bluuebunny/crossref_metadata_2025 huggingface dataset:
Nurses' Electronic Medical Record Workarounds in Mental Healthcare Settings
Authors: Kweon Young-Ran , Lee Seonah
Published: May 2021

This study aimed to examine nurses' EMR workarounds in mental healthcare settings. Of the 52 nurses invited to participate in this study, 50 nurses (96.1%) completed the survey using the EMR nursing workaround instrument and open-ended questions. The data collected were analyzed using descriptive statistics and Pearson's correlation coefficients. The descriptive data were grouped into four units including the cases, contributing causes, and consequences of EMR workarounds, and suggestions for improving EMR implementation. The results showed scores above an average of 3.0 in all of the EMR workaround items, indicating the considerable involvement of nurses in EMR workarounds. The workarounds related to EMR use were using the physician's login account for medication access, performing retrospective documentation, performing documentation before an expected busy situation, and seeking and entering information on external medications. The workarounds associated with colleagues unfamiliar with EMR use included waiting for, filling in for, teaching, and assisting unskilled colleagues. This study identified the problems, consequences, and suggestions associated with EMR implementation for psychiatric patient care. This study added useful information for the administrative, technical, and clinical improvement of EMR implementation in mental healthcare practice.
Management Strategies for Patients With Epithelioid Hemangioendothelioma
Authors: Yurkiewicz Ilana R. , Zhou Maggie , Ganjoo Kristen N. , Charville Gregory W. , Bolleddu Sanjana , Lohman Marti , Bui Nam
Published: May 2021

Background:

Epithelioid hemangioendothelioma (EHE) is a malignant vascular neoplasm representing ∼1% of sarcomas. Due to its rarity, its clinical course is not well characterized and optimal treatment remains unknown.

Materials and Methods:

This was a retrospective review of patients with EHE treated at Stanford University between 1998 and 2020. Demographic characteristics, pathology results, treatment modalities, and clinical outcomes were collected from the electronic medical records.

Results:

A total of 58 patients had a mean age of 50.6 years and a slight female predominance (52%). Primary disease sites were liver (33%), soft tissue (29%), lung (14%), bone (9%), and mediastinum (9%). A majority (55%) had advanced or metastatic disease. Median overall survival (OS) was 16.9 years, with OS 89% at 1 year, 68% at 5 years, and 64% at 10 years. The longest median OS was associated with soft tissue sites and shortest with lung and mediastinal disease (P=0.03). The localized disease had improved median OS compared with metastatic disease (P=0.02). There was no OS difference between tumors >3 cm and those equal or smaller (P=0.85). Surgery was a common treatment (71%), while radiation and ablation were sometimes used (28% and 9%, respectively). The median time to initiating therapy of any kind was 68 days. The median time to systemic therapy was 114 days.

Conclusions:

We report on the clinical characteristics and outcomes of patients with EHE at a large academic center. Treatment options included surgical excision, liver transplant, ablation, radiation, and systemic therapy. A subset of patients had indolent disease not requiring treatment upfront.
Home-Based Reiki by Informal Caregivers
Authors: Chen Yea-Jyh , Petrinec Amy , Stephenson Pamela S. , Radziewicz Rosanne M. , Sheehan Denice
Published: May 2021

This pilot study explored whether Reiki delivered by family caregivers to cancer patients in a home setting was feasible in reducing cancer symptoms and enhancing health-related outcomes. An explanatory sequential mixed-methods study design was applied using pre-/post-Reiki questionnaires and post-Reiki interviews. Six patient-caregiver dyads from an outpatient clinic and cancer support facilities in northeast America performed daily Reiki at home for 3 weeks. Differences with symptoms, mental well-being, health-related quality of life, and satisfaction with at-home Reiki as well as qualitative content analyses were evaluated. Positive feedback was reported after at-home Reiki practice. Large statistical effects were identified for improving fatigue, memory, mood, nausea, and emotional well-being (P < .10, r = 0.51-0.59). All participants were satisfied and 83.3% of them would recommend self-practice home Reiki. High involvement and adherence to the intervention protocol illustrated intervention fidelity. The qualitative data revealed 2 major categories, perceived benefits and barriers. Overall Reiki benefits outweighed barriers in relation to time commitment and place distractions/positioning. Our preliminary findings support that the at-home Reiki protocol had potential benefits and was feasible and acceptable by both community-dwelling patients and their family caregivers in promoting cancer-related outcomes. Further studies with larger samples are warranted to examine the effectiveness of home-based Reiki for a patient-centered cancer care modality.
Trypan-Assisted Automated Endothelial Cell Loss Measurements Compared With Specular Microscopy
Authors: Bedard Peter , Justin Jeff J. , Hou Joshua H.
Published: May 2021

Purpose:

The aims of this study were 1) to compare area of cell loss (ACL) on trypan staining with ACL on specular imaging and 2) to evaluate the use of automated software for measuring ACL on trypan staining.

Methods:

Donor corneas with transplant-grade endothelium were mechanically injured with an 18-gauge cannula and a Fogla deep anterior lamellar keratoplasty dissector tip to create an easily identifiable “bullseye” pattern of cell death. Each cornea was then stained with trypan blue 0.06% for 90 seconds and imaged at 2× magnification. ACL on staining was measured using manual (ImageJ, National Institute of Health, Bethesda, MD) versus automated software tools (custom-built Aphelion macro, ADCIS, S.A., Saint-Contest, France). The bullseye was then imaged using specular microscopy, and ACL was measured by tracing the dead cell borders. ACL was then compared between both modalities.

Results:

Eleven donor corneas were evaluated. Both manual (0.42 mm2) and automated (0.45 mm2) measurements of ACL after trypan staining underestimated mean ACL on specular imaging (0.54 mm2) (P < 0.01). However, on regression analysis, there was a good predictive correlation between automated trypan measurements and specular imaging (R2 = 0.99, residual SE = 0.0044, P < 0.01). When ACL on specular imaging was measured by tracing cell nuclei along the margin of injury (rather than cell borders) (0.45 mm2), there was no statistically significant difference between specular and automated trypan measurements (P = 0.95).

Conclusions:

Trypan-assisted automated measurements of ACL correlated well with ACL on specular imaging, suggesting that automated software may be a useful tool for evaluating endothelium in donor corneas.
Long-Term Results and Refractive Error After Cataract Surgery With a Scleral Incision in Eyes With Deep Anterior Lamellar Keratoplasty
Authors: Tourabaly Moïse , Knoeri Juliette , Georgeon Cristina , Borderie Marie , Bouheraoua Nacim , Borderie Vincent
Published: May 2021

Purpose:

Phacoemulsification in eyes with deep anterior lamellar keratoplasty (DALK) is associated with possible decreased graft survival and difficult IOL power calculation. We assessed cataract surgery in eyes with previous DALK.

Methods:

Thirty-three consecutive eyes with DALK and further phacoemulsification with scleral incision were included in this retrospective study. At each postoperative visit, eyes were assessed with manifest refraction, optical coherence tomography, specular corneal topography, and noncontact wide-field specular microscopy.

Results:

The average postkeratoplasty follow-up time was 102 months [95%-CI, (85–119)]. Cataract surgery was performed on average 43 months (30–56) after DALK. The average postphacoemulsification follow-up time was 58 months [42–74]. All grafts remained clear during follow-up. The best spectacle-corrected logarithm of the minimum angle of resolution visual acuity improved by 2.5 lines [1.8–3.1] on average after cataract surgery from 0.58 (20/77) to 0.34 (20/44) (P < 0.001). The spherical equivalent and intraocular pressure significantly improved from −4.1 D to −1.7 D and from 15.9 to 14.0 mm Hg, respectively. The corneal central thickness was not significantly modified, and the endothelial density decreased by 5.3% from 2081 to 1970 cells/mm2 (P = 0.003). The minimal difference between the achieved and predicted spherical equivalents [−0.05 D, (−2.33; +2.21)] was obtained with the Hoffer Q formula using the IOLMaster axial length and the Orbscan keratometry.

Conclusions:

Patients with DALK who underwent phacoemulsification with a scleral incision had a satisfying residual refractive error, very high graft survival, and very few complications. The Hoffer Q formula with the IOLMaster axial length and the specular corneal topography keratometry seems to be the most accurate for IOL calculation.
A Scoping Review of the Knowledge Base, Landscape, and Trends in Leadership Literature in Early Intervention, Early Childhood, and Early Childhood Special Education
Authors: Movahedazarhouligh Sara
Published: May 2021

Effective leadership is regarded as pivotal to the vitality of organizations. In early childhood programs, strong leadership is particularly critical because program leaders are the gatekeepers of quality. However, the fields of early intervention, early childhood, and early childhood special education (EI/EC/ECSE) continue to struggle with the challenges of being overlooked regarding leadership research, potentials, qualities, and abilities. This scoping review aimed to identify and synthesize the available evidence by understanding the nature and extent of leadership literature in EI/EC/ECSE between 2000 and 2018. Collectively, 1,416 articles were reviewed. A total of 106 articles that met the inclusion criteria were summarized using a number of variables. The review confirmed the long existing paucity of leadership research in EC and more specifically in EI and ECSE with specific findings in terms of research scopes and approaches. Presentation and discussion of findings along with implications for future research are provided.
Analysis of Trends and Outcomes of 90 and 180 Day Readmissions After Left Ventricular Assist Device Implantation
Authors: Briasoulis Alexandros , Ueyama Hiroki , Kuno Toshiki , Asleh Rabea , Briasouli Artemis , Doulamis Ilias , Malik Aaqib H.
Published: May 2021

Despite decreasing morbidity and mortality in left ventricular assist device (LVAD) recipients, readmission after implantation remains a major problem. Our aim was to investigate the trends and outcomes of 90 and 180 day readmission in this population. The National Readmission Database from 2012 to 2017 was queried to identify LVAD recipients. A total of 5,907 adults (90 day readmissions) and 3,653 adults (180 day readmissions) who survived LVAD implantation during the index admission were included in our analysis. Readmissions occurred in 45.6% and 65.1% by 90 and 180 days, respectively, with most readmissions occurring within the first 20 days. During the study period, mortality at index admission and readmission rate after discharge from index admission remained stable, whereas mortality during the readmission declined overtime both at 90 and 180 days. Heart failure was the most common cause for readmission (both 90 and 180 days), while its incidence also increased over the years. Among the reasons for readmission, intracranial bleeding, ischemic stroke, and device thrombosis were associated with highest mortality and gastrointestinal bleeding with the lowest. Intracranial bleeding, device thrombosis, and device infection were associated with longer length of stay. Multivariate logistic regression models identified gastrointestinal bleeding, length of stay during index admission, and end-stage renal disease requiring hemodialysis as risk factors of readmissions. Our study has unveiled several important factors associated with readmission and mortality. Approaches to identify and prevent readmissions early after LVAD implantation by addressing these factors may lead to lower morbidity, healthcare cost related to readmission, and improved quality of life.
Impact of CytoSorb Hemoadsorption on Sedation Requirements in Patients With Severe COVID-19 on Venovenous Extracorporeal Membrane Oxygenation
Authors: Lewis Tyler C. , Merchan Cristian , Toy Bridget , Goldenberg Ronald M. , Geraci Travis C. , Chang Stephanie H. , Galloway Aubrey C. , Smith Deane E. , Moazami Nader
Published: May 2021

Hemoadsorption with CytoSorb has been used as an adjunct in the treatment of severe coronavirus disease 2019 (COVID-19)-related respiratory failure. It remains unknown if CytoSorb hemoadsorption will alter sedative and analgesic dosing in critically ill patients on venovenous extracorporeal membrane oxygenation (VV-ECMO). We conducted a retrospective review of patients with severe COVID-19 requiring VV-ECMO for respiratory support. Patients who were enrolled in a clinical study of CytoSorb were compared with patients on VV-ECMO alone. Data were collected for the 72-hour CytoSorb therapy and an additional 72 hours post-CytoSorb, or a corresponding control time period. Sedative and analgesic doses were totaled for each day and converted to midazolam or fentanyl equivalents, respectively. The primary endpoint, change in sedative and analgesic requirements over time, were compared using a two-way mixed analysis of variance. Of the 30 patients cannulated for VV-ECMO for COVID-19, 4 were excluded, leaving 8 patients in the CytoSorb arm and 18 in the Control. There was no effect of CytoSorb therapy on midazolam equivalents over the 72-hour therapy (p = 0.71) or the 72 hours post-CytoSorb (p = 0.11). In contrast, there was a significant effect of CytoSorb therapy on fentanyl equivalents over the first 72 hours (p = 0.01), but this was not consistent over the 72-hours post-CytoSorb (p = 0.23). CytoSorb therapy led to significant increases in analgesic requirements without impacting sedative requirements. Further research is needed to define the relevance of CytoSorb hemoadsorption on critical care pharmacotherapy.
Treatment of Severe Acute on Chronic Liver Failure
Authors: Vipani Aarshi , Lindenmeyer Christina C. , Sundaram Vinay
Published: May 2021

Acute on chronic liver failure (ACLF) is a unique syndrome that afflicts patients with chronic liver disease and results in high short-term mortality, in the setting of organ system failures. Given this prognosis, there is an urgent need to understand risk factors for this condition, for appropriate medical management of organ failures, and for selection criteria for patients who may benefit from liver transplantation (LT). Although several definitions exist to identify ACLF, all of them are designed to identify patients with uniquely high mortality. Currently, management of severe ACLF relies on best supportive care for specific organ failures. Thromboelastography should guide the evaluation of coagulation pathways and hyperfibrinolysis in ACLF; prophylactic blood product transfusions and thrombopoetin agonists are not recommended. Combination therapy with terlipressin and albumin has been shown to be efficacious in the management of the hepatorenal syndrome but should be administered with caution in patients with ACLF-3. Recent data have characterized the role of beta-blockers and transjugular intrahepatic portosystemic shunt placement in the management of ACLF. Investigational therapies such as extracorporeal liver support and hepatocyte stem cell therapies have shown promise; larger scale studies may better define the subpopulations of patients with ACLF mostly likely to benefit from these evolving therapeutics. Regarding LT in ACLF, data suggest that even patients with 3 or more organ system failures may have a 1-year survival >80%. However, further efforts are needed to understand the predictors of post-LT survival to facilitate LT criteria for this condition.
Intestinal phosphorus absorption: recent findings in translational and clinical research
Authors: Hill Gallant Kathleen M. , Vorland Colby J.
Published: May 2021

Purpose of review

The purpose of this review is to discuss recent findings in intestinal phosphorus absorption pathways, particularly the contributions of paracellular versus transcellular absorption, and the differential findings from studies using in vitro versus in vivo techniques of assessing phosphorus absorption in experimental animal studies.

Recent findings

Experimental animal studies show that in vivo effects of low phosphorus diets, 1,25D, and chronic kidney disease on intestinal phosphorus absorption efficiency contradict effects previously established ex vivo/in vitro. Recent in vivo studies also suggest that the paracellular pathway accounts for the majority of phosphorus absorption in animals across very low to high luminal phosphate concentrations. The data from experimental animal studies correspond to recent human studies showing the effectiveness of targeted inhibition of paracellular phosphate absorption. Additionally, recent human studies have demonstrated that NaPi-2b inhibition alone does not appear to be effective in lowering serum phosphate levels in patients with chronic kidney disease. Pursuit of other transcellular phosphate transporter inhibitors may still hold promise.

In vivo animal and human studies have added to our understanding of intestinal phosphorus absorption pathways, regulation, and mechanisms. This is beneficial for developing effective new strategies for phosphate management in patients with chronic kidney disease.
Effects of Risk Factors on In Situ Expression of Proinflammatory Markers Correlated to Carotid Plaque Instability
Authors: Montanaro Manuela , Scimeca Manuel , Toschi Nicola , Bonanno Elena , Giacobbi Erica , Servadei Francesca , Ippoliti Arnaldo , Santeusanio Giuseppe , Mauriello Alessandro , Anemona Lucia
Published: May 2021

Background and Aims:

Several studies demonstrated a role of active chronic inflammatory infiltrate in carotid plaques progression suggesting a possible link between cardiovascular risk factors and inflammation-related plaque instability. The aim of this study is therefore to evaluate the possible effects of cardiovascular risk factors on in situ expression of proinflammatory markers associated with carotid plaque instability.

Methods and Results:

A tissue microarray containing carotid plaques from 36 symptomatic (major stroke or transient ischemic attack) and 37 asymptomatic patients was built. Serial sections were employed to evaluate the expression of some inflammatory markers by immunohistochemistry [CD3, CD4a, CD8, CD20, CD86, CD163, interleukin (IL)-2, IL-6, IL-17]. Immunohistochemical data were analyzed to study the possible associations between in situ expression of inflammatory biomarker and the main cardiovascular risk factors. Our data demonstrated that plaque instability is associated with the high in situ expression of some cytokines, such as IL-2, IL-6, IL-17. Besides the female sex, none of the risk factors analyzed showed a significant association between the in situ expression of these markers and unstable plaques. A significant increase of IL-6-positive and IL-17-positive cells was observed in unstable atheromatous plaques of female patients, as compared with unstable plaques of male patients.

Conclusions:

Plaque destabilization is certainly correlated with the presence of the major cardiovascular risk factors, however, our results showed that, with the exception of sex, their action in the evolutive process of plaque instability seems rather nonspecific, favoring a general release of proinflammatory cytokines.
Axillary Glomus Tumor Revealed by FDG PET/CT
Authors: Shen Guohua , Wang Rang , Pan Lili , Kuang Anren
Published: May 2021

Glomus tumors are vascular neoplasms arising from glomus bodies. They are typically found in tissues where glomus bodies are concentrated, including the subungual layer of the fingers or the deep dermis of the palm, wrist, forearm, and foot but rarely occur in the axillary region. Herein, we reported the MRI and FDG PET/CT findings of a glomus tumor presenting as an axillary mass in a 25-year-old woman.
Increased Uptake of 18F-THK5351 in Glioblastoma But Not in Primary Central Nervous System Lymphoma
Authors: Mitamura Katsuya , Norikane Takashi , Yamamoto Yuka , Miyake Keisuke , Nishiyama Yoshihiro
Published: May 2021

18F-THK5351 was initially developed to target tau aggregates in neurofibrillary tangles. However, it was also shown to bind to an enzyme, monoamine oxidase B, which is highly expressed in the outer mitochondrial membrane of astrocytes. In a case with glioblastoma, both l-[methyl-11C]-methionine PET and 18F-THK5351 PET showed increased uptake in the tumor. On the other hand, in another case with primary central nervous system lymphoma, l-[methyl-11C]-methionine PET showed increased uptake in the tumor, but 18F-THK5351 PET showed no abnormal uptake in the tumor. 18F-THK5351 PET might be helpful in differentiating between glioblastoma and primary central nervous system lymphoma.
The Importance of SPECT/CT in Preoperative Localization of Sentinel Lymph Nodes in 2 Patients With Acral Melanoma in the Foot
Authors: Zhang Shu , Zhu Shikun , Hua Surong , Zou Xiongfei , Luo Yaping
Published: May 2021

A 68-year-old woman with melanoma in the left heel underwent sentinel node lymphoscintigraphy and radioguided biopsy. The sentinel node lymphoscintigraphy with SPECT/CT detected 3 foci of increased activity in the popliteal fossa and inguinal region. When coregistered to CT, the sentinel node was localized in the inguinal region, and the popliteal foci were considered tracer retention in lymphatic vessel. In another patient with melanoma in the foot, sentinel node lymphoscintigraphy detected 3 foci of increased activity in the popliteal fossa and inguinal region, which were all identified to be nodal uptake in SPECT/CT. The sentinel node was finally localized in popliteal fossa in this patient.
Facial Suture Pathology in Syndromic Craniosynostosis
Authors: Wang Maxwell M. , Haveles Christos S. , Zukotynski Brian K. , Reid Russell R. , Lee Justine C.
Published: May 2021

Background

Facial deformities in syndromic craniosynostosis are not only functionally, psychosocially, and aesthetically impairing but also notoriously challenging to reconstruct. Whether facial suture synostosis plays a significant role in the pathogenesis of these deformities is inadequately studied in human patients.

Methods

The MEDLINE database was queried using a methodologically generated search term inventory. Article inclusion was adjudicated by 2 authors after independent review. Articles provided insight into facial suture involvement in either syndromic craniosynostosis patients or animal models of disease.

Results

Comprehensive review yielded 19 relevant articles meeting inclusion criteria. Mid-20th century craniofacial biologists characterized how patent facial sutures are essential for normal postnatal facial development. They also posited that premature ossification disrupts growth vectors, causing significant dysmorphologies. Recently, facial suture synostosis was found to cause midfacial deformities independent of cranial base pathology in mouse models of syndromic craniosynostosis. Few recent studies have begun exploring facial suture involvement in patients, and although they have paved the way for future research, they bear significant limitations.

Conclusions

The hypothesis that facial suture synostosis acts in conjunction with cranial base pathology to produce the prominent, multifocal facial deformities in syndromic craniosynostosis may fundamentally alter surgical management and warrants further investigation. Methodically evaluating the literature, this review synthesizes all basic science and human clinical research thus far on the role of facial sutures in syndromic craniosynostosis and elucidates important topics for future research. We ultimately identify the need for rigorous imaging studies that longitudinally evaluate facial osteology across patients with various craniosynostosis syndromes.
Oncologic Safety of Immediate Breast Reconstruction
Authors: Hammer Jennifer , Servaes Maxime , Berners Aline , Deconinck Christine , Pirson Geneviève , Fosseprez Philippe
Published: May 2021

Objective

The purpose of this study was to assess the oncologic safety of mastectomies associated with immediate breast reconstruction (IBR) in terms of recurrence and survival.

Methods

A retrospective review was conducted at a single center (CHU UCL Namur, Belgium). We analyzed the oncologic safety of IBR for patients with invasive and in situ breast cancer who underwent mastectomy associated with IBR. Patients who underwent palliative surgery and those with a diagnosis of breast sarcoma were excluded.

Results

We retrospectively analyzed 138 patients who underwent mastectomy and IBR between January 2012 and December 2019. Most reconstruction procedures used deep inferior epigastric perforator free flaps (55.1%). The reconstructive failure rate was 8.7%. Among the patients included, 5 cases of local cancer recurrence, 1 case of local cancer recurrence associated with distant metastasis, and 2 cases of systemic recurrence were identified during a mean follow-up of 49.3 months (range, 8–104 months) after surgery. Overall survival was 97.8%, and disease-free survival was 94.2%.

Conclusions

Patients had a low incidence of cancer recurrence in this review. Immediate breast reconstruction after mastectomy had no negative impact on recurrence or patient survival, even in patients with advanced disease. The study findings suggest that mastectomy associated with IBR can be a safe surgical option for patients with invasive and noninvasive breast cancers. Longer follow-ups are needed to confirm these preliminary results.
The Learning Curve
Authors: Le Nicole K. , Weinstein Brielle , Serraneau Karisa , Tavares Tina , Laronga Christine , Panetta Nicholas
Published: May 2021

Background

Cancer-related lymphedema will affect 10% to 50% of breast cancer survivors. Early data show that immediate lymphatic reconstruction may help prevent breast cancer lymphedema; however, the details have not been fully elucidated. The purpose of this study was to evaluate the cohort of our first 100 patients for trends in demographics, treatment, and technique.

Methods

At a tertiary care cancer center, high-risk breast cancer–related lymphedema patients underwent axillary reverse lymphatic mapping and immediate lymphatic reconstruction. After institutional review board approval, demographics, technique, and outcomes were recorded. The first 100 patients were analyzed to compare the differences between the first 50 versus the second 50 patient cohorts.

Results

Of the first 100 axillary reverse lymphatic mapping performed, there was a significant difference in neoadjuvant chemotherapy with 81% in the earlier cohort versus 98% in the later cohort (P = 0.01). An arborized technique was used more frequently in the second cohort (82% vs 54%, P = 0.01). The incidence of lymphedema was lower in the latter cohort (7 patients vs 1 patient, P = 0.03). The first cohort was 12.2 times more likely to develop lymphedema despite lymphatic reconstruction than the second cohort (P = 0.03).

Conclusions

The data demonstrate multiple trends in the learning curve associated with immediate lymphatic reconstruction at a single institution including improvements in identifying and dissecting lymphatic structures, performing more anastomoses per patient, using the arborized technique more frequently, performing the operation with shorter operative times, and reducing the incidence of lymphedema.
ABCC1 regulates cocaine-associated memory, spine plasticity and GluA1 and GluA2 surface expression
Authors: Chen Limei , Chen He , Xing Yanli , Li Juan
Published: May 2021

ATP-binding cassettes C1 (ABCC1s) are expressed in the neurons of the brain, but their function in neurological diseases is far from clear. In this study, we investigated the role of ABCC1 in the hippocampus in cocaine-associated memory and spine plasticity. We also investigated the role of ABCC1 in AMPA receptors (AMPARs) surface expression in primary prefrontal cortex (PFC) neurons following dopamine treatment, which was used to mimic exposure to cocaine. We found that cocaine increased ABCC1 expression in the hippocampus, and ABCC1-siRNA blocked cocaine-induced place preference. Furthermore, a morphological study showed that ABCC1-siRNA reduced the total spine density, including thin, stubby and mushroom spines in both cocaine and basal treatments compared with controls. Meanwhile, in vitro tests showed that ABCC1-siRNA decreased GluA1 and GluA2 surface expression induced by dopamine, while a decreased number of synapses in primary PFC neurons was observed following dopamine treatment. The data show that ABCC1 in the hippocampus is critically involved in cocaine-associated memory and spine plasticity and that dopamine induces AMPARs surface expression in primary PFC neurons. ABCC1 is thus presented as a new signaling molecule involved in cocaine addiction, which may provide a new target for the treatment of cocaine addiction.
Enteric glial cells exert neuroprotection from hyperglycemia-induced damage via Akt/GSK3β pathway
Authors: Luo Pan , He Wen-Xi , Li Cai , Chang Mu-Jun
Published: May 2021

Objective

Enteric glial cells (EGCs) can activate multiple pathways to inhibit the deleterious effects of acute and chronic insults. Our aim was to test the effect of EGCs on hyperglycemia-induced neuron damage and its underlying intracellular mechanisms.

Methods

A coculture model composed of EGCs and neuroblastoma cells (SH-SY5Y) was established to examine glial-mediated neuroprotection under high glucose conditions. The cell counting assay kit CCK-8 was used to measure cell viability. Flow cytometry was used to measure the induction of reactive oxygen species (ROS), change of mitochondrial membrane potential (MMP), cell cycle distribution, and apoptosis. The expressions of cyclin D1, cyclin E2, Bax, cleaved caspase-3, AKT, p-AKT, GSK-3β, and p-GSK-3β were tested using western blot.

Results

Exposure to high glucose (≥35 mM) reduced the viability of SH-SY5Y cells in a concentration- and time-dependent manner. Meanwhile, enhanced ROS generation and decrease of MMP were observed in SH-SY5Y cells when treated with high glucose. Furthermore, high glucose also caused SH-SY5Y cells arrest in G2 phase and apoptosis, accompanied by decreasing cyclin D1 and E2, and upregulating Bax and cleaved caspase-3. Coculture EGC lines or EGC-conditioned medium with SH-SY5Y prevented the neurotoxic effects. The p-AKT/AKT and p-GSK-3β/GSK-3β ratios were dramatically decreased in SH-SY5Y cells after high glucose incubation, which was restored after coculture with EGCs.

Conclusions

EGCs can protect neurons from hyperglycemia-induced injury by activating the Akt/GSK-3β pathway.
Case report: asenapine and anticholinergic toxicity
Authors: Sheehan Ann Kathleen , Richards-Bentley Christopher , Hawa Raed J. , Rasimas Joseph J.
Published: May 2021

While antipsychotic medications have long been associated with anticholinergic effects, asenapine has been purported to have no capacity for muscarinic cholinergic antagonism based on in vitro studies. Research in rat brain tissue has yielded different results, with one study finding more cholinergic M1-5 binding in the medial prefrontal cortex, dorsolateral frontal cortex and hippocampal CA1 and CA3 areas than would be predicted from in vitro findings. Moreover, it is structurally similar to other anticholinergic antipsychotics such as loxapine and, to a lesser degree, quetiapine, olanzapine and clozapine. This case report describes the anticholinergic toxidrome in a patient treated with benztropine and paroxetine at stable doses, with the emergence of the toxidrome after upward titration of asenapine. A broad differential was considered. With further consideration of the history, time-course, clinical features and physical examination, the presentation is most indicative of the anticholinergic toxidrome. Although not employed, physostigmine, the antidote for anticholinergic delirium, could help to differentiate this toxidrome and serve as a diagnostic and therapeutic intervention. We have presented this case to highlight the importance for clinicians to integrate history and bedside examination data with principles of pharmacology. In particular, asenapine should be added to the list of compounds with recognized anticholinergic potential.
Stress minimization for lattice structures. Part I: Micro-structure design
Authors: Ferrer A. , Geoffroy-Donders P. , Allaire G.
Published: May 2021

Lattice structures are periodic porous bodies which are becoming popular since they are a good compromise between rigidity and weight and can be built by additive manufacturing techniques. Their optimization has recently attracted some attention, based on the homogenization method, mostly for compliance minimization. The goal of our two-part work is to extend lattice optimization to stress minimization problems two-dimensionally. The present first part is devoted to the choice of a parametrized periodicity cell that will be used for structural optimization in the second part of our work. In order to avoid stress concentration, we propose a square cell microstructure with a super-ellipsoidal hole instead of the standard rectangular hole often used for compliance minimization. This type of cell is parametrized two-dimensionally by one orientation angle, two semi-axis and a corner smoothing parameter. We first analyse their influence on the stress amplification factor by performing some numerical experiments. Second, we compute the optimal corner smoothing parameter for each possible microstructure and macroscopic stress. Then, we average (with specific weights) the optimal smoothing exponent with respect to the macroscopic stress. Finally, to validate the results, we compare our optimal super-ellipsoidal hole with the Vigdergauz microstructure which is known to be optimal for stress minimization in some special cases.

This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Some open problems in the theory of composites
Authors: Milton Graeme W.
Published: May 2021

A selection of open problems in the theory of composites is presented. Particular attention is drawn to the question of whether two-dimensional, two-phase composites with general geometries have the same set of possible effective tensors as those of hierarchical laminates. Other questions involve the conductivity and elasticity of composites. Finally, some future directions for wave and other equations are mentioned.

This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Mathematical problems of nematic liquid crystals: between dynamical and stationary problems
Authors: Zarnescu Arghir
Published: May 2021

Mathematical studies of nematic liquid crystals address in general two rather different perspectives: that of fluid mechanics and that of calculus of variations. The former focuses on dynamical problems while the latter focuses on stationary ones. The two are usually studied with different mathematical tools and address different questions. The aim of this brief review is to give the practitioners in each area an introduction to some of the results and problems in the other area. Also, aiming to bridge the gap between the two communities, we will present a couple of research topics that generate natural connections between the two areas.

This article is part of the theme issue ‘Topics in mathematical design of complex materials’.
Reclassification of Streptomyces cinnamonensis as a later heterotypic synonym of Streptomyces virginiae
Authors: Komaki Hisayuki , Tamura Tomohiko
Published: May 2021

We studied the taxonomic relationship between

Streptomyces cinnamonensis

and

Streptomyces virginiae

. These type strains shared the same 16S rRNA gene sequence. Phylogenomic analysis supported them being closely related. Digital DNA–DNA relatedness and average nucleotide identity using whole genome sequences indicated that the two species represent the same genomospecies. They shared similar phenotypic characteristics and harboured the same set of secondary metabolite-biosynthetic gene clusters for polyketides and nonribosomal peptides in the genomes. Therefore, according to Rule 24b of the Bacteriological Code,

S. cinnamonensis

Okami 1952, 572AL (Approved Lists 1980) should be reclassified as a later heterotypic synonym of

S. virginiae

Grundy et al. 1952, 399AL (Approved Lists 1980) emend. Nouioui et al. 2018. Although 16S rRNA gene sequences were identical among type strains of

Streptomyces xanthophaeus

,

Streptomyces spororaveus

and

Streptomyces nojiriensis

and between those of

Streptomyces vinaceus

and

Streptomyces cirratus

, respectively, digital DNA–DNA relatedness indicated that these species are not synonymous.
ACTIVATE-2: A DOUBLE-BLIND RANDOMIZED TRIAL OF BCG VACCINATION AGAINST COVID19 IN INDIVIDUALS AT RISK
Authors: Tsilika Maria , Taks Esther , Dolianitis Konstantinos , Kotsaki Antigone , Leventogiannis Konstantinos , Damoulari Christina , Kostoula Maria , Paneta Maria , Adamis Georgios , Papanikolaou Ilias C. , Stamatelopoulos Kimon , Bolanou Amalia , Katsaros Konstantinos , Delavinia Christina , Perdios Ioannis , Pandi Aggeliki , Tsiakos Konstantinos , Proios Nektarios , Kalogianni Emmanouela , Delis Ioannis , Skliros Efstathios , Akinosoglou Karolina , Perdikouli Aggeliki , Poulakou Garyfallia , Milionis Haralampos , Athanassopoulou Eva , Kalpaki Eleftheria , Efstratiou Leda , Perraki Varvara , Papadopoulos Antonios , Netea Mihai G. , Giamarellos-Bourboulis Evangelos J.
Published: May 2021

BCG vaccination induces heterologous protection against respiratory tract infections, and in children improves survival independently of tuberculosis prevention. The phase III ACTIVATE-2 study assessed whether BCG could also protect against COVID19 in the elderly. In this double-blind, randomized trial, elderly Greek patients were randomized (1:1) to receive either BCG revaccination or placebo at hospital discharge, followed by 6 months observation for incidence of COVID19 infection. BCG revaccination resulted in 68% risk reduction for total COVID19 clinical and microbiological diagnoses (OR 0.32, 95% CI 0.13-0.79). Five patients in the placebo group and one in the BCG-vaccinated group had severe COVID19 that necessitated hospitalization. 3 months after BCG vaccination 1.3% of placebo and 4.7% of BCG-vaccinated volunteers had anti-SARS-CoV-2 antibodies. These data argue that BCG revaccination is safe and protects the elderly against COVID19. BCG revaccination may represent a viable preventive measure against COVID19.
Aerosol transport measurements and assessment of risk from infectious aerosols: a case study of two German cash-and-carry hardware/DIY stores
Authors: Hejazi Bardia , Schlenczek Oliver , Thiede Birte , Bagheri Gholamhossein , Bodenschatz Eberhard
Published: May 2021

We report experimental results on aerosol dispersion in two large German cash- and-carry hardware/DIY stores to better understand the factors contributing to disease transmission by infectious human aerosols in large indoor environments. We examined the transport of aerosols similar in size to human respiratory aerosols (0.3 µm–10 µm) in representative locations, such as high-traffic areas and restrooms. In restrooms, the observed decay of aerosol concentrations was consistent with well-mixed air exchange. In all other locations, fast decay times were measured, which were found to be independent of aerosol size (typically a few minutes). From this, we conclude that in the main retail areas, including at checkouts, rapid turbulent mixing and advection is the dominant feature in aerosol dynamics. With this, the upper bound of risk for airborne disease transmission to a susceptible is determined by direct exposure to the exhalation cloud of an infectious. For the example of the SARS-CoV-2 virus, we find when speaking without a face mask and aerosol sizes up to an exhalation (wet) diameter of 50 µm, a distance of 1.5 m to be unsafe. However, at the smallest distance between an infectious and a susceptible, while wearing typical surgical masks and for all sizes of exhaled aerosol, the upper bound of infection risk is only ∼5% and decreases further by a factor of 100 (∼0.05%) for typical FFP2 masks for a duration of 20 min. This upper bound is very conservative and we expect the actual risk for typical encounters to be much lower. The risks found here are comparable to what might be expected in calm outdoor weather.
Unawareness for chronic kidney disease is high in all stages, age groups and comorbidities – and higher in women than in men
Authors: Stolpe Susanne , Kowall Bernd , Scholz Christian , Stang Andreas , Blume Cornelia
Published: May 2021

Background

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular events, hospitalizations or mortality. In populations aged ≥40 years, CKD is as prevalent as diabetes or coronary heart disease. Awareness for CKD though is generally low in public, patients and physicians, which hinders early diagnosis and treatment to decelerate disease progress.

Method

We analyzed baseline data collected in 2010 from 3,334 participants with CKD stages 1-5 from German CKD cohorts and registries. CKD unawareness and 95%-confidence intervals (CI) was estimated according to patients’ answer to the question whether they had ever been told to suffer from a CKD. Prevalence ratios (PR) with 95%-CI were estimated in categories of age, sex, CKD stages, BMI, hypertension, diabetes and other relevant comorbidities.

Results

CKD unawareness was high, reaching 82% (95% CI: 80%-84%) for CKD stages 1 or 2, 71% (68%-73%) in CKD 3a, 49% (45%-54%) in CKD 3b and still 30% (24%-36%) in CKD4, in each stage increasing with age. CKD unawareness was similarly high in patients with hypertension, diabetes or cardiovascular comorbidities. Women were more often unaware than men (PR=1.07 (1.02;1.12)), this sex difference increased with increasing CKD stage. Macroalbuminuria (PR=0.90 (0.82; 1.00)), anemia (PR=0.78 (0.73; 0.83)) and BMI ≥40 (PR=0.88 (0.77; 1.00)) were associated with higher CKD awareness.

Conclusion

Even in older patients or in patients with comorbidities, CKD unawareness was high. Sex differences were largest in later stages. Guideline oriented treatment of patients with hypertension or diabetes could increase awareness. Patient-physician communication about CKD might be amendable.
Conflicts of Interest of Pediatric Journal Authors
Authors: Petlansky Rebecca L , Bekoe-Tabiri Amadea D , Bueno Vanessa N , Onwuka AnnMarie N , Gionfriddo Michael R , Piper Brian J
Published: May 2021

The Physician Payments Sunshine Act requires disclosure of payments made by drug and medical device manufacturers to physicians or teaching hospitals. Academic literature extensively documents gender disparities in the medical profession with regard to salary, promotion, and government funded research. This investigation sought to quantify potential conflicts of interest (CoIs) in pediatric medical journals, specifically examining sex differences. To identify potential CoIs, we examined manuscripts published prior to 2019 in six pediatric journals (JAMA Pediatrics, Pediatrics, The Journal of Pediatrics, Pediatric Blood and Cancer, Pediatric Critical Care Medicine, and The Pediatric Infectious Disease Journal). We collected physician demographics and specialty from the National Plan and Provider Enumeration System National Provider Identifier Registry and compensation data from both ProPublica’s Dollars for Docs (PDD) and Centers for Medicare and Medicaid Services Open Payments (CMSOP). Data was collected on 2,747 authors from 929 manuscripts. Of the 1,088 authors based in the United States with medical degrees (40.5% female), 510 (46.9%) had entries in PDD and CMSOP. Overall, 11,791 payments to these physician-authors totaled $9,586,089.97. Males were 19.6% more likely to receive payments (RR = 1.20, 95% CI [1.05, 1.37], p = 0.008). The mean amount received by males was $23,250.71 while that received by females was $10,970.78 (mean difference = 12,279.92, 95% CI = (2036.31, 22,523.54), p = 0.019). A comprehensive understanding of these CoIs can inform the disclosure policies of journals to promote transparency of authors.
DNA Methyltransferase 1 and 3a Expression in the Frontal Cortex Regulates Palatable Food Consumption
Authors: Manjegowda Mohan C , Joy-Gaba Jonathan , Wengert Eric , Saga Anusha U. , Warthen Daniel , Kuchler Amelie , Gaykema Ronald , Patel Manoj K. , Sheffield Nathan C. , Scott Michael M.
Published: May 2021

DNA methylation is an important regulatory mechanism in the control of neuronal function. Both during development and following exposure to salient stimuli, plasticity in the methylation of cytosine residues leads to a change in neuron excitability that subsequently sculpts animal behavior. However, although the response of DNA methyltransferase enzymes in adult neurons to stimuli such as drugs of abuse have been described, less is known about how these enzymes regulate methylation at specific loci to change the drive to ingest natural rewards. Specifically, we do not understand how changes in methylation within important brain areas known to regulate palatable food intake can affect ingestion, while a detailed investigation of the neurophysiological and genomic effects of perturbing methyltransferase function has not been pursued. By deleting DNA methyltransferase 1 and 3a in the mouse prefrontal cortex, we observed the requirement for these enzymes in the regulation of nutrient rich food consumption in the absence of any effect on the intake of low fat and low sugar chow. We also determined that the deletion profoundly affected neuron excitability within pyramidal cells resident in superficial layers II/III of the cortex but had little effect in deep layer V neurons. Finally, reduced representation bisulfite sequencing revealed both hypo and hypermethylation in response to methyltransferase deletion, an effect that was observed in binding sites for retinoic acid receptor beta (RARβ) located within regulatory regions of genes known to affect neuronal function. Together, our data suggest that alterations in the actions of RARβ could shift neuronal activity to reduce palatable food intake.