Sunday, July 3, 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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The impact of vitamin D on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity in myo‐inositol‐treated and myo‐inositol‐naïve women with autoimmune thyroiditis: A pilot study

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The impact of vitamin D on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity in myo-inositol-treated and myo-inositol-naïve women with autoimmune thyroiditis: A pilot study

The impact of vitamin D on thyroid antibody titers, thyrotropin levels and thyroid function tests is more pronounced in myo-inositol-treated (group A) than inositol-naïve (group B) women with autoimmune thyroiditis.


Abstract

What is Known and Objective

Vitamin D and myo-inositol reduce thyroid antibody titers in subjects with autoimmune thyroiditis. No previous study has investigated interactions between these agents. The aim of the current study was to determine whether the impact of exogenous vitamin D on thyroid autoimmunity and thyroid function in women with Hashimoto's thyroiditis depends on myo-inositol supplementation.

Methods

The study population consisted of three thyroid antibody- and insulin sensitivity-matched groups of women with autoimmune thyroiditis and high-normal or slightly elevated TSH levels. Forty-one women (21 in group A and 20 in group C) had been treated for at least 6 months with myo-inositol (group A), while 21 women (group B) had not received myo-inositol preparations. Over the entire study period (6 months), groups A and C continued treatment with myo-inositol (2 g daily), while groups A and B received exogenous vitamin D (4000 IU daily). Plasma titers of thyroid peroxidase and thyroglobulin antibodies, as well as plasma concentrations of glucose, insulin, TSH, free thyroid hormones, prolactin, and 25-hydroxyvitamin D (25-OH-D) were assessed at entry and 6 months later. Moreover, baseline and follow-up values of the structure parameters of thyroid homeostasis were calculated

Results and Discussion

In groups A and B, vitamin D improved insulin sensitivity and increased 25-OH-D levels. Although follow-up antibody titers in both these groups were lower than baseline ones, the impact of vitamin D on thyroid peroxidase and thyroglobulin antibodies was stronger in group A than in group B. Only in group A, vitamin D decreased TSH levels and increased SPINA-GT. There were no differences between baseline and follow-up free values of glucose, thyroid hormones, prolactin, Jostel's index, and SPINA-GD. The impact of vitamin D treatment on antibody titers correlated with treatment-induced changes in 25-OH-D levels and the degree of improvement in insulin sensitivity. In group C, glucose homeostasis markers, antibody titers and hormone levels remained at a similar level throughout the study period.

What is New and Conclusion

The obtained results suggest that the impact of vitamin D on thyroid autoimmunity and hypothalamic–pituitary–thyroid axis activity in subjects with autoimmune thyroiditis is more pronounced if they receive myo-inositol.

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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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Melatonin has an inhibitory effect on MCF‐7 and MDA‐MB‐231 human breast cancer cell lines by inducing autophagy and apoptosis

alexandrossfakianakis shared this article with you from Inoreader

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

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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

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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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