bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated In Vivo Genotoxicity Assessment of Procarbazine Hydrochloride Demonstrates Induction of Pig‐a and LacZ Mutations, and Micronuclei, in MutaMouse Hematopoietic Cells
Authors: Maurice Clotilde , Dertinger Stephen D. , Yauk Carole L. , Marchetti Francesco
Published: December 2018

Procarbazine hydrochloride (PCH) is a DNA‐reactive hematopoietic carcinogen with potent and well‐characterized clastogenic activity. However, there is a paucity of in vivo mutagenesis data for PCH, and in vitro assays often fail to detect the genotoxic effects of PCH due to the complexity of its metabolic activation. We comprehensively evaluated the in vivo genotoxicity of PCH on hematopoietic cells of male MutaMouse transgenic rodents using a study design that facilitated assessments of micronuclei and Pig‐a mutation in circulating erythrocytes, and lacZ mutant frequencies in bone marrow. Mice were orally exposed to PCH (0, 6.25, 12.5, and 25 mg/kg/day) for 28 consecutive days. Blood samples collected 2 days after cessation of treatment exhibited significant dose‐related induction of micronuclei in both immature and mature erythrocytes. Bone marrow and blood collected 3 and 70 days after cessation of treatment also showed significantly elevated mutant frequencies in both the lacZ and Pig‐a assays even at the lowest dose tested. PCH‐induced lacZ and Pig‐a (immature and mature erythrocytes) mutant frequencies were highly correlated, with R2 values ≥0.956, with the exception of lacZ vs. Pig‐a mutants in mature erythrocytes at the 70‐day time point (R2 = 0.902). These results show that PCH is genotoxic in vivo and demonstrate that the complex metabolism and resulting genotoxicity of PCH is best evaluated in intact animal models. Our results further support the concept that multiple biomarkers of genotoxicity, especially hematopoietic cell genotoxicity, can be readily combined into one study provided that adequate attention is given to manifestation times. Environ. Mol. Mutagen. 60:505–512, 2019. © 2018 Her Majesty the Queen in Right of Canada
Brain Death at Fifty: Exploring Consensus, Controversy, and Contexts
Authors: Truog Robert D. , Berlinger Nancy , Zacharias Rachel L. , Solomon Mildred Z.
Published: December 2018

This special report is published in commemoration of the fiftieth anniversary of the “Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death,” a landmark document that proposed a new way to define death, with implications that advanced the field of organ transplantation. This remarkable success notwithstanding, the concept has raised lasting questions about what it means to be dead. Is death defined in terms of the biological failure of the organism to maintain integrated functioning? Can death be declared on the basis of severe neurological injury even when biological functions remain intact? Is death essentially a social construct that can be defined in different ways, based on human judgment? These issues, and more, are discussed and debated in this report by leading experts in the field, many of whom have been engaged with this topic for decades.
A Path Not Taken: Beecher, Brain Death, and the Aims of Medicine
Authors: Belkin Gary
Published: December 2018

It has been fifty years since a report by an ad hoc committee of Harvard Medical School ushered in the widespread adoption of brain death as a definition of death. Yet brain death remains disputed as an acceptable definition within bioethics. The continuous debate among bioethicists has had three key recurring features: first and foremost, argument over alleged flaws in the conceptual logic and consistency of the “whole‐brain” approach as a description of the meaning of death; second, efforts to fix perceived limitations of brain death‐based practices to optimize transplantation, especially given that transplantation was the presumed original intended purpose of the definition; and third, a basic unease provoked by the experience of using the criteria and managing a body in this state of “irreversible coma.”

The third feature is the one I find the most compelling, though it is less explored, and it persists because of the failures of the prior two. Brain death remains strange—to medical personnel, families, philosophers. That is not because it hasn’t yet been logically argued well enough or conceptually framed adequately, but because those things don’t matter as much to resolving this strangeness as the bioethical approach to brain death over the last fifty years has assumed it does. It is necessary to look to other things that can anchor the aims of medicine in the midst of this strangeness.
A Conceptual Justification for Brain Death
Authors: Bernat James L.
Published: December 2018

Among the old and new controversies over brain death, none is more fundamental than whether brain death is equivalent to the biological phenomenon of human death. Here, I defend this equivalency by offering a brief conceptual justification for this view of brain death, a subject that Andrew Huang and I recently analyzed elsewhere in greater detail. My defense of the concept of brain death has evolved since Bernard Gert, Charles Culver, and I first addressed it in 1981, a development that paralleled advances in intensive care unit treatment. The century‐old concept of the organism as a whole provides the fundamental justification for the equivalency of brain death and human death. In our technological age, in which increasing numbers of components and systems of an organism can be kept alive, and for longer intervals, the permanent cessation of functioning of the organism as a whole is the phenomenon that best corresponds to its death.
DCDD Donors Are Not Dead
Authors: Joffe Ari
Published: December 2018

According to international scientific medical consensus, death is a biological, unidirectional, ontological state of an organism, the event that separates the process of dying from the process of disintegration. Death is not merely a social contrivance or a normative concept; it is a scientific reality. Using this paradigm, the international consensus is that, regardless of context, death is operationally defined as “the permanent loss of the capacity for consciousness and all brainstem function. This may result from permanent cessation of circulation or catastrophic brain injury. In the context of death determination, ‘permanent’ refers to loss of function that cannot resume spontaneously and will not be restored through intervention.” The word “permanent” replaces “irreversible” (used in the United States’ 1980 Uniform Declaration of Death Act) in this new definition, arguably invented to allow donation after circulatory determination of death (DCDD) while still complying with the dead donor rule. I will show that this invention fails, for at least four reasons.
Uncontrolled DCD: When Should We Stop Trying to Save the Patient and Focus on Saving the Organs?
Authors: Ortega‐Deballon Iván , Rodríguez‐Arias David
Published: December 2018

Uncontrolled donation after circulatory death, which occurs when an individual has experienced unexpected cardiac arrest, usually not in a hospital, generates both excitement and concern. On the one hand, uDCD programs have the capacity to significantly increase organ donation rates, with good transplant outcomes—mainly for kidneys, but also for livers and lungs. On the other hand, uDCD raises a number of ethical challenges. In this essay, we focus on an issue that is central to all uDCD protocols: When should we cease resuscitation and shift to organ preservation? Do current uDCD protocols prematurely consider as potential donors patients who could still have some chances of meaningful survival? Can the best interest of patients be fostered once they are considered and treated as potential donors?
A Defense of the Dead Donor Rule
Authors: Magnus David
Published: December 2018

Discussion of the “dead donor rule” is challenging because it implicates views about a wide range of issues, including whether and when patients are appropriately declared dead, the validity of the doctrine of double effect, and the moral difference between or equivalence of active euthanasia and withdrawal of life‐sustaining treatment. The DDR will be defined here as the prohibition against removal of organs necessary for the life of the patient—that is, the prohibition of intentionally ending the life of a patient through organ removal. At a minimum, it is difficult not to see the DDR as grounded in a set of laws, norms, values, and practices that are firmly entrenched and have a great deal of philosophical, religious, and legal support. Obviously, the primary argument against the DDR is that it is highly desirable that we continue to procure organs for transplantation, combined with the belief that those from whom we often and possibly typically procure organs are not “really” dead. If donors are not really dead, then we are left with a dilemma: either we abandon organ procurement, or we abandon the DDR. Such a move should be taken only if the way we currently delineate the dead (those from whom it is acceptable to remove organs) cannot be maintained or defended. I will suggest that this is not the case.
The Dead Donor Rule as Policy Indoctrination
Authors: Rodríguez‐Arias David
Published: December 2018

Since the 1960s, organ procurement policies have relied on the boundary of death—advertised as though it were a factual, value‐free, and unobjectionable event—to foster organ donation while minimizing controversy. Death determination, however, involves both discoveries of facts and events and decisions about their meaning (whether the facts and events are relevant to establish a vital status), the latter being subjected to legitimate disagreements requiring deliberation. By revisiting the historical origin of the dead donor rule, including some events that took place in France prior to the report by the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death, I want to recall that those who first promoted the DDR did not take into account any scientific rationale to support the new proposed criteria to determine death. Rather, through a process of factual re‐semantization, they authorized themselves to decide about the meaning of death in order to implicitly prioritize the interests of organ recipients over those of dying people.
The Public's Right to Accurate and Transparent Information about Brain Death and Organ Transplantation
Authors: Nair‐Collins Michael
Published: December 2018

The organ transplantation enterprise is morally flawed. “Brain‐dead” donors are the primary source of solid vital organs, and the transplantation enterprise emphasizes that such donors are dead before organs are removed—or in other words that the dead donor rule is followed. However, individuals meeting standard diagnostic criteria for brain death—unresponsiveness, brainstem areflexia, and apnea—are still living, from a physiological perspective. Therefore, removing vital organs from a heart‐beating, mechanically ventilated donor is lethal. But neither donors nor surrogates nor the public in general are typically informed of this obviously relevant information. Therefore, donors or surrogates do not provide valid consent for a lethal medical procedure. This is a serious moral failing on the part of the transplant community. To address this concern, I advocate for accurate and fully transparent communication of information to the public to allow for an informed civic dialogue about the ethics and legality of lethal organ procurement. Furthermore, I advocate that systems be put in place by the transplant community to allow for valid consent for lethal organ procurement.
Brain Death and the Law: Hard Cases and Legal Challenges
Authors: Pope Thaddeus
Published: December 2018

The determination of death by neurological criteria—“brain death”—has long been legally established as death in all U.S. jurisdictions. Moreover, the consequences of determining brain death have been clear. Except for organ donation and in a few rare and narrow cases, clinicians withdraw physiological support shortly after determining brain death. Until recently, there has been almost zero action in U.S. legislatures, courts, or agencies either to eliminate or to change the legal status of brain death. Despite ongoing academic debates, the law concerning brain death has remained stable for decades. However, since the Jahi McMath case in 2013, this legal certainty has been increasingly challenged. Over the past five years, more families have been emboldened to translate their concerns into legal claims challenging traditional brain death rules. While novel, these claims are not frivolous. Therefore, it is important to understand them so that we can address them most effectively.
Death: An Evolving, Normative Concept
Authors: Caplan Arthur
Published: December 2018

Constantin Reliu had been working for twenty years as a cook in Turkey when he returned to his hometown of Barlad, Romania, to discover that, there, he was dead. His former wife had, unbeknownst to him, at some point during his stay in Turkey registered him as deceased in Romania. He has since been living a legal nightmare trying to prove to Romanian authorities that he is, in fact, alive. Reliu is not alone in finding out that the legal system is not as attuned to physiological activity or biological assessment by doctors in determining death as one might think. If one starts with the assumption that death is a purely biological concept, solely the province of doctors, Reliu's story seems entirely unrelated to the concept of death in the medical context. A brain scan would not lead to a reversal of his being assessed as dead. The story is a reminder, however, that how death is used is not just biological, and therefore that the standard of death even in the clinic must answer to cultural considerations. Values, the law, and custom matter a great deal in determining who is alive and who is not, whether in the courtroom, the coroner's office, or the clinic.
The Other Animal of Transplant's Future
Authors: Sharp Lesley A.
Published: December 2018

As an anthropologist, I have long been interested in highly experimental science, with my work engaging the moral underpinnings of xenoscience and, more recently, lab animal research. The possibility of employing animals as human “matches” sparks enthusiastic responses among researchers who imagine various creatures as lucrative “donor species” or “source animals” whose organs might replace the failing parts of humans and render obsolete any future need for brain‐dead donors. When we attend to how xenoscientists imagine the promissory qualities of various species, we encounter a specialized logic of how and why one type of animal is valued over another.

Well‐established bioethical principles might assist us in framing our position in reference, say, to the limits of human suffering, or how to weigh the worth assigned to human versus animal lives, or how we conceive “the quality of life.” But sadly, subjective experience can creep in to shape and cloud those very stances we regard as bioethically principled. Rather than pursue such a well‐worn path, I suggest an alternative framework that privileges attentiveness to everyday thought and action over codified bioethics. This framework—described as “everyday” or “ordinary ethics” in anthropology—involves assuming a critical, self‐reflexive stance in reference to quotidian ways of seeing and knowing. Like John Berger, who famously asked, “Why Look at Animals?,” I ask, when we look at the lab‐based baboon, chimp, or pig, what do we see? How do we think of, or presume to know, the animal in question? How do we think about human‐animal relations in science?
Bodies in Transition: Ethics in Xenotransplantation Research
Authors: Jasanoff Sheila
Published: December 2018

Xenotransplantation, or the grafting of organs from one species to another, may seem at first a far cry from brain death, but there is rising hope in some quarters of the biomedical community that such transplants may reduce, even obviate, the need to harvest human organs—and hence eliminate the primary reason for needing an unambiguous definition of brain death. As with all research on the frontiers of biomedicine, xenotransplantation raises its own ethical quandaries. One concern that has long occupied ethical thought is the degree to which advances in science and technology should control the boundaries between the human and the nonhuman. Might the dimming of a previously entrenched bright line between species entail negative consequences for concepts, such as human dignity and bodily integrity, that historically anchored the protection of both human and animal subjects in biomedical treatment and research? To date, ethical thinking about xenotransplantation, and about gene editing, has largely been left in the hands of scientists, subject only to loose supervision by institutional review boards and animal welfare committees whose remit may be too narrow to address age‐old moral concerns.
The Case of Jahi McMath: A Neurologist's View
Authors: Shewmon D. Alan
Published: December 2018

From the start, I followed the case of Jahi McMath with great interest. In December 2013, she clearly fulfilled the diagnostic criteria for brain death. As a neurologist with a special interest in chronic brain death, I was not surprised that, after she was flown to New Jersey, where she became statutorily resurrected and was treated as a comatose patient, Jahi's condition quickly improved. In 2014, her family reported that she sometimes responded to simple motor commands. I shared the general skepticism regarding these reports, assuming that the family was in denial and was misinterpreting spinal myoclonus (a rapid, involuntary twitch generated by the spinal cord) as volitional. The family had noticed that when Jahi's heart rate was above eighty beats per minute, she was more likely to respond, as though the heart rate reflected some sort of inner level of arousal. So they began to make video recordings. I have been privileged to be entrusted with copies of these recordings, forty‐eight of which proved suitable for assessing alleged responsiveness. All have been certified by a forensic video expert as unaltered. The first thing that struck me was that the great majority of the alleged responses were not spinal myoclonus. In fact, they did not resemble any type of spontaneous, involuntary movement described in patients paralyzed from high spinal cord lesions.
Revisiting Death: Implicit Bias and the Case of Jahi McMath
Authors: Goodwin Michele
Published: December 2018

For nearly five years, bioethicists and neurologists debated whether Jahi McMath, an African American teenager, was alive or dead. While Jahi's condition provides a compelling study for analyzing brain death, circumscribing her life status to a question of brain death fails to acknowledge and respond to a chronic, if uncomfortable, bioethics problem in American health care—namely, racial bias and unequal treatment, both real and perceived. Bioethicists should examine the underlying, arguably broader social implications of what Jahi's medical treatment and experience represented. On any given day, disparities in the quality of health care and health outcomes for people of color in comparison to whites are evidenced in American hospitals and clinics. These disparities are not entirely explained by differences in patient education, insurance status, employment, income, expressed preference for treatments, and severity of disease. Instead, research indicates that, even for African Americans able to gain access to health care services and navigate institutional nuances, disparities persist across a broad range of services, including diagnostic screening and general medical care, mental health diagnosis and treatment, pain management, HIV‐related care, and treatments for cancer, heart disease, diabetes, and kidney disease.
Outcomes of parathyroidectomy for primary hyperparathyroidism with nonlocalizing preoperative imaging
Authors: Vuong Christopher , Frank Ethan , Simental Alfred A. , Han Peter , Perez Mia , Staton Michael , Hanna Bassem M. , Andrade Filho Pedro A.
Published: December 2018

Background

The purpose of this study was to evaluate our surgical experience in patients with primary hyperparathyroidism (PHPT) with nonlocalizing sestimibi and ultrasound scans.

Methods

A retrospective review of 521 patients treated from April 2005 to July 2017 at Loma Linda University Medical Center who received parathyroidectomy for PHPT. One hundred forty‐seven patients (28%) had double negative localization (nonlocalizing sestamibi and ultrasound).

Results

Surgical cure for PHPT was 97.3% and 99.2% with nonlocalized and localized disease, respectively, and complication rates were similar between groups. Preoperative parathyroid hormone and gland weight were significantly lower with nonlocalization. The incidence of multigland disease (MGD) was greater in patients with nonlocalization on sestamibi and ultrasound.

Conclusion

Nonlocalization of parathyroid glands was not associated with decreased cure rate or increased morbidity. The presence of MGD and requirement for more extensive surgery were greater in patients with nonlocalizing disease.
Tumor multifocality with vagus nerve involvement as a phenotypic marker of SDHD mutation in patients with head and neck paragangliomas: A 18F‐FDOPA PET/CT study
Authors: Amodru Vincent , Romanet Pauline , Scemama Ugo , Montava Marion , Fakhry Nicolas , Sebag Frédéric , Castinetti Frédéric , Lavieille Jean‐Pierre , Loundou Anderson , Varoquaux Arthur , Barlier Anne , Pacak Karel , Taïeb David
Published: December 2018

Background

18F‐FDOPA PET/CT was proved to be a highly sensitive imaging method for detecting head and neck paraganglioma (HNPGL). The primary aim of the study was to evaluate the relationship between tumor characteristics and the SDHx‐mutational status in a large series of patients with HNPGL evaluated by 18F‐FDOPA PET/CT.

Methods

A total of 104 patients with HNPGL (65 sporadic/39 SDHx‐mutated) were included.

Results

In comparison to SDHB/SDC/SDHx‐negative cases, patients with SDHD were younger at diagnosis and had a higher rate of multifocal, vagal, and carotid paraganglioma. In patients with SDHD, vagal paraganglia represented the primary site of tumor origin. Multicentric involvement of the vagus nerve alone or in association with other locations was found to be a typical feature of SDHD cases compared to other cases (odds ratio = 59.4).

Conclusion

The present study shows that tumor multifocality within the vagus nerve is a phenotypic marker of SDHD mutation. This information is essential in the choice of the therapeutic strategy.
Impact of the hematocrit value of the blood prime unit on patient hematocrit values after therapeutic plasma exchange in children weighing 10 kg or less
Authors: Aldarweesh Fatima , Schaser Karen , Weiss John , Connor Joseph
Published: December 2018

We report the impact of measuring the hematocrit (HCT) of blood prime units (BPUs) on postprocedure patient HCT values in a small child with transverse myelitis undergoing therapeutic plasma exchange (TPE). Initially, the BPU HCT values were not measured, according to our apheresis policy of using our blood center's estimated HCT value. This approach resulted in unexpected increasing elevations of our patient's post‐TPE HCT after the first two TPE procedures. Subsequent measurement of the BPU HCT prior to use stabilized the patient's post‐TPE HCT. To our knowledge, this is the first case report describing the impact of using the measured BPU HCT vs the estimated HCT for very small children undergoing therapeutic apheresis. Our standard operating procedure for very small children has been updated after this patient's case to include measurements of the HCT values of BPUs for children who weigh 10 kg or less.
Induction of autophagic cell death in human ovarian carcinoma cells by Antrodia salmonea through increased reactive oxygen species generation
Authors: Yang Hsin‐Ling , Lin Ruei‐Wan , Karuppaiya Palaniyandi , Mathew Dony Chacko , Way Tzong‐Der , Lin Hui‐Chang , Lee Chuan‐Chen , Hseu You‐Cheng
Published: December 2018

We reported in our previously executed studies that the fermented culture broth of Antrodia salmonea (AS), a mushroom used in Taiwanese folk medicine induced reactive oxygen species (ROS)‐mediated apoptosis in human ovarian carcinoma cells. In this study, we studied the anticancer efficacies of AS (0–240 μg/ml) by examining the key molecular events implicated in cell death associated with autophagy in SKOV‐3 and A2780 human ovarian carcinoma cells and clarified the fundamental molecular mechanisms. Treatment of ovarian carcinoma cells with AS‐induced autophagic cell death mediated by increased microtubule‐associated protein LC3‐II, GFP‐LC3 puncta, and acidic vesicular organelle (AVO) formation. These events are linked with the activation of p62/SQSTM1, the inhibition of ATG4B, the expression of ATG7, and the dysregulation of Beclin‐1/Bcl‐2 (i.e., B‐cell lymphoma 2). N‐acetylcysteine inhibited AS‐induced ROS generation, which in turn constricted AS‐induced LC3 conversion, AVO formation, and ATG4B inhibition, indicating ROS‐mediated autophagy cell death. In addition, the 3‐methyladenine (3‐MA) or chloroquine (CQ)‐induced autophagy inhibition decreased AS‐induced apoptosis. Additionally, apoptosis inhibition by Z‐VAD‐FMK, a pan‐caspase inhibitor, substantially suppressed AS‐induced autophagy. Furthermore, AS‐inhibited HER‐2/
neu and PI3K/AKT signaling pathways which were reversed by autophagy inhibitors 3‐MA and CQ. Thus, A. salmonea is a potential chemopreventive agent that is capable of activating ROS‐mediated autophagic cell death in ovarian carcinoma cells.
PCL/gelatin nanofibrous scaffolds with human endometrial stem cells/Schwann cells facilitate axon regeneration in spinal cord injury
Authors: Babaloo Hamideh , Ebrahimi‐Barough Somayeh , Derakhshan Mohammad Ali , Yazdankhah Meysam , Lotfibakhshaiesh Nasrin , Soleimani Masoud , Joghataei Mohammad‐Taghi , Ai Jafar
Published: December 2018

The significant consequences of spinal cord injury (SCI) include sensory and motor disability resulting from the death of neuronal cells and axon degeneration. In this respect, overcoming the consequences of SCI including the recovery of sensory and motor functions is considered to be a difficult tasks that requires attention to multiple aspects of treatment. The breakthrough in tissue engineering through the integration of biomaterial scaffolds and stem cells has brought a new hope for the treatment of SCI. In the present study, human endometrial stem cells (hEnSCs) were cultured with human Schwann cells (hSC) in transwells, their differentiation into nerve‐like cells was confirmed by quantitative real‐time reverse transcription polymerase chain reaction (qRT‐PCR) and immunocytochemistry techniques. The differentiated cells (co‐hEnSC) were then seeded on the poly ε‐caprolactone (PCL)/gelatin scaffolds. The SEM images displayed the favorable seeding and survival of the cells on the scaffolds. The seeded scaffolds were then transplanted into hemisected SCI rats. The growth of neuronal cells was confirmed with immunohistochemical study using NF‐H as a neuronal marker. Finally, the Basso, Beattie, and Bresnahan (BBB) test confirmed the recovery of sensory and motor functions. The results suggested that combination therapy using the differentiated hEnSC seeded on PCL/gelatin scaffolds has the potential to heal the injured spinal cord and to limit the secondary damage.
The effects of CCR7 and related signaling pathways on Leishmania major ‐infected human dendritic cells
Authors: Zhao Yumin , Dang Zhisheng , Wei Riming , Gui Weifeng , Zhang Yishu , Chong Shigui
Published: December 2018

Objectives

In our research, we aimed to investigate the roles of CC‐chemokine receptor 7 (CCR7) and relevant signaling pathways in
Leishmania major‐infected human dendritic cells (DCs).

Methods

Differentially expressed genes (DEGs) in L. major‐infected human DCs were selected out and visualized using R program. Kyoto Encyclopedia of Genes and Genomes pathway analysis was conducted for investigation of significantly enriched signaling pathways and Gene Ontology enrichment analysis was carried out for the unveiling of enriched Molecular Functions and Biological Processes in
L. major‐infected human DCs. Besides, Hub gene was screened out using weighted gene coexpression network analysis and Cytoscape. In addition, enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction were used for detection of relative expression of
CCR7, interleukin‐12 (IL‐12), and interferon‐γ (IFN‐γ) in
L. major‐infected human DCs and western blot analysis was used for detection of relative expression of CCR7 and other proteins in JAK‐STAT signaling pathway in
L. major‐infected human DCs.

Results

CCR7 was upregulated and both chemokine and JAK‐STAT signaling pathway were activated in
L. major‐infected human DCs. During the
L. major infection, total number of
L. major‐infected human DCs were increased, as well as the relative expression levels of
CCR7, IL‐12, and IFN‐γ and proteins in the JAK‐STAT signaling pathway. Overexpression of
CCR7 not only increased expression levels of IL‐12 and IFN‐γ but also activated the JAK‐STAT signaling pathway to affect the leishmaniasis progression.

Conclusion

L. major infection‐induced activation of
CCR7, as well as
JAK2 and
STAT1, might well upregulate the expression of
BAX yet suppress the expression of both
Bcl2 and
c‐Jun to affect leishmaniasis progression.
lncRNA GAS5 promotes M1 macrophage polarization via miR‐455‐5p/SOCS3 pathway in childhood pneumonia
Authors: Chi Xiaowen , Ding Beichen , Zhang Lijuan , Zhang Jiawen , Wang Jianmei , Zhang Wei
Published: December 2018

Objectives

We herein aimed to explore whether growth arrest‐specific 5 (GAS5) promotes M1 macrophage polarization in childhood pneumonia and to investigate the underlying mechanism.

Methods

Relative GAS5 and miR‐455‐5p expression and suppressor of cytokine signaling 3 (SOCS3) messenger RNA level were examined using quantitative reverse transcription polymerase chain reaction. Protein expression of SOCS3 and the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway‐related proteins was detected using western blot analysis. Luciferase activity assay was performed to test whether miR‐455‐5p could bind to GAS5 or SOCS3. The macrophage phenotype was determined using flow cytometry analysis and enzyme‐linked immunosorbent assay.

Results

The macrophage polarization toward the M2 phenotype was observed in peripheral blood from pneumonia children. Furthermore, GAS5 and SOCS3 expression were upregulated but miR‐455‐5p downregulated in human monocyte‐derived macrophages from pneumonia children compared with the control group. Furthermore, GAS5 acted as a sponge for miR‐455‐5p to facilitate SOCS3 expression. Moreover, miR‐455‐5p mimic and SOCS3 knockdown significantly reversed the GAS5 overexpression‐mediated suppression of the JAK2/STAT3 signaling and promotion of M1 polarization.

Conclusion

GAS5 promotes M1 macrophage polarization by acting as a competing endogenous RNA of miR‐455‐5p to facilitate SOCS3 expression in childhood pneumonia.
Respiratory‐triggered spin‐echo echo‐planar imaging‐based mr elastography for evaluating liver stiffness
Authors: Wang Hui , Tkach Jean A. , Trout Andrew T. , Dumoulin Charles L. , Dillman Jonathan R.
Published: December 2018

Background

Magnetic resonance elastography (MRE) has proven to be useful for assessing chronic liver disease. However, MRE images are acquired with breath‐holding (BH) to limit respiratory motion artifacts, which may be difficult in some patients.

Purpose

To implement a respiratory‐triggered (RT) spin‐echo echo‐planar imaging (SE‐EPI) MRE technique and to validate its performance through comparison to a BH SE‐EPI MRE technique.

Study Type

Prospective feasibility study.

Subjects

Twenty‐three adult volunteers (18 without and 5 with liver disease).

Field Strength/Sequences

1.5 T Philips Ingenia MR scanner; RT and BH SE‐EPI MRE sequences.

Assessment

Four axial images were obtained through the middle of the liver with each technique. Liver stiffness measurements (in kPa) were made from elastograms, with 95% confidence maps overlaid, for both MRE sequences.

Statistical Tests

Liver stiffness measurements were compared using the paired t‐test (two‐sided). Absolute agreement between the two techniques was evaluated using Lin's concordance coefficient (rc). Bland–Altman analysis was used to assess the mean bias between the techniques and 95% limits of agreement, using BH MRE as the reference standard.

Results

There was excellent agreement (rc = 0.98; 95% confidence interval: 0.96–0.99) between RT and BH SE‐EPI MRE. Mean (±SD) stiffness values from BH and RT SE‐EPI MRE techniques were 2.40 ± 1.15 kPa and 2.37 ± 1.06 kPa, respectively, with no significant difference (P = 0.54) and no significant bias (mean bias of +0.03 kPa; 95% limits of agreement: –0.39 to 0.45 kPa). Measurable regions of interest in the liver were slightly smaller with the RT technique (mean difference of 1.91 cm2; P = 0.04).

Data Conclusion

RT SE‐EPI MRE is feasible and yields comparable results to BH SE‐EPI MRE.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2019;50:391–396.
Culture‐dependent hunt and characterization of iron‐oxidizing bacteria in Baiyin Copper Mine, China, and their application in metals extraction
Authors: Sajjad Wasim , Zheng Guodong , Ma Xiangxian , Rafiq Muhammad , Irfan Muhammad , Xu Wang , Ali Barkat
Published: December 2018

The exploration of microbial diversity in extremely acidic habitats has provided a vital base for the progression of minerals biotechnology. Three indigenous iron‐oxidizing acidophilic bacterial strains were isolated through serial dilution of enriched bacterial culture from Baiyin Copper Mine Stope, China. The morphological, biochemical, physiological, and phylogenetic characteristics of isolates were investigated. These isolates were motile, Gram‐negative, and curved shape with pleomorphism except isolate WG101 that was a straight rod. The optimum growth pH and temperature for all isolates were 1.5 and 30 °C, respectively, and showed extreme acidophilic nature. All the isolates showed obligate chemoautotrophic nature and used ferrous iron and pyrite as an energy source, however, isolates WG102 and WG103 were unable to use sulfur, while isolate WG101 could use elemental sulfur and reduced inorganic sodium thiosulfate as an energy source. The phylogenetic analyses based on 16S rRNA sequences revealed that the isolates WG101, WG102, and WG103 were homologous with Acidithiobacillus ferrooxidans strain AS2 (99%), Leptospirillum ferriphilum strain YSK (98%), and Leptospirillum ferrooxidans strain L15 (98%), respectively. These bacterial isolates showed efficient copper and zinc dissolution from the ore. The metals dissolution rate of At. ferrooxidans strain WG101 was 54.5 ± 4.33% (copper) and 49.6 ± 5% (zinc). The metals recovery rate of L. ferriphilum strain WG102 was 45.7 ± 3.5% (copper) and 40.5 ± 2.5% (zinc). The recovery rate of copper and zinc was 49.6 ± 4% and 46.5 ± 3% respectively in the case of L. ferrooxidans strain WG103. The findings of this study are consistent with the notion that the indigenous bacteria are more efficient in minerals dissolution.
Improvement of cocktail tomato yield and consumer‐oriented quality traits by potassium fertilization is driven by the cultivar
Authors: Sonntag Frederike , Naumann Marcel , Pawelzik Elke , Smit Inga
Published: December 2018

BACKGROUND

The market for cocktail tomatoes is growing continuously, mainly because of their good taste. Titratable acids (TA), total soluble solids (TSS) and dry matter (DM) contents correlate positively with good taste. So far, the impact of different potassium (K) applications on yield and consumer‐oriented quality traits has not been comprehensively described for cultivars of smaller fruits. To fill this gap, we tested the effect of different K fertilization regimes on three cultivars of small‐sized or cocktail tomatoes.

RESULTS

A positive impact on quality parameters (TSS, TA, DM, color and firmness) was detected by raising the K fertilizer application for the cocktail tomato cultivars Primavera and Yellow Submarine. The cultivar Resi showed no response to fertilization, except for TSS and TA. Yield increased significantly by higher K application only in Primavera, the most productive cultivar. The K concentration in tomato rose with increasing K application.

CONCLUSION

Because TSS and TA increased in all cultivars, whereas only one cultivar showed an increase in yield, the results of the present study emphasize the importance of the application of cultivar‐specific mineral fertilizers on yield‐ and consumer‐oriented quality traits. © 2018 Society of Chemical Industry
Interactive effects of abscisic acid and nitric oxide on chilling resistance and active oxygen metabolism in peach fruit during cold storage
Authors: Zhang Qitong , Zhang Lili , Geng Biao , Feng Jianrong , Zhu Shuhua
Published: December 2018

Background

Cold conditions can accelerate the production of reactive oxygen species (ROS), and excessive ROS may attack biological macromolecules, disrupt related signal pathways, induce oxidative stress and influence plant metabolism. The cross‐talk between nitric oxide (NO) and abscisic acid (ABA) and the inhibitions by NO or ABA on oxidative damage have been reported in fruits. However, there are few reports about the roles of NO–ABA interactions in chilling stress and antioxidant defense in fruits during cold storage. This study was conducted to investigate the roles of NO, ABA and interactions between NO and ABA in response to chilling stress on peach fruit (Prunus persica (L.) Batsch, cv. ‘Xintaihong’).

Results

Treatments with 15 µmol L−1 NO, 100 µmol L−1 ABA and 15 µmol L−1 NO + 5 mmol L−1 sodium tungstate solution could reduce ROS content, alleviate lipid peroxidation and enhance antioxidant enzyme activities and antioxidant capacities. However, treatments with 5 µmol L−1 potassium 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (c‐PTIO), 5 mmol L−1 sodium tungstate and 100 µmol L−1 ABA + 5 µmol L−1 c‐PTIO differentially blocked these protective effects and significantly increased ROS content and lipid peroxidation of peaches under low‐temperature conditions.

Conclusions

Application of exogenous ABA could increase the resistance to cold‐induced oxidative stress by enhancing the efficiency of enzymatic and non‐enzymatic systems, which were partially mediated by NO. © 2018 Society of Chemical Industry
Enhanced stability of red‐fleshed apple anthocyanins by copigmentation and encapsulation
Authors: Xue Jia , Su Fan , Meng Yonghong , Guo Yurong
Published: December 2018

BACKGROUND

Red‐fleshed apples are a great source of natural colorants and functional food ingredients because of their high anthocyanin content. Generally, anthocyanins are highly unstable after extraction, which limits their wide applications in the food and pharmaceutical industries. This study was aimed at investigating the effects of combining copigmentation with encapsulation on the stability of anthocyanins from red‐fleshed apples. In this study, red‐fleshed apple anthocyanins were copigmented with caffeic acid, and then the copigmented complexes were encapsulated using gum arabic and maltodextrin using spray drying and freeze drying.

RESULTS

All anthocyanin microcapsules had high encapsulation efficiencies ranging from 93.84 to 96.85% with mean hydrodynamic diameter smaller than 350 nm. After heating at 80 °C for 2 h, the dispersions of microencapsulated anthocyanins with copigments exhibited the highest absorbance values at λmax (515 nm) (P < 0.05). Light stability experiments demonstrated that the half‐life of the red‐fleshed apple anthocyanins increased from 5 to 12 days after being treated with copigmentation and encapsulation. The drying methods (spray/freeze drying) did not significantly influence the stability of the microencapsulated anthocyanins.

CONCLUSIONS

Applying copigmentation and spray‐drying encapsulation in tandem has great potential for enhancing the stability of red‐fleshed apple anthocyanins. Thus, such anthocyanins with enhanced stability may be increasingly used in the food and pharmaceutical industries as value‐added natural food pigments. © 2018 Society of Chemical Industry
Sonography of Wrist Ganglion Cysts: Which Location Is Most Common?
Authors: Zhang Andrew , Falkowski Anna L. , Jacobson Jon A. , Kim Sung Moon , Koh Sung Hye , Gaetke‐Udager Kara
Published: December 2018

Objectives

The literature states that wrist ganglion cysts are most commonly dorsal; however, our experience suggests a volar location is more common. The purpose of this study was to identify the locations of ganglion cysts of the wrist as imaged with sonography.

Methods

After Institutional Review Board approval with informed consent waived, retrospective review of wrist sonography reports from January to April 2016 was completed. Only patients who had a comprehensive evaluation that included the dorsal and volar wrist were included. Ultrasound images were reviewed to characterize wrist ganglion cysts.

Results

The study group consisted of 98 subjects (78% female, 22% male) (median age, 51 years; range 13–79) with 124 wrist ganglion cysts, where 69% (86 of 124) were volar and 31% (38 of 124) were dorsal. Ganglion cysts were located between the radial artery and flexor carpi radialis in 63% (78 of 124), followed by a dorsal location superficial to the scapholunate ligament in 20% (25 of 124), other dorsal locations in 11% (13 of 124), and other volar locations in 6% (8 of 124). With dorsal ganglion cysts, the scapholunate ligament when imaged appeared normal in 91% (20 of 22). Ganglion cysts were multilocular/multilobular in all subjects.

Conclusions

The most common location for wrist ganglion cysts is in the volar wrist, particularly between the radial artery and flexor carpi radialis tendon, appearing multilocular or multilobular with a mean largest dimension of 1.0 cm. Given the propensity of ganglion cysts to occur at this site, attention to this area when imaging the wrist with sonography or magnetic resonance imaging should be considered.
The ablative fractional coagulation zone influences skin fluorescence intensities of topically applied test molecules—An in vitro study with fluorescence microscopy and fluorescence confocal microscopy
Authors: Banzhaf Christina A. , Ortner Vinzent K. , Philipsen Peter A. , Haedersdal Merete
Published: December 2018

Background

Ablative fractional laser (AFL) increases uptake of topically applied skin agents. The coagulation zone (CZ) surrounding vertically ablated channels may influence uptake of drugs.

Objectives

To investigate impact of CZ thickness on skin fluorescence intensities (FI) of a hydrophilic molecule by means of fluorescence microscopy (FM) and fluorescence confocal microscopy (FCM). Second, to compare FI of hydrophilic and lipophilic test molecules by FCM.

Study Design/Methods and Materials

Microchannels with CZ thicknesses of 0, 20, and 80 µm were generated by microneedles or AFL (10,600 nm). Channels were 700 µm deep and number of channels kept constant per skin area. After 4 hours of incubation, FI induced by sodium fluorescein (NAF, hydrophilic, logarithmic partition‐coefficient (logP) = −1.52, MW = 376.26) were quantified in both CZ and surrounding skin by FM (0–1,500 µm) and FCM (0–90 µm). FI of NAF and carboxyfluorescein (CAF, lipophilic, logP = 2.9, MW = 376.32) were compared by FCM.

Results

By FM, NAF‐induced FI were higher in CZ than in surrounding skin (P ≤ 0.001). Highest NAF‐FI were induced in skin pretreated with a thin CZ (CZ–20 µm), assessed by both FM and FCM and in particular, FI were higher than in skin pretreated with no CZ (CZ–0 µm) (FM P ≤ 0.041, FCM P < 0.012). Skin FI remained constant to a depth of 500 µm, which corresponded to approximate depth of microchannels (CZ–0 µm, CZ–20 µm, CZ–80 µm: 0–500 µm P ≥ 0.107). In accordance with FM data, FCM showed higher FI within CZ than in surrounding skin, but gradually decreased to zero at a depth of 90 µm. NAF‐FI were higher than CAF‐FI (P ≤ 0.036), and highest CAF‐FI were induced by CZ–0 µm and CZ–20 µm compared to CZ–80 µm (P ≤ 0.009).

Conclusions

The influence of the CZ thickness on skin FI differs between small hydrophilic and lipophilic test molecules. Results may have clinical relevance for laser‐assisted drug delivery. Lasers Surg. Med. 51:68–78, 2019. © 2018 Wiley Periodicals, Inc.
A Stochastic Analysis of the Damping Property of Filled Elastomers
Authors: Kulkarni Shank S. , Tabarraei Alireza
Published: December 2018

Finite elements modeling is used to investigate the damping property of Polymer composites consisting of a viscoelastic matrix and randomly dispersed elastic particles. The impact of vibration frequency, inclusions size and volume fraction on the damping capability of polymer composites are studied. It is shown that analytical micromechanics methods give accurate predictions only when inclusions volume fraction is small. The results show that loading frequency and inclusions volume fraction significantly impact the damping capability of polymer composites. The effect of domain boundary conditions on the simulation results is studied by conducting finite element modelings on representative volume elements (RVEs) which are subjected to periodic or mixed boundary conditions. The modeling results indicate that both boundary conditions lead to similar predictions for damping. Sensitivity analyses are conducted to assess how material properties influence the damping property. The sensitivity analyses show that an increase in the stiffness of the composite matrix leads to a reduction in the damping capability of polymer composites. In contrast, an increase in the stiffness of inclusions results in an increase in the damping capability of polymer composites. Moreover, the damping properties are improved if the relaxation time of the viscoelastic matrix is increased.
Norovirus antivirals: Where are we now?
Authors: Netzler Natalie E. , Enosi Tuipulotu Daniel , White Peter A.
Published: December 2018

Human noroviruses inflict a significant health burden on society and are responsible for approximately 699 million infections and over 200 000 estimated deaths worldwide each year. Yet despite significant research efforts, approved vaccines or antivirals to combat this pathogen are still lacking. Safe and effective antivirals are not available, particularly for chronically infected immunocompromised individuals, and for prophylactic applications to protect high‐risk and vulnerable populations in outbreak settings. Since the discovery of human norovirus in 1972, the lack of a cell culture system has hindered biological research and antiviral studies for many years. Recent breakthroughs in culturing human norovirus have been encouraging, however, further development and optimization of these novel methodologies are required to facilitate more robust replication levels, that will enable reliable serological and replication studies, as well as advances in antiviral development. In the last few years, considerable progress has been made toward the development of norovirus antivirals, inviting an updated review. This review focuses on potential therapeutics that have been reported since 2010, which were examined across at least two model systems used for studying human norovirus or its enzymes. In addition, we have placed emphasis on antiviral compounds with a defined chemical structure. We include a comprehensive outline of direct‐acting antivirals and offer a discussion of host‐modulating compounds, a rapidly expanding and promising area of antiviral research.