Τρίτη, 17 Ιουλίου 2018

Periprocedural management of patients with subarachnoid hemorrhage

Purpose of review Anesthesiologists and intensivists may be involved in the management of aneurysmal subarachnoid hemorrhage (aSAH) patients at various stages of care. This article will review the recent advances in the periprocedural management of aSAH patients. Recent findings New scoring systems to assess gravity and prognosis of aSAH patients have been evaluated and proposed. Rebleeding still remains, with early aneurysmal treatment, a major challenge in the first hours of aSAH management. In the last decades, the treatment of the aSAH has shifted from clipping to coiling and more recently, the use of flow diversion technique has been introduced in selected patients. Although these improvements allow treatment of more complex aneurysms, they have implications for the anesthesiologist, including requiring the management of anticoagulation with its inherent risks. Even though knowledge, monitoring, and management of postprocedural phase of aSAH patients has improved, vasospasm and cerebral-delayed ischemia still remain the major and devastating complications in the postoperative course of aSAH patients. Summary Despite recent progress in the scoring, diagnosis, and treatment of aSAH patients, the periprocedural management of these patients is still a major challenge for anesthesiologists and intensivists, who are involved from the first phase of the aneurysm rupture through the postoperative phases and vasospasm period. Correspondence to Dr Paolo Gritti, Department of Anaesthesia and Critical Care Medicine, Ospedale Papa Giovanni XXIII, Bergamo, Italy. Tel: +39 035 2675160/+39 339 8707380; fax: +39 035 2674979; e-mail: Grittip@libero.it Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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An update on regional analgesia for rib fractures

Purpose of review To provide an update on new strategies for pain management after rib fractures utilizing regional analgesia. Recent findings Pain management for patients with rib fractures can be very challenging. Traditionally, intravenous patient-controlled analgesia (IVPCA) with opioids, epidural, and paravertebral blocks have been used. These techniques, however, may be contraindicated or have limited application in certain patient populations. Recently, ultrasound-guided myofascial plane blocks such as the erector spinae plane (ESP) block and the serratus anterior plane (SAP) block have emerged as alternatives; providing excellent analgesia with minimal side effects. These blocks have the flexibility to be employed in a wide variety of circumstances where epidural and paravertebral approaches may not be feasible such as in anticoagulated patients and in patients with vertebral fractures where positioning options are limited. Myofascial blocks are less invasive and allow for broader and earlier application (e.g. in the emergency department). Further research on myofascial plane blocks is a priority. Summary Until recently, epidural, paravertebral, and intercostal blocks have been advocated as primary management techniques for pain associated with rib fractures. Newer myofascial plane blocks may play a key role in the future as part of alternative pain management strategies. Correspondence to Sanjib Das Adhikary, Department of Anaesthesiology and Perioperative Medicine, Penn State Hershey Medical Center, Penn State College of Medicine, 500, Univ. Drive, Hershey, PA 17033, USA. Tel: +1 717 8294201; e-mail: sadhikary1@pennstatehealth.psu.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Anesthesia for stroke rescue

Purpose of review To highlight the potential implications of recent advances in the management of large vessel occlusions for intraprocedural anesthetic management. Recent findings Stroke remains the leading cause of disability in the United States and the second leading cause of death in the world. Several randomized control trials published within the past decade have helped to make endovascular thrombectomy the standard of care for all eligible patients. However, whether intraprocedural anesthesia care practices may significantly improve in-hospital and out-of-hospital morbidity and mortality outcomes are not clear. Summary Management strategies that shorten the time to intervention and maintain blood pressure to preserve penumbral tissue may be beneficial. Future well powered studies are necessary to enable inferences on what type of anesthetic management is harmless, neurotoxic, or neural plasticity promoting. Correspondence to Ayòtúndé B. Fadayomi, MBBS, MPH, Center for Epidemiology, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. E-mail: ayofadayomi@mail.harvard.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Intraoperative neurophysiological monitoring in neuroanesthesia

Purpose of review The purpose of this review is to highlight the importance of making informed choices of anesthetics and evaluating the impact of depth of anesthesia, hemodynamic status and other factors capable of interfering with signal capture during intraoperative neurophysiological monitoring (IONM). Recent findings Over the last decades, neuromonitoring has advanced considerably, allowing for insights into neurological function during anesthesia and making it possible to assess intraoperative consciousness and neural integrity in real time. IONM is indicated in surgeries posing risk to targeted neural tissues and adjacent structures. The technique helps correlate surgical maneuvers with neurophysiological changes at high levels of sensitivity and specificity and can identify risk situations early enough to prevent postoperative neurological deficits. Summary Experience with IONM, the use of an adequate IONM modality, and knowledge of the effect of anesthetic techniques and agents on neurophysiological parameters are fundamental for reliable measurements. The current gold standard in IONM is total intravenous anesthesia without neuromuscular block. Correspondence to Rogean R. Nunes, MD, PhD, Rua Comendador Francisco d'Angelo 1185, De Lourdes, Fortaleza, Ceará, Brazil, CEP: 60.177-130. E-mail: rogean@yahoo.com Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Outcomes of regional anesthesia in cancer patients

Purpose of review To summarize the current evidence on the impact of regional anesthesia or analgesia on cancer recurrence. Recent findings Preclinical investigations suggest that regional anesthesia could have a positive impact on reducing cancer growth and progression. Regional anesthesia is also associated with better immunological and stress-related outcomes in patients undergoing major oncological surgery. Most recent retrospective studies do not show any benefit of regional anesthesia or analgesia on cancer recurrence or recurrence-free survival. Summary The available clinical evidence does not support the use of any anesthesia technique to improve the cancer-related survival after major oncological surgery. The results from four randomized controlled trials will shed light on this critical topic in perioperative medicine. Correspondence to Juan P. Cata, MD, Department of Anesthesiology and Perioperative Medicine, The University of Texas – MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77401, USA. Tel: +713 792 4582; e-mail: jcata@mdanderson.org Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Loneliness and cardiovascular reactivity to acute stress in younger adults

Publication date: Available online 17 July 2018

Source: International Journal of Psychophysiology

Author(s): Eoin Gavin Brown, Ann-Marie Creaven, Stephen Gallagher

Abstract

Loneliness is connected to poorer health outcomes with stress reactivity proposed as an underlying mechanism. The present study explored whether the relationship between loneliness and cardiovascular reactivity (CVR) varies across acute psychological stress tasks. Eighty-eight healthy younger adults completed a psychometric measure of loneliness and participated in a standardised cardiovascular stress-testing protocol, with a public speaking and a mental arithmetic task. Cardiovascular functioning was assessed before and during the acute stress exposure. Higher levels of loneliness significantly predicted lower total peripheral resistance (TPR) reactivity to the public speaking task but not to the arithmetic challenge. This suggests that the effect of loneliness on cardiovascular reactivity to acute stress may vary by stressor type. These findings are discussed in relation to future research.



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Azithromycin Resistance in Clinical Isolates of Salmonella enterica Serovars Typhi and Paratyphi in Bangladesh

Microbial Drug Resistance, Ahead of Print.


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Tooth fractures in the Krapina Neandertals

Publication date: Available online 17 July 2018

Source: Journal of Human Evolution

Author(s): Maria Giovanna Belcastro, Valentina Mariotti, Alessandro Riga, Benedetta Bonfiglioli, David W. Frayer

Abstract

Dental fractures can be produced during life or post-mortem. Ante-mortem chipping may be indicative of different uses of the dentition in masticatory and non-masticatory activities related to variable diets and behaviors. The Krapina collection (Croatia, 130,000 years BP), thanks to the large number of teeth (293 teeth and tooth fragments) within it, offers an excellent sample to investigate dental fractures systematically. Recorded were the distribution, position and severity of the ante-mortem fractures according to standardized methods. High frequencies of teeth with chipping in both Krapina adults and subadults suggest that the permanent and deciduous dentition were heavily subjected to mechanical stress. This is particularly evident when the frequencies of chipping are compared with those in modern humans (Upper Paleolithic and historic samples) that we analysed using the same methods. The distribution of chipping in the Krapina sample (anterior teeth are more affected) and its position (labial) suggest a systematic use of the anterior teeth for non-masticatory tasks.



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Biomechanical implications of the onset of walking

Publication date: Available online 17 July 2018

Source: Journal of Human Evolution

Author(s): Libby W. Cowgill, Rob'yn A. Johnston

Abstract

Changes in long bone strength associated with the onset of bipedal walking in humans have been previously documented in a longitudinal growth sample. However, it is unclear if this transition can be detected using archaeological, cross-sectional data, which likely encompass more cultural and biological variation than a single dataset of living children. Focusing on variation in cross-sectional polar second moment of area, we evaluate the ratios of femoral, tibial, and humeral strength in seven temporally diverse samples of individuals from birth to the age of eighteen years (n = 501), with subsequent comparisons to immature Late Pleistocene fossils. Using these samples, we determine whether changes related to the developmental onset of bipedality can be detected in a large, multi-population sample, test for differences in long bone strength ratios among Holocene groups that may indicate developmental differences in the onset of walking, and determine whether immature Late Pleistocene samples follow the same patterns as modern humans.

Despite great variation within the Holocene sample, clear changes in these ratios are apparent around the age of the onset of walking. Humeral-to-femoral strength increases briefly prior to the age of one, with a sharp decline in relative humeral strength thereafter until age four. A similar pattern is apparent in the ratio of humeral/tibial and femoral/tibial strength. While the general pattern is consistent across all human groups sampled, these ratios vary by skeletal population, which seems to be closely related to variation in tibial length among samples. Although the extremely small fossil sample makes differences difficult to interpret, Neandertals also differ from both Late Pleistocene and Holocene modern humans in their strength ratios. Further research in this area may provide additional information about the skeletal impact of the onset of walking in the past and in additional fossil taxa.



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A Guide to Understanding the Benefits of a Multidisciplinary Team Approach to Amyotrophic Lateral Sclerosis (ALS) Treatment

Publication date: Available online 17 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Lucas D. Driskell, Michele K. York, Patricia C. Heyn, Mohammed Sanjak, Claire MacAdam



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Driving After Mild Stroke

Publication date: Available online 17 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Hannes Devos, Ickpyo Hong, Amanda Frias, Suzanne Burns, Jaclyn Schwartz, Abiodun Akinwuntan



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Trigger point manual therapy for the treatment of chronic non-cancer pain in adults: a systematic review and meta-analysis

Publication date: Available online 17 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Diarmuid Denneny, Helena C. Frawley, Katrine Petersen, Rebecca McLoughlin, Suzanne Brook, Salma Hassan, Amanda C. de C Williams

Abstract
Objective

To determine the effectiveness of trigger point manual therapy (TPMT) for reducing chronic non-cancer pain and associated problems in adults, by analysing all relevant randomised controlled trials (RCTs).

Data Sources

We searched databases and clinical trials registers from their inception to May 2017.

Study Selection

We included RCTs in any language that recruited patients over the age of 18, with pain of three months duration or more. We assessed pain, function, and patient-reported improvement as outcomes.

Data Extraction

Two authors independently extracted and verified data. Meta-analysis was completed where possible, otherwise data were synthesised narratively.

Data Synthesis

We combined all data using a random-effects model and assessed the quality of evidence using GRADE. 19 trials (involving 1047 participants) met inclusion criteria, representing TPMT treatment for musculoskeletal, pelvic and facial pain. No effect was found for short-term pain relief (mean standardized difference -0.53, 95% CI -1.08 to 0.02). One small study showed a longer-term benefit for pain (mean standardized difference --2.00 (95% CI -3.40 to -0.60) but with low confidence in the effect. Significant gains emerged for function (mean standardized difference -0.77, 95% CI -1.27 to -0.26, and in patient global response (odds ratio 3.79, 95% CI 1.86 to 7.71) from four studies, but not for health-related quality of life.

Conclusions

Evidence for TPMT for chronic non-cancer pain is weak and it cannot currently be recommended.



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Normative values for sleep parameters in pre-schoolers using actigraphy

Publication date: September 2018

Source: Clinical Neurophysiology, Volume 129, Issue 9

Author(s): Lassi Sahlberg, Helena Lapinleimu, Marko Elovainio, Hanni Rönnlund, Irina Virtanen

Abstract
Objective

There are currently no reference values for actigraphy-measured sleep length and fragmentation in preschool children. We created standardized parameters using a community sample.

Methods

Ninety-seven 2-to-6-year-old children (56 boys) wore an actigraph on their non-dominant wrist for seven days. The data was extracted and scored, calculating total sleep time, sleep latency, sleep efficiency, fragmentation index, circadian rhythm length, cosine peak and light/dark ratio. Subjects were divided into groups of 2–3-year-olds, 4–5-year-olds and 6-year-olds. Means and standard deviations were calculated, and reference values were created using the 2.5th and the 97.5th percentiles.

Results

Reference intervals were 7 h 23 min–9 h 47 min for 24-hour total sleep time, 0.2–48.4 min for sleep latency, 69–87% for sleep efficiency, 23–53% for fragmentation index, 23 h 39 min–24 h 24 min for circadian rhythm length, 12:37–15:53 for the timing of the cosine peak, and 1.14–5.63 for the light-dark ratio. With increasing age, daily sleep time, sleep latency, sleep fragmentation, and napping decreased.

Conclusions

We were able to create previously non-established reference values, including trends with increasing age, on actigraphy-assessed sleep in preschool children.

Significance

Sleep disorders in young children are easier to evaluate against normative data.



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Developmental expression of the zebrafish Arf-like small GTPase paralogs arl13a and arl13b

Publication date: September 2018

Source: Gene Expression Patterns, Volume 29

Author(s): Ping Song, Brian D. Perkins

Abstract

Members of the Arf-like (Arl) family of small GTP-binding proteins regulate a number of cellular functions and play important roles in cilia structure and signaling. The small GTPase Arl13a is a close paralog to Arl13b, a small GTPase required for normal cilia formation that causes Joubert Syndrome when mutated. As mutation of arl13b causes a slow retinal degeneration in zebrafish (Song et al., 2016), we hypothesized that expression of arl13a may provide functional redundancy. We determined the expression domains of arl13a and arl13b during zebrafish development and examined subcellular localization by expression of fluorescence fusion proteins. Both genes are widely expressed during early cell division and gastrulation and Arl13a and Arl13b both localize to microtubules in ciliated and dividing cells of the early zebrafish embryo. Between 2 and 5 days post fertilization (dpf), arl13b is expressed in neural tissues while expression of arl13a is downregulated by 2 dpf and restricted to craniofacial structures. These results indicate that arl13a and arl13b have evolved different roles and that arl13a does not function in the zebrafish retina.



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VCSRA: A fast and accurate multiple sequence alignment algorithm with a high degree of parallelism

Publication date: Available online 17 July 2018

Source: Journal of Genetics and Genomics

Author(s): Dong Dong, Wenhe Su, Wenqiang Shi, Quan Zou, Shaoliang Peng



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Cathepsin B inhibition ameliorates the non-alcoholic steatohepatitis through suppressing caspase-1 activation

Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease. NLRP3 inflammasome activation has been widely studied in the pathogenesis of NAFLD. Cathepsin B (CTSB) is a ubiquitous cysteine cathepsin, and the role of CTSB in the progression and development of NAFLD has received extensive concern. However, the exact roles of CTSB in the NAFLD development and NLRP3 inflammasome activation are yet to be evaluated. In the present study, we used methionine choline-deficient (MCD) diet to establish mice NASH model. CTSB inhibitor (CA-074) was used to suppress the expression of CSTB. Expressions of CTSB and caspase-1 were evaluated by immunohistochemical staining. Serum IL-1β and IL-18 levels were also determined. Palmitic acid was used to stimulate Kupffer cells (KCs), and protein expressions of CTSB, NLRP3, ASC (apoptosis-associated speck-like protein containing CARD), and caspase-1 in KCs were detected. The levels of IL-1β and IL-18 in the supernatant of KCs were evaluated by enzyme-linked immunosorbent assay (ELISA). Our results showed that CTSB inhibition improved the liver function and reduced hepatic inflammation and ballooning, and the levels of pro-inflammatory cytokines IL-1β and IL-18 were decreased. The expressions of CTSB and caspase-1 in liver tissues were increased in the NASH group. In in vitro experiments, PA stimulation could increase the expressions of CTSB and NLRP3 inflammasome in KCs, and CTSB inhibition downregulated the expression of NLRP3 inflammasome in KCs, when challenged by PA. Moreover, CTSB inhibition effectively suppressed the expression and activity of caspase-1 and subsequently secretions of IL-1β and IL-18. Collectively, these results suggest that CTSB inhibition limits NLRP3 inflammasome-dependent NASH formation through regulating the expression and activity of caspase-1, thus providing a novel anti-inflammatory signal pathway for the therapy of NAFLD.



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Genome Report: Whole Genome Sequence of the Parasitoid Wasp Microplitis demolitor That Harbors an Endogenous Virus Mutualist

Microplitis demolitor(Hymenoptera: Braconidae) is a parasitoid used as a biological control agent to control larval-stage Lepidoptera and serves as a model for studying the function and evolution of symbiotic viruses in the genus Bracovirus. Here we present the M. demolitor genome (assembly version 2.0), with a genome size of 241 Mb, and a N50 scaffold and contig size of 1.1 Mb and 14 Kb, respectively. Using RNA-Seq data and manual annotation of genes of viral origin, we produced a high-quality gene set that includes 18,586 eukaryotic and 171 virus-derived protein-coding genes. Bracoviruses are dsDNA viruses with unusual genome architecture, in which the viral genome is integrated into the wasp genome and is comprised of two distinct components: proviral segments that are amplified, circularized, and packaged into virions for export into the wasp's host via oviposition; and replication genes. This genome assembly revealed that at least two scaffolds contain both nudivirus-like genes and proviral segments, demonstrating that at least some of these components are near each other in the genome on a single chromosome. The updated assembly and annotation are available in several publicly accessible databases; including the National Center for Biotechnology Information and the Ag Data Commons. In addition, all raw sequence data available for M. demolitor have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the 'microgastroid complex'), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes. have been consolidated and are available for visualization at the i5k Workspace. This whole genome assembly and annotation represents the only genome-scale, annotated assembly from the lineage of parasitoid wasps that has associations with bracoviruses (the 'microgastroid complex'), providing important baseline knowledge about the architecture of co-opted virus symbiont genomes.



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Rapid Low-Cost Assembly of the Drosophila melanogaster Reference Genome Using Low-Coverage, Long-Read Sequencing

Accurate and comprehensive characterization of genetic variation is essential for deciphering the genetic basis of diseases and other phenotypes. A vast amount of genetic variation stems from large-scale sequence changes arising from the duplication, deletion, inversion, and translocation of sequences. In the past 10 years, high-throughput short reads have greatly expanded our ability to assay sequence variation due to single nucleotide polymorphisms. However, a recent de novo assembly of a second Drosophila melanogaster reference genome has revealed that short read genotyping methods miss hundreds of structural variants, including those affecting phenotypes. While genomes assembled using high-coverage long reads can achieve high levels of contiguity and completeness, concerns about cost, errors, and low yield have limited widespread adoption of such sequencing approaches. Here we resequenced the reference strain of D. melanogaster (ISO1) on a single Oxford Nanopore MinION flow cell run for 24 hours. Using only reads longer than 1 kb or with at least 30x coverage, we assembled a highly contiguous de novo genome. The addition of inexpensive paired reads and subsequent scaffolding using an optical map technology achieved an assembly with completeness and contiguity comparable to the D. melanogaster reference assembly. Comparison of our assembly to the reference assembly of ISO1 uncovered a number of structural variants (SVs), including novel LTR transposable element insertions and duplications affecting genes with developmental, behavioral, and metabolic functions. Collectively, these SVs provide a snapshot of the dynamics of genome evolution. Furthermore, our assembly and comparison to the D. melanogaster reference genome demonstrates that high-quality de novo assembly of reference genomes and comprehensive variant discovery using such assemblies are now possible by a single lab for under $1,000 (USD).



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Comparison of clinical efficacy of transforaminal and caudal epidural steroid injection in lumbar and lumbosacral disc herniation: A systematic review and meta-analysis

Epidural steroid injection (ESI) has been used to treat back or radicular pain from lumbar and lumbar and lumbosacral disc herniation (LDH). However, the superiority of transforaminal injection (TFESI) to caudal injection (CESI) remains controversial.

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Digital biomarkers of spine and musculoskeletal disease from accelerometers: Defining phenotypes of free-living physical activity in knee osteoarthritis and lumbar spinal stenosis

Lumbar spinal stenosis (LSS) and knee osteoarthritis (OA) are two of the leading causes of disability worldwide. In order to provide disease-specific prescriptions for physical activity, there is a clear need to better understand physical activity in daily life (performance)in these populations.

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Egr-1 transactivates WNT5A gene expression to inhibit glucose-induced β-cell proliferation

Publication date: Available online 17 July 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): XingEr Wu, ZeHong Li, Kang Chen, PeiHong Yin, Lei Zheng, ShiJun Sun, XiaoYu Chen

Abstract

Selective β-cell loss is a characteristic of type 2 diabetes mellitus (T2DM). Inhibition of glucose-stimulated β-cell proliferation is one of the in vivo results of the lipotoxicity of saturated fatty acids (SFAs). However, the mechanism by which lipotoxicity inhibits β-cell proliferation is still unclear. In this study, we found palmitate, a saturated fatty acid, inhibited the β-cell proliferation induced by high glucose through the induction of Wnt5a expression in vitro and in vivo. We also found that Wnt5a was both sufficient and necessary for inhibition of β-cell proliferation. Additionally, Egr-1, but not NF-κB, FOXO1, Smad2, Smad3, SP1 or SP3 mediated the expression of Wnt5a. Deletion and site-directed mutagenesis of the WNT5A promoter revealed that activation of WNT5A gene transcription depends primarily on a putative Egr-binding sequence between nucleotides −52 to −44, upstream of the transcription start site. Furthermore, Egr-1 bound directly to this sequence in response to palmitate treatment, both in vitro and in vivo. Moreover, after mice islets were treated with Egr inhibitors, the expression of Wnt5a decreased significantly and the glucose-induced β-cell proliferation inhibited by palmitate was resumed. These findings establish Wnt5a as an Egr-1 target gene in β-cells, uncovering a novel Egr-1/Wnt5a pathway by which saturated free fatty acids block glucose-induced β-cell proliferation. Our study lends support for the potential of Egr-1 inhibitors or Wnt5a antibodies as therapeutics for the treatment of T2DM.



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YAP transcriptionally regulates ErbB2 to promote liver cell proliferation

Publication date: Available online 17 July 2018

Source: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms

Author(s): Evan Y. Wang, Jung-Chien Cheng, Avinash Thakur, Yuyin Yi, Shu-Huei Tsai, Pamela A. Hoodless

Abstract

The Hippo signaling pathway is implicated in regulation of liver size and dysregulation of this pathway contributes to tumorigenesis. The transcriptional targets and downstream pathways of the Hippo pathway effector YAP that contribute to liver growth have yet to be well-characterized. We examined the liver transcriptome in response to YAP overexpression and identify the ErbB signaling pathway as a mediator of cell growth downstream of YAP. ErbB2 is transcriptionally regulated by YAP in both the mouse liver and in HepG2 human hepatoma cells. Knockdown of YAP or pharmacological inhibition with verteporfin reduced ERBB2 levels in HepG2 cells. Analysis of ChIP-seq data revealed enrichment of the transcription factor TEAD4 at the ERBB2 promoter. Using luciferase reporter and chromatin immunoprecipitation assays, we show that YAP and TEAD4 directly bind to and activate a regulatory element in the ErbB2 promoter in both the mouse liver and HepG2 cells. Functionally, knockdown of YAP reduced EGF-induced ERBB2-mediated HepG2 cell proliferation and PI3K/AKT activation. Our findings highlight a mechanism by which YAP exerts its effects on liver cell proliferation through the ErbB signaling pathway by directly regulating the transcription of ErbB2.

Graphical abstract

Unlabelled Image



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Appropriateness in prescribing PPIs: a position paper of the Italian Society of Gastroenterology (SIGE) − Study Section “Digestive Diseases in Primary Care”

The introduction of proton pump inhibitors (PPIs) into clinical practice about thirty years ago has greatly improved our therapeutic approach to acid-related diseases for their well-recognized efficacy and safety.Despite the well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and this phenomenon poses serious queries that include the onset of potential adverse effects and the increase in health care costs. The major reason explaining this worrying market expansion is the inappropriate use of PPIs.

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Management of hilum infiltrating tumors of the liver: The impact of experience and standardization on outcome



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Unexpected intestinal bypass



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Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients

Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted.

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Appropriateness in prescribing PPIs: a position paper of the Italian Society of Gastroenterology (SIGE) − Study Section “Digestive Diseases in Primary Care”

The introduction of proton pump inhibitors (PPIs) into clinical practice about thirty years ago has greatly improved our therapeutic approach to acid-related diseases for their well-recognized efficacy and safety.Despite the well-defined indications, however, the use of PPIs continues to grow every year in both western and eastern countries and this phenomenon poses serious queries that include the onset of potential adverse effects and the increase in health care costs. The major reason explaining this worrying market expansion is the inappropriate use of PPIs.

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Management of hilum infiltrating tumors of the liver: The impact of experience and standardization on outcome



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Unexpected intestinal bypass



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Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients

Diabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted.

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Examining Temporal Trends in Documentation of Pregnancy Intentions in Family Planning Health Centers Using Electronic Health Records

Abstract

Objectives Few studies have examined the extent to which providers assess pregnancy intentions during clinical encounters. Our objective was to assess temporal trends in documentation of patient pregnancy intentions in electronic health records (EHR). Methods In this retrospective observational study using EHR data from 627,399 female patients visiting 214 family planning centers in 2012–2014, we assessed changes in the prevalence of pregnancy intention documentation with piecewise log-binomial regression models. We examined bivariate associations between patient/visit characteristics and pregnancy intention documentation in each year, and associations between patients' pregnancy intentions and contraceptive methods. Results The proportion of patients with a documented pregnancy intention increased sharply from the end of 2012 (42%) to the midpoint of 2013 (85%; adjusted quarterly prevalence ratio [APR] = 1.40, 95% CI 1.36–1.45). Thereafter, the rate of change slowed as documentation approached the maximum possible frequency (93%; APR = 1.01, 95% CI 1.00–1.02). Documentation varied by all patient/visit characteristics in 2012 and 2013; in 2014, there were no clinically significant differences. Among patients with a documented intention, 97% were not planning a pregnancy in the next year. Women not planning a pregnancy were more likely to use a most/moderately effective contraceptive method than those planning a pregnancy (73 vs. 35%, p < 0.0001). Conclusions for Practice Improvements in pregnancy intention documentation co-occurred with changes to EHR templates (e.g., placement of structured data fields) and with provider-focused initiatives promoting reproductive life planning. Patients' pregnancy intentions aligned with contraceptive use; however, these findings cannot address whether assessment of intentions affects contraceptive use.



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Sexual Orientation Disparities in Pregnancy and Infant Outcomes

Abstract

Objectives Little is known about maternal and infant health among sexual minority women (SMW), despite the large body of research documenting their multiple preconception risk factors. This study used data from the 2006–2015 National Survey of Family Growth (NSFG) to investigate sexual orientation inequities in pregnancy and birth outcomes, including miscarriage, stillbirth, preterm birth, and birth weight. Methods Women reported 19,955 study eligible pregnancies and 15,996 singleton live births. Sexual orientation was measured using self-reported identity and histories of same-sex sexual experiences (heterosexual-WSM [women who only report sex with men]; heterosexual-WSW [women who report sex with women]; bisexual, and lesbian). Logistic regression models were used that adjusted for several maternal characteristics. Results Compared to heterosexual-WSM, heterosexual-WSW (OR 1.25, 95% CI 1.00–1.58) and bisexual and lesbian women (OR 1.77, 95% CI 1.34–2.35) were more likely to report miscarriage, and bisexual and lesbian women were more likely to report a pregnancy ending in stillbirth (OR 2.85, 95% CI 1.40–5.83). Lesbian women were more likely to report low birth weight infants (OR 2.64, 95% CI 1.38–5.07) and bisexual and lesbian women were more likely to report very preterm births (OR 1.84, 95% CI 1.11–3.04) compared to heterosexual-WSM. Conclusions for Practice This study documents significant sexual orientation inequities in pregnancy and birth outcomes. More research is needed to understand the mechanisms that underlie disparate outcomes and to develop interventions to improve sexual minority women's maternal and infant health.



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Conservation of mRNA quality control factor Ski7 and its diversification through changes in alternative splicing and gene duplication [Genetics]

Eukaryotes maintain fidelity of gene expression by preferential degradation of aberrant mRNAs that arise by errors in RNA processing reactions. In Saccharomyces cerevisiae, Ski7 plays an important role in this mRNA quality control by mediating mRNA degradation by the RNA exosome. Ski7 was initially thought to be restricted to Saccharomyces...

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Safety and efficacy of elbasvir and grazoprevir in Japanese hemodialysis patients with genotype 1b hepatitis C virus infection

Abstract

Background

The prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is high and results in a poor prognosis. Thus, safer and more effective treatment regimens are required. In this prospective multicenter study, we investigated the efficacy and safety of the novel HCV-NS5A-inhibitor, elbasvir, and protease inhibitor, grazoprevir in Japanese hemodialysis patients with genotype 1b HCV infection.

Methods

This study is registered at the UMIN Clinical Trials Registry as UMIN00002578. A total of 23 Japanese dialysis patients with genotype 1b HCV infection who were treated with elbasvir and grazoprevir between January 2017 and March 2018 and followed for more than 12 weeks after treatment completion were included. We evaluated the sustained virologic response at 12 weeks after treatment completion (SVR12) and safety during treatment.

Results

Of the 23 patients, 7 had advanced liver fibrosis and 2 had a signature resistance-associated variant of NS5A (NS5A RAVs)-L31M/V or Y93H at baseline. All patients completed therapy, and 96.7% (22/23) of the patients achieved SVR12. All patients with advanced liver fibrosis and signature NS5A RAVs at baseline achieved SVR12 with a high safety profile. No patient experienced lethal or severe adverse events during therapy, and the most common adverse event was anemia. One patient, who was a non-responder to this therapy, had a history of failure with daclatasvir and asunaprevir therapies and had NS5A RAVs of A92K at baseline, but not signature NS5A RAVs.

Conclusions

Grazoprevir and elbasvir combination is highly effective and safe for hemodialysis patients with genotype 1b HCV infection.



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Cricket Injury Epidemiology in the Twenty-First Century: What is the Burden?

Abstract

Background

At the turn of the century, a new format of cricket [Twenty20 (T20)] was introduced that has led to more matches being played. Since then, it has been debated whether T20 cricket has increased the risk of overuse injuries.

Objectives

The primary aim of this study was to meta-analyse the cricket injury rates in the twenty-first century. The secondary aims were to explore the risk factors and mechanisms of injury by analysing correlates such as age, format, era of play, country, player type, etc., and to conduct a qualitative analysis of the published studies.

Methods

Several databases were searched using keywords "cricket" and "injur*" and 24 papers reporting cricket injuries fitted the inclusion criteria. Fifteen papers included data on exposure time and were used to calculate injury rates to perform sub-group analysis.

Results

Pooled data on 12,511 players revealed 7627 injuries, and the 1.12 million hours of cricket play from 15 studies reporting exposure time showed an injury rate of 53.16 (95% confidence interval 51.84–54.52) per 10,000 h of play. There were no statistically significant differences in injury rates based on age, format, era of play, country, player type and injury definitions. Bowling biomechanics and workload were identified as the major risk factors for bowling injuries.

Conclusions

This review shows that injury rates in junior and amateur cricket are higher than the injury rates of comparable cohorts playing other popular non-contact or quasi-contact team sports. There is not enough evidence to conclude that T20 cricket has increased injury rates.



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NAEMSP applauds formation of FDA drug shortages task force

WASHINGTON, D.C. — The National Association of EMS Physicians (NAEMSP) applauds the Food and Drug Administration's (FDA) formation of a Drug Shortages Task Force, which was created at the urging of Congress, NAEMSP and other medical groups representing physicians and medical professionals throughout the U.S. NAEMSP - an organization of more than 1,500 physicians and EMS professionals...

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Maternal Depression Scale: Do “Drop-In” Laborist Patients Have Increased Postpartum Screening Risks Compared to Patients with Adequate Prenatal Care?

Abstract

Objectives The Edinburgh Postnatal Depression Scale (EPDS) identifies women with depressive symptoms in pregnancy. Our primary objective was to determine the prevalence of EPDS screen-positive women delivering on our no prenatal care (laborist) service and to compare these patients to private patients delivering with prenatal care. Methods Retrospective cohort analysis of EPDS scores during January 1, 2015 to June 18, 2015 was conducted. Scores ≥ 10 were considered at-risk. Results were analyzed as an aggregate and then as no prenatal care versus prenatal care. Characteristics for patients with at-risk scores (EPDS ≥ 10) versus low-risk scores (EPDS < 10) were quantified. Results Analysis occurred on 970 women. EPDS ≥ 10 occurred in 12.4% (n = 120/970). Positive EPDS score was 21.1% without prenatal care versus 10.9% with adequate prenatal care (P = 0.003). Maternal demographics and delivery characteristics were clinically similar in patients with prenatal care compared to no prenatal care. Private insurance was more common in patients with prenatal care compared to no prenatal care (23.5 versus 8.1%, P = 0.0001). However, analysis of patients with EPDS > 10 showed non-significant distributions of ethnicity, private insurance, Medicaid, or no insurance compared to patients with EPDS < 10. Conclusion for Practice Patients without prenatal care who arrive solely for urgent "drop-in" delivery have a measurable increased risk factor for postpartum depressive symptoms. Ethnicity and payor status were related to adequacy of prenatal care but were not significant variables when analyzing patients with EPDS > 10. Laborist services providing care to "drop-in" patients should recognize this increased risk and develop policies for screening, referral and follow-up of at-risk patients.



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Reflecting on Alma Ata 1978: forty years on

The Alma Ata declaration was a product of its time. It came about from a recognition that, in an increasingly prosperous world, many people were being left behind. In the world's poorest countries, tens of thousands of people were dying every year from entirely avoidable conditions, lacking access to even the most basic health services. At the same time, those in the richest countries were benefiting from pharmaceutical and technological advances that would have been undreamed of even a decade earlier.

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Russia: thirty years in transition

Thirty years ago, in 1988, the Communist Party of the USSR held its 19th Conference, declaring a turn from the totalitarian past to a democratic future, to life built upon common human values. The country entered a deep transformation, 'perestroika'. The year 1988 ended with Gorbachev meeting Reagan. In 3 years Russia would declare independence from the greater USSR. The Soviet Union had outlived its vitality and usefulness and voluntarily imploded. A useful comparator is Europe, 1945, ruined in the Great War. The next 30 years Europe saw flourishing of technology, trade, governance and prosperity. Though 30 years have elapsed since the Soviet fall, Russia remains in a churning transition of doubtful accomplishment unleavened by the passage of time. Indeed, since 1988, Russia has forfeited any real chance of improving the nation's health and health care system.

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European Public Health News

In this European Public Health news, I am pleased to see that all authors formulate a strong call for European collaboration. Azzopardi Muscat warns for 'letting our guard down' as new challenges and new factors influencing public health emphasize the need for European collaboration in public health research, advocacy and action. Jakab proudly presents the setting up of a joint monitoring framework (JMF) at European level, aimed to ensure that harmonized, integrated health information systems work in tandem with health-research systems to inform policy-makers and the public with the best available information and evidence from local and global sources. Andriukaitis highlights the European Commission's proposed action plan to joint action with EU countries to help stop the spread of vaccine preventable diseases. Zeegers Paget highlights that it all starts with a few committed and engaged public health professionals to set things in motion, taking the recent First World Congress on Migration, ethnicity, race and health as an example. Erzen highlights the joint effort of many public health professionals and organizations to ensure the high scientific quality of the programme in Ljubljana. Just remember, it takes one (wo)man to start, it takes us all to engage.

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The coexistence of copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) at a locus can result in distorted calculations of the significance in associating SNPs to disease

Abstract

With the recent advance in genome-wide association studies (GWAS), disease-associated single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) have been extensively reported. Accordingly, the issue of incorrect identification of recombination events that can induce the distortion of multi-allelic or hemizygous variants has received more attention. However, the potential distorted calculation bias or significance of a detected association in a GWAS due to the coexistence of CNVs and SNPs in the same genomic region may remain under-recognized. Here we performed the association study within a congenital scoliosis (CS) cohort whose genetic etiology was recently elucidated as a compound inheritance model, including mostly one rare variant deletion CNV null allele and one common variant non-coding hypomorphic haplotype of the TBX6 gene. We demonstrated that the existence of a deletion in TBX6 led to an overestimation of the contribution of the SNPs on the hypomorphic allele. Furthermore, we generalized a model to explain the calculation bias, or distorted significance calculation for an association study, that can be 'induced' by CNVs at a locus. Meanwhile, overlapping between the disease-associated SNPs from published GWAS and common CNVs (overlap 10%) and pathogenic/likely pathogenic CNVs (overlap 99.69%) was significantly higher than the random distribution (p < 1 × 10−6 and p = 0.034, respectively), indicating that such co-existence of CNV and SNV alleles might generally influence data interpretation and potential outcomes of a GWAS. We also verified and assessed the influence of colocalizing CNVs to the detection sensitivity of disease-associated SNP variant alleles in another adolescent idiopathic scoliosis (AIS) genome-wide association study. We proposed that detecting co-existent CNVs when evaluating the association signals between SNPs and disease traits could improve genetic model analyses and better integrate GWAS with robust Mendelian principles.



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Ledipasvir/sofosbuvir effectively treats hepatitis C virus infections in an underserved population

Digestive Diseases and Sciences

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Obesity and weight gain are associated with progression of fibrosis in patients with non-alcoholic fatty liver disease

Clinical Gastroenterology and Hepatology

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Lower annual rate of progression of short-segment vs long-segment Barrett’s esophagus to esophageal adenocarcinoma

Clinical Gastroenterology and Hepatology

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Obesity is independently associated with higher annual burden and costs of hospitalization in patients with inflammatory bowel diseases

Clinical Gastroenterology and Hepatology

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Altered levels of cytokines in patients with irritable bowel syndrome are not correlated with fatigue

International Journal of General Medicine

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Cytonuclear integration and co-evolution

Cytonuclear integration and co-evolution

Cytonuclear integration and co-evolution, Published online: 17 July 2018; doi:10.1038/s41576-018-0035-9

Eukaryotic cells must regulate not only their nuclear genomes but also the intimate functional interplay with organelle genomes, such as those in mitochondria and plastids. This Review discusses the functional and evolutionary implications of cellular genomes being partitioned between the nucleus and organelles, including the translocation of genes and gene products, chimeric enzyme complexes and insights into molecular co-evolution.

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Laparoscopic resection of retroperitoneal paraganglioma behind the Spiegel lobe in a kyphotic patient: A rare case report

Asian Journal of Endoscopic Surgery, EarlyView.


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Early gastric cancer successfully treated by endoscopic submucosal resection 1 year after laparoscopic sleeve gastrectomy with duodenal‐jejunal bypass

Asian Journal of Endoscopic Surgery, EarlyView.


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Cytonuclear integration and co-evolution



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Correction to: Factors Predictive of Complete Excision of Large Colorectal Neoplasia Using Hybrid Endoscopic Submucosal Dissection: A KASID Multicenter Study

The original version of the article unfortunately contained errors in author affiliation. Affiliation of third and ninth author was incorrectly assigned.



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State Requirements for Prenatal Syphilis Screening in the United States, 2016

Abstract

Objectives This study assesses U.S. state laws related to prenatal syphilis screening, including whether these laws align with CDC screening recommendations and include legal penalties for failing to screen. Methods Statutes and regulations regarding syphilis screening during pregnancy and at delivery effective in 2016 were examined for all 50 U.S. states and the District of Columbia (DC). Targeted search terms were used to identify laws in legal research databases. The timing of the screening mandates for each state law was coded for: (1) first visit, (2) third trimester, and (3) delivery. Descriptive statistics were calculated to examine the number of states with each type of requirement and whether requirements adhered to the CDC STD treatment guidelines. Results Only six states (11.8%) do not require prenatal syphilis screening. Of states with screening requirements (n = 45), the majority (84.3%) require testing at first prenatal visit or soon after. 17 states (33.3%) require screening during the third trimester with five requiring screening only if the patient is considered at high risk. 8 (15.7%) states require screening at delivery with five requiring testing only if the woman is at high risk. 14 (27.5%) states include punishments for failing to screen (civil penalties, criminal penalties and license revocation). Conclusions for Practice Most states had prenatal syphilis screening requirements; a minority corresponded to or extended CDC recommendations. States vary in when they require testing, who must be tested, and whether a failure to screen could result in a punishment for the provider.



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Hypoxic Depression of Pacemaker Activity of Interstitial Cells of Cajal: A Threat of Gastrointestinal Dysmotility and Necrosis. A Simulation Study

Hypoxic-ischemic injury is a known risk factor of necrotizing enterocolitis (NEC), an inflammatory bowel disease of neonates, one of the most common causes of intestinal failures associated with total bowel and/or segmental disorders of intestinal motility. The gastrointestinal motility is based, to a significant extent, on pacemaker action of the interstitial cells of Cajal (ICCs) on intestinal smooth muscle cells (SMCs). We explored how the hypoxia affects ICC pacemaker activity manifested in oscillations of the cell membrane potential Em and intracellular calcium concentration [Ca2+]i, factors determined by interplay of calcium-handling mechanisms of the endoplasmic reticulum (ER) and mitochondria. The hypoxic action was simulated by a reduction of the mitochondrial bulk membrane potential (ΔΨ*) or maximal rates of Ca2+-ATPase pumps of the plasmalemma or ER (PMCA or SERCA, respectively). Loss of ΔΨ* resulted, first, in an increase in the oscillation period and, finally, in the transition of ICCs to the down-state with resting Em and basal [Ca2+]i levels. Depression of SERCA brought the ICC to the downstate with small-amplitude oscillations of Em and [Ca2+]i near the resting/basal levels. Suppression of the PMCA pump caused transition of ICCs into the up-state characterized by a persistent depolarization shift of the Em and [Ca2+]i significantly exceeding the down-state levels. Hence, hypoxic suppression of any of the above energy-consuming mechanisms led, thought in different ways, to the cessation of ICC pacemaker activity, which may have crucial pathological consequences for ICC-driven periodic contractions of electrically coupled SMCs; this can be manifested as gastrointestinal dysmotility and/or NEC.



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