receptor expression in diabetes mellitus.

Conclusions

Platelet P2Y
12
receptor expression is significantly increased and the receptor is constitutively activated in patients with type 2 diabetes mellitus, which contributes to platelet hyperactivity and limits antiplatelet drug efficacy in type 2 diabetes mellitus.
Physical Activity and Prognosis in the TOPCAT Trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist)
Authors: Hegde Sheila M. , Claggett Brian , Shah Amil M. , Lewis Eldrin F. , Anand Inder , Shah Sanjiv J. , Sweitzer Nancy K. , Fang James C. , Pitt Bertram , Pfeffer Marc A. , Solomon Scott D.
Published: June 2017

Background:

Physical activity (PA) is inversely associated with adverse cardiovascular outcomes in healthy populations, but the impact of physical activity in patients with heart failure (HF) with preserved ejection fraction is less well characterized.

Methods:

The baseline self-reported PA of 1751 subjects enrolled in the Americas region of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) was categorized as poor, intermediate, or ideal PA with American Heart Association criteria. PA was related to the primary composite outcome (HF hospitalization, cardiovascular mortality, or aborted cardiac arrest), its components, and all-cause mortality with the use of multivariable Cox models.

Results:

The mean age at enrollment was 68.6±9.6 years. Few patients met American Heart Association criteria for ideal activity (11% ideal, 14% intermediate, 75% poor). Over a median follow-up of 2.4 years, the primary composite outcome occurred in 519 patients (397 HF hospitalizations, 222 cardiovascular deaths, and 6 aborted cardiac arrests). Compared with those with ideal baseline PA, poor and intermediate baseline PA was associated with a greater risk of the primary outcome (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.28–3.28; HR, 1.95; 95% CI, 1.15–3.33, respectively), HF hospitalization (HR, 1.93; 95% CI, 1.16–3.22; HR, 1.84; 95% CI, 1.02–3.31), cardiovascular mortality (HR, 4.36; 95% CI, 1.37–13.83; HR, 4.05; 95% CI, 1.17–14.04), and all-cause mortality (HR, 2.95; 95% CI, 1.44–6.02; HR, 2.05; 95% CI, 0.90–4.67) after multivariable adjustment for potential confounders.

Conclusions:

In patients with HF with preserved ejection fraction, both poor and intermediate self-reported PA were associated with higher risk of HF hospitalization and mortality.

Clinical Trial Registration:

URL:
https://clinicaltrials.gov
. Unique identifier: NCT00094302.
Dorandis neue Ausgabe von Diogenes Laertios
Authors: Lucarini Carlo M.
Published: June 2017

Dorandi hat eine hervorrangende Ausgabe von Diogenes Laertios aufgestellt. Der vorliegende Beitrag zeigt, dass das Antigraphon von BFP eine Majuskelhandschrift war, und dass die Excerpta Vaticana und Suidas aus derselben Überlieferung geschöpft haben. Es wird auch erwiesen, dass die Excerpta Vaticana den ps.-Hesychios (De viris illustribus) voraussetzen. Außerdem werden mehr als hundert neue Konjekturen vorgeschlagen.
Naqāʾiḍ Poetry in the Post-Umayyad Era
Authors: Alqarni Hussain Mohammed
Published: June 2017

Naqāʾiḍ(biting refutations) are a type of lampoon in which two poets exchange satirical poems that make use of the same prosodic meter and rhyme. Although satire had already been a staple of Arabic poetry in the pre-Islamic era,naqāʾiḍwere further developed and enhanced as an art form in the Umayyad period thanks to three poets: Jarīr, al-Farazdaq and al-Akhṭal.

A distinctive feature of earlynaqāʾiḍwas the centrality of tribalism as a key motivator of composition. This paper seeks to show thatnaqāʾiḍpoetry did not disappear, as some have suggested, nor did it become limited to the personal or sectarian; rather, it continued to flourish throughout the Abbasid period as an expression of tribal pride. Two cases ofnaqāʾiḍfrom the Abbasid period are investigated; the poets in question were regarded as belonging to the group ofsāqat al-shuʿarāʾ(rearguard poets).
A new species of the Neotropical spittlebug genus Catrimania Fennah, 1968 (Hemiptera: Cercopidae) with a dichotomous key to species of the genus
Authors: CARVALHO GERVÁSIO SILVA , PALADINI ANDRESSA
Published: June 2017

A new species of the Neotropical spittlebug genus Catrimania Fennah from Ecuador, C. tiobino sp. nov., is described. A dichotomous key to species of the genus is provided.
Weakening and Shifting of the Saharan Shallow Meridional Circulation during Wet Years of the West African Monsoon
Authors: Shekhar Ravi , Boos William R.
Published: June 2017

The correlation between increased Sahel rainfall and reduced Saharan surface pressure is well established in observations and global climate models and has been used to imply that increased Sahel rainfall is caused by a stronger shallow meridional circulation (SMC) over the Sahara. This study uses two atmospheric reanalyses to examine interannual variability of Sahel rainfall and the Saharan SMC, which consists of northward near-surface flow across the Sahel into the Sahara and southward flow near 700 hPa out of the Sahara. During wet Sahel years, the Saharan SMC shifts poleward, producing a drop in low-level geopotential and surface pressure over the Sahara. Statistically removing the effect of the poleward shift from the low-level geopotential eliminates significant correlations between this geopotential and Sahel precipitation. As the Saharan SMC shifts poleward, its midtropospheric divergent outflow decreases, indicating a weakening of its overturning mass flux. The poleward shift and weakening of the Saharan SMC during wet Sahel years is reproduced in an idealized model of West Africa; a wide range of imposed sea surface temperature and land surface albedo perturbations in this model produce a much larger range of SMC variations that nevertheless have similar quantitative associations with Sahel rainfall, as in the reanalyses. These results disprove the idea that enhanced Sahel rainfall is caused by strengthening of the Saharan SMC. Instead, these results are consistent with the hypothesis that a stronger SMC inhibits Sahel rainfall, perhaps by advecting midtropospheric warm and dry air into the precipitation maximum.
STEM Teaching and Learning Strategies of High School Parents With Homeschool Students
Authors: Gann Courtney , Carpenter Dan
Published: June 2017

The purpose of this research study was to investigate the teaching and learning strategies used by homeschool parents with high school students. A qualitative case study was used which began with the administration of an open-ended questionnaire to a homeschool community in the southern United States. Twenty-nine parents completed the questionnaire, and 10 of those volunteered to participate in the follow-up procedures, which included interviews, observations, and document collection. Results indicate that parents use a variety of teaching and learning strategies including individualized instruction, mastery learning, self-directed study, collaboration with peers and adults, and application and connection of information.
Expanding Employment Discrimination Protections for Individuals with Disabilities: Evidence from California
Authors: Button Patrick
Published: June 2017

Effective 2001, California passed the Prudence Kay Poppink Act, which broadened California’s disability employment discrimination law to cover individuals with less-severe disabilities by lowering the burden of proof to establish a disability. Using both difference-in-differences and difference-in-difference-in-differences regression analyses and data from the Current Population Survey, the author estimates how this act affected the labor market outcomes for individuals with disabilities. The results suggest that the act signiﬁcantly increased employment for individuals with disabilities, with the effect persisting at least partially up to six years later.
Angels of mercy or smiling western invaders? Community’s perception of NGOs in northwest Pakistan
Authors: Jamal Aamir , Baldwin Clive
Published: June 2017

Using a qualitative Delphi method, this study explored how the Pashtun community, living across the border of Afghanistan and Pakistan, perceives the role and significance of non-governmental organizations (NGOs). The study also examined deep-rooted causes of the resistance to NGO-based development and suggested best practice strategies. Analysis of the Delphi finding showed consensus that most NGOs are perceived with deep suspicions and fear among the Pashtun society. Most of these suspicions and elements of mistrust were echoed in terms of an extension of western imperialism, violations of local cultures, spreading immorality, corruption and lack of credibility, and transparency. We discuss the implications for social work practice.
From the Cult of Chivalry to the Cult of Personality: The Seventh-century Transformation in Pallava Statecraft
Authors: Devadevan Manu V.
Published: June 2017

Between the fourth and sixth centuries ce, Pallava statecraft in South India revolved largely around the practice of making land grants to brāhmaṇa beneficiaries. These activities were concentrated in the rural agrarian belts of coastal Andhra and parts of Karnataka. The image of the king in these grants was stereotypical: a chivalrous ruler, wedded to the ideals of valour, protecting his people and swearing devotion towards his father and god. These were ideals that might have appealed to the imagination of a rural world in an agrarian milieu. However, in the early seventh century ce, when South Asia witnessed a ‘third phase of urbanization’, the Pallavas turned towards Tamil Nadu, where a powerful class of peasant proprietors, the nātṭṭār, existed. In this changed historical setting, the Pallavas moved away in a significant manner from the practice of awarding land grant and making interventions into the production relations and other regimes of agrarian control. Instead, they turned towards the creation of a refined urban aesthetic infrastructure centring on the cult of the royal personality. This involved the propagation of newer images of the king, extending patronage to literary practices, drama and music, and building temples for āgamic deities such as Śiva and Viṣṇu on a scale large enough to promote ingenious forms of architecture and iconography. This new aesthetic infrastructure was widely influential, eventually spread to other parts of the subcontinent, transforming the practice of statecraft in South Asia.
Short-form 6D assessment in compression module of the American College of Phlebology Patient Reported Outcome Venous Registry
Authors: Chi Yung-Wei , Durbin-Johnson Blythe , Schul Marlin
Published: June 2017

Objective

The goal of this American College of Phlebology Patient Reported Outcome Venous Registry analysis was to examine the clinical efficacy of compression stockings using short-form 6D questionnaire (SF-6D).

Method

SF-6D scores were modeled over time using linear mixed effects model. Changes of SF-6D score from baseline to the last encounter were examined using a paired t-test. Analysis of variance was used to compare changes from baseline in SF-6D scores between C classifications. All analyses were conducted using SAS software, version 9.4 (SAS Institute, Cary NC).

Results

Baseline mean SF-6D score was 0.83 and at follow-up, 0.85. Mean SF-6D change was +0.02 points (P = .001) over an average time period of 5.5 months. Patients’ SF-6D scores were estimated to increase by +0.03 points (P = .005) per year of usage of compression stockings. SF-6D score changes across C classifications did not demonstrate significant differences (P = .265).

Conclusion

There was an improvement of SF-6D score in the registry participants who used circular knit compression stockings.
A study of burden of care and its correlates among family members supporting relatives and loved ones with traumatic spinal cord injuries
Authors: Castellano-Tejedor Carmina , Lusilla-Palacios Pilar
Published: June 2017

Objective:

To understand and describe in a sample of caregivers of persons with spinal cord injury, their burden of care, resilience and life satisfaction and to explore the relationship between these variables.

Design:

Cross-sectional design.

Setting:

One Spinal Cord Injury Acute Inpatient Unit from a general hospital.

Subjects:

Seventy-five relatives of persons with spinal cord injuries (84% women) with a mean age of 48.55 ( SD = 12.55) years.

Interventions:

None.

Measures:

Demographics (neurological loss and severity according to the American Spinal Injury Association criteria), the Zarit Burden Interview, the Resilience Scale and the Life Satisfaction Checklist.

Results:

All caregivers experienced feelings of different intensities of burden (52% mild-to-moderate, 43% moderate-to-severe and 5% severe), and none of them expressed little or no burden at the assessment moment. Caregivers’ main worries were “dependence” and “the future of the injured.” Resilience was medium-to-high (mean = 141.93, SD = 23.44) for the whole sample with just a minority of them revealing low (15%) or very low resilience (7%). The highest scores were obtained in relation to “caregivers’ independence” and “meaning of their lives.” Life satisfaction scores were medium-to-high (mean = 36.6, SD = 6). These scores were not related to demographics or the severity of the injury. Zarit Burden Interview scores were negatively correlated to Resilience Scale ( r = −.370, P = .001) and Life Satisfaction Checklist scores ( r = −.412, P < .001).

Conclusion:

More resilient and satisfied caregivers experienced lower burden. Burden is moderate-to-high and mainly related to uncertainty about the future, caregivers’ insecurity with caregiving and dependence of the injured.
The Case for #BlackGirlMagic
Authors: Walton Quenette L. , Oyewuwo-Gassikia Olubunmi Basirat
Published: June 2017

This article puts forth a culturally relevant practice framework that integrates components of intersectionality and strengths-based perspectives. This framework incorporates key factors of Black women’s social identities and builds on their strengths to provide a richer understanding of how depression is experienced in their lives. To arrive at this framework, we provide a brief summary of intersectionality; use a case study to examine the influence of race, class, and gender on Black women’s lived experiences with depression; and apply the framework—#BlackGirlMagic—to the case study. Lastly, future directions for practice, research, and policy are explored.
Exploring the Phenotype in Mild Cognitive Impairment to Aid the Prediction of Those at Risk of Transitioning to Parkinson Disease and Dementia With Lewy Bodies
Authors: Szeto Jennifer Y. Y. , Halliday Glenda M. , Naismith Sharon L. , Lewis Simon J. G.
Published: June 2017

To date, only limited research has concurrently investigated the presence of rapid eye movement sleep behavior disorder (RBD) and other features associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB) in people presenting with mild cognitive impairment (MCI). As a first step towards a longitudinal research project, the present study explored the relationships between MCI, RBD, and depression in 108 older adults who presented with subjective memory complaints but were not known to have a neurodegenerative condition. The present study found that RBD was a frequent feature in individuals with MCI (35%). Furthermore, MCI patients with RBD were more likely to exhibit nonamnestic MCI (89%) rather than an amnestic MCI phenotype (χ2 = 4.99, P = .025). Specifically, nonamnestic MCI patients with RBD had selective deficits in executive function and verbal memory, as well as a higher level of depressive symptoms. This cognitive and psychiatric profile is aligned with PD and DLB patients at their time of initial diagnosis and suggests that targeting nonamnestic MCI patients who report RBD with additional biomarker testing including smell, color vision, and neuroimaging (eg, dopamine transporters scan and transcranial ultrasonography) may aid in early diagnosis and prediction of these α-synucleinopathies.
An analysis of the impact of draft tube modifications on the performance of a Kaplan turbine by means of computational fluid dynamics
Authors: Schiffer Juergen , Benigni Helmut , Jaberg Helmut
Published: June 2017

Due to the low electricity prices in central Europe, cost optimisations related to all parts of a new hydropower plant have become increasingly important. In case of a run-of-river hydropower plant using a vertical axis Kaplan turbine, one of the cost drivers are the excavation works. Thus, a decisive factor for the reduction of construction costs is the minimisation of the construction depth of the elbow-type draft tube. In course of the design phase of a new hydropower plant in Austria, an analysis of the impact of draft tube modifications on the performance of the Kaplan turbine was carried out by applying computational fluid dynamics. The net head of the turbine with a diameter of D = 3.15 m accounts for Hnet = 9.00 m and the maximum discharge per unit is Qmax = 57.5 m3/s. After it was proven that there is a good agreement of the numerically calculated and experimentally measured turbine efficiency for the original turbine configuration, various draft tube designs were tested in order to find out their impact on the turbine efficiency and to analyse the sources of draft tube losses in detail. Finally, it was possible to find a new draft tube design representing a compromise of reduced construction costs and acceptable turbine efficiency.
Development of finite element model for customized prostheses design for patient with pelvic bone tumor
Authors: Iqbal Taimoor , Shi Lei , Wang Ling , Liu Yaxiong , Li Dichen , Qin Mian , Jin Zhongmin
Published: June 2017

The aim of this study was to design a hemi-pelvic prosthesis for a patient affected by pelvic sarcoma. To investigate the biomechanical functionality of the pelvis reconstructed with designed custom-made prosthesis, a patient-specific finite element model of whole pelvis with primary ligaments inclusive was constructed based on the computed tomography images of the patient. Then, a finite element analysis was performed to calculate and compare the stress distribution between the normal and implanted pelvis models when undergoing three different static conditions—both-leg standing, single-leg standing for the healthy and the affected one. No significant differences were observed in the stresses between the normal and reconstructed pelvis for both-leg standing, but 20%–40% larger stresses were predicted for the peak stress of the single-leg standing (affected side). Moreover, two- to threefold of peak stresses were predicted within the prostheses compared to that of the normal pelvis especially for single-leg standing case, however, still below the allowable fatigue limitation. The study on the load transmission functionality of prosthesis indicated that it is crucial to carry out finite element analysis for functional evaluation of the designed customized prostheses before three-dimensional printing manufacturing, allowing better understanding of the possible peak stresses within the bone as well as the implants for safety precaution. The finite element model can be equally applicable to other bone tumor model for biomechanical studying.
Glyoxal toxicity in isolated rat liver mitochondria
Authors: Goudarzi M , Kalantari H , Rezaei M
Published: June 2017

Glyoxal is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose, and degradation of glycated proteins. Glyoxal has been linked to oxidative stress and can cause a number of cellular damages, including covalent modification of amino and thiol groups of proteins to form advanced glycation end products. However, the mechanism of glyoxal toxicity has not been fully understood. In this study, we have focused on glyoxal toxicity in isolated rat liver mitochondria. Isolated mitochondria (0.5 mg protein per milliliter) were prepared from the Wistar rat liver using differential centrifugation and incubated with various concentrations of glyoxal (1, 2.5, 5, 7.5, and 10 mM) for 30 min. The activity of mitochondrial complex II was determined by measurement of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) conversion. The mitochondrial membrane potential (MMP), lipid peroxidation (MDA), reactive oxygen species (ROS) formation, glutathione (GSH) content, and protein carbonylation were also assessed. After an incubation of isolated liver mitochondria with glyoxal, disrupted electron transport chain, increased mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane damage, GSH oxidation, and protein carbonylation ensued as compared to the control group ( p < 0.05). Glyoxal toxicity in isolated rat liver mitochondria was dose-dependent. In conclusion, glyoxal impaired the electron transport chain, which is the cause of increased ROS and MDA production, depletion of GSH, and disruption of MMP. Mitotoxicity of glyoxal might be related to the pathomechanisms involved in diabetes and its complications.
Longitudinal Studies on the Microcirculation around the TheraCyte™ Immunoisolation Device, Using the Laser Doppler Technique
Authors: Rafael E. , Gazelius B. , Wu G. S. , Tibell A.
Published: June 2017

Encapsulation of cellular grafts in an immunoisolation membrane device may make it possible to perform transplantation without having to give immunosuppressive drugs. A common problem is the development of an avascular fibrotic zone around the implants, leading to impaired graft survival. The TheraCyte™ macroencapsulation device has therefore been designed to facilitate neovascularization of the device's surface. In this study, we evaluated the microcirculation around empty TheraCyte™ devices implanted SC in rats at various times after implantation, using a laser Doppler probe introduced via the device port. Studies were performed on day 1 or at 1, 2, and 4 weeks or at 2, 3, and 12 months after implantation. The mean flow was 158 ± 42, 148 ± 50, 133 ± 28, 72 ± 17, 138 ± 41, 165 ± 43, and 160 ± 29 perfusion units (PU), respectively. Thus, the microcirculation around the device was significantly reduced at 4 weeks after implantation (p < 0.01) while, from 2 months onwards the circulation had improved and did not differ significantly from that on day 1. The present study shows time-related changes in the microcirculatory flow around TheraCyte™ macroencapsulation devices that agree with our previous microdialysis studies on in vivo exchange of insulin and glucose between the device and the circulation. Laser Doppler flowmetry seems to provide a reliable technique for screening blood perfusion around macroencapsulation devices.
Effects of Flt-3 Ligand in Combination with TPO on the Expansion of Megakaryocytic Progenitors
Authors: Li Karen , Yang Mo , Lam Audrey Carmen , Yau Fung Wan , Yuen Patrick Man Pan
Published: June 2017

As an early acting growth factor, flt-3 ligand (FL) promotes the ex vivo expansion of hematopoietic stem and progenitor cells. The effect and mechanism of FL on the development of the megakaryocytic lineage remain unclear. In this study, we compared the effects of FL and stem cell factor (SCF) in combination with other megakaryocyte-promoting cytokines on the differentiation and proliferation of megakaryocytic progenitors and investigated the expression of flt-3 receptors on megakaryocytic cell lines. In liquid cultures of enriched CD34+ cells from human umbilical cord blood for 14 days, FL plus thrombopoietin (TPO), interleukin-3 (IL-3), and IL-6 promoted the expansion of nucleated cells, CD34+ cells, CD34+CD38– cells, and megakaryocyte colony-forming units (CFU-MK) by 300 ± 115-, 23.8 ± 11.3-, 33.9 ±28.6-, and 584 ± 220-fold, respectively. Replacing FL with SCF significantly decreased the yield of all cell types. Using murine bone marrow (BM) cells, we demonstrated that FL at a range of 0–100 ng/ml had no significant mitogenic effect on CFU-MK formation. TPO increased CFU-MK (p < 0.001) but the effect was not significantly modified by FL. While one human acute lymphoblastic leukemia sample expressed high levels of flt-3 receptor, the four megakaryocytic cell lines (Meg-01, CHRF-288-11, M-07e, and Dami) did not show any positive expression. Our data suggest that the present cytokine combination and expansion conditions provide an effective and potentially useful system for the clinical expansion of cord blood for bone marrow transplantation (BMT). FL alone did not stimulate megakaryocytopoiesis, possibly due to the lack of receptor expression on megakaryocytes. The effect of FL in augmenting the expansion of CFU-MK in liquid culture might be due to the early action of FL at the pluripotent stem cell stage.
Conditionally Immortalized, Multipotential and Multifunctional Neural Stem Cell Lines as an Approach to Clinical Transplantation
Authors: Gray J. A. , Grigoryan G. , Virley D. , Patel S. , Sinden J. D. , Hodges H.
Published: June 2017

Experiments are described using rats with two kinds of brain damage and consequent cognitive deficit (in the Morris water maze, three-door runway, and radial maze): 1) ischemic damage to the CA1 hippocampal cell field after four-vessel occlusion (4VO), and 2) damage to the forebrain cholinergic projection system by local injection of excitotoxins to the nuclei of origin or prolonged ethanol administration. Cell suspension grafts derived from primary fetal brain tissue display a stringent requirement for homotypical cell replacement in the 4VO model: cells from the embryonic day (E)18–19 CA1 hippocampal subfield, but not from CA3 or dentate gyrus or from E16 basal forebrain (cholinergic rich) led to recovery of cognitive function. After damage to the cholinergic system, conversely, recovery of function was seen with cell suspension grafts from E16 basal forebrain or cholinergic-rich E14 ventral mesencephalon, but not with implants of hippocampal tissue. These two models therefore provided a test of multifunctionality for a clonal line of conditionally immortalized neural stem cells, MHP36, derived from the E14 “immortomouse” hippocampal anlage. Implanted above the damaged CA1 cell field in 4VO-treated adult rats, these cells (multipotential in vitro) migrated to the damaged area, reconstituted the gross morphology of the CA1 pyramidal layer, took up both neuronal and glial phenotypes, and gave rise to cognitive recovery. Similar recovery of function and restoration of species-typical morphology was observed when MHP36 cells were implanted into marmosets with excitotoxic CA1 damage. MHP36 implants led to recovery of cognitive function also in two experiments with rats with excitotoxic damage to the cholinergic system damage, either unilaterally in the nucleus basalis or bilaterally in both the nucleus basalis and the medial septal area. Thus, MHP36 cells are both multipotent (able to take up multiple cellular phenotypes) and multifunctional (able to repair diverse types of brain damage).
Towards a Protocol for the Preparation and Delivery of Striatal Tissue for Clinical Trials of Transplantation in Huntington's Disease
Authors: Watts Colin , Dunnett Stephen B.
Published: June 2017

There is a growing body of scientific evidence contributing to the development of clinical transplantation programs in patients with Huntington's disease. Phase I clinical trials have already commenced in France and North America and are starting in the near future in Sweden and the UK. Protocols for patient selection, surgical implantation, and pre- and postoperative follow-up are well defined. However, considerable variability exists with respect to the harvesting, preparation, and timing of implantation of the donor material. In this article we review the scientific evidence on which a rational protocol for donor tissue preparation and delivery may be based. Strategies aimed at minimizing the variability of tissue preparation should reduce the variability of functional outcome of striatal transplantation observed in animal models of Huntington's disease.
Porcine Xenografts in Parkinson's Disease and Huntington's Disease Patients: Preliminary Results
Authors: Fink J. Stephen , Schumacher James M. , Ellias Samuel L. , Palmer E. Prather , Saint-Hilaire Marie , Shannon Kathleen , Penn Richard , Starr Philip , Vanhorne Craig , Kott H. Stephen , Dempsey Peter K. , Fischman Alan J. , Raineri Ronald , Manhart Carolyn , Dinsmore Jonathan , Isacson Ole
Published: June 2017

The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale “off” state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.
Transplantation Options for Therapeutic Central Nervous System Remyelination
Authors: Blakemore William F. , Franklin Robin J. M.
Published: June 2017

Persistent demyelination, in addition to being the major pathology of multiple sclerosis and the leucodystrophies, is also a feature of spinal cord trauma where there is evidence that it contributes to the functional deficit. In experimental animals it is possible to remyelinate demyelinated CNS axons by transplanting cultures containing central or peripheral myelinogenic cells. Using functional testing we have been able to show that transplant-mediated remyelination results in restoration of function lost as a consequence of demyelination. Glial cell transplantation may therefore provide a therapeutic strategy for remyelinating areas of chronic demyelination. This article reviews issues that have to be addressed before glial transplantation can be undertaken in humans. These include: what cells to use, where would the cells come from, and can we predict how much remyelination will be achieved? It concludes that the most promising approach will be to use neural multipotential stem cells isolated from embryonic CNS, expanded in vitro as neurospheres and then committed to oligodendrocyte lineage differentiation prior to implantation. However, even with such preparations, which have considerable myelinating potential, the extent of remyelination that will be achieved cannot currently be predicted with any degree of certainty.
Analysis of Multivariables during Porcine Liver Digestion to Improve Hepatocyte Yield and Viability for Use in Bioartificial Liver Support Systems
Authors: Wang Lisheng , Sun Junhong , Wang Chuanmin , Woodman Kevin , Li Li , Wu Lujia , Harbour Colin , Johnston Brendan , Shi Liwei , Horvat Margret , Koutalistras Nick , Luo Xianfeng , Watson Jenny , Sheil A. G. R.
Published: June 2017

In order to achieve optimal BALSS function, preparation of porcine hepatocytes with high yield, viability, and P450 activity is known to be important. To date hepatocyte yields have varied from 0.58 × 1010 to 3.45 × 10 and viabilities from 75% to 95% within and between laboratories, even when using the same digestion methods and procedures, indicating that hepatocyte isolation during porcine liver digestion is not fully optimized. The aim of this work was to identify the critical parameters affecting cell recovery during porcine liver harvesting by investigating 21 variables involved in the process, including pig body and liver weight, different digestion times of perfusates, pH, a range of concentrations of sodium and chloride in EDTA, and collagenase perfusates. Univariate and multivariate analysis of a retrospective study (n = 23) revealed that low perfusate pH during the process of digestion had a positive effect on hepatocyte yield (p < 0.05), while high (relative) concentrations of sodium and chloride in the perfusates had significant negative effects on hepatocyte viability (both p < 0.05). Sodium and chloride had narrow optimal ranges for achieving a >90% viability. These findings were then tested in a prospective study (n = 10) and further verified. High hepatocyte viabilities (91.8 ± 1.6%, p = 0.036) and yields (2.56 ± 0.48 × 1010) were achieved consistently, and P450IA1 activity was increased after sodium and chloride concentrations and pH in the perfusates were controlled. The physiological mechanism by which sodium and chloride affects hepatocyte viability during porcine liver digestion is discussed.