Αρχειοθήκη ιστολογίου

Σάββατο 12 Ιανουαρίου 2019

Episodic Migraine Comorbidities: Avoiding Pitfalls and Taking Therapeutic Opportunities

Abstract

Migraine is a common neurologic disorder. This article will discuss a few factors that influence migraine (mostly episodic) and its treatment, such as sleep, obstructive sleep apnea (OSA), obesity, and affective disorders, as well as autoimmune diseases. Practitioners must be aware of these coexisting conditions (comorbidities) as they affect treatment. It is noted in literature that both the quantity (too much or too few hours) and the quality (OSA related) of sleep may worsen migraine frequency. An associated risk factor for OSA, obesity also increases migraine frequency in episodic migraine cases. A bidirectional relationship with migraine along with depression and anxiety is debated in the literature. Retrospective cohort studies are undecided and lack statistical significance, but prospective studies do show promising results on treatment of anxiety and depression as a means of improving migraine control. Finally, we address the topic of autoimmune diseases and migraine. While few studies exist at this time, there are cohort study groups looking into the association between rheumatoid arthritis, hypothyroidism, and antiphospholipid antibody. There is also evidence for the link between migraine and vascular diseases, including coronary and cerebral diseases. We suggest that these comorbid conditions be taken into account and individualized for each patient along with their pharmaceutical regimen. Physicians should seek a multifactorial treatment plan including diet, exercise, and healthy living to reduce migraine frequency.



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Erratum to "Traumatic Brain Injury in Children under Age 24 Months : Analysis of Demographic Data, Risk Factors, and Outcomes of Post-traumatic Seizure" by Yoon SY, et al. (J Korean Neurosurg Soc 60 : 584-590, 2017).

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Erratum to "Traumatic Brain Injury in Children under Age 24 Months : Analysis of Demographic Data, Risk Factors, and Outcomes of Post-traumatic Seizure" by Yoon SY, et al. (J Korean Neurosurg Soc 60 : 584-590, 2017).

J Korean Neurosurg Soc. 2019 Jan;62(1):130

Authors:

PMID: 30630299 [PubMed - in process]



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Clinical Significance of Radical Surgery in the Treatment of Silent Corticotroph Adenoma.

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Clinical Significance of Radical Surgery in the Treatment of Silent Corticotroph Adenoma.

J Korean Neurosurg Soc. 2019 Jan;62(1):114-122

Authors: Kim J, Yoon SJ, Moon JH, Ku CR, Kim SH, Lee EJ, Kim SH, Kim EH

Abstract
OBJECTIVE: Silent corticotroph adenomas (SCA) are endocrine-inactive pituitary adenomas with positive immunohistochemistry staining for adrenocorticotropic hormone (ACTH). We investigated whether SCA-associated clinical profiles were more aggressive than hormonally negative adenomas (HNA).
METHODS: Among 627 patients with pathologically proven endocrine-inactive pituitary adenomas between 2004 and 2013, positive immunohistochemistry revealed 55 SCAs and 411 HNAs. Surgical outcomes and radiological and endocrinological characteristics were compared.
RESULTS: Strong female predominance was observed in the SCA group (p<0.001). Cavernous sinus invasion was identified in 22 (40%) SCA patients and 72 (17.6%) HNA patients (p<0.001). There were no differences in ACTH or cortisol levels between the two groups. The incidence of preoperative hypopituitarism and postoperative hormonal outcome did not differ between two groups. Total resection was achieved in 35 patients (63.7%) with SCA and 332 patients (80.8%) with HNA (p=0.007). When tumors were completely removed, recurrence rates were not statistically different between two groups (p=0.60). When complete resection was not achieved, tumors regrew from these remnants in seven patients (35.0%) with SCA and 12 patients (15.2%) with HNA (p=0.05).
CONCLUSION: Total surgical resection for SCA is often challenging as these tumors frequently invade a cavernous sinus. Early remnant tumor intervention is justified, because untreated residual pituitary tumors regrow when patients were followed up for a long time. Prophylactic radiotherapy is not warranted for completely resected SCAs as tumor recurrence is uncommon.

PMID: 30630298 [PubMed]



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Clinical Significance of Preoperative Embolization for Non-Hypervascular Metastatic Spine Tumors.

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Clinical Significance of Preoperative Embolization for Non-Hypervascular Metastatic Spine Tumors.

J Korean Neurosurg Soc. 2019 Jan;62(1):106-113

Authors: Yoo SL, Kim YH, Park HY, Kim SI, Ha KY, Min HK, Seo JY, Oh IS, Chang DG, Ahn JH, Kim YW

Abstract
OBJECTIVE: The efficacy of preoperative embolization for hypervascular metastatic spine disease (MSD) such as renal cell and thyroid cancers has been reported. However, the debate on the efficacy of preoperative embolization for non-hypervascular MSD still remains unsettled. The purpose of this study is to determine whether preoperative embolization for non-hypervascular MSD decreases perioperative blood loss.
METHODS: A total of 79 patients (36 cases of preoperative embolization and 43 cases of non-embolization) who underwent surgery for metastatic spine lesions were included. Representative hypervascular tumors such as renal cell and thyroid cancers were excluded. Intraoperative and perioperative estimated blood losses (EBL), total number of transfusion and calibrated EBL were recorded in the embolization and non-embolization groups. The differences in EBL were also compared along with the type of surgery. In addition, the incidence of Adamkiewicz artery and complications of embolization were assessed.
RESULTS: The average age of 50 males and 29 females was 57.6±13.5 years. Lung (30), hepatocellular (14), gastrointestinal (nine) and others (26) were the primary cancers. The demographic data was not significantly different between the embolization and the non-embolization groups. There were no significant differences in intraoperative EBL, perioperative EBL, total transfusion and calibrated EBL between two groups. However, intraoperative EBL and total transfusion in patients with preoperative embolization were significantly lower than in non-embolization in the corpectomy group (1645.5 vs. 892.6 mL, p=0.017 for intraoperative EBL and 6.1 vs. 3.9, p=0.018 for number of transfusion). In addition, the presence of Adamkiewicz artery at the index level was noted in two patients. Disruption of this major feeder artery resulted in significant changes in intraoperative neuromonitoring.
CONCLUSION: Preoperative embolization for non-hypervascular MSD did not reduce perioperative blood loss. However, the embolization significantly reduced intraoperative bleeding and total transfusion in corpectomy group. Moreover, the procedure provided insights into the anatomy of tumor and spinal cord vasculature.

PMID: 30630297 [PubMed]



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Anomalous Muscles of the Wrist Encountered During Endoscopic Carpal Tunnel Surgery.

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Anomalous Muscles of the Wrist Encountered During Endoscopic Carpal Tunnel Surgery.

J Korean Neurosurg Soc. 2019 Jan;62(1):90-95

Authors: Park SH

Abstract
OBJECTIVE: Anomalous muscles of the wrist are infrequently encountered during carpal tunnel surgery. Anatomic variants of the palmaris longus (PL), flexor digitorum superficialis, lumbricalis and abductor digiti minimi (ADM) have been reported but are usually clinically insignificant. Anomalies of the wrist muscles, encountered during endoscopic carpal tunnel surgery have rarely been described. I conducted this study to evaluate muscular anomalies of the volar aspect of the wrist, encountered during endoscopic carpal tunnel surgery.
METHODS: I studied a consecutive series of 1235 hands in 809 patients with carpal tunnel syndrome who underwent single-portal endoscopic carpal tunnel release (ECTR) from 2002 to 2014. Nine hundred seventy-three hands in 644 patients who had minimal 6-month postoperative follow-up were included in the study. The postoperative surgical outcome was assessed at least 6 months after surgery.
RESULTS: In eight patients, anomalous muscles were found under the antebrachial fascia at the proximal wrist crease and superficial to the ulnar bursa, passing superficial to the transverse carpal ligament . Those anomalous muscles were presumed to be variants of the PL or accessory ADM muscle, necessitating splitting and retraction to enter the carpal tunnel during the ECTR procedure. Other muscle anomalies were not seen within the carpal tunnel on the endoscopic view. The surgical outcome for all eight wrists was successful at the 6-month postoperative follow-up.
CONCLUSION: Carpal tunnel surgeons, especially those using an endoscope should be familiar with unusual findings of anomalous muscles of the wrist because early recognition of those muscles can contribute to avoiding unnecessary surgical exploration and unsuccessful surgical outcomes.

PMID: 30630296 [PubMed]



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Parkinson's Disease as Risk Factor in Osteoporosis and Osteoporotic Vertebral Fracture : Prevalence Study Using National Inpatient Sample Database in Korea.

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Parkinson's Disease as Risk Factor in Osteoporosis and Osteoporotic Vertebral Fracture : Prevalence Study Using National Inpatient Sample Database in Korea.

J Korean Neurosurg Soc. 2019 Jan;62(1):71-82

Authors: Lee JY, Lim NG, Chung CK, Lee JY, Kim HJ, Park SB

Abstract
OBJECTIVE: To determine the prevalence of osteoporosis (OP) and osteoporotic vertebral fracture (OVF) in people with Parkinson's disease (PD) in Korea and its association with socioeconomic status.
METHODS: Using Health Insurance Review and Assessment Service-National Inpatient Sample (HIRA-NIS) data from 2009 to 2013, we estimated the annual prevalence of PD, OP, and OVF and investigated its association with socioeconomic status using data from National Health Insurance (NHI) beneficiaries and Medical Aid (MA) recipients. This study was supported by research funding from Korean Society for Bone and Mineral Research 2015. There were no study-specific biases related to conflicts of interest.
RESULTS: The number of PD patients in the HIRA-NIS increased each year from 2009 to 2013. Among patients with PD, the standardized prevalence rates of OP and OVF increased from 2009 to 2013; from 23.2 to 27.8 and from 2.8 to 4.2, respectively. Among patients with PD with OP, the prevalence of OVF were 12.2% and 15.1% in 2009 and 2013, respectively. The standardized prevalence rates of PD with OP and PD with OVF were significantly higher in MA recipients than in NHI beneficiaries.
CONCLUSION: The prevalence of PD both with OP and with OVF increased and the prevalence was higher in MA recipients than in NHI beneficiaries. These findings may suggest that age over 65 years, female and low income may be a significant factor related to PD occurring with OP and OVF.

PMID: 30630295 [PubMed]



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Four-Year Experience Using an Advanced Interdisciplinary Hybrid Operating Room : Potentials in Treatment of Cerebrovascular Disease.

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Four-Year Experience Using an Advanced Interdisciplinary Hybrid Operating Room : Potentials in Treatment of Cerebrovascular Disease.

J Korean Neurosurg Soc. 2019 Jan;62(1):35-45

Authors: Jeon HJ, Lee JY, Cho BM, Yoon DY, Oh SM

Abstract
OBJECTIVE: To describe our experiences with a fully equipped high-end digital subtraction angiography (DSA) system within a hybrid operating room (OR).
METHODS: A single-plane DSA system with 3-dimensional rotational angiography, cone-beam computed tomography (CBCT), and real-time navigation software was used in our hybrid OR. Between April 2014 and January 2018, 191 sessions of cerebrovascular procedures were performed in our hybrid OR. After the retrospective review of all cases, the procedures were categorized into three subcategorical procedures : combined endovascular and surgical procedure, complementary rescue procedure during intervention and surgery, and frameless stereotaxic operation.
RESULTS: Forty-nine of 191 procedures were performed using hybrid techniques. Four cases of blood blister aneurysms and a ruptured posterior inferior cerebellar artery aneurysm were treated using bypass surgery and endovascular trapping. Eight cases of ruptured aneurysm with intracranial hemorrhage (ICH) were treated by partial embolization and surgical clipping. Six cases of ruptured arteriovenous malformation with ICH were treated by Onyx embolization of nidus and subsequent surgical removal of nidus and ICH. Two (5.4%) of the 37 cases of pre-mature rupture during clipping were secured by endovascular coil embolization. In one (0.8%) complicated case of 103 intra-arterial thrombectomy procedures, emergency surgical embolectomy with bypass surgery was performed. In 27 cases of ICH, frameless stereotaxic hematoma aspiration was performed using XperGuide® system (Philips Medical Systems, Best, the Netherlands). All procedures were performed in single sessions without any procedural complications.
CONCLUSION: Hybrid OR with a fully equipped DSA system could provide precise and safe treatment strategies for cerebrovascular diseases. Especially, we could suggest a strategy to cope flexibly in complex lesions or unexpected situations in hybrid OR. CBCT with real-time navigation software could augment the usefulness of hybrid OR.

PMID: 30630294 [PubMed]



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Selective Temporary Stent-Assisted Coil Embolization for Intracranial Wide-Necked Small Aneurysms Using Solitaire AB Retrievable Stent.

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Selective Temporary Stent-Assisted Coil Embolization for Intracranial Wide-Necked Small Aneurysms Using Solitaire AB Retrievable Stent.

J Korean Neurosurg Soc. 2019 Jan;62(1):27-34

Authors: Heo HY, Ahn JG, Ji C, Yoon WK

Abstract
OBJECTIVE: Stent-assisted coil embolization of intracranial wide-necked aneurysm requires long-term postoperative antiplatelet therapy to prevent in-stent thrombosis. This study aimed to demonstrate results of temporary stent placement for coiling wide necked small intracranial aneurysms, which eliminated need for antiplatelet agents, and to discuss its feasibility and safety.
METHODS: Data of 156 patients who underwent stent-assisted coil embolization between 2011 and 2014 were retrospectively analyzed. Thirteen cases of temporary stent-assisted coil embolization were included, and their clinical and radiological results were evaluated.
RESULTS: The aneurysms treated were all unruptured except one case. All of them had wide neck with mean dome-to-neck ratio of 0.96 and were small-sized aneurysms with mean maximal diameter of 4.2 mm. There was no technical failure in retrieval of stent after completion of embolization of the target aneurysm. Immediate angiography revealed 11 complete and two partial embolization (one residual neck and one residual aneurysm). Two cases encountered thrombosis complication, and they were managed without neurological sequelae. The mean follow-up period was 43 months, angiographic follow-up revealed two cases with minor recurrence, and clinical outcome was good with modified Rankin scale score of 0.
CONCLUSION: Temporary stent-assisted coil embolization of small wide-necked intracranial aneurysm using fully retrievable stent appears safe and effective. Further application and evaluation of this technique in more cases with larger size aneurysm is warranted.

PMID: 30630293 [PubMed]



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Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening.

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Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening.

J Korean Neurosurg Soc. 2019 Jan;62(1):10-26

Authors: Lee EJ, Fomenko A, Lozano AM

Abstract
Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer's disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

PMID: 30630292 [PubMed]



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Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure.

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Variability of Platelet Reactivity on Antiplatelet Therapy in Neurointervention Procedure.

J Korean Neurosurg Soc. 2019 Jan;62(1):3-9

Authors: Yi HJ, Hwang G, Lee BH

Abstract
As more intracranial aneurysms and other cerebrovascular pathologies are treated with neurointervention procedure, thromboembolic events that frequently lead to serious neurological deficit or fatal outcomes are increasing. In order to prevent the thromboembolic events, antiplatelet therapy is used in most procedures including coil embolization, stenting, and flow diversion. However, because of variable individual pharmacodynamics responses to antiplatelet drugs, especially clopidogrel, it is difficult for clinicians to select the adequate antiplatelet regimen and its optimal dose. This article reviews the neurointervention literature related to antiplatelet therapy and suggests a strategy for tailoring antiplatelet therapy in individual patients undergoing neurointervention based on the results of platelet function testing.

PMID: 30630291 [PubMed]



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Editorial Statistics and Best Reviewers Award 2018 for Journal of Korean Neurosurgical Society.

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Editorial Statistics and Best Reviewers Award 2018 for Journal of Korean Neurosurgical Society.

J Korean Neurosurg Soc. 2019 Jan;62(1):1-2

Authors: Chung M, Kim BT

Abstract

PMID: 30630290 [PubMed]



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The Diagnostic Performance of Ultrasonography and Computed Tomography in Differentiating Superficial from Deep Lobe Parotid Tumors

Abstract

Objectives

To validate and compare ultrasound (US) versus computed tomography (CT) criteria in the localization of superficial/deep lobe tumors of the parotid gland.

Design and Setting

This was a retrospective study of diagnostic tests performed from January 2008 to June 2017.

Participants

We included adult patients who were referred for a neck ultrasonography examination due to parotid tumors, and who subsequently underwent parotid surgery.

Main outcome measures

We assessed the location of parotid tumors, comparing the minimum fascia–tumor distance (MFTD) criterion on an US with eight CT criteria. We analyzed receiver operating characteristic (ROC) curves of the MFTD for malignant, benign, and all parotid tumors, and compared the accuracy, sensitivity, and specificity of the optimal MFTD with those of CT anatomical criteria.

Results

A total of 166 parotid tumors were included. The mean (SD) MFTD in superficial lobe tumors was significantly shorter than that of deep lobe tumors (1.2 [0.7] vs 2.8 [1.9] mm, effect size: 1.84; 95% CI, 1.27 to 2.41). The areas under the ROC curve were 0.63 for malignant tumors and 0.88 for benign tumors. The optimal MFTD cut point was 2.4 mm for the 154 benign parotid tumors and the accuracy, sensitivity, and specificity were 90%, 80% and 91%, respectively. For the 136 benign parotid tumors that underwent CT examination, three criteria had an accuracy of over 90% (FNline, tMasseter and Conn's arc), but the sensitivities were all below 50%.

Conclusions

MFTD is more feasible for benign tumors than for malignant tumors for the localization of parotid tumors. For benign parotid tumors, US is enough to guide operations.

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Computerised tomography in the investigation of otalgia of unknown origin; our experience in 100 patients

Abstract

Otalgia is a common presenting symptom in the specialty of ENT. In its primary form it is caused by conditions and diseases affecting the outer, middle or inner ear structures, thus giving rise to pain and discomfort around the ear itself. However, in its secondary form (referred), pain can be remote from the source and thus provide greater diagnostic challenge due to the possibility of occult disease that is not well visualised.

This article is protected by copyright. All rights reserved.



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Heterostructures Comprised of Co/β‐Mo2C‐Encapsulated N‐Doped Carbon Nanotubes as Bifunctional Electrodes for Water Splitting

Herein, we demonstrate heterostructures comprised of Co/β‐Mo2C@N‐CNTs hybrids for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline electrolyte. The Co can not only create well‐defined heterointerface with β‐Mo2C but also overcome the poor OER activity of β‐Mo2C, leading to enhanced electrocatalytic activity for HER and OER. DFT calculations further prove that by cooperating the N‐CNTs, Co, and β‐Mo2C results in lower the energy barriers of intermediates, thus greatly enhances the HER and OER performance. This work not only provides a simple strategy to construct heterostructures with nonprecious metals, but also presents an in‐depth insight into the HER and OER mechanism in alkaline solution.



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Mitochondria-driven elimination of cancer and senescent cells

Journal Name: Biological Chemistry
Issue: Ahead of print


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Applications of cellulose and chitin/chitosan derivatives and composites as antibacterial materials: current state and perspectives

Abstract

The bacterial infections have always a serious problem to public health. Scientists are developing new antibacterial materials to overcome this problem. Polysaccharides are promising biopolymers due to their diverse biological functions, low toxicity, and high biodegradability. Chitin and chitosan have antibacterial properties due to their cationic nature, while cellulose/bacterial cellulose does not possess any antibacterial activity. Moreover, the insolubility of chitin in common solvents, the poor solubility of chitosan in water, and the low mechanical properties of chitosan have restricted their biomedical applications. In order to solve these problems, chemical modifications such as quaternization, carboxymethylation, cationization, or surface modification of these polymers with different antimicrobial agents, including metal and metal oxide nanoparticles, are carried out to obtain new materials with improved physiochemical and biological properties. This mini review describes the recent progress in such derivatives and composites with potential antibacterial applications.



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Automated identification for autism severity level: EEG analysis using empirical mode decomposition and second order difference plot

Publication date: Available online 11 January 2019

Source: Behavioural Brain Research

Author(s): Hikmat Hadoush, Maha Alafeef, Enas Abdulhay

Abstract
Background

Previous automated EEG-based diagnosis of autism spectrum disorders (ASD) using various nonlinear EEG analysis methods were limited to distinguish only children with ASD from those normally developed without approaching their autistic features severity.

Objectives

Identifying potential differences between children with mild and sever ASD based on EEG analysis using empirical mode decomposition (EMD) and second-order difference plot (SODP) models, and determining the accuracy of such model outcome measures to distinguish ASD severity levels.

Methods

Resting-state EEG data recorded for 36 children, who divided equally into two matched groups of mild and sever ASD. EMD analysis was applied to their EEG data to identify intrinsic mode functions (IMFs) features, SODP patterns, elliptical area and central tendency measure (CTM) values. Artificial neural network then used to determine the accuracy of this models outcome measures in distinguishing between the two ASD groups.

Results

Children with sever ASD showed smaller, less twitches and oscillation of IMFs features, more stochastic SODP plotting, less CTM values, and higher ellipse area values compared to the children with mild ASD, which indicates their greater EEG variabilities and their greater inability to suppress their improper behavior. ANN ended with model sensitivity and specificity of 100% and 94.7%, respectively, and 97.2% overall accuracy of distinguishing between ASD groups.

Conclusion

Children with sever and mild ASD had different IMFs features, SODP plotting, elliptical area and CTM values. In addition, these EMD outcome measures could serve as a sensitive automated tool to distinguish different severity levels in children with ASD.



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Sleep restriction alters the temporal expression of major histocompatibility complex class II molecules in murine lymphoid tissues

Publication date: Available online 11 January 2019

Source: Behavioural Brain Research

Author(s): Esther Ghanem, Samar Al Bitar, Robert Dib, Colette S. Kabrita

Abstract

Inadequate sleep is a major health concern of modern societies in view of the increased morbidity and mortality rates from physiological disturbances, including compromised adaptive immune responses. Many studies investigated the effect sleep restriction (SR) on the normal immune response in terms of leukocyte number and circulating cytokine and T helper cell (Th) profiles, but none considered the major histocompatibility complex (MHC), namely class II molecules. As no information exists about the normal temporal expression of MHC class II, the present study aimed at understanding how SR affects the adaptive immune response via altering the 1) normal daily expression profile and 2) overall constitutive levels of murine MHC class II by leukocytes' isolates from spleen and axillary lymph nodes. Male C57BL/6 mice were acclimatized to 12:12 light/dark cycle (lights on at 0700, corresponding to Zeitgeber time (ZT) 0) for a week before splitting into 2 groups: control (C) and SR (exposed to a 12 and 18 hours of activity, respectively). SR was carried for one week before lymphoid tissues from both C and SR mice were sampled at the following time points: ZT0, ZT5, ZT10, ZT13, and ZT18. Spleen and lymph node cells were assessed for leukocyte number and MHC class II expression at the preselected time points using flow cytometry. SR resulted in a 21% decrease in granulocyte and 24% increase in agranulocyte numbers. MHC class II expression in both lymphoid tissues of C mice varied synchronously across the preselected times of day; they were relatively high just prior to activity onset and later in this period. Comparatively, the diurnal protein profile was altered in both lymphoid tissues of SR: 1) the rise of MHC class II expression during the rest period occurred 4-5 hours earlier and 2) the cyclical pattern during the activity period was blunted and protein expression was maintained at relatively high levels. MHC class II expression was higher in the lymph nodes and lower in the spleen of SR than C, though these differences did not reach statistical significance. In SR; however, the average protein level was significantly higher in lymph nodes than spleen (376.0 + 184.9 vs 188.6 + 42.2, respectively; p = .002) and higher in the granulocytes relative to agranulocytes. Our findings provide empirical evidence of a constitutive diurnal expression pattern for MHC class II molecules that is prone to upregulation upon SR, namely in lymph nodes, and specifically expressed by granulocytes. We speculate that, in mice, chronic sleep deprivation would further dysregulate MHC class II expression that might result in aberrant T cell activation with probable immune-associated pathological diseases such as allergies, autoimmunity, and tumors.



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Is early appendectomy in adults diagnosed with acute appendicitis mandatory? A prospective study

Prompt appendectomy has long been the standard of care for acute appendicitis in order to prevent complications such as perforation, abscess formation, and diffuse purulent or fecal peritonitis, all resulting ...

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Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis.

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Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis.

Front Neurosci. 2018;12:977

Authors: Zhang J, Shi X, Hao N, Chen Z, Wei L, Tan L, Chen Y, Feng H, Chen Q, Zhu G

Abstract
Statins, known for their lipid-lowering effects, also have immunomodulatory properties. This study aims to examine whether systematic simvastatin administration could decrease polymorphonuclear neutrophils (PMNs) infiltration into brain tissue, as well as alleviate neuroinflammation in a rat model of intracerebral hemorrhage (ICH). The ICH model was induced in adult male Sprague-Dawley rats by an injection of autologous blood. Animals randomly received simvastatin (i.p. 2 mg/kg) or vehicle daily from 5 days before ICH until sacrificed. Routine blood counts, brain water content, neurological scoring, immunofluorescence and RT-PCR were conducted to evaluate the anti-inflammatory effect of simvastatin following ICH. Furthermore, flow cytometric and western blotting analysis were implemented for elucidating the mechanisms involved in simvastatin-induced reduction of neutrophil brain-invading. Elevated PMNs count and neutrophil-to-lymphocyte ratio in circulation were detected in rat model of ICH, which was reversed by using simvastatin. Simvastatin effectively alleviated PMNs infiltration and proinflammatory factors release in perihematomal area, as well as attenuated ICH-induced brain edema and neurological deficits. Simvastatin significantly downregulated the expression of antiapoptotic protein-Mcl-1 while increased the level of proapoptotic protein-Bax and cleaved caspase 3 in PMNs. Simvastatin treatment significantly alleviated PMNs brain-infiltrating and subsequent neuroinflammatory reaction after ICH, in part by accelerating peripheral PMNs apoptosis through disorganized the expression of apoptotic related proteins. Our data provided new evidence for simvastatin application on patients with ICH.

PMID: 30631264 [PubMed]



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Similar Neural Correlates of Planning and Execution to Inhibit Continuing Actions.

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Similar Neural Correlates of Planning and Execution to Inhibit Continuing Actions.

Front Neurosci. 2018;12:951

Authors: Omata K, Ito S, Takata Y, Ouchi Y

Abstract
Inhibition of action is involved in stopping a movement, as well as terminating unnecessary movement during performance of a behavior. The inhibition of single actions, known as response inhibition (Inhibition of the urge to respond before or after actions) has been widely investigated using the go/no-go task and stop signal task. However, few studies focused on phase and volition-related inhibition after an action has been initiated. Here, we used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of planning and execution underlying the voluntary inhibition of ongoing action. We collected fMRI data while participants performed a continuous finger-tapping task involving voluntary and involuntary (externally directed) inhibition, and during the initiation of movement. The results revealed areas of significantly greater activation during the preparation of inhibition of an ongoing action during voluntary inhibition, compared with involuntary inhibition, in the supplementary (SMA) and pre-supplementary motor areas, dorsolateral prefrontal cortex, inferior frontal gyrus (IFG), inferior parietal lobe, bilateral globus pallidus/putamen, bilateral insula and premotor cortex. Focusing on the period of execution of inhibition of ongoing actions, an event-related fMRI analysis revealed significant activation in the SMA, middle cingulate cortex, bilateral insula, right IFG and inferior parietal cortex. Additional comparative analyses suggested that brain activation while participants were planning to inhibit an ongoing action was similar to that during planning to start an action, indicating that the same neural substrates of motor planning may be recruited even when an action is ongoing. The present finding that brain activation associated with inhibiting ongoing actions was compatible with that seen in response inhibition (urge to stop before/after actions) suggests that common inhibitory mechanisms for motor movement are involved in both actual and planned motor action, which makes our behavior keep going seamlessly.

PMID: 30631263 [PubMed]



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Increasing Human Performance by Sharing Cognitive Load Using Brain-to-Brain Interface.

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Increasing Human Performance by Sharing Cognitive Load Using Brain-to-Brain Interface.

Front Neurosci. 2018;12:949

Authors: Maksimenko VA, Hramov AE, Frolov NS, Lüttjohann A, Nedaivozov VO, Grubov VV, Runnova AE, Makarov VV, Kurths J, Pisarchik AN

Abstract
Brain-computer interfaces (BCIs) attract a lot of attention because of their ability to improve the brain's efficiency in performing complex tasks using a computer. Furthermore, BCIs can increase human's performance not only due to human-machine interactions, but also thanks to an optimal distribution of cognitive load among all members of a group working on a common task, i.e., due to human-human interaction. The latter is of particular importance when sustained attention and alertness are required. In every day practice, this is a common occurrence, for example, among office workers, pilots of a military or a civil aircraft, power plant operators, etc. Their routinely work includes continuous monitoring of instrument readings and implies a heavy cognitive load due to processing large amounts of visual information. In this paper, we propose a brain-to-brain interface (BBI) which estimates brain states of every participant and distributes a cognitive load among all members of the group accomplishing together a common task. The BBI allows sharing the whole workload between all participants depending on their current cognitive performance estimated from their electrical brain activity. We show that the team efficiency can be increased due to redistribution of the work between participants so that the most difficult workload falls on the operator who exhibits maximum performance. Finally, we demonstrate that the human-to-human interaction is more efficient in the presence of a certain delay determined by brain rhythms. The obtained results are promising for the development of a new generation of communication systems based on neurophysiological brain activity of interacting people. Such BBIs will distribute a common task between all group members according to their individual physical conditions.

PMID: 30631262 [PubMed]



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Establishment and characterization of an immortalized renal cell line of the Chinese tree shrew ( Tupaia belangeri chinesis )

Abstract

The Chinese tree shrew holds a great potential as a viable animal model in biomedical research, especially for infectious diseases and neuropsychiatric disorders. A thorough understanding of the innate immunity, which represents the first line that defends the host against viral infection, of the Chinese tree shrew, is needed. However, the progress is hindered by the lack of a proper cell line for research usage. In this study, we established a cell line that is applicable to the study of tree shrew innate immune responses against viral infections. The Chinese tree shrew primary renal cells (TSPRCs) were immortalized by simian virus 40 large T antigen (SV40LT) transduction, and the immortalized cells were termed TSR6 (tree shrew renal cell #6). TSR6 showed a similar morphology to TSPRCs and expressed the epithelial cell-specific marker cytokeratin 18 (KRT18). In addition, TSR6 could be transfected by transfection reagent and was suitable for CRISPR/Cas9-mediated gene editing. Infection of Newcastle disease virus (NDV) or herpes simplex virus 1 (HSV-1) in TSR6 induced the mRNA expression of tree shrew interferon-β (tIFNB1) and myxovirus resistance protein 1 (tMx1) in a dose- and time-dependent manner. Collectively, we successfully established a tree shrew renal cell line and demonstrated that this cell line was suitable for the study of the innate immune response to viral infections.



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Results of PONDx, a prospective multicenter study of the Oncotype DX® breast cancer assay: Real-life utilization and decision impact in French clinical practice.

Results of PONDx, a prospective multicenter study of the Oncotype DX® breast cancer assay: Real-life utilization and decision impact in French clinical practice.

Breast. 2019 Jan 03;44:39-45

Authors: Curtit E, Vannetzel JM, Darmon JC, Roche S, Bourgeois H, Dewas S, Catala S, Mereb E, Fanget CF, Genet D, Forest AM, Bernier C, Pivot X

Abstract
Adjuvant chemotherapy shows clear benefits in HER2-positive and triple-negative breast cancer (BC). Its benefits are less universal in BCs expressing hormone receptors. The 21-gene Oncotype DX® Breast Recurrence Score test was designed for HR+, HER2- early-stage BC before decision on adjuvant chemotherapy. Its validity and utility was demonstrated prospectively across multiple studies. The observational study PONDx characterized the use of Oncotype DX® Breast in routine practice in France and evaluated its decision impact. Of 882 ER-positive BC patients (67% postmenopausal), most (79%) had N0/Nmic node involvement, grade 2 tumors (68%), tumor size 1-5 cm (88%), and ductal histology (78%). BCs with histopathologically elevated recurrence risk included grade 3: 18%; N1: 21%; Ki67 > 20%: 31%. Recurrence Score results by prognostic category were: <18: 54%, 18-30: 36%; >30: 10%. Compared to recommendations before individual availability of the score, results prompted net absolute reductions in chemotherapy recommendations of 36% (total population), and 29% (grade 3 and/or Ki67 > 20% histologies). Decisions reflected prognostic implications: in the Recurrence Score <18 category, 95% of patients received recommendations of hormonal therapy only, in the >30 category, 97.5% were recommended additional chemotherapy; 95% followed the final recommendations of their physicians. The Recurrence Score provides independent predictive and prognostic information in ER + N0/N1 early BC, including high-risk subgroups. PONDx further characterizes the population where the test is beneficial in real-life use and fits current clinical needs. Oncotype DX® Breast enables relevant net reductions in chemotherapy use, sparing patients from serious toxicities. Its therapeutic implications are highly accepted by physicians and patients.

PMID: 30634106 [PubMed - as supplied by publisher]



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Trastuzumab gold-conjugates: synthetic approach and in vitro evaluation of anticancer activities in breast cancer cell lines.

Trastuzumab gold-conjugates: synthetic approach and in vitro evaluation of anticancer activities in breast cancer cell lines.

Chem Commun (Camb). 2019 Jan 11;:

Authors: Curado N, Dewaele-Le Roi G, Poty S, Lewis JS, Contel M

Abstract
We describe the preparation of gold(i)-compounds that are amenable to efficient bioconjugation with monoclonal antibodies via activated ester or maleimide linkers. New Trastuzumab-gold conjugates were synthesized and fully characterized. These bioconjugates are significantly more cytotoxic (sub-micromolar range) to HER2-positive breast cancer cells than the gold complexes and Trastuzumab.

PMID: 30632546 [PubMed - as supplied by publisher]



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Predictive and prognostic value of circulating blood lymphocyte subsets in metastatic breast cancer.

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Predictive and prognostic value of circulating blood lymphocyte subsets in metastatic breast cancer.

Cancer Med. 2019 Jan 10;:

Authors: Yang J, Xu J, E Y, Sun T

Abstract
The treatment of breast cancer (BC) has improved greatly in recent years, however, the limitations of current therapeutic modalities underscore the need to define new prognostic tools and develop highly targeted therapies. The aims of the present study were to explore the effects of circulating blood lymphocyte subsets on the survival of metastatic breast cancer (MBC) patients and to evaluate their predictive and prognostic value. The clinical data of 482 patients with MBC were retrospectively analyzed, and patients were grouped according to molecular types of BC. The distribution of peripheral blood lymphocyte subsets at the time of first metastasis was examined by flow cytometry, and the distribution of lymphocyte subsets in each group was categorized into ''high or low'' subgroups using the upper quartile point as the cutoff. The relationship between the distribution of lymphocyte subsets and progression-free survival (PFS) as well as overall survival (OS) was evaluated in diverse molecular MBCs. In multivariate analysis, CD4+ was a negative independent predictor of PFS (hazard ratio [HR] = 0.538, 95% confidence interval [CI] = 0.313-0.926, P = 0.025) and CD3+ was a poor independent prognostic factor for OS (HR = 0.437, 95% CI = 0.248-0.772, P = 0.004) in the human epidermal growth factor receptor 2 (HER2)-positive group. Neither the CD8+ , CD19+ , and CD56+ lymphocyte subsets nor the CD4+ /CD8+ ratio in peripheral blood was significant predictive or prognostic factors. In conclusion, higher circulating levels of CD4+ and CD3+ at first diagnosis in HER2-overexpressing MBC were significantly associated with worse survival outcomes. Low levels of plasma CD4+ and CD3+ were associated with increased anti-HER2 benefit in HER2-positive MBC. The present results indicate that these factors can be used as predictive and prognostic indicators of the outcome of patients with MBC.

PMID: 30632318 [PubMed - as supplied by publisher]



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Anterior Lumbar Interbody Fusion (ALIF) using a personalised approach: Is custom the future of implants for ALIF surgery?

Anterior Lumbar Interbody Fusion (ALIF) using a personalised approach: Is custom the future of implants for ALIF surgery?

World Neurosurg. 2019 Jan 08;:

Authors: Mobbs RJ, Parr WC, Choy WJ, McEvoy A, Walsh WR, Phan K

Abstract
BACKGROUND: Spine surgery has the potential to benefit from the use of 3D printing technology (additive manufacturing) particularly in cases of complex anatomical pathologies. Custom devices have the potential to reduce operative times, reduce blood loss, provide immediate stability and potentially improve fusion rates.
CASE DESCRIPTION: A 34-year-old male presented with 3-year history of bilateral L5 radiculopathy due to bilateral L5 pars defect, and L5/S1 Degenerative Disc Disease and severe foraminal stenosis. ALIF surgery was determined to be the most efficacious method for distraction of the disc space to increase the foraminal volume and stabilization of the motion segment. Surgical decompression and reconstruction was performed in combination with a 3D printed, custom interbody implant. Custom design features included; corrective angulation to restore lumbar lordosis, pre-planned screw holes in the 3D implant and device endplate interface geometry designed to shape-match with the patient's endplate anatomy.
CONCLUSIONS: The use of Patient Specific Implants has reduced operative time significantly, which may offset costs of increased time spent pre-planning the procedure. Surgical procedures can be pre-planned using 3D models reconstructed from patient CT and/or MRI scans. Planning can be aided by 3D printed models of patient anatomy, which surgeons can use to train prior to performing complex procedures. When considering implants and prostheses, the use of 3D printing allows a superior anatomical fit for the patient compared to generic devices, with the potential to improve restoration of none-pathological anatomy.

PMID: 30633990 [PubMed - as supplied by publisher]



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A Case of T-Cell Large Granular Lymphocytic Leukemia and Renal Immunoglobulin Heavy Chain Amyloidosis.

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A Case of T-Cell Large Granular Lymphocytic Leukemia and Renal Immunoglobulin Heavy Chain Amyloidosis.

Am J Case Rep. 2019 Jan 11;20:43-47

Authors: Fu J, Lee LX, Zhou P, Fogaren T, Varga C, Comenzo RL

Abstract
BACKGROUND T-cell large granular lymphocytic leukemia (T-LGL) is a rare hematological malignancy that currently has no standard therapy. Immunoglobulin heavy chain amyloidosis (AH) involving the kidney is a rare condition and the pathology, diagnosis, clinical characteristics, and prognosis are becoming understood. This report is of a rare case of T-LGL associated with renal AH and discusses the approach to management. CASE REPORT A 57-year-old woman presented with symptoms of fatigue and she had proteinuria. A diagnosis of T-LGL associated with renal AH was made, which is an association that has not been previously reported in the literature. Given the dysregulation of her immune function due to her underlying T-LGL and her comorbidities, treatment options were limited. She was clinically stable and was initially observed. After one year, her symptoms of fatigue became worse, and her proteinuria increased. Treatment was initiated with the triple drug combination of bortezomib, cyclophosphamide, and dexamethasone (CyBorD) with consideration for future hematopoietic stem cell transplantation (HSCT). Her clinical condition improved, with a reduction in proteinuria. CONCLUSIONS A rare case of T-LGL and renal AH is presented. Currently, there is no standard therapy for T-LGL and AH amyloidosis, and the approach, in this case, was to manage the patient initially with CyBorD triple chemotherapy.

PMID: 30631033 [PubMed - in process]



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Impact of Occlusal Intercuspal Angulation on the Quality of CAD/CAM Lithium Disilicate Crown

Abstract

Purpose

Modification of intercuspal angulation (ICA) influences the amount of tooth structure removal, which may impact the retention and resistance form of the preparation. This study evaluated the impact of ICA on the marginal gap of CAD/CAM crowns and the influence that tooth structure removal, caused by variation of ICA, has on the resistance and retention form of the preparation.

Materials and Methods

Sixty ivorine molars were manufactured with various ICAs (100°, 110°, 120°, 140°, 160°, and 180°; 10 per group). The preparations were digitized using an intraoral scanner, and the crowns were designed using a design software. The designed crowns were then manufactured from lithium disilicate using a 3‐axis milling machine, with the "detailed mode" selected for the manufacturing. The marginal gap of each crown was evaluated using a stereomicroscope at 20 × magnification. Then, the marginal integrity and the resistance form of the preparation were assessed by tactile‐visual evaluation, and they were given a categorical score. Crowns were then secured on their associated preparations using a temporary luting agent, and retention force was measured on a universal testing machine under tension with a 0.5 mm/min crosshead speed. Wilcoxon test followed by post‐hoc tests (α = 0.05) were used to evaluate the impact of the ICA on the marginal gap and the retention form of preparation. Fisher's exact followed by post‐hoc tests (α = 0.05) were used to assess the impact of the occlusal preparation design on the marginal integrity and the resistance form of the preparation.

Results

The marginal gap was significantly larger for ICA‐180 preparations (72 μm), compared to the other groups (ICA‐180 vs ICA‐100, ICA‐110, ICA‐120, and ICA‐160 p = 0.0001; ICA‐180 vs ICA‐140 p = 0.0017). None of the crowns for ICA‐180 preparations had clinically acceptable resistance form. Preparations with ICAs of 100°, 110°, and 120° had a significantly higher value of retention than the other groups (ICA‐100 vs ICA‐120 p = 0.0119; ICA‐100 vs ICA‐140, ICA‐160, and ICA‐180 p < 0.0001; ICA‐110 vs ICA‐140, ICA‐160,and ICA‐180 p = 0.0001; ICA‐120 vs ICA‐180 p = 0.0017).

Conclusions

Crowns fabricated for preparations with various ICAs had clinically acceptable marginal adaptation. Variation in ICA impacts the loss of tooth structure. This loss of tooth structure may influence the resistance and retention form of the preparation.

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Status dystonicus: a diagnosis delayed.

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Status dystonicus: a diagnosis delayed.

BMJ Case Rep. 2018 Sep 12;2018:

Authors: Arshad MF, Ahmad E, Biddanda AN, Sharif M

Abstract
Status dystonicus, also known as the dystonic storm or dystonic crisis, is rare but may prove fatal due to respiratory and bulbar complications. In adults, the condition is rare and possibly under-reported. The lack of awareness of this condition among emergency and acute physicians may lead to an incorrect or delayed diagnosis, which should be avoided. We report a case of a 23-year-old man with athetoid cerebral palsy who presented to a district general hospital with uncontrolled dystonic movements, which were diagnosed as status dystonicus. This was successfully treated with intravenous clonidine, with full recovery returning to baseline functional state.

PMID: 30209149 [PubMed - indexed for MEDLINE]



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Determinants of health and wellbeing in refractory epilepsy and surgery: The Patient Reported, ImpleMentation sciEnce (PRIME) model.

Determinants of health and wellbeing in refractory epilepsy and surgery: The Patient Reported, ImpleMentation sciEnce (PRIME) model.

Epilepsy Behav. 2019 Jan 08;92:79-89

Authors: Rapport F, Shih P, Faris M, Nikpour A, Herkes G, Bleasel A, Kerr M, Clay-Williams R, Mumford V, Braithwaite J

Abstract
This paper offers a new way of understanding the course of a chronic, neurological condition through a comprehensive model of patient-reported determinants of health and wellbeing: The Patient Reported ImpleMentation sciEnce (PRIME) model is the first model of its kind to be based on patient-driven insights for the design and implementation of initiatives that could improve tertiary, primary, and community healthcare services for patients with refractory epilepsy, and has broad implications for other disorders; PRIME focuses on: patient-reported determinants of health and wellbeing, pathways through care, gaps in treatment and other system delays, patient need and expectation, and barriers and facilitators to high-quality care provision; PRIME highlights that in the context of refractory epilepsy, patients value appropriate, clear, and speedy referrals from primary care practitioners and community neurologists to specialist healthcare professionals based in tertiary epilepsy centers. Many patients also want to share in decisions around treatment and care, and gain a greater understanding of their debilitating disease, so as to find ways to self-manage their illness more effectively and plan for the future. Here, PRIME is presented using refractory epilepsy as the exemplar case, while the model remains flexible, suitable for adaptation to other settings, patient populations, and conditions; PRIME comprises six critical levels: 1) The Individual Patient Model; 2) The Patient Relationships Model; 3) The Patient Care Pathways Model; 4) The Patient Transitions Model; 5) The Pre- and Postintervention Model; and 6) The Comprehensive Patient Model. Each level is dealt with in detail, while Levels 5 and 6 are presented in terms of where the gaps lie in our current knowledge, in particular in relation to patients' journeys through healthcare, system intersections, and individuals adaptive behavior following resective surgery, as well as others' views of the disease, such as family members.

PMID: 30634157 [PubMed - as supplied by publisher]



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Early endocannabinoid system activation attenuates behavioral impairments induced by initial impact but does not prevent epileptogenesis in lithium-pilocarpine status epilepticus model.

Early endocannabinoid system activation attenuates behavioral impairments induced by initial impact but does not prevent epileptogenesis in lithium-pilocarpine status epilepticus model.

Epilepsy Behav. 2019 Jan 05;92:71-78

Authors: Suleymanova EM, Borisova MA, Vinogradova LV

Abstract
Mood and anxiety disorders, as well as memory impairments, are important factors affecting quality of life in patients with epilepsy and can influence the antiepileptic therapy. Clinical studies of psychiatric comorbidities are quite complicated to design and interpret, so animal studies of behavioral impairments associated with seizures can be of use. We investigated the effect of early administration of endocannabinoid receptor agonist WIN-55,212-2 on the development of spontaneous seizures, long-term behavioral and memory impairments, and neurodegeneration in the hippocampus on the lithium-pilocarpine model of status epilepticus (SE). We also studied the role of spontaneous seizures in the development of pathologic consequences of the SE. Our results showed that behavioral impairments found in the elevated plus maze test depended mostly on the consequences of SE itself and not on the development of spontaneous seizures while hyperactivity in the open-field test and light-dark chamber was more prominent in rats with spontaneous seizures. Administration of WIN-55,212-2 decreased emotional behavior in the elevated plus maze but did not affect hyperactive behavior in the open-field test. Spatial memory impairment developed both in the presence or absence of spontaneous seizures and was not affected by administration of WIN-55,212-2. Both administration of endocannabinoid receptor agonist WIN-55,212-2 and the presence of spontaneous seizures affected SE-induced neuronal loss in the hippocampus.

PMID: 30634156 [PubMed - as supplied by publisher]



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Electroconvulsive therapy: 80 years old and still going strong.

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Electroconvulsive therapy: 80 years old and still going strong.

World J Psychiatry. 2019 Jan 04;9(1):1-6

Authors: Gazdag G, Ungvari GS

Abstract
Electroconvulsive therapy (ECT), which is among the oldest and most controversial treatments in the field of psychiatry, has its 80th birthday this year. In this brief historical overview, the discovery of the therapeutic effects of convulsive therapy by Laszló Meduna, and the circumstances that motivated Ugo Cerletti and Lucio Bini to use electricity as a means of seizure induction are described. Meduna's original theory about the antagonism between epilepsy and schizophrenia has been replaced by hypotheses on the mechanism of action of ECT. The position of ECT in modern psychiatry is also discussed with special attention to its most important clinical indications, including catatonia, and pre- and postpartum affective and psychotic states that are responsive to ECT and in which ECT may even be lifesaving. Adverse effects and comparison of ECT with recently developed brain stimulation methods are also reviewed. The negative media portrayal of ECT and its earlier misuse may have contributed to its negative professional and public perceptions indicated repeatedly in attitude surveys. This negative attitude has played an important role in the decreasing use of ECT in the developed world and a reduction in access to ECT, which constitutes a violation of psychiatric patients' right to an effective treatment.

PMID: 30631748 [PubMed]



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A Novel Nonsense Mutation of PHF6 in a Female with Extended Phenotypes of Borjeson-Forssman-Lehmann Syndrome.

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A Novel Nonsense Mutation of PHF6 in a Female with Extended Phenotypes of Borjeson-Forssman-Lehmann Syndrome.

J Clin Res Pediatr Endocrinol. 2019 Jan 11;:

Authors: Zhang X, Fan Y, Liu X, Ang Zhu M, Sun Y, Yan H, He Y, Ye X, Gu X, Yu Y

Abstract
Borjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked disease caused by PHF6 mutations. Classic BFLS is featured by intellectual disability (ID), developmental delay (DD), obesity, epilepsy, characteristic face and anomalies of fingers and toes. Endocrinological phenotypes and relevant outcome of treatment in this condition remains to be delineated. Here we report a patient with presentations beyond the classic BFLS - the patient exhibited complete growth hormone deficiency, and adverse effects were elicited after hormonal treatment. Horseshoe kidney was found in this patient, which is also atypical in BFLS. A heterozygous nonsense mutation c.673C>T(p.R225X) of PHF6 gene was identified in the patient, inherited from her unaffected mother. Both the patient and her mother showed highly skewed X-inactivation. We reviewed the phenotypes of all reported BFLS cases, and summarized the endocrine presentations in literature. The report of this first Asian patient with extended phenotypes further delineated the genetic and phenotypic spectrum of BFLS, and the adverse effect presented in this case cautions the use of hormonal treatment in this condition.

PMID: 30630810 [PubMed - as supplied by publisher]



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Diffuse Low-Grade Glioma-Related Epilepsy.

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Diffuse Low-Grade Glioma-Related Epilepsy.

Neurosurg Clin N Am. 2019 Jan;30(1):43-54

Authors: Pallud J, McKhann GM

Abstract
The World Health Organization classifies diffuse low-grade gliomas (DLGGs) are highly epileptogenic primary brain tumors; epileptic seizures occur in more than 90% of cases. Epileptic seizures and drug resistance progress during the course of DLGGs. The glioma-related epileptogenic mechanisms are multifactorial; epileptogenic foci lie within the infiltrated peritumoral neocortex. A short seizure duration before surgery and a large extent of resection are the main predictors of postoperative seizure control in DLGGs. A supratotal resection of a DLGG can improve postoperative seizure control. Epileptic seizure at diagnosis positively affects DLGGs malignant transformation and overall survival.

PMID: 30470404 [PubMed - indexed for MEDLINE]



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Alterations in the Brain Microenvironment in Diffusely Infiltrating Low-Grade Glioma.

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Alterations in the Brain Microenvironment in Diffusely Infiltrating Low-Grade Glioma.

Neurosurg Clin N Am. 2019 Jan;30(1):27-34

Authors: Torres D, Canoll P

Abstract
Glioma cells diffusely infiltrate the surrounding brain tissue where they intermingle with nonneoplastic brain cells, including astrocytes, microglia, oligodendrocytes and neurons. The infiltrative margins of glioma represent the structural and functional interface between neoplastic and nonneoplastic brain tissue that underlies neurologic alterations associated with glioma, including epilepsy and neurologic deficits. Technological advancements in molecular analysis, including single cell sequencing, now allow us to assess alterations in specific cell types in the brain tumor microenvironment, which can enhance the development of novel therapies that target glioma growth and glioma-induced neurologic symptoms.

PMID: 30470402 [PubMed - indexed for MEDLINE]



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The impact of service and hearing dogs on health-related quality of life and activity level: a Swedish longitudinal intervention study.

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The impact of service and hearing dogs on health-related quality of life and activity level: a Swedish longitudinal intervention study.

BMC Health Serv Res. 2018 06 27;18(1):497

Authors: Lundqvist M, Levin LÅ, Roback K, Alwin J

Abstract
BACKGROUND: Individuals with severe disability often require personal assistance and help from informal caregivers, in addition to conventional health care. The utilization of assistance dogs may decrease the need for health and social care and increase the independence of these individuals. Service and hearing dogs are trained to assist specific individuals and can be specialized to meet individual needs. The aim of this study was to describe and explore potential consequences for health-related quality of life, well-being and activity level, of having a certified service or hearing dog.
METHODS: A longitudinal interventional study with a pre-post design was conducted. At inclusion, all participants in the study had a regular (untrained) companion dog. Data were collected before training of the dog started and three months after certification of the dog. Health-related quality of life was assessed with EQ-5D-3L, EQ-VAS and RAND-36. Well-being was measured with WHO-5 and self-esteem with the Rosenberg Self-Esteem Scale. In addition, questions were asked about physical activity and time spent away from home and on social activities. Subgroups were analyzed for physical service and diabetes alert dogs.
RESULTS: Fifty-five owner-and-dog pairs completed the study (30 physical service dogs, 20 diabetes alert dogs, 2 epilepsy alert dogs, and 3 hearing dogs). Initially, study participants reported low health-related quality of life compared with the general population. At follow-up, health-related quality of life measured with the EQ-VAS, well-being and level of physical activity had improved significantly. In the subgroup analysis, physical service dog owners had lower health-related quality of life than diabetes alert dog owners. The improvement from baseline to follow-up measured with EQ-5D statistically differed between the subgroups.
CONCLUSIONS: The target population for service and hearing dogs has an overall low health-related quality of life. Our study indicates that having a certified service or hearing dog may have positive impact on health-related quality of life, well-being and activity level. Service and hearing dogs are a potentially important "wagging tail aid" for this vulnerable population, able to alleviate strain, increase independence, and decrease the risk of social isolation.
TRIAL REGISTRATION: The trial was retrospectively registered in http://bit.ly/12EVq09 , NCT03270592. September, 2017.

PMID: 29945630 [PubMed - indexed for MEDLINE]



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Comparison of Cationic Liposome and PAMAM Dendrimer for Delivery of Anti-Plk1 siRNA in Breast Cancer Treatment.

Comparison of Cationic Liposome and PAMAM Dendrimer for Delivery of Anti-Plk1 siRNA in Breast Cancer Treatment.

Pharm Dev Technol. 2019 Jan 11;:1-27

Authors: Bulbake U, Kommineni N, Ionov M, Bryszewska M, Khan W

Abstract
Delivery of negatively charged, high molecular weight and unstable siRNA is difficult. The present study describes the development and comparison of cationic liposomes (CLs) and polyamidoamine (PAMAM) dendrimer generation 4 (PG4) nanocarriers of gene for cancer therapy. CLs and PG4 were complexed with anticancer siRNA (siPlk1) to form siPlk1-CLs lipoplex and siPlk1-PG4 dendriplex. siPlk1-CLs/PG4 complexes were characterized for average particle size, zeta potential, fluorescence and integrity of siPlk1 by agarose gel electrophoresis, ethidium bromide intercalation assay, circular dichroism, protection against RNase and stability in serum. The complexation of CLs/siPlk1 and PG4/siPlk1 were at a 100/1 and 2/1 charge ratio respectively. The CLs and PG4 were effective in protecting siPlk1 from RNase activity, also they enhanced the siPlk1 serum stability. Additionally, siPlk1-CLs and siPlk1-PG4 were evaluated by cell culture studies. In vitro anticancer activity study using MCF-7 cells showed that siPlk1-CLs and siPlk1-PG4 causes nearly similar cell death. Both siPlk1-CLs and siPlk1-PG4 resulted in enhanced cellular uptake of siPlk1 in MDA-MB-231 cells compared to naked siPlk1 solution. Cell cycle analysis suggested that increased cell population arrest in subG1 phase by siPlk1-CLs and siPlk1-PG4 compared to naked siPlk1 solution. These observations suggested that CLs and PG4 can be a potential carrier for siPlk1 delivery in breast cancer treatment.

PMID: 30633621 [PubMed - as supplied by publisher]



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IL28RA inhibits human epidermal keratinocyte proliferation by inhibiting cell cycle progression.

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IL28RA inhibits human epidermal keratinocyte proliferation by inhibiting cell cycle progression.

Mol Biol Rep. 2019 Jan 10;:

Authors: Yin X, Zhang S, Li B, Zhang Y, Zhang X

Abstract
Interleukin (IL) 28 receptor α (IL28RA) is a well-known candidate for psoriasis susceptibility based on previous genome-wide association study (GWAS) analysis. However, the function of IL28RA in psoriasis has not been elucidated. In the present study, the expression of IL28RA was significantly decreased in lesional tissues from patients with plaque psoriasis when compared with the expression observed in adjacent non-lesional tissues. In vitro studies further demonstrated that in the presence of IL-29, HaCaT keratinocytes with IL28RA knockdown exhibited a faster rate of proliferation than control cells, and an enhanced ratio of cells in the S and G2/M phase. By contrast, IL28RA overexpression inhibited the proliferation of HaCaT keratinocytes and caused cell cycle arrest at the G0/G1 phases. Western blot analysis revealed that knockdown of IL28RA upregulated cyclinB1 expression and downregulated cyclinE expression; the opposite results were observed in the IL28RA-overexpressing HaCaT cells. Finally, a mechanistic study revealed that IL28RA functions through the activation of the Janus kinase-signal transducer and activator of transcription signaling pathway to exert its anti-proliferative effect. These results suggested that weak expression of IL28RA may contribute to the pathogenesis of psoriasis and that IL28RA may be an effective drug target for the treatment of psoriasis. However, further in vivo studies are required.

PMID: 30632069 [PubMed - as supplied by publisher]



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The anti-tumor activity of brown seaweed oligo-fucoidan via lncRNA expression modulation in HepG2 cells.

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The anti-tumor activity of brown seaweed oligo-fucoidan via lncRNA expression modulation in HepG2 cells.

Cytotechnology. 2019 Jan 10;:

Authors: Yan MD, Lin HY, Hwang PA

Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death in Asia. HCC is less sensitive to chemotherapy and is known to express multidrug resistant genes to acquire resistance to chemotherapeutic agents, therefore the development of a potent HCC suppressor is essential in treating HCC. Our previous reports demonstrated that oligo-fucoidan from the brown seaweed Sargassum hemiphyllum elevates microRNA-29b to inhibit epithelial-mesenchymal transition in hepatoma cells. In this study, we aimed to examine in vitro effect of oligo-fucoidan in hepatocellular carcinoma through apoptosis and long noncoding RNA (lncRNA) pathway. Oligo-fucoidan was studied for its anti-hepatoma cells by MTT and DNA ladder analysis. And the mechanism was studied by flow cytometry, qPCR and western blot analysis. In this study, oligo-fucoidan induced sub-G1 phase cell cycle arrest and activation of caspases, indicating that the intrinsic and extrinsic apoptotic pathways were involved in the mechanism of oligo-fucoidan-induced cell death. Moreover, oligo-fucoidan significantly increased the expression of p53, p21, and p27, while cyclin-B1 and -D1 were decreased at the mRNA and protein levels. Finally, we showed that targeting apoptosis and cell cycle pathways could also contribute to the induction of the lncRNA-Saf and lncRNA-p21. Through human lncRNA profiler array analysis, the differential expression of lncRNAs in HCC cells following oligo-fucoidan exposure was further examined. These findings indicated that lncRNAs switched oligo-fucoidan-induced apoptosis, which might be potentially valuable in HCC adjuvant therapy.

PMID: 30632031 [PubMed - as supplied by publisher]



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Association of Gpx1 fluctuation in cell cycle progression.

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Association of Gpx1 fluctuation in cell cycle progression.

In Vitro Cell Dev Biol Anim. 2019 Jan 10;:

Authors: Aktar K, Kafi A, Dahiya R

Abstract
This research demonstrates fluctuation of glutathione peroxidase1 (Gpx1) throughout cell cycle progression with significant decreased expression at mitosis of HeLa cell. This was achieved with western blot (WB) analysis of target proteins from each phase of synchronized cells. The synchronizations were performed with double thymidine (T/T) for G1/S arrest and thymidine followed by nocodazole (T/N) for G2/M arrest. The G1/S arrested cells were released in fresh medium for 3, 6, 9, 10, and 15h to obtain cell at each phase such as gap1 (G1), synthesis (S), gap2 (G2), mitosis (M), and gap1 (G1) phase, respectively, for investigating Gpx1 expression throughout a complete cycle. The synchronizations were confirmed using fluorescence activated cell sorting (FACS) and WB analysis of phase-specific markers. The fluctuations of Gpx1 expression were verified with universal protein actin and peroxiredoxin1 (Prx1) which are stable throughout the cell cycle. Intriguingly, immunoblots showed the level of Gpx1 decreases at mitosis phase and increased during mitotic exit to G1 phase in HeLa cells, while Prx1 protein level remained constant. The fractionation experiments reveal that only the cytosolic Gpx1 was decreased while their levels at mitochondria remain constant. The highest levels of mitochondrial ROS were measured in mitosis phase with FACS analysis using Mito sox indicating that antioxidant activity of Gpx1 for detoxifying excessive induced endogenous reactive oxygen species (ROS) in the mitosis phase could be the reason for such decreasing level. For unfolding the molecular mechanism of such decreased expression, the Gpx1 was investigated at transcriptional, translational, and proteosomal level. The results revealed that translational mechanism is involve in the decreased expression rather than transcriptional or proteosomal degradation at mitosis phase. This finding supports that Gpx1 is involved in the cell cycle progression through regulation of endogenous ROS. Based on this observation, further research could uncover their possible association with the infinitive division of a cancer cell.

PMID: 30632027 [PubMed - as supplied by publisher]



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Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro.

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Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro.

Front Microbiol. 2018;9:3126

Authors: Lundberg L, Fontenot J, Lin SC, Pinkham C, Carey BD, Campbell CE, Kehn-Hall K

Abstract
Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Like other RNA viruses, VEEV replicates in the cytoplasm of infected cells and eventually induces apoptosis. The capsid protein, which contains a nuclear localization and a nuclear export sequence, induces a shutdown of host transcription and nucleocytoplasmic trafficking. Here we show that infection with VEEV causes a dysregulation of cell cycling and a delay in the G0/G1 phase in Vero cells and U87MG astrocytes. Cells infected with VEEV encoding a capsid NLS mutant or treated with the capsid-importin α interaction inhibitor G281-1485 were partially rescued from this cell cycle dysregulation. Pathway analysis of previously published RNA-sequencing data from VEEV infected U87MG astrocytes identified alterations of canonical pathways involving cell cycle, checkpoint regulation, and proliferation. Multiple cyclins including cyclin D1, cyclin A2 and cyclin E2 and other regulators of the cell cycle were downregulated in infected cells in a capsid NLS dependent manner. Loss of Rb phosphorylation, which is a substrate for cyclin/cdk complexes was also observed. These data demonstrate the importance of capsid nuclear localization and/or importin α binding for inducing cell cycle arrest and transcriptional downregulation of key cell cycle regulators.

PMID: 30631316 [PubMed]



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Enhancer Domains in Gastrointestinal Stromal Tumor Regulate KIT Expression and are Targetable by BET Bromodomain Inhibition.

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Enhancer Domains in Gastrointestinal Stromal Tumor Regulate KIT Expression and are Targetable by BET Bromodomain Inhibition.

Cancer Res. 2019 Jan 10;:

Authors: Hemming ML, Lawlor MA, Andersen JL, Hagan T, Chipashvili O, Scott TG, Raut CP, Sicinska E, Armstrong SA, Demetri GD, Bradner JE

Abstract
Gastrointestinal stromal tumor (GIST) is a mesenchymal neoplasm characterized by activating mutations in the related receptor tyrosine kinases KIT and PDGFRA. GIST relies on expression of these unamplified receptor tyrosine kinase (RTK) genes through a large enhancer domain, resulting in high expression levels of the oncogene required for tumor growth. Although kinase inhibition is an effective therapy for many GIST patients, disease progression from kinase resistance mutations is common and no other effective classes of systemic therapy exist. In this study, we identify regulatory regions of the KIT enhancer essential for KIT gene expression and GIST cell viability. Given the dependence of GIST upon enhancer-driven expression of RTKs, we hypothesized that the enhancer domains could be therapeutically targeted by a BET bromodomain inhibitor (BBI). Treatment of GIST cells with BBIs led to cell cycle arrest, apoptosis, and cell death, with unique sensitivity in GIST cells arising from attenuation of the KIT enhancer domain and reduced KIT gene expression. BBI treatment in KIT-dependent GIST cells produced genome-wide changes in the H3K27ac enhancer landscape and gene expression program, which was also seen with direct KIT inhibition using a tyrosine kinase inhibitor (TKI). Combination treatment with BBI and TKI led to superior cytotoxic effects in vitro and in vivo, with BBI preventing tumor growth in TKI-resistant xenografts. Resistance to select BBI in GIST was attributable to drug efflux pumps. These results define a therapeutic vulnerability and clinical strategy for targeting oncogenic kinase dependency in GIST.

PMID: 30630822 [PubMed - as supplied by publisher]



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Expression of KLF9 in pancreatic cancer and its effects on the invasion, migration, apoptosis, cell cycle distribution, and proliferation of pancreatic cancer cell lines.

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Expression of KLF9 in pancreatic cancer and its effects on the invasion, migration, apoptosis, cell cycle distribution, and proliferation of pancreatic cancer cell lines.

Oncol Rep. 2018 Dec;40(6):3852-3860

Authors: Zhong Z, Zhou F, Wang D, Wu M, Zhou W, Zou Y, Li J, Wu L, Yin X

Abstract
Kruppel-like factor 9 (KLF9), a transcription factor, is critical for the inhibition of growth and development of tumors, whereas its effects in pancreatic cancer remains unclear. The purpose of the present study was to investigate the expression and functional significance of KLF9 in vitro, by assessing the expression of KLF9 in pancreatic cancer tissue samples and its association with the total survival of patients and clinicopathological data. The levels of KLF9 expression in adjacent tissues and pancreatic cancer tissues were detected using immunohistochemistry. Using western blot analyses, we assessed KLF9 expression in human pancreatic cancer cell lines. Using flow cytometric analysis and CCK-8, we evaluated the effects of KLF9 expression on cell apoptosis, the cell cycle and proliferation of pancreatic cancer cells. Its effects on migration and cell invasion were detected by performing Transwell assay. By conducting western blot analyses, we evaluated the expression of relative target proteins (involved in invasion, migration, apoptosis, and cell cycle distribution. Our results revealed that in both tissue samples and cell lines (particularly in BxPC-3 and PANC-1 cells) of pancreatic cancer, KLF9 exhibited relatively lower expression. In addition, low KLF9 expression was related to the differentiation (P<0.001) and depth of vascular invasion (P=0.016) and was associated with a poor overall survival rate. In PANC-1 and BxPC-3 cells, KLF9 overexpression decreased the proliferation of pancreatic cancer cells, induced apoptosis, blocked the cell cycle at the S phase, and inhibited the migration and invasion of tumor cells. KLF9 overexpression downregulated MMP-9, MMP-2 Bcl-2, N-cadherin and cyclin B, and upregulated the levels of E-cadherin, Bax, p53, CDK4 and cyclin D1. On the whole, our findings indicated that KLF9 exhibited low expression in pancreatic cancer, and upregulation of KLF9 may inhibit the progression of pancreatic cancer. KLF9 may have potential diagnostic and therapeutic values in this type of cancer.

PMID: 30542730 [PubMed - indexed for MEDLINE]



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Neuromuscular complications of immune checkpoint inhibitors.

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Neuromuscular complications of immune checkpoint inhibitors.

Presse Med. 2018 Nov - Dec;47(11-12 Pt 2):e253-e259

Authors: Psimaras D

Abstract
Immune checkpoint inhibitors have been increasingly used in patients with various cancers. Despite favourable oncological outcomes these treatments have also been associated with immune-related adverse events. Neurological irAE are rare but potentially severe and neuromuscular complications are the most common. This is a new group of neurologic complications of systemic anticancer therapies, often responsive to immune-modulating therapies. Early recognition and treatment are crucial for timely improvement of functional outcome and requires a multidisciplinary approach.

PMID: 30413332 [PubMed - indexed for MEDLINE]



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[Sarcoid-like granulomatosis in cancer patients treated with immune checkpoints inhibitors].

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[Sarcoid-like granulomatosis in cancer patients treated with immune checkpoints inhibitors].

Rev Mal Respir. 2018 Nov;35(9):963-967

Authors: Faviez G, Bousquet E, Rabeau A, Rouquette I, Collot S, Goumarre C, Meyer N, Prevot G, Mazieres J

Abstract
INTRODUCTION: Immune checkpoint inhibitors are becoming a standard treatment for many different cancers. Their toxicities are variable and include organ-specific dysimmune injuries and the development of systemic diseases.
CASE REPORT: We report 3 cases of sarcoid-like granulomatosis that occurred during treatment of various types of primary cancer by immune checkpoint inhibitors: lung adenocarcinoma, small cell lung cancer and melanoma. The clinical presentation, radiologic pattern and severity of this toxicity were variable. The diagnosis was made on biopsy with pathological examination and exclusion of differential diagnoses, particularly infection. In such cases, immunotherapy should be discontinued and subsequent rechallenge discussed later. Systemic corticosteroids should be considered depending on the severity of symptoms.
CONCLUSIONS: Knowledge of this toxicity is crucial as the clinical signs and radiological patterns may suggest tumour progression.

PMID: 30220489 [PubMed - indexed for MEDLINE]



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[Tumour assessment criteria for immune checkpoint inhibitors].

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[Tumour assessment criteria for immune checkpoint inhibitors].

Rev Mal Respir. 2018 Oct;35(8):828-845

Authors: Wasielewski E, Cortot AB

Abstract
The development of immune checkpoint inhibitors in thoracic oncology has led to a reconsideration of the rules for radiological tumor assessment. The RECIST criteria are widely used for the assessment of conventional treatments but are not suitable for anti-tumoral immunotherapy. The mechanism of action of this new class of drugs may induce specific patterns of response, which are not fully assessed by the RECIST criteria. Several new criteria have been proposed to better detect these patterns of response. The changes usually include confirmation of progression, new ways of assessing new lesions, and a larger role for clinical assessment. Nevertheless, harmonization and validation of these criteria remains indispensable. In this review, we will detail the different criteria that are currently available, and discuss their strengths and weaknesses.

PMID: 30166076 [PubMed - indexed for MEDLINE]



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Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy.

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Long-term follow up of metastatic melanoma patients treated with Thymosin alpha-1: investigating immune checkpoints synergy.

Expert Opin Biol Ther. 2018 07;18(sup1):77-83

Authors: Danielli R, Cisternino F, Giannarelli D, Calabrò L, Camerini R, Savelli V, Bova G, Dragonetti R, Di Giacomo AM, Altomonte M, Maio M

Abstract
BACKGROUND: Immune checkpoint blockade antibodies (imAbs), such as the anti Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) ipilimumab (IPI) raised overall survival (OS) in metastatic melanoma (MM). Further, long-term OS is a crucial endpoint in MM. Thymosin alpha-1 (Tα1) with dacarbazine (DTIC) showed activity in a phase II trial and a compassionate use program (EAP). We report on long-term follow-up of patients treated with Tα1 to investigate the preconditioning role of Tα1 in imAbs-treated patients.
METHODS: Records of patients with melanoma treated with Tα1 within a phase II trial and EAP program were reviewed comparing median OS among patients that sequentially received anti-CTLA-4 imAb and Tα1. Further, the effect of Tα1 on IPI long-term survivor patients was investigated.
RESULTS: Among patients treated with Tα1, 21/61 patients received sequentially even anti CTLA-4 imAbs. Median OS at the data cut-off was 57.8 and 7.4 months in patients treated sequentially with anti-CTLA-4 imAbs or not, respectively. Moreover, pretreatment with Tα1 in all (95) IPI-evaluable patients confirmed a significant increase in long-term OS.
CONCLUSION: This is the first report on long-term follow-up of Tα1-treated patients. Moreover, an advantage in OS in patients sequentially treated with Tα1 and IPI was seen that suggests a synergistic effect.

PMID: 30063847 [PubMed - indexed for MEDLINE]



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[Immunotherapy in lung cancer: New concepts].

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[Immunotherapy in lung cancer: New concepts].

Rev Mal Respir. 2018 Jun;35(6):642-651

Authors: Goubet AG, Livartowski A, Romano E

Abstract
Improvements in knowledge about the complexity of the tumor microenvironment have paved the way for a revolution in lung cancer treatment with the emergence of immune checkpoint inhibitors. The immune checkpoints negatively regulate immune cells and lead to a dormant state: the immune cells are then unable to interact effectively with their targets. The immune checkpoint inhibitors are monoclonal antibodies that block immune checkpoints and permit reactivation of the immune response against the tumor. Although immune checkpoint inhibitors are effective as monotherapy, several other immune targets exist. The better understanding of the involvement of these new targets in the immune response against tumors is leading to the design of new compounds and new therapeutic approaches.

PMID: 29941206 [PubMed - indexed for MEDLINE]



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Late-occurring toxicity induced by an immune checkpoint blockade in adjuvant treatment of a stage III melanoma patient.

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Late-occurring toxicity induced by an immune checkpoint blockade in adjuvant treatment of a stage III melanoma patient.

Eur J Cancer. 2018 05;95:130-132

Authors: Mandalà M, Merelli B, Indriolo A, Tondini C

PMID: 29559189 [PubMed - indexed for MEDLINE]



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Immune checkpoint therapy in proteinuric kidney disease.

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Immune checkpoint therapy in proteinuric kidney disease.

Eur J Cancer. 2018 05;95:120-122

Authors: Takenaka T, Kawai Y, Amano T

PMID: 29530540 [PubMed - indexed for MEDLINE]



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Results and challenges of immune checkpoint inhibitors in colorectal cancer.

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Results and challenges of immune checkpoint inhibitors in colorectal cancer.

Expert Opin Biol Ther. 2018 05;18(5):561-573

Authors: Emambux S, Tachon G, Junca A, Tougeron D

Abstract
INTRODUCTION: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and clinical outcome has improved substantially during the last two decades with targeted therapies. The immune system has a major role in cancers, especially the CD8 + T cells specific to tumor antigens. However, tumors can escape immune response by different mechanisms including upregulation of inhibitory immune checkpoint receptors, such as well-known Programmed cell Death protein-1 (PD-1)/Programmed cell Death Ligand 1 (PD-L1) interaction, leading CD8 + T cells to a state of anergy. Immunotherapy, with the so-called immune checkpoint inhibitors (CPIs), has recently been approved in treatment of multiple cancers due to its prolonged disease control and acceptable toxicities. The recent groundbreaking success involving anti-PD-1 CPIs in metastatic CRC with deficient mismatch repair system (dMMR) is promising, with several trials ongoing. Major challenges are ahead in order to determine how, when and for which patients we should use these CPIs in CRC. Areas covered: This review highlights some promises and challenges concerning personalized immunotherapy in CRC. First results and ongoing breakthrough trials are presented. The crucial role of biomarkers in selecting patient is also discussed. Expert opinion: As of now, dMMR and POLE mutations (DNA polymerase ε) with ultramutator phenotype are the most powerful predictive biomarkers of CPI efficacy. The most challenging issue is pMMR mCRC and determination of how to convert a 'nonimmunogenic' neoplasm into an 'immunogenic' neoplasm, a combination of CPIs with radiation or MEK inhibitor probably being the most relevant strategy. Next-generation sequencing (NGS) assays to quantify mutational load could be more reliable predictive biomarkers of CPIs efficacy than PD-L1 expression or immune scores.

PMID: 29471676 [PubMed - indexed for MEDLINE]



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A systematic review protocol of stigma among children and adolescents with epilepsy

Epilepsy is a neurological condition that is highly prevalent among children and adolescents with 80% of the victims living in low- and middle-income countries (LMIC). Epilepsy is associated with high levels o...

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Strategies for incorporating patient-reported outcomes in the care of people with chronic kidney disease (PRO kidney): a protocol for a realist synthesis

Patient-reported outcomes and experience measures (jointly referred to here as PROs) are internationally recognized as a means for patients to provide information about their quality of life, symptoms, and exp...

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Future Oncology; +26 new citations

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Future Oncology

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NAD Metabolism in Cancer Therapeutics.

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NAD Metabolism in Cancer Therapeutics.

Front Oncol. 2018;8:622

Authors: Yaku K, Okabe K, Hikosaka K, Nakagawa T

Abstract
Cancer cells have a unique energy metabolism for sustaining rapid proliferation. The preference for anaerobic glycolysis under normal oxygen conditions is a unique trait of cancer metabolism and is designated as the Warburg effect. Enhanced glycolysis also supports the generation of nucleotides, amino acids, lipids, and folic acid as the building blocks for cancer cell division. Nicotinamide adenine dinucleotide (NAD) is a co-enzyme that mediates redox reactions in a number of metabolic pathways, including glycolysis. Increased NAD levels enhance glycolysis and fuel cancer cells. In fact, nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme for NAD synthesis in mammalian cells, is frequently amplified in several cancer cells. In addition, Nampt-specific inhibitors significantly deplete NAD levels and subsequently suppress cancer cell proliferation through inhibition of energy production pathways, such as glycolysis, tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. NAD also serves as a substrate for poly(ADP-ribose) polymerase (PARP), sirtuin, and NAD gylycohydrolase (CD38 and CD157); thus, NAD regulates DNA repair, gene expression, and stress response through these enzymes. Thus, NAD metabolism is implicated in cancer pathogenesis beyond energy metabolism and considered a promising therapeutic target for cancer treatment. In this review, we present recent findings with respect to NAD metabolism and cancer pathogenesis. We also discuss the current and future perspectives regarding the therapeutics that target NAD metabolic pathways.

PMID: 30631755 [PubMed]



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