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Πέμπτη 11 Αυγούστου 2022

Discovery of novel 1,2,4‐triazole phenylalanine derivatives targeting an unexplored region within the interprotomer pocket of the HIV capsid protein

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Abstract

HIV capsid (CA) protein is a promising target for developing novel anti-HIV drugs. Starting from highly anticipated CA inhibitors PF-74, we used scaffold hopping strategy to design a series of novel 1,2,4-triazole phenylalanine derivatives by targeting an unexplored region composed of residues 106-109 in HIV-1 CA hexamer. Compound d19 displayed excellent antiretroviral potency against HIV-1 and HIV-2 strains with EC50 values of 0.59 µM and 2.69 µM, respectively. Additionally, we show via surface plasmon resonance spectrometry (SPR) that d19 preferentially interacts with the hexameric form of CA, with a significantly improved hexamer/monomer specificity ratio (Ratio = 59) than PF-74 (Ratio = 21). Moreover, we show via SPR that d19 competes with CPSF-6 for binding to CA hexamers with IC50 value of 33.4 nM. Like PF-74, d19 inhibits the replication of HIV-1 NL4.3 pseudo typed virus in both early and late stages. In addition, molecular docking and molecular dynamics simulations provide binding mode information of d19 to HIV-1 CA and rationale for improved affinity and potency over PF-74. Overall, the lead compound d19 displays a distinct chemotype form PF-74, improved CA affinity, and anti-HIV potency.

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Necrotizing Sialometaplasia in a Medically Compromised Patient

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jamanetwork.com

This case report describes a woman in her 50s with type 2 diabetes mellitus, hypertension, and hypertensive kidney disease who presented with oral lesions with a duration of 1 month and was subsequently diagnosed with necrotizing sialometaplasia.
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Stimulation Rate and Voice Pitch Perception in Cochlear Implants

alexandrossfakianakis shared this article with you from Inoreader
We describe two experiments with 16 Nu cleus® CI users, where we controlled modulation characteristics and carrier rate using Spectral and Temporal Enhanced Processing (STEP), a novel experimental multichannel sound coder. We used a fixed set of threshold and comfortable stimulation levels for each subject, obtained from clinical MAPs. In the first experiment, we determined equivalence for voice pitch ranking and voice gender categorization between the Advanced Combination Encoder (ACE), a widely used clinical strategy in Nucleus® recipients, and STEP for fundamental frequencies (F0) 120–250 Hz. In the second experiment, loudn ess was determined as a function of the input amplitude of speech samples for carrier rates of 1000, 500, and 250 pps per channel. Then, using equally loud soun...
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Temporal Envelope Coding of the Human Auditory Nerve Inferred from Electrocochleography: Comparison with Envelope Following Responses

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AbstractNeural coding of the slow amplitude fluctuations of sound (i.e., temporal envelope) is thought to be essential for speech understanding; however, such coding by the human auditory nerve is poorly understood. Here, neural coding of the temporal envelope by the human auditory nerve is inferred from measurements of the compound action potential in response to an amplitude modulated carrier (CAPENV) for modulation frequencies ranging from 20 to 1000  Hz. The envelope following response (EFR) was measured simultaneously with CAPENV from active electrodes placed on the high forehead and tympanic membrane, respectively. Results support the hypothesis that phase locking to higher modulation frequencies (>  80 Hz) will be stronger for CAPENV, compared to EFR, consistent with the uppe...
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Regenerative endodontic therapy for external lateral inflammatory resorption following traumatic dental injuries. Evidence assessment of best practices

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

External inflammatory resorption (EIR) following dental trauma is often caused by an injury to the lining of the cementoblasts and to the non-mineralized tissues (i.e., precementum) covering the root surface. Although EIR frequently occurs apically, it can also develop on the lateral root surfaces, which is termed external inflammatory lateral resorption (EILR). ELIR is a severe complication that can lead to significant root loss and tooth extraction.

Aim

The aim of this project was to review the current evidence in the literature on regenerative endodontic therapy (RET) for ELIR following traumatic injuries and assess the best treatment practices.

Methodology

Publications appearing in PubMed electronic database, from January 1, 2001 to January 9, 2022 were studied. Inclusion criteria were: (a) Publications in the English language; (b) Publications on regenerative endodontic therapy and ELIR; (c) Teeth subjected to dental trauma; and (d) Presence of intracanal bleeding and blood clots. Exclusion criteria were: (a) Conference proceedings; (b) Lectures; (c) Abstracts and (d) Letters to the editor; (e) Publications not in the English language. Additionally, a manual search was conducted. The data collected was analysed, and a descriptive statistical analysis was performed.

Results

A total of 355 publications were analysed, of which 9 met all inclusion criteria, which comprised of case reports and case series studies. In 10 (58.8%) teeth, Triple Antibiotic Paste (TAP) was used for an average of 26 days. Double Antibiotic Paste (DAP) was used in 3 (17.6 %) teeth for an average of 14 days. In 3 (17.6 %) cases, calcium hydroxide (Ca(OH)2) was used as intracanal medication for 14 days and negative pressure irrigation was applied once on 1 (6 %) tooth.

Conclusions

RET demonstrated a good treatment modality producing biologic repair and improving prognosis in cases of ELIR in post-traumatic tooth/pulp injuries. Hence, a meticulous follow up should be conducted when RET is performed in order to identify treatment failure and substitute it with long-term Ca(OH)2 root canal dressing. The key limitation in our review is that all publications included were either case reports or case series that usually tend to report successful outcome.

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Sodium‐glucose cotransporter‐2 inhibitor‐induced euglycemic diabetic ketoacidosis: A case report

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Sodium-glucose cotransporter-2 inhibitor-induced euglycemic diabetic ketoacidosis: A case report

SGLT-2i-induced euDKA.


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