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

alexandrossfakianakis shared this article with you from Inoreader

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.

This article is protected by copyright. All rights reserved.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Association of summer temperatures and acute kidney injury in South Korea: a case-crossover study

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Due to climate change, days with high temperatures are becoming more frequent. Although the effect of high temperature on the kidneys has been reported in research from Central and South America, Oceania, North America and Europe, evidence from Asia is still lacking. This study aimed to examine the association between short-term exposure to high temperatures and acute kidney injury (AKI) in a nationwide study in South Korea.
Methods
We used representative sampling data from the 2002–2015 National Health Insurance Service–National Sample Cohort in South Korea to link the daily mean temperatures and AKI cases that occurred in the summer. We used a bidirectional case-crossover study design with 0–7 lag days before the emergency room visit for AKI. In addition, we stratified the data into six income levels to identify the susceptible population.
Results
A total of 1706 participants were included in this st udy. The odds ratio (OR) per 1°C increase at 0 lag days was 1.051, and the ORs per 1°C increase at a lag of 2 days were both 1.076. The association between exposure to high temperatures and AKI was slightly greater in the low-income group (OR = 1.088; 95% CI: 1.049–1.128) than in the high-income group (OR = 1.065; 95% CI: 1.026–1.105).
Conclusions
In our study, a relationship between exposure to high temperatures and AKI was observed. Precautions should be taken at elevated temperatures to minimize the risk of negative health effects.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Mental health considerations in patients undergoing complex head and neck reconstruction

alexandrossfakianakis shared this article with you from Inoreader

SocialThumb.00020840.DC.jpeg

Purpose of review To summarize recent advances in the psycho-oncology literature, with a focus on findings relevant to the head and neck cancer patient. Recent findings Patients with cancer are at an increased risk of suicide and self-harm. Head and neck cancer patients are among the highest risk compared with other cancer patients. Unique challenges pertaining to disfigurement and voicelessness may, in part, explain these observations. Patient-reported outcome measures can be used to help identify high-risk patients. Summary Psychosocial support needs are highest for head and neck cancer patients. Patient-reported outcome measures should be integrated within clinical workflows to identify high-risk patients.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Investigations Into Obesity and the Risk of Malignant Disease in Pediatric Thyroid Nodules—Reply

alexandrossfakianakis shared this article with you from Inoreader

jamanetwork.com

In Reply We thank Gallant et al for their interest in our recent publication regarding the association of body mass index (BMI) with thyroid cancer in children with thyroid nodules. We agree that differences in design may account for some discrepancies between our study and theirs. Different methods of calculating BMI z-scores might play a role, although our selection of the Centers for Disease Control and Prevention nomograms reflects their wide use in clinical practice. Similarly, our use of nodule diameter rather than nodule volume reflects current recommendations for thyroid nodule evaluation, and is unlikely to be relevant given the excellent correlation of these measures in our cohort (r = 0.97; 95% CI, 0.96-0.97).
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Necrotizing Sialometaplasia in a Medically Compromised Patient

alexandrossfakianakis shared this article with you from Inoreader

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.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Risk of Stroke After Definitive Radiotherapy—Cause for Concern or Modest Risk?

alexandrossfakianakis shared this article with you from Inoreader

jamanetwork.com

With the rapidly increasing prevalence of oropharyngeal squamous cell carcinoma (OPSCC), largely driven by the human papillomavirus (HPV) epidemic, and with relative equipoise between radiation-based and surgery-based treatment protocols, there has been renewed interest in describing differences in functional outcomes between the 2 treatment modalities. Radiation is theoretically related to stroke risk due to carotid artery intimal injury, which could lead to the development of atherosclerosis. Both carotid artery stenosis and carotid intima-medial thickness have been shown to be associated with radiation therapy providing a biologic basis for the findings. A retrospective population-based cohort study of veterans with OPSCC authored by Sun et al reported a 12.5% imputed stroke risk within 10 years after treatment. The major finding of t his study is that there was an observed 23% relative risk reduction of stroke in patients treated with definitive surgery as compared with those treated with definitive radiotherapy. Although there were notable differences between the groups at baseline, in particular higher T- and N-stage as well as worse ECOG performance status and Charlson Comorbidity Index in the nonsurgical group, the authors conducted propensity score–based analyses to account for these imbalances. Interestingly, there was no increase in stroke risk among surgical patients treated with adjuvant radiation as compared with those treated with surgery alone. (Other population-based studies have observed the same.)
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Mortality After Pediatric Tonsillectomy

alexandrossfakianakis shared this article with you from Inoreader

jamanetwork.com

Tonsillectomy is one of the most common surgeries performed in children. In recent years, sleep-disordered breathing has replaced chronic tonsillitis as the most common indication for tonsillectomy in children. While tonsil surgery is safe and effective at relieving upper airway obstruction in most children, it can result in serious complications such as posttonsillectomy hemorrhage and respiratory compromise. Rarely, mortality can occur. Rates of mortality related to pediatric tonsillectomy, reported at 1 in 55 000, have been estimated from various sources including physician survey, malpractice claims, and database reviews. In the study published in JAMA, "Association of Patient Characteristics With Postoperative Mortality in Children Undergoing Tonsillectomy in 5 US States," Edmonson et al aimed to identify clinical predictors o f posttonsillectomy mortality from the Healthcare Cost and Utilization Project for patients younger than 21 years in 5 US states from 2005 to 2017. The authors report the overall mortality at 7 deaths per 100 000 tonsillectomies, which—while rare—is over twice the reported aggregate mortality for the 10 most common pediatric surgeries.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Sudden Sensorineural Hearing Loss and COVID-19 Vaccination Revisited

alexandrossfakianakis shared this article with you from Inoreader

jamanetwork.com

To the Editor Widespread vaccination against SARS-CoV-2 is critical in turning the tide on the COVID-19 pandemic, but achieving widespread acceptance has proven elusive. Fear of adverse effects has been a recurring theme in surveys of the public vaccination hesitancy. Therefore, studies investigating the incidence of sudden sensorineural hearing loss (SSNHL) after COVID-19 vaccination garner intense interest. Whereas Formeister and colleagues find no association between COVID-19 vaccination and incidence of hearing loss in their cross-sectional analysis, Yanir et al identify a possible association but with very small effect size and without consistent demographic groups. Ulrich and colleagues conclude that the benefits of COVID-19 vaccination exceed the possible cost of rare instances of SSNHL. Analyses involving large data sets often un cover statistically significant differences that are not necessarily clinically meaningful, and spurious associations can arise owing to chance or bias.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

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...
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

Temporal Envelope Coding of the Human Auditory Nerve Inferred from Electrocochleography: Comparison with Envelope Following Responses

alexandrossfakianakis shared this article with you from Inoreader
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...
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:

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.
View on Web
Αναρτήθηκε από στις Δεν υπάρχουν σχόλια:
Εγγραφή σε: Αναρτήσεις (Atom)