upper respiratory tract infection; +23 new citations

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2018/04/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

Histol Histopathol. 2018 Apr 25;:11994

Authors: Marini M, Rosa I, Ibba-Manneschi L, Manetti M

Abstract
Telocytes (TCs) represent a new distinct type of cells found in the stromal compartment of many organs, including the skeletal, cardiac and smooth muscles. TCs are morphologically defined as interstitial cells with a small cellular body from which arise very long (up to hundreds of micrometers) and thin moniliform processes (named telopodes) featuring the alternation of slender segments (called podomers) and small dilated portions (called podoms) accommodating some organelles. Although these stromal cells are mainly characterized by their ultrastructural traits, in the last few years TCs have been increasingly studied for their immunophenotypes, microRNA profiles, and gene expression and proteomic signatures. By their long-distance spreading telopodes, TCs build a three-dimensional network throughout the whole stromal space and communicate with each other and neighboring cells through homocellular and heterocellular junctions, respectively. Moreover, increasing evidence suggests that TCs may exert paracrine functions being able to transfer genetic information and signaling molecules to other cells via the release of different types of extracellular vesicles. A close relationship between TCs and stem/progenitor cell niches has also been described in several organs. However, the specific functions of TCs located in the muscle interstitium remain to be unraveled. Here, we review the morphological and possible functional aspects of TCs in skeletal, cardiac and smooth muscle tissues. The potential involvement of TCs in muscle tissue pathological changes and future possibilities for targeting TCs as a novel promising therapeutic strategy to foster muscle tissue regeneration and repair are also discussed.

PMID: 29693711 [PubMed - as supplied by publisher]

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Hierarchical Cluster Analysis of Semicircular Canal and Otolith Deficits in Bilateral Vestibulopathy.

Hierarchical Cluster Analysis of Semicircular Canal and Otolith Deficits in Bilateral Vestibulopathy.

Front Neurol. 2018;9:244

Authors: Tarnutzer AA, Bockisch CJ, Buffone E, Weber KP

Abstract
Background: Gait imbalance and oscillopsia are frequent complaints of bilateral vestibular loss (BLV). Video-head-impulse testing (vHIT) of all six semicircular canals (SCCs) has demonstrated varying involvement of the different canals. Sparing of anterior-canal function has been linked to aminoglycoside-related vestibulopathy and Menière's disease. We hypothesized that utricular and saccular impairment [assessed by vestibular-evoked myogenic potentials (VEMPs)] may be disease-specific also, possibly facilitating the differential diagnosis.
Methods: We searched our vHIT database (n = 3,271) for patients with bilaterally impaired SCC function who also received ocular VEMPs (oVEMPs) and cervical VEMPs (cVEMPs) and identified 101 patients. oVEMP/cVEMP latencies above the 95th percentile and peak-to-peak amplitudes below the 5th percentile of normal were considered abnormal. Frequency of impairment of vestibular end organs (horizontal/anterior/posterior SCC, utriculus/sacculus) was analyzed with hierarchical cluster analysis and correlated with the underlying etiology.
Results: Rates of utricular and saccular loss of function were similar (87.1 vs. 78.2%, p = 0.136, Fisher's exact test). oVEMP abnormalities were found more frequent in aminoglycoside-related bilateral vestibular loss (BVL) compared with Menière's disease (91.7 vs. 54.6%, p = 0.039). Hierarchical cluster analysis indicated distinct patterns of vestibular end-organ impairment, showing that the results for the same end-organs on both sides are more similar than to other end-organs. Relative sparing of anterior-canal function was reflected in late merging with the other end-organs, emphasizing their distinct state. An anatomically corresponding pattern of SCC/otolith hypofunction was present in 60.4% (oVEMPs vs. horizontal SCCs), 34.7% (oVEMPs vs. anterior SCCs), and 48.5% (cVEMPs vs. posterior SCCs) of cases. Average (±1 SD) number of damaged sensors was 6.8 ± 2.2 out of 10. Significantly (p < 0.001) more sensors were impaired in patients with aminoglycoside-related BVL (8.1 ± 1.2) or inner-ear infections (8.7 ± 1.8) compared with Menière-related BVL (5.5 ± 1.5).
Discussion: Hierarchical cluster analysis may help differentiate characteristic patterns of BVL. With a prevalence of ≈80%, utricular and/or saccular impairment is frequent in BVL. The extent of SCC and otolith impairment was disease-dependent, showing most extensive damage in BVL related to inner-ear infection and aminoglycoside-exposure and more selective impairment in Menière's disease. Specifically, assessing utricular function may help in the distinction between aminoglycoside-related BVL and bilateral Menière's disease.

PMID: 29692756 [PubMed]

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"Arch Endocrinol Metab"[jour]; +16 new citations

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Arch Endocrinol Metab"[jour]

These pubmed results were generated on 2018/04/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Sub-lobar dysplasia - A comprehensive evaluation with neuroimaging, magnetoencephalography and histopathology.

Sub-lobar dysplasia - A comprehensive evaluation with neuroimaging, magnetoencephalography and histopathology.

Epilepsy Behav Case Rep. 2018;9:22-25

Authors: Raghavendra K, Chaitanya G, Goutham B, Mahadevan A, Mundlamuri RC, Bharath RD, Narayannan M, Rao MB, Arivazhagan A, Satishchandra P, Sinha S

Abstract
Sublobar dysplasia, a rare cortical malformation has been defined in only 8 patients to date. It was identified on the basis of histopathological features and MRI findings. We report a right temporal sublobar dysplasia, with detailed evaluation including neuroimaging, magnetoencephalography and histopathology to further characterize the pathology. Additional pathological features included a deep collateral sulcus in the basal right temporal lobe, thinned out right corticospinal tract, and bilateral asymmetric basal ganglia changes. Magnetoencephalograpy localized the seizure focus to the posterior margin of the dysplasia. Histopathological evaluation helped exclude other types of dysplasia. Similar to a previous study, the child had Engel 1a outcome.

PMID: 29692965 [PubMed]

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Cerebrolysin and aquaporin 4 inhibition improve pathological and motor recovery after ischemic stroke.

Cerebrolysin and aquaporin 4 inhibition improve pathological and motor recovery after ischemic stroke.

CNS Neurol Disord Drug Targets. 2018 Apr 25;:

Authors: Catalin B, Pirici I, Balseanu TA, Stan A, Tudorica V, Balea M, Mindrila I, Albu CV, Mohamed G, Pirici D, Muresanu DF

Abstract
BACKGROUND: Edema represents one of the earliest negative markers of survival and consecutive neurological deficit following stroke. The mixture of cellular and vasogenic edema makes treating this condition complicated, and to date, there is no pathogenically oriented drug treatment for edema, which leaves parenteral administration of a hypertonic solution as the only non-surgical alternative.
OBJECTIVE: New insights into water metabolism in the brain have opened the way for molecular targeted treatment, with aquaporin 4 channels (AQP4) taking center stage. We aimed here to assess the effect of inhibiting AQP4 together with the administration of a neurotropic factor (Cerebrolysin) in ischemic stroke.
METHODS: Using a permanent medial cerebral artery occlusion rat model, we administrated a single dose of the AQP4 inhibitor TGN-020 (100 mg/kg) at 15 minutes after ischemia followed by daily Cerebrolysin dosing (5ml/kg) for seven days. Rotarod motor testing and neuropathology examinations were next performed.
RESULTS: We showed first that the combination treatment animals have a better motor function preservation at seven days after permanent ischemia. We have also identified distinct cellular contributions that represent the bases of behavior testing, such as less astrocyte scarring and a larger neuronal-survival phenotype rate in animals treated with both compounds than in animals treated with Cerebrolysin alone or untreated animals.
CONCLUSION: Our data shows that water diffusion inhibition and Cerebrolysin administration after focal ischemic stroke reduces infarct size, leading to a higher neuronal survival in the peri-core glial scar region.

PMID: 29692268 [PubMed - as supplied by publisher]

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Exploding Head Syndrome as Aura of Migraine with Brainstem Aura: A Case Report.

Exploding Head Syndrome as Aura of Migraine with Brainstem Aura: A Case Report.

J Oral Facial Pain Headache. 2018 Spring;32(2):e34-e36

Authors: Rossi FH, Gonzalez E, Rossi EM, Tsakadze N

Abstract
This article reports a case of exploding head syndrome (EHS) as an aura of migraine with brainstem aura (MBA). A middle-aged man presented with intermittent episodes of a brief sensation of explosion in the head, visual flashing, vertigo, hearing loss, tinnitus, confusion, ataxia, dysarthria, and bilateral visual impairment followed by migraine headache. The condition was diagnosed as MBA. Explosive head sensation, sensory phenomena, and headaches improved over time with nortriptyline. This case shows that EHS can present as a primary aura symptom in patients with MBA.

PMID: 29694468 [PubMed - in process]

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Towards an objective test of chronic tinnitus: Properties of auditory cortical potentials evoked by silent gaps in tinnitus-like sounds.

Towards an objective test of chronic tinnitus: Properties of auditory cortical potentials evoked by silent gaps in tinnitus-like sounds.

Hear Res. 2018 Apr 17;:

Authors: Paul BT, Schoenwiesner M, Hébert S

Abstract
A common method designed to identify if an animal hears tinnitus assumes that tinnitus "fills-in" silent gaps in background sound. This phenomenon has not been reliably demonstrated in humans. One test of the gap-filling hypothesis would be to determine if gap-evoked cortical potentials are absent or attenuated when measured within background sound matched to the tinnitus sensation. However the tinnitus sensation is usually of low intensity and of high frequency, and it is unknown if cortical responses can be measured with such "weak" stimulus properties. Therefore the aim of the present study was to test the plausibility of observing these responses in the EEG in humans without tinnitus. Twelve non-tinnitus participants heard narrowband noises centered at sound frequencies of 5 or 10 kHz at sensation levels of either 5, 15, or 30 dB. Silent gaps of 20 ms duration were randomly inserted into noise stimuli, and cortical potentials evoked by these gaps were measured by 64-channel EEG. Gap-evoked cortical responses were statistically identifiable in all conditions for all but one participant. Responses were not significantly different between noise frequencies or levels. Results suggest that cortical responses can be measured when evoked by gaps in sounds that mirror acoustic properties of tinnitus. This design can validate the animal model and be used as a tinnitus diagnosis test in humans.

PMID: 29692331 [PubMed - as supplied by publisher]

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Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort.

Papillary thyroid microcarcinoma: characteristics at presentation, and evaluation of clinical and histological features associated with a worse prognosis in a Latin American cohort.

Arch Endocrinol Metab. 2018 Feb;62(1):6-13

Authors: Domínguez JM, Nilo F, Martínez MT, Massardo JM, Muñoz S, Contreras T, Carmona R, Jerez J, González H, Droppelmann N, León A

Abstract
Objective We aimed to describe the presentation of papillary microcarcinoma (PTMC) and identify the clinical and histological features associated with persistence/recurrence in a Latin American cohort. Subjects and methods Retrospective study of PTMC patients who underwent total thyroidectomy, with or without radioactive iodine (RAI), and who were followed for at least 2 years. Risk of recurrence was estimated with ATA 2009 and 2015 classifications, and risk of mortality with 7th and 8th AJCC/TNM systems. Clinical data obtained during follow-up were used to detect structural and biochemical persistence/recurrence. Results We included 209 patients, predominantly female (90%), 44.5 ± 12.6 years old, 183 (88%) received RAI (90.4 ± 44.2 mCi), followed-up for a median of 4.4 years (range 2.0-7.8). The 7th and 8th AJCC/TNM system classified 89% and 95.2% of the patients as stage I, respectively. ATA 2009 and ATA 2015 classified 70.8% and 78.5% of the patients as low risk, respectively. Fifteen (7%) patients had persistence/recurrence during follow-up. In multivariate analysis, only lymph node metastasis was associated with persistence/recurrence (coefficient beta 4.0, p = 0.016; 95% CI 1.3-12.9). There were no PTMC related deaths. Conclusions Our series found no mortality and low rate of persistence/recurrence associated with PTMC. Lymph node metastasis was the only feature associated with recurrence in multivariate analysis. The updated ATA 2015 and 8th AJCC/TNM systems classified more PTMCs than previous classifications as low risk of recurrence and mortality, respectively.

PMID: 29694628 [PubMed - in process]

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High-dose chemotherapy with autologous stem cell transplantation spares re-irradiation for recurrent intracranial germinoma.

High-dose chemotherapy with autologous stem cell transplantation spares re-irradiation for recurrent intracranial germinoma.

Pediatr Blood Cancer. 2018 Apr 25;:e27104

Authors: Kubota H, Umeda K, Kagehiro K, Tanaka K, Daifu T, Hamabata T, Nodomi S, Kato I, Hiramatsu H, Arakawa Y, Mizowaki T, Adachi S

Abstract
The clinical outcome of high-dose chemotherapy (HDC) with autologous stem cell transplantation was retrospectively analyzed in six patients with recurrent intracranial germinoma. Prior to HDC, all patients achieved complete remission after platinum and ifosfamide-based chemotherapy. A melphalan-based conditioning regimen was administered in either a single cycle or multiple sequential cycles. Five of the six patients are alive and free from disease, with a median survival of 65 months, among which four patients avoided re-irradiation. In a significant proportion of patients, recurrent intracranial germinoma is curable by HDC without re-irradiation, provided that the disease remains sensitive to salvage chemotherapy.

PMID: 29693779 [PubMed - as supplied by publisher]

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An evaluation of the antioxidant and anticancer properties of complex compounds of copper(II), platinum(II), palladium(II) and ruthenium(III) for use in cancer therapy.

An evaluation of the antioxidant and anticancer properties of complex compounds of copper(II), platinum(II), palladium(II) and ruthenium(III) for use in cancer therapy.

Mini Rev Med Chem. 2018 Apr 23;:

Authors: Szczepanska AK, Malinowska K, Majsterek I

Abstract
The incidence of head and neck cancer increases every year, and represents a significant problem for Molecular Biology at the beginning of the twenty-first Century. Despite advances in treatment, most studies still strive to deepen the understanding of the mechanisms of cancerogenesis. In order to develop more effective methods of diagnosis and therapy, it is necessary to understand the molecular basis of the neoplastic transformation process. Such findings obtained by research into Molecular Biology, Molecular Epidemiology and Genetics have brought significant progress in understanding the complex, multi-step process which takes place during tumor formation. For many years, there has been great interest in the use of complex compounds, particularly complexes between heterocyclic compounds and the metals Pt (II), Pd (II), Cu (II) and Ru (III). One such compound is an azole called pyrazole; the azoles are known to have analgesic, antipyretic, anti-tumor, anti-inflammatory and anti-fungal effects. Improved synthetic and separation methods, and biochemical techniques have improved the identification of compounds with biological activity. The main aim of this review is to present complexes with Pt (II), Pd (II), Cu (II) and Ru (III) ions which demonstrate antioxidant and anti-cancer properties.

PMID: 29692246 [PubMed - as supplied by publisher]

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Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

Telocytes in skeletal, cardiac and smooth muscle interstitium: morphological and functional aspects.

Histol Histopathol. 2018 Apr 25;:11994

Authors: Marini M, Rosa I, Ibba-Manneschi L, Manetti M

Abstract
Telocytes (TCs) represent a new distinct type of cells found in the stromal compartment of many organs, including the skeletal, cardiac and smooth muscles. TCs are morphologically defined as interstitial cells with a small cellular body from which arise very long (up to hundreds of micrometers) and thin moniliform processes (named telopodes) featuring the alternation of slender segments (called podomers) and small dilated portions (called podoms) accommodating some organelles. Although these stromal cells are mainly characterized by their ultrastructural traits, in the last few years TCs have been increasingly studied for their immunophenotypes, microRNA profiles, and gene expression and proteomic signatures. By their long-distance spreading telopodes, TCs build a three-dimensional network throughout the whole stromal space and communicate with each other and neighboring cells through homocellular and heterocellular junctions, respectively. Moreover, increasing evidence suggests that TCs may exert paracrine functions being able to transfer genetic information and signaling molecules to other cells via the release of different types of extracellular vesicles. A close relationship between TCs and stem/progenitor cell niches has also been described in several organs. However, the specific functions of TCs located in the muscle interstitium remain to be unraveled. Here, we review the morphological and possible functional aspects of TCs in skeletal, cardiac and smooth muscle tissues. The potential involvement of TCs in muscle tissue pathological changes and future possibilities for targeting TCs as a novel promising therapeutic strategy to foster muscle tissue regeneration and repair are also discussed.

PMID: 29693711 [PubMed - as supplied by publisher]

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Urbanorum Spp: First Report in Brazil.

Urbanorum Spp: First Report in Brazil.

Am J Case Rep. 2018 Apr 25;19:486-490

Authors: de Aguiar RPS, Alves LL

Abstract
BACKGROUND The first scientific case related to Urbanorum spp protozoan infection was identified in Peru in 1994. Considering there are few cases catalogued, the aim of this study was to register the first case of Urbanorum spp infection in Brazil. CASE REPORT A thin 41-year-old female patient with dark skin, weighing 55 to 60 kg attended the Buriti Municipal Central Laboratory, in Maranhão, Brazil to undergo routine exams. Among the exams requested was a parasitological exam of feces, which was processed according to the protocol of Hoffman, Pons, and Janer (HPJ) or Lutz, an easy, simple, and low-cost parasitological technique. This method consists in spontaneous sedimentation of a filtered homogenate of feces sample and water. The sample was stained with Lugol and examined under light microscopy at 10× and 40×. We detected a light-yellow structure with rounded shape and several filaments similar to pseudopods. The microscopic analysis raised doubts about the identity and pathogenicity of this microorganism. CONCLUSIONS This study reports the first case of Urbanorum spp infection in Brazil, where the current environmental conditions have contributed to new parasitological cases. Therefore, further studies are recommended to identify unknown cases of Urbanorum spp infection in other regions of the country to create a national registry related to this new protozoan.

PMID: 29693648 [PubMed - in process]

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upper respiratory tract infection; +23 new citations

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

upper respiratory tract infection

These pubmed results were generated on 2018/04/26

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update.

Novel fluoropyrimidine-based chemotherapy for advanced well-differentiated neuroendocrine tumors: a clinical update.

Expert Opin Pharmacother. 2018 Apr 25;:1-13

Authors: Zhang H, Shen G, Zhang S, Du F, Cao Y, Jiang J, Zheng F, Ma X, Wang Z, Ren D, Ahmad R, Zhao F, Zhao J

Abstract
INTRODUCTION: Patients with advanced well-differentiated neuroendocrine tumors (NETs) who have bulky and/or symptomatic and/or rapidly progressive disease require chemotherapy treatment. Areas covered: This review summarizes the accumulating evidence for treatment with fluorouracil-based chemotherapy in well-differentiated NETs. The main clinical studies, toxicity and predictors of fluorouracil- based chemotherapy regimens in well-differentiated NETs are discussed, along with the current issues, future research directions and therapeutic prospects. Expert opinion: Somatostatin analogs may control symptoms of hormone excess and tumor growth in patients with well-differentiated metastatic NETs, and biological therapies may improve progression-free survival for these patients. However, chemotherapy leads to higher objective response rates and symptom control by reducing tumor bulk. The low response rate and significant toxicities of conventional chemotherapy regimens limit their widespread use. Fortunately, some novel fluoropyrimidine-based treatment including fluorouracil, capecitabine, or S-1 based chemotherapy with or without antiangiogenic agents have been investigated in recent years. These treatments showed significant efficacy and less toxicity in pancreatic and non-pancreatic metastatic well-differentiated NETs. Additionally, non-pancreatic well-differentiated NETs have also achieved similar tumor response or survival comparable to pancreatic NETs. Moreover, some predictors of response to these treatment regimens have been evaluated.

PMID: 29693454 [PubMed - as supplied by publisher]

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Towards an objective test of chronic tinnitus: Properties of auditory cortical potentials evoked by silent gaps in tinnitus-like sounds.

Towards an objective test of chronic tinnitus: Properties of auditory cortical potentials evoked by silent gaps in tinnitus-like sounds.

Hear Res. 2018 Apr 17;:

Authors: Paul BT, Schoenwiesner M, Hébert S

Abstract
A common method designed to identify if an animal hears tinnitus assumes that tinnitus "fills-in" silent gaps in background sound. This phenomenon has not been reliably demonstrated in humans. One test of the gap-filling hypothesis would be to determine if gap-evoked cortical potentials are absent or attenuated when measured within background sound matched to the tinnitus sensation. However the tinnitus sensation is usually of low intensity and of high frequency, and it is unknown if cortical responses can be measured with such "weak" stimulus properties. Therefore the aim of the present study was to test the plausibility of observing these responses in the EEG in humans without tinnitus. Twelve non-tinnitus participants heard narrowband noises centered at sound frequencies of 5 or 10 kHz at sensation levels of either 5, 15, or 30 dB. Silent gaps of 20 ms duration were randomly inserted into noise stimuli, and cortical potentials evoked by these gaps were measured by 64-channel EEG. Gap-evoked cortical responses were statistically identifiable in all conditions for all but one participant. Responses were not significantly different between noise frequencies or levels. Results suggest that cortical responses can be measured when evoked by gaps in sounds that mirror acoustic properties of tinnitus. This design can validate the animal model and be used as a tinnitus diagnosis test in humans.

PMID: 29692331 [PubMed - as supplied by publisher]

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c-Fos and Arc/Arg3.1 expression in auditory and visual cortices after hearing loss: Evidence of sensory crossmodal reorganization in adult rats.

Related Articles

c-Fos and Arc/Arg3.1 expression in auditory and visual cortices after hearing loss: Evidence of sensory crossmodal reorganization in adult rats.

J Comp Neurol. 2017 Aug 15;525(12):2677-2689

Authors: Pernia M, Estevez S, Poveda C, Plaza I, Carro J, Juiz JM, Merchan MA

Abstract
Cross-modal reorganization in the auditory and visual cortices has been reported after hearing and visual deficits mostly during the developmental period, possibly underlying sensory compensation mechanisms. However, there are very few data on the existence or nature and timeline of such reorganization events during sensory deficits in adulthood. In this study, we assessed long-term changes in activity-dependent immediate early genes c-Fos and Arc/Arg3.1 in auditory and neighboring visual cortical areas after bilateral deafness in young adult rats. Specifically, we analyzed qualitatively and quantitatively c-Fos and Arc/Arg3.1 immunoreactivity at 15 and 90 days after cochlea removal. We report extensive, global loss of c-Fos and Arc/Arg3.1 immunoreactive neurons in the auditory cortex 15 days after permanent auditory deprivation in adult rats, which is partly reversed 90 days after deafness. Simultaneously, the number and labeling intensity of c-Fos- and Arc/Arg3.1-immunoreactive neurons progressively increase in neighboring visual cortical areas from 2 weeks after deafness and these changes stabilize three months after inducing the cochlear lesion. These findings support plastic, compensatory, long-term changes in activity in the auditory and visual cortices after auditory deprivation in the adult rats. Further studies may clarify whether those changes result in perceptual potentiation of visual drives on auditory regions of the adult cortex.

PMID: 28472857 [PubMed - indexed for MEDLINE]

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Cricothyroidotomy In Situ Simulation Curriculum (CRIC Study): Training Residents for Rare Procedures.

Related Articles

Cricothyroidotomy In Situ Simulation Curriculum (CRIC Study): Training Residents for Rare Procedures.

Simul Healthc. 2017 Apr;12(2):76-82

Authors: Petrosoniak A, Ryzynski A, Lebovic G, Woolfrey K

Abstract
INTRODUCTION: Technical skill acquisition for rare procedures can be challenging given the few real-life training opportunities. In situ simulation (ISS), a training technique that takes place in the actual workplace, is a promising method to promote environmental fidelity for rare procedures. This study evaluated a simulation-based technical skill curriculum for cricothyroidotomy using deliberate practice, followed by an ISS evaluation session.
METHODS: Twenty emergency medicine residents participated in a two-part curriculum to improve cricothryoidotomy performance. A pretest established participant baseline technical skill. The training session consisted of two parts, didactic teaching followed by deliberate practice using a task-training manikin. A posttest consisted of an unannounced, high-fidelity ISS, during an emergency department shift. The primary outcome was the mean performance time between the pretest and posttest sessions. Skill performance was also evaluated using a checklist scale and global rating scale.
RESULTS: Cricothyroidotomy performance time improved significantly from pretest to posttest sessions (mean difference, 59 seconds; P < 0.0001). Both checklist and global rating scales improved significantly from the pretest to the posttest with a mean difference of 1.82 (P = 0.002) and 6.87 (P = 0.0025), respectively. Postcourse survey responses were favorable for both the overall curriculum experience and the unannounced ISS.
CONCLUSIONS: This pilot study demonstrated that unannounced ISS is feasible and can be used to effectively measure cricothyroidotomy performance among EM residents. After a two-part training session consisting of didactic learning and deliberate practice, improved cricothyroidotomy skill performance was observed during an unannounced ISS in the emergency department. The integration of ISS in cricothyroidotomy training represents a promising approach; however, further study is needed to establish its role.

PMID: 28704285 [PubMed - indexed for MEDLINE]

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High glucose promotes tumor cell proliferation and migration in lung adenocarcinoma via the RAGE‑NOXs pathway.

High glucose promotes tumor cell proliferation and migration in lung adenocarcinoma via the RAGE‑NOXs pathway.

Mol Med Rep. 2018 Apr 23;:

Authors: Liao YF, Yin S, Chen ZQ, Li F, Zhao B

Abstract
Over the past few decades, it has been demonstrated that hyperglycemia can promote lung carcinoma growth, potentially through significantly increased glucose metabolism; however, the underlying mechanism remains to be fully elucidated. In the present study, treatment with a high concentration of glucose (HG) significantly promoted the proliferation and migration of A549 cells. Receptor for advanced glycation end‑products (RAGE) has previously been demonstrated to be associated with diabetes mellitus and oxidative stress, and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) are considered to be initiating factors of oxidative stress. Therefore, an MTT assay, wound‑healing assay, quantitative polymerase chain reaction and western blotting assays were used to analyze the RAGE‑NOX‑4 pathway and to determine its potential involvement in glycometabolism‑associated tumorigenesis. The present study demonstrated that HG could increase the protein expression of RAGE and NOX‑4, whereas the inhibitor of RAGE (anti‑RAGE antibody) could suppress this effect. Futhermore, the inhibitor of NOX [diphenyl iodonium chloride (DPI)] could reduce the protein expression of RAGE and NOX‑4. Furthermore, inhibition of RAGE led to the downregulation of vascular endothelial growth factor (VEGF) and hypoxia‑inducible factor‑1α (HIF‑1α), thus suggesting that HG may influence angiogenesis and tumor metabolism via the RAGE‑NOXs pathway. The present study also demonstrated that the RAGE‑blocking antibody downregulated NOX‑4 and subsequently reduced the production of downstream inflammatory factors, whereas DPI did not affect the mRNA expression of RAGE but it did reduce the protein level of RAGE and then attenuate the inflammatory response. These results indicated that inhibition of RAGE or NOXs may promote the reduced expression of VEGF and HIF‑1α, and NOXs may be downstream targets of RAGE, thus indicating a HG‑RAGE‑NOXs‑VEGF/HIF‑1α association. Furthermore, the results indicated that HG may serve a role in the development of lung adenocarcinoma, mediated by the RAGE‑oxidative stress pathway; therefore, the regulation of this glucose‑associated pathway may be a promising novel direction for oncotherapy. However, while certain antidiabetic agents have been verified to exert inhibitory effects on tumor growth, they can also have long‑term adverse effects on the body, which may limit the value of these drugs as anticancer treatments. In conclusion, the present study suggested a novel attempt to suppress glucose‑induced tumor growth using a RAGE inhibitor such as soluble RAGE while avoiding the risk of glucose fluctuation.

PMID: 29693146 [PubMed - as supplied by publisher]

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IL-17 polarization of MAIT cells is derived from the activation of two different pathways.

Related Articles

IL-17 polarization of MAIT cells is derived from the activation of two different pathways.

Eur J Immunol. 2017 11;47(11):2002-2003

Authors: Guggino G, Di Liberto D, Lo Pizzo M, Saieva L, Alessandro R, Dieli F, Triolo G, Ciccia F

Abstract
MAIT cells are expanded in salivary glands of patients with Sjogren's syndrome and are IL-17 polarized. IL-7 and IL-23 induce IL-17 production activating two different pathways: IL-7 stimulation induces in fact a significant STAT3 and HIF1alpha upregulation, conversely, IL-23 stimulation significantly induces RORc overexpression in MAIT cells of patients with Sjogren's syndrome.

PMID: 28815578 [PubMed - indexed for MEDLINE]

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Improved survival in Medicare patients with multiple myeloma: findings from a large nationwide and population-based cohort.

Related Articles

Improved survival in Medicare patients with multiple myeloma: findings from a large nationwide and population-based cohort.

Med Oncol. 2017 Sep;34(9):153

Authors: Chen Y, Lairson DR, Chan W, Du XL

Abstract
The aim of this study was to examine whether novel agents proteasome inhibitor bortezomib and immunomodulatory drugs lenalidomide and thalidomide are effective in prolonging overall survival (OS) for patients with newly diagnosed multiple myeloma (MM) in the real-world practice setting. A nationwide and population-based retrospective cohort of elderly patients with advanced newly diagnosed MM from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare linked data. Survival was compared between cases in 2005-2009 and in 2000-2004, and between patients treated with anti-MM therapy and the untreated among cases in 2005-2009, using Cox proportional hazards models, Kaplan-Meier methods, and propensity score adjustment to further control for baseline confounding. Of 8839 patients, 4028 (45.6%) cases were in 2000-2004 and 4811 (54.4%) in 2005-2009. OS was significantly longer for patients in 2005-2009 than patients in 2000-2004 (27.9 vs. 20.0 months, P < 0.001). The hazard ratio for OS for cases in 2005-2009 compared with those in 2000-2004 was 0.78 (95% CI 0.74-0.82). Among 4811 cases in 2005-2009, 54% (n = 2587) received anti-MM therapy. Compared to those untreated, OS was significantly longer (41.1 vs. 27.9 months, P < 0.001) and hazard ratio was 0.58 (95% CI 0.54-0.62) in the treated patients. This study demonstrated improved survival in newly diagnosed MM patients in a more recent 5-year cohort compared with those in the previous 5 years. The survival benefit was significant across different demographic and patient characteristics. However, there were still a substantial number of MM patients not receiving anti-MM therapy.

PMID: 28776319 [PubMed - indexed for MEDLINE]

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Eligibility for phase 3 clinical trials of systemic therapy in real-world patients with metastatic renal cell cancer managed in a rural region.

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Eligibility for phase 3 clinical trials of systemic therapy in real-world patients with metastatic renal cell cancer managed in a rural region.

Med Oncol. 2017 Sep;34(9):149

Authors: Nieder C, Syed MA, Dalhaug A, Pawinski A, Norum J

Abstract
Previous research has identified disparities between urban and rural cancer care, including clinical trial access. Therefore, we addressed three different questions in patients with metastatic renal cell cancer managed according to national guidelines in a rural Norwegian standard practice setting. (1) How many patients would have been eligible for three recent landmark randomized clinical trials? (2) Is survival different between eligible and non-eligible patients receiving first-line systemic therapy? (3) Is survival different between eligible patients and published trial results? We performed a retrospective analysis of 101 consecutive patients (2006-2016). Only 52% of the patients were eligible for the first-line study of pazopanib versus sunitinib. The main reasons for violating inclusion or exclusion criteria were presence of brain metastases, absence of clear cell histology, and poor performance status. Even fewer patients were eligible for trials of nivolumab and cabozantinib in pre-treated patients. Eligible patients had significantly better survival than non-eligible patients, median 29.2 versus 8.5 months (p = 0.0001). These results confirm that many patients from rural practices do not fulfill all mandatory trial eligibility criteria. However, eligible patients managed according to national guidelines had survival outcomes in line with published first-line trial results.

PMID: 28748331 [PubMed - indexed for MEDLINE]

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Astilbin decreases proliferation and improves differentiation in HaCaT keratinocytes.

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Astilbin decreases proliferation and improves differentiation in HaCaT keratinocytes.

Biomed Pharmacother. 2017 Sep;93:713-720

Authors: Zhang C, Xu Q, Tan X, Meng L, Wei G, Liu Y, Zhang C

Abstract
Psoriasis is a common chronic dermatosis characterized by keratinocyte hyperproliferation accompanied by inflammatory reactions. Pathological changes upset the balance between keratinocyte proliferation, differentiation, and death in psoriatic lesions, suggesting that molecules with topical anti-inflammatory, anti-proliferation and anti-angiogenesis abilities may be useful for its treatment. The flavonoid astilbin is the major active component extracted from the rhizome of Smilax glabra, which has been widely used in China to treat inflammatory and autoimmune diseases. Here, we investigate the potential of astilbin as a treatment for psoriasis. We reveal that astilbin inhibits the growth of HaCaT keratinocytes. Detailed study shows that astilbin leads to S phase arrest of the cell cycle by induction of p53 and p21 and activated-AMPK. Additionally, astilbin induced keratinocyte differentiation correlated with suppression of keratin 5 (KRT5) and KRT14 proteins (the markers of epidermal basal layer) and induction KRT1 and KRT10 proteins (occurring in the upper layers). Moreover, astilbin regulates the expression of VEGF in human HaCaT keratinocytes. These results suggest that astilbin may be a promising agent for psoriasis treatment.

PMID: 28700975 [PubMed - indexed for MEDLINE]

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Chemically modified tetracyclines an emerging host modulator in chronic periodontitis patients: A randomized, double-blind, placebo-controlled, clinical trial.

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Chemically modified tetracyclines an emerging host modulator in chronic periodontitis patients: A randomized, double-blind, placebo-controlled, clinical trial.

Microb Pathog. 2017 Sep;110:279-284

Authors: Alyousef AA, Divakar DD, Muzaheed

Abstract
Although periodontal diseases are caused by some of the specific pathogens, most of the tissue damage is caused by the host reaction to disease and not actually by the infections. Therefore, host modulatory therapy (HMT) has advanced benefit for the treatment of periodontitis, which works basically by reducing tissue destruction and regeneration in periodontium by altering the critical aspects of host response regulation and up regulating defensive regenerative responses. The present study was conducted with the goal to test an innovative therapeutic option using chemically modified tetracycline in patients affected with generalized, moderate and severe chronic periodontitis. We assumed that CMT might have the potential to provoke an assessable clinical result and pharmacologically impede the level inflammatory flow. CMT (incyclinide) treated group had significantly higher CAL (clinical attachment) values than Placebo Control suggesting an improved CAL in CMT treatment. Host modulation therapy width incyclinide can be as an adjunct to conventional nonsurgical therapies without antimicrobial resistance. Progress was noticed in the clinical parameters but not the serum CRP level in our study establishing the role of CMTs in controlling chronic periodontitis. Also CMT treatment indicates its role in anti-inflammatory process as it inhibited IL-12 and TNF alpha but IL-10 level was not affected. However, more randomized placebo-controlled clinical trials with large sample size are required in order to authenticate the usage of CMTs in chronic periodontitis treatment. Based on this understanding, exploration of the novel, low-cost synthetic inhibitors that can be used as potential therapeutic agents, has been tested.

PMID: 28687322 [PubMed - indexed for MEDLINE]

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Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer.

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Intratumoural interleukin 12 gene therapy stimulates the immune system and decreases angiogenesis in dogs with spontaneous cancer.

Vet Comp Oncol. 2017 Dec;15(4):1187-1205

Authors: Cicchelero L, Denies S, Haers H, Vanderperren K, Stock E, Van Brantegem L, de Rooster H, Sanders NN

Abstract
Interleukin 12 (IL-12) is a powerful immunostimulatory cytokine with a strong antitumoural activity. In this work, the immunological, anti-angiogenic and clinical effects of three consecutive intratumoural IL-12 electrogene therapy (EGT) treatments were evaluated in nine dogs with spontaneous cancer. In all the dogs, tumour biopsies and blood samples were taken prior, during and after the intratumoural IL-12 EGT (on days 1, 8, 35 and 1, 3, 8, 15, 35, respectively). An initial decrease in immune cells was followed by an increase above baseline 1-3 weeks after treatment initiation. Interestingly, the decrease in peripheral leukocytes 2 days after the first intratumoural IL-12 EGT coincided with erythema and tumour swelling. Transient increases of IL-12 and interferon γ were measured in the serum and the tumour tissue, whereas IL-10 transiently increased only in the serum. The effect of intratumoural IL-12 EGT on the levels of IL-24 and vascular endothelial growth factor in the sera and tumour biopsies differed per dog. Via contrast-enhanced ultrasound (US) (on days 1, 8 and 35), we demonstrated that intratumoural IL-12 EGT resulted in a significant decrease of the relative blood volume and blood flow speed in the tumour compared with baseline. Metastases were present in two dogs. In one of these dogs, IL-12 EGT of the primary tumour caused a transient partial regression of the metastases, but not of the primary tumour. The second dog with metastases did not survive long enough to complete the entire treatment cycle. Despite encouraging immunostimulatory and anti-angiogenic effects after intratumoural IL-12 EGT, no clinically relevant outcomes were observed in this study, as persistent tumour regression could not be obtained. On the other hand, the laboratory and US results hold great promise for combinatorial strategies of intratumoural IL-12 EGT with conventional antitumour (immuno)therapies.

PMID: 27506827 [PubMed - indexed for MEDLINE]

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Serum Prolactin Level in Chronic Urticaria: Is promocriptine inducing remission in chronic urticaria?

Serum Prolactin Level in Chronic Urticaria: Is promocriptine inducing remission in chronic urticaria?

J Dermatolog Treat. 2018 Apr 25;:1-20

Authors: Soliman M, Khattab FM, Nasr M

Abstract
BACKGROUND: Chronic urticaria (CU) is a disturbing disease with a negative impact on quality of life. Despite of several clinical studies on CU patients, its pathogenesis is poorly understood. Prolactin (PRL) is peptide hormone has immunomodulatory effects in some immune inflammatory skin diseases.
AIM: To elucidate any possible relationship between the immunomodulatory effects of Prolactin (PRL) and CU. Besides, the study aims to investigate the crucial role of antiprolactin drugs in the management of CU patients.
PATIENTS AND METHODS: The serum PRL level of 80 female patients with CU was measured using the electrochemiluminescence immunoassay. The activity of CU was assessed by European Academy of Allergology and Clinical Immunology; Global Allergy and Asthma European Network; European Dermatology Forum (EAACI/GA2LEN/EDF) activity score. Patients with high PRL level had been given anti prolactin therapy to normalize their PRL levels. Then, the disease activity was reassessed in these patients.
RESULTS: The serum PRL level was high in 8 of 40 (20%) patients (43.18±12.81). Half of patients with high PRL level had remission after treatment of hyperprolactinemia (p = 0.001).
CONCLUSION: Serum PRL levels could not be considered as a marker of the disease activity in CU patients.

PMID: 29694255 [PubMed - as supplied by publisher]

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Improving Research in Radiation Oncology through Interdisciplinary Collaboration.

Improving Research in Radiation Oncology through Interdisciplinary Collaboration.

Radiat Res. 2018 Apr 25;:

Authors: Burmeister JW, Tracey MW, Kacin SE, Dominello MM, Joiner MC

Abstract
The contribution of radiation oncology to the future of cancer treatment depends significantly on our continued clinical progress and future research advancements. Such progress relies on multidisciplinary collaboration among radiation oncologists, medical physicists and radiobiologists. Cultivating collaborative educational and research opportunities among these three disciplines and further investing in the infrastructure used to train both clinicians and researchers will therefore help us improve the future of cancer care. This article evaluates the success of a short-term educational environment to foster multidisciplinary collaboration. The NIH-funded educational course developed at Wayne State University, called "Integration of Biology and Physics into Radiation Oncology" (IBPRO), was designed to facilitate the engagement of radiation oncologists, medical physicists and radiobiologists in activities that enhance collaborative investigation. Having now been delivered to nearly 200 participants over the past four years, the relative success of IBPRO in fostering productive interdisciplinary collaboration and producing tangible research outcomes can be evaluated. The 140 IBPRO participants from the first three years were surveyed to quantify the effectiveness of the course. In total, 62 respondents reported developing 23 institutional protocols, submitting more than 25 research grants (nine of which have been funded thus far), and publishing more than 30 research manuscripts attributable to participation in IBPRO. Nearly one-half (45%) of respondents reported generating at least one of these research metrics attributable to participation in IBPRO and these participants reported an average of over four such quantitative research metrics per respondent. This represents a very substantial contribution to radiation oncology research by a relatively small number of researchers within a relatively short time. Nearly one-half of respondents reported ongoing collaborative working relationships generated by IBPRO. In addition, approximately one-half of respondents stated that specific information presented at IBPRO changed the way they practice, and over 80% of respondents practicing in a clinical setting stated that, since participation in IBPRO, they have approached clinical dilemmas more collaboratively. We believe that educational opportunities such as IBPRO can have a significant impact on interdisciplinary collaborative research. In addition, such interventions have the ability to effect significant clinical change. Both of these should have a positive impact on future advancements in radiation oncology and affect the future contribution of radiation oncology to the treatment of cancer.

PMID: 29693501 [PubMed - as supplied by publisher]

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Implementation of inclusive education for children with intellectual and developmental disabilities in African countries: a scoping review.

Implementation of inclusive education for children with intellectual and developmental disabilities in African countries: a scoping review.

Disabil Rehabil. 2018 Apr 25;:1-18

Authors: Okyere C, Aldersey HM, Lysaght R, Sulaiman SK

Abstract
PURPOSE: To advance understanding of practices that support inclusion of children with intellectual and developmental disabilities in inclusive education classrooms in Africa by conducting a review of the extant literature.
METHODS: Five academic databases were searched supplemented by a hand search of key journals and references of included studies. Two authors independently screened studies via a reference manager (Covidence) which allowed for blinding. A third author was consulted in cases of conflict.
RESULTS: Thirty articles that provided empirical evidence of inclusive education implementation were included. Eight articles highlighted practices that support inclusion of children with intellectual and developmental disabilities. Using Bronfenbrenner's bioecological framework, findings revealed that inclusive education implementation is influenced by factors on the bio level, micro level, meso level, and macro level. Recommendations for promoting inclusive education implementation are provided.
CONCLUSIONS: Inclusion goes beyond teachers and requires strong commitment of other stakeholders such as families and governments. To guarantee the smooth inclusion of children with special education needs and particularly with intellectual and developmental disabilities, a set of practices validated through rigorous research as supportive and unique and that can be universal to Africa is wise. Implications for rehabilitation A number of strategies were identified that can improve the classroom inclusion of children with intellectual and developmental disabilities. Development of policies that support such strategies could improve implementation. Inclusion goes beyond teachers. Rehabilitation professionals (i.e. occupational therapists) and educational professionals should partner to identify practical solutions to the challenges of creating inclusive environments for children with special education needs. Committing more resources and time towards the development and implementation of special education policies can advance the successful inclusion of children with special education needs.

PMID: 29693469 [PubMed - as supplied by publisher]

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Motivation in rehabilitation and acquired brain injury: can theory help us understand it?

Motivation in rehabilitation and acquired brain injury: can theory help us understand it?

Disabil Rehabil. 2018 Apr 25;:1-7

Authors: Kusec A, Velikonja D, DeMatteo C, Harris JE

Abstract
BACKGROUND: In acquired brain injury (ABI) populations, low motivation to engage in rehabilitation is associated with poor rehabilitation outcomes. Motivation in ABI is thought to be influenced by internal and external factors. This is consistent with Self-determination Theory, which posits that motivation is intrinsic and extrinsic. This paper discusses the benefit of using Self-determination Theory to guide measurement of motivation in ABI.
METHODS: Using a narrative review of the Self-determination Theory literature and clinical rehabilitation research, this paper discusses the unique role intrinsic and extrinsic motivation has in healthcare settings and the importance of understanding both when providing rehabilitation in ABI.
RESULTS: Based on the extant literature, it is possible that two independently developed measures of motivation for ABI populations, the Brain Injury Rehabilitation Trust Motivation Questionnaire-Self and the Motivation for Traumatic Brain Injury Rehabilitation Questionnaire, may assess intrinsic and extrinsic motivation, respectively.
CONCLUSION: Intrinsic and extrinsic motivation in ABI may be two equally important but independent factors that could provide a comprehensive understanding of motivation in individuals with ABI. This increased understanding could help facilitate behavioural approaches in rehabilitation. Implications for Rehabilitation Conceptualization of motivation in ABI would benefit from drawing upon Self-determination Theory. External factors of motivation such as the therapeutic environment or social support should be carefully considered in rehabilitation in order to increase engagement. Assessing motivation as a dual rather than a global construct may provide more precise information about the extent to which a patient is motivated.

PMID: 29693464 [PubMed - as supplied by publisher]

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Living with limb loss: everyday experiences of "good" and "bad" days in people with lower limb amputation.

Living with limb loss: everyday experiences of "good" and "bad" days in people with lower limb amputation.

Disabil Rehabil. 2018 Apr 25;:1-10

Authors: Day MC, Wadey R, Strike S

Abstract
PURPOSE: To provide an understanding of the everyday experiences of individuals with a limb amputation.
METHODS: Twenty-two participants (14 female, 8 male) with a mean-age of 42 years (SD = 10 years) were recruited to take part in two focus groups. The participants reported a range of lower-limb amputations (i.e., congenital, acquired, transfemoral, trantibial, unilateral, and bilateral) and on an average were 5 years post-surgery (SD = 7 years). Each focus group comprised of 11 participants and was moderated by either the first or second author. The moderator asked participants to discuss their everyday experiences of life with an amputation using Charmaz's good day/bad day approach. Focus groups were transcribed verbatim and analyzed using an inductive thematic analysis.
RESULTS: Four themes were identified: pain, organization and planning, the embodied experience after amputation, and interactions with others.
CONCLUSIONS: These themes provide a key resource for understanding daily fluctuations in physical, social, and psychological functioning. Implications for Rehabilitation Lower limb amputation can result in daily fluctuations in physical, social, and psychological functioning. These fluctuations can be illustrated through experiences of pain, planning and organization, embodied experiences, and interactions with others. At a policy level, evaluations of daily living after an amputation should be based on a longitudinal assessment.

PMID: 29693463 [PubMed - as supplied by publisher]

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From core belief challenge to posttraumatic growth in para sport athletes: moderated mediation by needs satisfaction and deliberate rumination.

From core belief challenge to posttraumatic growth in para sport athletes: moderated mediation by needs satisfaction and deliberate rumination.

Disabil Rehabil. 2018 Apr 25;:1-9

Authors: Hammer C, Podlog L, Wadey R, Galli N, Forber-Pratt AJ, Newton M

Abstract
PURPOSE: To examine how deliberate rumination and psychological need satisfaction interact to facilitate posttraumatic growth for para sport athletes with acquired disability.
METHODS: Utilizing a sample of 70 para sport athletes, the hypothesized mediating role of deliberate rumination was examined via a simple mediation model. The interaction between needs satisfaction and deliberate rumination and their effect on posttraumatic growth was examined utilizing a moderated mediation procedure.
RESULTS: Disruption to one's core beliefs was significantly associated with posttraumatic growth. This relationship, was in part, explained by the deliberate rumination engaged in soon after the trauma. Needs satisfaction, while a significant predictor of posttraumatic growth, did not moderate the indirect effect.
CONCLUSIONS: Although deliberate rumination at both timeframes and needs satisfaction were independently associated with posttraumatic growth, they did not interact in the hypothesized manner to influence posttraumatic growth. There remains a need to better understand how the experience of posttraumatic growth is achieved amongst individuals with acquired disability, and the role that para sport may play in this process. Implications for rehabilitation The disruption to one's core beliefs caused by acquiring a physical disability is not only a natural experience but also a necessary antecedent to posttraumatic growth. As such, rehabilitation practitioners ought to normalize these types of challenges when working with individuals with acquired disability. Practitioners may help to facilitate growth outcomes by encouraging individuals to deliberately ruminate about their acquired disability. That is, practitioners can help those with acquired disability to seek meaning and understanding about their disability or the precipitating event. For those who struggle to deliberately ruminate in the immediate disability aftermath, practitioners may encourage para sport participation to potentially prompt constructive cognitive processing. Individuals with acquired disabilities would also be well served by rehabilitation practitioners and para sport organizations that provide opportunities for basic psychological needs satisfaction. Specifically, individuals with acquired disabilities should be given the opportunity to demonstrate physical competence, make meaningful relationships, and feel a sense of volitional control over their rehabilitation or para sport participation. For example, practitioners and para sport organizations could establish mentorship programs wherein individuals with more recent disabilities can be mentored by those with greater disability experience.

PMID: 29693460 [PubMed - as supplied by publisher]

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Transcranial doppler ultrasonography cerebral blood flow dynamics study of neurosurgical patients in peri-agonal period with fixed dilated or non-reacting pupils.

Transcranial doppler ultrasonography cerebral blood flow dynamics study of neurosurgical patients in peri-agonal period with fixed dilated or non-reacting pupils.

Br J Neurosurg. 2018 Apr 25;:1-6

Authors: Shrestha P, Ansari SR, Ghimire RK, Gongal DN, Devkota UP

Abstract
INTRODUCTION: Fixed dilated and unreactive pupils are a harbinger of imminent death in neurosurgical patients, signifying that the brainstem is not functioning. Transcranial Doppler (TCD) ultrasonography is a noninvasive, bedside method of determining the flow velocities in the basal cerebral arteries, used extensively in various neurosurgical conditions.
AIMS AND OBJECTIVES: To study the cerebral blood flow dynamics of neurosurgical patients in peri-agonal period with fixed dilated or non reacting pupils using TCD.
MATERIALS AND METHODS: Repeated TCD studies were done in patients with fixed dilated or unreactive pupils in a tertiary care, neurosurgical hospital over a year, recording the various waveforms and indices as Pulsatility Index (PI), Resistivity Index, Peak systolic flow velocity (PSV), End diastolic flow velocity (EDV), Mean cerebral blood flow velocity (MCBFV) of their middle cerebral artery in their peri-agonal period. The subsequent change in the indices as the patients died or improved was analyzed.
RESULTS: A total of 104 TCD studies were done on 57 patients. Mean initial PI and MCBFV in the patients that died were 1.52 ± 0.76 and 28.55 ± 14.92 cm/sec respectively; and in the patients that showed neurosurgical recovery was 1.11 ± 0.28 and 36.52 ± 8.56 cm/sec respectively. Four out of 57 patients showed neurosurgical recovery and all of them had an initial PI less than 1.4 and they showed decrement in PI and increment in MCBFV on subsequent TCD study. The specificity and positive predictive value of the TCD waveform in predicting death was 100%, however, it had low sensitivity (47.17%) and negative predictive value (12.5%).
CONCLUSION: The various indices and waveforms of TCD can be useful in assessing the cerebral blood flow dynamics in patients with various traumatic and non-traumatic ailments in the peri-agonal period; and hence help in their management as well as in the confirmation of brainstem death.

PMID: 29693475 [PubMed - as supplied by publisher]

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Single piece fronto-temporo-orbito-zygomatic craniotomy: a personal experience and review of surgical technique.

Single piece fronto-temporo-orbito-zygomatic craniotomy: a personal experience and review of surgical technique.

Br J Neurosurg. 2018 Apr 25;:1-7

Authors: Sharma M, Shastri S

Abstract
BACKGROUND: Fronto-Temporo-Orbito-Zygomatic (FTOZ) craniotomy has progressed from its humble beginnings. Numerous variations including one piece, two piece and even three piece FTOZ craniotomies have been described. The ideal technique still remains elusive and its use remains restricted to a few specialised centres even when benefits far outweigh the surgical difficulties.
OBJECTIVE: To analyse 11 cases in which single piece FTOZ craniotomy was used and to review the steps of surgery along with its advantages.
METHODS: A total of 11 cases of skull base lesions were operated over a period of 30 months and followed up for a minimum period of 6 months. They were analysed for intraoperative benefits, requirement of cerebral retraction, surgical difficulties, post op recovery, complications faced and post-op cosmetic appearance.
RESULT: A total of nine cases had tumours of skull base including Spheno-Petro-Clival meningiomas, Trigeminal schwannomas, Solitary fibrous histiocytoma and two had giant aneurysms of P1 segment. Intraoperative cerebral retraction was significantly less. There were two post-op deaths. Three patients had temporary and 1 patient had permanent third nerve deficit. There was no injury to periorbital fat and post op cosmetic appearance was good.
CONCLUSION: Single piece FTOZ craniotomy is no more difficult than two or three piece craniotomy, rather it facilitates a rapid craniotomy closure with excellent handling of single piece of bone. It provides a wide, multidirectional access to skull base. Lesions become shallow and their access easier. Benefits far outweigh the difficulties if any, and its use should be encouraged even at centres outside of the specialised units.

PMID: 29693472 [PubMed - as supplied by publisher]

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Penetrating head injury due to angle grinder: an occupational hazard.

Penetrating head injury due to angle grinder: an occupational hazard.

Br J Neurosurg. 2018 Apr 25;:1-5

Authors: Khan KA, Gandhi A, Sharma V, Jain S

Abstract
Penetrating head injury is a life threatening condition. In the workplace, these are mostly non missile type, low velocity civilian injuries caused by sharp objects. Angle grinders are used to cut stones, metal etc, and cause penetrating head injuries due to shattered rotating discs from the grinder at home and workplaces. We report a series of three cases of penetrating head injuries due to unsafe use of angle grinders. The relevant literature is reviewed and management of such cases is discussed.

PMID: 29693468 [PubMed - as supplied by publisher]

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Quantitative analysis of the perimeniscal position of the inferior lateral genicular artery (ILGA): magnetic resonance imaging study.

Quantitative analysis of the perimeniscal position of the inferior lateral genicular artery (ILGA): magnetic resonance imaging study.

Surg Radiol Anat. 2018 Apr 24;:

Authors: Park J, Lee SS, Kim TW

Abstract
PURPOSE: The inferior lateral genicular artery (ILGA) passes around the lateral knee joint, adjacent to the lateral meniscus (LM). ILGA injuries in total knee arthroplasty or arthroscopic surgery can result in recurrent hemarthrosis or painful pseudoaneurysms. Detailed information about the perimeniscal position of the ILGA relative to the LM is necessary to avoid these complications.
METHODS: 3-T MR images of 100 knees (mean age 36.3 ± 11.2 years) were retrospectively reviewed. The perimeniscal area was divided into four regions: the anterior, middle, popliteal hiatus, and posterior zones. In each zone, the ILGA diameter, superoinferior position (assessed as the height of the ILGA from the LM base), and distance between the meniscocapsular junction and the ILGA were measured.
RESULTS: The distance between the ILGA and meniscocapsular junction was significantly smaller in the middle zone than in the other three zones (anterior 5.3 ± 0.8 mm, middle 1.4 ± 0.4 mm, popliteal hiatus 6.1 ± 1.0 mm, and posterior 5.6 ± 1.5 mm, p < 0.05). In the superoinferior position, the height of the ILGA was 3.4 ± 0.9 mm in the anterior zone, 0.4 ± 1.3 mm in the middle zone, - 1.9 ± 1.8 mm in the popliteal hiatus zone, and - 1.3 ± 4.3 mm in the posterior zone. When the LM bottom is the base, the ILGA was located superiorly in the anterior zone, close to the base in the middle zone, and inferiorly in the popliteal hiatus zone.
CONCLUSIONS: To avoid ILGA injury, close attention is necessary during surgical procedures involving the meniscocapsular junction of the LM, especially at the meniscal base in the middle zone.

PMID: 29694643 [PubMed - as supplied by publisher]

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A "golden age" in skull base and rhinology research.

A "golden age" in skull base and rhinology research.

Int Forum Allergy Rhinol. 2018 May;8(5):561-562

Authors: Bleier BS

PMID: 29694736 [PubMed - in process]

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Single piece fronto-temporo-orbito-zygomatic craniotomy: a personal experience and review of surgical technique.

Single piece fronto-temporo-orbito-zygomatic craniotomy: a personal experience and review of surgical technique.

Br J Neurosurg. 2018 Apr 25;:1-7

Authors: Sharma M, Shastri S

Abstract
BACKGROUND: Fronto-Temporo-Orbito-Zygomatic (FTOZ) craniotomy has progressed from its humble beginnings. Numerous variations including one piece, two piece and even three piece FTOZ craniotomies have been described. The ideal technique still remains elusive and its use remains restricted to a few specialised centres even when benefits far outweigh the surgical difficulties.
OBJECTIVE: To analyse 11 cases in which single piece FTOZ craniotomy was used and to review the steps of surgery along with its advantages.
METHODS: A total of 11 cases of skull base lesions were operated over a period of 30 months and followed up for a minimum period of 6 months. They were analysed for intraoperative benefits, requirement of cerebral retraction, surgical difficulties, post op recovery, complications faced and post-op cosmetic appearance.
RESULT: A total of nine cases had tumours of skull base including Spheno-Petro-Clival meningiomas, Trigeminal schwannomas, Solitary fibrous histiocytoma and two had giant aneurysms of P1 segment. Intraoperative cerebral retraction was significantly less. There were two post-op deaths. Three patients had temporary and 1 patient had permanent third nerve deficit. There was no injury to periorbital fat and post op cosmetic appearance was good.
CONCLUSION: Single piece FTOZ craniotomy is no more difficult than two or three piece craniotomy, rather it facilitates a rapid craniotomy closure with excellent handling of single piece of bone. It provides a wide, multidirectional access to skull base. Lesions become shallow and their access easier. Benefits far outweigh the difficulties if any, and its use should be encouraged even at centres outside of the specialised units.

PMID: 29693472 [PubMed - as supplied by publisher]

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Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique.

Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique.

Dis Markers. 2018;2018:5298057

Authors: Chen Y, Lu Y, Kuyaxi P, Cheng J, Zhao J, Zhao Q, Musha P, Zhang H, Yuan H

Abstract
We aim to identify the mutations of deafness genes using massively parallel DNA sequencing in the 12 Uyghur families. SNPscan method was used to screen against the 124 sites in the common deafness genes in probands. Subjects with SNPscan negativity were subject to massively parallel DNA sequencing for the sequencing of 97 genes known to be responsible for hearing loss. Eight families (66.7%) showed biallelic mutations in probands, including MYO15A mutation (6892C>T in J02 family, 9514C>T/7894G>T in J07 family, and 9514C>T in J16 family), MYO7A mutation (1258A>T in J03 family), TMC1 mutation (773G>A in J09 family and 1247T>G/1312G>A in J11 family), and PCDH15 mutation (4658delT in J08 and J13 families). Six novel types of mutation were identified including 6892C>T, 9514C>T/7894G>T, and 9514C>T in MYO15A gene, 1258A>T in MYO7A, 773G>A in TMC1, and 4658delT in PCDH15. The ratio of nonsense mutation and frameshift mutation was comparatively high. All these indicated that the mutation types reported in this study were rare. In conclusion, rare deafness genes were identified in the Uyghur families using massively parallel DNA sequencing, part of which were suggested to be related to the pathogenesis of the disease.

PMID: 29692870 [PubMed - in process]

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Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina.

Autophagy: A Role in the Apoptosis, Survival, Inflammation, and Development of the Retina.

Ophthalmic Res. 2018 Apr 25;:1-8

Authors: Lin W, Xu G

Abstract
Autophagy is a lysosomal degradation process that maintains cellular homeostasis by removing dysfunctional organelles and unfolded proteins. Increasing evidence has shown that autophagy proteins are involved in retinal physiology and pathology and that defective autophagy contributes to retinal degeneration. In retinal diseases, autophagy plays a dual role: promoting retinal cell survival and death. Autophagy at a normal level helps retinal cells defend themselves against harmful stress; however, excessive autophagy results in retinal deterioration. Both synergistic and antagonistic roles of autophagy and apoptosis in the retina have been reported in the literature. In this review, we summarize the roles of autophagy in the development of the retina and retinal diseases. This review highlights the importance of autophagy in retinal diseases, and targeting autophagy may provide a new therapeutic approach for retinal diseases.

PMID: 29694961 [PubMed - as supplied by publisher]

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Current Mechanistic Concepts in Ischemia and Reperfusion Injury.

Current Mechanistic Concepts in Ischemia and Reperfusion Injury.

Cell Physiol Biochem. 2018 Apr 20;46(4):1650-1667

Authors: Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW, Li CY, Li CJ

Abstract
Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

PMID: 29694958 [PubMed - as supplied by publisher]

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MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress.

MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress.

Cell Rep. 2018 Apr 24;23(4):1005-1019

Authors: Nemani N, Carvalho E, Tomar D, Dong Z, Ketschek A, Breves SL, Jaña F, Worth AM, Heffler J, Palaniappan P, Tripathi A, Subbiah R, Riitano MF, Seelam A, Manfred T, Itoh K, Meng S, Sesaki H, Craigen WJ, Rajan S, Shanmughapriya S, Caplan J, Prosser BL, Gill DL, Stathopulos PB, Gallo G, Chan DC, Mishra P, Madesh M

Abstract
Mitochondria shape cytosolic calcium ([Ca2+]c) transients and utilize the mitochondrial Ca2+ ([Ca2+]m) in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+-induced shape change that is distinct from mitochondrial fission and swelling. [Ca2+]c elevation, but not MCU-mediated Ca2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST). MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca2+-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca2+ sensor that decodes metazoan Ca2+ signals as MiST.

PMID: 29694881 [PubMed - in process]

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Cdc14 phosphatase promotes TORC1-regulated autophagy in yeast.

Cdc14 phosphatase promotes TORC1-regulated autophagy in yeast.

J Mol Biol. 2018 Apr 22;:

Authors: Kondo A, Golam Mostofa M, Miyake K, Terasawa M, Islam N, Yeasmin AMST, Waliullah TM, Kanki T, Ushimaru T

Abstract
Cdc14 protein phosphatase is critical for late mitosis progression in budding yeast, although its orthologs in other organisms, including mammalian cells, function as stress-responsive phosphatases. We found herein unexpected roles of Cdc14 in autophagy induction after nutrient starvation and target of rapamycin complex 1 (TORC1) kinase inactivation. TORC1 kinase phosphorylates Atg13 to repress autophagy in nutrient-rich conditions, but if TORC1 becomes inactive upon nutrient starvation or rapamycin treatment, Atg13 is rapidly dephosphorylated and autophagy is induced. Cdc14 phosphatase was required for optimal Atg13 dephosphorylation, pre-autophagosomal structure formation, and autophagy induction after TORC1 inactivation. In addition, Cdc14 was required for sufficient induction of ATG8 and ATG13 expression. Moreover, Cdc14 activation provoked autophagy even in normal conditions. This study identified a novel role of Cdc14 as the stress-responsive phosphatase for autophagy induction in budding yeast.

PMID: 29694832 [PubMed - as supplied by publisher]

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Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression.

Andrographolide protects mouse astrocytes against hypoxia injury by promoting autophagy and S100B expression.

Braz J Med Biol Res. 2018;51(6):e7061

Authors: Du J, Zhang C, Na X, Li A, Zhang Q, Li K, Ding Y

Abstract
Andrographolide (ANDRO) has been studied for its immunomodulation, anti-inflammatory, and neuroprotection effects. Because brain hypoxia is the most common factor of secondary brain injury after traumatic brain injury, we studied the role and possible mechanism of ANDRO in this process using hypoxia-injured astrocytes. Mouse cortical astrocytes C8-D1A (astrocyte type I clone from C57/BL6 strains) were subjected to 3 and 21% of O2 for various times (0-12 h) to establish an astrocyte hypoxia injury model in vitro. After hypoxia and ANDRO administration, the changes in cell viability and apoptosis were assessed using CCK-8 and flow cytometry. Expression changes in apoptosis-related proteins, autophagy-related proteins, main factors of JNK pathway, ATG5, and S100B were determined by western blot. Hypoxia remarkably damaged C8-D1A cells evidenced by reduction of cell viability and induction of apoptosis. Hypoxia also induced autophagy and overproduction of S100B. ANDRO reduced cell apoptosis and promoted cell autophagy and S100B expression. After ANDRO administration, autophagy-related proteins, S-100B, JNK pathway proteins, and ATG5 were all upregulated, while autophagy-related proteins and s100b were downregulated when the jnk pathway was inhibited or ATG5 was knocked down. ANDRO conferred a survival advantage to hypoxia-injured astrocytes by reducing cell apoptosis and promoting autophagy and s100b expression. Furthermore, the promotion of autophagy and s100b expression by ANDRO was via activation of jnk pathway and regulation of ATG5.

PMID: 29694508 [PubMed - in process]

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Hypoxia-induced autophagy promotes gemcitabine resistance in human bladder cancer cells through hypoxia-inducible factor 1α activation.

Hypoxia-induced autophagy promotes gemcitabine resistance in human bladder cancer cells through hypoxia-inducible factor 1α activation.

Int J Oncol. 2018 Apr 24;:

Authors: Yang X, Yin H, Zhang Y, Li X, Tong H, Zeng Y, Wang Q, He W

Abstract
Overcoming the chemoresistance of bladder cancer is a pivotal obstacle in clinical treatments. Hypoxia widely exists in solid tumors and has been demonstrated to contribute to chemoresistance through hypoxia-inducible factor 1α (HIF‑1α)-mediated autophagy in several types of cancer. However, it is unclear whether HIF‑1α-mediated autophagy and chemoresistance occur in bladder cancer. The present study demonstrated that HIF‑1α was overexpressed in 20 bladder cancer tissues compared with matched paracarcinoma tissues. Gemcitabine-induced apoptosis during hypoxia was significantly reduced compared with that observed under normoxic conditions. In addition, hypoxia activated autophagy and enhanced gemcitabine-induced autophagy. Combined treatment using gemcitabine and an autophagy inhibitor (3-methyladenine) under hypoxia significantly increased gemcitabine cytotoxicity. Furthermore, it was demonstrated that hypoxia-activated autophagy depended on the HIF‑1α/BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)/Beclin1 signaling pathway. Suppressing HIF‑1α inhibited autophagy, BNIP3 and Beclin1, as well as enhanced gemcitabine-induced apoptosis in bladder cancer cells under hypoxic conditions. Consequently, the results of the present study demonstrated that hypoxia-induced cytoprotective autophagy counteracted gemcitabine-induced apoptosis through increasing HIF‑1α expression. Therefore, targeting HIF‑1α-associated pathways or autophagy in bladder cancer may be a successful strategy to enhance the sensitivity of bladder cancer chemotherapy.

PMID: 29693166 [PubMed - as supplied by publisher]

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Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer.

Spermidine‑induced growth inhibition and apoptosis via autophagic activation in cervical cancer.

Oncol Rep. 2018 Apr 18;:

Authors: Chen Y, Zhuang H, Chen X, Shi Z, Wang X

Abstract
Cervical cancer is the most common malignancy of the female reproductive tract, and the poor response to prophylactic vaccines and the toxicity of high‑dose chemotherapeutic drugs have limited their clinical application. Spermidine, a natural polyamine detected in all eukaryotic organisms, exhibits functions that promote longevity in multiple model systems and may constitute a promising agent for cancer treatment. However, the potential effectiveness of spermidine in cervical cancer has not yet been fully elucidated, and the underlying molecular mechanisms remain unclear. In the present study, we aimed to assess the effects of spermidine on proliferation and apoptosis of HeLa cells (a cervical cancer cell line). Firstly, CCK‑8 and flow cytometric assays revealed that spermidine reduced the proliferation of HeLa cells in a dose‑dependent fashion by arresting the cell cycle at the S phase. Secondly, flow cytometry incorporating Annexin V‑FITC/PI‑staining revealed that spermidine promoted the apoptosis of HeLa cells, and western blot analysis revealed that spermidine activated autophagy. Finally, spermidine‑activated autophagy mediated the inhibition of cell proliferation by spermidine and spermidine‑induced apoptosis in HeLa cells. Collectively, these results revealed a novel function for spermidine in inhibiting cellular proliferation and inducing apoptosis of HeLa cells by activating autophagy, which may have important implications for the use of spermidine in cervical cancer therapy.

PMID: 29693131 [PubMed - as supplied by publisher]

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Optineurin Functions for Optimal Immunity.

Optineurin Functions for Optimal Immunity.

Front Immunol. 2018;9:769

Authors: Slowicka K, van Loo G

Abstract
Optineurin (OPTN) was identified 20 years ago in a yeast-two-hybrid screen with a viral protein known to inhibit the cytolytic effects of tumor necrosis factor. Since then, OPTN has been identified as a ubiquitin-binding protein involved in many signaling pathways and cellular processes, and mutations in the OPTN gene have been associated with glaucoma, Paget's disease of bone and neurodegenerative pathologies. Its role in autophagy, however, has attracted most attention in recent years and may explain (some of) the mechanisms behind the disease-associated mutations of OPTN. In this brief review, we focus on the role of OPTN in inflammation and immunity and describe how this may translate to its involvement in human disease.

PMID: 29692786 [PubMed]

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PP242 Counteracts Glioblastoma Cell Proliferation, Migration, Invasiveness and Stemness Properties by Inhibiting mTORC2/AKT.

PP242 Counteracts Glioblastoma Cell Proliferation, Migration, Invasiveness and Stemness Properties by Inhibiting mTORC2/AKT.

Front Cell Neurosci. 2018;12:99

Authors: Mecca C, Giambanco I, Bruscoli S, Bereshchenko O, Fioretti B, Riccardi C, Donato R, Arcuri C

Abstract
Glioblastoma multiforme (GBM) is the most malignant brain tumor and is associated with poor prognosis due to its thorny localization, lack of efficacious therapies and complex biology. Among the numerous pathways driving GBM biology studied so far, PTEN/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) signaling plays a pivotal role, as it controls cell survival, proliferation and metabolism and is involved in stem cell maintenance. In front of recent and numerous evidences highlighting mTOR upregulation in GBM, all the strategies developed to inhibit this pathway have been substantially unsuccessful. Our study focused on mTOR complex 2 (mTORC2) to understand its involvement in GBM cell growth, proliferation, migration and invasiveness. We utilized an in vitro model, characterized by various genetic alterations (i.e., GL15, U257, U87MG and U118MG cell lines) in order to achieve the clonal heterogeneity observed in vivo. Additionally, being the U87MG cell line endowed with glioblastoma stem cells (GSCs), we also investigated the role of the PTEN/PI3K/AKT/mTOR pathway in this specific cell population, which is responsible for GBM relapse. We provide further insights that explain the reasons for the failure of numerous clinical trials conducted to date targeting PI3K or mTOR complex 1 (mTORC1) with rapamycin and its analogs. Additionally, we show that mTORC2 might represent a potential clinically valuable target for GBM treatment, as proliferation, migration and GSC maintenance appear to be mTORC2-dependent. In this context, we demonstrate that the novel ATP-competitive mTOR inhibitor PP242 effectively targets both mTORC1 and mTORC2 activation and counteracts cell proliferation via the induction of high autophagy levels, besides reducing cell migration, invasiveness and stemness properties.

PMID: 29692710 [PubMed]

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Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics.

Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics.

Mediators Inflamm. 2018;2018:6195958

Authors: Oikonomou V, Renga G, De Luca A, Borghi M, Pariano M, Puccetti M, Paolicelli G, Stincardini C, Costantini C, Bartoli A, Zelante T, Romani L

Abstract
Phagocytes fight fungi using canonical and noncanonical, also called LC3-associated phagocytosis (LAP), autophagy pathways. However, the outcomes of autophagy/LAP in shaping host immune responses appear to greatly vary depending on fungal species and cell types. By allowing efficient pathogen clearance and/or degradation of inflammatory mediators, autophagy proteins play a broad role in cellular and immune homeostasis during fungal infections. Indeed, defects in autophagic machinery have been linked with aberrant host defense and inflammatory states. Thus, understanding the molecular mechanisms underlying the relationship between the different forms of autophagy may offer a way to identify drugable molecular signatures discriminating between selective recognition of cargo and host protection. In this regard, IFN-γ and anakinra are teaching examples of successful antifungal agents that target the autophagy machinery. This article provides an overview of the role of autophagy/LAP in response to fungi and in their infections, regulation, and therapeutic exploitation.

PMID: 29692681 [PubMed - in process]

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Low Shear Stress Regulating Autophagy Mediated by the p38 Mitogen Activated Protein Kinase and p53 Pathways in Human Umbilical Vein Endothelial Cells.

Low Shear Stress Regulating Autophagy Mediated by the p38 Mitogen Activated Protein Kinase and p53 Pathways in Human Umbilical Vein Endothelial Cells.

Chin Med J (Engl). 2018 May 05;131(9):1132-1133

Authors: Liu HZ, Li L, Chen SL, Wei JR, Zhang JX, Liu J, Guo JW, Qu XL, Chu P

PMID: 29692393 [PubMed - in process]

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Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism.

Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism.

Sci Signal. 2018 Apr 24;11(527):

Authors: Lu X, Altshuler-Keylin S, Wang Q, Chen Y, Henrique Sponton C, Ikeda K, Maretich P, Yoneshiro T, Kajimura S

Abstract
Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes that emerge in response to external stimuli, such as chronic cold exposure. We have previously shown that after the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through autophagy-mediated mitochondrial degradation. We investigated the upstream pathway that mediates mitochondrial clearance and report that Parkin-mediated mitophagy plays a key role in the beige-to-white adipocyte transition. Mice genetically deficient in Park2 showed reduced mitochondrial degradation and retained thermogenic beige adipocytes even after the withdrawal of external stimuli. Norepinephrine signaling through the PKA pathway inhibited the recruitment of Parkin protein to mitochondria in beige adipocytes. However, mitochondrial proton uncoupling by uncoupling protein 1 (UCP1) was dispensable for Parkin recruitment and beige adipocyte maintenance. These results suggest a physiological mechanism by which external cues control mitochondrial homeostasis in thermogenic fat cells through mitophagy.

PMID: 29692364 [PubMed - in process]

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The Relationship Between Dopamine Neurotransmitter Dynamics and the Blood-Oxygen-Level-Dependent (BOLD) Signal: A Review of Pharmacological Functional Magnetic Resonance Imaging.

The Relationship Between Dopamine Neurotransmitter Dynamics and the Blood-Oxygen-Level-Dependent (BOLD) Signal: A Review of Pharmacological Functional Magnetic Resonance Imaging.

Front Neurosci. 2018;12:238

Authors: Bruinsma TJ, Sarma VV, Oh Y, Jang DP, Chang SY, Worrell GA, Lowe VJ, Jo HJ, Min HK

Abstract
Functional magnetic resonance imaging (fMRI) is widely used in investigations of normal cognition and brain disease and in various clinical applications. Pharmacological fMRI (pharma-fMRI) is a relatively new application, which is being used to elucidate the effects and mechanisms of pharmacological modulation of brain activity. Characterizing the effects of neuropharmacological agents on regional brain activity using fMRI is challenging because drugs modulate neuronal function in a wide variety of ways, including through receptor agonist, antagonist, and neurotransmitter reuptake blocker events. Here we review current knowledge on neurotransmitter-mediated blood-oxygen-level dependent (BOLD) fMRI mechanisms as well as recently updated methodologies aimed at more fully describing the effects of neuropharmacologic agents on the BOLD signal. We limit our discussion to dopaminergic signaling as a useful lens through which to analyze and interpret neurochemical-mediated changes in the hemodynamic BOLD response. We also discuss the need for future studies that use multi-modal approaches to expand the understanding and application of pharma-fMRI.

PMID: 29692706 [PubMed]

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Computational Testing for Automated Preprocessing 2: Practical Demonstration of a System for Scientific Data-Processing Workflow Management for High-Volume EEG.

Computational Testing for Automated Preprocessing 2: Practical Demonstration of a System for Scientific Data-Processing Workflow Management for High-Volume EEG.

Front Neurosci. 2018;12:236

Authors: Cowley BU, Korpela J

Abstract
Existing tools for the preprocessing of EEG data provide a large choice of methods to suitably prepare and analyse a given dataset. Yet it remains a challenge for the average user to integrate methods for batch processing of the increasingly large datasets of modern research, and compare methods to choose an optimal approach across the many possible parameter configurations. Additionally, many tools still require a high degree of manual decision making for, e.g., the classification of artifacts in channels, epochs or segments. This introduces extra subjectivity, is slow, and is not reproducible. Batching and well-designed automation can help to regularize EEG preprocessing, and thus reduce human effort, subjectivity, and consequent error. The Computational Testing for Automated Preprocessing (CTAP) toolbox facilitates: (i) batch processing that is easy for experts and novices alike; (ii) testing and comparison of preprocessing methods. Here we demonstrate the application of CTAP to high-resolution EEG data in three modes of use. First, a linear processing pipeline with mostly default parameters illustrates ease-of-use for naive users. Second, a branching pipeline illustrates CTAP's support for comparison of competing methods. Third, a pipeline with built-in parameter-sweeping illustrates CTAP's capability to support data-driven method parameterization. CTAP extends the existing functions and data structure from the well-known EEGLAB toolbox, based on Matlab, and produces extensive quality control outputs. CTAP is available under MIT open-source licence from https://ift.tt/2r1I6QV.

PMID: 29692705 [PubMed]

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