The mechanical properties of biological tissues are increasingly recognized as important factors in developmental and pathological processes. Most existing mechanical measurement techniques either necessitate destruction of the tissue for access or provide insufficient spatial resolution. Here, we show for the first time a systematic application of confocal Brillouin microscopy to quantitatively map the mechanical properties of spinal cord tissues during biologically relevant processes in a contact-free and non-destructive manner.
https://ift.tt/2KpVJ3W
Παρασκευή 3 Αυγούστου 2018
Mechanical mapping of spinal cord development and repair in living zebrafish larvae using Brillouin microscopy
Plaque psoriasis following Kawasaki disease and varicella
We describe the case of a 15-month-old boy with Kawasaki disease who developed varicella 7 days after the beginning of the disease and diffuse plaque psoriasis after 43 days. Associations between Kawasaki disease and psoriasis, between Kawasaki disease and varicella and between varicella and psoriasis have all been reported in the literature. The triple association of Kawasaki disease, varicella and psoriasis is very rare. Neither the double nor the triple associations are well known among a diverse group of practitioners.
https://ift.tt/2MkKRGn
A differential diagnosis for annular lesions: contact dermatitis to transdermal rivastigmine patches
Description
During an appointment for an unrelated condition at a dermatology clinic, a 75-year-old man was noted to have a number of annular lesions on his trunk. The patient mentioned that he had been prescribed transdermal rivastigmine patches (Alzest 4.6mg/24h) for memory impairment 4 months previously. These were applied and left on for 24 hours before being replaced. He noticed that each patch left a red, pruritic area.
The patient was otherwise well, his only medication being an antihypertensive. He did not have any drug allergies or sensitivity to plasters.
On examination, there were multiple annular lesions scattered over his trunk with a predilection for the flanks (figure 1). These demonstrated an evolution of clinical features; more recent lesions were erythematous, inflamed plaques (figure 1A) which progressed into brown, postinflammatory patches (figure 1B) which gradually faded. All the lesions were well demarcated, circular and approximately 40 mm in diameter.
...
https://ift.tt/2LZN1i2
Simultaneously measuring image features and resolution in live-cell STED images
Reliable interpretation and quantification of cellular features in fluorescence microscopy require an accurate estimate of microscope resolution. This is typically obtained by measuring the image of a non-biological proxy for a point-like object, such as a fluorescent bead. While appropriate for confocal microscopy, bead-based measurements are problematic for Stimulated Emission Depletion (STED) and similar techniques where the resolution depends critically on the choice of fluorophore and acquisition parameters.
https://ift.tt/2Obca6R
Modeling reveals a key mechanism for light-dependent phase shifts of Neurospora circadian rhythms
Light shifts and synchronizes the phase of the circadian clock to daily environments, which is critical for maintaining the daily activities of an organism. It has been proposed that such light-dependent phase shifts are triggered by light-induced upregulation of a negative element of the core circadian clock (i.e. frq, Per1/2) in many organisms including fungi. However, we find that the upregulation of the frq gene expression alone is unable to reproduce the observed light-dependent phase responses using systematic mathematical modeling of the Neurospora crassa circadian clock.
https://ift.tt/2n6yO4C
Modeling in vivo interstitial hydration-pressure relationships in skin and skeletal muscle
A theoretical understanding of hydrostatic pressure- fluid volume relationships, or equations of state, of interstitial fluid in skin and skeletal muscle through mathematical/physical modeling is lacking. Here we investigate at the microscopic level forces that seem to underlie and determine the movements of fluid and solid tissue elements on the microscopic as well as on the macroscopic level. Effects that occur during variation of hydration due to interaction between expanding glycosaminoglycans (GAGs) and the collagen interstitial matrix of tissue seem to be of major importance.
https://ift.tt/2KraCTY
Protein Motion and Configurations in a Form-Fitting Nanopore: Avidin in ClyA
We probe the molecular dynamics and states of an avidin protein as it is captured and trapped in a voltage biased ClyA nanopore using time-resolved single-molecule electrical conductance signals. The data for very large numbers of single-molecule events are analyzed and presented by a new method that provides clear visual insight into the molecular scale processes. Avidin in ClyA has surprisingly rich conductance spectra that reveal transient and more permanently trapped protein configurations in the pore and how they evolve into one another.
https://ift.tt/2n9umlC
Influence of microscopic interactions on the flexible mechanical properties of viral DNAs
During the packaging and ejection of viral DNA, the mechanical properties play an essential role in viral infection. Some of these mechanical properties are originated from different microscopic interactions of the encapsulated DNA in the capsid. Based on an updated mesoscopic model of the interaction potential by Parsegian et al., an alternative continuum-elastic model of the free energy of the confined DNA in the capsid is developed in this paper. With this model we not only quantitatively identify the respective contributions from hydration repulsion, electrostatic repulsion, entropy and elastic bending, but also predict the ionic effect of viral DNA's mechanical properties during the packaging and ejection.
https://ift.tt/2O6sGVB
Spatial proliferation of epithelial cells is regulated by E-cadherin force
Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. Prior experiments have shown that externally applied forces, such as stretch, result in increased proliferation in an E-Cadherin force-dependent manner. In this study the spatial regulation of cell proliferation in large epithelial colonies was examined. Surprisingly, cells at the center of the colony still had increased proliferation as compared to cells in confluent monolayers. E-cadherin forces were found to be elevated for both cells at the edge and center of these larger colonies when compared to confluent monolayers.
https://ift.tt/2Kn5VdK
Impact of Home Care Admission Nurses' Goals on Electronic Health Record Documentation Strategies at the Point of Care
Home care nurses have multiple goals at the patient admission visit. Electronic health records support some of these goals, including high-quality documentation, but nurses may not complete the electronic documentation at the point of care. To characterize admission nurses' practices at the point of care and lay the foundation for design recommendations, this study investigates admission nurses' documentation strategies with respect to entering electronic data and how nursing goals affect them. We conducted 10 observations of home care agency admissions with five admission nurses in rural Pennsylvania. We collected screenshots and recorded the admission process. We asked the nurses questions outside the point of care. We coded the nurses' strategies at the data-entry screen level. Using thematic analysis, we investigated the influence of nursing goals on documentation strategies. Subject matter experts reviewed our findings. Several goals affect nurses' documentation strategies: ensure data accuracy, reduce time in the patient's home, and prevent infection. Home care admission nurses distribute the electronic documentation temporally due to their goals. Nurses developed memory aids to support completion of the documentation after leaving the patients' homes. Design and training should support the distributed manner in which home care nurses document patient encounters. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This project was supported by grant number R01HS024537 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. Corresponding author: Yushi Yang, PhD, College of Computing and Informatics, 3141 Chestnut St, Drexel University, Philadelphia, PA 19104 (yangyushi@gmail.com). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2OEIBvc
https://ift.tt/2OEIBvc
Factors Affecting Consumer Acceptance of an Online Health Information Portal Among Young Internet Users
Despite the proliferation of health and nursing informatics applications in the past decade, factors influencing consumer acceptance of the applications are not well understood. This study was conducted to investigate factors affecting acceptance of a consumer-used nursing informatics application (ie, online health information portal) within the framework of the Technology Acceptance Model. A cross-sectional study was conducted in which 201 Chinese young adults were invited to participate in usability testing with a typical health information portal and to complete a self-report questionnaire measuring the model's constructs and five hypothesized variables drawn from consumer and portal characteristics. Hierarchical regression analyses were used to test research hypotheses. Fifteen of the 22 research hypotheses were supported. Perceived ease of use and perceived usefulness predicted satisfaction and behavioral intention, respectively, over and above the portal and consumer characteristics examined in the study. All portal and consumer characteristics had significant, although varied, impacts on the original model constructs. This study demonstrated that an adapted Technology Acceptance Model, extended with portal and consumer characteristics, provides an effective means to understand consumer acceptance of health portals. The findings hold important implications for design and implementation strategies to increase the likelihood of acceptance of consumer-used nursing informatics applications. This work received funding support from the Young Talents Foundation of Ministry of Education of Guangdong, China (grant 2016KQNCX143), the Natural Science Foundation of Shenzhen University (grants 827000228 and 827000033), CES-Kingfar Excellent Young Scholar Joint Research Funding (grant CES-KF-2016-2018), and the Start-up Grant of Shenzhen University (grant 2016041). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Corresponding Address: Xingda Qu, PhD, Institute of Human Factors and Ergonomics, College of Mechatronics and Control Engineering, Shenzhen University, 3688 Nanhai Ave, Shenzhen City, Guangdong Province, China (quxd@szu.edu.cn). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2ADCnZD
https://ift.tt/2ADCnZD
Medial Open Transversus Abdominis Plane (MOTAP) Catheters Reduce Opioid Requirements and Improve Pain Control Following Open Liver Resection: A Multicenter, Blinded, Randomized Controlled Trial
Objective: Conventional management of pain following open liver resection involves intravenous, patient-controlled analgesia (IV PCA) or epidural analgesia. The objective of this trial was to assess the efficacy of a regional technique called Medial Open Transversus Abdominis Plane (MOTAP) catheter analgesia compared with IV PCA. Methods: This was a blinded, randomized, controlled parallel-arm trial conducted at 2 high-volume centers. Patients undergoing liver resection through a subcostal incision were enrolled. Using a standardized technique, 2 catheters were placed after resection: one in the plane between internal oblique and transversus abdominis and the other in the posterior rectus sheath. Patients were randomized to receive ropivacaine 0.2% (ROP) or saline (NS) through both catheters for 72 hours. All patients received IV PCA with hydromorphone as part of a multimodality analgesia program. Primary outcome was opioid use over the first 48 hours. Results: One hundred fifty-three patients were included in the analysis (71 ROP, 82 NS). Patients receiving ROP used significantly less opioid than patients with NS at 48 hours (median 39.6 mg morphine-equivalent vs 49.2 mg, P = 0.033) and at 72 hours (median 50.0 vs 66.4 mg, P = 0.046). Pain scores at rest and with coughing were significantly lower at all time points in patients who received ROP (P = 0.002). Median length of hospital stay was 5 days in patients receiving ROP and 6 days in patients who received NS (P = 0.035). There was no difference between groups in complications [ROP 20 (28.2%) vs NS 26 (31.7%), P = 0.63]. Conclusion: MOTAP catheter analgesia reduces opioid requirements, pain, and length of hospital stay compared with IV PCA following open liver resection with subcostal incisions.https://ift.tt/2ukDnLX
Sequential treatment combining cladribine-based re-induction, myeloablative allogeneic HSCT, and prophylactic donor lymphocyte infusion: a promising treatment for refractory acute myeloid leukemia
Abstract
We describe the first multicenter prospective study to assess the efficacy, safety, and immune reconstitution of a novel sequential transplant approach in 24 patients with primary induction failure/relapsed acute myeloid leukemia (AML). The sequential regimen consisted of cladribine 5 mg/m2/day and cytarabine 2 g/m2/day for 5 days and mitoxantrone 7 mg/m2/day for 3 days, followed by myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) using intravenous busulfan (3.2 mg/kg/day) for 4 days and cyclophosphamide (60 mg/kg/day) for 2 days. Patients in CR without acute graft-versus-host disease at day + 90 received prophylactic donor lymphocyte infusion (pDLI). At the time of transplantation, a marrow blast infiltration > 20% or any level of circulating blasts was found in 62.5% of patients. The cumulative incidence of relapse at 2 years was 29.8%. Overall survival (OS) was 74.5% at 1 year and 56.5% at 2 years. Leukemia-free survival (LFS) at 1 and 2 years was 62.5 and 50.5%, respectively. Multivariate analysis demonstrated that haploidentical related donor, pDLI, and experiencing chronic graft-versus-host disease (cGVHD) were protective from relapse. Total T cells and T cell subsets in peripheral blood recovered at 3 months post-HSCT. The expressions of immune checkpoints (cytotoxic T lymphocyte antigen 4 and programmed death 1) were extremely low in T cells over the first 1 year post-transplantation.
https://ift.tt/2OImyE6
Different adaptation rates to abrupt and gradual changes in environmental dynamics
Abstract
Adaptation to an abrupt change in the dynamics of the interaction between the arm and the physical environment has been reported as occurring more rapidly but with less retention than adaptation to a gradual change in interaction dynamics. Faster adaptation to an abrupt change in interaction dynamics appears inconsistent with kinematic error sensitivity which has been shown to be greater for small errors than large errors. However, the comparison of adaptation rates was based on incomplete adaptation. Furthermore, the metric which was used as a proxy of the changing internal state, namely the linear regression between the force disturbance and the compensatory force (the adaptation index), does not distinguish between internal state inaccuracy resulting from amplitude or temporal errors. To resolve the apparent inconsistency, we compared the evolution of the internal state during complete adaptation to an abrupt and gradual change in interaction dynamics. We found no difference in the rate at which the adaptation index increased during adaptation to a gradual compared to an abrupt change in interaction dynamics. In addition, we separately examined amplitude and temporal errors using different metrics, and found that amplitude error was reduced more rapidly under the gradual than the abrupt condition, whereas temporal error (quantified by smoothness) was reduced more rapidly under the abrupt condition. We did not find any significant change in phase lag during adaptation under either condition. Our results also demonstrate that even after adaptation is complete, online feedback correction still plays a significant role in the control of reaching.
https://ift.tt/2Oac52Z
Fighting a losing battle: Midwives experiences of workplace stress
Publication date: Available online 3 August 2018
Source: Women and Birth
Author(s): Sadie Geraghty, Craig Speelman, Sara Bayes
Abstract
Aim
The aim of this study was to examine the nature of midwives' work-related stress and the implications, if any, for midwives overall emotional well-being and career decisions.
Methods
A classic Glaserian grounded theory methodology was used, which included 21 in-depth individual face-to-face interviews with registered midwives.
Findings
The core category that emerged from the data labelled 'Fighting a Losing Battle' consisted of the causal, contextual and conditional factors that together form the core problem faced by the midwives. Participants depicted contemporary midwifery practice environments as 'war like' and described levels of work-related stress that, for many, were unbearable and led them to conclude that the job was not worth it.
Conclusion
This study reveals that as the number and extent of stressors increase, the negative implications and effects for midwives rise as the opportunities to 'do' midwifery in the way they value decrease, and that commitment to and engagement with the work diminishes. Although the midwives said that midwifery itself could be stressful, their responses clearly identify that it is not the actual job but other related, contextual and other environmental factors that make it so.
https://ift.tt/2n87LpD
Evaluating broad-scale system change using the Consolidated Framework for Implementation Research: challenges and strategies to overcome them
The objective of this paper is to demonstrate the utility of the CFIR framework for evaluating broad-scale change by discussing the challenges to be addressed when planning the assessment of broad-scale change...
https://ift.tt/2OGhAHZ
Magnitude and factors associated with medication discrepancies identified through medication reconciliation at care transitions of a tertiary hospital in eastern Ethiopia
The aim of this study is to determine the magnitude of medication discrepancies and its associated factors at transitions in care of a Specialized University Hospital in eastern Ethiopia.
https://ift.tt/2ACSJ4X
Magnitude of stunting and its determinants in children aged 6–59 months among rural residents of Damot Gale district; southern Ethiopia
The objective of this study is assessing magnitude of stunting and its predictors among children aged 6–59 months in Damot Gale district, South Ethiopia. Community based cross sectional study was done at Damot...
https://ift.tt/2vhGAgG
The jasmonate receptor COI1 is required for AtPep1-induced immune responses in Arabidopsis thaliana
Plant cells detect the presence of potentially pathogenic microorganisms in the apoplast via plasma membrane-localized receptors. Activated receptors trigger phosphorylation-mediated signaling cascades that pr...
https://ift.tt/2ADrHdv
Identification of high risk groups with shorter survival times after onset of the main reason for suicide: findings from interviews with the bereaved in Japan
We sought to (1) measure survival lengths after the onset of the main reason for the target's suicide, (2) identify the highest-risk groups and the contributors to early death, in Japan, and (3) clarify peculi...
https://ift.tt/2vhGuWm
The Oncolytic Adenovirus XVir-N-31 as a Novel Therapy in Muscle-Invasive Bladder Cancer
Human Gene Therapy, Ahead of Print.
https://ift.tt/2OIhXSm
Diagnosis and Treatment of Primary Central Nervous System Angiitis
Abstract
Purpose of review
Primary central nervous system angiitis (PCNSA) is a rare disease. Varying clinical pictures coupled with lack of sensitive and specific diagnostic tests lead to challenges in management of these patients. This unfortunately may lead to both under- or over-diagnosis and unnecessary treatment. It is important to recognize the different conditions that may mimic the clinical and radiologic presentation. We present a contemporary literature review that should update physicians who encounter this patient population.
Recent findings
Recent additions to the literature in form of case reports and single-center series show that digital subtraction angiography was the most widely used test to diagnose PCNSA. It is also important to note that brain biopsy is still considered "gold standard" and should be pursued as it not only has information that establishes the diagnosis but also may help in ruling out the diagnosis from mimics. In around 39% of suspected cases, an alternate diagnosis was eventually confirmed highlighting the importance of a comprehensive work-up. For treatment, almost all the literature supports the use of glucocorticoids as the initial treatment and if the patient has a relapse or develops steroid toxicity then the second most commonly used agent was cyclophosphamide. There are increasing reports of benefits with other agents such as methotrexate, azathioprine, mycophenolate, infliximab, and etanercept.
Summary
The diagnosis and management of PCNSA continues to be a challenge. Formation of prospective patient registries with continued immunologic research for novel targets and immunomodulatory modalities may hold promise for future care of these patients.
https://ift.tt/2vESb90
Cigarette smoke upregulates SPRR3 by favoring c-Jun/Fra1 heterodimerization in human bronchial epithelial cells
Future Oncology, Ahead of Print.
https://ift.tt/2MgAinO
Utility of polaprezinc in reducing toxicities during radiotherapy: a literature review
Future Oncology, Ahead of Print.
https://ift.tt/2LV4Oa7
Electrical activity of the human amygdala during all-night sleep and wakefulness
Several studies have established a close relationship between sleep and emotion (Deliens et al., 2014). In particular, rapid eye movement (REM) sleep has been implicated in emotion during dreams and nightmares (Desseilles et al., 2011; Ross et al., 1994), also in posttraumatic sleep disorder (Mellman et al., 2002), and in next day emotional regulation. For example, emotional reactivity to threatening images is exacerbated after selective REM sleep deprivation (Rosales-Lagarde et al., 2012), as are fear responses to previously extinguished stimuli (Spoormaker et al., 2012).
https://ift.tt/2n6T1Ya
Heart rate variability and impact of central pacemaker on cardiac activity
The study of heart rate variability (HRV) has become increasingly popular in the last decade, spanning from basic physiological mechanisms to psychosocial correlates and clinical applications. In this issue of Clinical Neurophysiology, Hamasaki et al. (2018) report on the coincidence of hemifacial spasm (HFS) and significant HRV increase in the low frequency (LF) band around 0.1 Hz and acceleration of heart rate. HFS caused by arterial compression of the facial nerve may be explained by various possible causes.
https://ift.tt/2Oa4OjH
Ultrasound-guided, open-source microneurography: Approaches to improve recordings from peripheral nerves in man
Microneurography is an established technique that allows recordings to be made from peripheral nerves in humans (Vallbo and Hagbarth, 1968, Vallbo et al. , 2004). This includes the ability to record from afferent neurones conducting in the C-fibre range (Torebjork and Hallin, 1974), which are predominantly nociceptors. In the pain field, the normal response characteristics of several classes of nociceptors have been defined and a growing body of work is now identifying pathophysiological changes in human disease (Donadio and Liguori, 2015).
https://ift.tt/2n8JrE7
Auditory N100 gating in patients with schizophrenia: A systematic meta-analysis
Several event-related potential (ERP) components have been considered as biological markers for schizophrenia, such as the auditory mismatch negativity (MMN), auditory P50 gating, or P3 (Thibaut et al., 2015). For these ERP components, there has been decade-long clinical research, with first reports of deficiencies in schizophrenia dating back more than 45 years (Roth and Cannon, 1972). Recent meta-analyses suggest relatively large, trait-related deficits in schizophrenia patients, with patients showing smaller MMN and P3 amplitudes, a delayed P3 response, and less efficient P50 gating, as compared to healthy controls (MMN: Erickson et al., 2016; P3: Jeon and Polich, 2003; P50 gating: de Wilde et al., 2007; Patterson et al., 2008).
https://ift.tt/2Kp0jQh
A glimpse into the future of clinical neurophysiology: Can we use machines to interpret EEG?
To help diagnose epilepsy, the clinical neurophysiologist reviews and analyzes EEG recordings, a subtle and time-consuming skill. Historically, researchers have improved this diagnostic process by identifying epileptiform markers and by automating their detection (e.g. Gibbs and Gibbs, 1952; Kellaway et al., 1959; Gotman and Gloor, 1976; Gotman, 1982). One recently developed approach that can extract and classify signal features is deep learning, an application based on artificial neural nets with the neural elements arranged in multiple layers.
https://ift.tt/2LQenb8
Spasticity in adults with cerebral palsy and multiple sclerosis measured by objective clinically applicable technique
Spasticity occurs frequently following lesions of central motor pathways in neurological disorders such as stroke (Malhotra et al., 2009; Sommerfeld et al., 2012), spinal cord injury (Sheean, 2002), multiple sclerosis (MS) (Sinkjaer et al., 1993; Mayer, 1997) and cerebral palsy (CP) (Gracies, 2005). Spasticity is most commonly defined as a velocity dependent increase in muscle tone with exaggeration of the stretch reflex circuitry (Lance, 1980). However, in the clinic a somewhat broader understanding of spasticity, which also includes sustained muscle contractions such as spasms and spastic dystonia as well as alterations in muscle properties, prevails (Malhotra et al., 2009).
https://ift.tt/2OaWgtb
Inhibition and attentional control in pedophilic child sexual offenders – An event-related potential study
Deficits in response inhibition and attentional control as impairment of executive functions have been presumed to play a role in child sexual abuse by pedophiles, as primarily revealed by neuropsychological testing of such individuals (Eastvold et al., 2011; Joyal et al., 2014; Schiffer and Vonlaufen, 2011; Suchy et al., 2009). Pedophilic and non-pedophilic child molesters showed e.g. increased false alarm rates in a Go/Nogo-task, as compared to both healthy and forensic controls (Schiffer and Vonlaufen, 2011).
https://ift.tt/2LQei7k
Reply to “Work-up for mitochondrial small fiber neuropathy requires application of skin biopsies”
In reply to the letter of Finsterer (2018) we further analyzed our cohort of patients with mitochondrial diseases (MDs), in order to confirm our results.
https://ift.tt/2Oa4Nw9
Physical activity effects on the individual alpha peak frequency of older adults with and without genetic risk factors for Alzheimer’s Disease: A MEG study
For more than two decades, an enormous effort has been devoted to the search for pharmacological therapies that could palliate the devastating effects of Alzheimer's Disease (AD). Most of these therapies relied on the so-called "amyloid hypothesis" (Hardy and Higgins, 1992), that is considered the leading explanation for the disease. Unfortunately, clinical trials testing agents that interfere with amyloid production failed to improve cognition or to slow down the deterioration process, while produced substantial side effects (Drachman, 2014; Intlekofer and Cotman, 2013).
https://ift.tt/2nb4PZw
Normative values for sleep parameters in pre-schoolers using actigraphy
Sleep disturbances are relatively common in children. Primary care providers have reported that approximately 20% of their 0-to-4-year-old patients had sleeping difficulties (Honaker and Meltzer, 2016). The prevalence of manifest sleep problems reported by parents range between 11 and 12% (Honaker and Meltzer, 2016), and at least one symptom of insomnia is reported in approximately 40% of children (Archbold et al., 2002). The high prevalence of sleeping problems in children calls for reliable diagnostic tools for the clinicians.
https://ift.tt/2KmaLbb
Work-up for mitochondrial small fiber neuropathy requires application of skin biopsies
With interest, I read the article from Luigetti et al. about the work-up for small fiber neuropathy in genetically confirmed patients with a mitochondrial disorder (MID) (m.3243A > G (n = 7), m.8344A > G (n = 4), single mtDNA deletion (n = 9), multiple mtDNA deletions (n = 7)) (Luigetti et al., 2018). By application of the Sudoscan, the sympathetic skin response (SSR), and laser-evoked potentials (LEP), the authors found that 33% of the 27 patients had autonomic small fiber dysfunction by application of the Sudoscan, that only 3/27 patients had an abnormal SSR, and that LEP confirmed the Sudocan findings.
https://ift.tt/2LTpOhY
Is hemifacial spasm affected by changes in the heart rate? A study using heart rate variability analysis
Hemifacial spasm (HFS), a movement disorder characterized by involuntary muscle contraction of one side of the face. HFS impairs not only daily activities but also social activities of patients. Because the central etiology of HFS is mechanical compression by offending arteries to the root exit zone (REZ) of the facial nerve (Campbell and Keedy, 1947; Gardner, 1962; McLaughlin et al., 1999), microvascular decompression is a standard surgical treatment, in which the arteries are microsurgically separated from the facial nerve REZ, and provides favorable outcome (Barker et al., 1995; Chung et al., 2000; Samii et al., 2002).
https://ift.tt/2Kmasgx
Neuromodulation of lower limb motor responses with transcutaneous lumbar spinal cord direct current stimulation
The spinal cord (SC) is a complex structure that contains its own neuronal circuits modulated by higher encephalic function. The motor information descends via the corticospinal tracts to synapse with the alpha and gamma motor neurons located in the anterior horns, directly or via spinal interneurons. SC is not only a bidirectional communication pathway between brain and the periphery, but it also contains local circuits known to permit locomotion movements and segmental spinal reflexes (Iglesias et al., 2008).
https://ift.tt/2LRuQf1
Intestinal obstruction as a cause of death in the mentally disabled
Abstract
Two cases of intestinal obstruction in the mentally disabled are reported. The first case concerns 61-year-old oligophrenic woman who resided in a nursing home, where she was found hypotensive and unresponsive. Upon opening the peritoneal cavity at autopsy, extremely dilated (measuring on average 12 cm in diameter) loops of the colon emerged– they compressed the small intestine and other intraperitoneal organs, lifting both hemidiaphragms deep into the pleural cavity. Lodged firmly into the rectum, a partly disintegrated sanitary pad was found. In the second case, young man with Down syndrome was found dead in his room in a nursing facility. At autopsy, a massively dilated stomach and intestinal loops emerged, interposing one of the loops between the liver and right hemidiaphragm (pushing it to the 3rd intercostal space). This was caused by a volvulus – the cecum, the entire ascending colon and hepatic flexure were gangrenous, dilated (the maximum diameter was 15 cm) and twisted in a full circle around the mesenteric attachment. There were no signs of colon perforation. In both cases, intellectual disability was at the core of poor communication and delayed medical treatment, which led to a fatal outcome. Caregivers must be trained to recognize distress in the mentally disabled, especially since the symptoms and signs of gastrointestinal diseases may be subtle, or at least less recognizable. By performing careful physical examination medical staff should search more cautiously for these signs. Any suspicion of mistreatment or neglect of the mentally impaired requires a medico-legal investigation and autopsy.
https://ift.tt/2OIn9FW
Outcomes of Multi-Level Vertebrectomy for Spondylodiscitis
Publication date: Available online 3 August 2018
Source: The Spine Journal
Author(s): Nissim Ackshota, Alysa Nash, Ian Bussey, Mark Shasti, Luke Brown, Vijay Vishwanath, Zanaib Malik, Kelley E. Banagan, Eugene Y. Koh, Steven C. Ludwig, Daniel E. Gelb
Abstract
BACKGROUND CONTEXT
The incidence of pyogenic vertebral osteomyelitis (PVO) continues to increase in the United States, highlighting the need to recognize unique challenges presented by these cases and develop effective methods of surgical management. To date, no prior research has focused on the outcomes of PVO requiring two or more contiguous corpectomies.
PURPOSE
To describe our experience in the operative management of PVO in 56 consecutive patients who underwent multilevel corpectomies (≥2 vertebral bodies) via a combined approach.
STUDY DESIGN/SETTING
Single institution retrospective cohort review between January 2002 and December 2015. All patients had been treated at an academic tertiary referral center by one of two fellowship-trained orthopaedic spine surgeons.
PATIENT SAMPLE
Patient records were cross-referenced with International Classification of Diseases osteomyelitis codes and paravertebral abscess code. Inclusion criteria for the study were patients within the cohort who had adequate medical records for review, a minimum patient age of 18 years, active vertebral osteomyelitis as an indication for surgical intervention, a minimum of 1-year radiographic follow-up, and surgical intervention that included at least two complete vertebral corpectomies. Subsequently, 56 patients met the inclusion criteria and were reviewed for this retrospective analysis.
OUTCOME MEASURES
Outcomes of interest were readmission and reoperation rates related to treatment of PVO, 30-day and 1-year mortality rates, radiographic outcomes, perioperative complications, infection control, and length of stay.
METHODS
After IRB approval, retrospective review was performed on records of all adults with PVO refractory to standard nonoperative treatment who underwent complete corpectomy of two or more contiguous vertebrae at a single institution between January 2002 and December 2015. This study was unfunded, and no potential conflict of interest-associated biases were present.
RESULTS
Fifty-six patients were identified (63% male; mean age 56.8 years; mean radiographic follow-up 2.8 years). Median LOS was 13 days with nearly half readmitted (47%) after a median of 222.5 days after surgery. Twelve (22%) posterior revisions were required after a median 54 days for infection, painful or failed hardware, proximal junction kyphosis, adjacent level disease, or extension of the fusion. Thirty-day and 1-year mortality rate was 7.14% and 19.6%, respectively, with an infectious etiology as the most common cause of death.
CONCLUSIONS
Multi-level vertebral corpectomy for treatment of refractory vertebral osteomyelitis is associated with relatively high rates of complications and mortality compared to historical controls for 1 or 2 level procedures. We found clinical resolution and absence of complications requiring return to the operating room in 75% of patients when complete extirpation of the involved vertebrae is achieved. Our findings suggest multilevel anterior corpectomies with posterior stabilization may be a reasonable surgical option when approaching patients with complicated spondylodiscitis.
https://ift.tt/2LRmKTx
Lymphogranuloma Venereum Proctitis
A 47-year-old man with a medical history of human immunodeficiency virus infection, primary syphilis, hepatitis A, typhoid fever, and tubercular polyneuritis presented with rectorrhagia and anal flowing. The patient was homosexual and reported unprotected anal intercourse 3 weeks before. The human immunodeficiency virus infection was controlled by antiretroviral therapy (elvitegravir, emtricitabine, tenofovir alafenamide, cobicistat), with an undetectable viral load and a normal CD4 T-cell count.
https://ift.tt/2O9Y5q9
Involution of Portal Hypertensive Gastric and Duodenal Polyps Following Liver Transplantation
A 49 year-old man with alcoholic cirrhosis presented with upper gastrointestinal bleeding and ascites. Endoscopy showed grade 2 esophageal varices with innumerable sessile polyps of the stomach and duodenum with diffuse hemorrhage (Figures A and B), which were treated with epinephrine injection and hemostatic clips. Over the following months, the patient had frequent hospitalizations for recurrent bleeding from the polyps and refractory ascites. Endoscopic biopsy of the polyps showed hyperplastic duodenal mucosa with vascular ectasia (Figure C, arrows) and patchy erosion (Figure C, arrowheads).
https://ift.tt/2LZXQjP
Endoglin targeting in colorectal tumor microenvironment
On endothelial cells, the TGFβ/BMP-9 co-receptor endoglin emerged as a promising anti-angiogenic target in colorectal cancer (CRC). Its promiscuous expression in cancer associated fibroblasts (CAFs) emerges to facilitate metastasis. The multi-target impact of neutralizing endoglin may offer added benefit in controlling CRC.
https://ift.tt/2Me7RH5
Pericytes elicit resistance to vemurafenib and sorafenib therapy in thyroid carcinoma via the TSP-1/TGF{beta}1 axis
Purpose: The BRAFV600E oncogene modulates the papillary thyroid carcinoma (PTC) microenvironment, in which pericytes are critical regulators of tyrosine-kinase (TK)-dependent signaling pathways. Although BRAFV600E and TK inhibitors are available, their efficacy as bimodal therapeutic agents in BRAFV600E-PTC is still unknown. Experimental Design: We assessed the effects of vemurafenib (BRAFV600E inhibitor) and sorafenib (TKI) as single agents or in combination in BRAFWT/V600E-PTC and BRAFWT/WT cells using cell-autonomous, pericyte co-culture, and an orthotopic mouse model. We also used BRAFWT/V600E-PTC and BRAFWT/WT-PTC clinical samples to identify differentially expressed genes fundamental to tumor microenvironment. Results: Combined therapy blocked tumor cell proliferation, increased cell death, and decreased motility via BRAFV600E inhibition in thyroid tumor cells in vitro. Vemurafenib produces cytostatic effects in orthotopic tumors, whereas combined therapy (likely reflecting sorafenib activity) generates biological fluctuations with tumor inhibition alternating with tumor growth. We demonstrate that pericytes secrete TSP-1 and TGFβ1, and induce the rebound of pERK1/2, pAKT and pSMAD3 levels to overcome the inhibitory effects of the targeted therapy in PTC cells. This leads to increased BRAFV600E-PTC cell survival and cell death refractoriness. We find that BRAFWT/V600E-PTC clinical samples are enriched in pericytes, and TSP1 and TGFβ1 expression evoke gene-regulatory networks and pathways in the microenvironment essential for BRAFWT/V600E-PTC cell survival. Critically, antagonism of the TSP-1/TGFβ1 axis reduces tumor cell growth and overcomes drug resistance. Conclusions: Pericytes shield BRAFV600E-PTC cells from targeted therapy via TSP-1 and TGFβ1, suggesting this axis as a new therapeutic target for overcoming resistance to BRAFV600E and TK inhibitors.
https://ift.tt/2LVWUx9
Astragalus membranaceus (Fisch.) Bunge repairs intestinal mucosal injury induced by LPS in mice
Astragalus membranaceus (Fisch.) Bunge is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer...
https://ift.tt/2vyB1cP
NOTCH1 Signaling Hijacks the Stress Response to Promote T-ALL [Research Watch]
The heat shock transcription factor HSF1 is upregulated in patients with T-ALL.
https://ift.tt/2M1evn9
IFN-Driven Endogenous Retroviruses Can Drive Tumor Innate Immunity [Research Watch]
IFN-inducible endogenous retroviruses promote mesenchymal tumor cell–mediated immunosuppression.
https://ift.tt/2MjuzO2
Lysine Methyltransferase and Demethylases Regulate DNA Amplifications [Research Watch]
Transient site-specific DNA copy-number gains (TSSG) are controlled by histone lysine methylation dynamics.
https://ift.tt/2vfDc5W
DUB3 Deubiquitinates BRD4 to Promote Prostate Cancer Progression [Research Watch]
DUB3-mediated BRD4 stabilization overcomes SPOP-mediated degradation to confer BET inhibitor resistance.
https://ift.tt/2MipbuL
Advice Offered for Sharing Research Results [News in Brief]
Expert committee outlines 12 recommendations on returning research findings to study participants.
https://ift.tt/2LZEFHa
CDC: E-Cigarette Sales in the United States Climb As Prices Fall
FRIDAY, Aug. 3, 2018 -- There was a large increase in sales of electronic cigarettes (e-cigarettes) and related products in the United States in recent years as their prices fell, according to a study published online Aug. 2 in the U.S. Centers for...
https://ift.tt/2Meiji0
Some Bacteria Now More Tolerant of Alcohol-Based Sanitizers
FRIDAY, Aug. 3, 2018 -- Some types of bacteria are developing tolerance of alcohol-based hand sanitizers used in hospitals, according to a study published in the Aug. 1 issue of Science Translational Medicine. The introduction of these sanitizers...
https://ift.tt/2OIQlfN
Parent-Child Interactive Intervention Cuts Depression
FRIDAY, Aug. 3, 2018 -- An intervention targeting depression in very young children can be effective in community settings, according to a study published online June 20 in The American Journal of Psychiatry. Joan L. Luby, M.D., from Washington...
https://ift.tt/2MeiidW
Variation in Specialty Drug Coverage Across Health Plans
FRIDAY, Aug. 3, 2018 -- There is considerable variation in specialty drug coverage across commercial health plans, according to a study published in the July issue of Health Affairs. James D. Chambers, Ph.D., from Tufts Medical Center in Boston, and...
https://ift.tt/2OIQgsv
Skin Appears to Be Key Pathway for Absorption of BBQ Fumes
FRIDAY, Aug. 3, 2018 -- Dermal absorption is a more important pathway than inhalation for the intake of low-molecular-weight polycyclic aromatic hydrocarbons (PAHs) during barbecuing, according to a study published recently in Environmental Science...
https://ift.tt/2MhL8Kc
Elevated inflammatory cytokine expression in CSF from patients with symptomatic thoracic disc herniations correlates with increased pain scores
Publication date: Available online 2 August 2018
Source: The Spine Journal
Author(s): Pablo Andrade, Erwin M.J. Cornips, Claudia Sommer, Marc A. Daemen, Veerle Visser-Vandewalle, Govert Hoogland
Abstract
Background
The pathophysiology of pain in symptomatic thoracic disc herniation (TDH) patients remains poorly understood. Mere mechanical compression of the spinal cord and/or the exiting nerve root by a prolapsed disc cannot explain the pathogenesis of pain in all cases. Previous studies report a direct correlation between the levels of proinflammatory cytokines in disc biopsies and the severity of leg pain in patients with lumbar disc herniations. A similar correlation in patients with TDHs has not been investigated.
Purpose
To correlate the cerebrospinal fluid (CSF) expression of cytokines and pain-related amino acids with preoperative pain scores in patients with symptomatic TDHs.
Study Design
A prospective human study of CSF samples and clinical outcome scores.
Methods
Using ELISA and high-performance liquid chromatography (HPLC), we determined inflammatory cytokine levels (TNF-α, IL-1β and IL-10) and amino acid levels (glutamate, aspartate, GABA, glycine and arginine) in CSF samples from ten TDH patients and ten control subjects who did not suffer an inflammatory disease nor pain related to spinal cord compression, and subsequently correlated these levels with preoperative pain scores. Differences between both groups were evaluated by a Whitney-U-test. In order to estimate the correlation between cytokine or amino acid expression and pain scores, data were analyzed using linear regression analysis.
Results
No inflammatory cytokines were found in CSF samples from control subjects, whereas TNF-α, IL-1β and IL-10 were detectable by ELISA in all CSF samples from TDH patients. TNF-α and IL-10, but not IL-1β levels moderately correlated with preoperative pain scores. Elevated TNF-αlevels positively correlated with high pain scores; elevated IL-10 levels negatively correlated with high pain scores. Amino acids were detectable in all samples from both groups. There were no significant differences between the groups in any of the amino acids measured with HPLC.
Conclusion
Increased proinflammatory cytokine expression is associated with elevated pain scores in symptomatic TDH patients. On the other hand, there is no conclusive correlation between the intensity of pain and the local or systemic presence of amino acids associated with pain transmission.
https://ift.tt/2viUoau
Spinal epidural lipomatosis is a previously unrecognized manifestation of metabolic syndrome
Publication date: Available online 2 August 2018
Source: The Spine Journal
Author(s): Shinichi Ishihara, Nobuyuki Fujita, Koichiro Azuma, Takehiro Michikawa, Mitsuru Yagi, Takashi Tsuji, Michiyo Takayama, Hideo Matsumoto, Masaya Nakamura, Morio Matsumoto, Kota Watanabe
Abstract
Background Context
Spinal epidural lipomatosis (SEL) is a condition in which excess lumbar epidural fat (EF) deposition often leads to compression of the cauda equina or nerve root. Although SEL is often observed in obese adults, no systematic research investigating the potential association between SEL and metabolic syndrome has been conducted.
Purpose
To elucidate potential association between SEL and metabolic syndrome.
Study design
An observational study used data of a medical checkup.
Patient sample
We retrospectively reviewed data from consecutive subjects undergoing medical checkups. A total of 324 subjects (174 men and 150 women) were enrolled in this study.
Outcome measures
The correlation of EF accumulation with demographic data and metabolic related factors were evaluated.
Methods
The degree of EF accumulation was evaluated based on the axial views of lumbar magnetic resonance imaging. Visceral and subcutaneous fat areas were measured at the navel level using abdominal computed tomography. Metabolic syndrome was diagnosed according to the criteria of the Japanese Society of Internal Medicine. The correlation of SEL with metabolic syndrome and metabolic-related conditions was statistically evaluated.
Results
The degree of EF accumulation demonstrated a significant correlation to body mass index, abdominal circumference, and visceral fat area. However, age, body fat percentage, and subcutaneous fat area showed no correlation with the degree of EF accumulation. Logistic regression analysis revealed that metabolic syndrome [odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.5–9.6] was significantly associated with SEL. Among the diagnostic criteria for metabolic syndrome, visceral fat area ≥ 100 cm2 (OR = 4.8, 95% CI = 1.5–15.3) and hypertension (OR = 3.5, 95% CI = 1.1–11.8) were observed to be independently associated with SEL.
Conclusion
This is the first study to demonstrate that metabolic syndrome is associated with SEL in a relatively large, unbiased population. Our data suggest that metabolic-related conditions are potentially related to EF deposition and that SEL could be a previously unrecognized manifestation of metabolic syndrome.
https://ift.tt/2AChjmv
Dialysis is an independent risk factor for perioperative adverse events, readmission, reoperation and mortality for patients undergoing elective spine surgery
Publication date: Available online 2 August 2018
Source: The Spine Journal
Author(s): Taylor D. Ottesen, Ryan P. McLynn, Cheryl K. Zogg, Blake N. Shultz, Nathaniel T. Ondeck, Patawut Bovonratwet, Kirthi S. Bellamkonda, Lee E. Rubin, Jonathan N. Grauer
Abstract
Background Context
The prevalence of dialysis-dependent patients in the United States is growing. Prior studies evaluating the risk of perioperative adverse events for dialysis-dependent patients are either institutional cohort studies limited by patient numbers or administrative database studies limited to inpatient data.
Purpose
The current study utilizes a large, national sample with 30-day follow-up to investigate dialysis as risk factor for perioperative complications independent of patient demographics or comorbidities.
Study Design/Setting
Retrospective cohort study.
Patient Sample
Patients undergoing elective spine surgery with or without dialysis from the 2005-2015 NSQIP database.
Outcome Measures
Post-operative complications within 30 days and binomial reoperation, readmission, and mortality within 30 days.
Methods
National Surgical Quality Improvement Program (NSQIP) 2005-2015 databases were queried for adult dialysis-dependent and dialysis-independent patients undergoing elective spinal surgery. Differences in 30-day outcomes were compared using risk-adjusted multivariate regression and coarsened exact matching analysis for adverse events, unplanned readmission, reoperation, and mortality. The percentage of complications occurring before versus after hospital discharge was also assessed. The authors have no financial disclosures related to this study.
Results
A total of 467 dialysis and 173,311 non-dialysis patients met inclusion criteria. Controlling for age, sex, BMI, functional status, and American Society of Anesthesiologists (ASA) class, dialysis patients were found to be at significantly greater odds of any adverse event (Odds ratio [OR]=2.52 before, 2.17 after matching, p=<0.001), major adverse event (OR=2.90 before, 2.52 after matching, p=<0.001), and minor adverse event (OR=1.50 before matching, p=<0.025, but not significantly different after matching). Further, dialysis patients were significantly more likely to return to the operating room (OR= 2.77 before, 2.50 after matching, p=<0.001), have unplanned readmissions (OR=2.73 before, 2.37 after matching, p=<0.001), and die within 30 days (OR=3.77 before, 2.71 after matching, p=<0.001). Adverse events occurred post discharge for 51.78% of non-dialysis patients and for 43.80% of dialysis patients.
Conclusions
Dialysis patients undergoing elective spine surgery are at significantly higher risk for aggregated adverse outcomes, return to the operating room, readmission, and death than non-dialysis patients, even after controlling for patient demographics and overall health (as indicted by ASA class). These differences need to be considered when determining treatment options. Additionally, with bundled payments expected in spine surgery, physicians and hospitals need to account for increased costs and liabilities when working with dialysis patients.
https://ift.tt/2vh7FRb
Predictive Factors of Positive Online Patient Ratings of Spine Surgeons
Publication date: Available online 1 August 2018
Source: The Spine Journal
Author(s): Saisanjana Kalagara, Adam E.M. Eltorai, J. Mason DePasse, Alan H. Daniels
Abstract
Background
Online physician rating websites are increasingly utilized by patients to evaluate their doctors. The purpose of this investigation was to evaluate factors associated with better spine surgeon ratings.
Methods
Orthopedic spine surgeons were randomly selected from the North American Spine Society directory utilizing a random number generator. Surgeon profiles on three physician rating websites, www.HealthGrades.com, www.Vitals.com, and www.RateMDs.com, were analyzed to gather qualitative and quantitative data on patients' perceptions of the surgeons. Independent variables from the websites were analyzed in relation to overall physician or patient satisfaction rating. Comments were coded by subject into three categories: professional competence, bedside manner, and practice characteristics.
Results
A total of 250 surgeons were evaluated, and 92% (n = 230) of these doctors had at least one rating among the three websites. The surgeons with a higher average rating had significantly better trust (p < 0.01), scheduling (p < 0.01), staff (p < 0.01), helpfulness (p < 0.01), and punctuality (p < 0.01) scores but significantly less experience (p < 0.05). A linear regression model for the average rating of each surgeon (R2 value = 0.754) yielded only three significant variables: trustworthiness (p < 0.01), experience match (p < 0.05), and the average number of negative comments on surgeon professional competence (p < 0.05). Trustworthiness (beta = 0.749) was the strongest predictor variable of physician rating, followed by number of negative professional competence comments (beta= -0.132) and experience match (beta = -0.112).
Conclusions
This investigation assessed spine surgeon online patient ratings and categorized factors which patients associate with quality care. Trustworthiness was the most significant predictor of positive ratings, while ease of scheduling, quality of staff, helpfulness, and punctuality were also associated with higher patient ratings. Understanding what patients value may help optimize care of spine surgery patients.
https://ift.tt/2AEUxtV
Mechanism of formation of intravertebral clefts in osteoporotic vertebral compression fractures: an in vitro biomechanical study
Publication date: Available online 31 July 2018
Source: The Spine Journal
Author(s): Wang Chongyan, Zhang Xuyang, Li Shengyun, Liu Junhui, Shan Zhi, Wang Jiasheng, Chen Jian, Fan Shunwu, Zhao Fengdong
Abstract
Background context
Intravertebral clefts (IVCs) are vacuum like cavities commonly associated with osteoporotic vertebral compression fractures (OVCFs). IVCs promote cement leakage during kyphoplasty, suggesting a physical link with the basivertebral foramen, although this is uncertain.
Purpose
The present study aims to create IVCs in mechanical experiments on cadaveric spines in order to clarify their pathogenesis, structure, and links with the basivertebral foramen.
Study design and methods
Fifteen three-vertebra lumbar specimens from five cadavers aged 68-71 were subjected to axial compressive overload followed by cyclic loading in flexion and extension to create an OVCF together with an IVC. CT scans and radiographs were used to confirm structural changes and micro-CT was used to measure trabecular bone properties in five specimens. Unipedicular vertebroplasty was then performed on 10 damaged specimens until fluoroscopy revealed extravasation of cement.
Results
In every specimen, loading created an OVCF with an IVC. Dissection and imaging showed that the IVC was always connected with the basivertebral foramen. The central vertebral region, including the IVC, had the lowest connectivity density, trabecular number, and bone volume fraction, and the highest trabecular separation. Vertebroplasty caused cement leakage through the basivertebral foramen in nine specimens and into an adjacent disc in one specimen.
Conclusion
Cyclic loading in flexion and extension applied to a fractured osteoporotic vertebra can create an IVC which then allows cement leakage via the basivertebral foramen.
https://ift.tt/2OIMiA7
Biomechanical and Histological Assessment of a Novel Screw Retention Technology in an Ovine Lumbar Fusion Model
Publication date: Available online 31 July 2018
Source: The Spine Journal
Author(s): Jeremiah Easley, Christian M. Puttlitz, Ross Palmer, Nicole Ramo, Celeste Abjornson, Frank P. Cammisa, Kirk McGilvray
Abstract
Background Context
Screw loosening is a prevalent failure mode in orthopaedic hardware, particularly in osteoporotic bone or revision procedures where the screw-bone engagement is limited.
Purpose
The objective of this study was to evaluate the efficacy of a novel screw retention technology (SRT) in an ovine lumbar fusion model.
Study Design/Setting
This was a biomechanical, radiographic, and histology study utilizing an ovine lumbar spine model.
Methods
: Fifty-four (n = 54) sheep lumbar spines (L2-L3) underwent posterior lumbar fusion (PLF) via pedicle screw fixation, connecting rod, and bone graft. Three experimental variants were investigated: positive control (ideal clinical scenario), negative control (simulation of compromised screw holes), and SRT treatments (SRT). Biomechanical and histological analysis of the functional spinal unit (FSU) was determined as a function of healing time (0, 3, and 12 months post-operative).
Results
Screw pull-out, screw break-out, and FSU stability of the SRT treatments were generally equivalent to the positive control group, and considerably better than the negative control group. Histomorphology of the SRT treatment screw region of interest (ROI) observed an increase in bone percentage and decrease in void space during healing, consistent with ingrowth at the implant interface. The PLF ROI observed similar bone percentage throughout healing between the SRT treatment and positive control. Less bone formation was observed for the negative control.
Conclusions
The results of this study demonstrate that the SRT improved screw retention and afforded effective FSU stabilization to achieve solid fusion in an otherwise compromised fixation scenario in a large animal model.
https://ift.tt/2AFmfqA
Glomerular filtration rate change during chronic hepatitis C treatment with Sofosbuvir/Ledipasvir in HCV/HIV Coinfected patients treated with Tenofovir and a boosted protease inhibitor: an observational prospective study
Concomitant use of ledipasvir and boosted protease inhibitors (PIs) may increase the risk of tenofovir (TDF) nephrotoxicity, since both these drugs increase TDF levels. Our aim was to evaluate glomerular filtr...
https://ift.tt/2LXCROF
Doxycycline-induced photosensitivity in patients treated for erythema migrans
Doxycycline is one of the recommended antibiotics for treating erythema migrans (EM). Since EM predominantly occurs during summer, the potential of doxycycline to induce photosensitivity is of concern. In stud...
https://ift.tt/2Mgrnme
Specific EEG markers in POLG1 Alpers’ syndrome
Alpers-Huttenlocher syndrome (AHS) is a rare, mitochondrial disease with high mortality.(Cohen and Naviaux 2010) It is characterized by refractory seizures, episodic psychomotor regression, ataxia, cortical blindness and liver failure.(Saneto and Naviaux 2010; Harding 1990) Disease onset is often during childhood, but can range from three months to 36 years of age.(Cohen and Naviaux 2010; Tzoulis et al. 2006) Epilepsy is an important diagnostic factor in AHS and has a focal onset with occipital lobe predeliction.(Engelsen et al.
https://ift.tt/2vmcvN5
Photoacoustic imaging reconstruction using combined nonlocal patch and total-variation regularization for straight-line scanning
For practical straight-line scanning in photoacoustic imaging (PAI), serious artifacts caused by missing data will occur. Traditional total variation (TV)-based algorithms fail to obtain satisfactory results, ...
https://ift.tt/2Oc5AwW
Sound differences between electronic and acoustic stethoscopes
The area of application of electronic stethoscopes in medical diagnostics covers the scope of usability of the acoustic stethoscopes, from which they have evolved and which they could potentially replace. Howe...
https://ift.tt/2n8IHPp
Interactive effect of acute and chronic glycemic indexes for severity in acute ischemic stroke patients
Diabetes mellitus is a well-established risk factor for ischemic stroke and is known to increase stroke risk by 2–6 fold. Numerous studies have reported the relationship between parameters for glycemic status ...
https://ift.tt/2vB2qL9
Spigelman Stage IV Duodenal Polyposis Does Not Precede a Majority of Duodenal Cancer Cases in Patients with Familial Adenomatous Polyposis
The greatest known risk factor for duodenal cancer in FAP is Spigelman Stage (SS) IV duodenal polyposis. Endoscopic surveillance is recommended in FAP patients with SS 0-IV and prophylactic duodenectomy should be considered in SS IV. Cancer occurs in patients without SS IV polyposis. We assessed the relationship of SS and other factors with duodenal cancer in FAP.
https://ift.tt/2n8HlEj
Erythropoietin mimetic peptides and erythropoietin fusion proteins for treating anemia of chronic kidney disease
Purpose of review First generation erythropoiesis stimulating agents (ESAs) have short duration of action which requires administration once weekly or greater. Second generation ESAs were developed which have longer duration of action and can be administered one to two times monthly. Erythropoietin (EPO) mimetic peptides (EMPs) activate the EPO receptor but have no structural analogy to EPO, offering the potential for lower cost as they are not biologic drugs. The first approved EMP, peginesatide, was withdrawn from the market within a year of its approval because of fatal anaphylactic reactions. In this review, we summarize recent progress regarding the development of newer, possibly less toxic, EMPs. We also summarize the development of EPO fusion proteins which fuse EPO with a portion of an immunoglobulin molecule or another EPO molecule, achieving a longer duration of action and less frequent dosing. Recent findings AGEM400(hydroxyethyl starch) and pegolsihematide are EMPs in phase II clinical trials. Three EPO fusion proteins are under development, two in phase I and one in phase II. Summary The future success of EMPs is limited by the prior experience with peginesatide and EPO fusion proteins do not offer cost savings or longer duration of action than currently available ESAs.https://ift.tt/2LOllx3
Iron therapy for managing anaemia in chronic kidney disease
Purpose of review Iron deficiency is a major contributory cause to the development of anaemia in chronic kidney disease (CKD), and thus, iron replacement therapy plays a critical role in the management of this condition. The two main routes for administering iron are oral and intravenous, and there have been a number of new publications relevant to both routes of administration. Recent findings Recent developments on the topic of iron management in CKD include the introduction of new oral iron preparations, as well as two recent meta-analyses on iron therapy in CKD (one on oral versus intravenous iron, and one on high- versus low-dose intravenous iron in haemodialysis patients). There is also increasing interest in other strategies to improve iron availability, such as intradialytic iron, hypoxia-inducible factor stabilization and antihepcidin strategies. Summary Even despite the latest publications in this field, we are still left with serious gaps in our evidence base on how best to provide supplemental iron to CKD patients. Most of the evidence suggests that intravenous iron is superior to oral iron in increasing haemoglobin and minimizing the use of erythropoiesis-stimulating agents, but the safety of intravenous iron remains a controversy. The PIVOTAL study will hopefully provide informative data to fill some of the gap in the evidence-base and inform best clinical practice.https://ift.tt/2LRekvE
Renal tubular solute transport and oxygen consumption: insights from computational models
Purpose of review To maintain electrolyte homeostasis, the kidneys reabsorb more than 99% of the filtered Na+ under physiological conditions, resulting in less than 1% of the filtered Na+ excreted in urine. In contrast, due to distal tubular secretion, urinary K+ output may exceed filtered load. This review focuses on a relatively new methodology for investigating renal epithelial transport, computational modelling and highlights recent insights regarding renal Na+ and K+ transport and O2 consumption under pathophysiological conditions, with a focus on nephrectomy. Recent findings Recent modelling studies investigated the extent to which the adaptive response to nephrectomy, which includes elevation in single-nephron glomerular filtration rate and tubular transport capacity, may achieve balance but increases O2 consumption per nephron. Simulation results pointed to potential mechanisms in a hemi-nephrectomized rat that may attenuate the natriuresis response under K+ load, or that may augment the natriuretic, diuretic and kaliuretic effects of sodium glucose cotransporter 2 inhibition. Summary Computational models provide a systemic approach for investigating system perturbations, such as those induced by drug administration or genetic alterations. Thus, computational models can be a great asset in data interpretation concerning (but not limited to) renal tubular transport and metabolism.https://ift.tt/2vBMmZA
Distal tubule basolateral potassium channels: cellular and molecular mechanisms of regulation
Purpose of review Multiple clinical and translational evidence support benefits of high potassium diet; however, there many uncertainties underlying the molecular and cellular mechanisms determining effects of dietary potassium. Kir4.1 and Kir5.1 proteins form a functional heteromer (Kir4.1/Kir5.1), which is the primary inwardly rectifying potassium channel on the basolateral membrane of both distal convoluted tubule (DCT) and the collecting duct principal cells. The purpose of this mini-review is to summarize latest advances in our understanding of the evolution, physiological relevance and mechanisms controlling these channels. Recent findings Kir4.1 and Kir5.1 channels play a critical role in determining electrolyte homeostasis in the kidney and blood pressure, respectively. It was reported that Kir4.1/Kir5.1 serves as potassium sensors in the distal nephron responding to variations in dietary intake and hormonal stimuli. Global and kidney specific knockouts of either channel resulted in hypokalemia and severe cardiorenal phenotypes. Furthermore, knock out of Kir5.1 in Dahl salt-sensitive rat background revealed the crucial role of the Kir4.1/Kir5.1 channel in salt-induced hypertension. Summary Here, we focus on reviewing novel experimental evidence of the physiological function, expression and hormonal regulation of renal basolateral inwardly rectifying potassium channels. Further investigation of molecular and cellular mechanisms controlling Kir4.1 and Kir4.1/Kir5.1-mediating pathways and development of specific compounds targeting these channels function is essential for proper control of electrolyte homeostasis and blood pressure.https://ift.tt/2vvo0Re
Hypoxia-inducible factor stabilizers for treating anemia of chronic kidney disease
Purpose of review Small-molecule inhibitors of prolyl hydroxylase domain enzymes (PHD inhibitors) are novel renal anemia therapies that increase endogenous erythropoietin (EPO) production by stabilizing hypoxia-inducible factor (HIF). This review summarizes recent findings and future perspectives of PHD inhibitors (HIF stabilizers) in chronic kidney disease (CKD)-associated anemia. Recent findings Clinical trials have demonstrated that HIF stabilizers effectively increase hemoglobin levels of both nondialysis and dialysis CKD patients without causing serious adverse effects. HIF stabilizers not only restore EPO production but also optimize iron metabolism by reducing hepcidin levels. Considering the pleiotropic roles of the PHD–HIF pathway, HIF stabilizers might have both advantageous and disadvantageous effects in humans, in addition to erythropoiesis. Results of studies in animal models have suggested that HIF stabilizers alleviate ischemia–reperfusion injury and play protective roles against metabolic diseases. In contrast, a theoretical concern exists regarding the potential for tumorigenesis due to HIF stabilization. Summary At least five HIF stabilizers are now in phase III trials and may appear on the market in 1–2 years. The long-term effects and safety of HIF stabilization should be carefully examined in future basic and clinical studies.https://ift.tt/2naJsaK
Will there still be a role for the originator erythropoiesis-simulating agents after the biosimilars and the hypoxia-inducible factor stabilizers approval?
Purpose of review To discuss if there will still be a role for the originator ESAs after the already available biosimilars and the approval of HIF stabilizers in the near future. Recent findings Current treatment with erythropoiesis-simulating agents (ESAs) is effective and generally well tolerated, but requires parenteral injections. It is also surrounded by safety concerns and is still expensive. Functional iron deficiency is the major obstacle for efficient ESA therapy. ESA resistance may develop, calling for high ESA doses, further increasing the side effects associated with ESA use. Biosimilars were introduced for reducing costs. In searching for an ideal antianemic drug, new investigational strategies have been proposed including the attractive alternative hypoxia-inducible factor (HIF) stabilizers, which stimulate endogenous EPO production. However, we should caution in translating the historical results referring to the side effects of ESAs to current clinical practice, considering that hemoglobin targets and ESAs doses are now much lower. We could anticipate that side effects will be much less. Summary According to preliminary data, orally administered HIF stabilizers could provide pharmacological advantages over the existing ESAs. These will need confirmation by the findings of large, phase-3, clinical trials. Finally, cost will be an important issue determining their future use.https://ift.tt/2LRdWNI
Epithelial sodium channel biogenesis and quality control in the early secretory pathway
Purpose of review The epithelial sodium channel, ENaC, is responsible for Na+ reabsorption in several epithelia and is composed of homologous α, β, and γ subunits. Here, we will explore the differential regulation of ENaC subunits during biogenesis in the early secretory pathway. Recent findings ENaC subunits are subject to numerous posttranslational modifications, including glycosylation, protease activation, disulfide bond formation, palmitoylation, and glycosylation, each of which modulate channel function. For example, glycan addition is regulated by sodium and affects protease activation at the cell surface, protein trafficking, sodium-dependent regulation, and sodium transport. Glycosylation of the α subunit also determines whether a chaperone, Lhs1/GRP170, selects the protein for endoplasmic reticulum-associated degradation. Recognition by this chaperone is blocked by assembly of the ENaC transmembrane domains. In contrast, cytosolic lysines are acetylated in the early secretory pathway, which inhibits ubiquitination and endocytosis at the cell surface. Summary As sodium reabsorption by ENaC in the distal nephron regulates salt and water homeostasis, ENaC function is critical for human health. Therefore, identifying and characterizing modifiers of ENaC in the early secretory pathway may provide both new therapeutic targets and further our basic understanding of membrane protein assembly and regulation.https://ift.tt/2vAJwnR
Adaptive remodeling of renal Na+ and K+ transport during pregnancy
Purpose of review Renal ion transport undergoes dramatic changes during the course of gestation. These adaptations are necessary to meet the dynamic requirements of pregnancy and support fetal development. Pregnancy is characterized by a high demand for both sodium and potassium. Recently there has been work in the field profiling the modifications of the renal tubules in pregnancy to meet these demands. The purpose of this review is to summarize these findings. Recent findings The work to date suggests an important role for the distal nephron in both the renal sodium and potassium reabsorption during pregnancy. There is strong evidence that renal sodium reabsorption is mediated by the epithelial sodium channel (ENaC). Whereas renal potassium reabsorption is mediated by upregulation of potassium retaining transporters (HKA2) and downregulation of potassium secreting channels (ROMK, BK). Summary Fetal growth restriction and hypertensive disorders of pregnancy including preeclampsia are marked by suboptimal maternal plasma volume expansion, which is determined by renal electrolyte handling. Therefore, understanding the physiologic demand for sodium and potassium in pregnancy and the adaptations required to support these needs is necessary for the effective treatment of diseased states of pregnancy.https://ift.tt/2vvnNxq
Activin receptor ligand traps in chronic kidney disease
Purpose of review Sotatercept and luspatercept are recombinant soluble activin type-II receptor-IgG-Fc fusion proteins that are tested in clinical trials for the treatment of various types of anemias, including renal anemia. The mechanism of the action of the novel drugs is incompletely understood, but it seems to be based on the inactivation of soluble proteins of the transforming growth factor-ß (TGFß) family. This review considers pros and cons of the clinical use of the drugs in reference to the current therapy with recombinant erythropoiesis-stimulating agents (ESAs). Recent findings One or more activin type-II receptor (ActRII) ligands appear to inhibit erythroid precursors, for example growth and differentiation factor 11. Trapping of these ligands by the recombinant ActRII fusion proteins, sotatercept and luspatercept increases red blood cell numbers and hemoglobin levels in humans. Reportedly, the novel compounds were well tolerated in trials on healthy volunteers and patients suffering from anemia due to chronic kidney disease or malignancies. On approval, the drugs may prove particularly useful in patients suffering from ineffective erythropoiesis, such as in myelodysplastic syndrome, multiple myeloma or ß-thalassemia, where ESAs are of little use. Independent of their effect on erythropoiesis, ActRII ligand traps were found to exert beneficial effects on renal tissue in experimental animals. Summary ESAs are likely to remain standard of care in renal anemia. There is a need for a better understanding of the effects of ActRII ligand traps on TGFß-like proteins. The novel drugs have not been approved for sale as therapeutics so far. Their long-term efficacy and safety still needs to be proven, particularly with respect to immunogenicity. Antifibrotic effects may be worthy to be investigated in humans.https://ift.tt/2n8N4da
Role of microRNAs in aldosterone signaling
Purpose of review The review describes studies investigating the role of microRNAs in the signaling pathway of the mineralocorticoid hormone, aldosterone. Recent findings Emerging evidence indicates that aldosterone alters the expression of microRNAs in target tissues thereby modulating the expression of key regulatory proteins. Summary The mineralocorticoid hormone aldosterone is released by the adrenal glands in a homeostatic mechanism to regulate blood volume. The long-term renal action of aldosterone is to increase the retrieval of sodium from filtered plasma to restore blood pressure. Emerging evidence indicates aldosterone may alter noncoding RNAs (ncRNAs) to integrate this hormonal response in target tissue. Expression of the best characterized small ncRNAs, microRNAs, is regulated by aldosterone stimulation. MicroRNAs modulate protein expression at all steps in the renin–angiotensin–aldosterone-signaling (RAAS) system. In addition to acting as a rheostat to fine-tune protein levels in aldosterone-responsive cells, there is evidence that microRNAs down-regulate components of the signaling cascade as a feedback mechanism. The role of microRNAs is, therefore, as signal integrator, and damper in aldosterone signaling, which has implications in understating the RAAS system from both a physiological and pathophysiological perspective. Recent evidence for microRNA's role in RAAS signaling will be discussed.https://ift.tt/2vvnHpy
ATRX loss is an independent predictor of poor survival in pancreatic neuroendocrine tumours
Pancreatic neuroendocrine tumours (PanNETs) are rare neoplasms accounting for 1-2% of all pancreatic tumours. The biological behaviour of PanNETs is heterogeneous and unpredictable, adding to the difficulties of clinical management. The DAXX (death domain associated protein) and ATRX (alpha-thalassemia/mental retardation syndrome X-linked) genes encode proteins involved in SWI/SNF-like chromatin remodelling. Somatic inactivating mutations in DAXX and ATRX are frequent in PanNETs, mutually exclusive, and associated with telomere dysfunction resulting in genomic instability and alternate lengthening of telomeres.
https://ift.tt/2vBLPXA
The correlation of NLRC3 expression to the progression and prognosis of hepatocellular carcinoma
NLRC3 is a member of the NLR (nucleotide-binding domain and leucine-rich repeat) family protein that plays a role in inflammation and immunity. Although chronic inflammation has been identified as a hallmark of cancer, whether NLRC3 expression correlated to the development and prognosis of hepatocellular carcinoma (HCC) is unclear. In the present study, we first used Oncomine and OncoLnc database to determine the clinical significance of NLRC3 in HCC. Then we performed quantitative real-time polymerase chain reaction (qRT-PCR), western-blot and immunohistochemical staining (IHC), and analyzed the correlation between NLRC3 expression and clinicopathological features in HCC of Chinese population.
https://ift.tt/2LPWnO6
Death of an Arabian mare due to incomplete treatment of fetal maceration: a case report
Abstract
Ten-year-old Arabian mare was referred to the Veterinary Teaching Hospital of Shahid Bahonar University of Kerman, central Iran, in lateral recumbency with anorexia and severe weakness. On clinical examination, the mare was depressed, tachypneic (55 breaths/min), tachycardic (50 beats/min), and had a body temperature of 36.5 °C. Stronger heart tone than normal was detectable by stethoscope and mucous membranes were hyperemic. At necropsy, a distended uterus containing a large amount of malodorous thin sanguineous exudate, inflammatory debris, and fetal bones indicated fetal maceration that previously had been diagnosed by an inexperienced clinician but had not been cured exactly. Treatment consisting of intravenous administration of isotonic fluids, anti-inflammatory agent, and antibiotic was not successful and the mare died 3 h after the onset of the treatment. The current report is the first report of fetal maceration in Arabian mares and it seems that in the present case, incomplete treatment resulted in the retained fetal materials that caused severe toxemia and death.
https://ift.tt/2vyzhAw
Characteristics of ventilator-associated pneumonia due to hypervirulent Klebsiella pneumoniae genotype in genetic background for the elderly in two tertiary hospitals in China
Aerobactin is a critical factor for the hypervirulent Klebsiella pneumoniae (hvKp), but data for the aerobactin-positive genotype of hvKp in elderly persons with ventilator-associated pneumonia (VAP) is limited. ...
https://ift.tt/2Mloh0g
PEDIATRIC AUTOIMMUNE LIVER DISEASE AND EXTRA-HEPATIC IMMUNE-MEDIATED COMORBIDITIES
Autoimmune liver disease (AILD) includes autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). AILD is often associated with other extra-hepatic immune-mediated disorders (EDs), but there are few pediatric studies available to date. In this study we evaluated the association between AILD and EDs in our pediatric series.
https://ift.tt/2M2d0VO
Normal values of esophageal distensibility and distension-induced contractility measured by functional luminal imaging probe panometry
Functional luminal imaging probe (FLIP) panometry provides a comprehensive evaluation of esophageal functional at the time of endoscopy, including assessment of esophageal distensibility and distension-induced esophageal contractility. However, the few and inconsistent findings from healthy individuals pose challenges to application of FLIP to research and clinical practice. We performed FLIP panometry in asymptomatic volunteers.
https://ift.tt/2AENMbH
Acceptability, Accuracy and Safety of Disposable Transnasal Capsule Endoscopy for Barrett’s Esophagus Screening
Screening for Barrett's esophagus (BE) with conventional esophagogastroduodenoscopy (C-EGD) is expensive. We assessed the performance of a clinic-based, single use transnasal capsule endoscope (EG Scan II) for the detection of BE, compared to C-EGD as the reference standard.
https://ift.tt/2OI2sd6
Measurement of Dynamic Force Acted on Water Strider Leg Jumping Upward by the PVDF Film Sensor
https://ift.tt/2vzG9NP
Quiz: 4 things EMS providers need to know about pulmonary embolism
When a patient's life is in your hands, you need to know the risk factors, signs and symptoms of PE
https://ift.tt/2ABJ7HF
Neutrophil Extracellular Traps Generated by Low Density Neutrophils Obtained from Peritoneal Lavage Fluid Mediate Tumor Cell Growth and Attachment
Here, we present a method in which human low-density neutrophils (LDN), recovered from postoperative peritoneal lavage fluid, produce massive neutrophil extracellular traps (NETs) and efficiently trap free tumor cells that subsequently grow.
https://ift.tt/2LQDr1p
Simon effects in action sequences
Abstract
Most actions we perform in daily life consist of multiple movement elements. In two Simon task experiments, we investigated the impact of stimulus–response compatibility on planning and execution of action sequences. A total of 38 participants were instructed to perform action sequences consisting of multiple key presses (two to four key presses) as response to a left- or right-presented colored stimulus. Within one block, the requested action sequences were of the same length but differed in their spatial features. The results show Simon effects in reaction time for up to four-element long action sequences. The effects became especially apparent when participants were forced to finish action planning before action execution by the implementation of a no-go condition (Experiment 2). Simon effects in movement time emerged for two movement element actions, only. That is, dimensional overlap between spatial features embedded in an action sequence as well as in an imperative stimulus can affect action initiation.
https://ift.tt/2n5U36K
Quantitative Cell Biology of Neurodegeneration in Drosophila Through Unbiased Analysis of Fluorescently Tagged Proteins Using ImageJ
https://ift.tt/2KqEZcS
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
A protocol for in vitro induction of endothelial-mesenchymal transition (EndMT), which is useful for investigating cellular signaling pathways involved in EndMT, is described. In this experimental model, EndMT is induced by treatment with TGF-β in MS-1 endothelial cells.
https://ift.tt/2M1FYFp
Rare Event Detection Using Error-corrected DNA and RNA Sequencing
Next-generation sequencing (NGS) is a powerful tool for genomic characterization that is limited by the high error rate of the platform (~0.5–2.0%). We describe our methods of error-corrected sequencing that allow us to obviate the NGS error rate and detect mutations at variant allele fractions as rare as 0.0001.
https://ift.tt/2KpMj8W
Patient-specific image-based bone marrow dosimetry in Lu-177-[DOTA 0 ,Tyr 3 ]-Octreotate and Lu-177-DKFZ-PSMA-617 therapy: investigation of a new hybrid image approach
Abstract
Background
The bone marrow (BM) is a main organ at risk in Lu-177-PSMA-617 therapy of prostate cancer and Lu-177-Octreotate therapy of neuroendocrine tumours. BM dosimetry is challenging and time-consuming, as different sequential quantitative measurements must be combined. The BM absorbed dose from the remainder of the body (ROB) can be determined from sequential whole-body planar (WB-P) imaging, while quantitative Lu-177-SPECT allows for more robust tumour and organ absorbed doses. The aim was to investigate a time-efficient and patient-friendly hybrid protocol (HP) for the ROB absorbed dose to the BM. It combines three abdominal quantitative SPECT (QSPECT) scans with a single WB-P acquisition and was compared with a reference protocol (RP) using sequential WB-P in combination with sequential QSPECT images. We investigated five patients receiving 7.4 GBq Lu-177-Octreotate and five patients treated with 3.7 GBq Lu-177-PSMA-617. Each patient had WB-P and abdominal SPECT acquisitions 24 (+ CT), 48, and 72 h post-injection. Blood samples were drawn 30 min, 80 min, 24 h, 48 h, and 72 h post-injection. BM absorbed doses from the ROB were estimated from sequential WB-P images (RP), via a mono-exponential fit and mass-scaled organ-level S values. For the HP, a mono-exponential fit on the QSPECT data was scaled with the activity of one WB-P image acquired either 24, 48, or 72 h post-injection (HP24, HP48, HP72). Total BM absorbed doses were determined as a sum of ROB, blood, major organ, and tumour contributions.
Results
Compared with the RP and for Lu-177-Octreotate therapy, median differences of the total BM absorbed doses were 13% (9–17%), 8% (4–15%), and 1% (0–5%) for the HP24, HP48, and HP72, respectively. For Lu-177-PSMA-617 therapy, total BM absorbed doses deviated 10% (2–20%), 3% (0–6%), and 2% (0–6%).
Conclusion
For both Lu-177-Octreotate and Lu-177-PSMA-617 therapy, BM dosimetry via sequential QSPECT imaging and a single WB-P acquisition is feasible, if this WB-P image is acquired at a late time point (48 or 72 h post-injection). The reliability of the HP can be well accepted considering the uncertainties of quantitative Lu-177 imaging and BM dosimetry using standardised organ-level S values.
https://ift.tt/2OIoFYn
Abstracts from the Chinese Journal of Hypertension
Association Between Hypertensive Disorders in Pregnancy and the Detection of New-Onset Arteriosclerosis
https://ift.tt/2nbm9gS
https://ift.tt/2nbm9gS
Abstracts from the Chinese Journal of Hypertension
Parathyroid Hormone Levels Are Positively Correlated With Left Ventricular Hypertrophy in Patients With Primary Aldosteronism
https://ift.tt/2vzXfeN
https://ift.tt/2vzXfeN
Response to “Yogurt Intake and Risk of Cardiovascular Disease Among Hypertensive Individuals: Is It Time for a Clinical Trial?”
To the Editor: We thank Elias et al. for their letter to the editor regarding our recent publication, "Yogurt intake and risk of cardiovascular disease among hypertensive individuals."1 The authors raised several interesting points that we would like to address. With respect to the absence of a "reference group" of nonhypertensive individuals, we emphasize that we purposefully selected those with prevalent high blood pressure (HBP) for inclusion in this study for two reasons—first, to ensure greater comparability between regular yogurt consumers and nonconsumers (our internal referent group), and, second, because the mechanisms by which yogurt may impact cardiovascular disease risk may well extend beyond blood pressure control. We designed this analysis to address an important gap in the scientific literature since no previous studies had evaluated the relative incidence of cardiovascular disease associated with the level of yogurt consumption among those with prevalent HBP.
https://ift.tt/2n7iSyZ
https://ift.tt/2n7iSyZ
In Memoriam: Alberto Zanchetti (Parma 27 July 1926–Milan 24 March 2018)
Professor Alberto Zanchetti passed away on 24 March 2018 at the age of almost 92 years. He had been in an excellent physical and a brilliant mental shape until a month before. Unfortunately, soon after returning from a lecture tour in Latin America, he accidentally fell and suffered a brain trauma from which he did not recover.
https://ift.tt/2vvUc7e
https://ift.tt/2vvUc7e
Effect of lentiviral vector-mediated KSR1 gene silencing on the proliferation of renal tubular epithelial cells and expression of inflammatory factors in a rat model of ischemia/reperfusion injury
Abstract
Renal ischemia/reperfusion (I/R) is a common cause of acute renal failure in many clinical settings. Our study aimed to elucidate the role of lentiviral vector-mediated KSR1 gene silencing in inflammatory factor expression and proliferation of renal tubular epithelial cells (RTECs) in a rat model of I/R injury. Male Sprague–Dawley (SD) rats were used for I/R model establishment and subject to different treatments, followed by the measurement of neurological severity score (NSS), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, 47-kDa heat-shock protein (HSP47), KSR1, and factors related to the Ras/MAPK pathway, as well as cell apoptosis. As compared with the blank group, the neurologic impairment induced by I/R in the siKSR1, U0126, and siKSR1 + U0126 groups was alleviated. Compared with the control group, the other five groups showed increased levels of TNF-α, IL-6, IL-1β, HSP47, N-ras, Raf-1, c-fos, TNF-α, IL-6, p38 MAPK, and cell apoptosis, accompanied by a declined mRNA and protein level of Bcl-2. As compared with the blank and NC groups, the siKSR1, U0126, and siKSR1 + U0126 groups showed decreased levels of TNF-α, IL-6, IL-1β, HSP47, N-ras, Raf-1, c-fos, TNF-α, IL-6, p38 MAPK, cleaved caspase-3, cleaved caspase-9, p53, and cell apoptosis, accompanied by an increased mRNA and protein level of Bcl-2. Our findings demonstrated that KSR1 gene silencing might inhibit the expression of inflammatory factors in RTECs and promote their proliferation by inactivating the Ras/MAPK pathway in the rat model of I/R injury.https://ift.tt/2LPraKW
PIM1 overexpression in T-cell lymphomas protects tumor cells from apoptosis and confers doxorubicin resistance by upregulating c-myc expression
Abstract
T-cell lymphomas (TCLs) are a malignancy characterized by tumor aggression and resistance to traditional chemotherapy. Disruption of the extrinsic cell death pathway is essential for resistance to chemotherapy. PIM1 serves as a crucial modulator in cancers. However, the role of PIM1 in TCLs remains unclear. In this study, we studied the roles of PIM1 in established T-lymphoma cell lines Jurkat and HUT-78. CCK-8 assay was conducted to evaluate cell survival and flow cytometry was performed to evaluate cell death of TCL cells. siRNAs were used to knockdown the expression of PIM1 and c-myc. qRT-PCR was used to evaluate the mRNA expression levels of c-myc and PIM1. Western blot analysis was used to evaluate the protein expression levels of PIM1, c-myc, STAT3, and phospho-STAT3. Doxorubicin was used to determine the effect of PIM1 on apoptosis. Our results showed that PIM1 expression was markedly enhanced and induced c-myc expression in TCL cells. Doxorubicin inhibited the expressions of c-myc and PIM1, and triggered the extrinsic cell death of TCLs by suppressing the JAK-STAT3 signaling pathway. Moreover, PIM1 silencing via siRNA suppressed c-myc expression, promoted the cell death of TCLs, and increased doxorubicin sensitivity. Conversely, PIM1 overexpression in TCL cells induced c-myc expression, suppressed TCL cell death, and promoted doxorubicin resistance. Collectively, our results demonstrate that PIM1 overexpression in TCLs participates in cancer cell protection from apoptosis and leads to doxorubicin resistance by inducing c-myc expression, indicating that PIM1 may be a promising target in TCL treatment.https://ift.tt/2vvU080
GlnR positive transcriptional regulation of the phosphate-specific transport system pstSCAB in Amycolatopsis mediterranei U32
Abstract
Amycolatopsis mediterranei U32 is an important industrial strain for the production of rifamycin SV. Rifampicin, a derivative of rifamycin SV, is commonly used to treat mycobacterial infections. Although phosphate has long been known to affect rifamycin biosynthesis, phosphate transport, metabolism, and regulation are poorly understood in A. mediterranei. In this study, the functional phosphate transport system pstSCAB was isolated by RNA sequencing and inactivated by insertion mutation in A. mediterranei U32. The mycelium morphology changed from a filamentous shape in the wild-type and pstS1+ strains to irregular swollen shape at the end of filamentous in the ΔpstS1 strain. RT-PCR assay revealed that pstSCAB genes are co-transcribed as a polycistronic messenger. The pstSCAB transcription was significantly activated by nitrate supplementation and positively regulated by GlnR which is a global regulator of nitrogen metabolism in actinomycetes. At the same time, the yield of rifamycin SV decreased after mutation (ΔpstS1) compared with wild-type U32, which indicated a strong connection among phosphate metabolism, nitrogen metabolism, and rifamycin production in actinomycetes.https://ift.tt/2LNYgKZ
Combination of Immunotherapy Drugs Approved for Metastatic Colorectal Cancer
The FDA has approved the combination of the immune checkpoint inhibitors ipilimumab (Yervoy) and nivolumab (Opdivo) for the treatment of patients with metastatic colorectal cancer whose tumor cells have defects that affect their ability to repair DNA.
https://ift.tt/2MfP1Q5
Surgical resection of hepatic and rectal metastases of pancreatic acinar cell carcinoma (PACC): a case report
Abstract
Background
Pancreatic acinar cell carcinoma (PACC), a rare variant of pancreatic malignancy, is generally managed the same way as pancreatic ductal adenocarcinoma (PDAC). Surgical resection is the gateway to curing it; however, once it metastasizes (usually to the liver, lungs, lymph nodes, or peritoneal cavity), systemic chemotherapy has been the only option, but with unfavorable results.
Case presentation
A 67-year-old man with symptoms of loss of appetite and weight underwent surgery for malignancy of the pancreatic tail extending into the entire pancreas. The pathological diagnosis was PACC following total pancreatectomy. Twenty-four months after the pancreatectomy, a solitary liver metastasis was treated by partial hepatectomy, and, subsequently, 4 months later, he presented with melena. Further examination revealed a type-2 rectal tumor. Histological examination following biopsy revealed it to be rectal metastasis of PACC, and it was treated by abdominoperineal resection. Subsequently, the patient did not have tumor recurrence as of 40 months after pancreatectomy.
Conclusions
This is a rare case of PACC presenting with metachronal metastases in the liver and rectum, and we successfully treated them by surgical resections. Since the malignant behavior of PACC is usually less than that of PDAC, surgical resection could be an option even for metastatic lesions when the number and extent of metastases are limited.
https://ift.tt/2MgTiCI
Barrett’s oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux
Abstract
Background
Early detection of oesophageal cancer improves outcomes; however, the optimal strategy for identifying patients at increased risk from the pre-cancerous lesion Barrett's oesophagus (BE) is not clear. The Cytosponge, a novel non-endoscopic sponge device, combined with the biomarker Trefoil Factor 3 (TFF3) has been tested in four clinical studies. It was found to be safe, accurate and acceptable to patients.
The aim of the BEST3 trial is to evaluate if the offer of a Cytosponge-TFF3 test in primary care for patients on long term acid suppressants leads to an increase in the number of patients diagnosed with BE.
Methods
The BEST3 trial is a pragmatic multi-site cluster-randomised controlled trial set in primary care in England. Approximately 120 practices will be randomised 1:1 to either the intervention arm, invitation to a Cytosponge-TFF3 test, or the control arm usual care. Inclusion criteria are men and women aged 50 or over with records of at least 6 months of prescriptions for acid-suppressants in the last year. Patients in the intervention arm will receive an invitation to have a Cytosponge-TFF3 test in their general practice. Patients with a positive TFF3 test will receive an invitation for an upper gastro-intestinal endoscopy at their local hospital-based endoscopy clinic to test for BE.
The primary objective is to compare histologically confirmed BE diagnosis between the intervention and control arms to determine whether the offer of the Cytosponge-TFF3 test in primary care results in an increase in BE diagnosis within 12 months of study entry.
Discussion
The BEST3 trial is a well-powered pragmatic trial testing the use of the Cytosponge-TFF3 test in the same population that we envisage it being used in clinical practice. The data generated from this trial will enable NICE and other clinical bodies to decide whether this test is suitable for routine clinical use.
Trial registration
This trial was prospectively registered with the ISRCTN Registry on 19/01/2017, trial number ISRCTN68382401.
https://ift.tt/2ADGrcB
Enrichment of cancer stem cells via β-catenin contributing to the tumorigenesis of hepatocellular carcinoma
Abstract
Background
Hepatocellular carcinoma (HCC) is among the deadliest cancers due to its heterogeneity, contributing to chemoresistance and recurrence. Cancer stem-like cells (CSCs) are suggested to play an important role in HCC tumorigenesis. This study investigates the role of Wnt/β-catenin pathway in CSC enrichment and the capabilities of these CSCs in tumor initiation in orthotopic immunocompetent mouse model.
Methods
HCC-CSCs were enriched using established serum-free culture method. Wnt/β-catenin pathway activation and its components were analyzed by western blot and qRT-PCR. The role of β-catenin in enrichment of CSC spheroids was confirmed using siRNA interference. Tumorigenic capabilities were confirmed using orthotopic immunocompetent mouse model by injecting 2 × 106 Hepa1–6 CSC spheroids or control cells in upper left liver lobe.
Results
The serum-free cultured Hepa1–6 cells demonstrated self-renewal, spheroid formation, higher EpCAM expression, increased Hoechst-33342 efflux, and upregulated Wnt/β-catenin signaling. Wnt/β-catenin pathway upregulation was implicated with the downstream targets, i.e., c-MYC, Cyclin-D1, and LEF1. Also, we found that GSK-3β serine-9 phosphorylation increased in Hepa1–6 spheroids. Silencing β-catenin by siRNA reversed spheroid formation phenotype. Mice injected with Hepa1–6 CSC spheroids showed aggressive tumor initiation and growth compared with mice injected with control cells.
Conclusions
Successfully induced Hepa1–6 spheroids were identified with CSC-like properties. Aberrant β-catenin upregulation mediated by GSK-3β was observed in the Hepa1–6 spheroids. The β-catenin mediated CSC enrichment in the induced spheroids possesses the capability of tumor initiation in immunocompetent mice. Our study suggests plausible cell dedifferentiation mediated by β-catenin contributes to CSC-initiated HCC tumor growth in vivo.
https://ift.tt/2vlmfqT
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
