| Bridging larger gaps in peripheral nerves using neural prosthetics and physical therapeutic agents Muhammad Sana Ullah Sahar, Matthew Barton, Geoffrey Douglas Tansley Neural Regeneration Research 2019 14(7):1109-1115 Peripheral nerve injuries are relatively common and can be caused by a variety of traumatic events such as motor vehicle accidents. They can lead to long-term disability, pain, and financial burden, and contribute to poor quality of life. In this review, we systematically analyze the contemporary literature on peripheral nerve gap management using nerve prostheses in conjunction with physical therapeutic agents. The use of nerve prostheses to assist nerve regeneration across large gaps (> 30 mm) has revolutionized neural surgery. The materials used for nerve prostheses have been greatly refined, making them suitable for repairing large nerve gaps. However, research on peripheral nerve gap management using nerve prostheses reports inconsistent functional outcomes, especially when prostheses are integrated with physical therapeutic agents, and thus warrants careful investigation. This review explores the effectiveness of nerve prostheses for bridging large nerve gaps and then addresses their use in combination with physical therapeutic agents. |
| Magnesium: Pathophysiological mechanisms and potential therapeutic roles in intracerebral hemorrhage Jason J Chang, Rocco Armonda, Nitin Goyal, Adam S Arthur Neural Regeneration Research 2019 14(7):1116-1121 Intracerebral hemorrhage (ICH) remains the second-most common form of stroke with high morbidity and mortality. ICH can be divided into two pathophysiological stages: an acute primary phase, including hematoma volume expansion, and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion. To date, all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control, surgical evacuation, and hemostasis. However, none of these trials has resulted in improved clinical outcomes. Magnesium is a ubiquitous element that also plays roles in vasodilation, hemostasis, and blood-brain barrier preservation. Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms. Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume, hematoma expansion, and clinical outcome in patients with ICH. These associations, coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH, suggest that magnesium may be a viable target of study in future ICH studies. |
| Network-centric medicine for peripheral nerve injury: Treating the whole to boost endogenous mechanisms of neuroprotection and regeneration David Romeo-Guitart, Caty Casas Neural Regeneration Research 2019 14(7):1122-1128 Peripheral nerve injuries caused by accidents may lead to paralysis, sensory disturbances, anaesthesia, and lack of autonomic functions. Functional recovery after disconnection of the motoneuronal soma from target tissue with proximal rupture of axons is determined by several factors: motoneuronal soma viability, proper axonal sprouting across inhibitory zones and elongation toward specific muscle, effective synapse contact rebuilding, and prevention of muscle atrophy. Therapies, such as adjuvant drugs with pleiotropic effects, that promote functional recovery after peripheral nerve injury are needed. Toward this aim, we designed a drug discovery workflow based on a network-centric molecular vision using unbiased proteomic data and neural artificial computational tools. Our focus is on boosting intrinsic capabilities of neurons for neuroprotection; this is in contrast to the common approach based on suppression of a pathobiological pathway known to be associated with disease condition. Using our workflow, we discovered neuroheal, a combination of two repurposed drugs that promotes motoneuronal soma neuroprotection, is anti-inflammatory, enhances axonal regeneration after axotomy, and reduces muscle atrophy. This drug discovery workflow has thus yielded a therapy that is close to its clinical application. |
| Exogenous neural stem cell transplantation for cerebral ischemia Ling-Yi Liao, Benson Wui-Man Lau, Dalinda Isabel Sánchez-Vidaña, Qiang Gao Neural Regeneration Research 2019 14(7):1129-1137 Cerebral ischemic injury is the main manifestation of stroke, and its incidence in stroke patients is 70–80%. Although ischemic stroke can be treated with tissue-type plasminogen activator, its time window of effectiveness is narrow. Therefore, the incidence of paralysis, hypoesthesia, aphasia, dysphagia, and cognitive impairment caused by cerebral ischemia is high. Nerve tissue regeneration can promote the recovery of the aforementioned dysfunction. Neural stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain tissue. Neural stem cell transplantation for ischemic stroke has been a hot topic for more than 10 years. This review discusses the treatment of ischemic stroke with neural stem cells, as well as the mechanisms of their involvement in stroke treatment. |
| Potential therapeutic molecular targets for blood-brain barrier disruption after subarachnoid hemorrhage Hideki Kanamaru, Hidenori Suzuki Neural Regeneration Research 2019 14(7):1138-1143 Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities. Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure, followed by global cerebral ischemia. Post-subarachnoid hemorrhage ischemia, tissue injuries as well as extravasated blood components and the breakdown products activate microglia, astrocytes and Toll-like receptor 4, and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades. Once blood-brain barrier is disrupted, brain tissues are directly exposed to harmful blood contents and immune cells, which aggravate brain injuries furthermore. Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins. Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage, but the exact mechanisms remain unclear. Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage. This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage. |
| Choroid plexus tumor necrosis factor receptor 1: A new neuroinflammatory piece of the complex Alzheimer's disease puzzle Sophie Steeland, Roosmarijn E Vandenbroucke Neural Regeneration Research 2019 14(7):1144-1147 Due to the aging of the population and despite the enormous scientific effort, Alzheimer’s disease remains one of the biggest medical and pharmaceutical challenges in current medicine. Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer’s disease. Tumor necrosis factor is a master inflammatory cytokine that signals via tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2, but that also regulates several brain functions in health and disease. However, clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer’s disease led to inconclusive results, partially because not only the pro-inflammatory tumor necrosis factor/tumor necrosis factor receptor 1, but also the beneficial tumor necrosis factor/tumor necrosis factor receptor 2 signaling was antagonized in these trials. We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer’s disease patients, signaling via tumor necrosis factor receptor 1. In agreement with this, choroidal tumor necrosis factor/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer’s disease mouse models. Interestingly, both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer’s disease-associated inflammation, choroidal morphology and cognitive functioning. Here, we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor/tumor necrosis factor receptor 1 signaling in (early) Alzheimer’s disease, and the consequences this might have on the disease progression. As the main hypothesis in Alzheimer’s disease clinical trials is still based on the amyloid beta-cascade, the importance of Alzheimer’s disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer’s disease and prevent the irreversible neurodegeneration and resulting memory decline. |
| Transcriptional dysregulation in neurodegenerative diseases: Who tipped the balance of Yin Yang 1 in the brain? Zhefan Stephen Chen, Ho Yin Edwin Chan Neural Regeneration Research 2019 14(7):1148-1151 Yin Yang 1 (YY1) is a multi-functional transcription factor that regulates gene expression in a range of cell types, including neurons. It controls neuronal differentiation, as well as neuronal specification and migration during the development of the mammalian nervous system. Besides, YY1 also mediates the transcription of genes that are required for neuronal survival. An impairment of the transcriptional function of YY1 causes neuronal death. This review summarizes recent research findings that unveil the dysfunction of YY1 in multiple neurodegenerative disorders. The expression of disease proteins perturbs the function of YY1 via distinct molecular mechanisms, including recruitment to protein aggregates, protein degradation and aberrant nuclear/cytoplasmic shuttling. Understanding the pathogenic roles of YY1 will further broaden our knowledge of the disease mechanisms in distinct neurodegenerative disorders. |
| Effects of Ginkgo biloba extract EGb761 on neural differentiation of stem cells offer new hope for neurological disease treatment Chao Ren, Yong-Qiang Ji, Hong Liu, Zhe Wang, Jia-Hui Wang, Cai-Yi Zhang, Li-Na Guan, Pei-Yuan Yin Neural Regeneration Research 2019 14(7):1152-1157 Stem cell transplantation has brought new hope for the treatment of neurological diseases. The key to stem cell therapy lies in inducing the specific differentiation of stem cells into nerve cells. Because the differentiation of stem cells in vitro and in vivo is affected by multiple factors, the final differentiation outcome is strongly associated with the microenvironment in which the stem cells are located. Accordingly, the optimal microenvironment for inducing stem cell differentiation is a hot topic. EGb761 is extracted from the leaves of the Ginkgo biloba tree. It is used worldwide and is becoming one of the focuses of stem cell research. Studies have shown that EGb761 can antagonize oxygen free radicals, stabilize cell membranes, promote neurogenesis and synaptogenesis, increase the level of brain-derived neurotrophic factors, and replicate the environment required during the differentiation of stem cells into nerve cells. This offers the possibility of using EGb761 to induce the differentiation of stem cells, facilitating stem cell transplantation. To provide a comprehensive reference for the future application of EGb761 in stem cell therapy, we reviewed studies investigating the influence of EGb761 on stem cells. These started with the composition and neuropharmacology of EGb761, and eventually led to the finding that EGb761 and some of its important components play important roles in the differentiation of stem cells and the protection of a beneficial microenvironment for stem cell transplantation. |
| Amelioration of Alzheimer's disease pathology and cognitive deficits by immunomodulatory agents in animal models of Alzheimer's disease Bridget Martinez, Philip V Peplow Neural Regeneration Research 2019 14(7):1158-1176 The most common age-related neurodegenerative disease is Alzheimer’s disease (AD) characterized by aggregated amyloid-β (Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles, together with loss of cholinergic neurons, synaptic alterations, and chronic inflammation within the brain. These lead to progressive impairment of cognitive function. There is evidence of innate immune activation in AD with microgliosis. Classically-activated microglia (M1 state) secrete inflammatory and neurotoxic mediators, and peripheral immune cells are recruited to inflammation sites in the brain. The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects. Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials. Treatment with immunomodulatory/anti-inflammatory agents early in the disease process, while not preventive, is able to inhibit the inflammatory consequences of both Aβ and tau aggregation. The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD. The majority of the animal studies reviewed had used transgenic models of early-onset AD. More effort needs to be given to creat models of late-onset AD. The effects of a combinational therapy involving two or more of the tested pharmaceutical agents, or one of these agents given in conjunction with one of the cell-based therapies, in an aged animal model of AD would warrant investigation. |
| Precision medicine in pantothenate kinase-associated neurodegeneration Mónica Alvarez-Cordoba, Marina Villanueva-Paz, Irene Villalón-García, Suleva Povea-Cabello, Juan M Suárez-Rivero, Marta Talaverón-Rey, Javier Abril-Jaramillo, Ana Belén Vintimilla-Tosi, José A Sánchez-Alcázar Neural Regeneration Research 2019 14(7):1177-1185 Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas, mainly the basal ganglia. The predominant clinical symptoms include spasticity, progressive dystonia, Parkinson’s disease-like symptoms, neuropsychiatric alterations, and retinal degeneration. Among the neurodegeneration with brain iron accumulation disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2 (PANK2) which catalyzed the first reaction of the coenzyme A biosynthesis pathway. Currently there is no effective treatment to prevent the inexorable course of these disorders. The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN. Recently, we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules, mitochondrial dysfunction and a pronounced increase of markers of oxidative stress. In addition, PKAN fibroblasts showed a morphological senescence-like phenotype. Interestingly, pantothenate supplementation, the substrate of the PANK2 enzyme, corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression. However, pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein. The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts. Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations. Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment. The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate. The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available, and monitoring its effect on the pathophysiological changes, can help for a better therapeutic strategy. In addition, these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future. |
Δευτέρα 25 Φεβρουαρίου 2019
Neural Regeneration Research (Neural Regen Res)
Mediterranean diet, alkaline water may be as effective as PPIs for laryngopharyngeal reflux
Alkaline water is water that's less acidic than regular tap water. This means it is rich in alkalizing compounds, including calcium, silica, potassium, magnesium, and bicarbonate.https://www.precisionnutrition.com/alkaline-water-legit-or-hoax
Seeing little relief with PPIs for patients, study author looked to dietary treatment for LPR
Treatment of laryngopharyngeal reflux (LPR) with alkaline water and the Mediterranean diet may be as effective as treatment with proton-pump inhibitors (PPIs), according to research published online in JAMA Otolaryngology–Head & Neck Surgery in September. Like gastroesophageal reflux disease, a similar condition, LPR occurs when acidic gastric juices in the stomach back up into the esophagus, but in LPR, the gastric juices reach the throat, resulting in symptoms such as hoarseness, sore throat, cough, and excessive mucous.
In the study, researchers conducted a retrospective medical chart review comparing the change in Reflux Symptom Index (RSI) in two groups of patients, those treated between 2010 and 2012 with PPIs and standard reflux precautions and those treated between 2013 and 2015 with a plant-based Mediterranean diet and alkaline water that had a pH of at least 8. The team found that 54.1% of patients in the PPI group achieved a clinically meaningful reduction of at least 6 points, but 62.5% in the dietary group achieved similar results. Furthermore, those in the dietary group achieved a greater reduction in RSI: 39.8% compared with 27.2% in the PPI group.
"It's pretty clear that this data suggests that we, as health care professionals, need to start getting patients educated so they understand how important a role diet plays," said study lead author Craig H. Zalvan, MD, FACS, chief of otolaryngology and medical director at The Institute for Voice and Swallowing Disorders at Phelps Hospital in Sleepy Hollow, NY.
Zalvan said he thought to study dietary treatment for LPR after seeing that a sizable number of patients don't get much relief with PPIs.
"The standard of care for LPR has always been PPIs, and many of my patients got better with them, but a bunch didn't. At most it helps about 50% of patients," Zalvan said. "I looked at chronic diseases like heart disease, diabetes, and stroke, and their successful treatment with a plant-based diet, so I thought there's got to be a better way to treat LPR with diet [as well] and not have people constantly taking pills."
Zalvan added that the idea to incorporate alkaline water into treatment stemmed from prior research conducted by Jaime Koufman, MD, at the Voice Institute of New York in New York City, which suggests that alkaline water may benefit patients with reflux because it deactivates pepsin and acts as an acid buffer.
Zalvan said that as medication experts and readily accessible members of the health care team, pharmacists can help boost the signal about treatment options for LPR.
"Pharmacists can reinforce that PPIs are meant to be short-term medications for an acute problem, and that in order to get off them, diet will play a major part," Zalvan said. "If patients come to me and I say they should try diet, and then they go to the pharmacy and the pharmacist says they should try diet, patients are more likely to try diet."
For the full article, please visit www.pharmacytoday.org for the November 2017 issue of Pharmacy Today.
Gas-Phase Hydrogen/Deuterium Scrambling in Negative-Ion Mode Tandem Mass Spectrometry
Abstract
Hydrogen/deuterium exchange coupled with mass spectrometry (HDX MS) has become a powerful method to characterize protein conformational dynamics. Workflows typically utilize pepsin digestion prior to MS analysis to yield peptide level structural resolution. Tandem mass spectrometry (MS/MS) can potentially facilitate determination of site-specific deuteration to single-residue resolution. However, to be effective, MS/MS activation must minimize the occurrence of gas-phase intramolecular randomization of solution-generated deuterium labels. While significant work has focused on understanding this process in positive-ion mode, little is known about hydrogen/deuterium (H/D) scrambling processes in negative-ion mode. Here, we utilize selectively deuterated model peptides to investigate the extent of intramolecular H/D scrambling upon several negative-ion mode MS/MS techniques, including negative-ion collision-induced dissociation (nCID), electron detachment dissociation (EDD), negative-ion free radical–initiated peptide sequencing (nFRIPS), and negative-ion electron capture dissociation (niECD). H/D scrambling was extensive in deprotonated peptides upon nCID and nFRIPS. In fact, the energetics required to induce dissociation in nCID are sufficient to allow histidine C-2 and Cβ hydrogen atoms to participate in the scrambling process. EDD and niECD demonstrated moderate H/D scrambling with niECD being superior in terms of minimizing hydrogen migration, achieving ~ 30% scrambling levels for small c-type fragment ions. We believe the observed scrambling is likely due to activation during ionization and ion transport rather than during the niECD event itself.
https://ift.tt/2tBU31k
Electron Attachment and Electron Ionization of Formic Acid Clusters Embedded in Helium Nanodroplets
Abstract
We report the results of an experimental study of electron ionization of large helium nanodroplets doped with formic acid (FA). Several homologous series of cluster anions are observed, including [FAn-H]−, undissociated FAn−, and these ions complexed with one or more H2O. Some major features resemble those observed upon sputtering of frozen FA films but they differ significantly from results obtained by electron attachment to bare FA clusters in the gas phase. The FAn− and (H2O)[FAn-H]− series show abrupt onsets above n = 2 and 5, respectively. A prominent resonance in the anion yield occurs at 22.5 eV due to the formation of an intermediate He−*. Also observed are homologous series of [FA-H]− or [FA2-H]− complexed with helium. The cation chemistry is dominated by the production of protonated formic acid clusters, [FAnH]+, but various other homologous cluster ion series are observed as well.
Graphical Abstract
https://ift.tt/2H2E2cX
Breast Reduction and Mastopexy for Repair of Asymmetry After Breast Conservation Therapy: Lessons Learned
Abstract
Background
Breast conservation therapy (BCT) can cause breast distortion and asymmetry. Repair of this asymmetry by means of breast reduction or mastopexy procedures can be challenging and harbor considerably high rates of complications.
Methods
In this retrospective study, we describe our experience in repairing post-BCT breast asymmetry by performing breast reduction or mastopexy. The surgical protocol we followed consisted of stringent patient selection, thorough surgical planning, basic surgical refinements, and patient education for enhancing the likelihood of achieving a good outcome with minimal surgical complications.
Results
Our search of the departmental database identified 25 patients with breast asymmetry who had undergone breast reduction or mastopexy between 2009 and 2017. Corrective surgery was performed 4 years on average after the completion of radiotherapy, and those patients included eleven who had undergone breast reduction and fourteen who had undergone mastopexy on the radiated side. Two patients (8%) had major complications that required further surgery (major fat necrosis, wound infection, and breast deformation), and five patients (20%) had minor complications (infection, minor fat necrosis, wound dehiscence, and nipple congestion). All complications developed on the radiated breast. There was no correlation between the occurrence of complications and patients' demographics, tumor type, tumor location, and breast tissue resection (p > 0.05).
Conclusion
Only two of our 25 patients had major complications following breast reduction and mastopexy for the repair of asymmetry post-BCT. Following our four-step protocol was instrumental in leading to the successful performance of these procedures.
Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
https://ift.tt/2Ea2GFw
Changes in the Indices of Body Image Concern, Sexual Self-Esteem and Sexual Body Image in Females Undergoing Cosmetic Rhinoplasty: A Single-Group Trial
Abstract
Introduction
Psychological factors play a major role in the tendency toward cosmetic surgery. Variety seeking, making changes in one's face and reducing apparent dissatisfaction, improving body image and increasing sexual self-esteem can be considered as some psychological aspects of cosmetic surgery. The present study was conducted with the aim of evaluating the changes in the indices of body image concern, sexual self-esteem and sexual body image in patients undergoing rhinoplasty.
Method
This study was a single-group pretest–posttest quasi-experimental design. The research data were collected from March 2015 to January 2016. For this purpose, of the patients seeking nose surgery who referred to beauty centers in Mashhad, 40 subjects were selected through purposive method sampling and completed a Body Image Concern Inventory, Sexual Self-Esteem Index for Women and Body Exposure during Sexual Activities Questionnaire before and after rhinoplasty. These data were collected after obtaining informed consent, conducting a structured clinical interview and completing the demographic checklist.
Findings
Data analysis demonstrated that there is a significant improvement in the index of female body image concern after rhinoplasty (p < 0.05). In the indices of sexual self-esteem and sexual body image, the analyses showed no significant difference between the pretest and posttest scores (p > 0.05).
Conclusion
Cosmetic surgery leads to the reduced body image concern of women but has no effect on sexual self-esteem and sexual body image. It seems that the psychological function of patients does not change significantly by rhinoplasty dimensions.
Level of Evidence III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
https://ift.tt/2T0siyP
Experimental Insight into the Hemodynamics and Perfusion of Radiological Contrast in Patent and Non-patent Aortic Dissection Models
Abstract
Purpose
In a curved vessel such as the aortic arch, the velocity profile closer to the aortic root is normally skewed towards the inner curvature wall, while further downstream along the curve, the velocity profile becomes skewed towards the outer wall. In an aortic dissection (AD) disease, blood velocities in the true lumen (TL) and false lumen (FL) are hypothesized to depend on the proximity of the entry tear to the root of aortic arch. Faster velocity in the FL can lead to higher hemodynamic loading, and pose tearing risk. Furthermore, the luminal velocities control the perfusion rate of radiological contrast media during diagnostic imaging. The objective in this study is to investigate the effect of AD disease morphology and configuration on the blood velocity field in the TL and FL, and on the relative perfusion of radiological enhancement agents through the dissection.
Methods
Eight in vitro models were studied, including patent and non-patent FL configurations. Particle image velocimetry (PIV) was used to quantify the AD velocity field, while laser-induced fluorescence (LIF) was implemented to visualize dynamical flow phenomena and to quantify the perfusion of injected dye, in mimicry of contrast-enhanced computed tomography (CT).
Results
The location of the proximal entry tear along the aortic arch in a patent FL had a dramatic impact on whether the blood velocity was higher in the TL or FL. The luminal velocities were dependent on the entry/reentry tear size combination, with the smaller tear (whether distal or proximal) setting the upper limit on the maximal flow velocity in the FL. Upon merging near the distal reentry tear, the TL/FL velocity differential gave rise to the roll up and shedding of shear layer vortices that convected downstream in close proximity to the wall of the non-dissected aorta. In a non-patent FL, the flow velocity was practically null with all the blood passing through the TL. LIF imaging showed much slower perfusion of contrast dye in the FL compared to the TL. In a patent FL, however, dye had a comparable perfusion rate appearing around the same time as in the TL.
Conclusions
Blood velocities in the TL and FL were highly sensitive to the exact dissection configuration. Geometric case A1R, which had its proximal entry tear located further downstream along the aortic arch, and had its entry and reentry tears sufficiently sized, exhibited the highest FL flow velocity among the tested models, and it was also higher than in the TL, which suggest that this configuration had elevated hemodynamic loading and risk for tearing. In contrast-enhanced diagnostic imaging, a time-delayed acquisition protocol is recommended to improve the detection of suspected cases with a non-patent FL.
https://ift.tt/2SqjdtN
Chondrocutaneous Bilateral Advancement Flap with Postoperative Radiation Therapy for a Helical Rim Keloid
Abstract
Keloids can be recalcitrant, and a well-planned treatment strategy is essential. Multiple ear piercings have recently become popular, particularly among younger age groups. Management of keloids that develop after piercing of the ear cartilage may be particularly problematic. Helical rim keloids are difficult to excise because of the complex, three-dimensional, cartilaginous structure of the helix and its thin and tightly adherent covering layer of skin. The chondrocutaneous advancement flap introduced by Antia and Buch may be a useful reconstructive option for a helical rim keloid after marginal loss of a segment of the helix as a result of trauma, a burn, or excision of a malignant tumor. However, this technique is limited to wounds that involve only the helix. In this technical note, we describe the use of a chondrocutaneous bilateral advancement flap with postoperative radiation therapy to treat a more invasive and relatively large keloid on the scapha. This technique is straightforward and safe in terms of preserving the blood supply. The addition of adjuvant radiation therapy can help to decrease the risk of recurrence and preserve the morphological structure of the ear and patient satisfaction.
Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
https://ift.tt/2StqOYA
A Revision Mandibuloplasty: Causes, Indications, Surgical Methods and Treatment Outcomes
Abstract
Background
This paper aims to propose a classification system to categorize patients undergoing revision mandibuloplasty according to their dissatisfaction types. This paper also introduces various appropriate revision techniques and evaluates their outcomes. Through this classification system and suggested surgical techniques, surgeons can settle the disappointments experienced by patients after their primary mandibuloplasty, by realizing more natural-looking results.
Methods
The study subjects consisted of 184 patients who underwent a revision mandibuloplasty from October 2010 to March 2016, conducted by a single surgeon at a single institution. The authors were able to classify the dissatisfaction into two primary types—(1) lack of an overall slender frontal facial contour and (2) unnatural and asymmetrical overall facial appearance due to over- or inaccurate resection of the bone. A self-evaluation of patient's subjective satisfaction based on the scale from 1 to 5, both after the primary operation and after revision surgery, was compared.
Results
Dissatisfaction type I accounted for 145 patients (78.8 percent). The number of patients classified into dissatisfaction type II was 39 (21.2 percent). Of the patients categorized into type I, those undergoing revision surgeries due to an under-corrected mandibular tubercle and parasymphysis showed the most remarkable improvement in self-satisfaction score after reoperation—from 2.3 to 4.0.
Conclusion
To realize a natural-looking outcome in facial look through mandibular contouring, it is important not only to carefully consider the ratio and shape essential for an optimal slender facial contour, but also to minimize unnecessary resection of the bone.
Level of Evidence IV
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
https://ift.tt/2XlnXVm
Multidisciplinary Management of Psoriatic Arthritis: The Benefits of a Comprehensive Approach
Abstract
Psoriatic arthritis (PsA) is a lifelong disease associated with extra-articular manifestations and several comorbidities, as well as reduced quality of life and psychosocial burden. Diagnostic delay is associated with poorer outcomes, while a short delay between symptom onset and diagnosis is linked with preservation of function. Overcoming the barriers to early diagnosis of PsA is often difficult to achieve in the absence of well-characterized disease markers and/or a definitive screening procedure. Once a diagnosis is made, approaches to care may differ between countries, but a treat-to-target approach can be advocated, with constant patient follow-up visits and specialist monitoring and treatment of comorbidities. Adequately addressing all aspects of care can help to drive patient-centered care and encourage better adherence. Given the mounting number of therapeutic options and the complexity of management of PsA, the disease can be optimally treated by a multidisciplinary approach, and a collaborative approach between rheumatologists and dermatologists can be advocated. The need for multidisciplinary management is reinforced by consensus among experts. Patient satisfaction has emerged as a central indicator of quality, and patient-centered care must remain a central goal for the care of patients with PsA. Definition of a minimum set of standards for care will help to achieve the goal of multidisciplinary care for patients with PsA. Optimal care of PsA and greater collaboration among clinicians should always be encouraged so that patients can receive the best possible quality of care.
Funding: Pfizer Italy.
https://ift.tt/2IyTEHv
Genetic neuromuscular disorders: living the era of a therapeutic revolution. Part 2: diseases of motor neuron and skeletal muscle
Abstract
This is the second part of a two-part document intended to discuss recent therapeutic progresses in genetic neuromuscular disorders. The present review is for diseases of motor neuron and skeletal muscle, some of which reached recently the most innovative therapeutic approaches. Nusinersen, an SMN2 mRNA splicing modifier, was approved as first-ever therapy of spinal muscular atrophy (SMA) by FDA in 2016 and by EMA in 2017. The orally administered small-molecule risdiplam, which increases SMN protein levels similarly but also in peripheral organs, is tested in ongoing phase 2 and 3 trials. After positive results with phase 1 treatment with AAV9-SMN, the first gene therapy for SMA, a phase 3 clinical trial is ongoing. Ataluren is the first approved drug for Duchenne muscular dystrophy (DMD) patients with premature stop codon mutations and its indication has been recently extended since the age of 2 years. Exon skipping technology was and is currently tested in many phase 3 trials, and eteplirsen received a conditional approval by FDA for patients amenable to exon 51 skipping, but not by EMA. Many other compounds with different mechanisms of action are now tested in DMD by phase 2 and 3 trials, including phase 1 gene therapy. Other innovative approaches are under investigation, i.e., gene therapy in X-linked myotubular myopathy and Pompe disease, and antisense oligonucleotides in myotonic dystrophy type 1. Positive evidences are discussed about lamotrigine and ranolazine in non-dystrophic myotonias, chaperons in Pompe disease, and nucleosides in mitochondrial DNA depletion induced by thymidine kinase 2 deficiency.
https://ift.tt/2ExPvQ9
Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction
Abstract
Background
The aim of this study was to explore the possible correlations of serum cystatin C level and cystatin C gene (CST3) polymorphism with vascular cognitive impairment in patients who had acute cerebral infarction.
Methods
A total of 152 patients with acute cerebral infarction were recruited in this case-control study. Patients were divided into vascular cognitive impairment (VCI) group (n = 71) and cognitive impairment no dementia (CIND) group (n = 81). The serum concentrations of cystatin C were measured with immunoturbidimetric assay while the gene polymorphisms of CST3 were determined by technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results
In the VCI group, serum cystatin C level was significantly higher than that in the control group. The frequency of the B allele was found to be higher in the VCI group as compared with that of the CIND group (18.5% vs 7.7%, p = 0.006). In logistic regression analysis, significant associations of VCI with high serum cystatin C level (OR 3.837 (1.176–12.520), p = 0.026) and CST3 B allele (OR 2.038 (1.048–3.963), p = 0.036) were also found.
Conclusions
A high cystatin C level and CST3 B allele confer risks for VCI after acute cerebral infarction. It is probable that measurement of the serum cystatin C level and detection of CST3 gene polymorphism would aid in the early diagnosis of VCI, but further studies are warranted.
https://ift.tt/2ExERJ1
The lncRNA UNC5B-AS1 promotes proliferation, migration, and invasion in papillary thyroid cancer cell lines
Abstract
The incidence of thyroid cancer detection is continually improving worldwide with the spread of diagnostic imaging and surveillance. Although we have made great progress, there are still unknown mechanisms of papillary thyroid cancer. We found that UNC5B-AS1 is a potential oncogene in thyroid cancer. Therefore, our study aimed to investigate the biological functions of the lncRNA UNC5B-AS1 in papillary thyroid cancer. As a result, RNA-seq data on primary papillary thyroid cancer (PTC) in the TCGA database were obtained. RT-qPCR was performed to evaluate the expression levels in thyroid tissue. We then analysed the expression level of UNC5B-AS1 and its association with clinicopathologic characteristics in the TCGA database. We downregulated UNC5B-AS1 using small interfering RNA and carried out assays of cell proliferation, colony formation, migration and invasion to explore the function of UNC5B-AS1 in PTC cell lines (TPC1 and BCPAP). These results suggested that the lncRNA UNC5B-AS1 was significantly upregulated in both the TCGA cohort and our tissue cohort. Upregulated UNC5B-AS1 correlated with lymph node metastasis (P < 0.001), tumor size (P = 0.002) and histological type (P = 0.013). We also achieved an area under the ROC curve (AUC) of 93.2% for our validated cohort, which was consistent with the AUC of 94.5% for the TCGA cohort, for differentiating between PTC tissues and normal tissues. Downregulating UNC5B-AS1 expression at the RNA level significantly inhibited cell proliferation, colony formation, migration, and invasion in PTC cell lines (TPC1 and BCPAP). This study demonstrated that the lncRNA UNC5B-AS1 plays an important role in tumourigenesis and metastasis of PTC and may be a potential therapeutic target for PTC.
https://ift.tt/2IxrNXZ
Generalist predator contributions to the control of Tetranychus urticae in strawberry crops documented by PCR-based gut content analysis
Abstract
The contribution of generalist insect predators to the control of the two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), an herbivorous pest of many crops, is poorly understood. One of the common insect predators in strawberries is the generalist predatory bug Anthocoris nemorum L. (Hemiptera: Anthocoridae), which has the potential to contribute to the control of pest populations. The feeding of adult A. nemorum on T. urticae was assessed by sampling individuals from an organic strawberry field in Denmark, and using PCR gut content analysis to detect remains of T. urticae within their gut. In the lab, we assessed that the DNA half-life detectability was 21.5 h. Significant numbers of field-collected A. nemorum tested positive for T. urticae prey DNA, with very high numbers in June (62.8%) and August (38.8%). This study presents conclusive evidence that the generalist predator A. nemorum can contribute to the decrease of T. urticae densities in strawberry fields, although the actual contribution in the present study is probably limited because predator populations were relatively low compared to T. urticae. The abundance of T. urticae did not increase significantly during the period of sampling, suggesting that a complex of natural enemies can achieve biological control of T. urticae in protected strawberries.
https://ift.tt/2H1uVcr
High risk of obstructive sleep apnea, insomnia, and daytime sleepiness among commercial motor vehicle drivers
Abstract
Purpose
We investigated the prevalence of sleep problems, such as obstructive sleep apnea (OSA), insomnia, and daytime sleepiness in commercial motor vehicle (CMV) drivers compared with that in the general population.
Methods
This is a cross-sectional study comparing sleep habits and sleep problems in 110 truck drivers with 1001 matched controls from the general population. The assessment was based on self-administered questionnaires that included the Berlin questionnaire, the insomnia severity index, and the Epworth sleepiness scale (ESS). Multivariate regression analysis was performed to determine whether CMV drivers were independently associated with these sleep problems compared with controls.
Results
The prevalence of a high risk of OSA and insomnia was 35.5% and 15.2%, respectively, in CMV drivers, which was significantly higher than in controls with a prevalence of 12.2% and 4.1%, respectively (P < 0.001 for both). Although CMV drivers showed higher ESS scores than controls, the prevalence of daytime sleepiness did not differ between the two groups (19.1% vs. 16.8%, P = 0.54). After adjusting for covariates, CMV drivers had 3.68 times higher odds (95% CI 2.29–5.84) of OSA and 2.97 times higher odds (95% CI, 1.46–6.06) of insomnia compared with controls. However, the degree of daytime sleepiness was not independently associated with CMV drivers.
Conclusions
The prevalence of OSA and insomnia in CMV drivers was higher than that in the general population. Daytime sleepiness was associated with increased BMI, depression, OSA, and short sleep duration, regardless of CMV driving as an occupational factor.
https://ift.tt/2VhZA9l
Pre-diagnostic 25-hydroxyvitamin D levels and survival in cancer patients
Abstract
Purpose
Our main aim was to explore whether pre-diagnostic circulating levels of 25-hydroxyvitamin D (25(OH)D) among older individuals with cancer were associated with overall and cancer-specific survival after diagnosis.
Design
We used data from the Reykjavik-AGES Study on participants (n = 4,619) without cancer at entry, when blood samples were taken for 25(OH)D standardized measurements. The association with cancer risk, all-cause- and cancer-specific mortality was assessed among those later diagnosed with cancer, comparing four 25(OH)D categories, using 50–69.9 nmol/L as the reference category.
Results
Cancer was diagnosed in 919 participants on average 8.3 years after blood draw. No association was observed between the reference group and other 25(OH)D groups and total cancer incidence. Mean age at diagnosis was 80.9 (± 5.7) years. Of those diagnosed, 552 died during follow-up, 67% from cancer. Low pre-diagnostic levels of 25(OH)D < 30 nmol/L were significantly associated with increased total mortality (HR: 1.39, 95% CI 1.03, 1.88) and non-significantly with cancer-specific mortality (HR: 1.33, 95% CI 0.93, 1.90). Among patients surviving more than 2 years after diagnosis, higher pre-diagnostic 25(OH)D levels (≥ 70 nmol/L) were associated with lower risk of overall (HR: 0.68, 95% CI 0.46, 0.99) and cancer-specific mortality (HR: 0.47, 95% CI 0.26, 0.99).
Conclusions
Among elderly cancer patients, low pre-diagnostic serum 25(OH)D levels (< 30 nmol/L) were associated with increased overall mortality.
https://ift.tt/2U6bsLf
A high gene flow in populations of Amblyomma ovale ticks found in distinct fragments of Brazilian Atlantic rainforest
Abstract
The genetic structure of populations of the tick Amblyomma ovale from five distinct areas of the Brazilian Atlantic rainforest was evaluated via DNA sequencing and associated with the presence of domestic dogs acting as hosts at the edge of forest fragments. Ticks were collected from domestic dogs and from the environment between 2015 and 2017. Four collection areas were located in the surroundings and within the Serra do Mar State Park, São Paulo State (23°37′21"S, 45°24′43"W), where dogs were bimonthly monitored along 2 years using camera traps and GSM trackers. To determine the spatial limits of genetic structure, ticks collected upon dogs living near the Serra do Baturié, Ceará State (4°15′40"S, 38°55′54"W) were included as well. A total of 39 haplotypes of 16S rRNA and Cox 1 mitochondrial genes sequences were observed, with 27 of them coming from areas within the Serra do Mar State Park. No haplotype was shared between the Serra do Mar and the Serra do Baturié indicating isolation of tick populations at the scale of 2000 km. Although three different haplotype lineages of A. ovale occurred within the Serra do Mar State Park, no genetic structure was found across the study sites within this park, suggesting high tick gene flow across a range of 45 km. Monitoring data from domestic dogs and wild carnivores showed that these species share the same habitats at the forest edge, with dogs playing a likely limited role in tick dispersal. Our findings have important implications for understanding the genetic structure of wide spread A. ovale along Brazilian rainforest remnants, which can further be associated to tick-borne infectious agents, such as Rickettsia parkeri, and used for predicting future patterns of tick diversity in the Brazilian Atlantic rainforest.
https://ift.tt/2U7kd81
Rickettsia raoultii and Rickettsia sibirica in ticks from the long-tailed ground squirrel near the China–Kazakhstan border
Abstract
Spotted fever group (SFG) rickettsiae cause infection in humans, domestic animals and wildlife. To date, no rickettsial agents have been reported in hard ticks from the long-tailed ground squirrel (Spermophilus undulatus). A total of 50 adult ticks and 48 nymphs were collected from S. undulatus in the border region of northwestern China. Tick species (identified according to morphological and molecular characteristics) included Dermacentor nuttalli, Dermacentor silvarum and Ixodes kaiseri. Based on the cytochrome c oxidase subunit I (COI) haplotype analysis, I. kaiseri from S. undulatus belongs to an ancestral. In addition, all tick samples were analyzed for the presence of rickettsiae by PCR amplification and sequencing of six genetic markers. Rickettsia raoultii and Rickettsia sibirica subsp. sibirica were shown to occur in adults and nymphs of D. nuttalli and D. silvarum. Rickettsia sibirica subsp. sibirica was also detected in an I. kaiseri adult. Dermacentor silvarum and I. kaiseri were found for the first time on S. undulatus. Rickettsia raoultii and R. sibirica subsp. sibirica were detected in two Dermacentor and one Ixodes species, respectively, suggesting that these rickettsiae circulate in the region of the China-Kazakhstan border by hard ticks infesting S. undulatus.
https://ift.tt/2BOl9qE
Relevance of Erk1/2-PI3K/Akt signaling pathway in CEES-induced oxidative stress regulates inflammation and apoptosis in keratinocytes
Abstract
2-Chloroethyl ethyl sulfide (CEES) is a well-known chemical warfare agent that induces cellular stress in exposed individuals. However, molecular mechanisms of CEES-induced oxidative stress–mediated metabolic deregulation are not clearly elucidated. Here we investigated CEES-induced free radical production act as key functional mediators of metabolic stress via Erk1/2 mitogen–activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K/Akt) signaling cascades in keratinocytes. We observed that CEES exposure disrupts the cellular antioxidant defense capacities leading to increase in free oxygen and nitrogen radical accumulation in keratinocytes. These unusual cellular abnormalities initiate cellular stress via Erk1/2-PI3K/Akt signaling pathways. Biochemical tools were used to analyze the changes in metabolites including sulfur amino acids (SAAs), namely, l-glutathione (GSH) and l-cysteine (Cys), in the presence of selective inhibitors of reactive oxygen/nitrogen species (ROS/RNS), Erk1/2, or PI3K/Akt after CEES exposure. Importantly, these metabolite changes were accompanied by a decrease in the glycolytic flux, consistent with the observed decrease in 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) concentration and these CEES-induced phenomena were attenuated by pretreatment of Erk1/2 or PI3-K/Akt inhibitors. On the other hand, CEES exposure disrupts the protein carbonylation (PC) and lipid peroxidation (LPO) in keratinocytes leading to inflammation, crash of the cell–cell communication, cell cycle deregulation, and apoptosis via Erk1/2-PI3K/Akt pathways. However, pretreatment of Erk1/2 or PI3K/Akt inhibitors attenuated the CEES action. Collectively, these results illustrated that accumulated free radicals act as key functional mediators for inflammation, and apoptosis via Erk1/2-PI3K/Akt regulatory signaling cascades induced by CEES exposure. Treatment of pharmacological Erk1/2-PI3K/Akt inhibitors attenuated the CEES-induced keratinocyte injury that may provide the basis for the development of therapeutic strategy to work against CEES exposure.
https://ift.tt/2U8LE1k
Mapping the Young’s Modulus Distribution of the Human Tympanic Membrane by Microindentation
Publication date: Available online 23 February 2019
Source: Hearing Research
Author(s): Huiyang Luo, Fang Wang, Chen Cheng, Don U. Nakmali, Rong Z. Gan, Hongbing Lu
Abstract
The human tympanic membrane (TM, or eardrum) is composed primarily of layers of collagen fibers oriented in the radial and circumferential directions, as well as epidermal and mucosal layers at the lateral and medial surfaces. The mechanical properties of the TM depend on the microstructures of the collagen fibers, which vary with location, resulting in a spatial variation of Young’s modulus. In this study, the Young’s modulus of the human TM is measured using microindentation. A 10 micron diameter spherical nanoindenter tip is used to indent the TM at different locations in the lateral and medial surfaces. Through a viscoelastic contact analysis, the steady state out-of-plane (through thickness) Young’s modulus at a constant strain rate for the TM is determined from the uniaxial relaxation modulus. The measured spatial distribution of Young’s modulus is reported for the entire TM pars tensa on both lateral and medial surfaces. The Young’s modulus, for the four TM quadrants, is analyzed statistically using a normal quantile-quantile (Q-Q) plot. The obtained S-shaped curve indicates a bi-modal Gaussian distribution in the Q-Q plot. The spatial distribution of the Young’s modulus is modeled by a bivariate Gaussian function in the polar coordinates over the entire TM on both the lateral and medial surfaces. It is shown that the anterior-superior quadrant has the smallest value of Young’s modulus. Differences are observed in the spatial distribution of the Young’s modulus for both the lateral and medial surfaces. For the medial surface, Young’s modulus varies mainly along the radial direction following a small-large-small trend, emanating from the umbo. For the lateral surface, the modulus at the anterior-superior quadrant shows the smallest modulus; the modulus decreases gradually along the radial directions. The quantitative results presented in this paper will help improve future simulation models of the middle ear by using spatial dependence of Young’s modulus over the entire TM.
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Mapping the Young’s Modulus Distribution of the Human Tympanic Membrane by Microindentation
Publication date: Available online 23 February 2019
Source: Hearing Research
Author(s): Huiyang Luo, Fang Wang, Chen Cheng, Don U. Nakmali, Rong Z. Gan, Hongbing Lu
Abstract
The human tympanic membrane (TM, or eardrum) is composed primarily of layers of collagen fibers oriented in the radial and circumferential directions, as well as epidermal and mucosal layers at the lateral and medial surfaces. The mechanical properties of the TM depend on the microstructures of the collagen fibers, which vary with location, resulting in a spatial variation of Young's modulus. In this study, the Young's modulus of the human TM is measured using microindentation. A 10 micron diameter spherical nanoindenter tip is used to indent the TM at different locations in the lateral and medial surfaces. Through a viscoelastic contact analysis, the steady state out-of-plane (through thickness) Young's modulus at a constant strain rate for the TM is determined from the uniaxial relaxation modulus. The measured spatial distribution of Young's modulus is reported for the entire TM pars tensa on both lateral and medial surfaces. The Young's modulus, for the four TM quadrants, is analyzed statistically using a normal quantile-quantile (Q-Q) plot. The obtained S-shaped curve indicates a bi-modal Gaussian distribution in the Q-Q plot. The spatial distribution of the Young's modulus is modeled by a bivariate Gaussian function in the polar coordinates over the entire TM on both the lateral and medial surfaces. It is shown that the anterior-superior quadrant has the smallest value of Young's modulus. Differences are observed in the spatial distribution of the Young's modulus for both the lateral and medial surfaces. For the medial surface, Young's modulus varies mainly along the radial direction following a small-large-small trend, emanating from the umbo. For the lateral surface, the modulus at the anterior-superior quadrant shows the smallest modulus; the modulus decreases gradually along the radial directions. The quantitative results presented in this paper will help improve future simulation models of the middle ear by using spatial dependence of Young's modulus over the entire TM.
from #Audiology via ola Kala on Inoreader https://ift.tt/2XqsHZI
Mapping the Young’s Modulus Distribution of the Human Tympanic Membrane by Microindentation
Publication date: Available online 23 February 2019
Source: Hearing Research
Author(s): Huiyang Luo, Fang Wang, Chen Cheng, Don U. Nakmali, Rong Z. Gan, Hongbing Lu
Abstract
The human tympanic membrane (TM, or eardrum) is composed primarily of layers of collagen fibers oriented in the radial and circumferential directions, as well as epidermal and mucosal layers at the lateral and medial surfaces. The mechanical properties of the TM depend on the microstructures of the collagen fibers, which vary with location, resulting in a spatial variation of Young’s modulus. In this study, the Young’s modulus of the human TM is measured using microindentation. A 10 micron diameter spherical nanoindenter tip is used to indent the TM at different locations in the lateral and medial surfaces. Through a viscoelastic contact analysis, the steady state out-of-plane (through thickness) Young’s modulus at a constant strain rate for the TM is determined from the uniaxial relaxation modulus. The measured spatial distribution of Young’s modulus is reported for the entire TM pars tensa on both lateral and medial surfaces. The Young’s modulus, for the four TM quadrants, is analyzed statistically using a normal quantile-quantile (Q-Q) plot. The obtained S-shaped curve indicates a bi-modal Gaussian distribution in the Q-Q plot. The spatial distribution of the Young’s modulus is modeled by a bivariate Gaussian function in the polar coordinates over the entire TM on both the lateral and medial surfaces. It is shown that the anterior-superior quadrant has the smallest value of Young’s modulus. Differences are observed in the spatial distribution of the Young’s modulus for both the lateral and medial surfaces. For the medial surface, Young’s modulus varies mainly along the radial direction following a small-large-small trend, emanating from the umbo. For the lateral surface, the modulus at the anterior-superior quadrant shows the smallest modulus; the modulus decreases gradually along the radial directions. The quantitative results presented in this paper will help improve future simulation models of the middle ear by using spatial dependence of Young’s modulus over the entire TM.
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Learning and Interlimb Transfer of New Gait Patterns Are Facilitated by Distributed Practice across Days
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Chandramouli Krishnan
Abstract
Background
Previous studies have shown that the extent to which learning with one limb transfers to the opposite, untrained limb (i.e., interlimb transfer) is proportional to the amount of prior learning (or skill acquisition) that has occurred in the training limb. Thus, it is likely that distributed practice—a training strategy that is known to facilitate learning—will result in greater interlimb transfer than massed practice.
Research Question
To evaluate the effects of massed and distributed practice on acquisition and interlimb transfer of leg motor skills during walking.
Methods
Forty-five subjects learned a new gait pattern that required greater hip and knee flexion during the swing phase of gait. The new gait pattern was displayed as a foot trajectory in the sagittal plane and participants attempted to match their foot trajectory to this template. Subjects in the massed practice group (n = 20) learned the task on a single day, whereas subjects in the distributed practice group (n = 25) learned the task that was spaced over two consecutive days (training phase). Following completion of training, subjects in both groups practiced the task with their untrained, opposite leg to evaluate interlimb transfer (transfer phase).
Results
Results indicated that the amount of skill acquisition (i.e., reductions in tracking error) on the training leg was significantly higher (P < 0.05) in the distributed practice group when compared with the massed practice group. Similarly, the amount of interlimb transfer was also significantly higher (P < 0.05) in the distributed practice group both at the beginning and end of the transfer phase.
Significance
The findings indicate that acquisition and interlimb transfer of leg motor skills are significantly greater when the task was learned using distributed practice, which may have implications for gait rehabilitation in individuals with unilateral deficits, such as stroke.
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EEG time-frequency analysis provides arguments for arm swing support in human gait control
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Joyce B. Weersink, Natasha M. Maurits, Bauke M. de Jong
Abstract
Background
Human gait benefits from arm swing, which requires four-limb co-ordination. The Supplementary Motor Area (SMA) is involved in multi-limb coordination. With its location anterior to the leg motor cortex and the pattern of its connections, this suggests a distinct role in gait control.
Research question
Is the SMA functionally implicated in gait-related arm swing?
Methods
Ambulant electroencephalography (EEG) was employed during walking with and without arm swing in twenty healthy subjects (mean age: 64.9yrs, SD 7.2). Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation (ERSP) analysis over both the putative SMA at electrode position Fz and additional sensorimotor regions.
Results
During walking with arm swing, midline electrodes Fz and Cz showed a step-related pattern of Event Related Desynchronization (ERD) followed by Event Related Synchronization (ERS). Walking without arm swing was associated with significant ERD-ERS power reduction in the high-beta/low-gamma band over Fz and a power increase over Cz. Electrodes C3 and C4 revealed a pattern of ERD during contralateral- and ERS during ipsilateral leg swing. This ERD power decreased in gait without arm swing (low-frequency band). The ERSP pattern during walking with arm swing was similar at CP1 and CP2: ERD was seen during double support and the initial swing phase of the right leg, while a strong ERS emerged during the second half of the left leg's swing. Walking without arm swing showed a significant power reduction of this ERD-ERS pattern over CP2, while over CP1, ERS during left leg's swing turned into ERD.
Conclusion
The relation between arm swing in walking and a step-related ERD-ERS pattern in the high-beta/low-gamma band over the putative SMA, points at an SMA contribution to integrated cyclic anti-phase movements of upper- and lower limbs. This supports a cortical underpinning of arm swing support in gait control.
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The relationship between hallux grip force and balance in people with diabetes
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Panagiotis E. Chatzistergos, Aoife Healy, Roozbeh Naemi, Lakshmi Sundar, Ambady Ramachandran, Nachiappan Chockalingam
Abstract
Background
Diabetes accelerates the decline in muscle strength in older people and substantially increases the risk for fall and injury. Weakening of lower extremity muscles, in particular, is a strong predictor for falls, but currently there is no established method for its assessment in clinics. The paper grip test (PGT) offers a qualitative assessment of hallux plantar flexor strength and its usefulness for predicting falls has been demonstrated in non-diabetic populations.
Research question
The aim of this study is to test whether the PGT can be used for a quantitative assessment of lower-extremity strength and to investigate its relationship with isometric muscle strength and balance in people with diabetes and peripheral neuropathy.
Methods
Isometric muscle strength of all muscle groups of the foot-ankle was assessed using a dynamometer in sixty-nine people with diabetes and neuropathy. Postural sway and the gripping force exerted by the participants during the PGT was measured for the same participants using a plantar pressure assessment system. These measurements were repeated in regular intervals for 18 months in a longitudinal observational cohort study.
Results
Cross-sectional analysis of baseline data showed that people who failed the PGT swayed more. Analysis of longitudinal data showed that increasing hallux grip force is significantly associated with reduced postural sway. No significant association was found between dynamometry-based measurements of strength and postural sway. Hallux grip force was significantly correlated to the strength of all muscle groups of the foot-ankle complex.
Significance
These results indicate that hallux grip force can assess the strength of the foot-ankle muscles and could potentially be used to identify people at risk of falling. This sets the basis for the development of new screening protocols to assess weakening of the muscles of the foot-ankle and to enhance risk assessment for falls in people with diabetes and peripheral neuropathy.
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Cancer incidence in the Agricultural Health Study after 20 years of follow-up
Abstract
Purpose
To evaluate cancer incidence in the Agricultural Health Study (AHS), a cohort of private pesticide applicators, their spouses, and commercial applicators, based on 12,420 cancers, adding 5,989 cancers, and 9 years of follow-up since last evaluation.
Methods
We calculated age, year, sex, and race-adjusted standardized incidence ratios (SIR) and 95% confidence intervals (CI) for cancer sites in the AHS relative to the general population.
Results
Overall AHS cancer incidence was lower than the general population (SIRprivate = 0.91, CI 0.89–0.93; SIRspouse = 0.89, CI 0.86–0.92; SIRcommercial = 0.83, CI 0.76–0.92), with notable deficits across applicators and spouses for oral cavity, pancreas, and lung cancers. Cancer excesses included prostate cancer, lip cancer, certain B-cell lymphomas (e.g., multiple myeloma), acute myeloid leukemia (AML), thyroid cancer, testicular cancer, and peritoneal cancer. The lung cancer deficit was strongest among applicators reporting potential exposure to endotoxin at study enrollment (tasks such as raising animals and handling stored grain).
Conclusions
Although an overall deficit in cancer was observed, there were notable exceptions, including newly observed excesses for AML, thyroid, testicular, and peritoneal cancers. Furthermore, endotoxin exposure may, in part, account for observed lung cancer incidence deficits. Cancer incidence patterns in the AHS suggest farm exposures' relevance to cancer etiology.
https://ift.tt/2SpWSwv
Learning and Interlimb Transfer of New Gait Patterns Are Facilitated by Distributed Practice across Days
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Chandramouli Krishnan
Abstract
Background
Previous studies have shown that the extent to which learning with one limb transfers to the opposite, untrained limb (i.e., interlimb transfer) is proportional to the amount of prior learning (or skill acquisition) that has occurred in the training limb. Thus, it is likely that distributed practice—a training strategy that is known to facilitate learning—will result in greater interlimb transfer than massed practice.
Research Question
To evaluate the effects of massed and distributed practice on acquisition and interlimb transfer of leg motor skills during walking.
Methods
Forty-five subjects learned a new gait pattern that required greater hip and knee flexion during the swing phase of gait. The new gait pattern was displayed as a foot trajectory in the sagittal plane and participants attempted to match their foot trajectory to this template. Subjects in the massed practice group (n = 20) learned the task on a single day, whereas subjects in the distributed practice group (n = 25) learned the task that was spaced over two consecutive days (training phase). Following completion of training, subjects in both groups practiced the task with their untrained, opposite leg to evaluate interlimb transfer (transfer phase).
Results
Results indicated that the amount of skill acquisition (i.e., reductions in tracking error) on the training leg was significantly higher (P < 0.05) in the distributed practice group when compared with the massed practice group. Similarly, the amount of interlimb transfer was also significantly higher (P < 0.05) in the distributed practice group both at the beginning and end of the transfer phase.
Significance
The findings indicate that acquisition and interlimb transfer of leg motor skills are significantly greater when the task was learned using distributed practice, which may have implications for gait rehabilitation in individuals with unilateral deficits, such as stroke.
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EEG time-frequency analysis provides arguments for arm swing support in human gait control
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Joyce B. Weersink, Natasha M. Maurits, Bauke M. de Jong
Abstract
Background
Human gait benefits from arm swing, which requires four-limb co-ordination. The Supplementary Motor Area (SMA) is involved in multi-limb coordination. With its location anterior to the leg motor cortex and the pattern of its connections, this suggests a distinct role in gait control.
Research question
Is the SMA functionally implicated in gait-related arm swing?
Methods
Ambulant electroencephalography (EEG) was employed during walking with and without arm swing in twenty healthy subjects (mean age: 64.9yrs, SD 7.2). Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation (ERSP) analysis over both the putative SMA at electrode position Fz and additional sensorimotor regions.
Results
During walking with arm swing, midline electrodes Fz and Cz showed a step-related pattern of Event Related Desynchronization (ERD) followed by Event Related Synchronization (ERS). Walking without arm swing was associated with significant ERD-ERS power reduction in the high-beta/low-gamma band over Fz and a power increase over Cz. Electrodes C3 and C4 revealed a pattern of ERD during contralateral- and ERS during ipsilateral leg swing. This ERD power decreased in gait without arm swing (low-frequency band). The ERSP pattern during walking with arm swing was similar at CP1 and CP2: ERD was seen during double support and the initial swing phase of the right leg, while a strong ERS emerged during the second half of the left leg’s swing. Walking without arm swing showed a significant power reduction of this ERD-ERS pattern over CP2, while over CP1, ERS during left leg’s swing turned into ERD.
Conclusion
The relation between arm swing in walking and a step-related ERD-ERS pattern in the high-beta/low-gamma band over the putative SMA, points at an SMA contribution to integrated cyclic anti-phase movements of upper- and lower limbs. This supports a cortical underpinning of arm swing support in gait control.
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The relationship between hallux grip force and balance in people with diabetes
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Panagiotis E. Chatzistergos, Aoife Healy, Roozbeh Naemi, Lakshmi Sundar, Ambady Ramachandran, Nachiappan Chockalingam
Abstract
Background
Diabetes accelerates the decline in muscle strength in older people and substantially increases the risk for fall and injury. Weakening of lower extremity muscles, in particular, is a strong predictor for falls, but currently there is no established method for its assessment in clinics. The paper grip test (PGT) offers a qualitative assessment of hallux plantar flexor strength and its usefulness for predicting falls has been demonstrated in non-diabetic populations.
Research question
The aim of this study is to test whether the PGT can be used for a quantitative assessment of lower-extremity strength and to investigate its relationship with isometric muscle strength and balance in people with diabetes and peripheral neuropathy.
Methods
Isometric muscle strength of all muscle groups of the foot-ankle was assessed using a dynamometer in sixty-nine people with diabetes and neuropathy. Postural sway and the gripping force exerted by the participants during the PGT was measured for the same participants using a plantar pressure assessment system. These measurements were repeated in regular intervals for 18 months in a longitudinal observational cohort study.
Results
Cross-sectional analysis of baseline data showed that people who failed the PGT swayed more. Analysis of longitudinal data showed that increasing hallux grip force is significantly associated with reduced postural sway. No significant association was found between dynamometry-based measurements of strength and postural sway. Hallux grip force was significantly correlated to the strength of all muscle groups of the foot-ankle complex.
Significance
These results indicate that hallux grip force can assess the strength of the foot-ankle muscles and could potentially be used to identify people at risk of falling. This sets the basis for the development of new screening protocols to assess weakening of the muscles of the foot-ankle and to enhance risk assessment for falls in people with diabetes and peripheral neuropathy.
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Learning and Interlimb Transfer of New Gait Patterns Are Facilitated by Distributed Practice across Days
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Chandramouli Krishnan
Abstract
Background
Previous studies have shown that the extent to which learning with one limb transfers to the opposite, untrained limb (i.e., interlimb transfer) is proportional to the amount of prior learning (or skill acquisition) that has occurred in the training limb. Thus, it is likely that distributed practice—a training strategy that is known to facilitate learning—will result in greater interlimb transfer than massed practice.
Research Question
To evaluate the effects of massed and distributed practice on acquisition and interlimb transfer of leg motor skills during walking.
Methods
Forty-five subjects learned a new gait pattern that required greater hip and knee flexion during the swing phase of gait. The new gait pattern was displayed as a foot trajectory in the sagittal plane and participants attempted to match their foot trajectory to this template. Subjects in the massed practice group (n = 20) learned the task on a single day, whereas subjects in the distributed practice group (n = 25) learned the task that was spaced over two consecutive days (training phase). Following completion of training, subjects in both groups practiced the task with their untrained, opposite leg to evaluate interlimb transfer (transfer phase).
Results
Results indicated that the amount of skill acquisition (i.e., reductions in tracking error) on the training leg was significantly higher (P < 0.05) in the distributed practice group when compared with the massed practice group. Similarly, the amount of interlimb transfer was also significantly higher (P < 0.05) in the distributed practice group both at the beginning and end of the transfer phase.
Significance
The findings indicate that acquisition and interlimb transfer of leg motor skills are significantly greater when the task was learned using distributed practice, which may have implications for gait rehabilitation in individuals with unilateral deficits, such as stroke.
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EEG time-frequency analysis provides arguments for arm swing support in human gait control
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Joyce B. Weersink, Natasha M. Maurits, Bauke M. de Jong
Abstract
Background
Human gait benefits from arm swing, which requires four-limb co-ordination. The Supplementary Motor Area (SMA) is involved in multi-limb coordination. With its location anterior to the leg motor cortex and the pattern of its connections, this suggests a distinct role in gait control.
Research question
Is the SMA functionally implicated in gait-related arm swing?
Methods
Ambulant electroencephalography (EEG) was employed during walking with and without arm swing in twenty healthy subjects (mean age: 64.9yrs, SD 7.2). Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation (ERSP) analysis over both the putative SMA at electrode position Fz and additional sensorimotor regions.
Results
During walking with arm swing, midline electrodes Fz and Cz showed a step-related pattern of Event Related Desynchronization (ERD) followed by Event Related Synchronization (ERS). Walking without arm swing was associated with significant ERD-ERS power reduction in the high-beta/low-gamma band over Fz and a power increase over Cz. Electrodes C3 and C4 revealed a pattern of ERD during contralateral- and ERS during ipsilateral leg swing. This ERD power decreased in gait without arm swing (low-frequency band). The ERSP pattern during walking with arm swing was similar at CP1 and CP2: ERD was seen during double support and the initial swing phase of the right leg, while a strong ERS emerged during the second half of the left leg’s swing. Walking without arm swing showed a significant power reduction of this ERD-ERS pattern over CP2, while over CP1, ERS during left leg’s swing turned into ERD.
Conclusion
The relation between arm swing in walking and a step-related ERD-ERS pattern in the high-beta/low-gamma band over the putative SMA, points at an SMA contribution to integrated cyclic anti-phase movements of upper- and lower limbs. This supports a cortical underpinning of arm swing support in gait control.
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The relationship between hallux grip force and balance in people with diabetes
Publication date: Available online 23 February 2019
Source: Gait & Posture
Author(s): Panagiotis E. Chatzistergos, Aoife Healy, Roozbeh Naemi, Lakshmi Sundar, Ambady Ramachandran, Nachiappan Chockalingam
Abstract
Background
Diabetes accelerates the decline in muscle strength in older people and substantially increases the risk for fall and injury. Weakening of lower extremity muscles, in particular, is a strong predictor for falls, but currently there is no established method for its assessment in clinics. The paper grip test (PGT) offers a qualitative assessment of hallux plantar flexor strength and its usefulness for predicting falls has been demonstrated in non-diabetic populations.
Research question
The aim of this study is to test whether the PGT can be used for a quantitative assessment of lower-extremity strength and to investigate its relationship with isometric muscle strength and balance in people with diabetes and peripheral neuropathy.
Methods
Isometric muscle strength of all muscle groups of the foot-ankle was assessed using a dynamometer in sixty-nine people with diabetes and neuropathy. Postural sway and the gripping force exerted by the participants during the PGT was measured for the same participants using a plantar pressure assessment system. These measurements were repeated in regular intervals for 18 months in a longitudinal observational cohort study.
Results
Cross-sectional analysis of baseline data showed that people who failed the PGT swayed more. Analysis of longitudinal data showed that increasing hallux grip force is significantly associated with reduced postural sway. No significant association was found between dynamometry-based measurements of strength and postural sway. Hallux grip force was significantly correlated to the strength of all muscle groups of the foot-ankle complex.
Significance
These results indicate that hallux grip force can assess the strength of the foot-ankle muscles and could potentially be used to identify people at risk of falling. This sets the basis for the development of new screening protocols to assess weakening of the muscles of the foot-ankle and to enhance risk assessment for falls in people with diabetes and peripheral neuropathy.
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Bioengineering of microbial transglutaminase for biomedical applications
Abstract
Microbial transglutaminase (mTGase) is commonly known in the food industry as meat glue due to its incredible ability to "glue" meat proteins together. Aside from being widely exploited in the meat processing industries, mTGase is also widely applied in other food and textile industries by catalysing the formation of isopeptide bonds between peptides or protein substrates. The advancement of technology has opened up new avenues for mTGase in the field of biomedical engineering. Efforts have been made to study the structural properties of mTGase in order to gain an in-depth understanding of the structure-function relationship. This review highlights the developments in mTGase engineering together with its role in biomedical applications including biomaterial fabrication for tissue engineering and biotherapeutics.
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Thiol-functionalized magnetic nanoparticles for static and dynamic removal of Pb(II) ions from waters
Abstract
The synthesis of magnetite (Fe3O4) nanoparticles (NPs) and the functionalization by means of a silane derivative (3-mercaptopropyl) trimethoxysilane (MPTMS) as a way for heavy metal capture, i.e., Pb2+ ions, has been investigated. A direct reaction between the active thiol organosilane molecule and the surface of the magnetite nanoparticle is described. The coated nanoparticles, presenting an average diameter of about 20 nm, have been extensively characterized from the morphological, chemical, and physical point of view. The capture of Pb2+ ions from aqueous solution has been performed both in static and dynamic mode, using in both cases a configuration of commercial NdFeB permanent magnets. The amount of heavy metal captured by the magnetic NPs as a function of time, as well as its fraction recovered by an EDTA solution, have been measured by inductively coupled plasma atomic emission spectrometry (ICP-AES). The Pb2+ capture from a spiked water solution (5 mg/L) is very fast, reaching 91% in static conditions after only 10 min. Furthermore, dynamic data also demonstrated the possibility to apply the toxic heavy metal capture method to large volumes.
Graphical abstract
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A retrospective study of the ideal operation time for preterm biliary atresia patients
Abstract
Objective
To study the ideal Kasai portoenterostomy (KPE) time for preterm infants with biliary atresia (BA) through evaluation of the postoperative effects.
Methods
Retrospectively, 34 preterm infants with BA from 2012 to 2016 were recruited in the present study. The following three groups were established according to their chronological and corrected age at the time of KPE operation: chronological age ≤ 90 days, chronological age > 90 days and corrected age ≤ 90 days, and corrected age > 90 days. For chronological age ≤ 90 days at operation, patients were further divided into another three groups: chronological age ≤ 60 days, chronological age > 60 days and corrected age ≤ 60 days, and corrected age > 60 days. Postoperative effects were then followed up and recorded.
Results
First, of those patients divided according to 90-day chronological and corrected age, postoperative total bilirubin levels (TBL), direct bilirubin levels (DBL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) of the group whose chronological age was ≤ 90 days were lower than the levels of the group whose chronological age was > 90 days and corrected age ≤ 90 days (P = 0.0472, P = 0.0358, P = 0.0083, and P = 0.0491), and the group whose corrected age was > 90 days (P = 0.0383, P = 0.0392, P = 0.0043, and P = 0.0107). Second, for those patients whose chronological age was ≤ 90 days, the group whose corrected age was > 60 days showed a higher ALT level than the other two groups with chronological age ≤ 60 days (P = 0.0472) and chronological age > 60 days and corrected age ≤ 60 days (P = 0.0258).
Conclusion
According to the present study, the ideal KPE time for preterm BA infants should meet two conditions: chronological age ≤ 90 days and corrected age ≤ 60 days. The groups with a chronological age ≤ 60 days, and chronological age > 60 days and corrected age ≤ 60 days show similar postoperative effects.
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When Jump Height is not a Good Indicator of Lower Limb Maximal Power Output: Theoretical Demonstration, Experimental Evidence and Practical Solutions
Abstract
Lower limb external maximal power output capacity is a key physical component of performance in many sports. During squat jump and countermovement jump tests, athletes produce high amounts of mechanical work over a short duration to displace their body mass (i.e. the dimension of mechanical power). Thus, jump height has been frequently used by the sports science and medicine communities as an indicator of the power output produced during the jump and by extension, of maximal power output capacity. However, in this article, we contend that squat jump and countermovement jump height are not systematically good indicators of power output produced during the jump and maximal power output capacity. To support our opinion, we first detail why, theoretically, jump height and maximal power output capacity are not fully related. Specifically, we demonstrate that individual body mass, push-off distance, optimal loading and the force-velocity profile confound the jump height–power relationship. We also discuss the relationship between squat jump or countermovement jump height and maximal power output capacity measured with a force plate based on data reported in the literature, which added to our own experimental evidence. Finally, we discuss the limitations of existing practical solutions (regression-based estimation equations and allometric scaling), and advocate using a valid, reliable and simple field-based procedure to compute individual power output produced during the jump and maximal power output capacity directly from jump height, body mass and push-off distance. The latter may allow researchers and practitioners to reduce bias in their assessment of lower limb mechanical power output by using jump height as an input with a simple yet accurate computation method, and not as the first/only variable of interest.
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Changes in Enterohepatic Circulation after Duodenal–Jejunal Bypass and Reabsorption of Bile Acids in the Bilio-Pancreatic Limb
Abstract
Background and Aims
Duodenal–jejunal bypass (DJB) shows great effects on weight loss and diabetes improvement. Previously, we reported that the bilio-pancreatic (BP) limb plays an important role in glycemic improvement and in serum bile acid (BA) level increase as reported by Miyachi et al. (Surgery 159(5):1360–71, 2016). This study aimed to investigate the mechanism of BA elevation after DJB and the relationship between these effects and BP-limb length.
Methods
Otsuka Long-Evans Tokushima Fatty rats with diabetes were randomly assigned into four groups: one sham group and three DJB groups. Three DJB groups were defined according to the BP-limb length: 0 cm, 15 cm, and 30 cm. The lengths of the alimentary limb and common channel were set equally in each DJB groups. Body weight, glucose tolerance, and BA levels in the liver, bile juice, portal vein, and intestinal contents were assessed postoperatively. Changes in enterohepatic circulation of BAs were assessed using labeled BA.
Results
BA elevation after DJB was higher with longer BP-limb. In the 30-cm group, the serum total BA level and BA levels in the portal vein, liver, and bile juice were greater than those in other groups. The enterohepatic circulation was shortened in the 15-cm and 30-cm groups.
Conclusions
Shortening of the "enterohepatic circulation" by early reabsorption of BAs in the BP-limb, not by the early influx of bile juice into the ileum, was the main cause of BA elevation after DJB. Thus, glycemic improvement and elevation of BA concentration after DJB depend on the BP-limb length.
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Romosozumab: First Global Approval
Abstract
Romosozumab (EVENITY™) is a humanised monoclonal antibody against sclerostin being developed by Amgen and UCB for the treatment of osteoporosis. On the basis of favourable results from several phase III trials in postmenopausal women with osteoporosis, and a single trial in men with osteoporosis, romosozumab is being considered for marketing approval in the US, EU and Canada, and was recently approved for marketing in Japan. This article summarizes the milestones in the development of romosozumab leading to this first approval for the treatment of osteoporosis in patients at high risk of fracture.
https://ift.tt/2Tcf15E
Toripalimab: First Global Approval
Abstract
Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. In December 2018, based on positive efficacy results of a phase 2 trial and safety data from several clinical studies, toripalimab received conditional approval in China for the treatment of unresectable or metastatic melanoma that has failed previous systemic therapy. This article summarizes the milestones in the development of toripalimab leading to this first global approval for the treatment of unresectable or metastatic melanoma.
https://ift.tt/2IzSOu3
Roxadustat: First Global Approval
Abstract
Roxadustat (Ai Rui Zhuo® in China) is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that is being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (CKD), non-dialysis-dependent CKD and in patients with myelodysplastic syndromes. The drug reversibly binds to and inhibits HIF-prolyl hydroxylase enzymes that are responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. Inhibition of these enzymes reduces HIF breakdown and promotes HIF activity, leading to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. It also reduces the expression of the peptide hormone hepcidin, improves iron availability and increases haemoglobin levels. HIF regulates the expression of genes in response to reduced oxygen levels, including genes required for erythropoiesis and iron metabolism. Roxadustat is approved in China and is under regulatory review in Japan for the treatment of anaemia in patients with dialysis-dependent CKD. Studies are underway to investigate long-term cardiovascular outcomes with roxadustat versus placebo (for non-dialysis-dependent CKD) or standard of care (for dialysis-dependent CKD). This article summarizes the milestones in the development of roxadustat leading to this first approval.
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