Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Κυριακή 3 Ιουλίου 2022

Habitual Exercise, Air Pollution, and Pneumonia Mortality: A Longitudinal Cohort Study of Approximately 0.4 Million Adults

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Abstract
This study aims to examine the combined associations of PM2.5 and exercise with deaths from pneumonia. We included 384,130 participants with an age of ≥18 years from Taiwan during 2001-2016. The adults were followed up until 31 May 2019 to obtain the vital status. We performed a time-dependent Cox regression model for statistical analysis. We found that the risk of pneumonia mortality reduced 55% [hazard ratio (HR): 0.45 (95% confidence intervals, CI: 0.36–0.55)] and 36% [0.64 (95%CI: 0.52–0.80)] in participants who took high-/moderate-level of exercise, respectively, as compared to the inactive. By contrast, every 10μg/m3 increase in chronic exposure to PM2.5 was associated with a 30% [1.30 (95%CI: 1.17–1.45)] higher risk of pneumonia mortality. The risk of pneumonia mortality decreased 72% (95%CI: 59%–80%) for the adults who took high-level exercise and simultaneously exposed to low-level PM2.5. A lower risk of pneumonia mortality was associated with both higher exercise and lower PM2.5 air pollution. For adults exposed to different levels of PM2.5, exercise benefits remained. Our findings suggest taking exercise is a safe and effective strategy to alleviate the burden of pneumonia mortality even for people who reside in a moderately-polluted area.
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How Peripheral Vestibular Damage Affects Velocity Storage: a Causative Explanation

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AbstractVelocity storage is a centrally-mediated mechanism that processes peripheral vestibular inputs. One prominent aspect of velocity storage is its effect on dynamic responses to yaw rotation. Specifically, when normal human subjects are accelerated to constant angular yaw velocity, horizontal eye movements and perceived angular velocity decay exponentially with a time constant circa 15 –30 s, even though the input from the vestibular periphery decays much faster (~ 6 s). Peripheral vestibular damage causes a time constant reduction, which is useful for clinical diagnoses, but a mechanistic explanation for the relationship between vestibular damage and changes in these behavi oral dynamics is lacking. It has been hypothesized that Bayesian optimization determines ideal velocity s...
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Pharmacokinetic variability of vancomycin in patients with nosocomial meningitis

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Pharmacokinetic variability of vancomycin in patients with nosocomial meningitis

This study suggests that the clinical condition and inflammatory response of a patient with meningitis influence the pharmacokinetics of vancomycin. Therefore, the dosage of vancomycin for the treatment of nosocomial bacterial meningitis must be adjusted according to changes in the clinical conditions and renal function of the patient, and thus, careful therapeutic drug monitoring is necessary.


Abstract

What is known and objective

High doses of vancomycin are required early in the treatment of nosocomial meningitis. However, the dosage is often reduced later during treatment, irrespective of renal function. This study was designed to investigate the pharmacokinetic variability of vancomycin and the associated factors throughout the treatment course for patients with nosocomial bacterial meningitis.

Methods

This study included 17 patients who received vancomycin for nosocomial bacterial meningitis at the Tokyo Women's Medical University Yachiyo Medical Center from April 2013 to May 2020. All patients had their serum vancomycin concentrations and cerebrospinal fluid (CSF) parameters measured within 7 days of initiating treatment (early period) and after 8 days (later period) of treatment.

Results and discussion

The relative error between the predicted serum vancomycin concentration and the measured value was significantly higher in the later period than in the early period. In 13 patients who did not have their dosing interval shortened, the vancomycin dosage/serum vancomycin concentration/estimated glomerular filtration rate (D/C/eGFR) ratio significantly decreased in the later period. Moreover, the rate of change in the D/C/eGFR ratio significantly correlated with that in the CSF protein and C-reactive protein levels.

What is new and conclusion

This study suggests that the clinical condition and inflammatory response of a patient with meningitis influence the pharmacokinetics of vancomycin. Therefore, the vancomycin dosage for the treatment of nosocomial bacterial meningitis must be adjusted according to changes in the clinical condition and renal function of the patient, necessitating careful therapeutic drug monitoring.

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Incremental value of risk factor variability for cardiovascular risk prediction in individuals with type 2 diabetes: results from UK primary care electronic health records

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Abstract
BackgroundCardiovascular disease (CVD) risk prediction models for individuals with type 2 diabetes are important tools to guide intensification of interventions for CVD prevention. We aimed to assess the added value of incorporating risk factors variability in CVD risk prediction for people with type 2 diabetes.
Methods
We used electronic health records (EHRs) data from 83 910 adults with type 2 diabetes but without pre-existing CVD from the UK Clinical Practice Research Datalink for 2004–2017. Using a landmark-modelling approach, we developed and validated sex-specific Cox models, incorporating conventional predictors and trajectories plus variability of systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, and glycated haemoglobin (HbA1c). Such models were compared against simpler models using single last observed values or means.
Results
The standard deviations (SDs) of SBP, HDL cholesterol and HbA1c were associat ed with higher CVD risk (P < 0.05). Models incorporating trajectories and variability of continuous predictors demonstrated improvement in risk discrimination (C-index = 0.659, 95% CI: 0.654–0.663) as compared with using last observed values (C-index = 0.651, 95% CI: 0.646–0.656) or means (C-index = 0.650, 95% CI: 0.645–0.655). Inclusion of SDs of SBP yielded the greatest improvement in discrimination (C-index increase = 0.005, 95% CI: 0.004–0.007) in comparison to incorporating SDs of total cholesterol (C-index increase = 0.002, 95% CI: 0.000–0.003), HbA1c (C-index increase = 0.002, 95% CI: 0.000–0.003) or HDL cholesterol (C-index increase= 0.003, 95% CI: 0.002–0.005).
Conclusion
Incorporating variability of predictors from EHRs provides a modest improvement in CVD risk discrimination for individuals with type 2 diabetes. Given that repeat measures are readily available in E HRs especially for regularly monitored patients with diabetes, this improvement could easily be achieved.
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Cone beam computed tomography volumetric airway changes after orthognathic surgery: a systematic review

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The aim of this systematic review was to provide a structured overview of three-dimensional airway volume changes in relation to various orthognathic surgeries. Clinical human studies performing pre- and postoperative three-dimensional airway volume assessments to investigate volumetric changes of the airway after orthognathic surgery were included. Pre-determined inclusion and exclusion criteria were applied in an extensive search of the PubMed, Embase, and Web of Science electronic databases. The cut-off date was set to January 1, 2022. (Source: International Journal of Oral and Maxillofacial Surgery)
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Exploring the impact of metabolic imaging in head and neck cancer treatment

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Abstract

Background

Target volume delineation is performed with anatomical imaging for head and neck cancer. Molecular imaging allows the recognition of specific tumor regions. Its inclusion in the pathway could lead to changes in delineation and resultant treatment plans.

Methods

PRISMA methodology was adhered to when selecting the articles for analysis and only full articles were quality assessed.

Results

Seventeen articles were included. Gross tumor volume (GTV) primary, GTV nodal, and other target volumes were evaluated. Positron emission tomography/computerized tomography (PET/CT) produced smaller primary GTVs, although not with diffusion-weighted imaging-magnetic resonance imaging (DWI-MRI) or PET/MRI. The impact of these image modalities on GTV nodal did not display any consistency. Additionally, there was considerable heterogeneity in metrics comparing delineations. Four studies included appraised the dosimetric impact of the changes in target volume delineation.

Conclusion

Quantifying the impact of molecular imaging is difficult, due to heterogeneity in reporting metrics in molecular imaging modalities and a paucity of detail regarding delineation method and guideline adherence.

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A comparison of four drug–drug interaction databases for patients undergoing haematopoietic stem cell transplantation

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A comparison of four drug–drug interaction databases for patients undergoing haematopoietic stem cell transplantation

We examined the 21-day treatment sheets of one hundred patients who underwent haematopoietic stem cell transplantation in two subscription-based and two open-access databases in terms of several categories for 2 years in a row. Fleiss' and Cohen's kappa statistics were used to analyse the databases' agreement levels. None of the databases detected all of the interactions, and the severity categories assigned to interactions were often different among the four-drug interaction database programmes. A total of 1393 and 1382 different drug–drug interactions were detected in the subsequent versions of the databases, namely the 2021 and 2022 versions. The Fleiss kappa overall agreement among databases was slight. Uptodate and Micromedex showed fair agreement, and other database pairs showed slight agreement in severity ratings. There was a poor agreement among databases for interactions seen in bone marrow transplantation patients. Therefore, it would be safer to use more than one d atabase in daily practice. Further work needs to be done to understand the agreement-level of databases for different types of interactions.


Abstract

What is known and objective

Patients who have undergone haematopoietic stem cell transplantation are prone to drug–drug interactions due to polypharmacy. Drug–drug interaction databases are essential tools for identifying interactions in this patient group. However, drug–drug interaction checkers, which help manage interactions, may have disagreements about assessing the existence or severance of the interactions. The study aimed to determine differences among popular drug–drug interaction databases from several angles for patients who underwent haematopoietic stem cell transplantation.

Methods

The 21-day treatment sheets of one hundred patients who underwent haematopoietic stem cell transplantation were examined in two subscription-based (Uptodate and Micromedex) and two open-access databases (Drugs.com and Epocrates) in terms of several categories two years in a row. Statistical analysis was utilized to understand the compatibility of databases in terms of severity scores, evidence levels, given references, and word counts in interaction reports. Fleiss' and Cohen's kappa statistics were used to analyse the databases' agreement levels.

Results and discussion

A total of 1393 and 1382 different drug–drug interactions were detected in subsequent versions of the databases, namely the 2021 and 2022 versions. The Fleiss kappa overall agreement among databases was slight. Uptodate and Micromedex showed fair agreement, and other database pairs showed slight agreement in severity ratings.

Conclusion

There was a poor agreement among databases for interactions seen in bone marrow transplantation patients. Therefore, it would be safer to use more than one database in daily practice. Further work needs to be done to understand the agreement level of databases for different types of interactions.

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Transcriptome analysis of human cholangiocytes exposed to carcinogenic 1,2-dichloropropane in the presence of macrophages in vitro

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The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals

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The Pharmacogenomics Journal, Published online: 02 July 2022; doi:10.1038/s41397-022-00284-6

The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals
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Melatonin has an inhibitory effect on MCF‐7 and MDA‐MB‐231 human breast cancer cell lines by inducing autophagy and apoptosis

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Abstract

The goal of this work was to see how melatonin affected Bax and Bcl-2 expression, as well as apoptosis and autophagy, in MCF-7 and MDA-MB-231 breast cancer cell lines, which have distinct hormonal sensitivities.

In this study, to investigate the IC50 value of melatonin, varied melatonin concentrations were administered to MCF-7 and MDA-MB-231 breast cancer cell lines. Moreover, cytotoxic activities were analyzed through MTT analysis. Five subgroups were created for both cell lines; control, IC50-MeL, hIC50-MeL, DMSO1 and DMSO2. To evaluate the apoptotic effect of melatonin, immunofluorescence staining methods of TUNEL, Bax, and Bcl-2 were used, and to examine the effects of autophagy, immunofluorescence staining methods of Beclin-1, LC3, and p62 were used.

In vitro results revealed upregulation of the expression of TUNEL and Bax in both MCF-7 and MDA-MB-231 cell lines regarding dose and time, but downregulation of Bcl-2 expression. Moreover, autophagy results were consistent with in vitro apoptosis results in both MCF-7 and MDA-MB-231 cell lines. We determined that the expressions of the autophagy markers Beclin-1, LC3, and p62 were increased. Our findings indicate that treatment of breast cancer cells with melatonin increased the inhibitory effect of melatonin on cell growth through both apoptosis and autophagy in vitro.

Consequently, it was concluded that melatonin might adjust the expression balance of markers that have a role in cell death mechanisms and significantly promote these mechanisms. Therefore, melatonin can inhibit the growth of breast cancer cells by inducing cell death.

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