bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological profile and effects of mitotane in adrenocortical carcinoma
Authors: Corso Claudia Rita , Acco Alexandra , Bach Camila , Bonatto Sandro José Ribeiro , de Figueiredo Bonald Cavalcante , de Souza Lauro Mera
Published: December 2020

Mitotane is the only adrenolytic drug approved by the Food and Drug Administration for treating adrenocortical carcinoma (ACC). This drug has cytotoxic effects on tumour tissues; it induces cell death and antisecretory effects on adrenal cells by inhibiting the synthesis of adrenocortical steroids, which are involved in the pathogenesis of ACC. However, high doses of mitotane are usually necessary to reach the therapeutic plasma concentration, which may result in several adverse effects. This suggests that important pharmacological processes, such as first pass metabolism, tissue accumulation and extensive time for drug elimination, are associated with mitotane administration. Few studies have reported the pharmacological aspects and therapeutic effects of mitotane. Therefore, the aim of this review was to summarize the chemistry, pharmacokinetics and pharmacodynamics, and therapeutic and toxic effects of mitotane. This review also discusses new perspectives of mitotane formulation that are currently under investigation. Understanding the pharmacological profile of mitotane can improve the monitoring and efficacy of this drug in ACC treatment and can provide useful information for the development of new drugs with specific action against ACC with fewer adverse effects.
Depression, anxiety, perceived stress, and their changes predicted medical adherence over 9 months among patients with coronary heart disease
Authors: Fan Yunge , Shen Biing‐Jiun , Tay Hung Yong
Published: December 2020

Objectives

Although effective medical treatments have proved to successfully improve prognoses and outcomes of patients with coronary heart disease (CHD), low adherence to treatments is still common among patients. Deleterious impact of psychological distress on medical adherence has been recognized; however, few studies examined the influence of change in psychological distress on attenuation in adherence. This study investigated whether three common manifestations of distress (depression, anxiety, and perceived stress) and their changes predicted decline in medical adherence among CHD patient over 9 months.

Design

A three‐wave longitudinal study.

Methods

Participants were 255 CHD patients with a mean age of 63 years. Psychological distress, medication adherence, and specific treatment adherence were assessed at baseline, 3 months, and 9 months. Hierarchical regression analyses were conducted to examine the influences of psychological distress on medical adherence over 9 months. All models were adjusted for baseline medication or specific adherence, demographic, and medical covariates.

Results

Baseline depression and its changes over time significantly predicted greater decline in both medication adherence (βs = .15–.20, ps < .05) and specific adherence (βs = −.21 to −.15, ps < .05). Anxiety showed a similar trend. For perceived stress, baseline and its change significantly predicted specific adherence over 9 months (βs = −.30 to −.23, ps < .01), but did not predict medication adherence at 3 and 9 months.

Conclusions

Findings underline the necessity of tracking various forms of psychological distress over time for CHD patients to promote medical adherence and further improve the disease prognosis.
Persecutory Entrapment and Flights in and out of Situations: A Question of Survival
Authors: Dubois‐Barnes Leila
Published: December 2020

This paper considers the occurrence of entrapment, invasion and phobic functioning ‘in’ and ‘out’(side) the consulting room as well as states of mind connected with safety and survival. Patient and therapist set sail on a troubled analytic journey beset by dangerous, terrifying mother imagoes, a mafia gang and a watchful life‐saving ally. It is an epic journey into the unknown that involves inter alia thrills, braving the elements and the antagonistic forces of Thanatos and Eros. ‘No one dies and no one is hurt’, but emotional storms are created in media res. The patient then takes many flights. Firstly, into the place of her worst ‘nightmare’ and secondly, into action and inaction. In reality, a truly secure space and object cannot be found – only a feeling of captivity and disintegration remains. The use and function of potent and evocative objects may be significant for the patient in terms of safeguarding against re‐experiencing primitive disasters, while achieving (a retroactive) control and mastery over the original trauma and helplessness. The author navigates a wide range of psychoanalytic theory, finding correspondence between classical and contemporary psychoanalytic traditions.
Growth, development, and phenotypic spectrum of individuals with deletions of 2q33.1 involving SATB2
Authors: Zarate Yuri A. , Bosanko Katherine A. , Thomas Mary Ann , Miller David T. , Cusmano‐Ozog Kristina , Martinez‐Monseny Antonio , Curry Cynthia J. , Graham John M. , Velsher Lea , Bekheirnia Mir Reza , Seidel Veronica , Dedousis Demitrios , Mitchell Anna L. , DiMarino Amy M. , Riess Angelika , Balasubramanian Meena , Fish Jennifer L. , Caffrey Aisling R. , Fleischer Nicole , Pierson Tyler Mark , Lacro Ronald V.
Published: December 2020

SATB2‐Associated syndrome (SAS) is an autosomal dominant, multisystemic, neurodevelopmental disorder due to alterations in SATB2 at 2q33.1. A limited number of individuals with 2q33.1 contiguous deletions encompassing SATB2 (ΔSAS) have been described in the literature. We describe 17 additional individuals with ΔSAS, review the phenotype of 33 previously published individuals with 2q33.1 deletions (n = 50, mean age = 8.5 ± 7.8 years), and provide a comprehensive comparison to individuals with other molecular mechanisms that result in SAS (non‐ΔSAS). Individuals in the ΔSAS group were often underweight for age (20/41 = 49%) with a progressive decline in weight (95% CI = −2.3 to −1.1, p < 0.0001) and height (95% CI = −2.3 to −1.0, p < 0.0001) Z‐score means from birth to last available measurement. ΔSAS individuals were often noted to have a broad spectrum of facial dysmorphism. A composite image of ΔSAS individuals generated by automated image analysis was distinct as compared to matched controls and non‐ΔSAS individuals. We also present additional genotype–phenotype correlations for individuals in the ΔSAS group such as an increased risk for aortic root/ascending aorta dilation and primary pulmonary hypertension for those individuals with contiguous gene deletions that include COL3A1/COL5A2 and BMPR2, respectively. Based on these findings, we provide additional care recommendations for individuals with ΔSAS variants.
Hypomethylation of NLRP3 gene promoter discriminates glucocorticoid‐resistant from glucocorticoid‐sensitive idiopathic nephrotic syndrome patients
Authors: Lucafò Marianna , Granata Simona , Bonten Erik J. , McCorkle Robert , Stocco Gabriele , Caletti Chiara , Selvestrel Davide , Cozzarolo Alessio , Zou Chan , Cuzzoni Eva , Pasini Andrea , Montini Giovanni , Gambaro Giovanni , Decorti Giuliana , Evans William , Zaza Gianluigi
Published: December 2020

To assess whether NLRP3 gene promoter methylation was able to discriminate glucocorticoid (GC)‐resistant from GC‐sensitive idiopathic nephrotic syndrome (INS), patients with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS), we measured the methylation level of NLRP3 promoter in DNA from peripheral blood cells of 10 adult patients with GC‐resistant FSGS already in hemodialysis and 18 patients with GC‐sensitive INS (13 MCD/5 FSGS) and in 21 pediatric patients with INS with MCD/FSGS before starting any treatment. Association of NLRP3 inflammasome with GC resistance was recapitulated in vitro in monocytic cell lines (THP‐1 and U937). In both adults and pediatric patients, NLRP3 promoter methylation was significantly reduced in GC‐resistant compared with GC‐sensitive patients. Indeed, NLRP3 methylation distinguished GC‐resistant and GC‐sensitive patients (area under the receiver operating characteristic curve [AUROC] 86.7% in adults, p = 0.00019, and 73.5% in children, p = 0.00097). NLRP3 knock‐down augmented sensitivity to GCs in THP‐1 cells, whereas NLRP3 inflammasome activation lowered GC receptor concentration, increasing GC resistance in U937 cells. Our results uncovered a new biological mechanism by which patients with INS may acquire GC resistance, that could be used in future as a novel noninvasive diagnostic tool.

Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Approximately 80% of patients with idiopathic nephrotic syndrome (INS) respond to glucocorticoids, with the remaining 20% being steroid‐resistant.

WHAT QUESTION DID THIS STUDY ADDRESS?

☑ Whether NLRP3 gene promoter methylation was able to discriminate glucocorticoid‐resistant from glucocorticoid (GC)‐sensitive INS.

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

☑ In both adults and children, NLRP3 promoter methylation was significantly reduced in leukocytes of patients with GC‐resistant compared with GC‐sensitive INS. NLRP3 inflammasome activation lowered GC receptor concentration and augmented GC resistance, whereas NLRP3 knockdown increased sensitivity to GCs in cell lines representative of monocytes (U937 and THP1).

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

☑ Our findings uncovered a new biological mechanism whereby patients with INS may develop resistance to GCs that could be used in the future as a novel noninvasive diagnostic tool.
Irradiation of the head reduces adult hippocampal neurogenesis and impairs spatial memory, but leaves overall health intact in rats
Authors: Lensu Sanna , Waselius Tomi , Mäkinen Elina , Kettunen Heikki , Virtanen Ari , Tiirola Marja , Penttonen Markku , Pekkala Satu , Nokia Miriam S.
Published: December 2020

Treatment of brain cancer, glioma, can cause cognitive impairment as a side‐effect, possibly because it disrupts the integrity of the hippocampus, a structure vital for normal memory. Radiotherapy is commonly used to treat glioma, but the effects of irradiation on the brain are still poorly understood, and other biological effects have not been extensively studied. Here, we exposed healthy adult male rats to moderate‐dose irradiation of the head. We found no effect of irradiation on systemic inflammation, weight gain or gut microbiota diversity, although it increased the abundance of Bacteroidaceae family, namely Bacteroides genus in the gut microbiota. Irradiation had no effect on long‐term potentiation in the CA3‐CA1 synapse or endogenous hippocampal electrophysiology, but it did reduce adult hippocampal neurogenesis and impaired short‐term spatial recognition memory. However, no overall cognitive impairment was observed. To summarize, our results suggest that in adult male rats head irradiation does not compromise health or cognition overall even though the number of new, adult‐born hippocampal neurons is decreased. Thus, the sole effects of head irradiation on the body, brain and cognition might be less harmful than previously thought, and the cognitive decline experienced by cancer patients might originate from physiological and mental effects of the disease itself. Therefore, to increase the translational value of animal studies, the effects of irradiation should be studied together with cancer, in older animals, using varying irradiation protocols and doses.
Mindfulness and Embodiment in Family Therapy: Overview, Nuances, and Clinical Applications in Poststructural Practices
Authors: Beaudoin Marie‐Nathalie , Maclennan Robert
Published: December 2020

This paper discusses the inclusion of ideas from mindfulness, embodiment, and associated brain research in poststructural family therapies. Connecting research and practice across diverse fields is presented as enriching therapeutic work, increasing clinical effectiveness, and broadening options for families seeking our assistance. Ways of incorporating mindfulness and embodiment are described and offer distinctively novel practices not typically used in traditional forms of poststructural therapies. These innovative practices are illustrated by clinical work with a mother and her five‐year‐ daughter who survived a dangerous health crisis and an extremely painful hospitalization. Therapeutic work with this family exemplifies how traumatic experiences are not always accessible through linguistic means alone. Working with interpersonal mind–body practices can uniquely contribute to relaxing the sympathetic nervous system and activating the social engagement branch of the parasympathetic nervous system. The inclusion of such practices can provide valuable opportunities to facilitate the emergence of preferred experiences of self for all family members.
Search for top‐down and bottom‐up drivers of latitudinal trends in insect herbivory in oak trees in Europe
Authors: Valdés‐Correcher Elena , Moreira Xoaquín , Augusto Laurent , Barbaro Luc , Bouget Christophe , Bouriaud Olivier , Branco Manuela , Centenaro Giada , Csóka György , Damestoy Thomas , Dobrosavljević Jovan , Duduman Mihai‐Leonard , Dulaurent Anne‐Maïmiti , Eötvös Csaba B. , Faticov Maria , Ferrante Marco , Fürjes‐Mikó Ágnes , Galmán Andrea , Gossner Martin M. , Hampe Arndt , Harvey Deborah , Gordon Howe Andrew , Kadiri Yasmine , Kaennel‐Dobbertin Michèle , Koricheva Julia , Kozel Alexander , Kozlov Mikhail V. , Lövei Gábor L. , Lupaștean Daniela , Milanović Slobodan , Mrazova Anna , Opgennoorth Lars , Pitkänen Juha‐Matti , Popova Anna , Popović Marija , Prinzing Andreas , Queloz Valentin , Roslin Tomas , Sallé Aurélien , Sam Katerina , Scherer‐Lorenzen Michael , Schuldt Andreas , Selikhovkin Andrey , Suominen Lassi , Tack Ayco J. M. , Tahadlova Marketa , Thomas Rebecca , Castagneyrol Bastien
Published: December 2020

Aim

The strength of species interactions is traditionally expected to increase toward the Equator. However, recent studies have reported opposite or inconsistent latitudinal trends in the bottom‐up (plant quality) and top‐down (natural enemies) forces driving herbivory. In addition, these forces have rarely been studied together thus limiting previous attempts to understand the effect of large‐scale climatic gradients on herbivory.

Location

Europe.

Time period

2018–2019.

Major taxa studied

Quercus robur.

Methods

We simultaneously tested for latitudinal variation in plant–herbivore–natural enemy interactions. We further investigated the underlying climatic factors associated with variation in herbivory, leaf chemistry and attack rates in Quercus robur across its complete latitudinal range in Europe. We quantified insect leaf damage and the incidence of specialist herbivores as well as leaf chemistry and bird attack rates on dummy caterpillars on 261 oak trees.

Results

Climatic factors rather than latitude per se were the best predictors of the large‐scale (geographical) variation in the incidence of gall‐inducers and leaf‐miners as well as in leaf nutritional content. However, leaf damage, plant chemical defences (leaf phenolics) and bird attack rates were not influenced by climatic factors or latitude. The incidence of leaf‐miners increased with increasing concentrations of hydrolysable tannins, whereas the incidence of gall‐inducers increased with increasing leaf soluble sugar concentration and decreased with increasing leaf C : N ratios and lignins. However, leaf traits and bird attack rates did not vary with leaf damage.

Main conclusions

These findings help to refine our understanding of the bottom‐up and top‐down mechanisms driving geographical variation in plant–herbivore interactions, and indicate the need for further examination of the drivers of herbivory on trees.
Chemical conversion of aged hepatocytes into bipotent liver progenitor cells
Authors: Huang Yu , Miyamoto Daisuke , Li Pei‐Lin , Sakai Yusuke , Hara Takanobu , Adachi Tomohiko , Soyama Akihiko , Hidaka Masaaki , Kanetaka Kengo , Gu Wei‐Li , Eguchi Susumu
Published: December 2020

Aim

In the aging society, understanding the influence of hepatocyte age on hepatocyte donation may inform efforts to expand alternative cell sources to mitigate liver donor shortage. A combination of the molecules Y27632, A‐83‐01, and CHIR99021 has been used to reprogram rodent young hepatocytes into chemically induced liver progenitor (CLiP) cells; however, whether it could also reprogram aged hepatocytes has not yet been elucidated.

Methods

Primary hepatocytes were isolated from aged and young donor rats, respectively. Hepatic histological changes were evaluated. Differences in gene expression in hepatocytes were identified. The in vitro reprogramming plasticity of hepatocytes as evidenced by CLiP conversion and the hepatocyte and cholangiocyte maturation capacity of reprogrammed CLIPs were analyzed. The effect of hepatocyte growth factor (HGF) on cell propagation was also investigated.

Results

The histological findings revealed ongoing liver damage with inflammation, fibrosis, senescence, and ductular reaction in aged livers. Microarray analysis showed altered gene expression profiles in hepatocytes from aged donors, especially with regard to metabolic pathways. Aged hepatocytes could be converted into CLiPs (Aged‐CLiPs) expressing progenitor cell markers, but with a relatively low proliferative rate compared with young hepatocytes. Aged‐CLiPs possessed both hepatocyte and cholangiocyte maturation capacity. HGF facilitated CLiP conversion in aged hepatocytes, which was partly related to the activation of Erk1 and Akt1 signaling.

Conclusions

Aged rat hepatocytes have retained reprogramming plasticity as evidenced by CLiP conversion in culture. HGF promoted proliferation and CLiP conversion in aged hepatocytes. Hepatocytes from aged donors may be used as an alternative cell source to mitigate donor shortage.
Recent advances in the pathology of heritable gastric cancer syndromes
Authors: Gullo Irene , van der Post Rachel S , Carneiro Fátima
Published: December 2020

Despite the relative rarity of hereditary gastric cancer syndromes, the prompt recognition of their specific clinical features and histopathological characteristics is pivotal in offering patients the most appropriate treatment. In this article, we address the three major inherited syndromes that primarily affect the stomach: hereditary diffuse gastric cancer (HDGC), caused by germline variants in CDH1 and CTNNA1; gastric adenocarcinoma and proximal polyposis of the stomach, caused by germline mutations in promoter 1B of APC; and familial intestinal gastric cancer, which has a poorly defined genetic cause. The main focus will be on HDGC, in light of the recent publication of updated clinical practice guidelines and emerging concepts regarding HDGC histopathology. In particular, we describe the broad morphological spectrum of HDGC lesions, stressing the importance of recognising indolent and aggressive phenotypes. Moreover, we discuss the increased risk of gastric (pre)malignancies developing in patients with other well‐defined hereditary cancer syndromes, such as familial adenomatous polyposis, Lynch syndrome, Peutz–Jeghers syndrome, juvenile polyposis, Li–Fraumeni syndrome, and hereditary breast and ovarian cancer syndrome.
Targeted therapy for upper gastrointestinal tract cancer: current and future prospects
Authors: Rosenbaum Matthew W , Gonzalez Raul S
Published: December 2020

Gastric and oesophageal carcinoma remain major causes of worldwide mortality and morbidity. Despite incredible progress in understanding tumour biology, few targeted treatment options have proved effective in prolonging survival, and adjuvant therapy is largely interchangeable in these carcinomas. Through large‐scale sequencing by the Cancer Genome Atlas and the Asian Cancer Research Group, numerous potential molecular targets have been discovered. Of the approved targeted therapies for gastric and oesophageal cancer, pathologists play a role in patient selection for the majority of them. Trastuzumab has been approved as a first‐line therapy in conjunction with standard treatment in adenocarcinomas with either 3+ HER2/neuexpression by immunohistochemistry orERBB2amplification by FISH. PD‐L1 immunohistochemistry showing a combined positive score of 1 or greater qualifies patients for third‐line pembrolizumab therapy, and identification of microsatellite instability‐high carcinomas may qualify patients for second‐line pembrolizumab. Ramucirumab, targeting VEGFR2, has also been approved for second‐line therapy in gastric carcinoma. Non‐surgical therapy for gastrointestinal stromal tumours relies mainly upon tyrosine kinase inhibitors, while new targeted therapy options for neuroendocrine neoplasms have recently emerged. Potential future options for targeted therapy in all these malignancies are being investigated in clinical trials, as this review will discuss.
Understanding the adoption and willingness to pay for internet of things services
Authors: Kasilingam Dharun , Krishna Rajneesh
Published: December 2020

Internet of Things (IOT) involves devices that can interact with one another by connecting to the internet and sending information, ultimately improving human lives. This research is one of the first in literature that seeks to understand the variables that influence consumer adoption of IOT products offered as services against a monthly premium. The influence of value dimensions on IOT on its adoption and consumer willingness to pay a premium was studied. A sample consisting of 1623 responses collected through an online survey was analysed using partial least squares structural equation modelling. The moderating role of age groups, gender and income levels was also analysed. Out of sample prediction and overfitting of the model were used to assess predictive validity both for the full data set and across groups using PLS Predict. Perceived playfulness, personal innovativeness and convenience value were the most significant variables affecting attitude and intention to use IOT services. Attitude mediated most relationships in the model. Moderation analysis using demographic variables of gender, age groups and income levels revealed significant differences in the strengths of the relationships in the model. Predictive validity assessment with PLS showed revealed high predictive power of the model for adoption outside the selected sample. The results can help marketers segment and design business strategies to expedite the diffusion and adoption of the technology in the market. The need for a shift in the B2C IOT market from product‐centric to a product‐as‐a‐service business to maximize value to consumers is thus proposed.
Antecedents and consequences of panic buying: The case of COVID‐19
Authors: Prentice Catherine , Quach Sara , Thaichon Park
Published: December 2020

Panic buying emerged as a significant phenomenon during the COVID‐19 pandemic. This study draws on the scarcity principle, crowd psychology and contagion theory to investigate the antecedents and consequences of panic buying. The antecedents included in this study are government measures, media and peer influence and the fear of missing out. The consequences are founded on a sense of security and guilt. Retailer intervention is included as a moderator to the proposed main effects. Data were collected from 341 consumers who engaged in panic buying and were residents of the United States and Australia during the COVID‐19 pandemic. Structural equation modelling was employed to test the proposed model. The results show that the proposed antecedents (except fear of missing out) were significantly related to panic buying, which in turn had a significant influence on panic buyers' psychological outcomes. The moderating effects of retailer intervention varied across different product categories. Discussion and implications of these findings are provided for policy makers, customers and practitioners.
Continuous rhythm monitoring‐guided anticoagulation after atrial fibrillation ablation
Authors: Pothineni Naga Venkata K. , Amankwah Nigel , Santangeli Pasquale , Schaller Robert D. , Supple Gregory E. , Deo Rajat , Nazarian Saman , Garcia Fermin C. , Dixit Sanjay , Callans David J. , Marchlinski Francis E. , Frankel David S.
Published: December 2020

Introduction

Oral anticoagulation (OAC) based on estimated stroke risk is recommended following catheter ablation (CA) of atrial fibrillation (AF), regardless of the extent of arrhythmia control. However, discontinuing OAC in selected patients may be safe. We sought to evaluate a strategy of OAC discontinuation following AF ablation guided by continuous rhythm monitoring.

Methods and Results

We prospectively studied AF ablations performed at our institution from June 2015 to December 2019. Patients that had pre‐existing cardiac implantable electronic devices (CIEDs) or underwent insertable cardiac monitor (ICM) implantation immediately following AF ablation were included. OAC was continued for 6 weeks following CA in all patients, following which OAC management was guided by CHA2DS2‐VASc score and continuous rhythm monitoring results, according to a prespecified protocol. AF recurrence was defined as ≥30 s (CIEDs) or ≥2 min (ICM). We studied 196 patients (mean age 64.7 ± 11.3 years, 66.8% male, 85.7% ICM, 14.3% CIEDs). Mean CHA2DS2‐VASc score was 2.2  ± 1.5. One‐year AF‐free survival following CA was 83% for paroxysmal AF and 63% for persistent AF patients. Over 3 year follow‐up, OAC was discontinued in 57 (33.7%) patients, mean 7.4 ± 7.1 months following ablation. Following discontinuation, OAC was restarted for AF recurrence in 9 (15.8%) patients, mean 11.7 ± 6.8 months after stopping. This discontinuation protocol led to a 21.9% reduction in overall time exposed to OAC. There were no thromboembolic or major bleeding events.

Conclusion

OAC can be discontinued in a significant percentage of patients following CA of AF. When guided by continuous rhythm monitoring, this practice does not unacceptably increase the risk of thromboembolic events
Endoscopic removal of entirely embedded esophagus‐penetrating foreign bodies (with video)
Authors: Wang Yun , Liu Zu‐Qiang , Xu Xiao‐Yue , Hu Hao , Qin Wen‐Zheng , Chen Wei‐Feng , Cai Ming‐Yan , Zhang Yi‐Qun , Zhong Yun‐Shi , Li Quan‐Lin , Zhou Ping‐Hong
Published: December 2020

Background and Aim

Traditionally, surgery is the only choice for esophageal foreign bodies (FBs) penetrating into the mediastinum or cervical para‐esophageal space. Recent progress in endoscopic techniques and devices has made it possible to perform endoscopic procedures in the mediastinum. Here, we describe a novel method to remove the entirely embedded esophagus‐penetrating FBs through an endoscopic approach.

Methods

Patients who underwent endoscopic removal of entirely embedded esophagus‐penetrating FBs were prospectively enrolled between December 2018 and June 2020. All procedures were performed by using five major steps: localization of the FB; mucosal incision; wound debridement, myotomy, and FB exposure; FB extraction; and closure of the esophageal wound.

Results

A total of five cases of entirely embedded esophagus‐penetrating FBs were evaluated, two in children and three in adults. All FBs were successfully removed and extracted using a therapeutic endoscope and a hook knife or a hybrid knife and a grasping forceps as accessories. The average procedure time was 19.0 ± 12.4 min (range 10–40 min). The major surgical procedure was avoided in all patients. The average length of hospital stay was 3.8 ± 2.5 days (range 2–8 days). There were no severe short‐term adverse events after all procedures. During the 1 month and 3 months follow‐up, no patient developed long‐term adverse events including stenosis of the esophagus and fistula formation.

Conclusions

Endoscopic approach was a safe and effective way to remove entirely embedded esophagus‐penetrating FBs.
Psychotropic Medication and Cognitive, Functional, and Neuropsychiatric Outcomes in Alzheimer's Disease (AD)
Authors: Oh Esther S. , Rosenberg Paul B. , Rattinger Gail B. , Stuart Elizabeth A. , Lyketsos Constantine G. , Leoutsakos Jeannie‐Marie S.
Published: December 2020

BACKGROUND/OBJECTIVES

There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort.

DESIGN

Longitudinal observational study.

SETTING

National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers.

PARTICIPANTS

8,034 participants with AD dementia.

MEASUREMENTS

Mini‐Mental State Exam (MMSE), Clinical Dementia Rating Scale‐Sum of Boxes (CDR‐SB), and Neuropsychiatric Inventory Questionnaire (NPI‐Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non‐SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest‐matched PS. The effect of medication treatment was assessed using linear mixed‐effects models.

RESULTS

Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR‐SB 5.5 (3.4), and NPI‐Q Total 4.5 (4.4). Mean duration of follow‐up was 2.9–3.3 years depending on medication class. Non‐SSRI antidepressant use was associated with better CDR‐SB (2‐year difference in change‐DIC: −0.38 [−0.61, −0.15], P = .001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: −0.91 [−1.54, −0.28] P = .005) and CDR‐SB scores (DIC: 0.50 [0.14, 0.86], P = .006). Notably, no drug class was associated with better NPI‐Q scores.

CONCLUSIONS

Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms.
Neuromuscular junction‐on‐a‐chip: ALS disease modeling and read‐out development in microfluidic devices
Authors: de Jongh Rianne , Spijkers Xandor M. , Pasteuning‐Vuhman Svetlana , Vulto Paul , Pasterkamp R. Jeroen
Published: December 2020

Amyotrophic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease affecting upper and lower motor neurons with no cure available. Clinical and animal studies reveal that the neuromuscular junction (NMJ), a synaptic connection between motor neurons and skeletal muscle fibers, is highly vulnerable in ALS and suggest that NMJ defects may occur at the early stages of the disease. However, mechanistic insight into how NMJ dysfunction relates to the onset and progression of ALS is incomplete, which hampers therapy development. This is, in part, caused by a lack of robust in vitro models. The ability to combine microfluidic and induced pluripotent stem cell (iPSC) technologies has opened up new avenues for studying molecular and cellular ALS phenotypes in vitro. Microfluidic devices offer several advantages over traditional culture approaches when modeling the NMJ, such as the spatial separation of different cell types and increased control over the cellular microenvironment. Moreover, they are compatible with 3D cell culture, which enhances NMJ functionality and maturity. Here, we review how microfluidic technology is currently being employed to develop more reliable in vitro NMJ models. To validate and phenotype such models, various morphological and functional read‐outs have been developed. We describe and discuss the relevance of these read‐outs and specifically illustrate how these read‐outs have enhanced our understanding of NMJ pathology in ALS. Finally, we share our view on potential future directions and challenges.

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Promotion of vascular integrity in sepsis through modulation of bioactive adrenomedullin and dipeptidyl peptidase 3
Authors: van Lier D. , Kox M. , Pickkers P.
Published: December 2020

Sepsis represents one of the major medical challenges of the 21st century. Despite substantial improvements in the knowledge on pathophysiological mechanisms, this has so far not translated into novel adjuvant treatment strategies for sepsis. In sepsis, both vascular tone and vascular integrity are compromised, and contribute to the development of shock, which is strongly related to the development of organ dysfunction and mortality. In this review, we focus on dipeptidyl peptidase 3 (DPP3) and adrenomedullin (ADM), two molecules that act on the vasculature and are involved in the pathophysiology of sepsis and septic shock. DPP3 is an ubiquitous cytosolic enzyme involved in the degradation of several important signalling molecules essential for regulation of vascular tone, including angiotensin II. ADM is a key hormone involved in the regulation of vascular tone and endothelial barrier function. Previous studies have shown that circulating concentrations of both DPP3 and ADM are independently associated with the development of organ failure and adverse outcome in sepsis. We now discuss new evidence illustrating that these molecules indeed represent two distinct pathways involved in the development of septic shock. Recently, both ADM‐enhancing therapies aimed at improving endothelial barrier function and vascular tone and DPP3‐blocking therapies aimed at restoring systemic angiotensin responses have been shown to improve outcome in various preclinical sepsis models. Given the current lack of effective adjuvant therapies in sepsis, additional research on the therapeutic application of these peptides in humans is highly warranted.
Association between periodontitis and the Mediterranean diet in young Moroccan individuals
Authors: Iwasaki Masanori , Ennibi Oum Keltoum , Bouziane Amal , Erraji Samir , Lakhdar Leila , Rhissassi Meryem , Ansai Toshihiro , Yoshida Akihiro , Miyazaki Hideo
Published: December 2020

Background & Objectives

Adherence to the Mediterranean diet (MedDiet) has been reported to be associated with a lower risk of various chronic diseases. This cross‐sectional study aimed to investigate the potential association between adherence to the MedDiet and periodontitis, which is highly prevalent in young Moroccan individuals.

Methods

We evaluated 1075 Moroccan individuals (72% women, mean [standard deviation] age = 20.2 [1.5] years). Adherence to the MedDiet was assessed using the MedDiet score (MDS) based on the frequency of intake of eight food groups (vegetables, legumes, fruits, cereals or potatoes, fish, red meat, dairy products, and olive oil). A value of 0 (unhealthy) or 1 (healthy) was assigned to each food group, and the MDS (range, 0‐8 points) was generated by adding the individual scores, with a higher score indicating better adherence to the MedDiet. The logistic regression model was used to evaluate the MDS (high [5‐8 points]/low [0‐4 points]) and each component score (1/0) with the presence of periodontitis, which was determined through full‐mouth periodontal examinations. Age, sex, and oral health behavior were considered as potential confounders.

Results

In total, 693 (64.5%) study participants showed high MDSs. Periodontitis was observed in 71 (6.6%) participants. No significant association between MDS and periodontitis was observed. Nonetheless, olive oil consumption, a component of the MDS, showed a significant inverse association with periodontitis (adjusted odds ratio = 0.55; 95% confidence interval, 0.32‐0.96).

Conclusions

The MedDiet was not significantly associated with periodontitis among young Moroccans. However, frequent consumption of olive oil may have a protective effect against periodontitis, although the temporal association needs to be clarified in further studies.
Home Radon Testing in Rural Appalachia
Authors: Stanifer Stacy R. , Rayens Mary Kay , Wiggins Amanda , Gross David , Hahn Ellen J.
Published: December 2020

Purpose

This study compared differences in sociodemographic characteristics, personal risk perception of lung cancer, lung cancer worry, and synergistic risk perception among rural Appalachia residents who completed home radon testing with those who did not, after receiving a free long‐term test kit at a rural primary care clinic. The study also examined the association between the Teachable Moment Model constructs and home radon testing.

Methods

The study was an exploratory correlational design with a convenience sample of (N = 58) adult participants recruited from 2 rural primary care clinics in Appalachia Kentucky. Participants completed a brief survey and were given a free long‐term home radon test kit. Multiple logistic regression was used to determine characteristics associated with home radon testing.

Findings

Twenty‐eight participants (48%) completed home radon testing. There were no differences in personal risk perception of lung cancer, lung cancer worry, or synergistic risk perception between those who completed home radon testing and those who did not. Age was the only significant factor associated with completion of radon testing (B = 0.077, P = .005). For every 5‐year increase in age, participants were 47% more likely to test their home for radon.

Conclusion

Providing free home radon test kits in the primary care setting shows promise in prompting radon testing in rural Appalachia. As radon‐induced lung cancer risk increases with exposure over time, health care providers in rural Appalachia need to encourage patients of all ages to test their home for radon, especially those who smoke or report smoking in the home.
Species delimitation of North AmericanNyssaspecies
Authors: Yang Yan‐Ting , Yang Xu‐Chen , Wang Ming‐Cheng , Zhong Lin‐Ling , Ma Rui , Ma Tao , Liu Jian‐Quan , Davis Charles C. , Xi Zhen‐Xiang
Published: December 2020

The development of next‐generation sequencing technologies allows researchers to address complex problems in species delimitation, especially for non‐model organisms. The taxonomic status of North AmericanNyssaspecies has long been debated and remains controversial. To elucidate the genetic structure and phylogenetic relationships of the five currently recognized North AmericanNyssaspecies, we conducted whole‐genome sequencing of representative individuals and identified genome‐wide single‐nucleotide polymorphisms (SNPs) by utilizing the recently released chromosome‐level assembly ofNyssa sinensisgenome. Population genetic and phylogenetic analyses consistently inferred four well‐supported genetic clusters from our sampled individuals, that is,N. aquatica, N. ogeche, N. sylvatica, andN. biflora–N. ursina. Although the identification ofN. bifloraandN. ursinais primarily based on the morphological characteristics of leaves and drupes, the present evidence, including our principal components analysis of leaf morphological traits, strongly supports the taxonomic designation ofN. bifloraandN. ursinaas a single species. In addition, these four genetic clusters were grouped into two major clades, that is, clade 1 (N. aquaticaandN. ogeche) and clade 2 (N. sylvaticaandN. biflora–N. ursina). Despite the fact that no evidence of widespread gene flow was found between these two major clades, our analyses revealed the possibility of introgression fromN. sylvaticaintoN. biflora, albeit at a relatively low frequency. This study demonstrates the use of whole‐genome sequences as a promising avenue for delimiting species boundaries and further advocates for an integrative approach in the assessment of species delimitation.
Safe administration of drug desensitizations in pediatric patients
Authors: Herr Sarah , Ferdman Ronald , Braskett Melinda
Published: December 2020

Purpose

Patients with certain types of allergic reactions to medication may safely receive the culprit medication through an elaborate allergy procedure called a drug desensitization. Nurses play a key role in this process which is only performed when a certain medication is absolutely indicated as optimal therapy. Nurses are instrumental in the planning stages of drug desensitizations for coordination of interdisciplinary care and anticipation of adverse effects. Thus, it is paramount that nurses performing this procedure understand the mechanism of desensitizations and have access to the resources needed to safely complete these procedures in pediatric patients.

Conclusion

Excellence in nursing clinical acumen and a detailed order set are essential to patient safety during dug desensitization. With the following methodology and coordination by nursing, we have had great success at Children's Hospital Los Angeles in over one hundred drug desensitizations in pediatric patients which allowed them to received first line therapies. We have created order sets from published references and years of clinical experience. The nursing care of adult patients undergoing drug desensitization procedures is well described in the literature but few resources exist for pediatric nurses. There is paucity of published nursing resources for pediatric drug desensitizations. Repeated PubMed searches for “pediatric drug desensitizations” in 2019‐2020, revealed only one recent reference geared toward physicians.

Practice Implications

With appropriate training, staffing, and coordination, drug desensitizations can be safely performed in pediatric patients with close observation by a multi‐disciplinary team. The bedside nurse has a pivotal role as coordinator and clinician for these high‐risk resource‐intensive procedures.
Altered gene expression signatures by calcitonin gene‐related peptide promoted mast cell activity in the colon of stress‐induced visceral hyperalgesia mice
Authors: Sun Hanliang , Ma Yanhan , An Shuhong , Wang Zhaojin
Published: December 2020

Background

Calcitonin gene‐related peptide (CGRP) is possibly involved in recruitment of mucosal mast cells (MCs) in the gut that may be associated with the development of irritable bowel syndrome (IBS), but the role of CGRP on the activation of MCs is still unknown.

Methods

Using RNA sequencing (RNA‐seq), we examined differentially expressed genes (DEGs) in mouse MCs following CGRP treatment. The expression of key genes in colonic MCs and their relationship with CGRP‐containing fibers were examined by immunofluorescence in chronic water‐avoidance stress (WAS)‐induced visceral hyperalgesia mice.

Key Results

A total of 29 DEGs were found significantly changed with 28 upregulated and 1 downregulated following treatment of MCs with CGRP. Bioinformatics analysis showed that key higher DEGs included those associated with response to corticotropin‐releasing hormone (CRH), regulation of transcription, MC activation, and proliferation. These processes are enriched for genes associated with stress‐induced MC activation in IBS. Western blot verified changes in representative DEGs (Nr4a3, Crem, Gpr35, FosB, Sphlk1) and real‐time cell analysis (RTCA) verified the MC proliferation. The vast majority of colonic MCs nearly CGRP‐containing fibers in WAS mice overexpressed only Nr4a3 with little to no FosB, Gpr35, Sphlk1, or Crem expression. Nr4a3 knockdown may attenuate the promotion effect of CGRP on MC viability.

Conclusions & Inferences

Our results suggest that CGRP is a critical regulator of key expressed genes in MC activation. Nr4a3 as a novel regulator of MC function may have an effect on stress‐induced visceral hyperalgesia, and this may represent the novel target for drug development.
Trait plasticity and trade‐offs shape intra‐specific variation in competitive response in a foundation tree species
Authors: Cope Olivia L. , Lindroth Richard L. , Helm Andrew , Keefover‐Ring Ken , Kruger Eric L.
Published: December 2020

The ability to tolerate neighboring plants (i.e. degree of competitive response) is a key determinant of plant success in high‐competition environments. Plant genotypes adjust their functional trait expression under high levels of competition, which may help explain intra‐specific variation in competitive response. However, the relationships between traits and competitive response are not well understood, especially in trees. In this study, we investigated among‐genotype associations between tree trait plasticity and competitive response.

We manipulated competition intensity in experimental stands of trembling aspen (Populus tremuloides) to address the covariance between competition‐induced changes in functional trait expression and aspects of competitive ability at the genotype level.

Genotypic variation in the direction and magnitude of functional trait responses, especially those of crown foliar mass, phytochemistry, and leaf physiology, was associated with genotypic variation in competitive response. Traits exhibited distinct plastic responses to competition, with varying degrees of genotypic variation and covariance with other trait responses.

The combination of genotypic diversity and covariance among functional traits led to tree responses to competition that were coordinated among traits yet variable among genotypes. Such relationships between tree traits and competitive success have the potential to shape stand‐level trait distributions over space and time.
Atmospheric blocking events: a review
Authors: Lupo Anthony R.
Published: December 2020

Even though meteorologists have been aware of atmospheric blocking for more than 100 years, it is a phenomenon still not well forecast or completely understood. Also, while there is not one standard accepted definition, there are some commonalities known about the understanding of blocking behavior. Blocking occurs less often than other destructive phenomena, but globally their occurrence has increased since the beginning of the century. The longevity of blocking means it can negatively impact agricultural and economic activity and human comfort by bringing extreme conditions not only to the areas where they occur but also to locations well upstream and downstream. Additionally, while it is known where blocking occurs and their general character has been well described, operational models still struggle to replicate the intensity and duration even though improvement has been noted in the timing and location of onset. Climatologically, models still underestimate their occurrence. In the last 40 years, investigators have used case study analysis and numerical and theoretical models to understand the onset and maintenance of blocking. Comparatively few have examined block decay. This review endeavors to cover the highlights of the history of blocking investigations, especially in the last few decades, in order to provide an understanding for a more general scientific audience.