Αρχειοθήκη ιστολογίου

Κυριακή 3 Ιουλίου 2022

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

alexandrossfakianakis shared this article with you from Inoreader

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

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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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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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Does three-dimensional intraglandular location predict malignancy in parotid tumors?

alexandrossfakianakis shared this article with you from Inoreader
Tumors arising within the parotid encompass a heterogeneous mix of benign and malignant neoplasms and other tissue growths. The purpose of this study was to determine the association between the location of intraparotid masses and the risk of malignancy. A retrospective cohort study was performed of patients diagnosed with parotid tumors following open tumor excision. The primary predictor variable was the location of the epicenter of the tumor in three-dimensional space, as determined from preoperative imaging. (Source: International Journal of Oral and Maxillofacial Surgery)
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Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist combined with hyperbaric oxygen therapy

alexandrossfakianakis shared this article with you from Inoreader
Abstract
Background
Radiotherapy is an important treatment option for central nervous system malignancies. However, cranial radiation induces hippocampal dysfunction and white matter injury; this leads to cognitive dysfunction, and results in a reduced quality of life in patients. Excitatory glutamate signaling through N-methyl-D-aspartate receptors (NMDARs) plays a central role both in hippocampal neurogenesis and in the myelination of oligodendrocytes in the cerebrum.
Methods
We will provide the method for quantifying neurogenesis in human subjects in live brain during the cancer therapy. Neuroimaging using behavioral task we originally create, to examine human hippocampal memory pathway in patients with brain disorders.
Results
Treatment with memantine, a non-competitive NMDAR antagonist, reversed impairment in hippocampal pattern separation networks as detected by functional magnetic resonance imaging. Hyperbaric preconditi oning of the patients just before radiotherapy with memantine most reversed white matter injury as detected by whole brain analysis with Tract-Based Spatial Statics. Neuromodulation combined with the administration of hyperbaric oxygen therapy and memantine during radiotherapy facilitated the restoration of hippocampal function and white matter integrity, and improved higher cognitive function in patients receiving cranial radiation.
Conclusions
The method for therapy and diagnosis of hippocampal function we developed can be applicable to the patients received cranial radiation to restore the cognitive decline. The monitoring can be followed during the therapy that production of new neurons by which ability of pattern separation is increased, then recovery of pattern completion, followed by new score elevation.
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Risk factors for high level cytomegalovirus viremia in liver transplant recipients and associated outcomes

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Purpose

To evaluate epidemiology, risk-factors and outcomes of high-level cytomegalovirus (CMV) viremia in liver transplant recipients.

Methods

Adult patients receiving a liver transplant between 1/1/2017-9/30/2020 were evaluated. Viral loads at UW Health Clinical Laboratories were required to allow for numerical comparison. Primary objective was incidence and outcomes of high-level (HL) CMV viremia (viral-load >100,000 IU/mL). Secondary objective was to elucidate risk factors to allow targeted interventions.

Results

209 patients met inclusion criteria; 175 kept their graft for at least 240 days. Of these 9 patients developed HL CMV, 28 developed low-level (LL CMV, viral-load 250–100,000 IU/mL) and 138 did not develop CMV viremia. When comparing these 3 groups via classic statistical methods time from transplant to viremia was similar (HL 158 ± 77 days, LL 150 ± 76 days). Clinical factors were also similar with the exception of donor seropositivity (HL 87.5%, LL 70.4%, No CMV 49.6%, p = 0.025). HL CMV was significantly associated with graft loss (p < 0.0001) on Kaplan-Meier analysis; graft loss in the LL CMV group did not differ from the No CMV group (p = 0.96)

To allow valid assessment of risk factors in the total study population (n = 209) models of time-varying covariates were used and Cox proportional hazards ratios were calculated. In this analysis HL CMV was associated with a significantly increased risk of graft loss (HR 5.6, p = 0.0016). When investigating risk factors associated with HL CMV, donor seropositivity significantly increased risk (HR 8.85, 95% CI 1.13–71.43, p = 0.038). Pre-transplant total bilirubin (HR 1.04, 95% CI 0.998–1.07, p = 0.06) trended towards significance. Recipient seronegativity, liver disease, clinical and allocation MELD, transplant surgery duration, age, sex, induction immunosuppression, and maintenance immunosuppression were not significantly associated with development of HL CMV.

Conclusion

HL CMV after liver transplant is uncommon but is associated with a significantly increased risk of graft loss that is not present in those patients who develop LL CMV or do not develop CMV viremia. Given these negative graft effects, CMV stewardship interventions targeting recipients of CMV seropositive allografts are warranted. Future larger scale studies evaluating the potential role of other factors in risk stratification are needed.

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