bluuebunny/crossref_metadata_2025 huggingface dataset:
Myocardial protection in the arterial switch operation: Custodiol versus cold blood cardioplegia
Authors: Pérez-Andreu Joaquín , Fernández-Doblas Joaquín , Sao Avilés Augusto , de la Torre García Teresa , Roses Noguer Ferrán , Abella Raúl F
Published: August 2019

OBJECTIVES

The optimal myocardial protective solution in the neonatal arterial switch operation remains controversial. The aim of this study was to demonstrate that Bretschneider’s histidine–tryptophan–ketoglutarate crystalloid solution (Custodiol) offers protection at least similar to that of cold blood cardioplegia.

METHODS

Patients who underwent the neonatal arterial switch operation with Custodiol between January 2016 and December 2018 (n = 23) were compared with an historical cohort from August 2010 to December 2015 in which cold blood cardioplegia was used (n = 41). A linear mixed-effect model for repeated measures was performed to test the recovery of myocardial function based on inotropic and vasoactive inotropic scores, cardiac enzyme release and left ventricular ejection fraction.

RESULTS

Patients in the cold blood cardioplegia group had higher inotropic scores in the first 24 h (0 h, P = 0.001 and 24 h, P = 0.006) and higher vasoactive inotropic scores in the first 72 h (0 h, 24 h and 48 h, P < 0.001; 72 h, P = 0.012). Cardiac troponin-I concentrations were higher in the cold blood cardioplegia group at postoperative hours 1–72 (1 h, 6 h, 12 h and 24 h, P < 0.001; 48 h, P = 0.001 and 72 h, P = 0.003). Creatinine-kinase-MB concentrations were higher in the cold blood cardioplegia group at postoperative hours 1–24 (1 h, 6 h and 12 h, P < 0.001; 24 h, P = 0.042). The left ventricular ejection fraction was higher in the Custodiol group just after the operation (P = 0.005), at 24 h (P = 0.001) and on the first day without inotropic support (P = 0.011).

CONCLUSIONS

Neonatal myocardium protected with Custodiol during the arterial switch operation presented optimal ventricular function recovery with less inotropic support and less myocardial damage compared with cold blood cardioplegia.
BEEF SPECIES-RUMINANT NUTRITION CACTUS BEEF SYMPOSIUM: A role for beef cattle in sustainable U.S. food production1
Authors: Gleason Claire B , White Robin R
Published: August 2019

The increasing global population, limited resource availability, and global focus on reducing greenhouse gas (GHG) emissions put pressure on animal agriculture industries to critically evaluate and optimize the role they play in a sustainable food production system. The objective of this review is to summarize evidence of the various roles that the U.S. beef industry plays in the U.S. and global agricultural systems. As the world’s largest beef producer, the United States reaps considerable economic benefit from the beef industry through strong domestic and international demand, as well as employment opportunities for many Americans. Beef production contributes to GHG emissions, land use, and water use, among other critical environmental impacts but provides an important source of essential micronutrients for human consumption. The U.S. beef industry provides sufficient product to meet the protein, vitamin B12, omega-3 and -6 fatty acid requirements of 43, 137, 47, and 487 million people, respectively. In the United States, beef production was estimated to account for 53% of GHG emissions from U.S. animal agriculture and 25% of GHG emissions from all of U.S. agriculture. Footprinting studies suggest that much of the land use and water use associated with beef production are attributed to the development of feed crops or pastureland. On a global scale, beef from U.S. origin is exported to numerous developed and developing countries, representing an important international nutrient routing. Along with other prominent beef-producing nations, the United States continues to pursue a greater level of sustainability in its cattle industry, which will bear important implications for future global food security. Efforts to reduce the environmental impacts of beef production will likely be the strongest drivers of enhanced sustainability.
Prewar Domestic Conditions and Civilians in War
Authors: Bulutgil H Zeynep
Published: August 2019

In the past fifteen years, the study of civilians in war (i.e., violence against civilians as well as civilian strategies for survival during wars) has emerged as a research agenda separate from the study of the causes of wars. Up to now, this research agenda has largely been dominated by studies that emphasize the military balance of power or the nature of material resources available to the fighting parties. The books under review in this article push the literature on civilians in war significantly forward by focusing on prewar social, political, and institutional factors. Based on the findings of the books, this review essay identifies three such factors. First, the organizational skills that civilian leaders develop in the prewar period shape resistance against military actors during wars. Second, political party affiliation, revealed through prewar elections, influences the patterns of violence against civilians during wars. Finally, the dominant state ideology that precedes wars can impact both civilian victimization and the extent to which civilians can evade such violence. The article both assesses the books’ contributions and offers ways in which these contributions can be refined by future research.
Unable
Authors: Brian C Kalt
Published: August 2019

Since President Trump’s election, Section 4 of the Twenty-Fifth Amendment has been a frequent topic of public discussion. It has also become a mainstay in television dramas, which usually present it inaccurately.The country needs this complicated but essential topic explained. Unable: The Law, Politics, and Limits of Section 4 of the Twenty-Fifth Amendment is designed to educate and inform the public about Section 4 in an even-handed and accessible way. This book is not about President Trump; it offers no opinions on his fitness for office. By the end of the book, though, it will be clear how Section 4 applies to him, as well as to any other arguably unfit president.Unable begins by explaining the basics of Section 4, correcting common misconceptions, and resolving some of its ambiguities. Part II explores history: presidential disability before Section 4; the creation of Section 4 in 1965; the (non)use of Section 4 since then; and Section 4’s portrayal in movies, books, and television. Part III presents a series of hypothetical scenarios that dramatize how Section 4 would work—or not work—in a wide variety of situations. Part IV concludes with some thoughts on how Section 4 interacts with constitutional law more generally, and some suggestions on how to improve Section 4’s operation.
Public Speaking and Presentation Skills
Authors: Schraeder Terry L.
Published: August 2019

Physicians, throughout their training and careers, are often asked to do a variety of different types of public speaking—from large academic settings and videotaped seminars to informal informational settings or impromptu discussions. Doctors are asked to speak on important clinical topics at hospital grand rounds; discuss preventative health with patients in the community; lecture about their research at a professional conference; respond at a press conference about a controversial issue; conduct a job interview through video broadcast; Skype with a team of academic researchers from around the world; or conduct themselves on camera for a telemedicine interaction with patients and colleagues. Individuals are usually filled with apprehension about speaking in front of a group. More often than not, many people will avoid talking in front of a live audience or a video camera if they possibly can. But opportunities to speak are important to take advantage of, whether self-directed or prompted by a request from a superior or an organization. Professional careers and personal connections can be enhanced by giving an outstanding presentation with excellent skills. Whether the goal is to slightly improve physicians’ presentation and communication skills or to perfect their public speaking performances, this chapter will help them. Today, many careers in medicine and throughout the healthcare profession require not only that physicians make presentations in person to large and small live audiences but also that they are camera-ready and know how to successfully perform in a video presentation or broadcast interview.
Scope of the Problem
Authors: McAnally Heath B.
Published: August 2019

This program and book are predicated on the relationship between chronic preoperative pain and worsened elective surgical outcomes. Preexisting chronic pain and associated factors (e.g., anxiety and pain catastrophizing, poor physical health maintenance, toxic substance use, etc.) predict poor outcomes including increased hospital length of stay and unplanned admissions/readmissions, chronic postsurgical pain (CPSP) and disability, chronic postoperative opioid use and dependence, and even surgical complications and failures. The potential cost of nonoptimized preoperative chronic pain in the context of these various suboptimal outcome measures is staggering and may well run into the tens if not hundreds of billions of dollars.
Cancer rehabilitation
Authors: Sivan Manoj , Phillips Margaret , Baguley Ian , Nott Melissa
Published: August 2019

Cancer has changed from being a condition with a poor prognosis where the emphasis was on treatment aimed at stopping or slowing the cancer to one which frequently is a chronic condition, or at least a condition in which survival may be measured in years rather than months. The natural consequence of this is that rehabilitation has become an important aspect of management, and a vital one if a person is to fully take advantage of successful cancer treatment. Different terminologies are used concerning rehabilitation so it may not be immediately obvious that it is provided: examples are that many of the components of cancer survivorship programmes are rehabilitative in nature and the term ‘supportive care’ often covers rehabilitation.
How monetary policy changes bank liability structure and funding cost
Authors: Girotti Mattia
Published: August 2019

US banks obtain most of their funding from a combination of low-interest deposits and high-interest deposits. Using local demographic variations as instruments for banks’ liability composition, I show that when monetary policy tightens, banks with a larger proportion of low-interest deposits on their balance sheet experience larger increases in their high-interest deposit rate and lend less. This happens because tight monetary policy reduces the supply of low-interest deposits to banks, and banks react by issuing more high-interest deposits. As it is increasingly expensive, that substitution is not complete, and leads to a reduction in lending.
Regression of Recurrent Spinal Cord High-Grade Glioma After Convection-Enhanced Delivery of Nimustine Hydrochloride: Case Reports and Literature Review
Authors: Endo Toshiki , Inoue Tomoo , Sugiyama Shinichiro , Saito Ryuta , Tominaga Teiji
Published: August 2019

BACKGROUND

Spinal cord high-grade glioma has poor prognosis. Especially, no treatment protocols have been established for recurrent cases.

OBJECTIVE

To apply a novel treatment method, convection-enhanced delivery (CED), for recurrent high-grade glioma. CED can deliver chemotherapeutic agents directly into the intramedullary lesion and possibly lead to remarkable regression of enlarging tumors that are, otherwise, difficult to control.

METHODS

Two patients developed high-grade glioma in the thoracic spinal cord. Partial resection and chemotherapy and radiotherapy induced remission of the disease. However, following the initial treatment, recurrence was noted in the spinal cord at 6 and 12 mo, respectively. No effective treatment was available for these recurrent lesions. Therefore, the authors decided to use CED to infuse nimustine hydrochloride (ACNU) directly into the spinal cord. During the procedure, the infusion cannula was inserted into the spinal cord lesion under intraoperative computed tomography scan.

RESULTS

After ACNU CED, successive magnetic resonance imaging confirmed remarkable shrinkages of the tumors in both cases. However, the patient's preinfusion symptoms, including bilateral lower extremity weakness, did not change after the treatment. Importantly, overall survivals of the 2 patients were as long as 67 and 33 mo.

CONCLUSION

The authors report the first 2 cases of recurrent spinal cord high-grade glioma. ACNU CED dramatically regressed enhanced mass lesions and provided local tumor controls in the spinal cord.
Neutral iron line in the supernova remnant IC 443 and implications for MeV cosmic rays
Authors: Nobukawa Kumiko K , Hirayama Arisa , Shimaguchi Aika , Fujita Yutaka , Nobukawa Masayoshi , Yamauchi Shigeo
Published: August 2019

We report a discovery of bright blob-like enhancements of an Fe i K$\alpha$ line in the northwest and the middle of the supernova remnant (SNR) IC 443. The distribution of the line emission is associated with molecular clouds interacting with the shock front, and is totally different from that of the plasma. The Fe i K$\alpha$ line has a large equivalent width. The most plausible scenario for the origin of the line emission is that the MeV protons accelerated in the shell leak into the molecular clouds and ionized the Fe atoms therein. The observed Fe i K$\alpha$ line intensity is consistent with the prediction of a theoretical model in which MeV protons are accelerated along with GeV and TeV protons at the SNR.
The use of rapamycin to treat vascular tumours and malformations: A single-centre experience
Authors: Tole Soumitra , Fantauzzi Michelle , Cottingham Diana , Amaral Joao G , John Philip R , Lara-Corrales Irene , Pope Elena , Carcao Manuel D
Published: August 2019

Objectives

To assess the safety and efficacy of rapamycin in treating children with vascular tumours and malformations.

Study design

We performed a retrospective review at a large tertiary care paediatric centre to assess the efficacy and safety of using rapamycin to treat vascular tumours and malformations. Response to therapy was defined by patient-reported symptom improvement, radiological reduction in size of lesions, and/or improvement of laboratory parameters.

Results

Forty-two patients (7 with vascular tumours and 35 with vascular malformations) have been treated with rapamycin. Despite 33 of 42 patients being diagnosed in the first year of life, the median age of initiating rapamycin was 11 years. Of the 38 children treated for a minimum of 4 months, 29 (76%) exhibited a clinical response. Twenty-one patients had follow-up imaging studies and of these, 16 (76%) had radiographic decrease in lesion size. Median time to demonstration of response was 49 days. All five children with vascular tumours and all three children with vascular malformations under the age of 4 years showed a clinical response. Response rate was lower for children ≥ 4 years of age (0/2, 0% for vascular tumours; 21/28, 75% for vascular malformations). No patient experienced an infection directly related to rapamycin or discontinued rapamycin due to toxicity.

Conclusions

Rapamycin is safe and efficacious in most children with select vascular tumours and malformations. Young children appear to respond better, suggesting that early initiation of rapamycin should be considered.
DETERMINATION OF ACTIVITY PROFILE OF 137CS IN CONCRETE CORE SAMPLES
Authors: Dolniak Jakub , Lištjak Martin , Slaninka Alojz , Nečas Vladimír
Published: August 2019

Decommissioning of nuclear building structures usually leads to large amounts of low-level radioactive waste. Using a reliable method to determine the contamination depth, it is indispensable prior to the start of decontamination works and for minimising the radioactive waste volume and the total workload. This paper deals with the possibilities of determination of depth distribution of activity of 137Cs and depth of contamination. The method described in this paper is based on concrete core sampling and laboratory gamma-ray spectroscopy measurements.
“It Has a Way of Getting in Your Blood When You’re Basque”: Basque Sheepherders, Race, and Labor, 1880–1959
Authors: Aquino Mariel
Published: August 2019

Despite their small numbers, Basque sheepherders became prototypical figures in the history the American West, viewed as elusive, mysterious men hidden in high pastures tending their enormous herds for months at a time. Basques became so associated with herding that even when the Immigration Act of 1924 placed severe restrictions on the number of Spanish nationals who could immigrate, American herders lobbied for special legislation that would allow them to keep importing sheepherders from Spain. This article contends that this preference for Basque herders arose not from Basques’ particular expertise but from narratives of their ancient origins and racial distinctiveness. Both Basques and non-Basques developed constructions of Basqueness that emphasized the group’s non-“Latin” status, thus placing Basques in an advantageous position in the American ethnoracial hierarchy relative to other Southern European ethnic groups. These narratives allowed sheepherding to be racialized as a Basque profession and also underlined Basques’ European Indigeneity—an Indigeneity that was to some extent transferred to the American West.
Comparison of two different methods in preoperative planning of the amount of lengthening in Z achilloplasty technique
Authors: Ozyalvac Osman Nuri , Akpinar Evren
Published: August 2019

Achilles tendon lengthening (ATL) surgery is a technique that is frequently used in the surgical treatment of contracture of the Achilles tendon seen in many pediatric orthopedic problems such as cerebral palsy, clubfoot, pes planovalgus and myelomeningocele. It is important to appropriately adjust the amount of ATL. However, the literature on the preoperative calculation of the required amount of tendon lengthening is limited. The aim of the study was to compare the reliability of the two different methods of predicting the amount of ATL. Eighteen feet of 16 patients who underwent ATL with Z-plasty technique were included in the study. The required amount of ATL was calculated as double blind according to the Cosine theorem and a method that was described by Garbarino et al. in 1985 and compared with the amounts of ATL applied during the operation. The mean amount of lengthening was 25.24 mm during surgery. The required amount of lengthening was 41.55 ± 11.0 mm, according to the Garbarino’s method. The required amount of lengthening was 23.93 ± 9.03 mm, according to the Cosine theorem. The quantities calculated according to the Cosine theorem showed excellent agreement with the amount of lengthening during surgery. The quantities calculated according to the Garbarino’s method showed poor agreement with the amount of lengthening during surgery. The calculation of the amount of ATL required in the treatment of the equinus deformity before surgery is possible by Cosine Theorem. The method of Cosine theorem is more reliable than the previous method described by Garbarino et al.
Absolute lymphocyte count as a prognostic biomarker for overall survival in patients with advanced melanoma treated with ipilimumab
Authors: Postow Michael A. , Chasalow Scott D. , Kuk Deborah , Panageas Katherine S. , Cheng Michael L. , Yuan Jianda , Wolchok Jedd D.
Published: August 2019

Biomarkers are needed to estimate which patients benefit most from combination ipilimumab and nivolumab immunotherapy. Rigorous biomarker analyses from prior ipilimumab randomized studies without nivolumab are likely to inform which biomarker analyses should be prioritized when examining patients treated with the combination. For the first time, the current analyses investigate absolute lymphocyte count (ALC) in randomized, controlled trials of ipilimumab without nivolumab to assess whether ALC is prognostic or predictive of ipilimumab treatment benefit. Data included patients (n = 1136) treated in the two randomized, controlled phase III studies MDX010-20 and CA184-024. ALC was measured at pretreatment baseline and every 3 weeks for up to 12 weeks, before each dose of ipilimumab. Cox proportional hazards models were used to estimate and test associations between ALC measures and overall survival (OS). In both randomized studies, baseline ALC and ALC halfway through induction (at week 6) were associated with OS not only in ipilimumab-treated patients but also in patients treated with non-ipilimumab control treatments. ALC increased in patients receiving ipilimumab, but this degree of change was not predictive of ipilimumab treatment benefit. Using data from randomized, controlled studies, we were able to conclude for the first time that baseline ALC, ALC halfway through induction (week 6) and the degree of ALC change from baseline to week 6 are prognostic biomarkers in melanoma patients, and do not appear to be predictive of ipilimumab treatment benefit. This more comprehensive understanding of ALC as a biomarker from ipilimumab trials will inform subsequent biomarker investigations in ongoing ipilimumab combination studies such as ipilimumab in combination with nivolumab.
Are We Witnessing a Paradigm Shift?: A Systematic Review of Social Media in Residency
Authors: Economides James M. , Choi Youna K. , Fan Kenneth L. , Kanuri Arjun P. , Song David H.
Published: August 2019

Background:

As social media’s applications continue to evolve, the pitfalls and dangers associated with misuse have been accentuated in the literature. Consequently, academic institutions across the nation have implemented social media policies. This study is aimed to evaluate the state of social media literature examining postgraduate trainees (residents/fellows).

Methods:

A systematic search was performed identifying peer-reviewed publications presenting original research. Studies published through December 8, 2018, focusing on social media use among postgraduate trainees were considered for inclusion.

Results:

Fifty-three studies were categorized into 4 domains: (1) resident recruitment, (2) graduate medical education, (3) professional development, and (4) academic scholarship. Thirty-four (64.15%) investigated social media’s impact on professional development, of which 16 (47.05%) highlighted the detrimental potential on trainee professionalism. The remaining 18 (52.94%) focused on promoting social media training during residency, and/or enhancing social media competency to benefit professional development. Fourteen (26.42%) rationalized social media use in augmenting graduate medical education. Ten (18.87%) assessed social media’s influence on resident recruitment, of which 7 (70%) depicted use as a screening instrument for program directors on resident applicants. Two (3.77%) of the studies introduced social media as a platform for academic scholarship with indicators as altmetrics.

Conclusions:

The well-established disadvantages of social media use by the postgraduate trainee continue to persist in the literature. However, there is recognition of social media as a valuable resource in influencing resident recruitment, graduate medical education, professional development, and academic scholarship, representing a paradigm shift—from cautiously avoidant to thoughtful capitalization on its immense potential.
Defining Quality Indicators for Breast Device Surgery: Using Registries for Global Benchmarking
Authors: Begum Husna , Vishwanath Swarna , Merenda Michelle , Tacey Mark , Dean Nicola , Elder Elisabeth , Mureau Marc , Bezic Ron , Carter Pamela , Cooter Rodney D. , Deva Anand , Earnest Arul , Higgs Michael , Klein Howard , Magnusson Mark , Moore Colin , Rakhorst Hinne , Saunders Christobel , Stark Birgit , Hopper Ingrid
Published: August 2019

Background:

Breast device registries monitor devices encompassing breast implants, tissue expanders and dermal matrices, and the quality of care and patient outcomes for breast device surgery. Defining a standard set of quality indicators and risk adjustment factors will enable consistency and adjustment for case-mix in benchmarking quality of care across breast implant registries. This study aimed to develop a set of quality indicators to enable assessment and reporting of quality of care for breast device surgery which can be applied globally.

Methods:

A scoping literature review was undertaken, and potential quality indicators were identified. Consensus on the final list of quality indicators was obtained using a modified Delphi approach. This process involved a series of online surveys, and teleconferences over 6 months. The Delphi panel included participants from various countries and representation from surgical specialty groups including breast and general surgeons, plastic and reconstructive surgeons, cosmetic surgeons, a breast-care nurse, a consumer, a devices regulator (Therapeutic Goods Administration), and a biostatistician. A total of 12 candidate indicators were proposed: Intraoperative antibiotic wash, intraoperative antiseptic wash, preoperative antibiotics, nipple shields, surgical plane, volume of implant, funnels, immediate versus delayed reconstruction, time to revision, reoperation due to complications, patient satisfaction, and volume of activity.

Results:

Three of the 12 proposed indicators were endorsed by the panel: preoperative intravenous antibiotics, reoperation due to complication, and patient reported outcome measures.

Conclusion:

The 3 endorsed quality indicator measures will enable breast device registries to standardize benchmarking of care internationally for patients undergoing breast device surgery.
Design and Development of a Novel Transtibial Cycling Prosthesis
Authors: Tiele Akira , Soni-Sadar Shivam , Rowbottom Jack , Patel Shilen , Mathewson Edward , Pearson Samuel , Hutchins David , Head John , Hutchins Stephen
Published: August 2019

Introduction

This article describes the design methodology, creation, and testing of a bespoke transtibial prosthesis, manufactured in part using three-dimensional (3D) printing technology, to enable more effective transmission of dynamic pressure through pedals during cycling. Asymmetry in motion can occur during cycling between the affected and contralateral lower limb. This pilot study was devised to enable development of a prototype prosthesis using a flexible ankle joint design for people with transtibial lower-limb absence for use when participating in amateur sports cycling.

Materials and Methods

Gait laboratory analysis and in-shoe plantar pressure measurement were used to simultaneously measure heel/ankle kinematics, plus pressure magnitude/distribution applied during cycling. A volunteer subject cycled on a static rig wearing either a standard unilateral transtibial prosthesis or a prototype prosthesis, which incorporated a simulated Achilles tendon. An able-bodied volunteer acted as a control.

Results

The results indicate that cycling with the prototype prosthesis reduced bilateral ankle and heel kinematic misalignment by 64% and reduced unwanted pedal pressure during the cycling recovery phase from 60 N to 50 N.

Conclusions

The use of 3D printing is a feasible option in the design and manufacture of lower-limb prostheses designed for cycling. Further research is needed to confirm this in a larger cohort of patients.
The Efficacy of Hypnotherapy in the Treatment of Functional Dyspepsia
Authors: Popa Stefan-Lucian , Chiarioni Giuseppe , David Liliana , Dumitrascu Dan Lucian
Published: August 2019

Background:

Functional dyspepsia (FD) is one of the most frequent functional gastrointestinal disorders and is defined using the Rome IV criteria as any combination of the following symptoms: postprandial fullness, early satiety, epigastric pain, and epigastric burning that are severe enough to interfere with the usual activities and occur at least 3 days per week over the past 3 months with an onset of at least 6 months before the presentation. The purpose of this systematic review is to analyze all the relevant studies in the literature that investigate the efficiency of hypnotherapy in FD.

Areas Of Uncertainty:

FD refractory to conservative treatment is a therapeutic challenge, and alternative treatment options are needed. Gut-oriented hypnotherapy has been reported an effective treatment for irritable bowel syndrome, but poorly tested in FD.

Data Sources:

We performed a search in 6 bibliographic databases (PubMed, Embase, Cochrane Library, Web of Science, Scopus, and LILACS) using customized search strategies for each engine. The search strategy included the following terms: (hypnosis, hypnotherapy, hypnotherapies, hypnogenesis, hypnotism, hypnotist, hypnotical suggestion, suggestion, and mesmerism) and {[functional and (dyspepsia or dyspeptic)] or FD}.

Results:

Taking the aforementioned criteria into account, the result was a review of 4 articles analyzing the efficacy of hypnotherapy in the treatment of FD, published in the past 20 years. The initial search identified 398 articles, of which 37 potentially appropriate articles were reviewed. Of these 37 articles, 4 articles were included in the review. The benefits observed by numerous studies go beyond the field of digestive pathology, patients describing a general improvement in physical and mental health.

Conclusions:

Current studies analyzing the efficacy of hypnotherapy in FD provide encouraging data, but additional randomized controlled trials are needed before a firm position on the effectiveness of hypnosis in FD.
Management of Diarrhea in Patients With Carcinoid Syndrome
Authors: Naraev Boris G. , Halland Magnus , Halperin Daniel M. , Purvis Amy J. , O'Dorisio Thomas M. , Halfdanarson Thorvardur R.
Published: August 2019

Neuroendocrine tumors (NETs) arise from enterochromaffin cells found in neuroendocrine tissues, with most occurring in the gastrointestinal tract. The global incidence of NETs has increased in the past 15 years, likely due to better diagnostic methods. Small-bowel NETs are frequently associated with carcinoid syndrome (CS). Carcinoid syndrome diarrhea occurs in 80% of CS patients and poses a substantial symptomatic and economic burden. Patients with CS diarrhea frequently suffer from diarrhea and flushing and report corresponding impairment in quality of life, requiring substantial changes in daily activities and lifestyle. Treatment paradigms range from surgical debulking to liver-directed therapies to treatment with somatostatin analogs, nonspecific anti-diarrheal agents, and a tryptophan hydroxylase inhibitor. Other causes of diarrhea, including steatorrhea, short bowel syndrome, and bile acid malabsorption, should be considered in NET patients with refractory diarrhea. More therapeutic options are needed for symptomatic management of patients with NETs, and better understanding of the pathophysiology can empower clinicians with improved patient care.
Inhibition of Lipolysis With Acipimox Attenuates Postburn White Adipose Tissue Browning and Hepatic Fat Infiltration
Authors: Barayan Dalia , Vinaik Roohi , Auger Christopher , Knuth Carly M. , Abdullahi Abdikarim , Jeschke Marc G.
Published: August 2019

Extensive burn injuries promote an increase in the lipolysis of white adipose tissue (WAT), a complication that enhances postburn hypermetabolism contributing to hyperlipidemia and hepatic steatosis. The systemic increase of free fatty acids (FFAs) due to burn-induced lipolysis and subsequent organ fatty infiltration may culminate in multiple organ dysfunction and, ultimately, death. Thus, reducing WAT lipolysis to diminish the mobilization of FFAs may render an effective means to improve outcomes postburn. Here, we investigated the metabolic effects of Acipimox, a clinically approved drug that suppresses lipolysis via inhibition of hormone-sensitive lipase (HSL). Using a murine model of thermal injury, we show that specific inhibition of HSL with Acipimox effectively suppresses burn-induced lipolysis in the inguinal WAT leading to lower levels of circulating FFAs at 7 days postburn (P < 0.05). The FFA substrate shortage indirectly repressed the thermogenic activation of adipose tissue after injury, reflected by the decrease in protein expression of key browning markers, UCP-1 (P < 0.001) and PGC-1α (P < 0.01). Importantly, reduction of FFA mobilization by Acipimox significantly decreased liver weight and intracellular fat accumulation (P < 0.05), suggesting that it may also improve organ function postburn. Our data validate the pharmacological inhibition of lipolysis as a potentially powerful therapeutic strategy to counteract the detrimental metabolic effects induced by burn.
On the defect tolerance of fetal membranes
Authors: Bircher Kevin , Ehret Alexander E. , Spiess Deborah , Ehrbar Martin , Simões-Wüst Ana Paula , Ochsenbein-Kölble Nicole , Zimmermann Roland , Mazza Edoardo
Published: August 2019

A series of mechanical experiments were performed to quantify the strength and fracture toughness of human amnion and chorion. The experiments were complemented with computational investigations using a ‘hybrid’ model that includes an explicit representation of the collagen fibre network of amnion. Despite its much smaller thickness, amnion is shown to be stiffer, stronger and tougher than chorion, and thus to determine the mechanical response of fetal membranes, with respect to both, deformation and fracture behaviour. Data from uniaxial tension and fracture tests were used to inform and validate the computational model, which was then applied to rationalize measurements of the tear resistance of tissue samples containing crack-like defects. Experiments and computations show that the strength of amnion is not significantly reduced by defects smaller than 1 mm, but the crack size induced by perforations for amniocentesis and fetal membrane suturing during fetal surgery might be larger than this value. In line with previous experimental observations, the computational model predicts a very narrow near field at the crack tip of amnion, due to localized fibre alignment and collagen compaction. This mechanism shields the tissue from the defect and strongly reduces the interaction of multiple adjacent cracks. These findings were confirmed through corresponding experiments, showing that no interaction is expected for multiple sutures for an inter-suture distance larger than 1 mm and 3 mm for amnion and chorion, respectively. The experimental procedures and numerical models applied in the present study might be used to optimize needle and/or staple dimensions and inter-suture distance, and thus to reduce the risk of iatrogenic preterm premature rupture of the membranes from amniocentesis, fetoscopic and open prenatal surgery.
A gelatin hydrogel to study endometrial angiogenesis and trophoblast invasion
Authors: Zambuto Samantha G. , Clancy Kathryn B. H. , Harley Brendan A. C.
Published: August 2019

The endometrium is the lining of the uterus and site of blastocyst implantation. Each menstrual cycle, the endometrium cycles through rapid phases of growth, remodelling and breakdown. Significant vascular remodelling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodelling enhance blood flow to the embryo ahead of placentation. Understanding the mechanisms of endometrial vascular remodelling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective of this study was to develop a tissue engineering platform to investigate the processes of endometrial angiogenesis and trophoblast invasion in a three-dimensional environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue, supports the formation of endometrial endothelial cell networks with human umbilical vein endothelial cells and human endometrial stromal cells as an artificial endometrial perivascular niche and the culture of an endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.
Establishment of maternal blood supply to the placenta: insights into plugging, unplugging and trophoblast behaviour from an agent-based model
Authors: Saghian Rojan , Bogle Gib , James Joanna L. , Clark Alys R.
Published: August 2019

The ability of the baby to receive nutrients and oxygenin uterodepends on the healthy development of the placenta. For maternal blood to adequately perfuse the placenta, it dramatically alters the arteries in the uterus that supply it with nutrient-rich blood right from the start of pregnancy. Placental cells (trophoblasts) invade both into the tissue of the uterus and into the maternal blood vessels nearest to the site of implantation (the spiral arteries (SAs)) and transform these allowing a relatively high and steady flow of nutrient-rich blood to perfuse the placenta. Trophoblasts also form plugs that occlude SAs, preventing maternal blood flow to the placenta until the late first trimester, at which point these plugs dislodge or disintegrate. Here we present an agent-based model of trophoblast migration within plugged SAs to tease apart the impact of chemical signals and mechanical factors on trophoblast behaviour. The model supports our previousin vitrohypothesis that plugging of the maternal arteries in early pregnancy can act to promote trophoblast invasion by providing a ‘low flow’ environment and extends our understanding by suggesting ‘weak spots’ in plug structure can lead to plug degeneration, allowing increased blood flow through the materno-fetal circulation.
Mechanics of cervical remodelling: insights from rodent models of pregnancy
Authors: Yoshida Kyoko , Jayyosi Charles , Lee Nicole , Mahendroo Mala , Myers Kristin M.
Published: August 2019

The uterine cervix undergoes a complex remodelling process during pregnancy, characterized by dramatic changes in both extracellular matrix (ECM) structure and mechanical properties. Understanding the cervical remodelling process in a term or preterm birth will aid efforts for the prevention of preterm births (PTBs), which currently affect 14.8 million babies annually worldwide. Animal models of pregnancy, particularly rodents, continue to provide valuable insights into the cervical remodelling process, through the study of changes in ECM structure and mechanical properties at defined gestation time points. Currently, there is a lack of a collective, quantitative framework to relate the complex, nonlinear mechanical behaviour of the rodent cervix to changes in ECM structure. This review aims to fill this gap in knowledge by outlining the current understanding of cervical remodelling during pregnancy in rodent models in the context of solid biomechanics. Here we highlight the collective contribution of multiple mechanical studies which give evidence that cervical softening coincides with known ECM changes throughout pregnancy. Taken together, mechanical tests on tissue from pregnant rodents reveal the cervix’s remarkable ability to soften dramatically during gestation to allow for a compliant tissue that can withstand damage and can dissipate mechanical loads.
Episiotomy: the biomechanical impact of multiple small incisions during a normal vaginal delivery
Authors: Oliveira Dulce , Pouca Maria Vila , Ferreira João , Mascarenhas Teresa
Published: August 2019

Childbirth-related injuries are one of the main causes of pelvic floor dysfunction. To attempt to avoid serious tears during delivery, an episiotomy can be performed. In this study, we intended to investigate the biomechanical performance of the pelvic floor muscles after performing different episiotomies using a physics-based computational model which includes the pelvic floor muscles and the fetus. Previous biomechanical studies have analysed the mechanical effects of single incisions of different lengths; in this study, we intend to analyse the implications of multiple small incisions, evaluating the reaction forces, the stress on the muscles and the loss of tissue integrity sustained by the pelvic floor. The obtained results predict that an episiotomy delivery reduces the likelihood of macroscopic levator trauma by decreasing the stress on the region of insertion of the rectal area of the
levator ani
in the
symphysis pubis
. From the mechanical point of view, multiple incisions do not bring benefits compared to larger incisions. However, nothing can be ascertained about the clinical benefit of such an approach.
Drug transport across the human placenta: review of placenta-on-a-chip and previous approaches
Authors: Pemathilaka Rajeendra L. , Reynolds David E. , Hashemi Nicole N.
Published: August 2019

In the past few decades, the placenta became a very controversial topic that has had many researchers and pharmacists discussing the significance of the effects of pharmaceutical drug intake and how it is a possible leading cause towards birth defects. The creation of an
in vitro
microengineered model of the placenta can be used to replicate the interactions between the mother and fetus, specifically pharmaceutical drug intake reactions. As the field of nanotechnology significantly continues growing, nanotechnology will become more apparent in the study of medicine and other scientific disciplines, specifically microengineering applications. This review is based on past and current research that compares the feasibility and testing of the placenta-on-a-chip microengineered model to the previous and underdeveloped
in vivo
and
ex vivo
approaches. The testing of the practicality and effectiveness of the
in vitro
,
in vivo
and
ex vivo
models requires the experimentation of prominent pharmaceutical drugs that most mothers consume during pregnancy. In this case, these drugs need to be studied and tested more often. However, there are challenges associated with the
in vitro
,
in vivo
and
ex vivo
processes when developing a practical placental model, which are discussed in further detail.
Labour and delivery: a clinician's perspective on a biomechanics problem
Authors: Feltovich Helen
Published: August 2019

Predicting how and when a pregnant woman will deliver her fetus has always been a problem for the clinician, and, consequently, there has been little progress made in preventing poor outcomes from pregnancies that deliver too soon or too late. In the opinion of the author, a maternal–fetal medicine specialist, rethinking labour within a biomechanical framework and studying it like an engineering problem could be a promising approach to unlocking the mysteries of labour.
Bioengineering in women's health, volume 2: pregnancy—from implantation to parturition
Authors: Miller Kristin S. , Myers Kristin , Oyen Michelle
Published: August 2019

This special issue of
Interface Focus
is the second of two sets of articles on the topic of bioengineering in women's health. This second issue in the series focuses on pregnancy, a dynamic time in a women's life that involves dramatic physiologic changes within a relatively small timeframe. Pregnancy demands endurance and resilience of one's body and represents a critical component of women's health research. The health of an individual leading up to, during and after pregnancy is paramount for reproductive health and the lifelong health of offspring. The articles in this issue explore physiological events that support reproduction spanning from embryo implantation, through gestation, to delivery and parturition. Specifically, the articles highlight essential developments in placenta, fetal membranes, cervix, pelvic floor and anthropometry research. The featured bioengineering disciplines deployed to study such complex biological processes are diverse, with articles detailing the latest advancements in computational modelling at various biological length-scales, biomaterial design, material modelling, non-invasive diagnostic techniques, microfluidic devices and experimental mechanics. This second issue continues the first in this series, on the physiology of the non-pregnant woman.
Seismic retrofitting of Māori wharenui in Aotearoa New Zealand
Authors: Crum Ambrosia , Brown Deidre , Fa'aui Tūmanako , Vallis Naomi , Ingham Jason M.
Published: August 2019

The design of Māori wharenui (meeting houses), refined over the last 180 years, has given rise to a distinctive typology that demonstrates an understanding of tectonic-narrative expression. It is a visual codex designed to be read. Set within the context of pre-disaster readiness, this current study investigated the resilience of Māori buildings and communities through a dual interpretation of seismic, regulatory and historical frameworks. The literature on Māori building technologies scarcely addresses matters of resilience and there is currently no formalized methodology to guide wharenui seismic retrofit practice. Through a macro level analysis of recently completed retrofit projects, this current study identified issues present in current practice. The resulting research presented a pathway for the future development of an approach (to inform methodologies) and strategy (to build capability) founded on the recognition of wharenui as a new category of building within building regulations. It is also recommended that research continues to develop alternative engineered solutions, expert knowledge bases and best practice guidelines.

This article is part of the theme issue ‘Environmental loading of heritage structures’.
Brick masonry industrial chimneys: assessment, evaluation and intervention
Authors: Guedes João M. , Lopes Valter , Quelhas Bruno , Costa Alexandre , Ilharco Tiago , Coelho Filipe
Published: August 2019

Masonry chimneys were key elements of post-industrial factory buildings. Built on a large scale in Portugal from the nineteenth century, factory buildings have been in use until the beginning of the twentieth century, afterwards being progressively abandoned, transformed or demolished. During this degradation process, the industrial chimneys are often separated from other structures and become isolated elements, i.e. sculptures to the memory of the site's past activity. Moreover, although most of these industries and chimneys were located outside ordinary living areas, they are actually surrounded by dwellings or placed inside leisure areas. This new framework demands safety evaluations of the chimneys, which involve preliminary on-site surveys. This work shows the analysis of the geometric and material data from on-site surveys and dynamic identification procedures carried out on 10 industrial brick masonry chimneys. In particular, it establishes correlations between the chimneys geometrical and mechanical characteristics and proposes simple procedures to help designers to assess the safety conditions of these chimneys and evaluate eventual reinforcement needs.

This article is part of the theme issue ‘Environmental loading of heritage structures’.