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Κυριακή 4 Σεπτεμβρίου 2022

B‐vitamins and homocysteine as determinants of bone health: a literature review of human studies

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Although there are several factors related to bone diseases such as physical activity, gender (oestrogen), race/ethnicity, smoking and alcohol habits, nutrition is a modifiable risk factor that could be employed to prevent or manage the onset of bone health diseases such as osteoporosis in humans. Aside from calcium and vitamin D, B-vitamins are a group of water-soluble vitamins that play a vital role in cell metabolism. In this review, current evidence on B-vitamins and bone health was assessed. Clinical trials (interventions) indicated that treatment with B-vitamins impact the concentrations of total plasma/serum homocysteine concentrations (tHcy), however, most studies reported a lack of an effect of low homocysteine concentrations on bone turnover markers, bone mineral density (BMD) or fracture risks. Current studies have been inconsistent in their reports on the role of B-vitamins and homocysteine in bone health. More data are therefore required to show the mechanism and effect of tHcy and B-vitamins on BMD, bone metabolism and fracture risk.

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Robotic lateral oropharyngectomy following diagnostic tonsillectomy is oncologically safe in patients with human papillomavirus‐related squamous cell cancer: Long‐term results

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Introduction

To report the long-term oncological and functional outcomes of en bloc TORS lateral oropharyngectomy to address the close/involved margin following diagnostic tonsillectomy in HPV-related SCC of unknown primary.

Material and methods

A single tertiary center observational cohort over a 4-year period. Primary outcome measures were disease-specific survival (DSS), overall survival (OS), and PSS NOD (Performance Status Scale-Normalcy of Diet) scores.

Results

TORS specimens did not evidence residual carcinoma in 93% of patients. Of 14 patients, 50% received surgery alone (median follow-up 57 months; range 46–96), the remainder surgery and adjuvant therapy (median follow-up of 58 months; range 51–69) with 100% DSS, OS and no deterioration of PSS NOD scores.

Conclusions

Long-term oncological outcomes confirm TORS lateral oropharyngectomy alone is an oncologically safe treatment. Due consideration of this approach is warranted to mitigate against the morbidity of adjuvant radiotherapy treatment in this group of patients.
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Development and validation of a risk score to differentiate viral and autoimmune encephalitis in adults

alexandrossfakianakis shared this article with you from Inoreader

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ABSTRACT
Background
Encephalitis represents a challenging condition to diagnose and treat. To assist physicians in considering autoimmune encephalitis (AE) sooner, we developed and validated a risk score.
Methods
The study was conducted as a retrospective cohort of patients with a diagnosis of definite viral encephalitis (VE) and AE from​​ February 2005 to December 2019. Clinically relevant and statistically significant features between cases of AE and VE we re explored in a bivariate logistic regression model and results were used to identify variables for inclusion in the risk score. A multivariable logistic model was used to generate risk score values and predict risk for AE. Results were externally validated.
Results
A total of 1,310 patients were screened. Of the 279 enrolled, 36 patients met criteria for definite AE and 88 criteria for definite VE. Patients with AE as compared to VE were more likely to have a subacute to chronic presentation (OR = 22.36; 95%CI 2.05–243.7), Charlson comorbidity index <2 (OR = 6.62; 95%CI 1.05–41.4), psychiatric and/or memory complaints (OR = 203.0; 95%CI 7.57–5445), and absence of robust inflammation in the cerebrospinal fluid defined as <50 white blood cells/microliter and protein <50 milligrams/deciliter (OR = 0.06; 95%CI 0.005–0.50). Using these 4 variables, patients were classified into 3 risk categories for AE: low (0-1), intermediate (2-3), and high (4). Results were externally validated and the performance of the score achieved an AUC of 0.918 (95%CI, 0.871-0.966).
Discussion
This risk score allows clinicians to estimate the probability of AE in patients presenting with encephalitis and may assist with earlier diagnosis and treatment.
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Should Linezolid Replace Clindamycin as the Adjunctive Antimicrobial of Choice in Group A Streptococcal Necrotizing Soft Tissue Infection and Toxic Shock Syndrome? A Focused Debate

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Abstract
Group A Streptococcus (GAS) necrotizing soft tissue infections and toxic shock syndrome remain high-mortality conditions. In vitro and animal model data, as well as multiple observational studies, suggest adjunctive clindamycin (i.e., given with a beta-lactam) reduces invasive GAS infection mortality by inhibiting exotoxin production. Unfortunately, clindamycin resistance in GAS has been rapidly increasing in the United States (US) since the mid-2010s, though the clinical significance of this remains unclear. Linezolid is a promising alternative adjunctive agent to which US GAS isolates remain near-universally susceptible, with a similar mechanism of action and similar in vitro evidence of GAS virulence factor attenuation. However, the clinical data supporting linezolid's value in severe GAS infections are far more limited. Here, the authors review the data and reasoning behind a general preference for clindamycin or linezolid in a focused, pro-con debate format.
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Estimating Waning of Vaccine Effectiveness: a Simulation Study

alexandrossfakianakis shared this article with you from Inoreader

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Abstract
Background
Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated.
Methods
To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-base d model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time.
Results
While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme.
Conclusions
While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data.
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Native and activated antithrombin inhibits TMPRSS2 activity and SARS‐CoV‐2 infection

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Host cell proteases such as TMPRSS2 are critical determinants of SARS-CoV-2 tropism and pathogenesis. Here, we show that antithrombin (AT), an endogenous serine protease inhibitor regulating coagulation, is a broad-spectrum inhibitor of coronavirus infection. Molecular docking and enzyme activity assays demonstrate that AT binds and inhibits TMPRSS2, a serine protease that primes the Spike proteins of coronaviruses for subsequent fusion. Consequently, AT blocks entry driven by the Spikes of SARS-CoV, MERS-CoV, hCoV-229E, SARS-CoV-2 and its variants of concern including Omicron, and suppresses lung cell infection with genuine SARS-CoV-2. Thus, AT is an endogenous inhibitor of SARS-CoV-2 that may be involved in COVID-19 pathogenesis. We further demonstrate that activation of AT by anticoagulants, such as heparin or fondaparinux, increases the anti-TMPRSS2 and anti-SARS-CoV-2 activity of AT, suggesting that repurposing of native and activated AT for COVID-19 tr eatment should be explored.

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COVID‐19 immunopathology: From acute diseases to chronic sequelae

alexandrossfakianakis shared this article with you from Inoreader

ABSTRACT

The clinical manifestation of COVID-19 mainly targets the lung as a primary affected organ, which is also a critical site of immune cells activation by SARS-CoV-2. However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology. The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID- 19.

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WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS

alexandrossfakianakis shared this article with you from Inoreader

ABSTRACT

Fast, accurate sequencing methods are needed to identify new variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome. Single Molecular Real Time (SMRT) Pacific Biosciences (PacBio) provides long, highly accurate sequences by circular consensus reads. This study compares the performance of a target capture SMRT Pacbio protocol for whole genome sequencing (WGS) of SARS-CoV-2 to that of an amplicon Pacbio SMRT sequencing protocol. The median genome coverage was higher (p<0.05) with the target capture protocol (99.3% [IQR: 96.3-99.5]) than with the amplicon protocol (99.3% [IQR :69.9-99.3]). The clades of 65 samples determined with both protocols were 100% concordant. After adjusting for Ct values, S gene coverage was higher with the target capture protocol than with the amplicon protocol. After stratification on Ct values, higher S gene coverage with the target capture protocol was observed only for samples w ith Ct>17 (p<0.01). Pacbio SMRT sequencing protocols appears to be suitable for WGS, genotyping and detecting mutations of SARS-CoV-2.

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Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Objective

To compare the color stability, translucency, and biaxial flexural strength (BFS) of differently glazed advanced lithium disilicate (ALDS) with those of lithium disilicate (LDS) and zirconia-reinforced lithium silicate (ZLS) after coffee thermocycling.

Materials and methods

Forty disk-shaped specimens were prepared from three lithium silicate based materials (CEREC Tessera, ALDS; IPS e.max CAD, LDS; Vita Suprinity, ZLS). ALDS specimens were divided into two subgroups according to glazing procedures (reduced glaze duration, ALDS-S and normal glaze duration, ALDS-N), while LDS and ZLS specimens were crystallized and glazed. Color coordinate measurements were performed before and after coffee thermocycling. Color differences (ΔE 00) and relative translucency parameters (RTP) were calculated. Specimens were then subjected to BFS test. Statistical analysis was performed by using 1- (ΔE 00 and BFS) and 2-way (RTP) ANOVA tests (α = 0.05).

Results

ΔE 00 values of tested materials were similar (df = 3, F = 0.150, p = 0.929). Two-way ANOVA showed the significant effect of material type, coffee thermocycling, and the interaction between these parameters on RTP values (p < 0.001). Both before and after thermocycling, LDS had the highest (p ≤ 0.001) and ZLS had the lowest (p < 0.001) RTP values, while ALDS-N had higher RTP than ALDS-S (p ≤ 0.001). Among tested materials, only LDS had similar RTP values before and after thermocycling (p = 0.865) as the other materials had lower RTP values after thermocycling (p < 0.001). ALDS-N had higher BFS values than ALDS-S (p = 0.005), while LDS had similar values to ALDS specimens (p ≥ 0.201). ZLS had the highest BFS (p ≤ 0.007).

Conclusions

ALDS had comparable values to those of other materials. However, reduced glazing duration resulted in decreased translucency and BFS of ALDS.

Clinical significance

ALDS may be an appropriate restorative material for those patients with increased coffee consumption considering its color stability and ability to maintain translucency, particularly when glazed by using a conventional porcelain furnace.
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