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Τρίτη 25 Οκτωβρίου 2022

Second‐degree burn induced by high‐concentration topical capsaicin with mobility sequelae: a case report

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Abstract

High-concentration topical capsaicin is used as a second line treatment for neuropathic pain. Transient, mild burning sensation and erythema are expected adverse drug reactions. Here, we report the first case of second degree burn after the application of a high-concentration topical capsaicin patch with secondary mobility sequelae. Nine months after the application, neuropathic pain still remained and the patient described mobility difficulties in daily activities, preventing her from returning to work. This report aims to raise the question of the benefit/risk ratio of high concentration topical capsaicin.

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Tone in Noise Detection in Children with a History of Temporary Conductive Hearing Loss

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AbstractChildren with a history of temporary conductive hearing loss (CHL) during early development may show long-term impairments in auditory processes that persist after restoration of normal audiometric hearing thresholds. Tones in noise provide a simplified paradigm for studying hearing in noise. Prior research has shown that adults with sensorineural hearing loss may alter their listening strategy to use single-channel energy cues for tone-in-noise (TIN) detection rather than rove-resistant envelope or spectral profile cues. Our objective was to determine the effect of early CHL on TIN detection in healthy children compared to controls. Children ages 4 –7 years, with and without a history of CHL due to otitis media with effusion (OME) before age 3 years, participated in a two-alte...
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Κυριακή 23 Οκτωβρίου 2022

Expression of Glial Cell‐Derived Neurotrophic Factor Receptors Within Nucleus Ambiguus During Rat Development

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Expression of Glial Cell-Derived Neurotrophic Factor Receptors Within Nucleus Ambiguus During Rat Development

In this paper, we show differences of Glial Cell-Derived Neurotrophic Factor (GDNF)receptors in the nucleus ambiguus during development from E14 to E20 and in the rat adulthood. We observed that there is timing of production of the different members of GDNF receptors in the motoneurons innervating the larynx and we try to establish differences between nucleus ambiguus and the other motor nuclei of the medulla oblongata such as facial and hypoglossus nuclei. These findings support the idea that GDNF may play a role during motor innervation of the rat larynx.


Objective

The nucleus ambiguus (NAmb) is a column of neurons in the medulla oblongata, involved in bulbar functions. Expression of Glial Cell-Derived Neurotrophic Factor (GDNF) and its receptors (GDNFR) is observed within the cell bodies during reinnervation following recurrent laryngeal nerve (RLN) injury. Little is known regarding GDNFR expression in the formation of the NAmb and the laryngeal innervation during embryogenesis. Understanding the timing and pattern of GDNFR expression in embryogenesis versus after RLN injury may provide insights into therapeutic targets for regeneration after RLN injury.

Study Design

Laboratory experiment.

Methods

Rat brainstems at E14.5/E16.5/E18.5/E20.5/adult were stained for GDNFR: GFRα-1/GFRα-2/GFRα-3/Ret. Islet1 and choline acetyltransferase were used as cell body markers. Sections were observed using fluorescent microscopy and quantified through manual cell counting.

Results

Expression of GFRα-1, GFRα-3, and Ret was identified within the NAmb, hypoglossal, and facial nuclei of the adult medulla. During development, GFRα-1 immunoreactivity was seen at E20.5. GFRα-2 expression was not observed at any timepoint. GFRα-3 expression began at E16.5. Ret expression within nerve fibers in the NAmb were observed beginning at E14.5, but never in the cell bodies.

Conclusion

Embryonic GDNFR expression in the NAmb differs from that of the adult after RLN injury. The developing brainstem experienced upregulation at discrete timepoints with signaling sustained through adulthood. In contrast, adult RLN-transected rats experienced patterns of up and down regulation. GFRα-1 may contribute to muscle targeting and neuromuscular junction maturation, GFRα-3 may contribute to both, as well as axon guidance. It is likely that GDNF is functioning via a Ret-independent pathway.

Level of Evidence

NA Laryngoscope, 2022

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A minimally invasive method for titanium mesh fixation with resorbable sutures in guided bone regeneration: A retrospective study

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Abstract

Objectives

Titanium mesh has become a mainstream choice for guided bone regeneration (GBR) owing to its excellent space maintenance. However, the traditional fixation method using titanium screws impacts surgery efficiency and increases patient trauma. We report a novel method of fixing a titanium mesh using resorbable sutures. We assessed the feasibility of resorbable sutures for fixing a titanium mesh and whether it can serve as a stable, universal, and minimally invasive fixation method for a broader application of titanium meshes.

Methods

Patients undergoing GBR with a digital titanium mesh fixed using titanium screws (TS group) and resorbable sutures (RS group) were observed at different time points. The stability of the fixation methods was evaluated on parameters such as titanium mesh spatial displacement, bone augmentation, and bone resorption.

Results

A total of 36 patients were included in this study. The exposure rate of the titanium mesh in the TS group was 16.67%, while no exposure was noted in the RS group. There was no significant difference in the parameters of titanium mesh spatial displacement, bone augmentation, and bone resorption between the two groups (p > 0.05).

Conclusion

The use of resorbable sutures for fixing a titanium mesh can achieve similar results to traditional fixation using titanium screws. Although this new fixation method can improve the efficiency of the surgery and reduce the risk of complications, the long-term clinical effects require further follow-up investigation.

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Epigenetic upregulation of Schlafen11 renders WNT- and SHH- activated medulloblastomas sensitive to cisplatin

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Abstract
Background
Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, survival markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response to DNA damaging agents in various cancers, to be one of the top prognostic markers in medulloblastomas. Hence, we explored the expression and functions of SLFN11 in medulloblastoma.
Methods
SLFN11 expression for each subgroup was assessed by immunohistochemistry in 98 medulloblastoma patient samples and by analyzing transcriptomic databases. We genetically or epigenetically modulated SLFN11 expression in medulloblastoma cell lines and determined cytotoxic response to the DNA damaging agents cisplatin and topoisomerase I inhibitor SN-38 in vitro and in vivo.
Results
High SLFN11 expressing cases exhibited significantly longer survival than low expressing cases. SLFN11 was highly expressed in the WNT-activated subgroup and in a proportion of the SHH-activated subgroup. While WNT activation was not a direct cause of the high expression of SLFN11, a specific hypomethylation locus on the SLFN11 promoter was significantly correlated with high SLFN11 expression. Overexpression or deletion of SLFN11 made medulloblastoma cells sensitive and resistant to cisplatin and SN-38, respectively. Pharmacological upregulation of SLFN11 by the brain-penetrant histone deacetylase-inhibitor RG2833 markedly increased sensitivity to cisplatin and SN-38 in SLFN11-negative medulloblastoma cells. Intracranial xenograft studies also showed marked sensitivity to cisplatin by SLFN11-overexpression in medulloblastoma cells.
Conclusio ns
High SLFN11 expression is one factor which renders favorable outcomes in WNT-activated and a subset of SHH-activated medulloblastoma possibly through enhancing response to cisplatin.
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Σάββατο 22 Οκτωβρίου 2022

Histopathologically defined intestinal metaplasia in lesser curvature of corpus prior to Helicobacter pylori eradication is a risk factor for gastric cancer development

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Abstract

Background and Aim

Helicobacter pylori eradication has been shown to reduce the risk of gastric cancer (GC), with the number of eradication therapy cases on the rise. However, GC can still occur after successful treatment, and the histological differences prior to eradication in patients with and without GC are unclear. This study investigated the pre-treatment histological risk factors for GC development following eradication therapy.

Methods

We retrospectively enrolled consecutive adult patients diagnosed as having H. pylori infection between April 2004 and December 2018. Atrophy and intestinal metaplasia (IM) were histologically assessed according to the updated Sydney System. The operative link on gastritis assessment and the operative link on gastric intestinal metaplasia (OLGIM) were evaluated as well.

Results

Of the 247 patients analyzed in this study, 11 (4.5%) experienced GC after eradication therapy. Histological IM scores in the GC group were significantly higher at all gastric biopsy sites (p < .05), and the proportion of OLGIM III/IV stage was significantly greater in GC patients (81.8% vs. 31.8%, p < .01). For GC prediction, the area under the receiver operating characteristic curve for IM score at the lesser curvature of the corpus was the highest among all biopsy sites and not inferior to OLGIM results.

Conclusions

Patients with histological IM prior to H. pylori eradication, especially at the lesser curvature of the corpus, may be at elevated risk for GC development after eradication therapy and require close surveillance.

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Streptococcus mutans dexA affects exopolysaccharides production and biofilm homeostasis

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Abstract

Objectives

: The study aimed to evaluate the role of Streptococcus mutans (S. mutans) dexA gene on biofilm structure and microecological distribution in multi-species biofilms.

Materials and Methods

: A multi-species biofilm model consisting of S. mutans and its dexA mutants, Streptococcus gordonii (S. gordonii) and Streptococcus sanguinis (S. sanguinis) was constructed, and bacterial growth, biofilm architecture and microbiota composition were determined to study the effect of the S. mutans dexA on multi-species biofilms.

Results

: Our results showed that either deletion or overexpression of S. mutans dexA had no effect on the planktonic growth of bacterium, while S. mutans dominated in the multi-species biofilms to form cariogenic biofilms. Furthermore, we revealed that the SmudexA+ group showed structural abnormality in the form of more fractures and blank areas. The morphology of the SmudexA group was sparser and more porous, with reduced and less agglomerated exopolysaccharides scaffold. Interestingly, the microbiota composition analysis provided new insights that the inhibition of S. gordonii and S. sanguinis was alleviated in the SmudexA group compared to the significantly suppressed condition in the other groups.

Conclusion

: In conclusion, deletion of S. mutans dexA gene re-modules biofilm structure and microbiota composition, thereby leading to decreased cariogenicity. Thus, the S. mutans dexA may be an important target for regulating the cariogenicity of dental plaque biofilms, expecting to be a probiotic for caries control.

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Cytomegalovirus in the transplant setting: where are we now and what happens next? A report from the International CMV Symposium 2021

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Abstract

The CMV Symposium in September 2021 was an international conference dedicated to cytomegalovirus (CMV) infection after solid organ or haematopoietic stem cell transplantation. This review provides an overview of the presentations given by the expert faculty, supplemented with educational clinical cases. Topics discussed include CMV epidemiology and diagnosis, the burden of CMV infection and disease, CMV-specific immunity and management of CMV in transplant settings. Major advances in the prevention and treatment of CMV in the past decade and increased understanding of CMV immunity has led to improved patient outcomes. In the future, management algorithms may be individualised based on the transplant recipient's immune profile which will mark the start of a new era for patients with CMV.

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Waning of first- and second-dose ChAdOx1 and BNT162b2 COVID-19 vaccinations: a pooled target trial study of 12.9 million individuals in England, Northern Ireland, Scotland and Wales

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Abstract
Background
Several SARS-CoV-2 vaccines have been shown to provide protection against COVID-19 hospitalization and death. However, some evidence suggests that notable waning in effectiveness against these outcomes occurs within months of vaccination. We undertook a pooled analysis across the four nations of the UK to investigate waning in vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) against severe COVID-19 outcomes.
Methods
We carried out a target trial design for first/second doses of ChAdOx1(Oxford–AstraZeneca) and BNT162b2 (Pfizer–BioNTech) with a composite outcome of COVID-19 hospitalization or death over the period 8 December 2020 to 30 June 2021. Exposure groups were matched by age, local authority area and propensity for vaccination. We pooled event counts across the four UK nations.
Results
For Doses 1 and 2 of ChAdOx1 and Dose 1 of BNT162b2, VE/rVE reached zero by approximately Days 60–80 and then went negative. By Day 70, VE/rVE was –25% (95% CI: –80 to 14) and 10% (95% CI: –32 to 39) for Doses 1 and 2 of ChAdOx1, respectively, and 42% (95% CI: 9 to 64) and 53% (95% CI: 26 to 70) for Doses 1 and 2 of BNT162b2, respectively. rVE for Dose 2 of BNT162b2 remained above zero throughout and reached 46% (95% CI: 13 to 67) after 98 days of follow-up.
Conclusions
We found strong evidence of waning in VE/rVE for Doses 1 and 2 of ChAdOx1, as well as Dose 1 of BNT162b2. This evidence may be used to inform policies on timings of additional doses of vaccine.
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