bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Care Pharmacist Services Align With Payment Reform and Provider “Joy of Practice”
Authors: Smith Marie
Published: October 2018

The implementation and expansion of primary care (PC) pharmacist medication optimization and management services has been hindered mainly by the lack of a payment mechanism for PC providers to engage pharmacist services. If pharmacists expect to be included in new PC team-based payment models, we need to actively engage in ongoing PC practice transformation discussions with PC organizational leaders. In this commentary, examples of integrated PC pharmacist services and payment models are provided to (1) reinforce the feasibility of pharmacist integration into expanded PC teams and (2) share with PC leaders, payers, and policy makers.
Correlation of Endoscopic and Histologic Severity Scores in Pediatric Ulcerative Colitis at First Presentation
Authors: Kovach Alexandra E , Moulton Dedrick E , Plummer Walton D , Dupont William D , Pacheco M Cristina
Published: October 2018

Detailed histologic scoring systems have been developed for the assessment of disease activity in ulcerative colitis. Literature from adult patients has shown some correlation between endoscopy and histology, and reproducibility of histologic scoring systems has also been supported. The effectiveness of endoscopic appearance at predicting histologic scores in pediatric patients has not been well studied, and none of the histologic scoring systems used in adults have had interobserver reproducibility assessed in pediatric patients. We reviewed endoscopic images and concurrent biopsies using Mayo and Geboes scores from the distal colon and rectum in untreated pediatric patients at the presentation of presumed ulcerative colitis based on clinical and endoscopic findings. Interobserver concordance was calculated by weighted-kappa statistic. The averaged histologic scores were compared to endoscopy scores using Spearman’s coefficient. Correlation between endoscopic score and each histologic score was weakly to moderately positive, whereas interobserver agreement for histologic scores was fair to moderate, suggesting that the Geboes scoring system has value in pediatric patients. For each histologic parameter, the average score was lower than the average endoscopic score. Examination of larger pediatric cohorts, treated patients, correlations of clinical outcomes with individual histologic parameters, and alternate scoring systems may contextualize these findings.
Quantified water intake in laboratory cats from still, free-falling and circulating water bowls, and its effects on selected urinary parameters
Authors: Robbins Michael T , Cline Martha G , Bartges Joseph W , Felty Erin , Saker Korinn E , Bastian Richard , Witzel Angela L
Published: October 2018

Objectives

The study objectives were to determine if the method of water presentation (still [S], circulating [C] or free-falling [FF] bowl systems) influences daily water consumption in cats in a controlled environment, and whether differences in water intake affect urine relative super saturation (RSS) for calcium oxalate and struvite, urine specific gravity (USG), urine osmolality (Uosmol) and urine volume.

Methods

Sixteen healthy laboratory cats fed a dry diet were individually housed with urine collection systems. Each cat underwent a randomized 2 week crossover period with all bowl systems, allowing a 1 week acclimation period between each crossover. Water intake was measured daily by bowl weight, accounting for spillage and evaporation. USG and urine volume were measured daily, whereas other urinary parameters were measured at various time points throughout each 14 day crossover period.

Results

Fourteen cats completed the study. Average daily water intake (ml/kg/day), urine volume, USG and urine RSS for struvite and calcium oxalate were not significantly different between water bowls. Uosmol was significantly higher in C compared with S and FF bowl systems ( P = 0.009 for both). Three individual cats demonstrated a significant water bowl preference (Cat 4: C >S, P = 0.039; Cat 10: FF >C, P = 0.005; Cat 11: S >C, P = 0.037).

Conclusions and relevance

Overall, water bowl type had no appreciable effect on water intake. Uosmol was the only urinary parameter found to be significantly different, and was higher for the C bowl. The implication of this is unknown, considering water intake did not differ significantly between bowls. Alternative methods to increase water intake should be implemented beyond providing unique water bowls in patients where augmented water intake would be beneficial for disease management.
Age is a critical determinant in recovery from multiple sclerosis relapses
Authors: Conway Brittani L , Zeydan Burcu , Uygunoğlu Uğur , Novotna Martina , Siva Aksel , Pittock Sean J , Atkinson Elizabeth J , Rodriguez Moses , Kantarci Orhun H
Published: October 2018

Objective:

To evaluate the impact of age on recovery from multiple sclerosis relapses.

Background:

Increasing disability in multiple sclerosis is a consequence of progressive disease and incomplete relapse recovery.

Methods:

The first and last-ever relapse data (357 relapses in 193 patients) from the Olmsted County population-based multiple sclerosis cohort were systematically reviewed for age, fulminance, location (optic nerve, brainstem/cerebellar, spinal cord), peak deficit, and maximum recovery. Three different relapse-outcome measures were studied both as paired analyses and as an overall group effect: change from peak deficit to maximum recovery in raw functional system score related to the relapse (ΔFSS), a previously published FSS-based relapse-impact model, and change from peak deficit to maximum recovery in Extended Disability Status Scale (ΔEDSS) score.

Results:

Older age was linearly associated with worse recovery in the ΔFSS outcome ( p = 0.002), ΔEDSS outcome ( p < 0.001), and the FSS-based relapse-impact model ( p < 0.001). A multivariate analysis of ΔFSS outcome linked poor recovery to older age ( p = 0.015), relapse location (transverse myelitis or brainstem/cerebellar syndrome; p < 0.001), and relapse fulminance ( p = 0.004).

Conclusion:

Multiple sclerosis-relapse recovery declines in a linear fashion with increased age, which should be considered when making treatment decisions.
Impacts of corporate social responsibility on the competitiveness of tourist enterprises: An empirical case of Ben Tre, Vietnam
Authors: Nguyen Thang Quyet , Long Nguyen Thanh , Nguyen Thanh-Lam
Published: October 2018

This study aims at identifying the influence of corporate social responsibility (CSR) on the competitiveness of tourist enterprises in an emerging tourism region – Mekong Delta in Vietnam with an empirical case of Ben Tre Province. Combining qualitative and quantitative research methods, we conducted a survey of 250 respondents including directors, deputy directors, managing and running tourism businesses. Through statistical tests of scale reliability, exploratory factor analysis, confirmatory factor analysis and structural equation modelling, we found that there are five perspectives of CSR significantly affecting the enterprise competitiveness, including (1) human-oriented CSR, (2) social activity–oriented CSR, (3) partner-oriented CSR, (4) environment-oriented CSR and (5) product and service quality–oriented CSR. Especially, this study identified the important roles of three new elements discovered through our expert interviews and group discussions, including ‘connection between business culture development strategy and the local and native cultures’, ‘tourism products/services promoting local special features’ and ‘tourism products/services promoting green environment’. From these findings, we proposed some managerial implications for policymakers to have proper policies in promoting CSR among tourist enterprises and improving their competitiveness.
The role of social embeddedness for remaining in non-desired workplaces and mental health consequences: Results from Scania Public Health Cohort
Authors: Bernhard-Oettel Claudia , Canivet Catarina , Aronsson Gunnar , StengÅRd Johanna , ÖStergren P-O
Published: October 2018

Aims: The aim of the study was to investigate the role of social embeddedness on and off the job in relation to remaining in non-desired workplaces (NDWs) and the development of mental health. Method: The study used questionnaire data from the Scania Public Health cohort ( N=2410) that were collected in 2000 (T1), 2005 (T2) and 2010 (T3). Logistic regression models were calculated to probe how NDWs and social embeddedness factors measured at baseline (T1) related to NDWs five years later (T2), and to investigate how NDWs and social embeddedness factors at T2 related to poor mental health at T3. Synergy indices were calculated in both analyses to test for additive v. interactive effects between NDWs and social embeddedness factors on the outcomes. Results: NDWs at baseline and low social embeddedness on and off the job was associated with NDWs at T2. For those in a desired workplace, low support from co-workers as well as low workplace affinity increased the risk to be in an NDW at T2. NDWs and low social embeddedness also associated with impaired mental health (T3). For those in an NDW, low support from co-workers as well as low workplace affinity increased the risk of poor mental health at T3. Conclusions: This study underlines the importance of social embeddedness for NDWs and the development of poor mental health over time. Particularly low social support from co-workers and low workplace affinity seem to be risk factors for future experience of an NDW and impaired mental health.
When context trumps culture: Persuasion in international business disputes
Authors: Zaidman Nurit , Itzhaki Rinat , Shenkar Oded
Published: October 2018

Persuasion plays an important role in international business interactions. Within this domain, it is often argued that persuasion is a form of communication and as such embedded in cultural norms. It is also argued that forms of persuasion differ across cultures. The data described in this study of persuasive tactics deployed by Israeli and Indian business professionals in their attempts to resolve disputes with their partners suggest otherwise. These data mainly comprise 142 coded letters, addressed to the correspondents’ business partner and to the mediator. The quantitative results of the study show similarities in the choice of persuasive tactics employed by Israeli and Indian correspondents, when writing to each other and when writing to the mediator. The quantitative and qualitative results show that these research subjects, from two culturally different populations, constructed their persuasion tactics and communication in a similar manner. Hence, despite the apparent cultural and communication differences between them, they both employed similar communication tactics. These intriguing data are explained in the light of the fact that both Indian and Israeli subjects were experiencing a situation which they subjectively perceived as one involving a threat of meaningful loss. These perceptions and emotional responses led the participants toward similar communication behavior. This study contributes to international management research, and particularly to intercultural communication research, by demonstrating that contextual conditions do cause culturally different populations to communicate similarly.
Migration, pluralism and ‘Earth’s consciousness’: Some reflections starting from Ettore Gelpiʼs thought
Authors: Riccardi Veronica
Published: October 2018

Known worldwide level as an expert in lifelong learning, Ettore Gelpi (1933–2002) devoted his most important ‘educational struggles’ to issues of discrimination in acquiring education, sustainable development, education for democracy and cultural pluralism. His engagement has involved all categories of ‘minority’, and he has been able to place the issues related to the coexistence of people with different cultures and languages within a wide, complex and interdisciplinary framework that beyond local and national boundaries. The aim of this chapter is to investigate the concept of intercultural education developed by Gelpi since all humans are unique, not only in language and traditions, but also with regard to countless other individual characteristics, we contend that humans are innately, intercultural. The main question is this: must we educate towards cultural pluralism or analyse how cultural pluralism can be educational? Probably, the latter assumption is the more valid: learning to live together in cultural diversity means above all to live an exchange with people from different cultures and is a real learning opportunity.
Botanical Formula LCS101: A Multi-Targeted Approach to Cancer Care
Authors: Maimon Yair , Samuels Noah , Cohen Zoya , Berger Raanan , Rosenthal David S.
Published: October 2018

Background and Purpose: LCS101 is a botanical formula extracted from 14 botanical components. While conventional oncology focuses on targeted medicine, research on LCS101 adopts a multi-targeted approach, examining its preclinical (in vitro, in vivo, and ex vivo) and clinical (randomized controlled trial, pragmatic) effects. This includes examining the formula’s impact on the immune system, selective anticancer effects, and improved chemotherapy-related symptoms and quality of life. Effects on the Immune System: In murine splenic cell cultures, LCS101 significantly increased T-cell proliferation and macrophage tumor necrosis factor-α production. Blood samples from healthy volunteers exposed to LCS101 showed a dose-dependent increase in natural killer cell activity; and a randomized controlled trial showed significantly lower rates of leucopenia/neutropenia and anemia in patients with breast cancer undergoing chemotherapy. Selective Anticancer Effects: In vitro LCS101 demonstrated selective growth inhibition (on XTT viability assay) in human breast and prostate cancer cell lines, without any harmful effects on normal human epithelial cells. The anticancer effects were attributed to reactive oxygen species activity. Cytotoxic effects of doxorubicin and 5-fluorouracil on breast cancer cell lines were significantly increased following exposure to LCS101, with a protective effect in normal cells. Symptom Relief and Quality of Life: Clinical research shows that patients taking LCS101 during chemotherapy are less likely to report symptoms such as fatigue, pain, nausea and vomiting. Conclusion: LCS101 exhibits multi-targeted effects, with significant implications for cancer care. Further research is needed to better understand the impact of these findings.
Multi-agent single-objective negotiation mechanism of personalized product supply chain based on personalized index
Authors: Yang Changhui , Xu Tingting , Yang Ruixia , Li Yinxia
Published: October 2018

In the multi-agent system of personalized product supply chain, negotiation can effectively solve conflict and realize cooperation. In this article, personalized index is defined and the calculation method of personalized index is presented. Then, the multi-agent negotiation model is constructed based on personalized index and the negotiation procedure is discussed. Finally, the validity of the model is demonstrated by an example. That will be provided theoretical and operational methods for personalized product supply chain management, is helpful to coordinate and control personalized product supply chain, and realize the efficient, flexible, and quick operation of personalized product supply chain.
Solving the dual-resource constrained flexible job shop scheduling problem with learning effect by a hybrid genetic algorithm
Authors: Wu Rui , Li Yibing , Guo Shunsheng , Xu Wenxiang
Published: October 2018

In this article, we investigate a novel dual-resource constrained flexible job shop scheduling problem with consideration of worker’s learning ability and develop an efficient hybrid genetic algorithm to solve the problem. To begin with, a comprehensive mathematical model with the objective of minimizing the makespan is formulated. Then, a hybrid algorithm which hybridizes genetic algorithm and variable neighborhood search is developed. In the proposed algorithm, a three-dimensional chromosome coding scheme is employed to represent the individuals, a mixed population initialization method is designed for yielding the initial population, and advanced crossover and mutation operators are proposed according to the problem characteristic. Moreover, variable neighborhood search is integrated to improve the local search ability. Finally, to evaluate the effectiveness of the proposed algorithm, computational experiments are performed. The results demonstrate that the proposed algorithm can solve the problem effectively and efficiently.
Multivariable case-based reason adaptation based on multiple-output support vector regression with similarity-related weight for parametric mechanical design
Authors: Qi Jin , Hu Jie
Published: October 2018

Using historical cases’ solutions to obtain feasible solution for new problem is fundamentally to successfully applying case-based reason technique in parametric mechanical design. As a well-known intelligent algorithm, the formulation of support vector regression has been taken for case-based reason adaptation, but the standard support vector regression can only be used as a univariate adaptation method because of its single-output structure, which would result in the ignorance of the possible interrelations among solution outputs. To handle the complicated case adaptation task with large number of problem inputs and solution outputs more efficiently, this study investigates the possibility of multivariable case-based reason adaptation with multiple output by applying multiple-output support vector regression. Furthermore, inspired by the fact that training sample which contains two closer cases can provide more useful information than others, this study adds the similarity-related weight into multiple-output support vector regression and gives high weights to the information provided by such useful training sample during multi-dimensional regression estimation. The superiority of proposed multiple-output support vector regression with similarity-related weight is validated by the actual design example and quantitative comparisons with other adaptation methods. The comparative results indicate that multiple-output support vector regression with similarity-related weight achieves the best performance for large-quantity case-based reason adaptation because of its higher accuracy and relatively lower cost.
The lived experience of people with intellectual disabilities in post-secondary or higher education
Authors: Corby Deirdre , Taggart Laurence , Cousins Wendy
Published: October 2018

The transformational role education plays in the lives of people with intellectual disabilities has not been fully examined. The purpose of this study was to explore and investigate the meanings people with intellectual disabilities construct of their experiences in post-secondary and higher education. Heideggerian hermeneutic phenomenology was the qualitative methodology adopted for the study. Individual interviews were conducted with 27 people with intellectual disabilities and analysed in stages. These stages included the creation of I-Poems offering a unique opportunity for individual participant voices to be heard. Three core themes emerged to describe living an authentic life: learning (with the emphasis on increased skills, independence and opportunities); relationships (in particular, the importance of friendships), and perceptions including the existing realities of life for those with intellectual disabilities. The findings advance previous work highlighting the link between living a more authentic life and how education transforms how people with intellectual disabilities view themselves.
Chronic myocardial infarction changed the excitatory–inhibitory synaptic balance in the medial prefrontal cortex of rat
Authors: Li Jing
Published: October 2018

The medial prefrontal cortex is a key area for the regulation of pain and emotion. However, the functional involvement of the medial prefrontal cortex for visceral nociception, at the neuronal or synaptic level, is obscure yet. In the present study, the properties of excitatory and inhibitory synaptic transmission within the layer II/III of rat medial prefrontal cortex after chronic myocardial infarction were studied. It is found that the excitation–inhibition ratio of the medial prefrontal cortex was greatly changed, with enhanced excitation and decreased inhibition inputs to the pyramidal cells of the medial prefrontal cortex, which largely due to decreased spike firing in gamma-aminobutyric acid-ergic neurons. Behaviorally, inhibition of gamma-aminobutyric acid-ergic synaptic transmission alleviated the visceral pain and anxiety. It is thus for the first time showing that the excitation–inhibition ratio is increased in the medial prefrontal cortex after chronic myocardial infarction, which may come from the reduced intrinsic activity of gamma-aminobutyric acid-ergic neurons and is important for regulating the angina pectoris and anxiety induced by chronic myocardial infarction.
Intraoperative Error Propagation in 3-Dimensional Spinal Navigation From Nonsegmental Registration: A Prospective Cadaveric and Clinical Study
Authors: Guha Daipayan , Jakubovic Raphael , Gupta Shaurya , Fehlings Michael G. , Mainprize Todd G. , Yee Albert , Yang Victor X. D.
Published: October 2018

Study Design:

Prospective pre-clinical and clinical cohort study.

Objectives:

Current spinal navigation systems rely on a dynamic reference frame (DRF) for image-to-patient registration and tool tracking. Working distant to a DRF may generate inaccuracy. Here we quantitate predictors of navigation error as a function of distance from the registered vertebral level, and from intersegmental mobility due to surgical manipulation and patient respiration.

Methods:

Navigation errors from working distant to the registered level, and from surgical manipulation, were quantified in 4 human cadavers. The 3-dimensional (3D) position of a tracked tool tip at 0 to 5 levels from the DRF, and during targeting of pedicle screw tracts, was captured in real-time by an optical navigation system. Respiration-induced vertebral motion was quantified from 10 clinical cases of open posterior instrumentation. The 3D position of a custom spinous-process clamp was tracked over 12 respiratory cycles.

Results:

An increase in mean 3D navigation error of ≥2 mm was observed at ≥2 levels from the DRF in the cervical and lumbar spine. Mean ± SD displacement due to surgical manipulation was 1.55 ± 1.13 mm in 3D across all levels, ≥2 mm in 17.4%, 19.2%, and 38.5% of levels in the cervical, thoracic, and lumbar spine, respectively. Mean ± SD respiration-induced 3D motion was 1.96 ± 1.32 mm, greatest in the lower thoracic spine ( P < .001). Tidal volume and positive end-expiratory pressure correlated positively with increased vertebral displacement.

Conclusions:

Vertebral motion is unaccounted for during image-guided surgery when performed at levels distant from the DRF. Navigating instrumentation within 2 levels of the DRF likely minimizes the risk of navigation error.
The evolution of informal land use in a Nigerian market
Authors: Alabi Adekunle Moruf , Lasisi Mubarak Olatunji , Azeez Maryam Abimbola
Published: October 2018

Urban growth is one of the indicators that reflects human interaction with the environment and has a direct effect on land use change. Continuous demand for space in Nigeria’s urban markets to accommodate shops and other retail outlets used for informal economic activities is accompanied by a change of use. This study examined the impact of informal economic activities on change of use in Bola Ige International Market, Ibadan. The concept of informal economy and the bid rent theory provided the conceptual/theoretical framework for this study. Geographical Information System was used to capture the change of use between 2006 and 2016. Land used for informal economic activities increased from 39.45% in 2006 to 55.35% in 2016, signifying a 15.9% increase. This implies that other land uses have been illegally converted and encroached. Transportation land use decreased from 31.47% in 2006 to 30.28% in 2011 and to 28.73% in 2016. Land used for open space (including parking space, and open trading area) which was 26.7% in 2006 reduced to 20.24% and 11.05% in 2011 and 2016, respectively. Most of the green areas (62.1%) have been converted to informal trading spaces between 2006 and 2016. Illegal change of use was credited to harsh economic condition in the country, and the engagement of the unemployed and retirees in informal sector economic activities. It was suggested that urban managers in conjunction with informed activists, researchers and citizens need to formulate and implement planning regulations that will integrate informal economic activities.
Latinx Students and Secondary Music Education in the United States
Authors: Escalante Samuel Isai
Published: October 2018

As of 2014, Latinx youth have comprised roughly a quarter of the U.S. population younger than 18 years. Yet Latinx students have not been found to participate in school ensembles at rates consistent with their proportion of the total student population. This disparity has yet to be fully explained by the research literature. The purpose of this review of literature is to synthesize what scholars understand about Latinx student participation in school ensembles. Literature was chosen based on the following research question: What factors may contribute to the disparity between the Latinx student population and the rate of Latinx participation in secondary school music ensembles, nationally? This review revealed several factors that may influence participation rates of Latinx students in secondary music ensembles, including curricular and systemic factors, music teacher attitudes toward diversity, Latinx parental involvement, and Latinx students’ interests. Implications for increasing participation and improving music education for Latinx students are discussed.
Numerical and experimental analysis of the effect of metal tie layers on improving electrical properties of gold coated poly (dimethylsiloxane) flexible multi-layered films during folding
Authors: Wen Bor-Jiunn , Wang Pen-Cheng , Hung Pin-Hsuan
Published: October 2018

To improve folding electrical properties of flexible electronics, this study presents a new adhesive stress analysis of depositing an adhesion layer between the conductive film electrode and the flexible substrate during folding test by a folding test platform. The folding test platform controls folding curvature of the flexible conductive substrates, folding times, and velocities in this study. Moreover, the electrical properties of flexible conductive substrates are measured during folding testing by the folding test platform. Eventually, this study successfully analyzes residual strain, adhesive stress, and electrical properties of flexible gold coated on polydimethylsiloxane substrates with chromium, nickel, and titanium adhesion layers up to 0.5/cm folding curvature during folding testing. The chromium adhesion layer had the best performance based on the largest adhesive stress, only 3.74 Ω resistance increase and 4.53 Ω maximum resistance up to 0.5/cm folding curvature during folding test by a folding test platform. The experimental result with chromium adhesion layer is consistent with adhesive stress analysis and provides a better adhesive strength between gold and polydimethylsiloxane than nickel and titanium materials for folding test. Therefore, adhesive stress analysis is adapted to evaluate the foldable electronics performance for improving folding characteristics easier.
Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia
Authors: Dickinson Michael , Cherif Honar , Fenaux Pierre , Mittelman Moshe , Verma Amit , Portella Maria Socorro O. , Burgess Paul , Ramos Pedro Marques , Choi Jeea , Platzbecker Uwe
Published: October 2018

Azacitidine treatment of myelodysplastic syndromes (MDSs) generally exacerbates thrombocytopenia during the first treatment cycles. A Study of Eltrombopag in Myelodysplastic Syndromes Receiving Azacitidine (SUPPORT), a phase 3, randomized, double-blind, placebo-controlled study, investigated the platelet supportive effects of eltrombopag given concomitantly with azacitidine. International Prognostic Scoring System intermediate-1, intermediate-2, or high-risk MDS patients with baseline platelets <75 × 109/L were randomized 1:1 to eltrombopag (start, 200 mg/d [East Asians, 100 mg/d], maximum, 300 mg/d [East Asians, 150 mg/d]) or placebo, plus azacitidine (75 mg/m2 subcutaneously once daily for 7 days every 28 days). The primary end point was the proportion of patients platelet transfusion-free during cycles 1 through 4 of azacitidine therapy. Based on planned interim analyses, an independent data monitoring committee recommended stopping the study prematurely because efficacy outcomes crossed the predefined futility threshold and for safety reasons. At termination, 28/179 (16%) eltrombopag and 55/177 (31%) placebo patients met the primary end point. Overall response (International Working Group criteria; complete, marrow, or partial response) occurred in 20% and 35% of eltrombopag and placebo patients, respectively, by investigator assessment. There was no difference in hematologic improvement in any cell lineage between the 2 arms. There was no improvement in overall or progression-free survival. Adverse events with ≥10% occurrence in the eltrombopag vs placebo arm were febrile neutropenia and diarrhea. Compared with azacitidine alone, eltrombopag plus azacitidine worsened platelet recovery, with lower response rates and a trend toward increased progression to acute myeloid leukemia. This trial was registered at www.clinicaltrials.gov as #NCT02158936.
Sensing of red blood cells with decreased membrane deformability by the human spleen
Authors: Safeukui Innocent , Buffet Pierre A. , Deplaine Guillaume , Perrot Sylvie , Brousse Valentine , Sauvanet Alain , Aussilhou Beatrice , Dokmak Safi , Couvelard Anne , Cazals-Hatem Dominique , Mercereau-Puijalon Odile , Milon Geneviève , David Peter H. , Mohandas Narla
Published: October 2018

The current paradigm in the pathogenesis of several hemolytic red blood cell disorders is that reduced cellular deformability is a key determinant of splenic sequestration of affected red cells. Three distinct features regulate cellular deformability: membrane deformability, surface area-to-volume ratio (cell sphericity), and cytoplasmic viscosity. By perfusing normal human spleens ex vivo, we had previously showed that red cells with increased sphericity are rapidly sequestered by the spleen. Here, we assessed the retention kinetics of red cells with decreased membrane deformability but without marked shape changes. A controlled decrease in membrane deformability (increased membrane rigidity) was induced by treating normal red cells with increasing concentrations of diamide. Following perfusion, diamide-treated red blood cells (RBCs) were rapidly retained in the spleen with a mean clearance half-time of 5.9 minutes (range, 4.0-13.0). Splenic clearance correlated positively with increased membrane rigidity (r = 0.93; P < .0001). To determine to what extent this increased retention was related to mechanical blockade in the spleen, diamide-treated red cells were filtered through microsphere layers that mimic the mechanical sensing of red cells by the spleen. Diamide-treated red cells were retained in the microsphilters (median, 7.5%; range, 0%-38.6%), although to a lesser extent compared with the spleen (median, 44.1%; range, 7.3%-64.0%; P < .0001). Taken together, these results have implications for understanding the sensitivity of the human spleen to sequester red cells with altered cellular deformability due to various cellular alterations and for explaining clinical heterogeneity of RBC membrane disorders.
Chronic blood exchange transfusions in the management of pre-capillary pulmonary hypertension complicating sickle cell disease
Authors: Turpin Matthieu , Chantalat-Auger Christelle , Parent Florence , Driss Françoise , Lionnet François , Habibi Anoosha , Maître Bernard , Huertas Alice , Jaïs Xavier , Weatherald Jason , Montani David , Sitbon Olivier , Simonneau Gérald , Galactéros Fréderic , Humbert Marc , Bartolucci Pablo , Savale Laurent
Published: October 2018

The long-term effects of chronic blood exchange transfusions (BETs) on pre-capillary pulmonary hypertension complicating sickle cell disease (SCD) are unknown.

13 homozygous SS SCD patients suffering from pre-capillary pulmonary hypertension and treated by chronic BETs were evaluated retrospectively. Assessments included haemodynamics, New York Heart Association Functional Class (NYHA FC), 6-min walk distance (6MWD) and blood tests.

Before initiating BETs, all patients were NYHA FC III or IV, median (range) 6MWD was 223 (0–501) m and median (range) pulmonary vascular resistance (PVR) was 3.7 (2–12.5) Wood Units. After a median number of 4 BET sessions, all patients had improved to NYHA FC II or III. Significant improvements in haemodynamics were observed, including a decrease in PVR (p=0.01). There was a trend to higher 6MWD (p=0.09). Median (range) follow-up time after initiation of BETs was 25 (6–53) months. During this period, two patients decided to stop BETs. One of them died from acute right heart failure and the other experienced worsening pulmonary hypertension. Two other patients died during follow-up at 25 and 54 months after BET initiation.

Chronic BETs may be a potential therapeutic option in pre-capillary pulmonary hypertension complicating SCD, leading to significant clinical and haemodynamic improvements. These data must be confirmed in a prospective study.
Preclinical Evaluation of Ropivacaine in 2 Liposomal Modified Systems
Authors: Rennó Carolina C. , Papini Juliana Z. B. , Cereda Cintia Maria Saia , Martinez Elizabeth , Montalli Victor Angelo , de Paula Eneida , Pedrazzoli Júnior José , Calafatti Silvana Aparecida , Tofoli Giovana Radomille
Published: October 2018

BACKGROUND:

Our research group has recently developed liposomes with ionic gradient and in a combined manner as donor and acceptor vesicles containing ropivacaine (RVC; at 2% or 0.75%). Looking for applications of such novel formulations for postoperative pain control, we evaluated the duration of anesthesia, pharmacokinetics, and tissue reaction evoked by these new RVC formulations.

METHODS:

The formulations used in this study were large multivesicular vesicle (LMVV) containing sodium acetate buffer at pH 5.5 or in a combined manner with LMVV as donor and large unilamellar vesicles (LUVs) as acceptor vesicles with an external pH of 7.4. Wistar rats were divided into 6 groups (n = 6) and received sciatic nerve block (0.4 mL) with 6 formulations of RVC (LMVVRVC0.75%, LMVV/LUVRVC0.75%, LMVVRVC2%, LMVV/LUVRVC2%, RVC 0.75%, and RVC 2%). To verify the anesthetic effect, the animals were submitted to the pain pressure test and the motor block was also monitored. Histopathology of the tissues surrounding the sciatic nerve region was also assessed 2 and 7 days after treatment. Rats (n = 6) were submitted to a hind paw incision, and mechanical hypersensitivity was measured via the withdrawal response using von Frey filaments after injection of the 6 formulations. Finally, New Zealand white rabbits (n = 6) received sciatic nerve block (3 mL) with 1 of the 6 formulations of RVC. Blood samples were collected predose (0 minutes) and at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360, 420, 480, and 540 minutes after injection. RVC plasma levels were determined using a triple-stage quadrupole mass spectrometer.

RESULTS:

Duration and intensity of the sensory block were longer with all liposomal formulations, when compared to the plain RVC solution (P < .05). Histopathological evaluation showed greater toxicity for the positive control (lidocaine 10%), when compared to all formulations (P < .05). After the hind paw incision, all animals presented postincisional hypersensitivity and liposomal formulations showed longer analgesia (P < .05). LMVVRVC0.75% presented higher time to reach maximum concentration and mean residence time than the remaining formulations with RVC 0.75% (P < .05), so LMVV was able to reduce systemic exposure of RVC due to slow release from this liposomal system.

CONCLUSIONS:

All new liposomal formulations containing 0.75% RVC were able to change the pharmacokinetics and enhance anesthesia duration due to slow release of RVC from liposomes without inducing significant toxic effects to local tissues.
Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis
Authors: Liang Chao , Du Fang , Wang Jiaxing , Cang Jing , Xue Zhanggang
Published: October 2018

BACKGROUND:

Propofol can cause degeneration of developing brain cells and subsequent long-term learning or memory impairment. However, at the early stage of embryonic development, the molecular mechanism of propofol-induced inhibition in neural stem cells (NSCs) neurogenesis is still unclear. The aim of this study was to determine the role of propofol in NSCs neurogenesis and, more importantly, to explore the underlying mechanism.

METHODS:

First, a single intraperitoneal injection of propofol was performed in pregnant mice, and 6 hours after administration of propofol, the hippocampus RNA and the protein of the embryos’ brains was extracted to analyze the expression of neuron-specific markers. Second, the primary NSCs were isolated from the hippocampus of mouse embryonic brain and then treated with propofol for cell viability, immunostaining, and transwell assays; more importantly, we performed RNA sequencing (RNA-seq) and q-reverse transcription polymerase chain reaction assays to identify genes regulated by propofol; the Western blot, small interfering RNA (SiRNA), and luciferase reporter assays were used to study the effects of propofol on calmodulin-dependent protein kinase (CaMk) II/5’ adenosine monophosphate-activated protein kinase (AMPK)/activating transcription factor 5 (ATF5) signaling pathway.

RESULTS:

Our results indicated that propofol treatment could inhibit the proliferation, migration, and differentiation of NSCs. The results of RNA-seq assays showed that propofol treatment resulted in downregulation of a group of Ca2+-dependent genes. The following mechanism studies showed that propofol regulates the proliferation, differentiation, and migration of NSCs through the CaMkII/phosphorylation of serine at amino acid position 485 (pS485)/AMPK/ATF5 signaling pathway.

CONCLUSIONS:

The results from study demonstrated that propofol inhibits the proliferation, differentiation, and migration of NSCs, and these effects are partially mediated by CaMkII/pS485/AMPK/ATF5 signaling pathway.
Dexamethasone Is Superior to Dexmedetomidine as a Perineural Adjunct for Supraclavicular Brachial Plexus Block: Systematic Review and Indirect Meta-analysis
Authors: Albrecht Eric , Vorobeichik Leon , Jacot-Guillarmod Alain , Fournier Nicolas , Abdallah Faraj W.
Published: October 2018

BACKGROUND:

Both dexamethasone and dexmedetomidine are effective peripheral nerve block (PNB) perineural adjuncts that prolong block duration. However, each is associated with side effects. With paucity of head-to-head comparisons of these adjuncts, the question of the best adjunct to mix with local anesthetics (LA) for PNB is unanswered. This meta-analysis aims to inform current practice and future research by identifying the superior adjunct by comparing dexamethasone and dexmedetomidine.

METHODS:

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, trials comparing the combination of perineural dexamethasone or dexmedetomidine with LA to LA alone for PNB were sought. The Cochrane Risk of Bias Tool was used to assess the methodological quality of trials, and indirect or network meta-analyses using random-effects modeling were planned. We designated duration of analgesia as a primary outcome. Secondary outcomes included sensory and motor block durations, sensory and motor block onset times, and the risks of hypotension, sedation, and neurological symptoms.

RESULTS:

Fifty trials were identified, including only 1 direct comparison, precluding a network meta-analysis. Indirect meta-analysis of 49 trials (3019 patients) was performed. Compared to dexmedetomidine, dexamethasone prolonged the duration of analgesia by a mean difference (95% confidence interval [CI]) of 148 minutes (37–259 minutes) (P = .003), without prolonging sensory/motor blockade. Dexmedetomidine increased rates of hypotension (risk ratio [95% CI], 6.3 [1.5–27.5]; P = .01) and sedation (risk ratio [95% CI], 15.8 [3.9–64.6]; P = .0001). Overall risk of bias was moderate, and publication bias was noted, resulting in downgrading evidence strength.

CONCLUSIONS:

There is low-quality evidence that both adjuncts similarly prolong sensory/motor blockade. However, dexamethasone may be a superior adjunct; it improves the duration of analgesia by a statistically significant increase, albeit clinically modest, equivalent to 2.5 hours more than dexmedetomidine, without the risks of hypotension or sedation. Future direct comparisons are encouraged.
The DNA Duplex as an Aqueous One-Dimensional Soft Crystal Scaffold for Photochemistry
Authors: Asanuma Hiroyuki , Murayama Keiji , Kamiya Yukiko , Kashida Hiromu
Published: October 2018

In this account, we demonstrate that DNA duplex is an ideal scaffold for photochemistry, particularly for comparison of photochemical theory with experiments. The well-defined structure of a DNA duplex can be regarded as an aqueous one-dimensional soft crystal composed of a chromophore-like base-pair assembly. When any base pair in the duplex is replaced with a chromophore, orientation, distance, and association number of chromophores can be precisely controlled. We have developed a new methodology for introduction of chromophores into DNA duplexes using d-threoninol. By using the DNA duplex as a scaffold, experiments on exciton interactions of chromophore assemblies can be compared with molecular exciton theory. A fluorescent resonance energy transfer (FRET) system was also constructed by introducing donor pyrene and acceptor perylene into the DNA duplex using d-threoninol monomers. Using this system, we demonstrated orientation-dependent FRET. We found that theories on both exciton interaction and FRET qualitatively coincide with experimental data and revealed the limitation of the point-dipole approximation. We also evaluated the intrinsic quantum yield of photodimerization of stilbene derivatives by suppressing a side reaction. We propose that there is a correlation of quantum yield of photodimerization with the energy gap of HOMO or LUMO, a hypothesis that deserves theoretical investigation.
Using machine learning to guide targeted and locally-tailored empiric antibiotic prescribing in a children's hospital in Cambodia
Authors: Oonsivilai Mathupanee , Mo Yin , Luangasanatip Nantasit , Lubell Yoel , Miliya Thyl , Tan Pisey , Loeuk Lorn , Turner Paul , Cooper Ben S.
Published: October 2018

Background: Early and appropriate empiric antibiotic treatment of patients suspected of having sepsis is associated with reduced mortality. The increasing prevalence of antimicrobial resistance reduces the efficacy of empiric therapy guidelines derived from population data. This problem is particularly severe for children in developing country settings. We hypothesized that by applying machine learning approaches to readily collect patient data, it would be possible to obtain individualized predictions for targeted empiric antibiotic choices.

Methods and Findings: We analysed blood culture data collected from a 100-bed children's hospital in North-West Cambodia between February 2013 and January 2016. Clinical, demographic and living condition information was captured with 35 independent variables. Using these variables, we used a suite of machine learning algorithms to predict Gram stains and whether bacterial pathogens could be treated with common empiric antibiotic regimens: i) ampicillin and gentamicin; ii) ceftriaxone; iii) none of the above. 243 patients with bloodstream infections were available for analysis. We found that the random forest method had the best predictive performance overall as assessed by the area under the receiver operating characteristic curve (AUC). The random forest method gave an AUC of 0.80 (95%CI 0.66-0.94) for predicting susceptibility to ceftriaxone, 0.74 (0.59-0.89) for susceptibility to ampicillin and gentamicin, 0.85 (0.70-1.00) for susceptibility to neither, and 0.71 (0.57-0.86) for Gram stain result. Most important variables for predicting susceptibility were time from admission to blood culture, patient age, hospital versus community-acquired infection, and age-adjusted weight score.

Conclusions: Applying machine learning algorithms to patient data that are readily available even in resource-limited hospital settings can provide highly informative predictions on antibiotic susceptibilities to guide appropriate empiric antibiotic therapy. When used as a decision support tool, such approaches have the potential to improve targeting of empiric therapy, patient outcomes and reduce the burden of antimicrobial resistance.
Peromelia – congenital transverse deficiency of the upper limb: A literature review and current prosthetic treatment
Authors: Farr S. , Catena N. , Martinez-Alvarez S. , Soldado F. ,   EPOS Upper Limb Study Group
Published: October 2018

Peromelia or congenital transverse deficiency describes a truncation of the upper limb below various limb levels. Recommendations regarding treatment vary and are mainly based on expert opinions. This paper summarizes the current literature regarding the aetiology, pathogenesis and specifically treatment algorithms for children with peromelia. We performed a non-systematic review of the current literature from MEDLINE/PubMed to obtain comprehensive up-to-date information about peromelia, focusing on current recommendations for the treatment of peromelia (e.g. prosthetic fitting, external stump lengthening). The current literature lacks clear evidence as to whether prosthetic treatment is superior to prosthetic non-usage. However, based on the available studies, children with transradial or transhumeral peromelia should preferably be fitted with passive/cosmetic prostheses at the age between six and 24 months, followed by active/myoelectric devices at the age of 2.5 to four years. It remains controversial whether early myoelectric prosthetic fitting can reduce prosthesis rejection times; however, cognitive readiness and the ability to absolve a guided training programme are seen as important prerequisites for myoelectric fitting. Children with very short stumps may benefit from stump lengthening using external fixators and prosthetic modification. The treatment of children with peromelia generally requires a guided, multidisciplinary team approach. A training programme is essential to optimize individuals’ performance in the execution of activities of daily living and decrease rejection risks whenever a myoelectric device is prescribed. Myoelectric fitting should preferably be commenced at no later than four years of age. However, long-term reports on the benefits of prosthetic treatment are still pending.