bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Targeted Interleukin‐27 Gene Therapy for Disrupting Malignant Crosstalk in Prostate Cancer Bone Metastases
Authors: Salameh Janelle Weslyn , Figueiredo Marxa L.
Published: April 2020

Although ~90% of prostate cancer patients with advanced disease will exhibit bone metastasis, current therapies focus on one aspect of the disease (either the tumor or the bone), with tumor elimination being the primary goal. Prostate cancer (PCa) cells ‘hijack’ bone homeostasis by disrupting the crosstalk between critical cells within the tumor/bone microenvironment (osteoblasts, osteoclasts, and immune cells), and utilizing this effector‐rich environment for cancer cell survival and growth. Crosstalk pathways primarily involve Interleukins (IL‐6 and IL‐11) and transforming growth factor β (TGFβ). Therefore, a key therapeutic objective in malignant skeletal disease management is to eliminate tumors while restoring bone homeostasis. Current treatments are limited to palliative radiotherapy, chemotherapy, or anti‐RANK treatments, all of which have considerable side effects such as osteonecrosis of the jaw or enhanced tumor invasion. An emerging approach to treating skeletal malignancies, osteoimmunology, investigates new multifunctional immune‐stimulatory agents that can simultaneously combat tumor growth and promote bone repair. Our group is interested in IL‐27, an immunomodulatory cytokine with great potential as a multifunctional cancer therapeutic. Its regulatory roles include antitumor immune responses (promoting Th1 differentiation), inhibition of tumor growth, and direct modification of tumor/bone crosstalk to support bone regeneration. We hypothesize that a secreted tumor‐targeted IL‐27 gene therapy approach would facilitate the accumulation of IL‐27 in the bone/tumor microenvironment, thus eliminating tumors while restoring bone. To test this hypothesis, we created a tumor‐targeted IL‐27 gene by incorporating a novel peptide (LSLITRL); an IL‐6 receptor antagonist known to inhibit angiogenesis and tumor growth; or a scrambled control peptide at the C‐terminus. To detect the expression, secretion, and tumor recognition specificity, IL‐27 constructs were fused to a NanoLuciferase expressing vector modified with a secretion signal at the N‐terminus. We have also assessed the potential for our proposed gene therapy in disrupting malignant characteristics of PCa in vitro in by assessing STAT‐1/‐3 activation and will be assessing bone cell mineralization in PCa/bone co‐cultures. Future studies will examine the therapeutic efficacy of secreted, tumor‐targeted IL‐27 in vivo.

Support or Funding Information

NCI R01CA196947‐S1
SPARC: Renal Denervation Attenuates DOCA‐salt Hypertension in the Mouse
Authors: Baumann Daniel C. , Van Helden Dusty , Evans Louise , Osborn John
Published: April 2020

Hypertension affects approximately one third of the adult population in the United States. Catheter based renal denervation (RDN) has emerged as a novel treatment for hypertension in patients. However, the mechanisms by which RDN lowers arterial pressure has not been fully determined. We hypothesize that an interaction between renal nerves (afferent and efferent) and renal inflammation contributes to hypertension. To test this hypothesis, we utilized a model of hypertension in the mouse produced by the combination of uni‐nephrectomy with deoxycorticosterone acetate (DOCA) and a high salt diet (DOCA‐salt). 10‐week‐old male C57BL6/J mice were implanted with radio‐telemetry probes in the carotid artery for measurement of arterial pressure. DOCA was administered via subcutaneous implantation of a silicon pellet containing 50 mg of DOCA. Sham mice received a drug free silicon pellet. Uni‐nephrectomy, pellet insertion, salt treatment, and RDN were all performed or started on the same day. RDN was performed through surgical ablation and peri‐axonal application of 10% phenol. Baseline arterial pressure was measured 3 days prior to induction of DOCA‐salt hypertension by radiotelemetry. Separate cohorts of mice were generated for protein quantification and histology, with urine and kidneys harvested 21 days post induction of DOCA‐salt hypertension. Cytokine protein quantification was obtained through Multiplex ELISA. All errors reported are SEM. Following 7 days of DOCA‐salt, mean arterial pressure (MAP) increased +44.8 ± 3.2 mmHg from baseline (153.1± 1.8 mmHg day 7 absolute value), comparted to −1.5 ± 5.5 mmHg in sham mice (105.6 ± 0.5 mmHg day 7 absolute value). RDN reduced this increase by more than 50% in RDN‐DOCA‐salt mice (+20.5 ± 5.0 mmHg delta, 131.6 ± 8.1 mmHg absolute). Renal and urinary cytokines and chemokines were increased in DOCA‐salt compared to sham treated mice. For example, renal MCP‐5 was 24.7 ± 7.2 pg/mg in DOCA‐salt mice compared to 5.0 ± 0.6 pg/mg in sham treated mice. Similarly, urinary MCP‐5 was significantly higher in in DOCA‐salt mice (12.4 ± 5.1 pg/mg) compared to sham mice (2.1 ± 1.1 pg/mg). IL‐1α and IL‐1β were both increased in DOCA‐salt kidneys (112.4 ± 19.2 pg/mg and 2.1 ± 0.4 pg/mg respectively) compared to sham kidneys (31.98 ± 4.4 pg/mg and 0.36 ± 0.06 pg/mg respectively). We also measured, by immunohistochemistry, an increase expression of the IL‐1 receptor in kidneys of DOCA‐salt mice compared to sham controls. We hypothesize that renal cytokines activate renal afferent nerves and ultimately elevate arterial pressure by activation of the sympathetic nervous system. Future studies will test this hypothesis by examining whether elimination of cytokine generated afferent nerve activity attenuates hypertension in DOCA‐salt mice.

Support or Funding Information

NIH: R01HL116476, MnOPT: T32DK083250–01A1, SPARC: 5U01DK116320‐03
Students Teaching Students: What Do Graduate Student Instructors Gain from Teaching Study Skills to Undergraduates?
Authors: Raborn Casey , Schaefer Audra
Published: April 2020

In recent years there have been several anatomy education doctoral programs that have emerged to train future educators and educational researchers in response to the growing demand for high quality anatomy educators. These programs are still quite novel, which merits examination of experiences gained by students currently enrolled in or those who have graduated from such programs as a means for determining how to best prepare individuals to effectively teach undergraduate and graduate/professional students in the basic sciences. This phenomenological study (IRB Protocol 2018‐0214) aimed to examine the experiences of individuals who, as graduate students, taught an optional 1‐credit hour learning skills course to undergraduate anatomy students. This course, MSCI M100, was designed to guide undergraduate students in developing effective study skills that would aid them as they concurrently complete an anatomy course. Seven individuals took part in a semi‐structured interview and their first‐person experience gained through teaching the undergraduate study skills course was described. Each of the individuals taught the course at least once during their time as a graduate student. Once the interviews were transcribed, thematic analysis of the interview transcripts was completed in which the transcripts were read and coded. These codes were further refined to capture common themes among the participants’ experience in teaching this course. Thorough investigation of the experiences these individuals gained when they taught MSCI M100 will help to determine the impact teaching this course has had in shaping these individuals as future educators in undergraduate or professional schools, and whether teaching this course, or similar courses, is a valuable experience that could be recommended for students in other (similar) programs.
Sex Differences in Periaqueductal Gray Kinase Activation After Morphine Tolerance
Authors: Ram Akila , Edwards Taylor M. , McCarty Ashley , Bobeck Erin N.
Published: April 2020

Morphine is a potent opioid analgesic with very high propensity for tolerance development. The analgesic and tolerance properties of opioids are partially regulated by the midbrain ventrolateral periaqueductal gray (vlPAG). There is a growing body of literature that highlights the sex differences in pain processing and opioid effects. However, the nature of sex differences at the level of kinase effectors of the μ‐receptor is unknown. Here, we investigate the intracellular kinase activation and localization patterns in the vlPAG of male and female mice following acute and chronic morphine treatment. Wild‐type mice were treated with morphine (10 mg/kg, i.p.) or saline in a chronic or acute administration paradigm. We performed fluorescence immunohistochemistry to map the localization and activation of extracellular signal‐regulated kinase 1/2 (ERK 1/2), protein kinase‐C (PKC), and protein kinase‐A (PKA). We observed elevated baseline levels of phosphorylated forms of the kinases ERK 1/2, PKC and PKA in females. We observed significantly greater activated ERK 1/2 in the vlPAG chronic morphine‐treated animals which co‐localized with the endosomal marker Eea1. We note that phosphorylated PKC tends to localize to the plasma membrane near the μ‐opioid receptor in the vlPAG following chronic morphine treatment. Further, we observed that although PKA activation is increased following chronic morphine treatment, there is a significant reduction in nuclear translocation of this kinase. Across these kinases, the magnitude of increase of kinase activation was more in males after morphine tolerance. Taken together, this study demonstrates a differential activation and localization of ERK 1/2, PKC and PKA across sexes and opens avenues to explore the role of chronic morphine treatment on G‐protein signaling and kinase nuclear transport.

Support or Funding Information

Brain and Behavior Research Foundation to ENB. Department of Biology, Utah State University
Bioengineered miR‐328‐3p modulates SLC2A1/GLUT1‐mediated glucose uptake and metabolism to exert synergistic antiproliferative effects with chemotherapeutics
Authors: Tu Mei-Juan , Yi Wan-Yong , Liu Zhenzhen , Zhang Chao , Yu Ai-Xi , Yu Ai-Ming
Published: April 2020

MicroRNAs (miRNAs or miRs) are small noncoding RNAs derived from genome to control target gene expresion. Recently we have developed a novel platform that offers high‐yield production of bioengineered miRNA agents (BERAs). This study was to produce and utilize novel fully‐humanized biologic miR‐328‐3p molecule (hBERA/miR‐328) to delineate the role of miR‐328‐3p in the control of nutrient uptake essential for cell metabolism. We first demonstrated successful high‐level expression of hBERA/miR‐328 in bacteria and purification to a high degree of homogeneity (> 98%). Biologic miR‐328‐3p prodrug was selectively processed to miR‐328‐3p to suppress the growth of highly‐proliferative human osteosarcoma (OS) cells. Besides GLUT1/SLC2A1, we identified and verified LAT1/SLC7A5 as a direct target for miR‐328‐3p. While reduction of LAT1 protein levels by miR‐328‐3p did not alter the homeostasis of amino acids within OS cells, suppression of GLUT1 led to a significantly lower glucose uptake and decline in intracellular levels of glucose and glycolytic metabolite lactate. Moreover, combination treatment with hBERA/miR‐328 and cisplatin or doxorubicin exerted a strong synergism in the inhibition of OS cell proliferationin. These findings support the utility of novel bioengineered RNA molecules and establish an important role of miR‐328‐3p in the control of nutrient transport and homeostasis behind cancer metabolism.

Support or Funding Information

This study was supported by grants R01GM133888 and R01CA225958 from the National Institutes of Health.
S1PR1 interacts with endoplasmic reticulum stress sensor, BiP, to regulate calcium homeostasis and endothelial barrier function
Authors: Anwar Mumtaz , Amin Md-Ruhul , Raghunathrao Vijay Avin , Mo Gary , Mehta Dolly
Published: April 2020

Endothelial–cell surface localized sphingosine 1 phosphate receptor 1 (S1PR1) is well known to enhance barrier function upon ligating S1P. We recently showed that S1P phosphorylation of S1PR1 at tyrosine (Y) 143 residue induces S1PR1 internalization and compromises barrier function. Here, we assessed the mechanism internalizing the Y143‐S1PR1 and how Y143‐S1PR1 disrupts barrier function. Herein, using TIRF and confocal imaging, we show that phosphorylated (Y143D‐S1PR1) S1PR1 mutant localizes at endoplasmic reticulum (ER). Inhibition of dynamin activity, a GTP‐dependent pinchase, rescued Y143D‐S1PR1 expression at the cell surface. However, dynamin inhibition had no effect on cell‐surface retention of S1PR1 or Y143F‐S1PR1. In other studies, we show that Y143D‐S1PR1 bound WT‐dynamin strongly while weakly with GTPase defective dynamin. Cell‐surface retained S1PR1 induces signaling including calcium mobilization and activation of MAP kinases by binding Gi heterotrimeric protein. Intriguingly, we show that internalized Y143D‐S1PR1 augmented Ca2+ entry which was blocked by pertussis toxin. Furthermore, phosphorylated receptor bound Gi indicating that internalized S1PR1 binds cytosolic Gi which then increases Ca2+ entry. We further showed Y143D‐S1PR1 mutant augmented Ca2+ entry by organizing stromal‐interaction molecule 1 (STIM1) dependent ER‐PM junction formation. To address the mediator involved in retaining Y143D‐S1PR1 at the ER, we performed mass spectrometric analysis and identified GRP78 (BiP), an endoplasmic resident protein, as the novel interacting partner of S1PR1. Depletion of BiP or STIM1 rescued barrier function even in presence of Y143D‐S1PR1. Thus, BiP recruits phosphorylated Y143D‐S1PR1 at the ER where S1PR1 mutant organizes ER‐PM junctions to mediate Ca2+ entry disrupting endothelial barrier function.

Support or Funding Information

NIH
Understanding Gαq/11 Localization and Trafficking in Uveal Melanoma
Authors: Randolph Clinita , Wedegaertner Philip
Published: April 2020

Constitutively activating mutations in Gαq and Gα11 (Gαq/11) have been reported in up to 93% of uveal melanomas. Although constitutively active Gαq/11 promote uveal melanoma tumorigenesis through activation of multiple downstream pathways, no therapies inhibit constitutively active Gαq/11. Studies suggest that increased palmitate turnover and increased cytoplasmic localization occur upon activation of some Gα subunits. The purpose of our studies is to understand the role of palmitoylation in trafficking and signaling of constitutively active Gαq/11 in uveal melanoma. Using live cell imaging and cellular fractionation of HEK 293 cells and uveal melanoma cells, constitutively active GαqQ209L and GαqQ209P show decreased localization at membranes compared to wild type Gαq, suggesting increased turnover of attached palmitate in constitutively active mutants. Moreover, immunofluorescence microscopy revealed that a palmitoylation‐deficient constitutively active mutant displays a complete loss of plasma membrane localization and an inability to signal as measured by Rho‐ and Rac‐dependent YAP translocation into the nucleus, TEAD‐dependent luciferase activity, and ERK phosphorylation. These studies demonstrate that palmitoylation of mutationally activated Gαq/11 is required for its signaling functions. Although live cell imaging and cellular fractionation experiments reveal decreased membrane localization of constitutively active Gαq compared to wild‐type Gαq, our studies suggest that complete loss of membrane localization abolishes constitutively active Gαq‐dependent signaling. Disruption of constitutively active Gαq/11 palmitoylation and localization may be an effective strategy for inhibiting constitutively active Gαq/11 oncogenic signaling in uveal melanoma.

Support or Funding Information

This research was funded by NIH grants F31CA224803‐Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship to Promote Diversity in Health, R01GM056444‐16, R01GM056444‐16S1‐Research Supplements to Promote Diversity in Health‐Related Research, and T32 GM100836.
Optimizing Extraction of Proteins from Carcinus Maenus After Removal of Low‐Molecular Weight Chitins
Authors: Stevens Rylie , Myracle Angela D. , Grant Jennifer E.
Published: April 2020

Crab shells as waste products are presently of economic interest only for the value of the chitin polymer present in their shells, which may be used to formulate foods or pharmaceutical products. Other materials in the crab shells, including protein, are discarded as waste. Crab shells have a large protein content A key question to examine is if there are bioactive proteins and/or peptides that have health benefits which could be recovered and utilized as a value added fraction from the waste stream. For example proteins isolated from crab shells have been found to contain antimicrobial and moderate antitumor agents (Sawssen, 2015.)

In this work, the procedures used for removal of low molecular weight (LMW) chitin were followed (Ye, 2016). After removal of LMW chitin, the acetic acid extraction of proteins from crab shells was optimized using 50%, 25% and 12% acetic acid. One of the challenges associated with the extraction of proteins from crab shells is the concomitant demineralization of the shells which results in a high calcium carbonate solution in solution. In this project, a variety of different methods for separating the protein from the acidic solution and the calcium carbonate were utilized including dialysis, polyethylene glycol precipitation strategies.

These findings will be of value to the community of researchers investigating either bioactive materials in the shells of marine organisms.
The effect of whole‐body skin cooling on dynamic cerebral autoregulation
Authors: Kobayashi Fumino , Kobayashi Maho , Nakata Hiroki , Kamijo Yoshi-ichiro , Crandall Craig , Shibasaki Manabu
Published: April 2020

The incidence of cerebrovascular accident is elevated during the winter season. Increases in blood pressure associated with an enhanced vasoconstricted state during cold exposure may contribute to this risk. We hypothesized that whole‐body skin cooling would impair dynamic cerebral autoregulation, perhaps due to both systemic and cerebral vasoconstriction. Supine resting data from fifteen young healthy participants were obtained before and during whole‐body skin cooling. In addition, subjects performed a simple cognitive task (Go/No‐go tasks) in each condition. Subjects also performed a separate time control trial while remaining in thermoneutral conditions. Dynamic cerebral autoregulation was assessed by transfer function analysis (TFA) of middle cerebral artery blood velocity and mean arterial pressure. Whole‐body cooling decreased mean skin temperature (P<0.001), while ear canal temperature and respiratory variables were maintained. The cold stress increased mean arterial blood pressure (P<0.01) while heart rate decreased (P<0.05). Vascular conductance of both the internal and external carotid arteries (Doppler ultrasound) decreased during cooling, indicating cerebral and systemic vasoconstriction, respectively. The TFA‐derived low frequency gain increased during the cold stress (P<0.05), indicative of reduced dynamic cerebral autoregulation. The Go/No‐go task did not alter the TFA‐derived gain during cooling. None of these variables were altered during the thermoneutral time control trial. These findings suggest that whole‐body skin cooling impairs dynamic cerebral autoregulation.

Support or Funding Information

Japan Society for the Promotion of Science 18H03166
Differences in effects of task repetition in three modalities Go/No‐go paradigams.
Authors: Hirai Minami , Ishikura Keiko , Sawai Norie , Kobayashi Fumino , Nakata Hiroki , Shibasaki Manabu
Published: April 2020

Previous studies suggested that learning, habituation, mental fatigue, or reduced motivation due to task repetition (time‐on‐task) decreased the peak amplitude and/or latency of components of event‐related potentials (ERPs), but the mechanism remains unclear. Also, the effect of the sensory modality on those changes has not been clarified. The difference in modality could modify cerebral blood flow or its distribution in the brain. We hypothesized that the effect of task repetition on ERPs was related to the sensory modality, and the changes in cerebral blood flow contributed to the difference. Subjects performed 6 sessions of Go/No‐go paradigms for 5 minutes with visual, auditory, and somatosensory stimuli on different days, and were allowed to rest for 5 minutes between sessions. In addition to electroencephalography, middle cerebral artery blood mean velocity and finger arterial pressure were continuously measured to evaluate dynamic cerebral autoregulation via transfer function analysis. The amplitude of P300 decreased with the time‐on‐task in all three modalities, and the latency of P300 delayed with the time‐ontask only with somatosensory stimuli. The reductions in amplitude were the greatest with the visual stimuli among the three modalities. The reductions in the amplitude of P300 were greater with No‐go stimuli than Go stimuli across the three modalities. Contrary to our hypothesis, dynamic cerebral autoregulation did not change throughout the trials. These results suggest that the effects of task repetition on ERPs were sensory modality‐dependent, while dynamic cerebral autoregulation during cognitive tasks might not contribute to changes in ERPs.

Support or Funding Information

Japan Society for the Promotion of Science 18H03166
Racial Disparities in Route of Hysterectomy for Benign Indications Within an Integrated Health Care System
Authors: Zaritsky Eve , Ojo Anthonia , Tucker Lue-Yen , Raine-Bennett Tina R.
Published: April 2020

(Abstracted from JAMA Network Open 2019;2(12):e1917004)

Over the past 2 decades, gynecologists have been performing fewer hysterectomies and have increased the use of minimally invasive techniques. When used for benign gynecological surgery, minimally invasive hysterectomies (MIHs)—including laparoscopic, vaginal, and robotic procedures)—have been shown to have several advantages compared with open abdominal hysterectomies.
Deep Versus Lobar Intraparenchymal Hemorrhage: Seizures, Hyperexcitable Patterns, and Clinical Outcomes
Authors: Sheikh Zubeda B. , Stretz Christoph , Maciel Carolina B. , Dhakar Monica B. , Orgass Hailey , Petroff Ognen A. , Hirsch Lawrence J. , Gilmore Emily J.
Published: April 2020

Objectives:

To compare electrographic seizures, hyperexcitable patterns, and clinical outcomes in lobar and deep intraparenchymal hemorrhage. Additionally, to characterize electrographic seizure and hyperexcitable pattern predictors in each group and determine seizure risk with thalamic involvement.

Design:

Retrospective cohort study.

Setting:

Tertiary academic medical center.

Patients:

Consecutive adult patients with nontraumatic intraparenchymal hemorrhage undergoing continuous electroencephalography at our center between January 2013 and December 2016.

Interventions:

Not applicable.

Measurements and Main Results:

Based on head CT closest to the initial continuous electroencephalography session, we classified intraparenchymal hemorrhage as isolated deep (no insular, subarachnoid, subdural extension) or lobar. Hyperexcitable patterns included the following: periodic discharges, spike-wave complexes, any rhythmic delta other than generalized. We used Fisher exact test for categorical and Mann-Whitney U test for continuous variables. Multivariable regression identified predictors of electrographic seizures, hyperexcitable patterns, and poor outcomes (score of 1–2 on Glasgow Outcome Scale) in lobar intraparenchymal hemorrhage. The cohort comprised of 128 patients, 88 lobar, and 40 deep intraparenchymal hemorrhage. Electrographic seizures occurred in 17% of lobar and 5% of deep intraparenchymal hemorrhage (p = 0.09). Hyperexcitable patterns were more frequent in the lobar group (44.3% vs 17.5%; p = 0.005). In multivariable analyses in the lobar group, lateralized rhythmic delta activity predicted electrographic seizures (odds ratio, 6.24; CI, 1.49–26.08; p = 0.012); insular involvement predicted hyperexcitable patterns (odds ratio, 4.88; CI, 1.36–17.57; p = 0.015); coma, temporal lobe involvement, intraparenchymal hemorrhage volume, and electrographic seizures predicted poor outcome. Thalamic involvement did not affect electrographic seizures or hyperexcitable patterns in either group.

Conclusions:

Electrographic seizures are frequent in lobar intraparenchymal hemorrhage, occurring in one in six monitored patients, as opposed to only 5% in isolated deep intraparenchymal hemorrhage not extending to cortex/insula, subarachnoid, or subdural spaces. Patients with lobar intraparenchymal hemorrhage and lateralized rhythmic delta activity were six times as likely to have electrographic seizures, which were associated with 5.47 higher odds of a poor outcome. Coma, temporal lobe involvement, hematoma volume, and electrographic seizures predicted poor outcome in lobar intraparenchymal hemorrhage.
Subtle Motor Signs as a Biomarker for Mindful Movement Intervention in Children with Attention-Deficit/Hyperactivity Disorder
Authors: Clark Dav , Seymour Karen E. , Findling Robert L. , Mostofsky Stewart H.
Published: April 2020

Objective:

Previous studies of Tai Chi or mindfulness-based interventions in attention-deficit/hyperactivity disorder (ADHD) have relied on self- or parent-reported outcome measures; however, there is a critical need for the validation of objective biomarkers of treatment. Therefore, we implemented a mindful movement intervention for children with ADHD, hypothesizing that an ADHD-relevant motor control measure could serve as a predictive biomarker of treatment-related improvement.

Methods:

Thirty-four participants were included, 8 to 12 year olds diagnosed with DSM-5 ADHD. Participants engaged in the mindful movement treatment, an 8-week program with 2 classes a week for 60 minutes. At pre- and post-treatment, ADHD symptoms and associated impairment and motor control via the Physical and Neurological Examination for Subtle Signs (PANESS) were assessed.

Results:

The results showed a significant reduction for PANESS Gaits and Station (p ≤ 0.001), total overflow (p = 0.009), and total score (p = 0.001) after treatment, with the largest effect for Gaits and Stations. The results also showed a significant reduction in symptoms of inattention (p ≤ 0.001), hyperactivity/impulsivity (p ≤ 0.001), oppositional defiant disorder (p = 0.001), and executive dysfunction (p ≤ 0.001). There were significant positive correlations between change in PANESS Gaits and Stations and change in both inattentive (p = 0.02) and hyperactive/impulsive symptoms (p = 0.02). There was also a significant positive correlation between change in the PANESS total score and change in inattentive (p = 0.007) and hyperactive/impulsive symptoms (p = 0.042). The change in the PANESS total score (β = 0.295, p = 0.002) predicted post-treatment ADHD severity above the change in inattentive or hyperactive/impulsive symptoms.

Conclusion:

The results suggest the effectiveness of a mindful movement treatment on ADHD symptoms and suggest the PANESS as a candidate motor biomarker for future mindful movement trials.

Clinical Trial Registration:

ClinicalTrials.gov, NCT02234557, https://clinicaltrials.gov/ct2/show/NCT02234557.
THE INCIDENCE OF NEOVASCULARIZATION IN CENTRAL SEROUS CHORIORETINOPATHY BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: Savastano M. Cristina , Rispoli Marco , Lumbroso Bruno
Published: April 2020

Purpose:

To evaluate the incidence of neovascularization (NV) secondary to central serous chorioretinopathy (CSC)—a condition belonging to the spectrum of pachychoroid disorders by means of optical coherence tomography angiography.

Methods:

One hundred and seventy five eyes with CSC were evaluated in this retrospective observational study. The eyes with acute or chronic CSC with no NV were included in Group 1, and those with NV were evaluated in Group 2. Only eyes that had undergone structural optical coherence tomography and optical coherence tomography angiography were included. Age, best-corrected visual acuity, and subfoveal choroidal thickness were evaluated in all eyes. In Group 2, the type and morphology of NV and the occurrence of exudation were considered.

Results:

Of a total of 175 eyes with CSC, 86 had the acute form and 89 the chronic. Approximately 140 belonged to Group 1 (80%) and 35 to Group 2 (20%). Approximately 39.2% of all patient with chronic CSC developed NV. Mean age in Groups 1 and 2 was 53.3 years (±10.9) and 66.6 years (±10.2), respectively. Mean best-corrected visual acuity in Groups 1 and 2 was 45.7 (±11.7) and 30.9 (±17.9) early treatment diabetic retinopathy study letters, respectively. Mean CCT in Group 1 and 2 was 417.5 µm (±123) and 344.2 µm (±165.9), respectively. In Group 2, all patients had Type 1 NV (100%); 29 eyes (83%) had filamentous feature, and 6 eyes (17%) had irregular shape. Silent nonexudative NV was observed in 7 eyes (20%), all belonging to Group 2.

Conclusion:

The use of optical coherence tomography angiography in everyday clinical practice allows for the accurate analysis of the chorioretinal vascular setting, with the identification of new vessels that could remain misdiagnosed.
A Prospective Cohort Study on the Safety of Infant Pentavalent (DTwP-HBV-Hib) and Oral Polio Vaccines in Two South Indian Districts
Authors: Arora Narendra Kumar , Das Manoja Kumar , Poluru Ramesh , Kashyap Neeraj Kumar , Mathew Thomas , Mathai John , Aggarwal Mahesh Kumar , Haldar Pradeep , Verstraeten Thomas , Zuber Patrick L. F. ,   the INCLEN Vaccine Safety Study Group
Published: April 2020

Background:

Safety of pentavalent (DTwP-HBV-Hib) vaccine has been a public concern in India and other countries. This study attempted to document the association of serious adverse events following immunization (AEFI, including hospitalizations and deaths of all causes) with the 3 doses of pentavalent and oral poliovirus (OPV) vaccines.

Methods:

A cohort of 30,688 infants in 2 south Indian districts were enrolled and followed-up between October 2014 and May 2016, following their first vaccination with DTwP-HBV-Hib and OPV at public health facilities. During weekly follow-ups, by telephone or home visits, the serious AEFIs (hospitalizations and deaths) occurring any time after each vaccination until 4 weeks after third dose were documented. The incidence risk ratios (IRRs) of serious AEFIs in the first (days 0–6) and fourth weeks (days 21–27) after the vaccine doses were compared using the poisson regression analysis.

Results:

Of the 30,688 infants enrolled, 30,208 received their third doses of vaccines. During the 4-week periods following each vaccination, there were 365 hospitalizations and 17 deaths. Adjusted incidence risk ratio of 3 doses combined for post-vaccination serious AEFIs during the first week compared with fourth week was 0.8 [95% confidence interval: 0.6–1.0].

Conclusions:

There was no increased risk of a serious AEFIs during the first week after any of the 3 doses of pentavalent and OPV vaccination compared with the fourth week. In the absence of any temporal clustering, mortality and hospitalization rates observed in vaccinated infants probably reflects the natural occurrence of such events.
Induction of Meal-related Symptoms as a Novel Mechanism of Action of the Duodenal-Jejunal Bypass Sleeve
Authors: McMaster Jessica J. , Rich Graeme G. , Shanahan Erin R. , Do Anh T. , Fletcher Linda M. , Kutyla Marguerite J. , Tallis Caroline , Jones Mike P. , Talley Nicholas J. , Macdonald Graeme A. , Chachay Veronique S. , Holtmann Gerald J.
Published: April 2020

Background:

Treatment with a duodenal-jejunal bypass sleeve (DJBS) induces clinically significant weight loss, but little is known about the mechanisms of action of this device.

Aim:

The aim of this study was to characterize the mechanisms of action of the DJBS and determine the durability of weight loss and metabolic improvements.

Materials and Methods:

We studied a cohort of 19 subjects with severe obesity and type 2 diabetes (baseline body mass index: 43.7±5.3 kg/m2). Anthropometry, body composition, blood pressure, biochemical measures, and dietary intake were monitored for 48 weeks after DJBS implantation, and then for 1 year after device removal. Gastric emptying and triglyceride absorption were measured at baseline, 8 weeks after implant, and within 3 weeks of device explant. Visceral sensory function was assessed at baseline, 4 weeks after implant, and within 3 weeks after explant.

Results:

Significant weight loss (P<0.01) occurred following DJBS placement, with a mean weight reduction of 17.0±6.5% at 48 weeks. The symptom burden following a standardized nutrient challenge was increased after DJBS implantation (P<0.05), returning to baseline after DJBS removal. Neither gastric emptying nor triglyceride absorption changed with the device in situ. A significant reduction in energy intake was observed [baseline: 7703±2978 kJ (1841±712 kcal), 24 weeks: 4824±2259 kJ (1153±540 kcal), and 48 weeks: 4474±1468 kJ (1069±351 kcal)]. After 1 year, anthropometry remained significantly improved, but there was no durable impact on metabolic outcomes.

Conclusions:

DJBS treatment resulted in substantial weight loss. Weight loss is related to reduced caloric intake, which seems linked to an augmented upper gastrointestinal symptom response, but not altered fat absorption.
Safety of diuretic administration during the early management of dyspnea patients who are not finally diagnosed with acute heart failure
Authors: Takagi Koji , Miró Òscar , Gayat Etienne , Llorens Pere , Wussler Desiree N. , Čerlinskaitė Kamilė , Msolli Mohamed Amine , Kavoliūnienė Aušra , Sekma Adel , Čelutkienė Jelena , Nouira Semir , Gil Víctor , Martínez-Nadal Gemma , Breidthardt Tobias , Kozhuharov Nikola , Martin Jasmin , Müller Christian , Mebazaa Alexandre
Published: April 2020

Objectives

Investigating whether it is safe or not to administrate diuretics to patients arriving at emergency departments in a stage of acute dyspnea but without a final diagnosis of acute heart failure.

Methods

We analyzed an unselected multinational sample of patients with dyspnea without a final diagnosis of acute heart failure from Global Research on Acute Conditions Team (France, Lithuania, Tunisia) and Basics in Acute Shortness of Breath Evaluation (Switzerland) registries. Thirty-day all-cause mortality and 30-day postdischarge all-cause readmission rate of treated patients with diuretics at emergency departments were compared with untreated patients by unadjusted and adjusted hazard and odds ratios. Interaction and stratified analyses were performed.

Results

We included 2505 patients. Among them, 365 (14.6%) received diuretics in emergency departments. Thirty-day mortality was 4.5% (treated/untreated = 5.2%/4.3%, hazard ratio: 1.22; 95% confidence interval, 0.75–2.00) and 30-day readmission rate was 11.3% (14.7%/10.8%, odds ratio: 1.41; 95% confidence interval, 0.95–2.11). After adjustment, no differences were found between two groups in mortality (hazard ratio: 0.86; 95% confidence interval, 0.51–1.44) and readmission (odds ratio: 1.15; 95% confidence interval, 0.72–1.82). Age significantly interacted with the use of diuretics and readmission (P = 0.03), with better prognosis when used in patients >80 years (odds ratio: 0.27; 95% confidence interval, 0.07–1.03) than in patients ≤80 years (odds ratio: 1.56; 95% confidence interval, 0.94–2.63).

Conclusions

Diuretic administration to patients presenting to emergency departments with dyspnea while they were undiagnosed and in whom acute heart failure was finally excluded was not associated with 30-day all-cause mortality and 30-day postdischarge all-cause readmission rate.
Evaluating the Discordant Relationship Between Tarlov Cysts and Symptoms of Pudendal Neuralgia
Authors: Lim Victoria M. , Khanna Rohit , Kalinkin Olga , Castellanos Mario E. , Hibner Michael
Published: April 2020

(Abstracted from Am J Obstet Gynecol 2020;222:70.e1–70.e6)

Pudendal neuralgia is a painful chronic neuropathic pelvic condition involving the pudendal nerve dermatome. It is often debilitating and can greatly decrease quality of life among both men and women.
Embryonic Aneuploidy Rates Are Equivalent in Natural Cycles and Gonadotropin-Stimulated Cycles
Authors: Hong Kathleen H. , Franasiak Jason M. , Werner Marie M. , Patounakis George , Juneau Caroline R. , Forman Eric J. , Scott Richard T.
Published: April 2020

(Abstracted from Fertil Steril 2019;112:670–676)

It is unclear whether controlled ovarian hyperstimulation (COH) using exogenous gonadotrophins during the in vitro fertilization (IVF) process elevates risk of meiotic or mitotic error, leading to aneuploidy. Several studies with mouse models have suggested that follicle-stimulating hormone (FSH) administration in vitro results in higher rates of aneuploidy, although studies utilizing mouse models are limited due to significantly different rates of aneuploidy and mechanistic differences between mice and humans.
Tridimensional Combined Gluteoplasty: Liposuction, Buttock Implants, and Fat Transfer
Authors: Cárdenas-Camarena Lázaro , Trujillo-Méndez Raúl , Díaz-Barriga Julio César
Published: April 2020

Background:

There are different procedures for gluteal augmentation. The authors describe their gluteal augmentation technique, which combines buttock implant placement, frame liposuction, and lipoinjection in the lateral third of the buttock and a plane superficial to the gluteal implant.

Methods:

Patients of both sexes who underwent aesthetic gluteal augmentation with a volume deficit of the lateral third and limited fat available for grafting were included. Liposuction was performed on the periphery of the gluteus, silicone implants were placed, and lipoinjection was performed in different areas.

Results:

Fifty-two patients were included between October of 2007 and December of 2018. The average age of the patients was 33.3 years (range, 23 to 49 years); 42 women and 11 male-to-female transgender patients were included. The implants used consisted of anatomical cohesive silicone, with the most commonly used size being 300 cc (range, 200 to 500 cc). The average volume of infiltrated fat in each hip and buttock was 243.1 cc (range, 100 to 370 cc) and 141.6 cc (range, 50 to 200 cc), respectively. Partial wound dehiscence was reported in six patients (11.5 percent). In one patient who had been treated with biopolymers, the implant became exposed. All patients reported that they were highly satisfied with the results of the procedure.

Conclusions:

The combination of liposuction, buttock implant placement, and lipoinjection of the buttocks and hips is a safe procedure with a low complication rate and high level of satisfaction. This procedure is recommended in patients who require augmentation of the central and lateral portions of the buttock with insufficient fat tissue for lipoinjection.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Nurse-Led Computerized Cognitive Training for Mild Cognitive Impairment: A Preliminary Study
Authors: Oh Min Woo , Ki Young Jin , Jeon Byoung Hyun , Kim Si Yeon , Oh Youngmin , Yoo Suwon , Cho Aeri , Seo Joo Han , Lee Goo Joo
Published: April 2020

Purpose

This preliminary study aimed to compare the outcomes of an occupational therapist-led and a nurse-led computerized cognitive training (CCT) for mild cognitive impairment (MCI) in older adults.

Design

A single-blind randomized controlled trial was performed.

Methods

Participants 65 years of age and older with MCI were randomly assigned to a group led by an occupational therapist or by a nurse. Both groups received CCT for 4 weeks.

Findings

Six participants in the occupational therapist-led group and nine in the nurse-led group completed CCT. The nurse-led group showed significant improvement in scores on the Seoul Verbal Learning Test–Elderly’s version immediate recall scores (p = .030) and the Korean-Boston Naming Test (p = .012).

Conclusions

Nurse-led CCT demonstrated improvement in some language and memory areas in older adults with MCI.

Clinical Relevance

This study supports the idea of educating nurses to use a CCT program for treating older adults with MCI to improve their cognitive function.
Dickens's nightmare: dreams, memory and trauma
Authors: Dickson Melissa
Published: April 2020

This article considers the role of stress in nineteenth-century literature and culture as both a catalyst for, and a symptom of, troubled sleep. Taking the figure of Charles Dickens as my principal case study, I investigate Dickens's fictional and non-fictional explorations of sleep as a space and time where traumatic memories might be relived and repeated, where grief and longing might be articulated, and, finally, where guilt and loss may give rise to sentimental visions of possible future reunions. The model of stress depicted here is that resulting from trauma, which manifests in later life as a psychological disturbance affecting sleep. For Dickens, I will argue, the state of the mind as it was emerging from sleep was fundamentally associated with human mortality and fragility, and it facilitated the possibility of crossing between different temporalities and states of being, while positing a kind of threshold to the past, the future and the dead.
Accounting for sleep loss in early modern England
Authors: Handley Sasha
Published: April 2020

How did people in the sixteenth and seventeenth centuries account for sleep loss? This article answers this question through an in-depth analysis of the life-writings of six early modern women and men that suffered from periodic or persistent episodes of sleep loss. It focuses on the ways in which these health crises were understood to impede the ordinary functions of body and mind, while also revealing how gendered discourses of illness shaped female and male explanations of sleep loss in different ways. The article is the first to identify early modern sleep loss as an acknowledged
cause
of poor mental health. It also sheds important light on how the distinctive medical culture of the period
ca
1500–1700 encouraged ordinary householders to protect the quality of their sleep by moderating their bedtimes, diets, emotions, and by preparing soporific remedies for the home. This evidence shows that restorative sleep was treasured as an unparalleled guardian and barometer of physical, mental and spiritual health.
Sleep and stress management in Enlightenment literature and poetry
Authors: Lawlor Clark , Blackwood Ashleigh
Published: April 2020

‘Sleep and stress management in Enlightenment literature and poetry’ argues that the relationship between sleep and stress, as we now call it, was well known in long eighteenth-century Britain. This period was one of changing theories about the nature of the body and mind due to the shift from received wisdom and religious dogma to modern experimental science, although there were some continuities with older ideas about regimen from classical medicine. The stresses known to disrupt sleep were often associated with unhealthy lifestyles and pressures of fashionable people of the upper classes, with the lower orders thought to be less susceptible to broken sleep because of their healthier modes of living (less sedentary, less corrupted by rich food and drink, earlier sleeping times more connected with natural rhythms). This article also argues that information about managing stress and sleep was delivered to a wide public audience, not only in prose self-help manuals, but also in ‘regimen’ poetry written by doctors. Highly popular poems such as Dr Edward Baynard's comicalHealth, A Poem(1719), and Dr John Armstrong'sThe Art of Preserving Health: A Poem(1744) gave medical lifestyle advice in an entertaining literary form that sugared the pill of dull lifestyle recommendations and treatments.
Sleep deprivation and stress: a reciprocal relationship
Authors: Nollet Mathieu , Wisden William , Franks Nicholas P.
Published: April 2020

Sleep is highly conserved across evolution, suggesting vital biological functions that are yet to be fully understood. Animals and humans experiencing partial sleep restriction usually exhibit detrimental physiological responses, while total and prolonged sleep loss could lead to death. The perturbation of sleep homeostasis is usually accompanied by an increase in hypothalamic–pituitary–adrenal (HPA) axis activity, leading to a rise in circulating levels of stress hormones (e.g. cortisol in humans, corticosterone in rodents). Such hormones follow a circadian release pattern under undisturbed conditions and participate in the regulation of sleep. The investigation of the consequences of sleep deprivation, from molecular changes to behavioural alterations, has been used to study the fundamental functions of sleep. However, the reciprocal relationship between sleep and the activity of the HPA axis is problematic when investigating sleep using traditional sleep-deprivation protocols that can induce stressper se. This is especially true in studies using rodents in which sleep deprivation is achieved by exogenous, and potentially stressful, sensory–motor stimulations that can undoubtedly confuse their conclusions. While more research is needed to explore the mechanisms underlying sleep loss and health, avoiding stress as a confounding factor in sleep-deprivation studies is therefore crucial. This review examines the evidence of the intricate links between sleep and stress in the context of experimental sleep deprivation, and proposes a more sophisticated research framework for sleep-deprivation procedures that could benefit from recent progress in biotechnological tools for precise neuromodulation, such as chemogenetics and optogenetics, as well as improved automated real-time sleep-scoring algorithms.
A Mathematical prediction of the time evolution of the Covid-19 pandemic in some countries of the European Union using Monte Carlo simulations
Authors: Ciufolini Ignazio , Paolozzi Antonio
Published: April 2020

In this paper we study the statistical evolution in time of the Covid-19 pandemic in Spain, Italy, Germany, Belgium, The Netherlands, Austria and Portugal, i.e., the countries of the European Union (EU) that have a number of positive cases higher than 12 thousand at April 7, 2020. France is the third country of the EU for number of cases but a jump in the data on April 3, 2020 does not allow, at least for the moment, to have a reliable prediction curve. The analysis is based on the use of a function of the type of a Gauss Error Function, with four parameters, as a Cumulative Distribution Function (CDF). A Monte Carlo analysis is used to estimate the uncertainty. The approach used in this paper is mathematical and statistical and thus does not explicitly consider a number of relevant issues, including number of nasopharyngeal swabs, mitigation measures, social distancing, virologic, epidemiological and models of contamination diffusion.