Κυριακή 13 Δεκεμβρίου 2020

High repetitive arginine in the anterior of PCV3 capsid protein is a severe obstacle for its expression in E. coli

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Porcine circovirus type 3 (PCV3) is a novel circovirus identified in sows with PDNS-like clinical signs and reproductive failure. The capsid protein (CAP) of PCV3 is expected to be an effective vaccine candida...
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Third and fourth pharyngeal arch anomalies, − are they thymopharyngeal duct remnants?

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Pharyngeal arch anomalies are the second most common form of head and neck congenital defect. The second arch anomalies are the most common, and compromise 95% of cases. Little is known about the 3rd and 4th a...
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Antidepressant‐like effect of low dose of scopolamine in the H/Rouen genetic mouse model of depression

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ABSTRACT

Rodent models of depression are useful for the investigation of cellular and neuronal mechanisms of antidepressant drugs and for the discovery of potential new targets. In this study, we examined the antidepressant‐like effect of scopolamine, a non‐selective muscarinic antagonist, in a genetic mouse model of depression obtained through a selective breeding strategy and called H/Rouen. In this model, we observed that scopolamine was active both in males and females at a lower dose (0.03 mg/kg) in the tail suspension test, 30 min following its administration, than observed in CD‐1 mice. In addition, we showed this antidepressant‐like effect was partly inhibited by an injection of 10 mg/kg of the AMPA receptor antagonist NBQX in both males and females, suggesting the antidepressant‐like effect of scopolamine was mainly driven by AMPA receptors in the H/Rouen mouse line. Altogether, our results showed the high sensitivity of the H/Rouen mouse model of depression to study the antidepressant‐like effects of pharmacological compounds.

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Adherence to nutritional interventions in head and neck cancer patients: a systematic scoping review of the literature

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Adherence to nutritional interventions in head and neck cancer patients: a systematic scoping review of the literature

The lack of attention on adherence to oral nutritional interventions in head and neck cancer patients limits our understanding of the extent of the research in this field. Thus, the present review aimed to systematically identify and map the research on adherence to oral nutritional interventions in head and neck cancer, as well as to identify existing gaps in knowledge. A scoping review methodology was employed. Despite identifying studies that have measured adherence to oral nutritional interventions, very few studies monitored its influence on clinical and nutritional outcomes in head and neck cancer patients or reported factors related to adherence.


Abstract

Background

Dietary counselling provided by a dietitian, with or without oral nutritional supplements, can impact on nutritional and clinical outcomes in head and neck cancer (HNC) patients undergoing radiotherapy. However, little is known about the role of adherence to oral nutritional interventions in this population. This review aimed to map the literature for evidence of adherence to oral nutritional interventions in HNC patients undergoing radiotherapy and to identify gaps in knowledge in this field.

Methods

A scoping review methodology was used to identify studies, extract data, and collate and summarise results. We searched Medline, Embase, Cochrane Central and CINAHL, from the earliest available time up to 8 January 2020.

Results

In total, 2315 unique articles were identified, 163 studies were assessed in full and niner were included in the scoping review. The use of different measures to assess adherence and variability in the timing of the assessments was noted across studies. Despite identifying studies that have measured adherence to oral nutritional interventions, very few studies monitored its influence on clinical and nutritional outcomes in HNC patients or reported factors related to adherence.

Conclusions

A robust evidence base is lacking for adherence to oral nutritional intervention in HNC patients. Overall, further studies evaluating the impact of oral nutritional interventions in HNC patients undergoing radiotherapy should measure adherence to the intervention. Early recognition of non‐adherence and the contributing factors could ensure intensification of nutritional support and better health outcomes.

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Comparing accuracy of lipoarabinomannan urine tests for diagnosis of pulmonary tuberculosis in children from four African countries: a cross-sectional study

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Publication date: Available online 11 December 2020

Source: The Lancet Infectious Diseases

Author(s): Esin Nkereuwem, Toyin Togun, Marie P Gomez, Rita Székely, Aurélien Macé, Dawda Jobe, Samuel G Schumacher, Beate Kampmann, Claudia M Denkinger, Ishaya Ibrahim Abok, Joshua Tsoukan Angyu, Aziz Diakité, Bassirou Diarra, Augustine Odo Ebonyi, Uzochukwu Egere, Marie P. Gomez, Musa Jallow, Dawda Jobe, Beate Kampmann, Bakary Konate

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Air‐to‐Air Meeting Technique in Radiofrequency Thermocoagulation of Trigeminal Neuralgia: A Case Report

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Abstract

Background

In a minority of cases with foramen ovales (FOs) are difficult to access due to single confounding anatomical variations. However, there is no method reported where the FO has been successfully targeted via single puncture in the presence of two or more anatomical variations.

Objectives

To observe the effect of a new stereotactic bidirectional approach guiding technique utilized in a patient who harbored a particularly difficult‐to‐access FO due to multiple anatomical variations.

Methods

During operation of a unique facial entry point's trigeminal neuralgia patient, make a stereotactic frame plane which identified by a three‐dimensional (3D) coordinates of the FO target and arc angle value, intersected with a ruler plane which determined through the 3D CT‐reconstruction's facial entry point data, to elucidate the appropriate trajectory. The authors coined the approach "Air‐to‐air meeting" method.

Results

We completed the RFT with a single puncture to successfully target the FO per the preoperative plan confirmed by C‐arm radiography. Postoperative pain scores using a visual analog scale decreased from 10 to 3 by the first day after the procedure. There were no permanent complications or morbidity from the surgery.

Conclusions

To the authors' knowledge, this is the first report describing a unique facial entry point determined by this technique for the treatment of a patient with trigeminal neuralgia.

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Subnasal Lip Lift and its Effect on Nasal Esthetics

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The subnasal lip lift has emerged as a standard procedure for treatment of the elongated upper lip. Despite its popularity, limited literature has studied its effect on nasolabial esthetics. The purpose of this study is to describe the effect of the subnasal lip lift on nasal and labial esthetic parameters.
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Utility of Routine CT Angiogram Screening for Blunt Carotid Injury in Isolated Mandible Fractures

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Determine the incidence of blunt carotid injury (BCAI) in the blunt trauma induced isolated mandible fracture population and determine the utility of CT angiography (CTA) screening for BCAI in this population.
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Mechanisms of Allergen Immunotherapy in Allergic Rhinitis

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Abstract

Purpose of Review

Allergic rhinitis (AR) is a chronic inflammatory immunoglobulin (Ig) E-mediated disease of the nasal mucosa that can be triggered by the inhalation of seasonal or perennial allergens. Typical symptoms include sneezing, rhinorrhea, nasal itching, nasal congestion and symptoms of allergic conjunctivitis. AR affects a quarter of the population in the United States of America and Europe.

Recent Findings

AR has been shown to reduce work productivity in 36–59% of the patients with 20% reporting deteriorated job attendance. Moreover, 42% of children with AR report reduced at-school productivity and lower grades. Most importantly, AR impacts the patient's quality of life, due to sleep deprivation. However, a proportion of patients fails to respond to conventional medication and opts for the allergen immunotherapy (AIT), which currently is the only disease-modifying therapeutic option. AIT can be administered by either subcutaneous (SCIT) or sublingual (SLIT) route. Both routes of administration are safe, effective, and can lead to tolerance lasting years after treatment cessation. Both innate and adaptive immune responses that contribute to allergic inflammation are suppressed by AIT. Innate responses are ameliorated by reducing local mast cell, basophil, eosinophil, and circulating group 2 innate lymphoid cell frequencies which is accompanied by decreased b asophil sensitivity. Induction of allergen-specific blocking antibodies, immunosuppressive cytokines, and regulatory T and B cell phenotypes are key pro-tolerogenic adaptive immune responses.

Conclusion

A comprehensive understanding of these mechanisms is necessary for optimal selection of AIT-responsive patients and monitoring treatment efficacy. Moreover, it could inspire novel and more efficient AIT approaches.

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Ender 3 - extruder stepper skipping

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I have a problem most likely very similar to some reported by other users: extruder stepper is visually skipping a step from time to time. It rapidly rotates in the direction opposite to the one it is supposed to rotate.

I noticed the following:

  • The extruder stepper jumps totally randomly - there is nothing specific in the pattern printed, position etc.
  • Stepper jumps more often on the infill, rarely on the walls.

Details about print:

  • PLA (Devil Design - various colors, they doesn't matter)
  • Filament guide installed on top, but not yet before the extruder (it is printing right now, I'm waiting for the ball bearings too)
  • Filament mounted on the top - in the place defined by Creality
  • Extruder is already replaced with the aluminium one
  • The mainboard is SKR E3 mini V2 (replaced recently)
  • 95% flow set in Cura
  • Printing on glass, leveled bed (the jumping occurs on all layers, not only first)
  • 215 °C hotend temperature, 60 °C bed temperature
  • Stepper motor current settings (from Merlin menu): 580 for X, Y & Z, 650 for E1

Other observations:

  • What's interesting is that extruder motor jumps even if I manually unwind some filament, so that the only force that it has to overcome is only pushing filament into the head.
  • I did a quick DIY wooden spool holder, so that the filament was fed almost horizontally. This actually seemed to make things worse - stepper jumped more often. I moved spool to the top again and it reduced jumping a little.
  • Prints are done beatifully (after changing the motherboard, that is) - no lost lines or layers, walls connected with infill, perfect first layer etc.

What may be the cause of stepper motor jumping? How can I solve it? Does it pose a threat to the motor or stepper? I need to print filament guide and spool holder with ball bearings, so that I can minimize force required by the extruder motor, but then the stepper will probably jump during the prints. I already damaged the original mainboard because of stuck filament, I don't want to destroy another one.

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Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma

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Summary

Background Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Methods The protein expression of BRAF and PIK3R1 as well as the lack of EGFR expression as analyzed by immunohistochemistry corroborated RNA-sequencing data. The expression of additional markers (AKT, SRC, mTOR, NF-κB, Ki-67) emphasized the aggressiveness of the tumor. Then, we screened a chemical library of > 1500 FDA-approved drugs and > 25,000 novel compounds in the ZINC database to find established drugs targeting BRAF47-438del and PIK3R1-G376R mutated proteins. Results Several compounds (including anthracyclines) bound with higher affinities than the control drugs (sorafenib and vemurafenib for BRAF and PI-103 and LY-294,002 for PIK3R1). Subsequent cytotoxicity analyses showed that anthracyclines might be suitable drug candidates. Aclarubicin revealed higher cytotoxicity than both sorafenib and vemurafenib, whereas idarubicin and daunorubicin revealed higher cytotoxicity than LY-294,002. Liposomal formulations of anthracyclines may be suitable to cross the blood brain barrier. Conclusions In conclusion, we identified novel small molecules via a drug repurposing approach that could be effectively used for personalized glioblastoma therapy especially for patients carrying BRAF47-438del and PIK3R1-G376R mutations.

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Prognostic Significance of Pain in Parotid Gland Malignancy

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Objectives/Hypothesis

To better understand the significance of pain as a predictor of disease severity in parotid gland malignancy.

Study Design

A retrospective chart review of patients treated for primary parotid gland malignancy at our institution between 1991 and 2020 was performed.

Methods

Patient records were retrospectively reviewed and relevant clinical parameters were collected. Patients were stratified into low stage (I and II) disease and high stage (III and IV) disease groups to analyze the independent effect of pain at initial presentation on disease recurrence rate and disease‐free survival using Kaplan–Meier survival curves and an independent two‐sample t‐test.

Results

Of 154 patients evaluated, there were 69 patients in the low stage group and 80 patients in the high stage group. Thirty‐seven high stage patients presented with pain. High stage patients with pain were significantly more likely to develop disease recurrence than high stage patients without pain (58.5% [22/37] versus 33.3% [13/39], P = .022). High stage patients with pain also had significantly decreased disease‐free survival time compared to high stage patients without pain (P = .027).

Conclusion

Pain on presentation appears to be a poor prognostic factor for patients with parotid gland malignancy. For patients with demonstrated high stage disease, pain is independently associated with increased risk of recurrence and decreased disease‐free survival time.

Level of Evidence

4 Laryngoscope, 2020

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